bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrocardiographic localization of ventricular arrhythmias successfully ablated from the distal great cardiac vein
Authors: Chang David , Gabriels James , Vaishnav Aditi , Kim Beom S. , Coleman Kristie , Khan Mohammad , Maisel Kyle , Ismail Haisam , Goldner Bruce , Willner Jonathan , Mitra Raman , John Roy M. , Patel Apoor , Epstein Laurence M. , Mountantonakis Stavros , Beldner Stuart
Published: July 2020

Background

Idiopathic ventricular arrhythmias (IVAs) from the left ventricular (LV) summit may be successfully ablated from the distal great cardiac vein (dGCV). Using a 12‐lead electrocardiogram (ECG) to localize IVAs that can be ablated from the dGCV is valuable for ablation planning.

Objective

To determine if a “w” wave, a notch in the Q wave in lead I, and other ECG features can identify IVAs that can be successfully ablated from the dGCV.

Methods

We reviewed outflow tract premature ventricular contraction (PVC) ablations performed at two centers between September 2010 and June 2018. Successful PVC ablations, in which the PVCs were mapped from the right ventricular outflow tract, coronary cusps, commissures, endocardial LV, and the coronary venous system including the dGCV were included. ECG characteristics were compared between patients with successful ablations in the dGCV and non‐dGCV sites.

Results

Of the 120 patients (age 56.8 ± 13.8 years, 45% female) that met the inclusion criteria, the dGCV was the successful ablation site in 18 patients (15%). Multivariate analysis with binary logistic regression showed that a “w” in lead I in combination with an early precordial pattern break and a maximum deflection index (MDI) ≥ 0.5 had sensitivity and specificity for a successful ablation in the dGCV of 94.4% and 96.1%, respectively.

Conclusion

Combining a “w” wave in lead I with an early precordial pattern break and an MDI ≥ 0.5 is highly sensitive and specific for identifying the dGCV as a successful ablation site for PVCs.
An in vitro model for hypertrophic adipocytes: Time‐dependent adipocyte proteome and secretome changes under high glucose and high insulin conditions
Authors: Qiao Qi , Bouwman Freek G. , Renes Johan , Mariman Edwin C. M.
Published: July 2020

Obesity is the consequence of a positive energy balance and characterized by enlargement of the adipose tissue, which in part is due to hyperplasia and hypertrophy of the adipocytes. Not much is known about the transition of normal mature adipocytes to the hypertrophic state, which in vivo is very hard to study. Here, we have maintained mature human SGBS cells as a surrogate for adipocytes, changes of morphological and molecular metabolism of the adipocytes were monitored over the first 4 days and the last 4 days. In total, 393 cellular proteins and 246 secreted proteins were identified for further analysis. During the first 4 days of high glucose and insulin, the adipocytes seemed to prefer pyruvate as energy source, whereas beta‐oxidation was down‐regulated supporting lipid loading. Over time, lipid droplet fusion instead of lipid uptake became relatively important for growth of lipid droplets during the last 4 days. Moreover, ECM production shifted towards ECM turnover by the up‐regulation of proteases over eight days. The present in vitro system provides insight into the metabolic changes of adipocytes under conditions of high glucose and insulin, which may help to understand the process of in vivo adipocyte hypertrophy during the development of obesity.
Ecological fitting is the forerunner to diversification in a plant virus with broad host range
Authors: Peláez Adrián , McLeish Michael J. , Paswan Ricky R. , Dubay Bhumika , Fraile Aurora , García‐Arenal Fernando
Published: July 2020

The evolution and diversification of ssRNA plant viruses are often examined under reductionist conditions that ignore potentially much wider biotic interactions. The host range of a plant virus is central to interactions at higher levels that are organized by both fitness and ecological criteria. Here we employ a strategy to minimize sampling biases across distinct plant communities and combine it with a high‐throughput sequencing approach to examine the influence of four habitats on the evolution of Watermelon mosaic virus (WMV). Local, regional and global levels of genetic diversity that correspond to spatial and temporal extents are used to infer haplotype relationships using network and phylogenetic approaches. We find that the incidence and genetic diversity of WMV were structured significantly by host species and habitat type. A single haplotype that infected 11 host species of a total of 24 showed that few constraints on host species use exist in the crop communities. When the evolution of WMV was examined at broader levels of organization, we found variation in genetic diversity and contrasting host use footprints that broadly corresponded to habitat effects. The findings demonstrated that nondeterministic ecological factors structured the genetic diversity of WMV. Habitat‐driven constraints underlie host use preferences.
Fatigability as a Predictor of Subclinical and Clinical Anemia in Well‐Functioning Older Adults
Authors: Simonsick Eleanor M. , Patel Kushang V. , Schrack Jennifer A. , Ferrucci Luigi
Published: July 2020

BACKGROUND/OBJECTIVES

Anemia is a common condition in older adults for which fatigue, the primary symptom, often goes unrecognized as individuals typically equilibrate their activity to avoid fatigue. Whether assessing fatigability (i.e., susceptibility to fatigue) facilitates identification of anemia is unknown. This study examines the association between fatigability and prevalent, incident, and persistent subclinical and clinical anemia in well‐functioning older adults.

DESIGN, SETTING, PARTICIPANTS

Longitudinal analysis of 905 well‐functioning men and women aged 60 to 89 years and followed for 1 to 5 years from the Baltimore Longitudinal Study of Aging conducted at the National Institute on Aging, Clinical Research Unit, Baltimore, MD.

MEASUREMENTS

Perceived fatigability was assessed as a rating of perceived exertion (RPE) from 6 to 20 following a 5‐minute treadmill walk at 1.5 mph (.67 m/s); fatigue was assessed as reported unusual tiredness in the past month. Clinical anemia was defined using World Health Organization hemoglobin cutpoints of below 13 g/dL and below 12 g/dL for men and women, respectively, and subclinical anemia was defined as 13.0 to 13.9 g/dL and 12.0 to 12.9 g/dL, respectively.

RESULTS

Overall, 14% of participants had clinical and 30% had subclinical anemia at baseline. Each increment (1 RPE) of fatigability was associated after covariate adjustment with 14% (95% confidence interval [CI] = 5–25%, P = .005) and 8% (CI = 1–17%; P = .031), respectively, greater likelihood of prevalent clinical and subclinical anemia. An average of 2.2 years later, each 1 RPE increment in baseline fatigability predicted an 11% (CI = 2–20%; P = .016) higher likelihood of incident and/or persistent subclinical and clinical anemia. Reports of unusual tiredness were associated with prevalent subclinical anemia only.

CONCLUSION

This study provides evidence that perceived fatigability may help identify well‐functioning older adults with borderline to clinical anemia who are on a trajectory of persistently suboptimal or worsening hemoglobin status. Assessing fatigability may facilitate earlier diagnosis of health conditions that underlie persistent suboptimal hemoglobin status. J Am Geriatr Soc 68:2297–2302, 2020.
Partners' experiences of living with men who have screening‐detected abdominal aortic aneurysms: A qualitative descriptive study
Authors: Ericsson Anna , Carlson Elisabeth , Ching Shirley Siu‐yin , Molassiotis Alex , Kumlien Christine
Published: July 2020

Aim

To describe partners' experiences of living with men with a screening‐detected abdominal aortic aneurysm (AAA).

Background

Diagnosis of a chronic life‐threatening disease affects the patients' as well as their partners' lives in different aspects. AAA, with rupture as the major consequence, is a life‐threatening disease that can affect the whole family. Screening programmes for AAA have been introduced in several countries to reduce the mortality rate. Although the awareness of having an AAA influences the individuals' quality of life and well‐being, it is still unclear how it affects their partners.

Design

Qualitative descriptive design.

Methods

Twenty‐one partners of men with AAA were purposely selected to participate in individual semi‐structured interviews between August 2017–February 2018 in Sweden. Data were transcribed and imported into NVivo‐12®. The data were analysed using qualitative content analysis. The study conforms to the COREQ checklist.

Results

Three categories were identified: (a) experiencing the unexpected; (b) being reminded of fragility; and (c) balancing a changing relationship. The partners had a positive attitude towards the screening process and were pleased that their husbands were under surveillance. Nevertheless, at the same time, the diagnosis caused worries and questions. The AAA diagnosis was constantly in the minds of the partners, which sometimes affected and limited daily activities. Furthermore, ambivalent feelings towards surgical treatment were described. The partners tried to support their men and encouraged them to achieve a healthy lifestyle.

Conclusion

The partners' well‐being and daily lives were impacted by the awareness of the screening‐detected AAA. Different degrees of worry were the most common reaction and were pervasive in all three categories.

Relevance for clinical practice

The result highlights the need to review routines or develop new strategies to include the partners in the process of screening and offer supplementary support and information.
School closure, COVID‐19 and lunch programme: Unprecedented undernutrition crisis in low‐middle income countries
Authors: Mayurasakorn Korapat , Pinsawas Bonggochpass , Mongkolsucharitkul Pichanun , Sranacharoenpong Kitti , Damapong Sa‐nga
Published: July 2020

The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS‐CoV‐2 infection is often mild or asymptomatic and that children may not be major SARS‐CoV‐2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low‐ and middle‐income countries depend on free school meals; unexpected long‐term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low‐ and middle‐income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.
Clinical feasibility and acceptability of adding cognitive behavioral therapy to pharmacotherapy for drug‐resistant overactive bladder in women: A single‐arm pilot study
Authors: Funada Satoshi , Watanabe Norio , Goto Takayuki , Negoro Hiromitsu , Akamatsu Shusuke , Uozumi Ryuji , Kishimoto Sanae , Ichioka Kentaro , Segawa Takehiko , Furukawa Toshi A , Ogawa Osamu
Published: July 2020

Objectives

Drug‐resistant overactive bladder (OAB) represents an unmet medical need in that treatment options are limited. We developed a treatment model based on cognitive behavioral therapy and evaluated its feasibility and acceptability for drug‐resistant OAB in women.

Methods

This was an open‐label, single‐arm, multicenter pilot study. We defined drug‐resistant OAB as OAB with moderate to severe symptoms despite pharmacotherapy for more than 12 weeks. A face‐to‐face intervention was prescribed as six sessions (30 minutes each) over 6 to 12 weeks according to a treatment manual. The effects were assessed by self‐reported questionnaires and frequency voiding charts (FVC) at baseline, during intervention, immediately after intervention, and at follow‐up.

Results

Ten patients participated in this study. Median age was 72 years, median OAB Symptom Score was nine points, and median duration of prior treatment for OAB was 5.5 years at baseline. Two participants dropped out of the study. Among the remaining patients, the scores of the OAB Questionnaire subscales improved (effect size: 0.75‐1.73), and the mean urinary frequency in the FVC also improved from baseline (9.0 times, SD: 2.1) to follow‐up (6.2 times, SD: 1.2). All participants were satisfied with the intervention. There were no adverse events during this study.

Conclusions

The new treatment based on cognitive behavioral therapy was well tolerated and feasible in women with drug‐resistant OAB. Further randomized research is needed to rigorously evaluate the efficacy of the treatment.
Beyond the icon: Core cognition and the bounds of perception
Authors: Clarke Sam
Published: July 2020

This paper refines a controversial proposal: That core systems belong to a perceptual kind, marked by the format of its representational outputs. Following Susan Carey, this proposal has been understood in terms of core representations having an iconic format, like certain paradigmatically perceptual outputs. I argue that they do not, but suggest that the proposal may be better formulated in terms of a broader analogue format type. Formulated in this way, the proposal accommodates the existence of genuine icons in perception, and avoids otherwise troubling objections.
Familial cases of pseudohypoaldosteronism type II harboring a novel mutation in the Cullin 3 gene
Authors: Nakano Kiyoshi , Kubota Yasuo , Mori Takayuki , Chiga Motoko , Mori Takayasu , Sonoda Shyunya , Ueda Daisuke , Asakura Isao , Ikegaya Takeshi , Kagawa Jiro , Uchida Shinichi , Kubota Akira
Published: July 2020

Pseudohypoaldosteronism type II (PHA II) is inherited in an autosomal dominant manner and is characterized by hypertension, hyperkalemia, and hyperchloremic metabolic acidosis. The enhancement of with‐no‐lysine kinase (WNK) functions is correlated to the pathogenesis of the condition. Cullin 3 (CUL3) forms an E3 ubiquitin ligase complex, and it can ubiquitinate WNK. Most CUL3 gene mutations are distributed in sites, such as intron 8 splice acceptor, intron 9 splice donor, and putative intron 8 splice branch sites, which are involved in the splicing of exon 9. These mutations result in the deletion of exon 9, which reduces the activity of ubiquitination against WNK and inhibits the degradation of WNK. In this report, we identified a novel CUL3 c.1312A>G mutation in familial cases. A mutation prediction software showed that the significance of these mutations was not clear. However, using the Human Splicing Finder 3.1 software, in silico analyses revealed that these mutations induced splicing alterations, which affected the sites of exon 9, altered the balance between predicted exonic splicing enhancers and silencers, and led to the deletions of exon 9. This study presented a novel pathogenic splicing variant to the CUL3 mutation and provided a reference for further research about the mechanisms of splicing. Moreover, it showed that not only amino acid substitution caused by nonsynonymous mutations but also splicing motif changes due to base substitutions have important roles in the pathogenesis of PHA II.
Do ICD diagnostics predict failure of ventricular tachycardia response to antitachycardia pacing and need for shock?
Authors: Al‐Damluji Mohammed S. , Singhvi Aditi , Snuckel Meghan , Zaghloul Ahmed , Kluger Jeffrey
Published: July 2020

Background

Among heart failure patients with implantable cardioverter defibrillators (ICDs), monomorphic ventricular tachycardia (MMVT) failing antitachycardia pacing (ATP) and terminated by shock renders higher mortality as compared to MMVT terminated by ATP only. It is unknown if the higher mortality in ATP failure reflects decompensated heart failure.

Objective

It was the purpose of the present study to determine if ICD heart failure diagnostics can predict the failure of ATP and the need to shock to terminate MMVT.

Methods

This was a single‐center retrospective review of 103 consecutive patients with Medtronic ICDs who had MMVT and received ICD therapy. Heart failure diagnostics preceding each MMVT event were reviewed including atrial fibrillation burden, patient activity, night heart rate, heart rate variability, Optivol® fluid index, and MMVT heart rate.

Results

A total of 452 MMVT events were analyzed, of which 23% required shock. Compared to MMVT that responded to ATP, MMVT that failed ATP and required shock had significantly faster heart rates and higher atrial fibrillation burden. Patient activity, night heart rate, heart rate variability, and OptiVol® fluid index were similar between ATP responsive MMVT events and those that failed ATP. In a multivariate analysis adjusting for baseline characteristics, higher atrial fibrillation burden and lower patient activity were associated with ATP failure and shock termination.

Conclusion

Device diagnostics associated with decompensated heart failure identified MMVT events that failed ATP and necessitated shock.
Ultrasound‐guided anatomical evaluation of right internal jugular vein in children aged 0‐2 years: A prospective observational study
Authors: Uzumcugil Filiz , Ekinci Saniye
Published: July 2020

Background

The right internal jugular vein is commonly preferred for central venous cannulation, and ultrasonographic assessment and guidance is the recommended technique for this procedure. Despite the safety and reliability of this technique, it requires specific training and experience as well as thorough knowledge of anatomy.

Aim

The position of the right internal jugular vein with respect to carotid artery and its transverse diameter free from overlap with the carotid artery were evaluated using ultrasound in patients aged 0‐2 years.

Methods

This single‐center, prospective, observational study included patients aged 0‐2 years who underwent elective surgery between July 2018 and July 2019. The diameters and anatomical position were evaluated using ultrasound. All parameters were compared between groups classified according to postmenstrual ages. The correlations of these parameters with weight and postmenstrual ages were analyzed.

Results

A total of 156 patients were included. The diameters (P < .001) and depth (P = .012) were smaller in patients with postmenstrual age <45 weeks. The anteroposterior diameter was significantly correlated with weight in patients with postmenstrual age <45 weeks, but not in older patients. Right internal jugular vein was lateral and anterolateral with respect to carotid artery in 51.3% and 42.9% of patients, respectively, and >80% of the transverse diameter was free from overlap with the carotid artery.

Conclusion

Our results support the current data for the high anatomical variability of the right internal jugular vein, highlighting the recommendation of the Rapid Central Vein Assessment (RaCeVA) protocol prior to and ultrasound guidance during catheterization of central veins.
A case of pediatric lymphomatoid papulosis treated with photodynamic therapy and narrowband ultraviolet B
Authors: Snider Sam , Costello Collin M. , Ederaine Sophia , Besch‐Stokes Jake , Severson Kevin J. , DiCaudo David J. , Pittelkow Mark R. , Mangold Aaron R.
Published: July 2020

We report a case of a 13‐year‐old boy with extensive lymphomatoid papulosis (LyP) involving his elbows, forearms, proximal thighs, and right hip, with treatment‐resistant nodules on his right forearm. He was treated with full‐body narrowband ultraviolet B and targeted photodynamic therapy (PDT) with 20% aminolevulinic acid (ALA). After two months, there was complete resolution of the right forearm nodules. Due to its minimal toxicity, PDT offers unique advantages and may be considered for pediatric LyP patients with symptomatic, localized disease resistant to conventional treatments.
Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics and Photochemical Properties†
Authors: Robinson‐Duggon José , Pizarro Nancy , Gunther Germán , Zúñiga‐Núñez Daniel , Edwards Ana María , Greer Alexander , Fuentealba Denis
Published: July 2020

Toluidine blue O (TBO) is a water‐soluble photosensitizer that has been used in photodynamic antimicrobial and anticancer treatments, but suffers from limited solubility in hydrophobic media. In an effort to incrementally increase TBO’s hydrophobicity, we describe the synthesis of hexanoic (TBOC6) and myristic (TBOC14) fatty acid derivatives of TBO formed in low to moderate percent yields by condensation with the free amine site. Covalently linking 6 and 14 carbon chains led to modifications of not only TBO’s solubility, but also its photophysical and photochemical properties. TBOC6 and TBOC14 derivatives were more soluble in organic solvents and showed hypsochromic shifts in their absorption and emission bands. The solubility in phosphate buffer solution was low for both TBOC6 and TBOC14, but unexpectedly slightly greater in the latter. Both TBOC6 and TBOC14 showed decreased triplet excited‐state lifetimes and singlet oxygen quantum yields in acetonitrile, which was attributed to heightened aggregation of these conjugates particularly at high concentrations due to the hydrophobic “tails.” While in diluted aqueous buffer solution, indirect measurements showed similar efficiency in singlet oxygen generation for TBOC14 compared to TBO. This work demonstrates a facile synthesis of fatty acid TBO derivatives leading to amphiphilic compounds with a delocalized cationic “head” group and hydrophobic “tails” for potential to accumulate into biological membranes or membrane/aqueous interfaces in PDT applications.
Reclassification of Chlamydomonas monticola as Heterochlamydomonas (Volvocales, Chlorophyceae)
Authors: Watanabe Shin
Published: July 2020

A unicellular flagellate described as Chlamydomonas monticola NIES‐157 was known to have two unequal flagella and informally stored as Heterochlamydomonas sp. in the culture collection. In this study, the strain NIES‐157 was revisited for clarifying its taxonomic status. In the 18S rDNA tree, this organism was resolved in a distinct position in the clade of Heterochlamydomonas (Reinhardtinia). In this strain, the two basal bodies were arranged in parallel as in H. inaequalis, and naked motile cells (putative gametes) were additionally observed. NIES‐157 was morphologically distinguished from other members of the genus in the nuclear position in motile cells. Based on these data, a transfer of C. monticola NIES‐157 to Heterochlamydomonas as H. monticola comb. nov. is proposed.
The Nature of Law and Potential Coercion
Authors: Woodbury‐Smith Kara
Published: July 2020

This paper argues for a novel understanding of the relationship between law and coercion. It firstly refutes Kenneth Himma’s claim that the authorisation of coercive enforcement mechanisms is a conceptually necessary feature of law. It then claims that the best way to understand the law is as coercion‐apt. The “coercion‐aptness” of law is clarified, in part, by appealing to an essential distinction between law and morality: Whereas it can be reasonable for the law to appeal to coercive means in order to motivate compliance, it seems decidedly unreasonable for morality to do so.
Regulatory reform in the era of new technological development: The role of organizational factors in the public sector
Authors: Park Soonae , Lee Don S. , Son Jieun
Published: July 2020

What is the role of organizational factors in fostering regulatory reform in response to new technological development? Existing studies provide useful frameworks to understand regulatory reform in rapidly changing circumstances but still lack a systematic analysis of how organizational factors affect regulatory reform in the public sector. To fill this gap, we examine the impact of several institutional elements that are central to defining organizational characteristics, such as job tasks, bureaucratic autonomy, and organizational culture. We theorize that regulatory reform is more likely when public sector organizations are more receptive to external changes, which are determined by these characteristics. We leverage original surveys from over 1,000 civil servants in Korea, one of the front runners in new technological development, and find support for our prediction. We find that the implementation of regulatory reforms is more likely when (i) organizational tasks are relevant to scientific and technological development, (ii) higher levels of bureaucratic autonomy are granted, (iii) agency heads demonstrate stronger leadership, and (iv) organizational culture is less authoritarian. Our study makes clear contributions to the literature on public management and regulation theory, and has important implications for regulatory reform in the face of new technological development.
Por uma Igreja com rosto amazônico. Implicações e tarefas
Authors: Brighenti Agenor
Published: July 2020

Uma Igreja com rosto amazônico é uma aspiração dos cristãos da floresta, ribeirinhos e das zonas urbanas, em uma região portadora de desafios que transcendem as próprias fronteiras. Por isso, o Sínodo da Amazônia levanta questões e acena tarefas para a Igreja como um todo. A pluriculturalidade e a pluri-religiosidade de seus povos desafia o cristianismo a expressar-se em uma eclesialidade pluriforme, respeitosa e acolhedora das diferenças. Isso só é possível com a configuração de igrejas autóctones, que tenham na inculturação da fé o referencial da evangelização. Por sua vez, igrejas culturalmente novas colocam o imperativo de uma consequente “conversão pastoral da Igreja” como um todo, incluídas suas estruturas.
Experiential Learning From a Classroom Desk: Exploring Student Perceptions of Applied Coursework
Authors: DeLuca Jaime R. , Fornatora Emily
Published: July 2020

Experiential learning promotes the development of a variety of skill competencies that will better prepare sport management students to enter the industry. In order to maximize opportunities for experiential learning, many sport management curricula incorporate applied coursework options in addition to internships, because the classroom serves as an important conduit for preprofessional learning in which faculty can both supervise and mentor students. It has become increasingly important to delineate the pedagogical and professional value of students’ experience of applied learning, because more programs have integrated these types of experiences into coursework; however, there has been limited research exploring this topic. Anchored in qualitative-data collection with students enrolled in four different applied courses, this research identifies three themes—curricular freedom, skill development, and relationship building—that highlight the categorical benefits and nuanced mechanisms through which knowledge is transferred in and through applied coursework.
Cystathione β-synthase regulates HIF-1α stability through persulfidation of PHD2
Authors: Dey Anindya , Prabhudesai Shubhangi , Zhang Yushan , Rao Geeta , Thirugnanam Karthikeyan , Hossen Md. Nazir , Dwivedi Shailendra Kumar Dhar , Ramchandran Ramani , Mukherjee Priyabrata , Bhattacharya Resham
Published: July 2020

A novel nexus of PHD2, HIF-1α, and CBS is found, which coordinately regulates PHD2 activity and hence HIF-1α stability.
Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy
Authors: Au Kin Man , Park Steven I. , Wang Andrew Z.
Published: July 2020

A trispecific natural killer cell engager platform has been successfully engineered for EGFR-targeted chemoimmunotherapy.
Fumarolic-like activity on carbonaceous chondrite parent body
Authors: Ganino Clément , Libourel Guy
Published: July 2020

First analogy between carbonaceous chondrite parent bodies metamorphism and high-temperature Kudryavy volcano fumaroles bodies.
General description for nonequilibrium steady states in periodically driven dissipative quantum systems
Authors: Ikeda Tatsuhiko N. , Sato Masahiro
Published: July 2020

We derive a generic solution for nonequilibrium steady states in periodically driven (Floquet) quantum systems.
Characterization of Large Deletion Mutants of Mycobacterium tuberculosis Selected for Isoniazid Resistance
Authors: Vilchèze Catherine , Saranathan Rajagopalan , Weinrick Brian , Jacobs William R.
Published: July 2020

Large genomic deletions (LGDs) (6 to 63 kbp) were observed in isoniazid-resistant
Mycobacterium tuberculosis
mutants derived from four
M. tuberculosis
strains. These LGDs had no growth defect
in vitro
but could be defective in intracellular growth and showed various sensitivities toward oxidative stress despite lacking
katG
. The LGD regions comprise 74 genes, mostly of unknown function, that may be important for
M. tuberculosis
intracellular growth and protection against oxidative stress.
Use of a Fluorescence-Based Assay To Measure Escherichia coli Membrane Potential Changes in High Throughput
Authors: Hudson M. Ashley , Siegele Deborah A. , Lockless Steve W.
Published: July 2020

Bacterial membrane potential is difficult to measure using classical electrophysiology techniques due to the small cell size and the presence of the peptidoglycan cell wall. Instead, chemical probes are often used to study membrane potential changes under conditions of interest. Many of these probes are fluorescent molecules that accumulate in a charge-dependent manner, and the resulting fluorescence change can be analyzed via flow cytometry or using a fluorescence microplate reader. Although this technique works well in many Gram-positive bacteria, it generates fairly low signal-to-noise ratios in Gram-negative bacteria due to dye exclusion by the outer membrane.
Involvement of NO
3
−
in Ecophysiological Regulation of Dissimilatory Nitrate/Nitrite Reduction to Ammonium (DNRA) Is Implied by Physiological Characterization of Soil DNRA Bacteria Isolated via a Colorimetric Screening Method
Authors: Heo Hokwan , Kwon Miye , Song Bongkeun , Yoon Sukhwan
Published: July 2020

Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) is an anaerobic microbial pathway that competes with denitrification for common substrates NO
3
−
and NO
2
−
. Unlike denitrification, which leads to nitrogen loss and N
2
O emission, DNRA reduces NO
3
−
and NO
2
−
to NH
4
+
, a reactive nitrogen compound with a higher tendency to be retained in the soil matrix. Therefore, stimulation of DNRA has often been proposed as a strategy to improve fertilizer efficiency and reduce greenhouse gas emissions. Such attempts have been hampered by lack of insights into soil DNRA bacterial ecophysiology. Here, we have developed a new screening method for isolating DNRA-catalyzing organisms from agricultural soils without apparent DNRA activity. Physiological characteristics of six DNRA isolates were closely examined, disclosing a previously overlooked link between NO
3
−
repression of NO
2
−
-to-NH
4
+
reduction and the C-to-N ratio regulation of DNRA activity, which may be a key to understanding why DNRA activity is rarely observed at substantial levels in nitrogen-rich agricultural soils.
Scnn1b
-Transgenic BALB/c Mice as a Model of Pseudomonas aeruginosa Infections of the Cystic Fibrosis Lung
Authors: Brao Kristen J. , Wille Brendan P. , Lieberman Joshua , Ernst Robert K. , Shirtliff Mark E. , Harro Janette M.
Published: July 2020

The opportunistic pathogen
Pseudomonas aeruginosa
is responsible for much of the morbidity and mortality associated with cystic fibrosis (CF), a condition that predisposes patients to chronic lung infections.
P. aeruginosa
lung infections are difficult to treat because
P. aeruginosa
adapts to the CF lung, can develop multidrug resistance, and can form biofilms. Despite the clinical significance of
P. aeruginosa
, modeling
P. aeruginosa
infections in CF has been challenging.
Who gets referred for knee or hip replacement? A theoretical model of the potential impact of evidence-based referral thresholds using data from a retrospective review of clinic records from an English musculoskeletal referral hub
Authors: Dakin Helen A , Eibich Peter , Gray Alastair , Smith James , Barker Karen L , Beard David , Price Andrew J
Published: July 2020

Objectives

To estimate the relationship between patient characteristics and referral decisions made by musculoskeletal hubs, and to assess the possible impact of an evidence-based referral tool.

Design

Retrospective analysis of medical records and decision tree model evaluating policy changes using local and national data.

Setting

One musculoskeletal interface clinic (hub) in England.

Participants

922 adults aged ≥50 years referred by general practitioners with symptoms of knee or hip osteoarthritis.

Interventions

We assessed the current frequency and determinants of referrals from one hub and the change in referrals that would occur at this centre and nationally if evidence-based thresholds for referral (Oxford Knee and Hip Scores, OKS/OHS) were introduced.

Main outcome measure

OKS/OHS, referrals for surgical assessment, referrals for arthroplasty, costs and quality-adjusted life years.

Results

Of 110 patients with knee symptoms attending face-to-face hub consultations, 49 (45%) were referred for surgical assessment; the mean OKS for these 49 patients was 18 (range: 1–41). Of 101 hip patients, 36 (36%) were referred for surgical assessment (mean OHS: 21, range: 5–44). No patients referred for surgical assessment were above previously reported economic thresholds for OKS (43) or OHS (45). Setting thresholds of OKS ≤31 and OHS ≤35 might have resulted in an additional 22 knee referrals and 26 hip referrals in our cohort. Extrapolating hub results across England suggests a possible increase in referrals nationally, of around 13 000 additional knee replacements and 4500 additional hip replacements each year.

Conclusions

Musculoskeletal hubs currently consider OKS/OHS and other factors when making decisions about referral to secondary care for joint replacement. Those referred typically have low OHS/OKS, and introducing evidence-based OKS/OHS thresholds would prevent few inappropriate (high-functioning, low-pain) referrals. However, our findings suggest that some patients not currently referred could benefit from arthroplasty based on OKS/OHS. More research is required to explore other important patient characteristics currently influencing hub decisions.
Chronic diseases and multimorbidity among unemployed and employed persons in the Netherlands: a register-based cross-sectional study
Authors: Yildiz Berivan , Schuring Merel , Knoef Marike G , Burdorf Alex
Published: July 2020

Objectives

The first objective of this study was to describe the age-specific prevalence of chronic diseases and multimorbidity among unemployed and employed persons. The second objective was to examine associations of employment status and sociodemographic characteristics with chronic diseases and multimorbidity.

Design

Data linkage of cross-sectional nationwide registries on employment status, medication use and sociodemographic characteristics in 2016 was applied.

Setting

Register-based data covering residents in the Netherlands.

Participants

5 074 227 persons aged 18–65 years were selected with information on employment status, medication use and sociodemographic characteristics.

Outcome measures

Multiple logistic regression analysis and descriptive statistics were performed to examine associations of employment and sociodemographic characteristics with the prevalence of chronic diseases and multimorbidity. The age-specific prevalence of six common chronic diseases was described, and Venn diagrams were applied for multimorbidity among unemployed and employed persons.

Results

Unemployed persons had a higher prevalence of psychological disorders (18.3% vs 5.4%), cardiovascular diseases (20.1% vs 8.9%), inflammatory diseases (24.5% vs 15.8%) and respiratory diseases (11.7% vs 6.5%) than employed persons. Unemployed persons were more likely to have one (OR 1.30 (1.29–1.31)), two (OR 1.74 (1.73–1.76)) and at least three chronic diseases (OR 2.59 (2.56–2.61)) than employed persons. Among unemployed persons, psychological disorders and inflammatory conditions increased with age but declined from middle age onwards, whereas a slight increase was observed among employed persons. Older persons, women, lower educated persons and migrants were more likely to have chronic diseases.

Conclusion

Large differences exist in the prevalence of chronic diseases and multimorbidity among unemployed and employed persons. The age-specific prevalence follows a different pattern among employed and unemployed persons, with a relatively high prevalence of psychological disorders and inflammatory conditions among middle-aged unemployed persons. Policy measures should focus more on promoting employment among unemployed persons with chronic diseases.
Comparison of quadriceps setting strength and knee extension strength tests to evaluate lower limb muscle strength based on health-related physical fitness values in elderly people
Authors: Ito Yuki , Aoki Takumi , Sato Takeru , Oishi Kan , Ishii Kojiro
Published: July 2020

Objective

Conventionally, knee extension strength is often used as the indicator for lower limb muscle strength; however, several recent studies have also used quadriceps setting strength. This study aimed to investigate and compare the association of quadriceps setting and knee extension strength with health-related physical fitness.

Methods

We evaluated quadriceps setting strength and isometric knee extension strength in 75 elderly subjects (mean age, 76.8±5.3 years) to determine their lower limb muscle strength. Health-related physical fitness was evaluated using the physical fitness test advocated by the Ministry of Education and Culture, Sports, Science and Technology in Japan. The test consists of the following components: grip strength, sit-up, sit and reach, one leg standing with eyes open, 10 m obstacle walk and 6 min walk.

Results

When adjusted for age, sex and body mass index, quadriceps setting strength was significantly correlated with grip strength, number of sit-ups, sit and reach distance, 10 m obstacle walking time and 6 min walking distance. In contrast, knee extension strength was associated only with grip strength and number of sit-ups.

Conclusion

More health-related physical fitness parameters with quadriceps setting strength than knee extension strength. Quadriceps setting strength may be superior to knee extension strength as a predictor of health-related physical fitness.
Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care
Authors: Lyckhage Louise Feldborg , Hansen Morten Lock , Toft Jens Christian , Larsen Susanne Lis , Brendorp Bente , Ali Ari Mohammad , Wienecke Troels
Published: July 2020

Background and purpose

The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor.

Methods

Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline.

Results

7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14–37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)).

Conclusions

A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.
Fibroblast activation protein-targeted-4-1BB ligand agonist amplifies effector functions of intratumoral T cells in human cancer
Authors: Trüb Marta , Uhlenbrock Franziska , Claus Christina , Herzig Petra , Thelen Martin , Karanikas Vaios , Bacac Marina , Amann Maria , Albrecht Rosemarie , Ferrara-Koller Claudia , Thommen Daniela , Rothschield Sacha , Savic Prince Spasenija , Mertz Kirsten D , Cathomas Gieri , Rosenberg Robert , Heinzelmann-Schwarz Viola , Wiese Mark , Lardinois Didier , Umana Pablo , Klein Christian , Laubli Heinz , Kashyap Abhishek S , Zippelius Alfred
Published: July 2020

Background

The costimulatory receptor 4-1BB (CD137, TNFRSF9) plays an important role in sustaining effective T cell immune responses and is investigated as target for cancer therapy. Systemic 4-1BB directed therapies elicit toxicity or low efficacy, which significantly hampered advancement of 4-1BB-based immunotherapy. Therefore, targeted delivery of 4-1BB agonist to the tumor side is needed for eliciting antitumor efficacy while avoiding systemic toxicity.

Methods

We analyzed the immunostimulatory properties of a fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL) by assessing tumor-infiltrating lymphocytes’ (TIL) activity from patients with non-small cell lung cancer and epithelial ovarian cancer.

Results

Combination treatment with FAP-4-1BBL and T cell receptor stimulation by either anti-CD3 or T cell bispecific antibodies significantly enhanced TIL activation and effector functions, including T cell proliferation, secretion of proinflammatory cytokines and cytotoxicity. Notably, costimulation with FAP-4-1BBL led to de novo secretion of interleukin (IL)−13. This was associated with cytokine-mediated tumor cell apoptosis, which was partially dependent on IL-13 alpha 1/2 receptors and STAT6 phosphorylation.

Conclusions

Our study provides mechanistic insights into T cell stimulation induced by FAP-4-1BBL in primary human tumors and supports the investigation of FAP-4-1BBL compound in early clinical trials.
How the Cerebellum and Prefrontal Cortex Cooperate During Trace Eyeblinking Conditioning
Authors: Caligiore Daniele , Mirino Pierandrea
Published: July 2020

Several data have demonstrated that during the widely used experimental paradigm for studying associative learning, trace eye blinking conditioning (TEBC), there is a strong interaction between cerebellum and medial prefrontal cortex (mPFC). Despite this evidence, the neural mechanisms underlying this interaction are still not clear. Here, we propose a neurophysiologically plausible computational model to address this issue. The model is constrained on the basis of two critical anatomo-physiological features: (i) the cerebello-cortical organization through two circuits, respectively, targeting M1 and mPFC; (ii) the different timing in the plasticity mechanisms of these parallel circuits produced by the granule cells time sensitivity according to which different subpopulations are active at different moments during conditioned stimuli. The computer simulations run with the model suggest that these features are critical to understand how the cooperation between cerebellum and mPFC supports motor areas during TEBC. In particular, a greater trace interval produces greater plasticity changes at the slow path synapses involving mPFC with respect to plasticity changes at the fast path involving M1. As a consequence, the greater is the trace interval, the stronger is the mPFC involvement. The model has been validated by reproducing data collected through recent real mice experiments.
The holotype of
Psephodus minutus
, Wellburn, 1901 (chondrichthyes, cochliodontiformes) is a gastropod steinkern
Authors: Itano Wayne M.
Published: July 2020

The holotype of
Psephodus minutus
Wellburn, from the Millstone Grit Group (Carboniferous, Lower Pennsylvanian Series, Marsdenian Substage) of Lancashire (now Greater Manchester), England, was originally interpreted as a set of three articulated tooth plates of a chondrichthyan fish. No figure was published with the description, though a drawing was published 32 years later. Examination of the specimen shows it to be a steinkern of an indeterminate high-spired gastropod.
Psephodus minutus
is thus rendered as a
nomen nudum
.
Geological model for the Menai Strait tunnel
Authors: Sandford K. , Mason G.
Published: July 2020

A 400 kV electricity transmission line is required to cross the Menai Strait to connect the proposed Wylfa Newydd nuclear power station on Ynys Mon (also known as Anglesey) with the mainland. Through an initial feasibility study, the preferred Menai Strait crossing option has been shown to require the construction of a tunnel. This region has a complex geological history, where the oldest strata, consisting of schist and tuff deposits, are interpreted as Precambrian. There are also Carboniferous bedrocks of interbedded limestones, mudstones and sandstones, and Ordovician siltstones and quartzite sandstones. The superficial deposits and landforms are understood to be almost entirely the signature of the last Devensian glaciation, except for occasional deposits and landforms resulting from fluctuations in sea-level. A 3D geological model has been created using published geological records and project-specific surveys, including field surveys, rock exposure mapping, ground investigations and geophysical surveys. This allows the visualization of the anticipated geology of the area, the identification of geological hazards and efficient design and planning for construction.

Thematic collection:
This article is part of the Ground models in engineering geology and hydrogeology collection available at:
https://www.lyellcollection.org/cc/Ground-models-in-engineering-geology-and-hydrogeology

Supplementary material
: An overview video is available at
https://doi.org/10.6084/m9.figshare.c.5045048
Cheiracanthid acanthodians from the lower fossil fish-bearing horizons (Eifelian, Middle Devonian) of the Orcadian Basin, Scotland
Authors: Burrow Carole J. , Newman Michael J. , den Blaauwen Jan L.
Published: July 2020

Vertebrate fossils are extremely rare below the Achanarras fish beds and equivalent strata in northern Scotland. Here we describe the cheiracanthid acanthodians from the lowest Middle Devonian of this region, comprising partial articulated specimens and squamation patches of two species
Cheiracanthus flabellicostatus
and
C. brevicostatus
. Both species were previously only known as isolated scales from the eastern Baltic and Russia. The stratigraphic range of the two species in Scotland extends up into the Achanarras equivalent fish beds in the Moray Firth.