bluuebunny/crossref_metadata_2025 huggingface dataset:
Subsurface and surface halophile communities of the chaotropic Salar de Uyuni
Authors: Martínez José M. , Escudero Cristina , Rodríguez Nuria , Rubin Sergio , Amils Ricardo
Published: January 2021

Salar de Uyuni (SdU) is the biggest athalosaline environment on Earth, holding a high percentage of the known world Li reserves. Due to its hypersalinity, temperature and humidity fluctuations, high exposure to UV radiation, and its elevated concentration of chaotropic agents like MgCl2, LiCl and NaBr, SdU is considered a polyextreme environment. Here, we report the prokaryotic abundance and diversity of 46 samples obtained in different seasons and geographical areas. The identified bacterial community was found to be more heterogeneous than the archaeal community, with both communities varying geographically. A seasonal difference has been detected for archaea. Salinibacter, Halonotius and Halorubrum were the most abundant genera in Salar de Uyuni. Different unclassified archaea were also detected. In addition, the diversity of two subsurface samples obtained at 20 and 80 m depth was evaluated and compared with the surface data, generating an evolutionary record of a multilayer hypersaline ecosystem.
‘Banner of an Atomic Regiment’: Morris Louis, Greenberg's Modernism, and Science, c. 1962
Authors: Curley John J.
Published: January 2021

Around 1962, ‘formalism’ could indicate methodological purity in the realms of both art and science. With camps in both disciplines attempting to minimize human intervention in the realm of decision‐making, ‘formalism’ could take on mechanical overtones, thereby linking art and science in profound ways. This essay considers the ways in which the austere abstract paintings of Morris Louis from the years surrounding 1960 bring these dual formalisms into focus. When viewed through the criticism of Clement Greenberg and the near‐unwavering faith President Kennedy's administration placed in new technocratic ways of waging war, Louis's paintings can be seen as beatified expressions of a mechanical rationality that also brought the world to the brink of nuclear apocalypse. Through deep engagement with Greenberg's criticism and media archives, the essay forges links between Greenberg's version of Louis and the dark sides of this rationality. The article concludes by locating ways to consider Louis's paintings outside of the Greenbergian straitjacket – recapturing the strangeness and chaotic nature of the painter's practice.
Biosynthesis of cofactor‐activatable iron‐only nitrogenase in Saccharomyces cerevisiae
Authors: López‐Torrejón Gema , Burén Stefan , Veldhuizen Marcel , Rubio Luis M.
Published: January 2021

Engineering nitrogenase in eukaryotes is hampered by its genetic complexity and by the oxygen sensitivity of its protein components. Of the three types of nitrogenases, the Fe‐only nitrogenase is considered the simplest one because its function depends on fewer gene products than the homologous and more complex Mo and V nitrogenases. Here, we show the expression of stable Fe‐only nitrogenase component proteins in the low‐oxygen mitochondria matrix of S. cerevisiae. As‐isolated Fe protein (AnfH) was active in electron donation to NifDK to reduce acetylene into ethylene. Ancillary proteins NifU, NifS and NifM were not required for Fe protein function. The FeFe protein existed as apo‐AnfDK complex with the AnfG subunit either loosely bound or completely unable to interact with it. Apo‐AnfDK could be activated for acetylene reduction by the simple addition of FeMo‐co in vitro, indicating preexistence of the P‐clusters even in the absence of coexpressed NifU and NifS. This work reinforces the use of Fe‐only nitrogenase as simple model to engineer nitrogen fixation in yeast and plant mitochondria.
Lactic acid bacteria as probiotics for the nose?
Authors: De Boeck Ilke , Spacova Irina , Vanderveken Olivier M. , Lebeer Sarah
Published: January 2021

Several studies have recently pointed towards an increased occurrence and prevalence of several taxa of the lactic acid bacteria (LAB) in the microbiota of the upper respiratory tract (URT) under healthy conditions versus disease. These include several species of the Lactobacillales such as Lacticaseibacillus casei, Lactococcus lactis and Dolosigranulum pigrum. In addition to physiological studies on their potential beneficial functions and their long history of safe use as probiotics in other human body sites, LAB are thus increasingly to be explored as alternative or complementary treatment for URT diseases. This review highlights the importance of lactic acid bacteria in the respiratory tract and their potential as topical probiotics for this body site. We focus on the potential probiotic properties and adaptation factors that are needed for a bacterial strain to optimally exert its beneficial activity in the respiratory tract. Furthermore, we discuss a range of in silico, in vitro and in vivo models needed to obtain better insights into the efficacy and adaptation factors specifically for URT probiotics. Such knowledge will facilitate optimal strain selection in order to conduct rigorous clinical studies with the most suitable probiotic strains. Despite convincing evidence from microbiome association and in vitro studies, the clinical evidence for oral or topical probiotics for common URT diseases such as chronic rhinosinusitis (CRS) needs further substantiation.
Preoperative predictors of restoration in quality of life after surgery for lung cancer
Authors: Ichimura Hideo , Kobayashi Keisuke , Gosho Masahiko , Nakaoka Kojiro , Yanagihara Takahiro , Ueda Sho , Saeki Yusuke , Maki Naoki , Kobayashi Naohiro , Kikuchi Shinji , Suzuki Hisashi , Goto Yukinobu , Sato Yukio
Published: January 2021

Background

The preoperative predictors of quality of life (QOL) in patients who undergo lung resection for lung cancer are poorly known. Here, we investigated these predictors in such patients using two QOL measures.

Methods

In this single‐institutional prospective cohort study, we administered the EQ‐5D‐5 levels (EQ‐5D‐5L) from January 2015, and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire with 30 items from April 2015 to April 2018 preoperatively (Pre) and at one month postoperatively (M1), and one year postoperatively (Y1). General health status was measured by the EQ‐5D visual analogue scale (VAS) and EORTC global health status/QOL (GHS) scores. Multivariable linear regression analyses were used to explore the preoperative predictors of QOL at Y1.

Results

A total of 223 patients were included in the study. The EQ‐5D VAS and EORTC GHS scores, at Pre, M1, and Y1, were 80 ± 15, 77 ± 15, and 84 ± 11; and 74 ± 19, 65 ± 20, and 78 ± 17, respectively. In the multivariable analyses, the albumin level, preoperative VAS score, and preoperative pain/discomfort and anxiety/depression were identified as predictors by the EQ‐5D VAS score. The preoperative EORTC GHS score, absence of diabetes mellitus, preoperative cognitive function score, and preoperative symptom score of pain were identified as predictors by the EORTC GHS score.

Conclusions

The EQ‐5D VAS and EORTC GHS scores traced similar trajectories of QOL. In both QOL measures, preoperative pain was found as a common predictor. These predictors may help improve patient/survivor care in the future.
A workflow for accurate metabarcoding using nanopore MinION sequencing
Authors: Baloğlu Bilgenur , Chen Zhewei , Elbrecht Vasco , Braukmann Thomas , MacDonald Shanna , Steinke Dirk
Published: January 2021

Metabarcoding has become a common approach to the rapid identification of the species composition in a mixed sample. The majority of studies use established short‐read high‐throughput sequencing platforms. The Oxford Nanopore MinIONTM, a portable sequencing platform, represents a low‐cost alternative allowing researchers to generate sequence data in the field. However, a major drawback is the high raw read error rate that can range from 10% to 22%.

To test whether the MinIONTM represents a viable alternative to other sequencing platforms, we used rolling circle amplification (RCA) to generate full‐length consensus DNA barcodes for a bulk mock sample of 50 aquatic invertebrate species with at least 15% genetic distance to each other. By applying two different laboratory protocols, we generated two MinIONTM runs that were used to build error‐corrected consensus sequences. A newly developed Python pipeline, ASHURE, was used for data processing, consensus building, clustering and taxonomic assignment of the resulting reads.

Our pipeline achieved median accuracies of up to 99.3% for long concatemeric reads (>45 barcodes) and successfully identified all 50 species in the mock community. The use of RCA was integral for increasing consensus accuracy but was also the most time‐consuming step of the laboratory workflow. Most concatemeric reads were skewed towards a shorter read length range with a median read length of up to 1,262 bp.

Our study demonstrates that Nanopore sequencing can be used for metabarcoding, but exploration of other isothermal amplification procedures to improve consensus accuracy is recommended.
Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans
Authors: Sebastiani Paola , Federico Anthony , Morris Melody , Gurinovich Anastasia , Tanaka Toshiko , Chandler Kevin B. , Andersen Stacy L. , Denis Gerald , Costello Catherine E. , Ferrucci Luigi , Jennings Lori , Glass David J. , Monti Stefano , Perls Thomas T.
Published: January 2021

Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age‐matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR < 1%), and two different protein signatures that predict longer survival in centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence‐associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co‐expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
Topical pain control for corneal abrasions: A systematic review and meta‐analysis
Authors: Yu Caberry W. , Kirubarajan Abirami , Yau Matthew , Armstrong Dawn , Johnson Davin E.
Published: January 2021

Objectives

Corneal abrasions are common ophthalmic presentations to emergency departments. Among emergency physicians and ophthalmologists, there are highly variable practice patterns with regard to management of resultant pain and discomfort. The goal of this study was to review and analyze the efficacy and safety of topical pain therapies for corneal abrasions, including topical anesthetics, nonsteroidal anti‐inflammatory drugs (NSAIDs), cycloplegics, steroids, pressure patching, and the use of a bandage contact lens (BCL).

Methods

The review followed the Preferred Reporting Items for Systematic Review and Meta‐analysis (PRISMA) guidelines. The protocol was established a priori and published on PROSPERO (CRD42020201288). MEDLINE, EMBASE, CENTRAL, and Web of Science were searched until December 31, 2020. Primary studies comparing topical pain therapies to another therapy or control were included. Primary outcomes included percentage of corneal abrasions healed at 24, 48, and 72 hours, as well as pain control at 24 and 48 hours. Secondary outcomes included use of oral analgesia and incidence of complications. Risk of bias was assessed using validated tools. Quality of evidence was assessed using the GRADE methodology.

Results

Overall, 33 studies (31 randomized controlled trials [RCTs], two cohort studies) comprising 4,167 patients with corneal abrasions were analyzed. Only the data for topical NSAIDs were of adequate evidence from which to draw conclusions; topical NSAIDs demonstrated significantly reduced pain scores at 24 hours (standardized mean differences [SMD] –0.69, 95% CI = –0.98 to –0.41) and 48 hours (SMD = –0.56, 95% CI = –1.02 to –0.10) as well as 53% (95% CI = 34% to 67%) lower oral analgesia use compared to control. Based on available data, topical anesthetics, cycloplegics, patching, and the use of a BCL did not result in any significant difference in pain scores or use of oral analgesia, while no studies examined topical steroids. No interventions resulted in healing delays or significantly higher rates of complications compared to controls.

Conclusions

There was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.
Delineating Developmental Periods in Adulthood Suggests Age‐Related Shifts in the Correlates of Alcohol Use and Problems
Authors: Ellingson Jarrod M. , Littlefield Andrew K. , Wood Phillip K. , Sher Kenneth J.
Published: January 2021

Background

Developmental context is related to the propensity to engage in alcohol use, the rate at which alcohol use changes, and the relevance of different risk factors to alcohol use disorder (AUD). Therefore, studies of change should consider developmental nuances, but change is often modeled to follow a uniform pattern, even across distinct developmental periods.

Methods

This study implemented a novel analytic approach to delineate developmental periods of alcohol behavior (n = 478, ages 18 to 35). This approach was further leveraged to examine age‐related shifts in the association of impulsivity risk factors (lack of planning, general sensation seeking, alcohol enhancement expectancies) with alcohol behavior (alcohol quantity*frequency, heavy drinking, AUD).

Results

A sequence of exploratory and confirmatory latent growth models (LGMs) suggested modeling separate linear change factors for alcohol behavior during the primary college (ages 18 to 21) and postcollege years (21 to 35). Bivariate LGMs estimated correlations for alcohol behavior changes with lack of planning, sensation seeking, and enhancement expectancies during these periods. The rate at which heavy drinking changed during the college years was positively correlated with general sensation seeking and lack of planning during this period (rs = 0.61 to 0.63). These correlations were significantly weaker during the postcollege years (rs = 0.29 to 0.34). Notably, the rate of change in alcohol behavior was strongly correlated with enhancement expectancies during the college (r = 0.45 to 0.70) and postcollege years (r = 0.45 to 0.61).

Conclusions

These findings highlight the importance of sensation seeking and lack of planning with regard to adult alcohol use, particularly in a college environment. There was also a strong link between the rates of change in alcohol behavior and enhancement expectancies across all waves. This study supports the utility of exploratory LGMs for delineating developmental periods of alcohol behavior, which are characterized by different processes.
Sex difference in the vulnerability to hippocampus plasticity impairment after binge‐like ethanol exposure in adolescent rat: Is estrogen the key?
Authors: Rabiant Kevin , Antol Johan , Naassila Mickael , Pierrefiche Olivier
Published: January 2021

Binge drinking during adolescence induces memory impairments, and evidences suggest that females are more vulnerable than males. However, the reason for such a difference is unclear, whereas preclinical studies addressing this question are lacking. Here we tested the hypothesis that endogenous estrogen level (E2) may explain sex differences in the effects of ethanol on hippocampus plasticity, the cellular mechanism of memory. Long‐term depression (LTD) in hippocampus slice of pubertal female rats was recorded 24 h after two ethanol binges (3 g/kg, i.p., 9 h apart). Neither the estrous cycle nor ethanol altered LTD. However, if ethanol was administered during proestrus (i.e., at endogenous E2 peak), LTD was abolished 24 h later, whereas NMDA‐fEPSPs response to a GluN2B antagonist increased. The abolition of LTD was not observed in adult female rats. Exogenous E2 combined with ethanol replicated LTD abolition in pubertal, prepubertal female, and in pubertal male rats without changes in ethanol metabolism. In male rats, a higher dose of ethanol was required to abolish LTD at 24‐h delay. In pubertal female rats, tamoxifen, an antagonist of estrogen receptors, blocked the impairing effects of endogenous and exogenous E2 on LTD, suggesting estrogen interacts with ethanol through changes in gene expression. In addition, tamoxifen prevented LTD abolition at 24 h but not at 48‐h delay. In conclusion, estrogen may explain the increased vulnerability to ethanol‐induced plasticity impairment seen in females compared with males. This increased vulnerability of female rats is likely due to changes in the GluN2B subunit that represent a common target between ethanol and estrogen.
Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking
Authors: De Falco Emanuela , White Shelby M. , Morningstar Mitchell D. , Ma Baofeng , Nkurunziza Lionnel T. , Ahmed‐Dilibe Anisah , Wellman Cara L. , Lapish Christopher C.
Published: January 2021

Alcohol use disorder (AUD) is characterized by impairments in decision‐making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision‐making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre‐existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set‐shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision‐making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables—in this case, impaired cognitive flexibility and heightened urgency, respectively—may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.
Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group
Authors: Cao Zhipeng , Ottino‐Gonzalez Jonatan , Cupertino Renata B. , Schwab Nathan , Hoke Colin , Catherine Orr , Cousijn Janna , Dagher Alain , Foxe John J. , Goudriaan Anna E. , Hester Robert , Hutchison Kent , Li Chiang‐Shan R. , London Edythe D. , Lorenzetti Valentina , Luijten Maartje , Martin‐Santos Rocio , Momenan Reza , Paulus Martin P. , Schmaal Lianne , Sinha Rajita , Sjoerds Zsuzsika , Solowij Nadia , Stein Dan J. , Stein Elliot A. , Uhlmann Anne , van Holst Ruth J. , Veltman Dick J. , Wiers Reinout W. , Yücel Murat , Zhang Sheng , Jahanshad Neda , Thompson Paul M. , Conrod Patricia , Mackey Scott , Garavan Hugh
Published: January 2021

Brain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega‐analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance‐general and substance‐specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.
Chronic opipramol treatment extinguishes cocaine craving through Rac1 in responders: A rat model study
Authors: Bareli Tzofnat , Ahdoot Hadas Levi , Ben‐Moshe Hila , Barnea Royi , Warhaftig Gal , Maayan Rachel , Roska Paola , Weizman Abraham , Yadid Gal
Published: January 2021

Ras‐related C3 botulinum toxin substrate 1 (Rac1), of the Rho small GTPase family, is a key regulator of actin cytoskeleton rearrangement and plays an important role in dendritic morphogenesis. Cocaine produces neuronal alterations, including structural changes in dendritic number and morphology. Emerging data indicate sigma‐1 receptors (σ‐1Rs) as a promising candidate for the prevention of cocaine craving. Opipramol is a σ‐1R agonist approved in some European countries for depression and anxiety. Here we report that opipramol, mediated by Rac1, attenuates cocaine‐seeking behavior in a rat model of self‐administration. The opipramol effect was shown in two phases. It decreased cocaine‐seeking behavior throughout the withdrawal phase and, interestingly, showed a significant reduction of cocaine‐primed reinstatement in 75% of the opipramol‐treated group (termed ‘responders’). All opipramol‐treated rats showed a decrease in σ‐1R mRNA expression levels in the nucleus accumbens (NAc) versus controls. Responders also exhibited significantly decreased NAc Rac1 mRNA expression levels, compared with non‐responder rats. Hence, Rac1 differentiated responders from non‐responders. Rac1 correlated positively with σ‐1R mRNA levels in opipramol responders. In another experiment, Rac1 inhibitor injected directly into the NAc core decreased active lever presses on the first day of extinction, indicating the critical role of Rac1 in the opipramol effect on drug seeking. We postulate that chronic activation of σ‐1R, through a dynamic interaction with Rac1, may suggest a new approach to treat substance use disorder (SUD). Rac1 inhibition is a prerequisite for decreasing drug seeking and rehabilitation, and this can be achieved by opipramol, a medication that can be given during detoxification.
Innate gut microbiota predisposes to high alcohol consumption
Authors: Ezquer Fernando , Quintanilla Maria Elena , Moya‐Flores Francisco , Morales Paola , Munita José Manuel , Olivares Belén , Landskron Glauben , Hermoso Marcela A. , Ezquer Marcelo , Herrera‐Marschitz Mario , Israel Yedy
Published: January 2021

Gut microbiota is known to be transferred from the mother to their offspring. This study determines whether the innate microbiota of rats selectively bred for generations as high alcohol drinkers play a role in their alcohol intake. Wistar‐derived high‐drinker UChB rats (intake 10‐g ethanol/kg/day) administered nonabsorbable oral antibiotics before allowing access to alcohol, reducing their voluntary ethanol intake by 70%, an inhibition that remained after the antibiotic administration was discontinued. Oral administration of Lactobacillus rhamnosus Gorbach–Goldin (GG) induced the synthesis of FGF21, a vagal β‐Klotho receptor agonist, and partially re‐invoked a mechanism that reduces alcohol intake. The vagus nerve constitutes the main axis transferring gut microbiota information to the brain (“microbiota‐gut‐brain” axis). Bilateral vagotomy inhibited rat alcohol intake by 75%. Neither antibiotic treatment nor vagotomy affected total fluid intake. A microbiota‐mediated marked inflammatory environment was observed in the gut of ethanol‐naïve high‐drinker rats, as gene expression of proinflammatory cytokines (TNF‐α; IL‐6; IL‐1β) was significantly reduced by nonabsorbable antibiotic administration. Gut cytokines are known to activate the vagus nerve, while vagal activation induces pro‐rewarding effects in nucleus accumbens. Both alcoholics and alcohol‐preferring rats share a marked preference for sweet tastes—likely an evolutionary trait to seek sweet fermented fruits. Saccharin intake by UChB rats was inhibited by 75%–85% by vagotomy or oral antibiotic administration, despite saccharin‐induced polydipsia. Overall, data indicate that the mechanisms that normally curtail heavy drinking are inhibited in alcohol‐preferring animals and inform a gut microbiota origin. Whether it applies to other mammals and humans merits further investigation.
2021 ISHNE/ HRS/ EHRA/ APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals
Authors: Varma Niraj , Cygankiewicz Iwona , Turakhia Mintu , Heidbuchel Hein , Hu Yufeng , Chen Lin Yee , Couderc Jean‐Philippe , Cronin Edmond M. , Estep Jerry D. , Grieten Lars , Lane Deirdre A. , Mehra Reena , Page Alex , Passman Rod , Piccini Jonathan , Piotrowicz Ewa , Piotrowicz Ryszard , Platonov Pyotr G. , Ribeiro Antonio Luiz , Rich Robert E. , Russo Andrea M. , Slotwiner David , Steinberg Jonathan S. , Svennberg Emma
Published: January 2021

This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self‐management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.
Effects of star anise (Illicium verum Hook.f.) essential oil administration under three different dietary energy levels on growth performance, nutrient, and energy utilization in broilers
Authors: Yu Caiyun , Yang Weiren , Jiang Shuzhen , Wang Tian , Yang Zaibin
Published: January 2021

This experiment was conducted to investigate the effect of star anise essential oil (SAO) supplementation in diets with different energy levels on growth performance, nutrient metabolic efficiency of broilers. One hundred and ninety‐two Arbor Acres male broiler chicks at 28 days of age were divided into a 3 × 4 factorial arrangement design with three dietary energy levels (13.41, 12.82, 12.23 MJ/kg) and 4 levels of SAO supplementation (0, 200, 400, and 600 mg/kg of diet). Dietary supplementation with SAO increased (p < .05) apparent metabolic efficiency of CP, EE, GE, and all of the amino acids except Trp. Significant interactions were noted between energy level and SAO administration for metabolic efficiency of CP, all of the amino acids except Cys. Inclusion of SAO enhanced apparent nutrient metabolic efficiency of broilers in a dose‐dependent manner, birds supplemented with 400 mg/kg of SAO in high‐energy diets appeared to contain highest nutrient metabolic efficiency, moreover, the metabolic efficiency of nutrients in low‐energy diets along with 200 or 400 mg/kg of SAO was similar with that in high‐energy diets without SAO, which indicated that the SAO might ameliorate the negative effects of reduced dietary metabolic energy on nutrient utilization in broilers.
Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan
Authors: Tanaka Mototsugu , Idei Mayumi , Sakaguchi Hiroshi , Kato Ryosuke , Sato Daisuke , Sawanobori Kenji , Kawarasaki Shuichi , Hata Toshiyuki , Yoshizaki Asako , Nakamura Miki , Ikuma Mutsuhiro
Published: January 2021

Aims

To clarify the rationales of delay or difference in the review of new drug applications among regulatory authorities for new drugs, those first approved in the world being in Japan.

Methods

Among 80 new drugs first approved in Japan from 2008 to 2019, we identified those subsequently approved in the USA or Europe. Significant delays in approval time (boxplot outliers) and the rationales for the delays were assessed among the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Results

Of the 80 Japan‐first approvals, 25 and 24 were approved in the USA and Europe, respectively, and their median approval times in Japan, the USA and Europe were 285, 334 and 477 days, respectively. Significant delays were identified for pirfenidone (1806 days, FDA), alogliptin benzoate (1856 days, FDA), insulin degludec (1457 days, FDA) and romosozumab (750 days, PMDA; 994 days, FDA; 748 days, EMA). Due to concerns about cardiovascular risk, alogliptin benzoate and insulin degludec were requested for additional clinical trials by the FDA, and romosozumab required a much longer review period than the standard approval time in all three regions.

Conclusions

Among the new drugs significantly delayed in approval time in Japan, the USA or Europe, there were some differences in the requirements, the participating regions and the assessment of clinical trials. The regulatory views on the cardiovascular risk also differed among the three regions. These divergences may be associated with the differences in approval histories.
Neurodevelopmental outcome at 24 months of healthy infants at birth with an umbilical artery blood pH ≤ 7 and/or hyperlactacidemia ≥ 7 mmol/L
Authors: Dain Clémence , Roze Jean‐christophe , Olivier Marion , Bossard Margot , Praud Mathilde , Flamant Cyril
Published: January 2021

Objective

The incidence of acidosis in term and healthy newborns and the consequences for their neurodevelopment are poorly understood. The aim of our study was to assess neurodevelopmental outcomes at 24 months of age via a parental questionnaire (ASQ, Ages and Stages Questionnaires) for a sample of infants born at term with an umbilical arterial blood pH ≤ 7 or/and hyperlactacidemia ≥ 7 mmol/L. In addition, we compared these groups’ neurodevelopmental outcomes with a control group.

Methods

During the 29 months of the study, we retrospectively included all children who had an umbilical artery (UA) cord blood pH ≤ 7 and/or lactates ≥ 7 mmol/L with good clinical adaptation. We also included a control group of term newborns with normal gases at birth. Ages and Stages questionnaires were sent to parents at 24 months of age.

Results

Among the 9016 births during the study, 7.1% of babies had a UA pH ≤ 7 and/or lactates ≥ 7 mmol/L. The ASQ was considered non‐optimal for 32.2% and 36.3% of respondents in the acidosis and control group, respectively, without any significant difference (P = 0.382). After matching for gestational age and sex, there was also no significant difference in the rate of non‐optimal ASQ. The percentage of abnormal communication was significantly higher in the control group (19.7% vs 11.4%, P = 0.015).

Conclusions

Isolated biochemical umbilical cord blood abnormalities in term or near‐term newborns with good adaptation do not appear to have a long‐term impact on development. These results are rather reassuring, and the absence of specific follow‐up for these children seems reasonable.
Fighting precarious work with institutional power: Union inclusion and its limits across spheres of action
Authors: O'Brady Sean
Published: January 2021

Research shows that union inclusion is critical to resisting precariousness, yet the role of institutional power is not adequately addressed. Through an investigation of eight retailers in four countries, this study uniquely examines how inclusive union strategies, cost competition and institutional power interact in different ‘spheres of action’. In the product market sphere, unions struggle to prevent labour cost competition between firms from eroding working conditions. In the production sphere, unions struggle to prevent labour cost competition between workers in a single firm from eroding working conditions. This article finds that multi‐level sources of institutional power are a precursor to effective union inclusion and articulating action towards threats from cost competition. I thereby argue that union efforts to resist precarious work are contingent on access to power from institutions. The article concludes with reflections on how institutional power relates to other forms of power.
‘I’ve Just Been Pretending I Can See This Stuff!’: Group member voice in decision‐making with a hidden profile
Authors: Nicholson Dawn H. , Hopthrow Tim , de Moura Georgina Randsley , Travaglino Giovanni A.
Published: January 2021

This research seeks to expand our knowledge of what underlies group performance in Hidden Profile decision tasks, adopting a mixed methods approach. We created a new mental simulation intervention designed to improve group decision outcomes and information exchange and tested it across two studies. We supplemented our quantitative statistical analysis with Thematic Analysis, to explore and better understand the motivations and utterances of individual group members, which we contend are key to increasing understanding of the challenges operating at individual and group levels in Hidden Profile decision tasks. Much group decision‐making research uses quantitative methodologies, searching for causal explanations of why things happen as they do in group processes. As a subset of this area, existent Hidden Profile research is centred in the quantitative domain. Yet qualitative research can improve the understanding of group phenomena, such as communication style, which is important in groups’ decision‐making. To our knowledge, no Hidden Profile research has taken a similar approach, so this paper makes a unique contribution. Results indicated the mental simulation had a positive effect on information exchange and decision quality in a Hidden Profile hiring task.
An overview of applied robust methods
Authors: Yuan Ke‐Hai , Gomer Brenna
Published: January 2021

Data in social sciences are typically non‐normally distributed and characterized by heavy tails. However, most widely used methods in social sciences are still based on the analyses of sample means and sample covariances. While these conventional methods continue to be used to address new substantive issues, conclusions reached can be inaccurate or misleading. Although there is no ‘best method’ in practice, robust methods that consider the distribution of the data can perform substantially better than the conventional methods. This article gives an overview of robust procedures, emphasizing a few that have been repeatedly shown to work well for models that are widely used in social and behavioural sciences. Real data examples show how to use the robust methods for latent variable models and for moderated mediation analysis when a regression model contains categorical covariates and product terms. Results and logical analyses indicate that robust methods yield more efficient parameter estimates, more reliable model evaluation, more reliable model/data diagnostics, and more trustworthy conclusions when conducting replication studies. R and SAS programs are provided for routine applications of the recommended robust method.
A single nucleotide polymorphism in the gene for GPR183 increases its surface expression on blood lymphocytes of patients with inflammatory bowel disease
Authors: Ruiz Florian , Wyss Annika , Rossel Jean‐Benoît , Sulz Michael Christian , Brand Stephan , Moncsek Anja , Mertens Joachim C. , Roth René , Clottu Aurélie S. , Burri Emanuel , Juillerat Pascal , Biedermann Luc , Greuter Thomas , Rogler Gerhard , Pot Caroline , Misselwitz Benjamin ,   Swiss IBD Cohort Study Group
Published: January 2021

Background and Purpose

Single nucleotide polymorphism rs9557195 within the gene of the G protein‐coupled receptor Epstein‐Barr virus‐induced gene 2 (EBI2/GPR183) has been associated with increased risk for inflammatory bowel diseases (IBD). GPR183 mediates the migration of intestinal immune cells and promotes colitis in animal models. Here, we study GPR183 surface expression of immune cells and associations of rs9557195 with GPR183 expression and IBD disease course.

Experimental Approach

We recruited 27 IBD patients (15 with ulcerative colitis [UC] and 12 with Crohn's disease [CD]) and eight healthy volunteers (HV). GPR183 expression was measured by FACS in subtypes of peripheral blood mononuclear cells. We analysed IBD disease course in 2301 patients (1335 with CD and 966 with UC) of the Swiss IBD cohort study.

Key Results

We found increased GPR183 expression in lymphocytes expressing chemokine receptors CCR6 or CCR9, implicated in IBD and on Th17 memory T cells. The GPR183 ligand 7α,25‐dihydroxycholesterol and the CCR6 ligand CCL20 stimulated migration of memory T cells in an additive manner. Further, IBD patients with the CC allele of rs9557195 had higher GPR183 surface expression compared to individuals with the TT allele. Swiss IBD cohort study patients carrying the rs9557195‐CC allele had higher psoriasis rates compared to individuals with the TT allele.

Conclusion and Implications

We demonstrate increased GPR183 surface expression on T cells with a potential role in gut inflammation. An SNP of the GPR183 locus was associated with GPR183 surface expression and psoriasis rates in IBD patients. Our data suggest a pro‐inflammatory role of GPR183 in IBD.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
Editorial Perspective: A call to collective action – improving the implementation of evidence in children and young people's mental health
Authors: Clarke Tim , Barwick Melanie
Published: January 2021

With growing mental health needs of children and young people and the increasing demand on children and young people’s mental health services, narrowing the evidence to practice implementation gap has never been more important. Implementation science and research provides useful theory, identification of barriers and facilitators as well as suggested strategies for improved uptake of evidence‐based treatments, but the application of these is often limited. Supporting optimal learning and implementation cultures based on collaborative, relational and pragmatic action planning is likely key. We propose suggested next steps and recommendations to move this agenda forward within the children and young people’s mental health field with a ‘call to action’. With the need for specific roles and clear accountability, we emphasise that between clinicians, researchers, consumers and policy makers this is everyone’s business.
Editorial: Evidence, policy and practice – gold standard, good enough or doing it differently?
Authors: Dubicka Bernadka
Published: January 2021

Welcome to the first issue of Child and Adolescent Mental Health (CAMH) in 2021 and also to my first issue as editor‐in‐chief. Needless to say, 2020 has been one of the most difficult years in living memory for many children and young people around the globe, and, as we discussed in our recent issues, the potential impact of COVID‐19 on children’s mental health is profound. The case for increased funding for child and adolescent mental health and investing in research has never been greater. Nevertheless, as we step into 2021, there are seeds of optimism as science drives forward treatment and vaccine developments.
Longitudinal Trajectories, Social and Individual Antecedents, and Outcomes of Problematic Internet Use Among Late Adolescents
Authors: Tóth‐Király István , Morin Alexandre J.S. , Hietajärvi Lauri , Salmela‐Aro Katariina
Published: January 2021

Given the detrimental effects associated with problematic internet use (PIU) and the need to better understand its nature and evolution, the present study examined the development of PIU in a sample of 1,750 adolescents (aged 16–19) from Finland over a 3‐year period. We documented the social (loneliness, perceived maternal and paternal behaviors) and individual (sex) antecedents, as well as the outcome implications (depressive symptoms, substance use, academic achievement) of PIU trajectories. Outcomes also predicted PIU trajectories. Latent curve modeling revealed an initially moderate, and subsequently decreasing trajectory of PIU. PIU was predicted by loneliness, paternal neglect, maternal care, depressive symptoms, and being male. In turn, PIU trajectories predicted increases in depressive symptoms and substance use, but decreases in academic achievement.
Paternal Sensitivity and Children’s Cognitive and Socioemotional Outcomes: A Meta‐Analytic Review
Authors: Rodrigues Michelle , Sokolovic Nina , Madigan Sheri , Luo Yiqi , Silva Victoria , Misra Shruti , Jenkins Jennifer
Published: January 2021

In a series of meta‐analyses, paternal sensitivity was associated with children’s (age range: 7 months–9 years) overall cognitive functioning (N = 3,193; k = 23; r = .19), including language skills (k = 9; r = .21), cognitive ability (k = 9; r = .18), and executive function (k = 8; r = .19). Paternal sensitivity was not associated with children’s overall socioemotional functioning (N = 2,924; k = 24; r = −.03) or internalizing problems, but it was associated with children’s emotion regulation (k = 7; r = .22) and externalizing problems (k = 19; r = −.08). In the broad cognitive functioning, executive function, broad socioemotional functioning, and externalizing problems meta‐analyses, child age was a significant moderator.
Influence of educational level on test and treatment for incident hypothyroidism
Authors: Møllehave Line Tang , Jacobsen Rikke Kart , Linneberg Allan , Skaaby Tea , Knudsen Nils , Jørgensen Torben , Kårhus Line Lund , Kriegbaum Margit , Grand Mia Klinten , Siersma Volkert , Lind Bent , Andersen Christen Lykkegaard , Nygaard Birte , Medici Bjarke Borregaard , Pedersen Inge Bülow , Ravn‐Haren Gitte , Thuesen Betina Heinsbæk
Published: January 2021

Objective

The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)‐measurement and initiation of levothyroxine treatment.

Design

Citizens in the greater Copenhagen Area during 2001‐2015 were included. Individual‐level data on educational level, diagnoses, GP‐contact, TSH‐measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH‐measurement and treatment initiation following a TSH‐measurement were analysed in Poisson regression models with generalized estimation equations.

Results

A TSH‐measurement was performed in 19% of 9,390,052 person years. The probability of TSH‐measurement was higher with short (RR 1.16 [95% CI 1.15–1.16]) and medium (RR 1.11 [95% CI 1.06–1.12]) compared with long education.

Treatment was initiated after 0.8% of 2,049,888 TSH‐measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39–0.57) and 0.78 (95%CI 0.67–0.91) for short and medium compared with long education. For TSH 5–10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02–1.12) for short and 1.08 (95% CI 1.03–1.13) for medium compared with long education.

Conclusion

The probability of TSH‐measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short‐medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.
DUALCOR: a phylogenetic comparative method to evaluate phylogenetic correlation between a character and a non‐evolving external variable
Authors: Giannini Norberto P. , Goloboff Pablo A.
Published: January 2021

A new phylogenetic comparative method called DUALCOR is presented to evaluate the evolutionary response of a character to non‐evolving external factors, such as environmental variables. The method treats the character as a typical evolving feature of an organism that is reconstructed on a given tree, whereas the external factor is treated as unrelated to the phylogeny. DUALCOR first calculates the correlation/regression between the observed values of the character and the external factor; then it maps the character onto the phylogeny, shuffles the changes among branches, and re‐evolves the character to yield new terminal values uncorrelated with the observed values of the external factor, allowing users to examine whether the observed degree of correlation can be attained at random. This is repeatedn(say, 999) times, thereby using the dual nature of characters to construct a permutation test that is shown to satisfy requirements of Generalized Monte Carlo procedures. In addition, we provide an empirical example with a reverse test where the external variable (features determined largely by non‐heritable factors) is the dependent variable.