bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward efficient photocatalysts for light-driven CO2 reduction: TiO2 nanostructures decorated with perovskite quantum dots
Authors: Liu Yunju , Lee Chen-Chin , Horn Mark W , Lee Hyeonseok
Published: March 2021

Nanostructured TiO2 is often used for photocatalytic CO2 conversion due to its favorable electronic properties and stability, being coupled with large surface area and unique electrical properties. However, pure TiO2, without any expensive cocatalysts, can not provide highly efficient CO2 conversion because its bandgap and resulted limited numbers of photogenerated electrons and holes limit efficient energy conversion. Here, we demonstrate TiO2 nanotube (TNT) photocatalysts equipped with two different perovskite quantum dots (PQDs) made of CH3NH3PbBr3 and CH3NH3PbI3. The fundamental properties of the PQDs and TNT/PQD photocatalysts are investigated and their potential for more efficient CO2 conversion are discussed, to our best knowledge, for the first time. TNT/CH3NH3PbI3 QD photocatalysts absorb a wider range of light energy and show superior charge transport characteristics due to less sensitivity against surface states at TNT/CH3NH3PbI3 QD interface than the TNT/CH3NH3PbBr3 photocatalysts.
New SAV-pressure correction methods for the Navier-Stokes equations: stability and error analysis
Authors: Li Xiaoli , Shen Jie , Liu Zhengguang
Published: March 2021

We construct new first- and second-order pressure correctionschemes using the scalar auxiliary variable approach for the Navier-Stokes equations. These schemes are linear, decoupled and only require solving a sequence of Poisson type equations at each time step. Furthermore, they are unconditionally energy stable. We also establish rigorous error estimates in the two dimensional case for the velocity and pressure approximation of the first-order scheme without any condition on the time step.
Obtaining Prevalence Estimates of Coronavirus Disease 2019: A Model to Inform Decision-Making
Authors: Sahlu Ida , Whittaker Alexander B
Published: March 2021

We evaluated whether randomly sampling and testing a set number of individuals for coronavirus disease 2019 (COVID-19) while adjusting for misclassification error captures the true prevalence. We also quantified the impact of misclassification error bias on publicly reported case data in Maryland. Using a stratified random sampling approach, 50,000 individuals were selected from a simulated Maryland population to estimate the prevalence of COVID-19. We examined the situation when the true prevalence is low (0.07%–2%), medium (2%–5%), and high (6%–10%). Bayesian models informed by published validity estimates were used to account for misclassification error when estimating COVID-19 prevalence. Adjustment for misclassification error captured the true prevalence 100% of the time, irrespective of the true prevalence level. When adjustment for misclassification error was not done, the results highly varied depending on the population’s underlying true prevalence and the type of diagnostic test used. Generally, the prevalence estimates without adjustment for misclassification error worsened as the true prevalence level increased. Adjustment for misclassification error for publicly reported Maryland data led to a minimal but not significant increase in the estimated average daily cases. Random sampling and testing of COVID-19 are needed with adjustment for misclassification error to improve COVID-19 prevalence estimates.
A Data-Based Approach to Evaluating Representation by Gender and Affiliation in Key Presentation Formats at the Annual Meeting of the Society for Epidemiologic Research
Authors: Nobles Carrie J , Lu Ya-Ling , Andriessen Victoria C , Bevan Suzanne S , Radoc Jeannie G , Alkhalaf Zeina , Schisterman Enrique F
Published: March 2021

The annual meeting of the Society for Epidemiologic Research (SER) is a major forum for sharing new research and promoting the career development of participants. Because of this, evaluating representation in key presentation formats is critical. For the 3,257 presentations identified at the 2015–2017 SER annual meetings, we evaluated presenter characteristics, including gender, affiliation, subject area, and h-index, and representation in 3 highlighted presentation formats: platform talks (n = 382), invited symposium talks (n = 273), and chairing a concurrent contributed session or symposium (n = 188). Data were abstracted from SER records, abstract booklets, and programs. Gender was assessed using GenderChecker software, and h-index was determined using the Scopus application programming interface. Log-binomial models were adjusted for participant characteristics and conference year. In adjusted models, women were less likely than men to present an invited symposium talk (relative risk = 0.60, 95% confidence interval: 0.45, 0.81) compared with all participants with accepted abstracts. Researchers from US public universities, US government institutions, and international institutions were less likely to present a symposium talk or to chair a concurrent contributed session or symposium than were researchers from US private institutions. The research areas that were most represented in platform talks were epidemiologic methods, social epidemiology, and cardiovascular epidemiology. Our findings suggest differences in representation by gender, affiliation, and subject area after accounting for h-index.
Perceived Intensity and Palatability of Fatty Culinary Preparations is Associated with Individual Fatty Acid Detection Threshold and the Fatty Acid Profile of Oils Used as Ingredients
Authors: Tarragon Ernesto , Cases Ceano-Vivas Pere , Gonzalez-Ogazón Pol , Moreno Juan José
Published: March 2021

The term oleogustus was recently proposed to describe a sixth basic taste that could guide preference for fatty foods and dishes to an extent. However, experimental data on food preference based on fatty acid (FA) content is scarce. Our aim was to examine the role of FA profile of oils and preparations as well as FA sensory thresholds on the palatability of salty and sweet culinary preparations representative of traditional Spanish Mediterranean cooking. In this study, we used three oils with similar texture and odor profile but different in their FA composition (saturated, monounsaturated, and polyunsaturated) and compared subjects in regard to their FA detection threshold and perceived pleasantness and intensity. Our results indicate that whereas saturated FAs cannot be detected at physiological concentrations, individuals can be categorized as tasters and nontasters, according to their sensory threshold to linoleic acid, which is negatively associated with perceived intensity (r = –0.393, P < 0.001) but positively with palatability (r = 0.246, P = 0.018). These differences may be due to a possible response to a fat taste. This sixth taste, or oleogustus. would allow establishing differences in taste intensity/palatability considering the FA profile of the culinary preparations. Given that tasters can detect linoleic and oleic acid at lower concentrations than nontasters, a greater amount of unsaturated FAs in culinary preparations could provoke an unpleasant experience. This finding could be relevant in the context of the culinary sector and to further our understanding of food preference and eating behavior.
A Novel Liquid Chromatographic Method for the Quantitative Determination of Degradation Products in Remdesivir Injectable Drug product
Authors: Reddy H Ramakrishna , Pratap S R , Chandrasekhar N , Shamshuddin S Z M
Published: March 2021

An effectual and stability signifying technique has been validated for the quantitative verification of degradation products in Remdesivir Injectable pharmaceutical products by employing high-performance liquid chromatography with ultraviolet detector. The process was optimized by using an octyldecylsilane chemically bonded column (Kromasil KR100-5 C18; USP L1 phase) with dimensions; 250 mm length × 4.5 mm inner diameter and 5-μm particle size. The method was validated as per International Conference on Harmonization and other current regulatory guidelines for analytical method validation. The anticipated process was found to be robust, accurate, specific, linear, precise, stable and rugged in the concentration ranging from quantification level to 200% of the specification level of specified and unknown degradation impurities. The technique was effectively applied to analyze degradation products in Remdesivir Injectable drug products.
Joint EAPCI/ACVC expert consensus document on percutaneous ventricular assist devices
Authors: Chieffo Alaide , Dudek Dariusz , Hassager Christian , Combes Alain , Gramegna Mario , Halvorsen Sigrun , Huber Kurt , Kunadian Vijay , Maly Jiri , Møller Jacob Eifer , Pappalardo Federico , Tarantini Giuseppe , Tavazzi Guido , Thiele Holger , Vandenbriele Christophe , van Mieghem Nicolas , Vranckx Pascal , Werner Nikos , Price Susanna
Published: March 2021

There has been a significant increase in the use of short-term percutaneous ventricular assist devices (pVADs) as acute circulatory support in cardiogenic shock and to provide haemodynamic support during interventional procedures, including high-risk percutaneous coronary interventions. Although frequently considered together, pVADs differ in their haemodynamic effects, management, indications, insertion techniques, and monitoring requirements. This consensus document summarizes the views of an expert panel by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and the Association for Acute Cardiovascular Care (ACVC) and appraises the value of short-term pVAD. It reviews the pathophysiological context and possible indications for pVAD in different clinical settings and provides guidance regarding the management of pVAD based on existing evidence and best current practice.
Silent embolism of a large thrombus in transit through the patent foramen ovale: a case report
Authors: Hegde Shruti , Kabadi Mitesh , Johnstone Michael
Published: March 2021

Background 

Detection of a thrombus in transit through a patent foramen ovale (PFO) is extremely rare due to the transient nature of the process. We report an unusual case of a large, paradoxical embolus in transit seen on echocardiography through a PFO that was not found upon atriotomy.

Case summary 

An 80-year-old woman presented to the emergency room with shortness of breath and right leg pain. She was haemodynamically stable on presentation, and her physical exam was unremarkable. An ultrasound of her right leg revealed a deep vein thrombus in the posterior tibial vein, and chest computed tomography angiography showed saddle pulmonary emboli. Transthoracic echocardiogram identified a large thrombus in transit through a PFO, which was confirmed with a transoesophageal echocardiogram (TOE). She underwent an emergency embolectomy. The thrombus in transit was confirmed by TOE prior to bypass initiation; however, no thrombi were found in any chambers of the heart following atriotomy. Her postoperative recovery was uneventful. She had no focal neurological deficits or any apparent signs of large vessel embolization.

Discussion

Cases of silent embolism have been reported in the literature, although they are rare. To our knowledge, this is the first case of a large thrombus in transit through a PFO in an elderly female that was confirmed by an intra-operative TOE but could not be found following atriotomy, with no obvious clinical signs of embolization.
Joint effects of HPV-related knowledge and socio-demographic factors on HPV testing behaviour among females in Shenzhen
Authors: Lin Wei , Chen Bin , Hu Haiyan , Yuan Shixin , Wu Bo , Zhong Chuyan , Huang Weikang , Liu Zhihua , Wang Yueyun
Published: March 2021

Background

Limited population-based studies explore the utilization and associated barriers or facilitators to cervical cancer screening in China. We attempted to investigate the associations of socio-demographic factors, HPV specific knowledge with HPV testing behaviour in Shenzhen, China.

Methods

A citywide cross-sectional survey was conducted from January to June 2015 in Shenzhen city by using a multistage stratified cluster sampling method. Socio-demographic information, awareness and specific knowledge of HPV, practice of HPV testing, and HPV vaccination-related attitude were collected. Multivariate logistic regression model was used to analyse possible associations.

Results

Approximately one third of total 8639 women aged from 30 to 60 years old had ever received HPV testing. Overall, 67.6% of all participants demonstrated low knowledge level of HPV. High HPV knowledge level was significantly associated with HPV testing behaviour (odds ratio: 3.792, 95% confidence interval: 3.400–4.230). The impact of residence and education on testing behaviour only turned to be significant if women had low level of HPV knowledge (P for multiplicative interactions: 0.001 and <0.001, respectively), whereas monthly income exerted promotion effects apparently among those with high knowledge level (P for multiplicative interaction: 0.037).

Conclusions

Our study revealed gaps in HPV knowledge and screening participation among Chinese women, and provided novel clues that women with high HPV knowledge level would be more appeal to involve in HPV testing behaviour. The influence of HPV-related knowledge on HPV testing also lies in the joint effects with socio-demographic factors, including residence, education and monthly income.
The adaptation of the ‘Healthcare Complaints Analysis Tool’ for general practice
Authors: O’Dowd Emily , Lydon Sinéad , O’Connor Paul
Published: March 2021

Background

Patient complaints about care in general practice are underutilized as a source of safety improvement data.

Objective

This study aimed to adapt a secondary care complaints analysis tool for use in general practice contexts and assess the validity, reliability and usability of the adapted tool.

Methods

The study was conducted in two phases. Phase A: The Healthcare Complaints Analysis Tool (HCAT) designed for use in secondary care was adapted for use in general practice using an iterative six-stage process. Phase B: Participants from key stakeholder groups [General practitioners (n = 5), complaints managers (n = 9), health service researchers (n = 4)]. Participants completed an online survey and analysed 20 fictionalized patient complaints using the adapted tool. Inter-rater reliability and agreement with a referent standard were analysed using Gwet’s AC1 statistic.

Results

Phase A: The HCAT was adapted to the Healthcare Complaints Analysis Tool (General Practice) [HCAT(GP)]. The HCAT(GP) tool consists of three domains (clinical, management and relationship problems), and seven categories. The HCAT(GP) had both content and face validity. Phase B: Inter-rater reliability was substantial for the HCAT(GP) categories (Gwet’s AC1 = 0.65). Within-group agreement on the seven HCAT(GP) categories was substantial to perfect (AC1 0.61–0.85). Participants had substantial to perfect agreement with the referent standard across the survey with a mean AC1 of 0.899 (Range 0.76–0.97).

Conclusions

This study reports the adaptation of the HCAT(GP) and has established that the tool has sufficient validity, reliability and usability. This adapted tool can be applied to general practice complaints to identify areas for improvement.
Gap and stand structural characteristics in a managed and an unmanaged old-growth oriental beech (Fagus orientalisLipsky) forest
Authors: Parhizkar Pejman , Sagheb-Talebi Khosro , Zenner Eric K , Hassani Majid , Sadeghzadeh Hallaj Mohammad Hosein
Published: March 2021

Simplified forest structures following even-age management have been associated with the loss of biodiversity, which may be avoided through disturbance-inspired silviculture. Here, we ask how much do gap characteristics in a managed old-growth differ from those in unmanaged old-growth subject only to natural dynamics? In this study, we compared important characteristics of gaps (e.g. canopy gap fraction, distribution of gap sizes) and gapmakers (e.g. size classes, frequency, decay classes) between a managed and an adjacent unmanaged old-growth Oriental beech (Fagus orientalis Lipsky) compartment in the Keladarsht region of northern Iran 10 years after a single harvest entry using single-tree selection. Canopy openings >100 m2 with visible remnants of gapmakers (i.e. stumps) were included in this study. Gap characteristics of both compartments were within typical ranges for old-growth beech. Nonetheless, small but potentially important differences between the two areas were observed. In the managed compartment, harvesting poor quality trees with structural defects and typical diameters at breast height >52.5 cm plus natural mortality resulted in 102 canopy gaps (1–6 gapmakers, averaging 3.5 gaps/ha, gap fraction 9.8 per cent) compared with 59 natural canopy gaps (1–7 gapmakers, averaging 2.6 gaps/ha, gap fraction 13.7 per cent) in the unmanaged compartment. In both compartments, medium-sized gaps (200–500 m2) were most prevalent. In the managed compartment, 60 per cent of gapmakers were large or very large (typically cut) compared with 39 per cent in the unmanaged compartment where large trees typically snapped and became snags. Uprooting, particularly of small and medium sized gapmakers, was less common in the managed than the unmanaged compartment. Our results indicate that even one single-tree selection harvest may lead to a short-term divergence in stand structure compared with the unmanaged forest. While such managed forests may no longer be considered as old-growth, divergences in canopy gap characteristics indicate that a more nuanced harvesting scheme that includes cutting some larger gaps may more closely mimic the canopy dynamics of this old-growth forest.
Single-cell data clustering based on sparse optimization and low-rank matrix factorization
Authors: Hu Yinlei , Li Bin , Chen Falai , Qu Kun
Published: March 2021

Unsupervised clustering is a fundamental step of single-cell RNA-sequencing (scRNA-seq) data analysis. This issue has inspired several clustering methods to classify cells in scRNA-seq data. However, accurate prediction of the cell clusters remains a substantial challenge. In this study, we propose a new algorithm for scRNA-seq data clustering based on Sparse Optimization and low-rank matrix factorization (scSO). We applied our scSO algorithm to analyze multiple benchmark datasets and showed that the cluster number predicted by scSO was close to the number of reference cell types and that most cells were correctly classified. Our scSO algorithm is available at https://github.com/QuKunLab/scSO. Overall, this study demonstrates a potent cell clustering approach that can help researchers distinguish cell types in single- scRNA-seq data.
Simplified equations for lower crustal flow driven by lateral pressure gradients
Authors: Perry-Houts Jonathan , Humphreys Eugene
Published: March 2021

Evidence from seismology, geology and geodynamic studies suggests that regional-scale lower crustal flow occurs in many tectonic settings. Pressure gradients caused by mantle processes and crustal density heterogeneity can provide driving force for lower crustal flow. Numerically modelling such flow can be computationally expensive. However, by exploiting symmetry in the physical system, it is possible to represent the vertical component of flow in terms of its lateral components, thereby reducing the problem’s spatial dimension by one. Here, we present a mathematical formulation for flow in a viscous channel below an elastic upper plate, which is optimized for solution by common numerical methods. Our formulation drastically reduces the computational load required to simulate lower crustal flow over large areas and long timescales. We apply this model to two example problems, with and without an elastic upper plate, identifying combinations of parameters that are capable of generating measurable geologic uplift.
Spectrum of strong-motion records for large magnitude Chilean earthquakes
Authors: Rivera Efraín , Ruiz Sergio , Madariaga Raúl
Published: March 2021

We studied the broad-band spectra of the eight largest earthquakes that have occurred in Chile in the last 25 yr using strong-motion records and 1-Hz high-rate GNSS (cGNSS) data. To avoid the numerical instability problem with the double integration of the accelerograms, we computed velocity spectra integrating the acceleration time-series in the spectral domain and compared them to time-differentiated the cGNSS displacement records. To compute the velocity spectrum, we used a multitaper algorithm so as to provide stability over the entire spectral band. We found that the velocity spectra of records obtained close to the main rupture of the earthquakes are different from classical Aki and Brune spectra. The velocity spectrum of large events in Chile presents a flat trend at low frequencies produced by the near-field waves. This trend converges at low frequencies to the static displacement as determined from GNSS data. For different magnitude earthquakes, we observe a transition in the ground-velocity spectrum from a decay of ${f^{ - 1}}$ at high frequencies and a flat trend at low frequencies to a more classical model with a peak at the corner frequency. The source-station distance influences the shape of the velocity spectrum at low frequencies, but there is no simple rule for the records available at present. At intermediate frequencies, the spectra are controlled by surface waves and S waves. We found a transition in the velocity spectrum for the 2014 Iquique earthquake, which indicates a change in the decay of the spectrum for stations at distances greater than ∼200 km. Finally, we show that the flat low-frequency trend of the velocity spectra determined from accelerograms, and the peak ground-displacement (PGD) determined from GNSS data scales with the moment to the power 2/3.
Loss of ten-eleven translocation 2 induces cardiac hypertrophy and fibrosis through modulating ERK signaling pathway
Authors: Tao Huikang , Xu Weize , Qu Wenzheng , Gao Hui , Zhang Jinyu , Cheng Xuejun , Liu Ning , Chen Jinghai , Xu Guo-Liang , Li Xuekun , Shu Qiang
Published: March 2021

The ten-eleven translocation (Tet) family of dioxygenases convert 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC-mediated epigenetic modifications play essential roles in diverse biological processes and diseases. Here, we show that Tet proteins and 5hmC display dynamic features during postnatal cardiac development and that Tet2 is the predominant dioxygenase present in heart. Tet2 knockout results in abnormal cardiac function, progressive cardiac hypertrophy and fibrosis. Mechanistically, Tet2 deficiency leads to reduced hydroxymethylation in the cardiac genome and alters the cardiac transcriptome. Mechanistically, Tet2 loss leads to a decrease of Hspa1b expression, a regulator of the extracellular signal-regulated protein kinase (Erk) signaling pathway, which leads to over-activation of Erk signaling. Acute Hspa1b knock down (KD) increased the phosphorylation of Erk and induced hypertrophy of cardiomyocytes, which could be blocked by Erk signaling inhibitor. Consistently, ectopic expression of Hspa1b was able to rescue the deficits of cardiomyocytes induced by Tet2 depletion. Taken together, our study’s results reveal the important roles of Tet2-mediated DNA hydroxymethylation in cardiac development and function.
Spontaneous seizures and elevated seizure susceptibility in response to somatic mutation of sodium channel Scn8a in the mouse
Authors: Yu Wenxi , Smolen Corrine E , Hill Sophie F , Meisler Miriam H
Published: March 2021

De novo mutations of neuronal sodium channels are responsible for ~5% of developmental and epileptic encephalopathies, but the role of somatic mutation of these genes in adult-onset epilepsy is not known. We evaluated the role of post-zygotic somatic mutation by adult activation of a conditional allele of the pathogenic variant Scn8aR1872W in the mouse. After activation of CAG-Cre-ER by tamoxifen, the mutant transcript was expressed throughout the brain at a level proportional to tamoxifen dose. The threshold for generation of spontaneous seizures was reached when the proportion of mutant transcript reached 8% of total Scn8a transcript, equivalent to expression of the epileptogenic variant in 16% of heterozygous neurons. Expression below this level did not result in spontaneous seizures, but did increase susceptibility to seizure induction by kainate or auditory stimulation. The relatively high threshold for spontaneous seizures indicates that somatic mutation of sodium channels is unlikely to contribute to the elevated incidence of epilepsy in the elderly population. However, somatic mutation could increase susceptibility to other seizure stimuli.
mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion
Authors: Taylor Henry , Yerlioglu Dilay , Phen Claudia , Ballauff Antje , Nedelkopoulou Natalia , Spier Isabel , Loverdos Inés , Busoni Veronica B , Heise Jürgen , Dale Peter , de Meij Tim , Sweet Kevin , Cohen Marta C , Fox Victor L , Mas Emmanuel , Aretz Stefan , Eng Charis , Buderus Stephan , Thomson Mike , Rojas Isabel , Uhlig Holm H
Published: March 2021

Ultra-rare genetic disorders can provide proof of concept for efficacy of targeted therapeutics and reveal pathogenic mechanisms relevant to more common conditions. Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A). Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate. No effective pharmacological therapy exists. A multi-center cohort analysis was performed to characterize phenotype and investigate the therapeutic effect of mammalian target of rapamycin (mTOR) inhibition (adverse events, disease progression, time to colectomy and mortality) in patients with JPI. Among 25 JPI patients identified (mean age of onset 13 months), seven received mTOR inhibitors (everolimus, n = 2; or sirolimus, n = 5). Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07–0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077). Long-term mTOR inhibitor treatment was well tolerated over an accumulated follow-up time of 29.8 patient years. No serious adverse events were reported. Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI. Inhibition of the phosphoinositol-3-kinase–AKT–mTOR pathway mitigates the detrimental synergistic effects of combined PTEN–BMPR1A deletion. This is the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome.
Collecting New Peak and Intermediate Infliximab Levels to Predict Remission in Inflammatory Bowel Diseases
Authors: Liefferinckx Claire , Bottieau Jérémie , Toubeau Jean-François , Thomas Debby , Rahier Jean-François , Louis Edouard , Baert Filip , Dewint Pieter , Pouillon Lieven , Lambrecht Guy , Vallée François , Vermeire Severine , Bossuyt Peter , Franchimont Denis
Published: March 2021

Background

The loss of response to infliximab is a challenge for clinicians in the management of inflammatory bowel disease (IBD). Mounting evidence suggests that therapeutic drug monitoring at induction may predict remission during maintenance. The aim of the study was to improve predictive models of remission by exploring new peak and intermediate infliximab measurements during induction.

Methods

This was a prospective multicenter study evaluating the pharmacokinetics of infliximab during induction in a pioneer cohort of 63 patients with IBD. Pharmacokinetics data including peak, intermediate, and trough levels were combined with clinical and biological parameters and were subsequently fed into tailored logistic regression and tree-based techniques to predict remission at week 30.

Results

Infliximab peak levels at week 2, intermediate levels at week 3, and trough levels at week 6 were correlated with remission at week 30. Predictive models exhibited an increased accuracy over the successive timepoints of the induction with key inputs such as albumin, C-reactive protein, eosinophils, neutrophils, lymphocytes, intermediate level at week 3, trough level at week 6, and age at diagnosis. Our predictive model of remission at week 30 was obtained with an area under the receiver operating characteristic curve of 0.9 ± 0.12, a sensitivity of 89%, and a specificity of 75%.

Conclusions

This study showed the clinical relevance of measuring new infliximab levels to predict remission in patients with IBD. These findings lay the foundation for a personalized medicine in which biotherapies could be monitored at an early stage, thereby improving patients’ clinical management.
Light at Night and Disrupted Circadian Rhythms Alter Physiology and Behavior
Authors: Bumgarner Jacob R , Nelson Randy J
Published: March 2021

Life on earth has evolved during the past several billion years under relatively bright days and dark nights. Virtually all organisms on the planet display an internal representation of the solar days in the form of circadian rhythms driven by biological clocks. Nearly every aspect of physiology and behavior is mediated by these internal clocks. The widespread adoption of electric lights during the past century has exposed animals, including humans, to significant light at night (LAN) for the first time in our evolutionary history. Importantly, endogenous circadian clocks depend on light for synchronization with the external daily environment. Thus, LAN can derange temporal adaptations. Indeed, disruption of natural light–dark cycles results in several physiological and behavioral changes. In this review, we highlight recent evidence demonstrating how LAN exposure can have serious implications for adaptive physiology and behavior, including immune, endocrine, and metabolic function, as well as reproductive, foraging, and migratory behavior. Lastly, strategies to mitigate the consequences of LAN on behavior and physiology will be considered.
External validity and clinical usefulness of a risk prediction model for 30 day unplanned hospitalization in patients receiving outpatient parenteral antimicrobial therapy
Authors: Durojaiye Oyewole Christopher , Morgan Robin , Chelaghma Naziha , Palit Joyeeta , Keil Christopher , Omer Rasha , Cartwright Katharine , Kritsotakis Evangelos I
Published: March 2021

Objectives

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a variety of infections. However, hospital readmissions remain relatively common. We examined the external validity and clinical usefulness of a previously derived risk prediction model for 30 day unplanned hospitalization in patients receiving OPAT.

Methods

A retrospective cohort study was conducted at two large teaching hospitals in the UK. The design comprised quasi-external temporal validation on patients from the same OPAT setting as the model development, and broader external validation on patients from a different setting. The model predictors were age, prior hospitalizations in the preceding 12 months, Charlson comorbidity score, concurrent IV antimicrobial therapy, type of infection and mode of OPAT treatment. Discriminative ability, calibration and clinical usefulness were assessed.

Results

Data from 2578 OPAT patients were analysed. The rates of 30 day unplanned hospitalization were 11.5% (123/1073), 12.9% (140/1087) and 25.4% (106/418) in the model derivation, temporal validation and broader external validation cohorts, respectively. The discriminative ability of the prediction model was adequate on temporal validation (c-statistic 0.75; 95% CI: 0.71–0.79) and acceptable on broader validation (c-statistic 0.67; 95% CI: 0.61–0.73). In both external cohorts, the model displayed excellent calibration between observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.

Conclusions

A simple risk prediction model for unplanned readmission in OPAT patients demonstrated reproducible predictive performance, broad clinical transportability and clinical usefulness. This model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care.
TPR1, a novel rifampicin derivative, demonstrates efficacy alone and in combination with doxycycline against the NIAID Category A priority pathogen Francisella tularensis
Authors: Cummings Jason E , Slayden Keaton W , Slayden Richard A
Published: March 2021

Background

Francisella tularensis is a highly virulent and contagious Gram-negative intracellular bacterium that causes the disease tularaemia in mammals and is classified as a Category A priority pathogen.

Methods

We utilized a systematic analysis of antibacterial potency, extent of dissemination by analysis of bacterial burden in a secondary vital organ, and survival rates to assess the efficacy of a novel rifampicin derivative, TPR1. The efficacy of TPR1 was evaluated alone and in combination with the standard of care drug, doxycycline, against type A F. tularensis Schu S4 using a lethal pulmonary model of infection in mice.

Results

TPR1 has an MIC value range of 0.125–4 mg/L against reference laboratory strain Schu S4 and a panel of clinical strains. TPR1 alone reduced the bacterial burden in the lungs and spleen at 40 mg/kg and 80 mg/kg, and no antagonism was observed when co-administered with doxycycline. Dosing at 40 mg/kg doxycycline reduced the bacterial burden by 1 log10 cfu in the lungs and 4 log10 cfu in the spleen in comparison to untreated controls. Co-administration of TPR1 and doxycycline demonstrated efficacy upon treatment withdrawal after 4 days of treatment, and 100% survival.

Conclusions

Significantly, TPR1 demonstrated efficacy when delivered alone and in combination with doxycycline, which provides compelling evidence of a superior treatment strategy that would normally rely on a single chemotherapeutic for efficacy. In addition, this work substantiates the use of rifampicin derivatives as a platform for the development of novel treatments to other bacterial agents in addition to tularaemia.
Bidirectional imputation of spatial GPS trajectories with missingness using sparse online Gaussian Process
Authors: Liu Gang , Onnela Jukka-Pekka
Published: March 2021

Objective

We propose a bidirectional GPS imputation method that can recover real-world mobility trajectories even when a substantial proportion of the data are missing. The time complexity of our online method is linear in the sample size, and it provides accurate estimates on daily or hourly summary statistics such as time spent at home and distance traveled.

Materials and Methods

To preserve a smartphone’s battery, GPS may be sampled only for a small portion of time, frequently <10%, which leads to a substantial missing data problem. We developed an algorithm that simulates an individual’s trajectory based on observed GPS location traces using sparse online Gaussian Process to addresses the high computational complexity of the existing method. The method also retains the spherical geometry of the problem, and imputes the missing trajectory in a bidirectional fashion with multiple condition checks to improve accuracy.

Results

We demonstrated that (1) the imputed trajectories mimic the real-world trajectories, (2) the confidence intervals of summary statistics cover the ground truth in most cases, and (3) our algorithm is much faster than existing methods if we have more than 3 months of observations; (4) we also provide guidelines on optimal sampling strategies.

Conclusions

Our approach outperformed existing methods and was significantly faster. It can be used in settings in which data need to be analyzed and acted on continuously, for example, to detect behavioral anomalies that might affect treatment adherence, or to learn about colocations of individuals during an epidemic.
Genetic Analysis of Formosan Subterranean Termite (Blattodea: Rhinotermitidae) Populations in California
Authors: Tseng Shu-Ping , Boone Jason , Boone Lowell , King Natalee , Taravati Siavash , Choe Dong-Hwan , Lee Chow-Yang
Published: March 2021

A new infestation of the Formosan subterranean termite, Coptotermes formosanus Shiraki (Blattodea: Rhinotermitidae), was discovered in Canyon Lake, Riverside County, California. We used three mitochondrial DNA (COI, COII, and 16S) and seven polymorphic microsatellite markers to characterize the genetic relationship of the colony with two other colonies that were collected in 1992 and 2018 in La Mesa, San Diego County. Maximum likelihood phylogeny of C. formosanus based on concatenated COI and COII sequences revealed that the two La Mesa populations (CA01 and CA02) and the Canyon Lake population (CA03) were from different maternal lineages. Based on the 14 COII haplotypes of C. formosanus found world-wide, CA01 and CA02 belonged to a haplotype widely distributed across the United States, while CA03 was grouped under a haplotype predominantly found in Asia. Microsatellite allele frequencies across all loci for both La Mesa populations were relatively similar, but significant genetic differences were found between CA02 and CA03 colonies (FST = 0.24; Dest = 0.30; G″ ST = 0.55; P < 0.01).
Sticking to One’s Guns: Mass Shootings and the Political Economy of Gun Control in the United States
Authors: Yousaf Hasin
Published: March 2021

How do events that highlight a policy issue impact political preferences? In this paper, I analyze the impact of mass shootings on voter behavior. I show that, conditional on population, mass shootings are largely random events. Using a difference-in-differences strategy, I find that mass shootings result in a 1.7 percentage point loss in Republican vote share in counties where they occur. Identification that relies on comparing successful and failed mass shootings yields similar results. Mass shootings lead to an increase in the salience of gun policy and increase the divide on gun policy among both voters and politicians. Democrats (Republicans) tend to demand even stricter (looser) gun control after mass shootings. These results suggest that increasing the salience of an issue may polarize the electorate.
Patterns of immune infiltration in gastric cancer and their clinical significance
Authors: Jin Yin , Tao Liping , Jin Shuqing , Cai Weiyang
Published: March 2021

Objective

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor-infiltrating immune cells activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer immune cell infiltration has not been identified so far.

Methods

In this study, we comprehensively analyzed the tumor-infiltrating immune cells abundance in gastric cancer for the first time by CIBERSORT. The meta-analysis, single-sample gene set enrichment analysis and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. The fraction of tumor-infiltrating immune cells subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes.

Results

Tumor-infiltrating immune cells are extensively involved in the pathogenesis and development of the gastric cancer. We discovered Tfh and activated CD4+ memory T cells were associated with poorer overall survival and Progression-free survival (PFS), but that naïve B cells were opposite for PFS. Unsupervised clustering analysis revealed there existed three tumor-infiltrating immune cells subgroups with distinct survival patterns. Specially, cluster 1 showed significantly better clinical outcome than other two clusters.

Conclusions

Collectively, our data explored the differences of tumor-infiltrating immune cells in gastric cancer, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.
Tumor Cellularity and Infiltrating Lymphocytes as a Survival Surrogate in HER2-Positive Breast Cancer
Authors: Chic Nuria , Luen Stephen J , Nuciforo Paolo , Salgado Roberto , Fumagalli Debora , Hilbers Florentine , Wang Yingbo , de Azambuja Evandro , Láng István , Di Cosimo Serena , Saura Cristina , Huober Jens , Prat Aleix , Loi Sherene
Published: March 2021

In early-stage HER2-positive breast cancer, biomarkers that guide deescalation and/or escalation of systemic therapy are needed. CelTIL score is a novel, combined biomarker based on stromal tumor-infiltrating lymphocytes and tumor cellularity and is determined in tumor biopsies at week 2 of anti-HER2 therapy only. We evaluated the prognostic value of CelTIL in 196 patients with early-stage HER2-positive disease treated with standard trastuzumab-based chemotherapy in the NeoALTTO phase III trial. Using a prespecified CelTIL cutoff, a better 5-year event-free survival and overall survival was observed between CelTIL-high and CelTIL-low score with a 76.4% (95% confidence interval [CI] = 68.0% to 85.0%) vs 59.7% (95% CI = 50.0% to 72.0%) (hazard ratio = 0.40, 95% CI = 0.17 to 0.94) and 86.4% (95% CI = 80.0% to 94.0%) vs 73.5% (95% CI = 64.0% to 84.0%) (hazard ratio = 0.43, 95% CI = 0.20 to 0.92), respectively. Statistical significance was maintained after adjusting for baseline tumor-infiltrating lymphocytes, hormone receptor status, pretreatment tumor size and nodal status, type of surgery, treatment arm, and pathological complete response. Further studies to support CelTIL as an early readout biomarker to help deescalate or escalate systemic therapy in HER2-positive breast cancer seem warranted.
Evaluation of a Multiethnic Polygenic Risk Score Model for Prostate Cancer
Authors: Plym Anna , Penney Kathryn L , Kalia Sarah , Kraft Peter , Conti David V , Haiman Christopher , Mucci Lorelei A , Kibel Adam S
Published: March 2021

Polygenic risk scores (PRSs) of common genetic variants have shown promise in prostate cancer risk stratification, but their validity across populations has yet to be confirmed. We evaluated a multiethnic PRS model based on 269 germline genetic risk variants (261 were available for analysis) using an independent population of 13 628 US men. The PRS was strongly associated with prostate cancer but not with any other disease. Comparing men in the top PRS decile with those at average risk (40%-60%), the odds ratio of prostate cancer was 3.89 (95% confidence interval = 3.24 to 4.68) for men of European ancestry and 3.81 (95% confidence interval = 1.48 to 10.19) for men of African ancestry. By age 85 years, the cumulative incidence of prostate cancer for European American men was 7.1% in the bottom decile and 54.1% in the top decile. This suggests that the PRS can be used to identify a substantial proportion of men at high risk for prostate cancer.
Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Authors: Prasanna Pataje G , Citrin Deborah E , Hildesheim Jeffrey , Ahmed Mansoor M , Venkatachalam Sundar , Riscuta Gabriela , Xi Dan , Zheng Guangrong , Deursen Jan van , Goronzy Jorg , Kron Stephen J , Anscher Mitchell S , Sharpless Norman E , Campisi Judith , Brown Stephen L , Niedernhofer Laura J , O’Loghlen Ana , Georgakilas Alexandros G , Paris Francois , Gius David , Gewirtz David A , Schmitt Clemens A , Abazeed Mohamed E , Kirkland James L , Richmond Ann , Romesser Paul B , Lowe Scott W , Gil Jesus , Mendonca Marc S , Burma Sandeep , Zhou Daohong , Coleman C Norman
Published: March 2021

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- and chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of “one-two punch” cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.
Intensive Parent–Child Interaction Therapy for Children with Traumatic Brain Injury: Feasibility Study
Authors: Garcia Dainelys , Rodríguez Gabriela M , Lorenzo Nicole E , Coto Jennifer , Blizzard Angela , Farias Alina , Smith Nicholas David W , Kuluz John , Bagner Daniel M
Published: March 2021

Objective

This study examined the feasibility and initial outcome of a time-limited and intensive format of Parent–Child Interaction Therapy (PCIT) for families of young children who have sustained a traumatic brain injury (TBI).

Methods

The nonrandomized open trial included 15 families with a child aged 2–5 years who had sustained a TBI and displayed clinically elevated levels of externalizing behavior problems. Families received clinic-based PCIT twice per week over an average of 6 weeks, with the exception of two families that received the same intensity and format of PCIT in the home.

Results

Ten of the 14 families who completed the baseline assessment (71%) completed the intervention and post and follow-up assessments. On average, caregivers completed homework practice on 52% of the days in between sessions. Caregivers reported high acceptability and satisfaction following the intervention, as well as decreases in child externalizing and internalizing behavior problems at the post-assessment and 2-month follow-up.

Conclusions

Results of this open trial provide preliminary support for the feasibility of a time-limited and intensive format of PCIT for families of young children who have sustained a TBI and have elevated levels of behavior problems. This study highlights a promising intervention approach for improving domains commonly affected by early childhood TBI and preventing the development of more severe and persistent problems.
Reflections on the Mentor-Mentee Relationship
Authors: Manthiram Kalpana , Edwards Kathryn M
Published: March 2021

A successful mentoring relationship can bring significant benefits to the mentee in terms of academic research productivity and career satisfaction. Through their mentees, mentors can also traverse new and fulfilling research directions. Here, we reflect on our own mentor-mentee relationship from both of our vantage points. We offer advice on how to choose a mentee/mentor, what each person needs to bring to the relationship, and how the relationship changes with time.

Summary: We reflect on how mentors and mentees can make their relationship fulfilling and successful for both.
Seed dormancy and weed emergence: from simulating environmental change to understanding trait plasticity, adaptive evolution, and population fitness
Authors: Nakabayashi Kazumi , Leubner-Metzger Gerhard
Published: March 2021

This article comments on:

Fernández Farnocchia RB, Benech-Arnold RL, Mantese A, Batlla D. 2021. Optimization of timing of next-generation emergence in Amaranthus hybridus is determined via modulation of seed dormancy by the maternal environment. Journal of Experimental Botany 72, 4283–4297.