bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical review of citrulline malate supplementation and exercise performance
Authors: Gough Lewis A. , Sparks S. Andy , McNaughton Lars R. , Higgins Matthew F. , Newbury Josh W. , Trexler Eric , Faghy Mark A. , Bridge Craig A.
Published: August 2021

As a nitric oxide (NO) enhancer, citrulline malate (CM) has recently been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance, as well as the recovery of muscular performance. The mechanism has been associated with enhanced blood flow to active musculature, however, it might be more far-reaching as either ammonia homeostasis could be improved, or ATP production could be increased via greater availability of malate. Moreover, CM might improve muscle recovery via increased nutrient delivery and/or removal of waste products. To date, a single acute 8 g dose of CM on either resistance exercise performance or cycling has been the most common approach, which has produced equivocal results. This makes the effectiveness of CM to improve exercise performance difficult to determine. Reasons for the disparity in conclusions seem to be due to methodological discrepancies such as the testing protocols and the associated test–retest reliability, dosing strategy (i.e., amount and timing), and the recent discovery of quality control issues with some manufacturers stated (i.e., citrulline:malate ratios). Further exploration of the optimal dose is therefore required including quantification of the bioavailability of NO, citrulline, and malate following ingestion of a range of CM doses. Similarly, further well-controlled studies using highly repeatable exercise protocols with a large aerobic component are required to assess the mechanisms associated with this supplement appropriately. Until such studies are completed, the efficacy of CM supplementation to improve exercise performance remains ambiguous.
Myelin densities in retinotopically defined dorsal visual areas of the macaque
Authors: Li Xiaolian , Zhu Qi , Vanduffel Wim
Published: August 2021

The visuotopic organization of dorsal visual cortex rostral to area V2 in primates has been a longstanding source of controversy. Using sub-millimeter phase-encoded retinotopic fMRI mapping, we recently provided evidence for a surprisingly similar visuotopic organization in dorsal visual cortex of macaques compared to previously published maps in New world monkeys (Zhu and Vanduffel, Proc Natl Acad Sci USA 116:2306–2311, 2019). Although individual quadrant representations could be robustly delineated in that study, their grouping into hemifield representations remains a major challenge. Here, we combined in-vivo high-resolution myelin density mapping based on MR imaging (400 µm isotropic resolution) with fine-grained retinotopic fMRI to quantitatively compare myelin densities across retinotopically defined visual areas in macaques. Complementing previously documented differences in populational receptive-field (pRF) size and visual field signs, myelin densities of both quadrants of the dorsolateral posterior area (DLP) and area V3A are significantly different compared to dorsal and ventral area V3. Moreover, no differences in myelin density were observed between the two matching quadrants belonging to areas DLP, V3A, V1, V2 and V4, respectively. This was not the case, however, for the dorsal and ventral quadrants of area V3, which showed significant differences in MR-defined myelin densities, corroborating evidence of previous myelin staining studies. Interestingly, the pRF sizes and visual field signs of both quadrant representations in V3 are not different. Although myelin density correlates with curvature and anticorrelates with cortical thickness when measured across the entire cortex, exactly as in humans, the myelin density results in the visual areas cannot be explained by variability in cortical thickness and curvature between these areas. The present myelin density results largely support our previous model to group the two quadrants of DLP and V3A, rather than grouping DLP- with V3v into a single area VLP, or V3d with V3A+ into DM.
ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype
Authors: Lerner Shaul , Eilam Raya , Adler Lital , Baruteau Julien , Kreiser Topaz , Tsoory Michael , Brandis Alexander , Mehlman Tevie , Ryten Mina , Botia Juan A. , Ruiz Sonia Garcia , Garcia Alejandro Cisterna , Dionisi-Vici Carlo , Ranucci Giusy , Spada Marco , Mazkereth Ram , McCarter Robert , Izem Rima , Balmat Thomas J. , Richesson Rachel ,   Members of the UCDC, Baumgartner Matthias R. , Bedoyan Jirair K. , Berry Gerard , Berry Susan A. , Burgard Peter , Burrage Lindsay , Coughlin Curtis , Diaz George A. , Enns Gregory , Gallagher Renata C. , Gropman Andrea , Harding Cary O. , Hoffmann Georg , Le Mons Cynthia , McCandless Shawn E. , Merritt J. Lawrence , Nagamani Sandesh C. S. , Schulze Andreas , Seminara Jennifer , Stricker Tamar , Tuchman Mendel , Waisbren Susan , Weisfeld-Adams James D. , Wong Derek , Yudkoff Marc , Gazit Ehud , Nagamani Sandesh C. S. , Erez Ayelet
Published: August 2021

Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders.
Determining the impact of postoperative complications in neurosurgery based on simulated longitudinal smartphone app-based assessment
Authors: Comfort Lion D. , Neidert Marian C. , Bozinov Oliver , Regli Luca , Stienen Martin N.
Published: August 2021

Background

Complications after neurosurgical operations can have severe impact on patient well-being, which is poorly reflected by current grading systems. The objective of this work was to develop and conduct a feasibility study of a new smartphone application that allows for the longitudinal assessment of postoperative well-being and complications.

Methods

We developed a smartphone application “Post OP Tracker” according to requirements from clinical experience and tested it on simulated patients. Participants received regular notifications through the app, inquiring them about their well-being and complications that had to be answered according to their assigned scenarios. After a 12-week period, subjects answered a questionnaire about the app’s functionality, user-friendliness, and acceptability.

Results

A total of 13 participants (mean age 34.8, range 24–68 years, 4 (30.8%) female) volunteered in this feasibility study. Most of them had a professional background in either health care or software development. All participants downloaded, installed, and applied the app for an average of 12.9 weeks. On a scale of 1 (worst) to 4 (best), the app was rated on average 3.6 in overall satisfaction and 3.8 in acceptance. The design achieved a somewhat favorable score of 3.1. One participant (7.7%) reported major technical issues. The gathered patient data can be used to graphically display the simulated outcome and assess the impact of postoperative complications.

Conclusions

This study suggests the feasibility to longitudinally gather postoperative data on subjective well-being through a smartphone application. Among potential patients, our application indicated to be functional, user-friendly, and well accepted. Using this app-based approach, further studies will enable us to classify postoperative complications according to their impact on the patient’s well-being.
Bacterial Viruses Subcommittee and Archaeal Viruses Subcommittee of the ICTV: update of taxonomy changes in 2021
Authors: Krupovic Mart , Turner Dann , Morozova Vera , Dyall-Smith Mike , Oksanen Hanna M. , Edwards Rob , Dutilh Bas E. , Lehman Susan M. , Reyes Alejandro , Baquero Diana P. , Sullivan Matthew B. , Uchiyama Jumpei , Nakavuma Jesca , Barylski Jakub , Young Mark J. , Du Shishen , Alfenas-Zerbini Poliane , Kushkina Alla , Kropinski Andrew M. , Kurtböke Ipek , Brister J. Rodney , Lood Cédric , Sarkar B. L. , Yigang Tong , Liu Ying , Huang Li , Wittmann Johannes , Chanishvili Nina , van Zyl Leonardo J. , Rumnieks Janis , Mochizuki Tomohiro , Jalasvuori Matti , Aziz Ramy K. , Łobocka Małgorzata , Stedman Kenneth M. , Shkoporov Andrey N. , Gillis Annika , Peng Xu , Enault François , Knezevic Petar , Lavigne Rob , Rhee Sung-Keun , Cvirkaite-Krupovic Virginija , Moraru Cristina , Moreno Switt Andrea I. , Poranen Minna M. , Millard Andrew , Prangishvili David , Adriaenssens Evelien M.
Published: August 2021

In this article, we – the Bacterial Viruses Subcommittee and the Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) – summarise the results of our activities for the period March 2020 – March 2021. We report the division of the former Bacterial and Archaeal Viruses Subcommittee in two separate Subcommittees, welcome new members, a new Subcommittee Chair and Vice Chair, and give an overview of the new taxa that were proposed in 2020, approved by the Executive Committee and ratified by vote in 2021. In particular, a new realm, three orders, 15 families, 31 subfamilies, 734 genera and 1845 species were newly created or redefined (moved/promoted).
Existence of giant mitochondria-containing sheet structures lacking cristae and matrix in the etiolated cotyledon of Arabidopsis thaliana
Authors: Fukushima Saki , Akita Kae , Takagi Tomoko , Kobayashi Keiko , Moritoki Nobuko , Sugaya Hajime , Arimura Shin-ichi , Kuroiwa Haruko , Kuroiwa Tsuneyoshi , Nagata Noriko
Published: August 2021

Mitochondria are essential organelles involved in the production and supply of energy in eukaryotic cells. Recently, the use of serial section scanning electron microscopy (S3EM) has allowed accurate three-dimensional (3D) reconstructed images of even complex organelle structures. Using this method, ultrathin sections of etiolated cotyledons were observed 4 days after germination of Arabidopsis thaliana in the dark, and giant mitochondria were found. To exclude the possibility of chemical fixation artifacts, this study confirmed the presence of giant mitochondria in high-pressure frozen samples. The 3D reconstructed giant mitochondria had a complex structure that included not only the elongated region but also the flattened shape of a disk. It contained the characteristic sheet structure, and the sheet lacked cristae and matrix but consisted of outer and inner membranes. Whether this phenomenon could be observed in living cells was investigated using the transformant with mitochondrial matrix expressing green fluorescent protein. Small globular mitochondria observed in light-treated samples were also represented in etiolated cotyledons. Although no giant mitochondria were observed in light-treated samples, they were found in the dark 3 days after germination and rapidly increased in number on the fourth day. Therefore, giant mitochondria were observed only in dark samples. These findings were supported by electron microscopy results.
Activation of proline metabolism maintains ATP levels during cocaine-induced polyADP-ribosylation
Authors: Dash Sabyasachi , Dash Chandravanu , Pandhare Jui
Published: August 2021

Cocaine is a commonly abused drug worldwide. Acute as well as repeated exposure to cocaine activates persistent cellular and molecular changes in the brain reward regions. The effects of cocaine are predominantly mediated via alterations in neuronal gene expression by chromatin remodeling. Poly(ADP-ribose) polymerase-1 (PARP-1) catalyzed PARylation of chromatin has been reported as an important regulator of cocaine-mediated gene expression. PARP-1 dependent ADP-ribosylation is an energy-dependent process. In this study, we investigated the cellular energy response to cocaine-induced upregulation of PARP-1 expression. Exposure of differentiated SH-SY5Y cells to varying concentrations of cocaine resulted in the induction of PARP-1 dependent PARylation of p53 tumor suppressor. Further analysis revealed that PARylation of p53 by cocaine treatment resulted in nuclear accumulation of p53. However, induction and nuclear accumulation of p53 did not correlate with neuronal apoptosis/cell death upon cocaine exposure. Interestingly, cocaine-induced p53 PARylation resulted in the induction of proline oxidase (POX)—a p53 responsive gene involved in cellular metabolism. Given that cocaine-induced p53 PARylation is an energy-dependent process, we observed that cocaine-induced PARP-1/p53/POX axes alters cellular energy metabolism. Accordingly, using pharmacological and genetic studies of PARP-1, p53, and POX, we demonstrated the contribution of POX in maintaining cellular energy during neuronal function. Collectively, these studies highlight activation of a novel metabolic pathway in response to cocaine treatment.
Informative value of referral letters from general practice for child and adolescent mental healthcare
Authors: Aydin S. , Crone M. R. , Siebelink B. M. , Numans M. E. , Vermeiren R. R. J. M. , Westenberg P. M.
Published: August 2021

Although referral letters (RLs) form a nodal point in a patient’s care journey, little is known about their informative value in child and adolescent mental healthcare. To determine the informative value of RLs to child and adolescent psychiatry, we conducted a chart review in medical records of minors registered at specialized mental healthcare between January 2015 and December 2017 (The Netherlands). Symptoms indicated in RLs originating from general practice (N = 723) were coded and cross-tabulated with the best estimate clinical classifications made in psychiatry. Results revealed that over half of the minors in the sample were classified in concordance with at least one reason for referral. We found fair to excellent discriminative ability for indications made in RLs concerning the most common psychiatric classifications (95% CI AUC: 60.9–70.6 for anxiety disorders to 90.5–100.0 for eating disorders). Logistic regression analyses suggested no statistically significant effects of gender, age, severity or mental healthcare history, with the exception of age and attention deficit hyperactivity disorders (ADHD), as RLs better predicted ADHD with increasing age (OR = 1.14, 95% CI 1.03–1.27). Contextual problems, such as difficulties studying, problems with parents or being bullied were indicated frequently and associated with classifications in various disorder groups. To conclude, general practitioners’ RLs showed informative value, contrary to common beliefs. Replication studies are needed to reliably incorporate RLs into the diagnostic work-up.
The contribution of resident physicians to hospital productivity
Authors: Perez-Villadóniga Maria J. , Rodriguez-Alvarez Ana , Roibas David
Published: August 2021

Resident physicians play a double role in hospital activity. They participate in medical practices and thus, on the one hand, they should be considered as an input. Also, they are medical staff in training and, on the other hand, must be considered as an output. The net effect on hospital activities should therefore be empirically determined. Additionally, when considering their role as active physicians, a natural hypothesis is that resident physicians are not more productive than senior ones. This is a property that standard logarithmic production functions (including Cobb–Douglas and Translog functional forms) cannot verify for the whole technology set. Our main contribution is the development of a Translog modification, which implies the definition of the input “doctors” as a weighted sum of senior and resident physicians, where the weights are estimated from the empirical application. This modification of the standard Translog is able, under suitable parameter restrictions, to verify our main hypothesis across the whole technology set while determining if the net effect of resident physicians in hospitals’ production should be associated to an output or to an input. We estimate the resulting output distance function frontier with a sample of Spanish hospitals. Our findings show that the overall contribution of resident physicians to hospitals’ production allows considering them as an input in most cases. In particular, their average productivity is around 37% of that corresponding to senior physicians.
What matters to people aged 80 and over regarding ambulatory care? A systematic review and meta-synthesis of qualitative studies
Authors: Herrler Angélique , Kukla Helena , Vennedey Vera , Stock Stephanie
Published: August 2021

The growing percentage of the population aged 80 and over is challenging for healthcare systems, as frailty and other complex health issues are common in this age group. In order to provide patient-centered ambulatory healthcare, their preferences and expectations need to be explored. Therefore, the aim of this study was to systematically search for and synthesize qualitative evidence on how people aged 80 and over believe ambulatory healthcare (medical and nursing care) should be delivered to them. Medline, PsycINFO, CINAHL, Web of Science Core Collection and Google Scholar were searched for full research reports of qualitative studies focusing on the preferences, wishes, needs, expectations and experiences of people aged 80 and over regarding ambulatory medical and nursing care. The results were screened by two independent reviewers using a two-step approach. The included studies were meta-synthesized using Thomas and Harden’s ‘thematic synthesis’ approach in order to gain a new, second-order interpretation of the findings of the primary studies. In the intermediate synthesis step, 14 aspects of healthcare structures and care relationships were identified as relevant. Based on these, three underlying wishes were found: feeling safe, feeling like a meaningful human being, and maintaining control and independence. The results of this review are in line with other research, such as reviews focusing on the preferences of the younger age group (65–80). However, the importance of aspects of care relationships as an integral part of favorable ambulatory healthcare and the wish to be strengthened as a meaningful human being are emphasized more strongly.
Social Influence and Uptake of Couples HIV Testing and Counselling in KwaZulu-Natal, South Africa
Authors: Johnson Matthew J. , Darbes Lynae A. , Hosegood Victoria , Johnson Mallory O. , Fritz Katherine , Ngubane Thulani , van Rooyen Heidi , McGrath Nuala
Published: August 2021

Social influences may create a barrier to couples HIV testing and counselling (CHTC) uptake in sub-Saharan Africa. This secondary analysis of data collected in the ‘Uthando Lwethu’ randomised controlled trial used discrete-time survival models to evaluate the association between within-couple average ‘peer support’ score and uptake of CHTC by the end of nine months’ follow-up. Peer support was conceptualised by self-rated strength of agreement with two statements describing friendships outside of the primary partnership. Eighty-eight couples (26.9%) took up CHTC. Results tended towards a dichotomous trend in models adjusted only for trial arm, with uptake significantly less likely amongst couples in the higher of four peer support score categories (OR 0.34, 95% CI 0.18, 0.68 [7–10 points]; OR 0.53, 95% CI 0.28, 0.99 [≥ 11 points]). A similar trend remained in the final multivariable model, but was no longer significant (AOR 0.59, 95% CI 0.25, 1.42 [7–10 points]; AOR 0.88, 95% CI 0.36, 2.10 [≥ 11 points]). Accounting for social influences in the design of couples-focused interventions may increase their success.
Birth Order and First Sexual Experience: Do Siblings Influence Sexual Debut in Adolescents?
Authors: Pasqualini Marta , Sacker Amanda , McMunn Anne
Published: August 2021

Birth order may foster specific roles for individuals within the family and set in train a dynamic that influences the development of specific behaviors. In this paper, we explored the relationship between birth order, sex, timing of sexual initiation, and its consequences for risky sexual behavior and sexual health. We conducted a path analysis to simultaneously estimate direct and indirect effects using data from the National Survey of Sexual Attitudes and Lifestyles (NATSAL-3). Whereas women born as only-children were more likely to sexually debut at later ages, middle-child boys were significantly more prone to initiate sexual intercourse earlier compared with first-borns. As expected, early sexual initiation was associated with riskier behaviors and sexual health outcomes. These associations were partially moderated by siblings role as confidants about sexuality. Our findings have implications for preventive programs aimed at promoting healthy sexual debuts and behaviors over the life span.
Bargaining and descriptive content: prospects for a teleosemantic ethics
Authors: Bergman Karl
Published: August 2021

Teleosemantics is the view that mental content depends on etiological function. Moral adaptationism is the view that human morality is an evolved adaptation. Jointly, these two views offer new venues for naturalist metaethics. Several authors have seen, in the conjunction of these views, the promise of assigning naturalistically respectable descriptive content to moral judgments. One such author is Neil Sinclair, who has offered a blueprint for how to conduct teleosemantic metaethics with the help of moral adaptationism. In this paper, I argue that the prospects for assigning descriptive content to moral judgments on the basis of teleosemantics are bad. I develop my argument in dialogue with Sinclair’s paper and argue that, although Sinclair’s account of the evolution of morality is plausible, the teleosemantic account of the descriptive content of moral judgments which he bases thereon suffers from crucial shortcomings. I argue further that, given some minimal plausible assumptions about the evolution of morality made by Sinclair, no assignment of descriptive content is possible. Contrary to prevailing assumptions, the combination of moral adaptationism and teleosemantics suggests that moral judgments lack descriptive content.
Optical coherence tomography tissue coverage and characterization at six months after implantation of bioresorbable scaffolds versus conventional everolimus eluting stents in the ISAR-Absorb MI trial
Authors: Rai Himanshu , Alfonso Fernando , Maeng Michael , Bradaric Christian , Wiebe Jens , Cuesta Javier , Christiansen Evald Høj , Cassese Salvatore , Hoppmann Petra , Colleran Roisin , Harzer Fiona , Bresha Jola , Nano Nejva , Schneider Simon , Laugwitz Karl-Ludwig , Joner Michael , Kastrati Adnan , Byrne Robert A.
Published: August 2021

Purpose

Data regarding vessel healing by optical coherence tomography (OCT) after everolimus-eluting bioresorbable scaffolds (BRS) or everolimus-eluting metallic stent (EES) implantation in acute myocardial infarction (AMI) patients is scarce. We compared OCT findings after BRS or EES implantation in patients with AMI enrolled in a randomized trial.

Methods

In ISAR-Absorb MI, AMI patients were randomized to BRS or EES implantation, with 6–8 month angiographic follow-up. This analysis includes patients who underwent OCT during surveillance angiography. Tissue characterization was done using grey-scale signal intensity analysis. The association between OCT findings and target lesion failure (TLF) at 2 years was investigated.

Results

OCT was analyzed in 103 patients (2237 frames, 19,827 struts) at a median of 216 days post-implantation. Of these, 70 were treated with BRS versus 32 with EES. Pre-(92.8 vs. 68.7%, p = 0.002) and post-dilation (51.4 vs. 12.5%, p < 0.001) were more common in BRS as compared to EES. Strut coverage was higher in BRS vs. EES (97.5% vs. 90.9%, p < 0.001). Mean neointimal thickness was comparable in both groups [85.5 (61.9, 124.1) vs. 69.5 (32.7, 127.5) µm, respectively, p = 0.20]. Mature neointimal regions were numerically more common in BRS (43.0% vs. 24.6%; p = 0.35); this difference was statistically significant in ST-elevation myocardial infarction patients (40.9% vs. 21.1%, p = 0.03).

At two-years, 8 (7.8%) patients experienced TLF. Mean neointimal area [0.61 (0.21, 1.33) vs. 0.41 (0.11, 0.75) mm2, p = 0.03] and mean neointimal coverage [106.1 (65.2, 214.8) vs. 80.5 (53.5, 122.1) µm, p < 0.01] were higher, with comparable tissue maturity, in lesions with versus without TLF.

Conclusions

In selected patients who underwent OCT surveillance 6–8 months after coronary intervention for AMI with differing implantation characteristics depending on the device type used, vessel healing was more advanced in BRS compared with EES, particularly in the STEMI subgroup.
In vitro and clinical investigations to determine the drug-drug interaction potential of entrectinib, a small molecule inhibitor of neurotrophic tyrosine receptor kinase (NTRK)
Authors: Meneses-Lorente Georgina , Fowler Stephen , Guerini Elena , Kowalski Karey , Chow-Maneval Edna , Yu Li , Mercier Francois , Ullah Mohammed , Umehara Kenichi , Brink Andreas , Buchheit Vincent , Zwanziger Elke , Phipps Alex , Djebli Nassim
Published: August 2021

Background Entrectinib is a CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, ROS1 and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe the in vitro and clinical studies investigating potential entrectinib drug-drug interactions. Methods In vitro studies with human biomaterials assessed the enzymes involved in entrectinib metabolism, and whether entrectinib modulates the activity of the major cytochrome P450 (CYP) enzymes or drug transporter P-glycoprotein. Clinical studies investigated the effect of a strong CYP3A4 inhibitor (itraconazole) and inducer (rifampin) on single-dose entrectinib pharmacokinetics. The effect of entrectinib on sensitive probe substrates for CYP3A4 (midazolam) and P-glycoprotein (digoxin) were also investigated. Results Entrectinib is primarily metabolized by CYP3A4. In vitro, entrectinib is a CYP3A4/5 inhibitor (IC50 2 μM) and a weak CYP3A4 inducer. Entrectinib inhibited P-glycoprotein (IC50 1.33 μM) but is a poor substrate. In healthy subjects, itraconazole increased entrectinib Cmax and AUC by 73% and 504%, respectively, and rifampin decreased entrectinib Cmax and AUC by 56% and 77%, respectively. Single dose entrectinib did not affect midazolam AUC, although Cmax decreased by 34%. Multiple dose entrectinib increased midazolam AUC by 50% and decreased Cmax by 21%. Single dose entrectinib increased digoxin AUC and Cmax by 18% and 28%, respectively, but did not affect digoxin renal clearance. Conclusions Entrectinib is a CYP3A4 substrate and is sensitive to the effects of coadministered moderate/strong CYP3A4 inhibitors and strong inducers, and requires dose adjustment. Entrectinib is a weak inhibitor of CYP3A4 and P-glycoprotein and no dose adjustments are required with CYP3A4/P- glycoprotein substrates.

Registration Number (Study 2) NCT03330990 (first posted online November 6, 2017) As studies 1 and 3 are phase 1 trials in healthy subjects, they are not required to be registered.
Prevalence of SARS-CoV-2 antibodies in Denmark: nationwide, population-based seroepidemiological study
Authors: Espenhain Laura , Tribler Siri , Sværke Jørgensen Charlotte , Holm Hansen Christian , Wolff Sönksen Ute , Ethelberg Steen
Published: August 2021

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3–1.9%) in May to 4.1% (95%CI: 3.1–4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12–29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32–56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.
Superposition with Lambdas
Authors: Bentkamp Alexander , Blanchette Jasmin , Tourret Sophie , Vukmirović Petar , Waldmann Uwe
Published: August 2021

We designed a superposition calculus for a clausal fragment of extensional polymorphic higher-order logic that includes anonymous functions but excludes Booleans. The inference rules work on $$\beta \eta $$

β
η

-equivalence classes of $$\lambda $$
λ
-terms and rely on higher-order unification to achieve refutational completeness. We implemented the calculus in the Zipperposition prover and evaluated it on TPTP and Isabelle benchmarks. The results suggest that superposition is a suitable basis for higher-order reasoning.
Do economic freedom, business experience, and firm size affect internationalization speed? Evidence from small firms in Chile, Colombia, and Peru
Authors: Felzensztein Christian , Saridakis George , Idris Bochra , Elizondo Gabriel P.
Published: August 2021

This paper focuses on SMEs from the Latin American region and aims to build on existing literature on the emergence of the institution-based view in combination with the resource-based view. We contribute to existing literature by extending the application of the aforementioned theories to firms in three under-researched countries in this region. Specifically, we contribute to the extant literature by providing empirical insights on how home country–specific resources and firm-specific resources can affect the internationalization speed of SMEs in Latin American region. In order to achieve our objectives, we empirically examine the role of economic freedom (EF), prior business/international experience, and firm size on speed of internationalization. We use a dataset of Latin American SMEs, employing Poisson and negative binomial (NB) regression techniques. Our data cover three main Latin American Pacific Rim economies—Chile, Colombia, and Peru—with similar economic specializations, geographical borders, and economic growth dynamics. We find that (1) some parts of Economic Freedom Index (EFI) accelerate the speed of internationalization, whereas other areas slow it down or have no effect. Specifically, the closer to full EF the home country is in terms of regulations and government, the shorter the time to internationalize. (2) More experienced management teams are more likely to translate their knowledge into faster international market entry, but this pays off only for larger sized SMEs in contrast to smaller ones due to complementarities between managerial resources and physical, financial, and organizational resources. (3) Finally, industry, firm location, and country destination can only weakly explain the speed of internationalization. The findings add to the literature on SME internationalization in emerging markets and point towards potential policies to stimulate growth by SMEs in these markets.
Early presence of Bythotrephes cederströmii (Cladocera: Cercopagidae) in lake sediments in North America: evidence or artifact?
Authors: DeWeese Nichole E. , Favot Elizabeth J. , Branstrator Donn K. , Reavie Euan D. , Smol John P. , Engstrom Daniel R. , Rantala Heidi M. , Schottler Shawn P. , Paterson Andrew M.
Published: August 2021

The spiny water flea (Bythotrephes cederströmii), a freshwater crustacean considered to be the world’s best-studied invasive zooplankter, was first recorded in North America in the Laurentian Great Lakes during the 1980s. Its arrival is widely considered to be the result of ocean-going cargo ships that translocated contaminated ballast water from Eurasia to the Great Lakes during the 1970–1980s. The subsequent first discovery of the species in inland lakes is consistent with the hypothesis that propagules dispersed initially from established Great Lakes populations. Here we present evidence of exoskeletal remains, including mandibles, tail spines, and resting eggs, in 210Pb-dated lake sediment cores, which suggests that B. cederströmii was already resident in four inland North American lakes (two in Minnesota, USA; two in Ontario, Canada) by at least the early 1900s. Densities of exoskeletal remains were low and relatively steady from first appearance until about 1990, after which time they increased in all cores. The earliest evidence that we found was a mandible at 33-cm depth (pre-1650) in the sediments of Three Mile Lake, Ontario, Canada. These unexpected findings challenge the current paradigm of B. cederströmii invasion, renew uncertainty about the timing and sequence of its colonization of North American lakes, and potentially question our ability to detect invasive species with traditional sampling methods. We attempted to eliminate errors in the dated stratigraphies of the exoskeletal remains that might have been introduced either methodologically (e.g., core-wall smearing) or naturally (e.g., bioturbation). Nonetheless, given the very low numbers of subfossils encountered, questions remain about the possible artifactual nature of our observations and therefore we regard our results as ‘preliminary findings’ at this time.
Religiosity, Meaning-Making and the Fear of COVID-19 Affecting Well-Being Among Late Adolescents in Poland: A Moderated Mediation Model
Authors: Krok Dariusz , Zarzycka Beata , Telka Ewa
Published: August 2021

Adolescents have come to be greatly affected by the COVID-19 pandemic and the ensuing containment measures in recent months. The aim of the present study was to examine the relations among religiosity, meaning-making, fear of COVID-19, and subjective well-being within a moderated mediation model. Three hundred and sixteen late adolescents (173 women and 143 men) in Poland volunteered to take part in the study. The results show that meaning-making mediated relationships between religiosity and life satisfaction, religiosity and positive affect, and religiosity and negative affect. In addition, these mediation effects were moderated by the fear of COVID-19. Specifically, the indirect effects were stronger for adolescents with high fear than for those with low fear, which indicates that fear of COVID-19 serves as a ‘warning’ factor.
Why Do Immigrant and Swedish Adolescents Engage in Ethnic Victimization? Common and Distinct Underlying Factors
Authors: Bayram Özdemir S. , Giles C. , Özdemir M.
Published: August 2021

Youth of immigrant background are at risk of experiencing victimization due to their ethnic or cultural background. However, limited knowledge is available regarding why youth victimize their immigrant peers, and whether the factors associated with engagement in ethnic victimization vary across adolescents of different background. To address this gap in knowledge, the present study aimed to elucidate the common or differential factors associated with engagement in ethnic victimization among immigrant and native youth. The analytical sample included seventh grade students residing in Sweden from 55 classrooms (N = 963, Mage = 13.11, SD = 0.41; 46% girls; 38% youth of immigrant background). The results showed that being morally disengaged and engaging in general victimization are the common denominators of engagement in ethnic victimization for immigrant and Swedish youth. Low levels of positive attitudes toward immigrants provide a foundation for ethnic victimization among Swedish youth, but not youth of immigrant background. Classroom ethnic composition was not significantly related to engagement in ethnic victimization in either group. Predictors of engagement in ethnic victimization seem to have similarities and differences among immigrant and Swedish youth. The factors involved require further attention in developing strategies to combat bias-based hostile behaviors in diverse school settings.
Students’ school climate perceptions: do engagement and burnout matter?
Authors: Molinari Luisa , Grazia Valentina
Published: August 2021

This study, conducted with a person-oriented approach, aimed to assess whether students who are positively engaged in school activities and daily practices perceive their school climate differently from students who feel distant and less engaged in school. To achieve this aim, by means of a Latent Profile Analysis with the 3-step approach, we first identified student profiles on the basis of their levels of school engagement and burnout, and then verified whether the school climate perceptions differed for the various profiles. The study involved 1065 Italian middle-school students (49% females, Mage = 11.77). School climate perceptions were assessed with the Multidimensional School Climate Questionnaire. Multidimensional measures were used for student engagement and school burnout. Four student profiles, labelled Cynically disengaged (5.9%), Moderately disengaged (21.6%), Peacefully engaged (46.1%) and Tenseley engaged (26.4%), were identified. The first two profiles involved low levels of engagement and high levels of cynical burnout, with the former showing more extreme scores. The other two profiles depicted engaged students, with the latter also revealing feelings of pressure and disillusion. The four profiles differed in their school climate perceptions, with the Peacefully engaged students reporting the highest scores and the Cynically disengaged students embodying the most critical perceptions. The study’s educational implications are discussed.
Co-Amoxiclav as empiric treatment of UTI in children: importance of surveillance in ensuring optimal empiric treatment choice
Authors: Trayer James , Horgan Michael , Prior Anna-Rose , Ryan Martin , Nadeem Montasser
Published: August 2021

Background Urinary tract infections are common and require prompt treatment. Objective To examine the resistance rates of co-amoxiclav in children with urinary tract infection and whether antimicrobial resistance is influenced by other variables. Methods The records and antibiotic susceptibility data of 209 patients admitted with symptomatic urinary tract infection between January 2018 and December 2019 were reviewed. Results We examined 209 patients [mean (SD) age 23.73 (32.86) months], of whom 176 (84.2%) had first urinary tract infection. Escherichia coli was isolated in 190 (90.1%). Uropathogens were sensitive to co-amoxiclav in 47.8% of patients and gentamicin in 95.2%. Combined co-amoxiclav with gentamicin demonstrated antimicrobial sensitivity in 96.2%. Antimicrobial resistance was associated with longer hospital stay (p-value < 0.02). An association was identified between co-amoxiclav resistance and recurrent urinary tract infections. Uropathogens were resistant to co-amoxiclav in 80/176 (45.5%) and 29/33 (87.9%) patients with first and recurrent urinary tract infections, respectively (p-value 0.001). No link was observed between antimicrobial resistance and atypical urinary tract infection. Conclusion Approximately half of children in this cohort had urinary tract infection due to uropathogens resistant to co-amoxiclav. Co-amoxiclav resistance is associate with recurrent infections and longer hospital stays. A combination of co-amoxiclav and gentamicin demonstrates > 96% susceptibility.
Short-term impact of crop diversification on soil carbon fluxes and balance in rainfed and irrigated woody cropping systems under semiarid Mediterranean conditions
Authors: Martínez-Mena María , Boix-Fayos Carolina , Carrillo-López Efrain , Díaz-Pereira Elvira , Zornoza Raúl , Sánchez-Navarro Virginia , Acosta Jose A. , Martínez-Martínez Silvia , Almagro María
Published: August 2021

Purpose

Diversification practices such as intercropping in woody cropping systems have recently been proposed as a promising management strategy for addressing problems related to soil degradation, climate change mitigation and food security. In this study, we assess the impact of several diversification practices in different management regimes on the main carbon fluxes regulating the soil carbon balance under semiarid Mediterranean conditions.

Methods

The study was conducted in two nearby cropping systems: (i) a low input rainfed almond (Prunus dulcis Mill.) orchard cultivated on terraces and (ii) a levelled intensively irrigated mandarin (Citrus reticulata Blanco) orchard with a street-ridge morphology. The almond trees were intercropped with Capparis spinosa or with Thymus hyemalis While the mandarin trees were intercropped with a mixture of barley and vetch followed by fava bean. Changes caused by crop diversifications on C inputs into the soil and C outputs from the soil were estimated.

Results

Crop diversification did not affect soil organic carbon stocks but did affect the carbon inputs and outputs regulating the soil carbon balance of above Mediterranean agroecosystems. Crop diversification with perennials in the low-input rainfed woody crop system significantly improved the annual soil C balance in the short-term. However, crop diversification with annual species in the intensively managed woody crop system had not effect on the annual soil C balance.

Conclusions

Our results highlight the potential of intercropping with perennials in rainfed woody crop systems for climate change mitigation through soil carbon sequestration.
Ready When the Big One Comes? Natural Disasters and Mass Support for Preparedness Investment
Authors: Bechtel Michael M. , Mannino Massimo
Published: August 2021

Societies can address collective threats such as natural disasters or pandemics by investing in preparedness (ex ante) or by offering compensation after an adverse event has occurred (ex post). What explains which of these options voters prefer? We study how personal exposure and policy knowledge affect mass support for long-term disaster preparedness, a type of long-term investment meant to cope with an increasingly destructive and frequent class of events. We first assess whether support for preparedness reflects personal affectedness and find that neither subjective nor geo-coded measures of disaster exposure predict policy preferences. Second, we explore whether this finding can be explained by misperceptions about the features of the available policy options. We find that revealing the damage reductions associated with preparedness systematically reduces opposition to long-term investment. These results suggest that opposition to preparing for collective threats may depend more on informational deficiencies than on personal experience with realized risks.
Prevalence vs impact: a mixed methods study of survivorship issues in colorectal cancer
Authors: Drury Amanda , Payne Sheila , Brady Anne-Marie
Published: August 2021

Purpose

This study aims to explore the prevalence of CRC survivorship issues and their impact on survivors’ quality of life (QoL).

Methods

This study utilised a mixed methods sequential explanatory design. Adult CRC survivors between 6- and 60-months post-diagnosis (n = 304) were purposively recruited from three hospitals and twenty-one cancer support centres in Ireland. QoL was evaluated using the EuroQol and FACT-C questionnaires and results compared to population norms. 22 survey participants took part in semi-structured interviews exploring the impact of survivorship issues on their daily lives.

Results

While CRC survivors reported QoL outcomes comparable to or better than normative populations, 54% were dissatisfied with their QoL. The most common survivorship issues reported included negative body image (74%), fatigue (68%), sexual dysfunction (66%) and sleep disturbance (59%). Thematic analysis of the qualitative data illustrated survivors’ attempts to live with the impact of cancer and its treatment (loss, fear, impact) and striving to contextualise, reframe and understand the consequences of cancer and its treatment (control, vigilance, benefit). Within these themes, the cross-domain impact of less prevalent symptoms including bowel dysfunction (28–57%) and peripheral neuropathy (47%) were widely discussed.

Conclusions

Although cancer survivors report positive QoL outcomes, many experience distressing physical, psychological and social effects. The findings suggest less common and difficult to manage symptoms are the greatest source of distress and unmet need. Support and information must be tailored to address survivors’ individual needs and preferences for support, informed by holistic person-centred assessment.
Phytochemical variability during vegetation of Chamerion angustifolium (L.) Holub genotypes derived from in vitro cultures
Authors: Dreger Mariola , Seidler-Łożykowska Katarzyna , Szalata Milena , Adamczak Artur , Wielgus Karolina
Published: August 2021

The purpose of the study was to evaluate Chamerion angustifolium (L.) Holub genotypes for preliminary selection and further breeding programs aimed at obtaining a suitable industrial form for the pharmaceutical applications. Clonally propagated plants representing 10 genotypes of Ch. angustifolium were regenerated under in vitro conditions, hardened and planted in the field. Studies included an evaluation of shoot proliferation, phytochemical assessment of in vitro and ex vitro plants as well as investigations of intraspecies variability regarding four phenological stages: vegetative, beginning of blooming, full blooming, and green fruit phases. Quantitative and qualitative analyses of bioactive compounds were performed using high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometer (HPLC–DAD–MS/MS) and high-performance liquid chromatography (HPLC) methods. The efficiency of shoot multiplication varied between genotypes from 8.12 to 21.48 shoots per explant. A high reproduction rate (> 20 shoots per explant) was recorded for four lines (PL_45, PL_44, PL_58, DE_2). Plants grown in vitro synthesized oenothein B (11.2–22.3 mg g−1 DW) and caffeic acid derivatives. Plants harvested from field contained the full spectrum of polyphenols characteristic for this species, and oenothein B and quercetin 3-O-glucuronide were the most abundant. The maximal content of oenothein B was determined in the vegetative phase of fireweed, while some flavonoids were found in the highest amount in full blooming phase. The results of analysis of variance indicated significant differences among genotypes in oenothein B, 3-O-caffeoylquinic acid and flavonoids accumulation in four phenological phases. PL_44 plants were characterized by high content of oenothein B and quercetin 3-O-glucuronide as well as a relatively high level of other flavonoids. Based on our phytochemical and micropropagation studies, PL_44 genotype was the best candidate for early selection and further breeding programs.