bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tackling the challenges of nanomedicines: are we ready?
Authors: Hertig John B , Shah Vinod P , Flühmann Beat , Mühlebach Stefan , Stemer Gunar , Surugue Jacqueline , Moss Rob , Di Francesco Tiziana 
Published: February 2021

Abstract

Purpose
This review provides an overview of the proceedings of the symposium “Tackling the Challenges of Nanomedicines: Are We Ready?” organized by the International Pharmaceutical Federation (FIP) Hospital Pharmacy Section and Non-Biological Complex Drugs (NBCDs) Working Group at the 2019 FIP World Congress of Pharmacy and Pharmaceutical Sciences. Debate centered on reasons underlying the current complex regulatory landscape for nanomedicines and their follow-on products (referred to as nanosimilars) and the pivotal role of hospital pharmacists in selecting, handling, and guiding usage of nanomedicines and nanosimilars.

Summary
The evaluation and use of nanomedicines are recognized among scientific, pharmaceutical, and regulatory bodies as complex. Interchangeability and substitutability of nanomedicines and nanosimilars are confounded by a lack of pharmaceutical and pharmacological equivalence, reflecting the inherent complex nature of these drug products and manufacturing processes. Consequences include implications for clinical safety and efficacy and, ultimately, comparability. Local regulatory approvals of some nanomedicines have occurred, but there is no standard to ensure streamlined evaluation and use of consistent measures of therapeutic equivalence of reference products and their nanosimilars. Hospital pharmacists are expected to be experts in the selection, handling, and substitution of nanomedicines and familiarize themselves with the limitations of current methods of assessing pharmaceutical and clinical equivalence of nanosimilars in order to ensure informed formulary decision-making and eventual patient benefit.

Conclusion
Supportive guidance for pharmacists focusing on the substitutability and/or interchangeability of nanomedicines and their nanosimilars is needed. Current FIP guidance for pharmacists on therapeutic interchange and substitution should be extended to include nanomedicines and nanosimilars.
Effects of vacuum soaking on the hydration, steaming, and physiochemical properties of japonica rice
Authors: Li Qiuyun , Li Sen , Guan Xiao , Huang Kai , Zhu Fengbo 
Published: February 2021

ABSTRACT
Soaking is an essential step in the processing of various rice products. In this study, the influences of vacuum soaking on hydration, steaming, and physiochemical properties of rice were investigated. Results showed that vacuum soaking accelerated water absorption as well as affected the mobility and density of water protons inside rice during soaking. Vacuum soaking could considerably shorten the optimal steaming time from 58 to 32 min and reduce the adhesiveness of steamed rice. Microstructure analysis of rice revealed that porous structure was formed on rice surface and the arrangement of starch granules became loosened after vacuum soaking. Moreover, vacuum soaking slightly reduced the relative crystallinity of rice starches without altering the crystalline type. The gelatinization temperature as well as the peak and trough viscosity was also decreased after vacuum soaking. Our study suggested that vacuum soaking was conducive to improve the soaking and steaming properties of rice.
Spontaneous quantity discrimination in a family-living lizard
Authors: Szabo Birgit , Noble Daniel W A , McCloghry Kaitlin J , Monteiro Marco E S , Whiting Martin J 
Published: February 2021

Abstract
While foraging or during social interactions, animals may benefit from judging relative quantity. Individuals may select larger prey or a patch with more food and, likewise, it may pay to track the number and type of individuals and social interactions. We tested for spontaneous quantity discrimination in the gidgee skink (Egernia stokesii), a family-living lizard. Lizards were presented with food quantities differing in number or size and were able to select the larger quantity of food items when they differed in number but not when items differed in size. We show, for the first time, superior spontaneous discrimination of items differing in number over size in a lizard species, which contrasts with previous findings. Our simple method, however, did not include controls for the use of continuous quantities, and further tests are required to determine the role of such information during quantity discrimination. Our results provide support for the use of the parallel individuation system for the discrimination of small quantities (four or fewer items). Lizards might, however, still use the approximate number system if items in larger quantities (more than four) are presented. Overall, we uncovered evidence that species might possess specific cognitive abilities potentially adapted to their niche with respect to quantity information (discrete and/or continuous) and the processing system used when judging quantities. Importantly, our results highlight the need for testing multiple species using similar testing procedures to gain a better understanding of the underlying causes leading to differences across species.
Contextual variations in calls of two nonoscine birds: the blue petrel Halobaena caerulea and the Antarctic prion Pachyptila desolata
Authors: Gémard Charlène , Planas-Bielsa Víctor , Bonadonna Francesco , Aubin Thierry 
Published: February 2021

Abstract
Bird vocalizations are critical cues in social interactions as they convey temporary information varying with the social context, for example, the signaler motivation when facing a rival or a potential mate. To date, literature mainly focused on learning birds. Burrowing petrels (Procellariidae) are nonlearning birds with a limited vocal repertoire. Bachelor males communicate with conspecifics with a single call emitted in three situations: in the absence of a certain auditory (spontaneous calls), toward females (female-directed calls), and toward males (male-directed calls). We first hypothesized that, although the call structure is preserved, temporal and spectral parameters vary between the three call types of bachelor males, translating different motivations (Motivation Hypothesis). To go further, we hypothesized that acoustic variations in male-directed calls indicate the signaler’s aggressive motivation and, therefore, the variations are similar whether calls are produced by breeder or bachelor males (Breeding Status Hypothesis). We tested the two hypotheses performing field playback experiments on two petrel species: the blue petrel (Halobaena caerulea) and the Antarctic prion (Pachyptila desolata). Despite the obvious call stereotypy, we observed temporal variations and frequency shifts when males react to a female or a male, which may translate the sexual or aggressive motivation of the signaler. Furthermore, the similarity of variations in male-directed calls of both breeder and bachelor males suggests the aggressive motivation. So far, vocal plasticity in nonlearning birds has been greatly underestimated. Here, we highlighted the expression of different motivations through vocal variations and the ability to produce frequency variations in species with genetically coded vocalizations.
Territoriality in Drosophila: indirect effects and covariance with body mass and metabolic rate
Authors: Tremblay Matteo , Rundle Howard D , Videlier Mathieu , Careau Vincent 
Published: February 2021

Abstract
Territoriality (i.e., defense of a resource) is the outcome of behavioral interactions that can result in selective advantages in many vertebrates and invertebrates. Since territoriality is expressed in a social context, an individuals’ territoriality may change according to the phenotype of the opponents that they are confronted with (termed “indirect effects”). Defending a territory may also confer energetic costs to individuals, which could be reflected in their standard metabolic rate (SMR), a key component of an ectotherms’ energy budget. Here, we measured territoriality using dyadic contests, body mass, and SMR using flow-through respirometry, twice in each of 192 adult male Drosophila melanogaster. Territoriality, body mass, and (whole-animal) SMR were all significantly repeatable. However, essentially all the among-individual variation in SMR was shared with body mass, as indicated by a very strong among-individual correlation (rind) between body mass and SMR. The among-individual correlation between territoriality and SMR also tended to be positive, suggesting the presence of underlying metabolic costs to territoriality. Although indirect effects on territoriality were present but weak (accounting for 8.4% of phenotypic variance), indirect effects on territoriality were negatively and significantly correlated with body mass. This indicates that larger individuals tended to suppress their opponents territoriality. Variation among individuals in their ability to suppress territoriality in others was not associated with their own territoriality or SMR.
Role of zinc in female reproduction
Authors: Garner Tyler Bruce , Hester James Malcolm , Carothers Allison , Diaz Francisco J 
Published: February 2021

Abstract
Zinc is a critical component in a number of conserved processes that regulate female germ cell growth, fertility, and pregnancy. During follicle development, a sufficient intracellular concentration of zinc in the oocyte maintains meiotic arrest at prophase I until the germ cell is ready to undergo maturation. An adequate supply of zinc is necessary for the oocyte to form a fertilization-competent egg as dietary zinc deficiency or chelation of zinc disrupts maturation and reduces the oocyte quality. Following sperm fusion to the egg to initiate the acrosomal reaction, a quick release of zinc, known as the zinc spark, induces egg activation in addition to facilitating zona pellucida hardening and reducing sperm motility to prevent polyspermy. Symmetric division, proliferation, and differentiation of the preimplantation embryo rely on zinc availability, both during the oocyte development and post-fertilization. Further, the fetal contribution to the placenta, fetal limb growth, and neural tube development are hindered in females challenged with zinc deficiency during pregnancy. In this review, we discuss the role of zinc in germ cell development, fertilization, and pregnancy with a focus on recent studies in mammalian females. We further detail the fundamental zinc-mediated reproductive processes that have only been explored in non-mammalian species and speculate on the role of zinc in similar mechanisms of female mammals. The evidence collected over the last decade highlights the necessity of zinc for normal fertility and healthy pregnancy outcomes, which suggests zinc supplementation should be considered for reproductive age women at risk of zinc deficiency.
Experiences with Technology Amongst an International Sample of Older Adults: Results from a Qualitative Interpretive Meta-Synthesis
Authors: Miller Vivian J , Roark Erin M , Fields Noelle L , Cronley Courtney 
Published: February 2021

AbstractIdentifying and implementing effective strategies to combat social exclusion and isolation is critical, given that eradicating social isolation has been identified as one of the social work profession’s main goals. Training older adults to use information and communications technology (ICT) effectively may be an appropriate intervention to combat and mitigate the negative impacts of social isolation within the aging population. ICT has demonstrated promise with older adults, with research demonstrating that older adults with higher technology use report better self-reported physical health and subjective well-being. Given this promise, the authors of this study seek to create more nuanced understanding of the experience of ICT usage, as told by an international sample of older adults using a qualitative interpretive meta-synthesis (QIMS). Using the QIMS methodology paired with phenomenological reduction, the authors synthesised nine (N = 9) qualitative studies through the lens of the World Health Organization’s age-friendly domains. This process resulted in three overarching themes that describe older adults’ experiences engaging with technology: ‘desire for empowerment’, ‘connection’ and ‘aging well’. Findings from this study highlight overall benefits of technology use among older adults aging in the community. This study concludes with implications for social work research and practice.
New Trajectory of Clinical and Biomarker Changes in Sporadic Alzheimer’s Disease
Authors: Zhuo Junjie , Zhang Yuanchao , Liu Yong , Liu Bing , Zhou Xiaoqing , Bartlett Perry F , Jiang Tianzi ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

Abstract
Identifying dynamic changes in biomarkers and clinical profiles is essential for understanding the progression of Alzheimer’s disease (AD). The relevant studies have primarily relied on patients with autosomal dominant AD; however, relevant studies in sporadic AD are poorly understood. Here, we analyzed longitudinal data from 665 participants (mean follow-up 4.90 ± 2.83 years). By aligning normal cognition (CN) baseline with a clinical diagnosis of mild cognitive impairment (MCI) or AD, we studied the progression of AD using a linear mixed model to estimate the clinical and biomarker changes from stable CN to MCI to AD. The results showed that the trajectory of hippocampal volume and fluorodeoxyglucose (FDG) was consistent with the clinical measures in that they did not follow a hypothetical sigmoid curve but rather showed a slow change in the initial stage and accelerated changes in the later stage from MCI conversion to AD. Dramatic hippocampal atrophy and the ADAS13 increase were, respectively, 2.5 and 1 years earlier than the MCI onset. Besides, cognitively normal people with elevated and normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. These results reveal that pre-MCI to pre-AD may be a better time window for future clinical trial design.
The Prenatal Origins of Human Brain Asymmetry: Lessons Learned from a Cohort of Fetuses with Body Lateralization Defects
Authors: Kienast Patric , Schwartz Ernst , Diogo Mariana C , Gruber Gerlinde M , Brugger Peter C , Kiss Herbert , Ulm Barbara , Bartha-Doering Lisa , Seidl Rainer , Weber Michael , Langs Georg , Prayer Daniela , Kasprian Gregor 
Published: February 2021

AbstractKnowledge about structural brain asymmetries of human fetuses with body lateralization defects—congenital diseases in which visceral organs are partially or completely incorrectly positioned—can improve our understanding of the developmental origins of hemispheric brain asymmetry. This study investigated structural brain asymmetry in 21 fetuses, which were diagnosed with different types of lateralization defects; 5 fetuses with ciliopathies and 26 age-matched healthy control cases, between 22 and 34 gestational weeks of age. For this purpose, a database of 4007 fetal magnetic resonance imagings (MRIs) was accessed and searched for the corresponding diagnoses. Specific temporal lobe brain asymmetry indices were quantified using in vivo, super-resolution-processed MR brain imaging data. Results revealed that the perisylvian fetal structural brain lateralization patterns and asymmetry indices did not differ between cases with lateralization defects, ciliopathies, and normal controls. Molecular mechanisms involved in the definition of the right/left body axis—including cilium-dependent lateralization processes—appear to occur independently from those involved in the early establishment of structural human brain asymmetries. Atypically inverted early structural brain asymmetries are similarly rare in individuals with lateralization defects and may have a complex, multifactorial, and neurodevelopmental background with currently unknown postnatal functional consequences.
Reductions in Gray Matter Linked to Epigenetic HIV-Associated Accelerated Aging
Authors: Lew Brandon J , Schantell Mikki D , O’Neill Jennifer , Morsey Brenda , Wang Tina , Ideker Trey , Swindells Susan , Fox Howard S , Wilson Tony W 
Published: February 2021

Abstract
A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22–72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.
Coronary microcirculation damage in anthracycline cardiotoxicity
Authors: Galán-Arriola Carlos , Vílchez-Tschischke Jean Paul , Lobo Manuel , López Gonzalo J , de Molina-Iracheta Antonio , Pérez-Martínez Claudia , Villena-Gutiérrez Rocio , Macías Álvaro , Díaz-Rengifo Iván A , Oliver Eduardo , Fuster Valentin , Sánchez-González Javier , Ibanez Borja 
Published: February 2021

Abstract

Aims
The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment.

Methods and results
Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime.

Conclusion
Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.
Human immunodeficiency viral infection and differences in interstitial ventricular fibrosis and left atrial size
Authors: Wu Katherine C , Haberlen Sabina A , Plankey Michael W , Palella Frank J , Piggott Damani A , Kirk Gregory D , Margolick Joseph B , Post Wendy S 
Published: February 2021

Abstract

Aims
The extent to which human immunodeficiency viral (HIV) infection is independently associated with myocardial disease in the era of combination antiretroviral therapy (cART) remains understudied. We assessed differences in cardiovascular magnetic resonance imaging (CMR) metrics among people living with HIV (PLWH) and without HIV (PWOH).

Methods and results
Among 436 participants (aged 54.7 ± 6.0 years, 29% women) from three cohorts, we acquired CMR cines, late gadolinium enhancement (LGE), and T1 mapping. Multivariable linear regressions were used to evaluate associations between HIV serostatus and CMR metrics. Baseline characteristics were similar by HIV serostatus; 63% were PLWH of whom 88% received cART and 73% were virally suppressed. Median left ventricular ejection fraction was normal and similar by HIV serostatus (73%, PWOH vs. 72%, PLWH, P = 0.43) as were right ventricular function, biventricular volumes, and masses. LGE prevalence was similar (32%, PWOH vs. 36%, PLWH, P = 0.46) with low scar extents (4.1, PWOH vs. 4.9 g, PLWH, P = 0.51) and few ischaemic scars (3%, PWOH vs. 4%, PLWH, P = 0.70). Extracellular volume fraction (ECV) was higher among PLWH (29.2 ± 4.1% vs. 28.3 ± 3.7%, P = 0.04) as was indexed maximum left atrial (LA) volume (LAVI, 29.7 ± 10.3 vs. 27.8 ± 8.7 mL/m2, P = 0.05). After multivariate adjustment, ECV was 0.84% higher among PLWH (P = 0.05) and LAVI was 2.45 mL/m2 larger (P = 0.01). HIV seropositivity and higher ECV contributed to higher LAVI (P &lt; 0.02). There were no associations between HIV disease severity and CMR metrics among PLWH.

Conclusion
HIV seropositivity was independently associated with greater diffuse non-ischaemic fibrosis and larger LA volume but no other differences in CMR metrics.