bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis
Authors: Wunsch Ewa , Stadnik Anna , Kruk Beata , Szczepankiewicz Benedykt , Kotarska Katarzyna , Krawczyk Marcin , Górnicka Barbara , Wójcicki Maciej , Milkiewicz Piotr
Published: February 2021

Chronic fatigue and an impairment of general health‐related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC‐40 and Short Form 36 (SF‐36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well‐being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one‐third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF‐36 and PBC‐40 domains. Recurrent PSC and unemployment negatively affected the well‐being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.
Hatchery-Origin Stray Rates and Total Run Characteristics for Pink Salmon and Chum Salmon Returning to Prince William Sound, Alaska, in 2013–2015
Authors: Knudsen E. Eric , Rand Peter S. , Gorman Kristen B. , Bernard David R. , Templin William D.
Published: February 2021

Pacific salmon hatcheries support important commercial fisheries for Pink Salmon Oncorhynchus gorbuscha and Chum Salmon O. keta in Prince William Sound (PWS), Alaska. State policy mandates that hatchery-produced fish must not negatively impact natural populations, which can occur during mixed fisheries and via ecological and genetic interactions. Therefore, we quantified the spatial and temporal overlap of natural- and hatchery-origin salmon (1) as they migrated into PWS and (2) in PWS spawning streams. Intensive sampling during 2013–2015, combined with ancillary agency harvest and hatchery composition data, also allowed us to estimate the hatchery, natural, and total run sizes. Estimated annual proportions (SE in parentheses) of hatchery fish in the preharvest run ranged from 0.55 (0.01) to 0.86 (0.03) for Pink Salmon and from 0.51 (0.03) to 0.73 (0.02) for Chum Salmon. Proportions of hatchery fish across all sampled PWS spawning streams were much lower, ranging from 0.05 (0.03) to 0.15 (0.07) for Pink Salmon and from 0.03 (0.03) to 0.09 (0.03) for Chum Salmon. In both species, relatively high instream proportions of hatchery fish tended to be geographically localized, while many streams exhibited low proportions. The estimated total PWS runs were 50–142 million Pink Salmon and 2.3–5.4 million Chum Salmon. Commercial fisheries harvested 94–99% of hatchery-origin fish of both species, 27–50% of natural-origin Pink Salmon, and 17–20% of natural-origin Chum Salmon. Despite very high harvest rates on hatchery-produced fish, an estimated 0.8–4.5 million hatchery Pink Salmon and 30,000–90,000 hatchery Chum Salmon strayed into PWS spawning streams. Our findings provide context for further research on the relative productivity of hatchery- and natural-origin salmon spawning in streams, density-dependent survival, improvements in fidelity to hatchery release sites, the influence of hatchery production on escapement management and policy, and refinements in harvest management precision in PWS.
Thermomechanical analysis of large deflection in shear deformable FG‐CNT reinforced composite beams using perturbation technique
Authors: Babaei Hadi , Kiani Yaser , Reza Eslami M.
Published: February 2021

Present investigation deals with the geometrically nonlinear bending response of functionally graded carbon nanotube reinforced composite (FG‐CNTRC) beams. It is assumed that beam is resting on a three‐parameter elastic foundation. Uniform thermal field is also included into the formulation and properties are considered as temperature dependent. Distribution of CNTs in the beam may be uniform or functionally graded according to linear distribution of volume fraction of CNTs across the thickness. The equivalent properties of the composite media are obtained with the aid of the refined rule of mixtures approach which is calibrated with the available data based on the molecular dynamics simulations. The governing equations of the beam are obtained based on first‐order, third‐order, and sinusoidal theories. To capture the large deformations, the von Kármán type of kinematic assumptions is included. Two types of boundary conditions are included which are immovable pinned and immovable clamped. The established equations are reformulated and transferred into dimensionless presentation. After that, using the powerful two step perturbation technique, closed form expressions are provided to trace the nonlinear load‐deflection paths of the beam. Results of this study are compared with the available data in the open literature. After that, novel results are provided to discuss the effects of boundary conditions, temperature change, foundation stiffness, slenderness ratio, CNT volume fraction, and distribution profiles. It is shown that graded pattern of CNTs and volume fraction of CNTs are two important factors on the geometrically nonlinear response of the CNTRC beam.
Functional Correlates and Impact of Dietary Lactoferrin Intervention and its Concentration‐dependence on Neurodevelopment and Cognition in Neonatal Piglets
Authors: Chen Yue , Wang Bing , Yang Changwei , Shi Yujie , Dong Zhizhong , Troy Frederic A.
Published: February 2021

Scope

Lactoferrin (Lf), a sialylated milk glycoprotein, promotes early neurodevelopment and cognition. Functional concentrations of Lf, however, remain unknown. Our objective is to determine the concentration‐dependency of Lf on genes associated with neurodevelopment and cognition in neonatal piglets.

Methods and results

Piglets are given milk replacer with Lf at concentrations of 155 (low) or 285 mg kg‐1 day‐1 (high) from postnatal days 3 to 38. Gene expression associated with neurodevelopment, cognition, and cognate proteins were quantitated. This study found 1) The rate of learning and long‐term memory was higher with 155 mg kg‐1 day‐1 assessed in an eight‐arm radial maze; 2) Global gene transcription profiling showed this lower concentration upregulated genes and functions correlated with neurodevelopment and cognition, while the higher concentration regulated cellular processes for neuroprotection; 3) Expression of BDNF genes and proteins were higher with both concentrations, while genes regulating BDNF signaling, including SLC6A3, IGF‐1 responded more to the lower concentration; 4) The lower concentration modulated genes in the five highest networks associated with cellularity and neurocognition, while the prevention of neurodevelopmental and neurological pathologies was associated with the higher concentration.

Conclusion

The lower concentrations of Lf enhanced neurodevelopment and cognition, while higher concentrations are greater neuroprotective, findings of potential novel clinical relevance.
Comparative treatment effectiveness of oral fingolimod and conventional injectable disease‐modifying agents in multiple sclerosis
Authors: Earla Jagadeswara R. , Hutton George J. , Thornton Douglas J. , Chen Hua , Johnson Michael L. , Aparasu Rajender R.
Published: February 2021

Study Objective

To compare the effectiveness of oral fingolimod and conventional injectable disease‐modifying agents (DMAs) using the composite endpoint of relapse or DMA treatment switch in patients with multiple sclerosis (MS).

Design

A retrospective longitudinal cohort study.

Data Source

IBM MarketScan Commercial Claims and Encounters Database from 2010–2012.

Patients

Adults (≥18 years) with MS diagnosis (ICD‐9‐CM:340) who newly initiated DMAs.

Intervention

Oral fingolimod and conventional injectable DMAs (interferon beta and glatiramer acetate).

Measurements

Composite endpoint of time to relapse or DMA treatment switch.

Main Results

The incident study cohort consisted of 1997 MS patients who initiated oral fingolimod (15.6%) or injectable (84.4%) DMAs. The proportion of patients who had a composite endpoint (relapse/DMA treatment switch) in oral fingolimod and injectable DMA users was found to be 16.72% and 27.16%, respectively. The Cox PH regression model with stabilized IPTW revealed that fingolimod is equally effective as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint of relapse or DMA switch (adjusted hazard ratio [aHR]: 0.67, 95% CI: 0.43–1.03). Additional analysis among patients who were adherent also found no significant difference in the composite endpoint (aHR: 0.70, 95% CI 0.49–1.15) between oral fingolimod and injectable DMA users.

Conclusions

Oral fingolimod has similar effectiveness as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint (relapse or DMA treatment switch). In addition, when assessed independently, oral fingolimod showed no difference in reducing the time to relapse or DMA treatment switch compared to injectable DMAs.
Measuring gas vesicle dimensions by electron microscopy
Authors: Dutka Przemysław , Malounda Dina , Metskas Lauren Ann , Chen Songye , Hurt Robert C. , Lu George J. , Jensen Grant J. , Shapiro Mikhail G.
Published: February 2021

Gas vesicles (GVs) are cylindrical or spindle‐shaped protein nanostructures filled with air and used for flotation by various cyanobacteria, heterotrophic bacteria, and Archaea. Recently, GVs have gained interest in biotechnology applications due to their ability to serve as imaging agents and actuators for ultrasound, magnetic resonance and several optical techniques. The diameter of GVs is a crucial parameter contributing to their mechanical stability, buoyancy function and evolution in host cells, as well as their properties in imaging applications. Despite its importance, reported diameters for the same types of GV differ depending on the method used for its assessment. Here, we provide an explanation for these discrepancies and utilize electron microscopy (EM) techniques to accurately estimate the diameter of the most commonly studied types of GVs. We show that during air drying on the EM grid, GVs flatten, leading to a ~1.5‐fold increase in their apparent diameter. We demonstrate that GVs' diameter can be accurately determined by direct measurements from cryo‐EM samples or alternatively indirectly derived from widths of flat collapsed and negatively stained GVs. Our findings help explain the inconsistency in previously reported data and provide accurate methods to measure GVs dimensions.
Mask blast with a new chemical logic of amino acids for improved protein function prediction
Authors: Pathak Amita , Roy Toran , Edubilli Avinash , Jayaram Bhyravabhotla
Published: February 2021

With the exponential increase in protein sequence data, there is an urgency to acquire a knowledge of function of the millions of sequences, using automated methods with high reliability. Conventional methods for annotating a protein sequence transfer the function of a homologous sequence with known functions based on evolutionary information. Here, we present a newer way of classifying amino acids based on chemical measures and demonstrate that, when integrated with mask BLAST, the chemical properties identified outperform current classifications of amino acids as well as evolutionary measures in function detection.
Drug discovery: Insights from the invertebrate Caenorhabditis elegans
Authors: Giunti Sebastián , Andersen Natalia , Rayes Diego , De Rosa María José
Published: February 2021

Therapeutic drug development is a long, expensive, and complex process that usually takes 12–15 years. In the early phases of drug discovery, in particular, there is a growing need for animal models that ensure the reduction in both cost and time. Caenorhabditis elegans has been traditionally used to address fundamental aspects of key biological processes, such as apoptosis, aging, and gene expression regulation. During the last decade, with the advent of large‐scale platforms for screenings, this invertebrate has also emerged as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets. In this review, we discuss the reasons why C. elegans has been positioned as an outstanding cost‐effective option for drug discovery, highlighting both the advantages and drawbacks of this model. Particular attention is paid to the suitability of this nematode in large‐scale genetic and pharmacological screenings. High‐throughput screenings in C. elegans have indeed contributed to the breakthrough of a wide variety of candidate compounds involved in extensive fields including neurodegeneration, pathogen infections and metabolic disorders. The versatility of this nematode, which enables its instrumentation as a model of human diseases, is another attribute also herein underscored. As illustrative examples, we discuss the utility of C. elegans models of both human neurodegenerative diseases and parasitic nematodes in the drug discovery industry. Summing up, this review aims to demonstrate the impact of C. elegans models on the drug discovery pipeline.
Evolution of convective characteristics during tropical cyclogenesis
Authors: Kilroy Gerard
Published: February 2021

Four idealized, high‐resolution (500 m horizontal grid spacing), numerical simulations are used to investigate the evolution of convective structures during tropical cyclogenesis. The simulations all begin with a weak initial axisymmetric cloud‐free vortex in a quiescent environment, but differ in the moisture level of the initial sounding and whether or not ice microphysical processes are considered. Irrespective of experimental setup, there is only a short period where shallow or congestus clouds dominate. The shallow cloud phase is slightly extended with the drier initial environmental sounding. The composite structure of the convective elements sampled changes markedly throughout the genesis period. For much of the genesis phase, vertical profiles of the mean convective cell show significant amounts of anticyclonic vorticity produced in cells in the inner core. Towards the end of the genesis phase, there is a large increase in the production of cyclonic vertical vorticity in inner‐core convection, and cyclonic vorticity becomes dominant at low‐mid levels. The evolution from roughly equal strength vertical profiles of cyclonic/anticyclonic vorticity at low‐mid levels to profiles where cyclonic vorticity dominates occurs at relatively low system wind speeds (Vmax less than 10 m·s−1). This finding indicates a change in the structure of vortical convection prior to rapid intensification. In outer‐core convection, there are roughly equal strength vertical vorticity dipoles produced throughout the genesis period.
Wood screw design: influence of thread parameters on the withdrawal capacity
Authors: Hoelz Kevin , Kleinhans Lukas , Matthiesen Sven
Published: February 2021

Self-tapping wood screws are important fasteners in timber construction. A characteristic of these screws is their high axial load-bearing capacity, which also depends on their withdrawal capacity. This is used for structural design and is thus an important optimization parameter for wood screws. To increase the withdrawal capacity, knowledge of the influence of the thread parameters, such as outer diameter, pitch or flank angle, is required. The influences of pitch and flank angle on the withdrawal capacity have not yet been sufficiently subjected to research and are therefore investigated in this study. A total of ten specially developed screw prototypes with pitches in the range of 3.04 mm and 5.9 mm and flank angles in the range of 35° and 45° are used. The screw prototypes are flat ribbed bars with uncoiled screw thread. The effect on the withdrawal capacity is measured using an experimental setup based on test standard EN 1382:2016. The pitch showed a significant influence (p = 0.000, f = 0.37) whereas the influence of flank angle was not significant (p = 0.283). A smaller pitch leads to a higher withdrawal capacity, irrespective of the flank angle. The experimental results are explained based on the theoretical models of bonding mechanisms and conical stress distribution. To optimize the withdrawal capacity of a ø 8 mm screw, a smaller pitch is preferable. The determined influence of the pitch can also be used to improve the accuracies of calculation models for the withdrawal capacity.
Social media in surgery: evolving role in research communication and beyond
Authors: Grossman Rebecca , Sgarbura Olivia , Hallet Julie , Søreide Kjetil
Published: February 2021

Purpose

To present social media (SoMe) platforms for surgeons, how these are used, with what impact, and their roles for research communication.

Methods

A narrative review based on a literature search regarding social media use, of studies and findings pertaining to surgical disciplines, and the authors’ own experience.

Results

Several social networking platforms for surgeons are presented to the reader. The more frequently used, i.e., Twitter, is presented with details of opportunities, specific fora for communication, presenting tips for effective use, and also some caveats to use. Details of how the surgical community evolved through the use of the hashtag #SoMe4Surgery are presented. The impact on gender diversity in surgery through important hashtags (from #ILookLikeASurgeon to #MedBikini) is discussed. Practical tips on generating tweets and use of visual abstracts are presented, with influence on post-production distribution of journal articles through “tweetorials” and “tweetchats.” Findings from seminal studies on SoMe and the impact on traditional metrics (regular citations) and alternative metrics (Altmetrics, including tweets, retweets, news outlet mentions) are presented. Some concerns on misuse and SoMe caveats are discussed.

Conclusion

Over the last two decades, social media has had a huge impact on science dissemination, journal article discussions, and presentation of conference news. Immediate and real-time presentation of studies, articles, or presentations has flattened hierarchy for participation, debate, and engagement. Surgeons should learn how to use novel communication technology to advance the field and further professional and public interaction.
The role of ego integrity and despair in older adults’ well-being during the COVID-19 crisis: the mediating role of need-based experiences
Authors: van der Kaap-Deeder Jolene , Vermote Branko , Waterschoot Joachim , Soenens Bart , Morbée Sofie , Vansteenkiste Maarten
Published: February 2021

The COVID-19 pandemic has affected people across the world, with important heterogeneity among older adults in how they respond to the challenges associated with this crisis. Relying on a cross-fertilization between Erikson’s personality theory and self-determination theory, this study aimed to examine possible sources of resilience (i.e., ego integrity and need satisfaction) and vulnerability (i.e., despair) in older adults’ (mal) adjustment, thereby additionally considering the role of multiple risk and protective factors (e.g., gender and marital status). During the second month of the lockdown period in Belgium, 693 older adults (Mage = 70.06, SD = 4.48, range: 65–89 years, 62.1% female) filled out online questionnaires concerning the study variables, while also completing assessments of several important sociodemographic factors. Structural equation modeling suggested that both ego integrity and despair related to indicators of well-being and psychological distress through experienced need satisfaction. Additionally, we found several factors to protect (e.g., higher perceived income) or diminish (e.g., being widowed) older adults’ well-being during these challenging times, with little evidence for a moderating role of these factors in associations between the psychological variables. Theoretical and practical implications of these results are discussed.
The role of disturbance in invasive plant establishment in a changing climate: insights from a drought experiment
Authors: Orbán Ildikó , Szitár Katalin , Kalapos Tibor , Körel-Dulay György
Published: February 2021

Climate change and disturbance are two major factors affecting the establishment of invasive species, yet few studies to date have assessed the individual and interactive effects of these two factors in a common setting. Disturbance has often been found to facilitate the establishment of invading species, while climate change may affect them positively or negatively through altering abiotic conditions, or indirectly by modifying species interactions. In a full-factorial field experiment in a semiarid temperate grassland in Central Hungary, we studied the effects of drought (40% rain exclusion throughout the year) and soil disturbance on the emergence, survival and aboveground biomass of four invasive plant species that represent different life forms and that are of concern in the region and at a broader scale. We added seeds of Ambrosia artemisiifolia (annual forb), Cenchrus incertus (annual grass), Asclepias syriaca (perennial forb) and Ailanthus altissima (deciduous tree) in drought and non-drought plots with and without soil disturbance. Ailanthus germinated poorly irrespective of treatments. Disturbance facilitated while drought suppressed seedling emergence in the other three species. Ambrosia was more sensitive to disturbance, while Cenchrus was more responsive to drought. Asclepias achieved substantial emergence in disturbed non-drought plots only, as drought strongly suppressed its emergence even in the presence of disturbance. Seedling survival and late-season aboveground biomass of Ambrosia and Cenchrus were positively affected by disturbance but were unaffected by drought, while no Asclepias seedling survived until late summer. Our results highlight that both drought and disturbance may considerably impact the establishment of invasive plants, with potential interactive effects, but responses may greatly differ among species and life stages. Overall, our findings in this study suggest that although drought may negatively affect seedling establishment, a drier climate may not suppress or eliminate invasive species if soil disturbance is present. They also highlight the importance of including disturbance in studies assessing the potential effects of climate change on plant invasions.
Engaging and Supporting Young Children and their Families in Early Childhood Mental Health Services: The Role of the Family Partner
Authors: Nayak Sameera S. , Tobias Carol , Wolfe Jessica , Roper Kate , Méndez-Peñate Larisa , Moulin Christy , Arty Malika , Scoglio Arielle A. J. , Kelleher Amy , Rue Jacqueline , Brigham Molly , Bradshaw Tarsha , Byars Natasha , Camacho Angelina , Douglas Sade , Molnar Beth E.
Published: February 2021

This study explores the role of family partners, peer professionals with lived experiences of raising a child with behavioral health needs, and their value in primary and community-care based mental health services for young children aged 0–8 years. Interviews and focus groups were conducted with staff, leadership, and caregiver participants (n = 38) from two early childhood mental health programs and analyzed using thematic analysis. Five interdependent themes emerged: (1) the centrality of lived experience to the family partner role; (2) the importance of the family partner in family engagement and relationship building; (3) the value added by the family partner in navigating systems; (4) the ability of the family partner to build skills and empower caregivers; (5) the role of the family partner in alleviating caregiver stress and other mental health concerns. Adapting and expanding the role of family partners will improve effective mental health care for children and their caregivers.
Do transportation network companies increase or decrease transit ridership? Empirical evidence from San Francisco
Authors: Erhardt Gregory D. , Mucci Richard Alexander , Cooper Drew , Sana Bhargava , Chen Mei , Castiglione Joe
Published: February 2021

Transportation network companies (TNCs), such as Uber and Lyft, have been hypothesized to both complement and compete with public transit. Existing research on the topic is limited by a lack of detailed data on the timing and location of TNC trips. This study overcomes that limitation by using data scraped from the Application Programming Interfaces of two TNCs, combined with Automated Passenger Count data on transit use and other supporting data. Using a panel data model of the change in bus ridership in San Francisco between 2010 and 2015, and confirming the result with a separate time-series model, we find that TNCs are responsible for a net ridership decline of about 10%, offsetting net gains from other factors such as service increases and population growth. We do not find a statistically significant effect on light rail ridership. Cities and transit agencies should recognize the transit-competitive nature of TNCs as they plan, regulate and operate their transportation systems.
Does Social Capital Affect Voter Turnout? Evidence from Italy
Authors: Fiorino Nadia , Galli Emma , Pontarollo Nicola
Published: February 2021

In this paper we develop a new composite indicator, named Social Catalyst, able to account for the complex and multifaceted nature of the social capital in a unitary measure. We use our indicator, as well as its components, to explore the relation between social capital and electoral participation in the parliamentary elections in Italy from 1994 to 2008, addressing the potential endogeneity bias. Our findings show that (i) the Social Catalyst positively and significantly affects voter turnout in both Chambers; (ii) among the different dimensions of social capital, social norms and associational networks play a prominent role in the Italian regional context.
Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury
Authors: Jiang Yuanxu , Xia Mingzhu , Xu Jing , Huang Qiang , Dai Zhongliang , Zhang Xueping
Published: February 2021

Dexmedetomidine (Dex), a highly selective α2-adrenergic receptor (α2AR) agonist, has an anti-inflammatory property and can alleviate pulmonary edema in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the mechanism is still unclear. In this study, we attempted to investigate the effect of Dex on alveolar epithelial sodium channel (ENaC) in the modulation of alveolar fluid clearance (AFC) and the underlying mechanism. Lipopolysaccharide (LPS) was used to induce acute lung injury (ALI) in rats and alveolar epithelial cell injury in A549 cells. In vivo, Dex markedly reduced pulmonary edema induced by LPS through promoting AFC, prevented LPS-induced downregulation of α-, β-, and γ-ENaC expression, attenuated inflammatory cell infiltration in lung tissue, reduced the concentrations of TNF-α, IL-1β, and IL-6, and increased concentrations of IL-10 in bronchoalveolar lavage fluid (BALF). In A549 cells stimulated with LPS, Dex attenuated LPS-mediated cell injury and the downregulation of α-, β-, and γ-ENaC expression. However, all of these effects were blocked by the PI3K inhibitor LY294002, suggesting that the protective role of Dex is PI3K-dependent. Additionally, Dex increased the expression of phosphorylated Akt and reduced the expression of Nedd4-2, while LY294002 reversed the effect of Dex in vivo and in vitro. Furthermore, insulin-like growth factor (IGF)-1, a PI3K agonists, promoted the expression of phosphorylated Akt and reduced the expression of Nedd4-2 in LPS-stimulated A549 cells, indicating that Dex worked through PI3K, and Akt and Nedd4-2 are downstream of PI3K. In conclusion, Dex alleviates pulmonary edema by suppressing inflammatory response in LPS-induced ALI, and the mechanism is partly related to the upregulation of ENaC expression via the PI3K/Akt/Nedd4-2 signaling pathway.
Breathing space for PM on the moon
Authors: Nickels Liz
Published: February 2021

PM producer Metalysis and the ESA are researching ways to extract metal powder from moon dust –leaving astronauts with something even more precious: oxygen for potential use in life support.
Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation
Authors: Du Xufei , Li Fei , Zhang Chao , Li Na , Huang Huaqiong , Shao Zhehua , Zhang Min , Zhan Xueqin , He Yicheng , Ju Zhenyu , Li Wen , Chen Zhihua , Ying Songmin , Shen Huahao
Published: February 2021

Eosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of eosinophils in asthmatic airway pathogenesis. However, their regulatory functions have not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described, which are mainly derived from eosinophils. UsingCcl6knockout mice, further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin (OVA) challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells (HSCs). Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma.
Strategies for Optic Pathways Decompression for Extra-Axial Tumors or Intracranial Aneurysms: A Technical Note
Authors: Mattogno Pier Paolo , Sturiale Carmelo Lucio , Rapisarda Alessandro , Olivi Alessandro , Albanese Alessio
Published: February 2021

Background Different types of skull base tumors and intracranial aneurysms may lead to compression of the optic pathways. Since most of them are biologically benign conditions, the first aim of surgery is preservation of optic nerves rather than the oncologic radicality.

Materials and methods Based on the progressive technical refinements coming from our institutional experience of optic nerve compression from aneurysms and extra-axial tumors, we analyzed the surgical steps to release nerves and chiasm during tumor debulking and aneurysm clipping.

Results We distinguished vascular and tumor lesions according to the main direction of optic nerve compression: lateral to medial, medial to lateral, inferior to superior, and anterior to posterior. We also identified four fundamental sequential maneuvers to release the optic nerve, which are (1) falciform ligament (FL) section, (2) optic canal unroofing, (3) anterior clinoid process drilling, and (4) optic strut removal. The FL section is always recommended when a gentle manipulation of the optic nerve is required. Optic canal unroofing is suggested in case of lateral-to-medial compression (i.e., clinoid meningiomas), medial-to-lateral compression (i.e., tuberculum sellae meningiomas), and inferior-to-superior compression (i.e., suprasellar lesions). Anterior clinoidectomy and optic strut removal may be necessary in case of lateral-to-medial compression from paraclinoid aneurysms or meningiomas.

Conclusions Preservation of the visual function is the main goal of surgery for tumors and aneurysms causing optic nerve compression. This mandatory principle guides the approach, the timing, and the technical strategy to release the optic nerve, and is principally based on the direction of the compression vector.
Ex Vivo Prediction of Comprehensive Coagulation Potential Using Simulated Blood Concentrations of Emicizumab in Patients with Acquired Hemophilia A
Authors: Takeyama Masahiro , Furukawa Shoko , Yada Koji , Ogiwara Kenichi , Shimonishi Naruto , Nakajima Yuto , Mizumachi Kuniyoshi , Noguchi-Sasaki Mariko , Shima Midori , Nogami Keiji
Published: February 2021

Introduction Emicizumab prophylaxis improves coagulation function in congenital hemophilia A, regardless of inhibitor presence. We recently reported that emicizumab enhanced the coagulant potentials, ex vivo, in plasmas from patients with acquired hemophilia A (PwAHAs) at diagnosis. However, coagulant effects of emicizumab in PwAHAs during the clinical course remain unclear.

Aim To assess ex vivo coagulant effects of emicizumab in PwAHAs during the clinical course.

Methods/Results Blood samples were obtained from 14 PwAHAs on (median) days 0 and 6 during a severe-bleeding phase, and days 27 and 59 during a reduced-bleeding phase with elevated endogenous factor VIII (FVIII) and decreased inhibitor titers. If administered a single dose of 3 or 6 mg/kg, or two doses at 6 mg/kg followed by 3 mg/kg, estimated plasma emicizumab concentrations (10/5/2.5, 20/10/5, and 30/15/7.5 µg/mL on days 0–7/30/60, respectively) could be used to represent potential changes, based on the half-life (T
1/2: ∼30 days). Emicizumab concentrations that covered maximum plasma concentrations of each dosage were used for spiking on day 0. Ex vivo addition of estimated emicizumab to PwAHA's plasma containing endogenous FVIII and/or inhibitor, without and with recombinant (r)FVIIa administration during immunosuppressive therapy, increased the calculated Ad|min1| values, assessed by clot waveform analysis, and their coagulant potentials were below normal levels. Rotational thromboelastometry revealed that ex vivo emicizumab addition resulted in the further improvement of coagulant potentials in whole bloods when combined with rFVIIa administration.

Conclusion Based on ex vivo and in vitro data, emicizumab has the potential to be effective in clinical situations for PwAHAs.
Trends in Acute Pulmonary Embolism Admission Rates and Mortality Outcomes in Australia, 2002–2003 to 2017–2018: A Retrospective Cohort Study
Authors: Hoskin Scott , Brieger David , Chow Vincent , Kritharides Leonard , Ng Austin Chin Chwan
Published: February 2021

Background Contemporary Australian epidemiological data on acute pulmonary embolism (PE) are lacking.

Objectives To determine the admission rates of acute PE in Australia, and to assess the temporal trends in short- and medium-term mortality following acute PE.

Methods Retrospective population-linkage study of all New South Wales residents admitted with a primary diagnosis of PE between January 1, 2002 and December 31, 2018 using data from the Centre for Health Record Linkage databases. Main outcome measures included temporal trends in total PE admissions and all-cause mortality at prespecified time points up to 1 year, stratified by gender.

Results There were 61,607 total PE admissions between 2002 and 2018 (mean ± standard deviation: 3,624 ± 429 admissions per annum; 50.42 ± 3.70 admissions per 100,000 persons per annum). The mean admission rate per annum was higher for females than for males (54.85 ± 3.65 vs. 44.91 ± 4.34 admissions per 100,000 persons per annum, respectively) and remained relatively stable for both genders throughout the study period. The main study cohort, limited to index PE admission only, comprised 46,382 persons (mean age: 64.6 ± 17.3 years; 44.4% males). The cumulative in-hospital, 30-day, 3-month, and 1-year mortality rates were 3.7, 5.6, 9.6, and 16.8%, respectively. When compared with 2002 as the reference year, there was a significant reduction in in-hospital (odds ratio [OR] = 0.34; 95% confidence interval [CI] = 0.25–0.46), 30-day (OR = 0.58, 95% CI = 0.46–0.73), and 1-year (hazard ratio = 0.74, 95% CI = 0.66–0.84) (all p < 0.001) mortality risk by 2017 after adjusting for age, gender, and relevant confounders. The survival improvements were seen in both genders and were greater for females than for males.

Conclusion Mortality following PE has improved with reductions observed in both short- and medium-term follow-ups between 2002 and 2018 with greater reductions in females despite their higher admission rates over time.
Archiving the Chilean Revolution
Authors: Ragas José
Published: February 2021

In October 2019, Santiago de Chile became the epicenter of a violent and massive protest against social inequality. Known as the Estallido Social (the Social Unrest), Chileans took to the streets seeking to dismantle the pervasive social and economic system inherited from Augusto Pinochet’s regime established half a century ago. Drawing from participant observations and interviews conducted during the protest, this essay examines the multiple efforts developed by scholars to document the vast repertoire of material generated during Santiago’s demonstrations (e.g., graffiti, signs, flags, testimonies, and merchandise). In doing so, I aim to situate the Estallido Social within the recent efforts deployed by museums, archives, and libraries to capture the changing nature and manifestations of global protests in the past few years.
Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d’Ivoire
Authors: Ouattara Allassane F , Bjerum Catherine M , Aboulaye Méité , Kouadio Olivier , Marius Vanga K , Andersen Britt , Lew Daphne , Goss Charles W , Weil Gary J , Koudou Benjamin G , King Christopher L
Published: February 2021

Background

Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of 3 years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis.

Methods

Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either 3 annual doses of IA (N = 52), 6 semiannual doses of ALB 400 mg (N = 45), or 6 semiannual doses of ALB 800 mg (N = 47). The primary outcome is amicrofilaremia at 36 months.

Results

IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, 95% confidence interval [CI]: 67–91; vs 48%, 95% CI: 32–66 and 57%, 95% CI: 41–73, respectively). Mean percentage reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, 95% CI: 88–100) than after ALB 400 mg (88%, 95% CI: 78–98) and ALB 800 mg (89%, 95% CI: 79–99) (P = .07 and P = .06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated.

Conclusions

Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas where ivermectin cannot be used.

Clinical Trials Registration

NCT02974049
Comparable Outcomes of Short-Course and Prolonged-Course Therapy in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Pooled Cohort Study
Authors: Thorlacius-Ussing Louise , Sandholdt Håkon , Nissen Jette , Rasmussen Jon , Skov Robert , Frimodt-Møller Niels , Dahl Knudsen Jenny , Østergaard Christian , Benfield Thomas
Published: February 2021

Background

The recommended duration of antimicrobial treatment for Staphylococcus aureus bacteremia (SAB) is a minimum of 14 days. We compared the clinical outcomes of patients receiving short-course (SC; 6–10 days), or prolonged-course (PC; 11–16 days) antibiotic therapy for low-risk methicillin-susceptible SAB (MS-SAB).

Methods

Adults with MS-SAB in 1995–2018 were included from 3 independent retrospective cohorts. Logistic regression models fitted with inverse probability of treatment weighting were used to assess the association between the primary outcome of 90-day mortality and treatment duration for the individual cohorts as well as a pooled cohort analysis.

Results

A total of 645, 219, and 141 patients with low-risk MS-SAB were included from cohorts I, II, and III. Median treatment duration in the 3 SC groups was 8 days (interquartile range [IQR], 7–10), 9 days (IQR, 8–10), and 8 days (IQR, 7–10). In the PC groups, patients received a median therapy of 14 days (IQR, 13–15), 14 days (IQR, 13–15), and 13 days (IQR, 12–15). No significant differences in 90-day mortality were observed between the SC and PC group in cohort I (odds ratio [OR], 0.85 [95% confidence interval {CI}, .49–1.41]), cohort II (OR, 1.24 [95% CI, .60–2.62]), or cohort III (OR, 1.15 [95% CI, .24–4.01]). This result was consistent in the pooled cohort analysis (OR, 1.05 [95% CI, .71–1.51]). Furthermore, duration of therapy was not associated with the risk of relapse.

Conclusions

In patients with low-risk MS-SAB, shorter courses of antimicrobial therapy yielded similar clinical outcomes as longer courses of therapy.
Propensity score-based analysis of long-term follow-up in patients supported with durable centrifugal left ventricular assist devices: the EUROMACS analysis
Authors: Potapov Evgenij V , Nersesian Gaik , Lewin Daniel , Özbaran Mustafa , de By Theo M M H , Stein Julia , Pya Yuri , Gummert Jan , Ramjankhan Faiz , Zembala Michael O , Damman Kevin , Carrel Thierry , Meyns Bart , Zimpfer Daniel , Netuka Ivan
Published: February 2021

OBJECTIVES

The HeartWare HVAD (HW) and the HeartMate3 (HM3) are presently the most commonly used continuous-flow left ventricular assist devices worldwide. We compared the outcomes of patients supported with either of these 2 devices based on data from the EUROMACS (European Registry for Patients with Mechanical Circulatory Support).

METHODS

A retrospective analysis of the survival and complications profile in propensity score-matched adult patients enrolled in the EUROMACS between 01 January 2016 and 01 September 2020 and supported with either an HW or HM3. Matching included demographic parameters, severity of cardiogenic shock and risk-modifying end-organ parameters that impact long-term survival. Survival on device and major postoperative adverse events were analysed.

RESULTS

Following 1:1 propensity score matching, each group consisted of 361 patients. Patients were well balanced (<0.1 standardized mean difference). The median follow-up was similar in both groups [396 (interquartile range (IQR) 112–771) days for HW and 376 (IQR 100–816) days for HM3]. The 2-year survival was similar in both groups [HW: 61% 95% confidence interval (CI) (56–67%) vs HM3: 68% 95% CI (63–73%) (stratified hazard ratio for mortality: 1.13 95% CI (0.83–1.54), P = 0.435].The cumulative incidence for combined major adverse events and unexpected readmissions was similar in both groups [subdistribution hazard ratio (SHR) 1.0 (0.84–1.21), P = 0.96]. Patients in the HW group demonstrated a higher risk of device malfunction [SHR 2.44 (1.45–3.71), P < 0.001], neurological dysfunction [SHR 1.29 (1.02–1.61), P = 0.032] and intracranial bleeding [SHR 1.76 (1.13–2.70), P = 0.012].

CONCLUSIONS

Mid-term survival in both groups was similar in a propensity-matched analysis. The risk of device malfunction, neurological dysfunction and intracranial bleeding was significantly higher in HW patients.
Pathogen Burden, Blood Biomarkers, and Functional Aging in Community-Dwelling Older Adults
Authors: Lu Yanxia , Tan Crystal Tze Ying , Gwee Xinyi , Yap Keng Bee , Fulop Tamas , Pan Fang , Larbi Anis , Ng Tze Pin
Published: February 2021

Background

Lifelong accumulation of latent or persistent or repeated infections may be a contributing factor to the deterioration of physical and cognitive function associated with functional aging, but the evidence is limited and the biological underpinnings are unclear.

Methods

We profiled the seropositivity for common viral, bacterial, and plasmodial pathogens of local importance in community-living older adults in 2 studies involving 745 older adults (mean age 67.0, SD: 7.7 years), and 142 older adults (mean age 72.7, SD: 8.3 years). Pathogen load was related to different sets of age-related physical and cognitive measures of functional aging and the Frailty Index (FI), and plasma levels of biomarkers of inflammation, innate and adaptive immunity, and other physiological functions.

Results

High pathogen load was associated with impaired gait speed (GS; p < .015), functional mobility (performance-oriented mobility assessment [POMA]; p < .029), cognitive function (Mini-Mental State Examination [MMSE]; p < .05), and increased FI; p < .05). High pathogen load was significantly associated with C3a complement activity (p < .001), matrix metalloproteinase-7, macrophage inflammatory protein-1α (p < .05), and monocyte chemoattractant protein 2 (p = .028). Blood biomarkers did not fully explain the observed association between pathogen load and functional aging measures.

Conclusions

This study provides novel evidence linking lifelong cumulated numbers of latent, persistent, or repeated infection to functional aging, plausibly via inflammatory and immune and other biological factors.
Invasive Aspergillosis After Influenza and Other Viral Respiratory Infections Among Intensive Care Unit Patients in a Commercially Insured Population in the United States, 2013–2018
Authors: Toda Mitsuru , Benedict Kaitlin , Jackson Brendan R
Published: February 2021

Influenza-associated aspergillosis (IAA) is an emerging phenomenon in intensive care unit patients with severe influenza. In a large US health insurance claims database, IAA was uncommon (0.3%) during 2013–2018. The low IAA frequency likely reflects underdiagnosis and differences in medical practices or epidemiologic differences.