bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review on Curcumin-Loaded Electrospun Nanofibers and their Application in Modern Medicine
Authors: Mitra Souradeep , Mateti Tarun , Ramakrishna Seeram , Laha Anindita
Published: February 2022

Herbal drugs are safe and show significantly fewer side effects than their synthetic counterparts. Curcumin (an active ingredient primarily found in turmeric) shows therapeutic properties, but its commercial use as a medication is unrealized, because of doubts about its potency. The literature reveals that electrospun nanofibers show simplicity, efficiency, cost, and reproducibility compared to other fabricating techniques. Forcespinning is a new technique that minimizes limitations and provides additional advantages to electrospinning. Polymer-based nanofibers—whose advantages lie in stability, solubility, and drug storage—overcome problems related to drug delivery, like instability and hydrophobicity. Curcumin-loaded polymer nanofibers show potency in healing diabetic wounds in vitro and in vivo. The release profiles, cell viability, and proliferation assays substantiate their efficacy in bone tissue repair and drug delivery against lung, breast, colorectal, squamous, glioma, and endometrial cancer cells. This review mainly discusses how polymer nanofibers interact with curcumin and its medical efficacy.
Abnormal bile acid-microbiota crosstalk promotes the development of hepatocellular carcinoma
Authors: Shen Rui , Ke Lixin , Li Qiao , Dang Xi , Shen Shunli , Shen Jianming , Li Shaoqiang , Liang Lijian , Peng Baogang , Kuang Ming , Ma Yi , Yang Zhonghan , Hua Yunpeng
Published: February 2022

Background

Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.

Methods

We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.

Results

We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.

Conclusions

We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.
Paleotsunami evidence in the Bahía Inglesa coast (Atacama, Chile) based on a multi-approach analysis
Authors: Carballeira R. , Peña-Monne J. L. , Otero X. L. , Sampietro-Vattuone M. M. , Castro-Correa C. P. , Soto-Bauerle M. V. , Pérez-Alberti A.
Published: February 2022

The Atacama coast is located in an area with a current high risk of tsunami, and the sedimentary deposits found in the Bahía Inglesa area, in the Morro sector, clearly indicate that this was also the case in the past. This investigation analyzes a paleotsunami sedimentary deposit consisting of a block field associated with three sand lobes oriented towards land on top of a marine terrace at an altitude of 70–75 m, which originated from a tsunamigenic event occurred between interglacial periods MIS 7 (ca. 210 ± 10 ky) and MIS5e (ca. 125 ± 5 ky). The deposits have been studied using a multiple approach combining geomorphological, sedimentological, biological, and geochemical criteria. The first type of criteria clearly indicate that the energy required to move the blocks and form the sand lobes could only have been generated by a tsunami. Sedimentological criteria constitute direct evidences of a marine origin due to the presence of siliceous remains from diatom species and spicules from strictly marine sponges, while geochemical criteria, such as the stable isotope signature and chemical composition, constitute evidence of a marine intrusion.
Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs
Authors: Chen Yufei , Traore Yannick L. , Walker Lyndon , Yang Sidi , Ho Emmanuel A.
Published: February 2022

We designed and engineered novel intravaginal ring (IVR) medical devices via fused deposition modeling (FDM) three-dimensional (3D) printing for controlled delivery of hydroxychloroquine, IgG, gp120 fragment (encompassing the CD4 binding site), and coumarin 6 PLGA-PEG nanoparticles (C6NP). The hydrophilic polyurethanes were utilized to 3D-print reservoir-type IVRs containing a tunable release controlling membrane (RCM) with varying thickness and adaptable micro porous structures (by altering the printing patterns and interior fill densities) for controlled sustained drug delivery over 14 days. FDM 3D printing of IVRs were optimized and implemented using a lab-developed Cartesian 3D printer. The structures were investigated by scanning electron microscopy (SEM) imaging and in vitro release was performed using 5 mL of daily-replenished vaginal fluid simulant (pH 4.2). The release kinetics of the IVR segments were tunable with various RCM (outer diameter to inner diameter ratio ranging from 1.12 to 2.61) produced from FDM 3D printing by controlling the printing perimeter to provide daily zero-order release of HCQ ranging from 23.54 ± 3.54 to 261.09 ± 32.49 µg/mL/day. IgG, gp120 fragment, and C6NP release rates demonstrated pattern and in-fill density-dependent characteristics. The current study demonstrated the utility of FDM 3D printing to rapidly fabricate complex micro-structures for tunable and sustained delivery of a variety of compounds including HCQ, IgG, gp120 fragment, and C6NP from IVRs in a controlled manner.

Graphical abstract
Strategies to successfully prevent COVID-19 outbreak in vulnerable uro-oncology patient population
Authors: Tamalunas Alexander , Schott Melanie , Ivanova Troya , Rodler Severin , Heinemann Volker , Stief Christian G. , Casuscelli Jozefina
Published: February 2022

Purpose

As COVID-19 pandemic persists with variants, and despite effective vaccination campaigns, breakthrough infections surge. We implemented strategies to protect vulnerable patients of the uro-oncologic outpatient clinic. We adopted proactive non-symptomatic risk reduction measures, which include non-symptomatic testing requirements for both patients and health care professionals (HCP), intensified patient tracing and contact reduction by implementation of digital health options. Here, we present our best practice example to safely guide oncology professionals and patients with metastasized genitourinary cancers through the current and future pandemics.

Methods

Solely for this purpose, we created a registry of collected data (current telephone numbers, e-mail addresses, vaccination status). We collected a nasopharyngeal swab from every patient upon presentation for treatment. We implemented bi-weekly RNA-PCR assay tests for HCP with patient contact, and limited personal contact at our facility through digital patient consultations.

Results

We started implementing our COVID prevention model at the beginning of the second wave in September 2020 and included 128 patients with urologic malignancies requiring systemic treatment. After COVID vaccination became available in December 2020, all of our HCP were fully vaccinated within 6 weeks and 97% of our patients (125/128) within 9 months. We performed 1410 nasopharyngeal swabs during in-house visits, thereby detecting two COVID-19 infections among our patients, who both survived and successfully continued treatment. To further reduce personal contact, half of our consultations were fully operated digitally, with 76% (97/128) of our patients participating in our digital health offers.

Conclusion

The willingness of patients and HCPs to participate in the study allowed us to implement strict standards to prepare for the ongoing and future pandemics in outpatient cancer units. Next to general preventive measures such as frequent hand disinfection, wearing facial masks, and keeping distance, an important measure to protect vulnerable uro-oncology patients is the capability to perform virus genome sequencing to trace transmission chains.
A Review of Testing Object-Based Environment Perception for Safe Automated Driving
Authors: Hoss Michael , Scholtes Maike , Eckstein Lutz
Published: February 2022

Safety assurance of automated driving systems must consider uncertain environment perception. This paper reviews literature addressing how perception testing is realized as part of safety assurance. The paper focuses on testing for verification and validation purposes at the interface between perception and planning, and structures the analysis along the three axes (1) test criteria and metrics, (2) test scenarios, and (3) reference data. Furthermore, the analyzed literature includes related safety standards, safety-independent perception algorithm benchmarking, and sensor modeling. It is found that the realization of safety-oriented perception testing remains an open issue since challenges concerning the three testing axes and their interdependencies currently do not appear to be sufficiently solved.
Identifying individual ungulates from fecal DNA: a comparison of field collection methods to maximize efficiency, ease, and success
Authors: Bach Bryan H. , Quigley Ashling B. , Gaynor Kaitlyn M. , McInturff Alex , Charles Kristin L. , Dorcy Janelle , Brashares Justin S.
Published: February 2022

Non-invasive genetic sampling can facilitate the identification of individual animals across a landscape, with applications to management and conservation. Fecal material is a readily available source of DNA, and various methods exist for collecting fecal samples for DNA preservation. In particular, swab methods offer considerable promise, but their utility in real-world field contexts remains relatively untested. We systematically compared multiple genetic fecal sampling methods across all stages of data collection and analysis, including sampling in the field, DNA extraction in the lab, and identification of individuals using microsatellite genotyping. We collected 112 fecal samples from black-tailed deer (Odocoileus hemionus columbianus) in the field in Mendocino County, California, across a range of sample conditions of unknown age. We systematically compared the efficiency, ease, and genotyping success of three methods for field collection and storage of ungulate fecal samples: whole pellets in ethanol, whole dry pellets in paper envelopes, and cotton swabs in buffer. Storage method, sample condition, and their interaction predicted genotyping success in the top binomial GLMMs. We found that swabbing pellets resulted in the greatest percentage of individually identifiable genotypes (81%, compared to 60% for dry samples and 56% for ethanol), despite lower DNA concentrations. While swabbing pellets requires a greater time investment in the field, the samples are easier and safer to store and transport, and subsequent labwork is more efficient as compared to whole-pellet collection methods. We, therefore, recommend the swab method for most contexts. We provide additional recommendations and field protocols based on subsequent collection of 2284 swab samples for a larger monitoring study of the deer population, given that this large number of samples spanned a range of sample conditions and time spent in storage.
Fatty acid composition of milk from mothers giving birth at extremely low gestation in Sweden
Authors: Sjöbom Ulrika , Cismaan Osman , Hansen-Pupp Ingrid , Wackernagel Dirk , Sävman Karin , Hellström Ann , Nilsson Anders K.
Published: February 2022

Preterm infants show postnatal deficits of long-chain polyunsaturated fatty acids (LCPUFAs) which are essential for adequate growth and neurodevelopment. Human milk is a primary source of fatty acids (FAs) for the preterm infant, and therefore, knowledge about milk FA levels is required to design appropriate supplementation strategies. Here, we expanded on our previous study (Nilsson et al., 2018, Acta Paediatrica, 107, 1020–1027) determining FA composition in milk obtained from mothers of extremely low gestational age (<28 weeks) infants on three occasions during lactation. There was a clear difference in FA composition in milk collected at Day 7 and milk collected at postmenstrual weeks (PMW) 32 or PMW 40. Notably, the proportion of LCPUFAs was low and declined significantly during milk maturation. These results strengthen previous data that the content of FAs required by the preterm infant is not supplied in sufficient amounts when the mother’s own milk is the sole source of these essential nutrients.
Overgroups of regular unipotent elements in reductive groups
Authors: Bate Michael , Martin Benjamin , Röhrle Gerhard
Published: February 2022

We study reductive subgroups H of a reductive linear algebraic group G – possibly nonconnected – such that H contains a regular unipotent element of G. We show that under suitable hypotheses, such subgroups are G-irreducible in the sense of Serre. This generalises results of Malle, Testerman and Zalesski. We obtain analogous results for Lie algebras and for finite groups of Lie type. Our proofs are short, conceptual and uniform.
A look back at a long-forgotten trigonometric function: the versine function and its inverse
Authors: Stewart Seán M.
Published: February 2022

Ask anyone who has studied mathematics to a moderate level how many trigonometric functions there are and one is likely to be presented with a range of answers depending on what the person being asked is most likely to remember. Perhaps the ‘calculator button’ three of sine, cosine, and tangent will come to mind as these are the three trigonometric functions found on any standard scientific calculator. At a stretch, perhaps the names for their respective reciprocals, cosecant, secant and cotangent, will be recalled. Beyond the modern standard six, looking at calculus or trigonometric texts published prior to 1900 one soon discovers others going by strange names such as versine, haversine, or coversine (see, for example, [1, pp. 53, 63]). There are at least six others with as many as perhaps ten to twelve having received a name at one time or another. Today all these additional trigonometric functions considered important enough to grace the pages of texts in centuries past have fallen by the wayside, to be largely forgotten in favour of the modern standard six. Of course the pedant amongst us would say there is only one trigonometric function, the sine function, which currently stands as the preferred fundamental trigonometric entity, with all others being simple variations of this function, and they would not be incorrect in asserting this. But having the current standard six seems about the right balance between the minimalistic on the one hand and convenience on the other hand.
Two short proofs of the formula
Authors: Markov Lubomir
Published: February 2022

Euler’s striking proof of the fact that the infinite sum

${1 \over {{1^2}}}\, + \,{1 \over {{2^2}}}\, + \,{1 \over {{3^2}}} + \,...\, + \,{1 \over {{n^2}}} + \,...\, = {{{\pi ^2}} \over 6}$
continues to charm all who become acquainted with it as well as to motivate the search for new proofs. With the introduction of the zeta function
$\zeta (s)\zeta = \sum\limits_{n = 1}^\infty {{1 \over {{n^s}}}} $
, the above sum is rewritten as
$\zeta (2)$
and the problem of its evaluation in closed form is often named after Basel - the city of Euler’s birth. Many solutions to the Basel problem exist today, with several original ones appearing on the pages of The Mathematical Gazette. The purpose of this Note is to present two short proofs, the first of which is a simplification of one in the literature and the second is believed to be new, of the equivalent fact that

$\sum\limits_{n = 0}^\infty {{1 \over {{{(2n + 1)}^2}}} = {{{\pi ^2}} \over 8}} .$
Equal sums, sums of squares and sums of cubes
Authors: Jameson G. J. O.
Published: February 2022

Consider the problem of finding triples of numbers (x1, x2, x3) and (y1, y2, y3) satisfying
(1)
$${x_1} + {x_2} + {x_3} = {y_1} + {y_2} + {y_3}$$
and (2)
$$x_1^2 + x_2^2 + x_3^2 = y_1^2 + y_2^2 + y_3^2.$$
AlepPBP2, but not AlepPBP3, may involve in the recognition of sex pheromones and maize volatiles inAthetis lepigone
Authors: Yang Hui-Hui , Xu Ji-Wei , Zhang Xiao-Qing , Huang Jian-Rong , Li Lu-Lu , Yao Wei-Chen , Zhao Pan-Pan , Zhang Dong , Liu Jia-Yi , Dewer Youssef , Zhu Xiu-Yun , Li Xiao-Ming , Zhang Ya-Nan
Published: February 2022

Athetis lepigoneMöschler (Lepidoptera, Noctuidae) is a common maize pest in Europe and Asia. However, there is no long-term effective management strategy is available yet to suppress its population. Adults rely heavily on olfactory cues to locate their optimal host plants and oviposition sites. Pheromone-binding proteins (PBPs) are believed to be responsible for recognizing and transporting different odorant molecules to interact with receptor membrane proteins. In this study, the ligand-binding specificities of two AlepPBPs (AlepPBP2 and AlepPBP3) for sex pheromone components and host plant (maize) volatiles were measured by fluorescence ligand-binding assay. The results demonstrated that AlepPBP2 had a high affinity with two pheromones [(Z)-7-dodecenyl acetate, Ki = 1.11 ± 0.1μM, (Z)-9-tetradecenyl acetate, Ki = 1.32 ± 0.15μM] and ten plant volatiles, including (-)-limonene,α-pinene, myrcene, linalool, benzaldehyde, nonanal, 2-hexanone, 3-hexanone, 2-heptanone and 6-methyl-5-hepten-2-one. In contrast, we found that none of these chemicals could bind to AlepPBP3. Our results clearly show no significant differences in the functional characterization of the binding properties between AlepPBP2 and AlepPBP3 to sex pheromones and host plant volatiles. Furthermore, molecular docking was employed for further detail on some crucial amino acid residues involved in the ligand-binding of AlepPBP2. These findings will provide valuable information about the potential protein binding sites necessary for protein-ligand interactions which appear as attractive targets for the development of novel technologies and management strategies for insect pests.
Beltrami–Bernoulli equilibria in weakly rotating self-gravitating fluid
Authors: Bhattacharjee Chinmoy
Published: February 2022

In the presence of a stationary gravitomagnetic field, a weakly rotating self-gravitating fluid relaxes into equilibrium flow configurations which admit both large- and small-scale structures. Unlike the traditional Beltrami equilibria in fluid, the equilibrium states in a rotating self-gravitating fluid in a gravitomagnetic field have structure similar to that of double curl Beltrami equilibria in plasma where the generalized vortical lines are aligned with the flow field. Different equilibrium flow configurations in the rotating fluid can be distinguished by the ratio between total energy and helicity. However, these fluid equilibria do not exhibit diamagnetic behaviours as observed in multi-species plasma equilibria.
The winner takes it all: dominance ofCalicophoron daubneyi(Digenea: Paramphistomidae) among flukes in Central European beef cattle
Authors: Červená Barbora , Anettová Lucia , Nosková Eva , Pafčo Barbora , Pšenková Ilona , Javorská Kristýna , Příhodová Pavla , Ježková Jana , Václavek Petr , Malát Kamil , Modrý David
Published: February 2022

In Europe, paramphistomosis caused byParamphistomumspp. was historically regarded as being of minor importance. However,Calicophoron daubneyihas recently been recognized as an emerging pathogen in Europe due to its increasing prevalence and negative impact on livestock production. In search for paramphistomid flukes, 5573 beef cattle fecal samples from 115 farms across the whole Czech Republic were examined from March 2019 to June 2021. The eggs of paramphistomid flukes were identified in 29.9% of samples. Internal transcribed spacer 2 sequences from 90 adult flukes and 125 fecal samples collected across Czech Republic confirmedC. daubneyiinfection in the Czech beef cattle. Ninety mitochondrial DNA sequences obtained from adultC. daubneyispecimens revealed 13 individual haplotypes, two of them recorded for the first time. AlthoughC. daubneyiis a new parasite in beef cattle herds in the Czechia, it clearly dominates the parasitological findings in the country's beef cattle. The common occurrence ofC. daubneyiin most of the beef cattle herds indicates environmental conditions suitable also for the life cycle ofFasciola hepaticaand risk of its emergence.
Negative symptoms in First-Episode Schizophrenia related to morphometric alterations in orbitofrontal and superior temporal cortex: the OPTiMiSE study
Authors: Demjaha Arsime , Galderisi Silvana , Glenthøj Birthe , Arango Celso , Mucci Armida , Lawrence Andrew , O'Daly Owen , Kempton Matthew , Ciufolini Simone , Baandrup Lone , Ebdrup Bjørn H. , Rodriguez-Jimenez Roberto , Diaz-Marsa Maria , Díaz-Caneja Covadonga Martinez , Winter van Rossum Inge , Kahn Rene , Dazzan Paola , McGuire Philip
Published: February 2022

Background

Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES).

Methods

T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed).

Results

The presence of PMN symptoms was associated with larger left inferior orbitofrontal volume (p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus (p = 0.007), but reduced CTh in the left superior temporal gyrus (p = 0.009).

Conclusions

The findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.
“Democracy Is Always Going to Be Hard”: An Interview with Charles Taylor
Authors: Costa Paolo
Published: February 2022

This interview with the Canadian philosopher Charles Taylor was designed and realized to celebrate his ninetieth birthday in November 2021. The interview touches on all the main themes of Taylor's oeuvre, from his view of philosophy to the inherent link between human intelligence and strong evaluations, from the Immanent Frame to postsecularity, from today's democratic crisis to the 1980s debate between liberals and communitarians, from Xi Jinping's China to the global health emergency, from spirituality to Philosophical Romanticism. It is both a hindsight analysis by a first-class thinker and a glance into the future by an incurable optimist.
Disturbance observer-based robust fixed-time integrated trajectory tracking control for space manipulator
Authors: Yao Qijia
Published: February 2022

This article investigates the fixed-time trajectory tracking control of a free-flying rigid space manipulator perturbed by model uncertainties and external disturbances. A novel robust fixed-time integrated controller is developed by integrating a nominal fixed-time proportional–differential-like controller with a fixed-time disturbance observer. It is strictly proved that the proposed controller can ensure the position and velocity tracking errors regulate to zero in fixed time even subject to lumped disturbance. Benefiting from the feedforward compensation, the proposed controller has the strong robustness and excellent disturbance attenuation capability. The effectiveness and advantages of the proposed control approach are validated through simulations and comparisons.
Antibiotic prescribing across age groups in the Kaiser Permanente Northern California population in association with different diagnoses, and with influenza incidence, 2010–2018
Authors: Goldstein Edward , Fireman Bruce H. , Klein Nicola P. , Lipsitch Marc , Ray G. Thomas
Published: February 2022

There is limited information on the volume of antibiotic prescribing that is influenza-associated, resulting from influenza infections and their complications (such as streptococcal pharyngitis and otitis media). Here, we estimated age/diagnosis-specific proportions of antibiotic prescriptions (fills) for the Kaiser Permanente Northern California population during 2010–2018 that were influenza-associated. The proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was higher in children aged 5–17 years compared to children aged under 5 years, ranging from 1.4% [95% CI (0.7–2.1)] in aged <1 year to 2.7% (1.9–3.4) in aged 15–17 years. For adults aged over 20 years, the proportion of influenza-associated antibiotic prescribing among all antibiotic prescribing was lower, ranging from 0.7% (0.5–1) for aged 25–29 years to 1.6% (1.2–1.9) for aged 60–64 years. Most of the influenza-associated antibiotic prescribing in children aged under 10 years was for ear infections, while for age groups over 25 years, 45–84% of influenza-associated antibiotic prescribing was for respiratory diagnoses without a bacterial indication. This suggests a modest benefit of increasing influenza vaccination coverage for reducing antibiotic prescribing, as well as the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication in persons aged over 25 years, both of which may further contribute to the mitigation of antimicrobial resistance.
What Can A [Feminist] Body Do? Immanent and Emergent Capacities of Bodies at Chinchorro and Wor Barrow
Authors: O'Dell Yvonne , Harris Oliver J.T.
Published: February 2022

What can a body do? To answer Baruch Spinoza's question, we engage with posthumanist feminist concepts of nomadic subjectivity and relations with non-humans. Through an exploration of two ‘patches’, the Chinchorro Mummies of the Atacama Desert in South America and the burials at Wor Barrow in the Neolithic of southern England, we suggest that these approaches open up a new way of encountering past bodies. What capabilities do bodies, past and present, have? This question is one in which bodies’ capacities are revealed as immanent, historically contextual and emergent.
Aortic migration of Amplatzer Piccolo™ ductal Occluder
Authors: Minocha Prashant K. , Sutton Nicole , Crawford Maya T. , Williams David , Ramirez Michelle , Chakravarti Sujata , Mosca Ralph , Kumar T. K. Susheel
Published: February 2022

We present the case of a 4-month-old, former 23-week premature baby who underwent patent ductus arteriosus device closure in the cardiac catheterisation lab with an Amplatzer Piccolo™ device at 12 weeks of life. This was complicated by late migration of the device into the aorta resulting in severe obstruction and requiring surgical intervention.
Telehealth services for cardiac neurodevelopmental care during the COVID-19 pandemic: a site survey from the Cardiac Neurodevelopmental Outcome Collaborative
Authors: Kasparian Nadine A. , Sadhwani Anjali , Sananes Renee , Blumenfeld Elizabeth , Butcher Jennifer L. , Cassidy Adam R. , Cox Stephany M. , Kenowitz Joslyn , Miller Thomas A. , Sanz Jacqueline H. , Wolfe Kelly R. , Ilardi Dawn
Published: February 2022

Objective:

COVID-19 has markedly impacted the provision of neurodevelopmental care. In response, the Cardiac Neurodevelopmental Outcome Collaborative established a Task Force to assess the telehealth practices of cardiac neurodevelopmental programmes during COVID-19, including adaptation of services, test protocols and interventions, and perceived obstacles, disparities, successes, and training needs.

Study Design:

A 47-item online survey was sent to 42 Cardiac Neurodevelopmental Outcome Collaborative member sites across North America within a 3-week timeframe (22 July to 11 August 2020) to collect cross-sectional data on practices.

Results:

Of the 30 participating sites (71.4% response rate), all were providing at least some clinical services at the time of the survey and 24 sites (80%) reported using telehealth. All but one of these sites were offering new telehealth services in response to COVID-19, with the most striking change being the capacity to offer new intervention services for children and their caregivers. Only a third of sites were able to carry out standardised, performance-based, neurodevelopmental testing with children and adolescents using telehealth, and none had completed comparable testing with infants and toddlers. Barriers associated with language, child ability, and access to technology were identified as contributing to disparities in telehealth access.

Conclusions:

Telehealth has enabled continuation of at least some cardiac neurodevelopmental services during COVID-19, despite the challenges experienced by providers, children, families, and health systems. The Cardiac Neurodevelopmental Outcome Collaborative provides a unique platform for sharing challenges and successes across sites, as we continue to shape an evidence-based, efficient, and consistent approach to the care of individuals with CHD.
Collectively playable wearable music: Practice-situated approaches to participatory relational inquiry
Authors: Thorn Seth D. , Willcox Halley L.
Published: February 2022

We present two practice-situated participatory investigations using networked wearable sensors to develop movement-responsive collectively playable musical instruments: a series of four collocated workshops for expert dancers and a distance learning course in which students use wearable technology to enhance embodied learning and feelings of connectedness telematically. We reflect on our exploration of techniques for structuring ensemble improvisations augmented with bespoke digital musical instruments using aggregate statistical measures, such as variance of participants’ physical orientation as an index of group intention. Participatory design exchanges top-down design methodologies with bottom-up approaches consulting actors’ interests. We follow this approach by evolving our instruments through abductive experiments and trial-and-error tinkering, without strong theories, methods, or models, using elementary signal processing techniques that are meaningfully understood and modified by participants. Our experiences suggest useful scaffolding techniques for educational transdisciplinary research-creation communities seeking to explore relational ensemble dynamics in telematic and/or physically collocated settings using accessible wearable technologies. Through creative inquiry and participation, technical objects can become bearers of sense and meaning rather than instating mystifying or alienating relations for the participants.
N400 Peculiarities During Intentional Inferences Production in Subjects With Schizotypal Traits
Authors: Bohec Anne-Lise , de Loye Claire , Baltazar Matias , Blanchet Alain , Rey Romain , Kostova Milena
Published: February 2022

Abstract. A deficit in context processing may underlie theory of mind (ToM) difficulties in schizophrenia, although few studies to date have explored the impact of contextual processing on ToM performances within the same task. We used electroencephalography to investigate the production of intentional inferences from highly versus weakly structured sentences in healthy participants with schizotypal traits. Thirty-four participants were divided into two groups according to their scores on the Schizotypal Personality Questionnaire (SPQ). The participants listened to stories that required a degree of understanding in order to produce an inference about the main character’s intention. Each story was followed by a target word that could either be highly predictable (HP), weakly predictable (WP), or incompatible with the context. The results indicate that the N400 component for WP targets was stronger in the high-SPQ group. This increase correlated with the negative dimension of schizotypy. This may reflect difficulties with generating intentional inferences when the context is insufficiently structured for high schizotypy participants.
Functional Significance of Individual Differences in P3 Network Spatial Configuration
Authors: Privitera Adam John , Tang Akaysha C.
Published: February 2022

Abstract. The amplitude and latency of the P3 component in the electroencephalogram (EEG) event-related potentials (ERPs) are among the most extensively used markers for individual differences in normal and abnormal brain functions. In contrast, individual variations in spatial topography of the temporally-defined P3 component are relatively under-explored. Development in EEG-based source imaging opened up the possibility that individual-specific spatial configuration of the neural network underlying the temporally-defined P3 component bear a novel source of information for marking an individual difference in behavioral and cognitive function. In testing this hypothesis, a hybrid method consisting of blind source separation (BSS), equivalent current dipole (ECD) modeling, and hits-vector-based analysis was applied to continuous un-epoched EEG data collected from 13 healthy human participants performing a visual color oddball task. By analyzing the spatial configuration of the network underlying the temporally-defined P3 component, hereafter referred to as the P3N, we discovered that the contribution of each constituent structure within the P3N is not uniform. Instead, frontal lobe structures have significantly more involvement than other constituent structures, as quantitatively characterized by cross-individual reliability and a within-individual contribution to the P3N. A factor analysis of the hits vector data revealed that although P3 latency and amplitude did not show significant correlations with measures of the behavioral outcomes, scores of two factors derived from the hits vectors selectively predict behavioral reaction time and response correctness. These results support the hypothesis that variations in P3 spatial configuration reflect not merely noise but individual-specific features with functional significance.
Physiological Responses to Narrative Anger Recall and Correlates to Anger, Forgiveness, and Rumination
Authors: Whinery Emily Dalrymple , Musleh Aya , Brown Emily A. , Alford Zachary , Anigbogu Joe C. , Ellingwood Lauren , Espinoza Marc-Anthony , Hawkins Greg , Kammer Kaisa , Krause Kevin , Olson Lisa E.
Published: February 2022

Abstract. Narrative recall, or describing an event from one’s past, is a common method to study anger in the laboratory. However, most research using this method has not included a neutral speaking control, and therefore the physiological response attributable to emotion versus the act of speech is unknown. We evaluated heart rate, blood pressure, skin conductance level, heart rate variability, and salivary alpha-amylase during silent baseline, neutral speaking, anger recall, and recovery periods, and correlated these measures with trait anger, forgiveness, and rumination ( n = 104). Only systolic blood pressure and skin conductance levels were elevated in the anger recall period above the values in the neutral speaking period, showing the need for this important control. Alpha-amylase was inversely correlated to forgiveness, particularly in females. A neutral speaking control is critical for anger recall protocols because the physiological responses are mostly due to speaking, not anger. Salivary alpha-amylase may be a promising autonomic marker in studies of forgiveness and anger.
Foreshock Activity Promoted by Locally Elevated Loading Rate on a 4‐m‐Long Laboratory Fault
Authors: Yamashita F. , Fukuyama E. , Xu S.
Published: February 2022

We report laboratory experimental results to reveal the factors that control the occurrence and magnitude of foreshocks. We conducted rock friction experiments using an apparatus that can shear 4‐m‐long rock specimens. We observed many stick‐slip events, as well as very slow (several tens of μm/s) but long‐lasting slips between those main events. These long‐term slow slips individually initiated from both the leading and trailing edges of the fault, and kept propagating steadily toward each other. Such steady slips did not immediately trigger any seismic events, regardless of the accumulated slip amount. After the coalescence of the two long‐term slow slip fronts, a second phase of slow slip with higher slip rate (several hundreds of μm/s)—called precursory slow slip, began at the central area and was accompanied by the occurrence of small seismic events (foreshocks). Subsequently, the main fast rupture eventually developed. We propose that the asperities that hosted foreshocks had similar size to the local critical nucleation length; the asperities slipped stably when the local loading rate was low, but could also slip unstably and radiated seismic waves when the local loading rate became high. We further found a clear positive correlation between foreshock magnitude and local slip rate. These results suggest that local loading rate has a significant influence on the occurrence and magnitude of foreshocks. Therefore, its effect should be taken into account during the studies of earthquake nucleation process and other similar phenomena such as Episodic Tremor and Slip (ETS), icequakes, and repeating earthquakes.
Oxygen Levels Measured in a Lung of the Deep Ocean
Authors: Dacey James
Published: February 2022

The Labrador Sea “inhales” oxygen and supplies it to deep-sea life across the world. But its breath could be threatened by climate change.
Human α-synuclein overexpression in mouse serotonin neurons triggers a depressive-like phenotype. Rescue by oligonucleotide therapy
Authors: Miquel-Rio Lluis , Alarcón-Arís Diana , Torres-López María , Cóppola-Segovia Valentín , Pavia-Collado Rubén , Paz Verónica , Ruiz-Bronchal Esther , Campa Leticia , Casal Carme , Montefeltro Andrés , Vila Miquel , Artigas Francesc , Revilla Raquel , Bortolozzi Analia
Published: February 2022

Anxiety and depression affect 35–50% of patients with Parkinson’s disease (PD), often precede the onset of motor symptoms, and have a negative impact on their quality of life. Dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD and contributes to a variety of non-motor symptoms. Furthermore, α-synuclein (α-Syn) aggregates were identified in raphe nuclei in the early stages of the disease. However, there are very few animal models of PD-related neuropsychiatric disorders. Here, we develop a new mouse model of α-synucleinopathy in the 5-HT system that mimics prominent histopathological and neuropsychiatric features of human PD. We showed that adeno-associated virus (AAV5)-induced overexpression of wild-type human α-Syn (h-α-Syn) in raphe 5-HT neurons triggers progressive accumulation, phosphorylation, and aggregation of h-α-Syn protein in the 5-HT system. Specifically, AAV5-injected mice displayed axonal impairment in the output brain regions of raphe neurons, and deficits in brain-derived neurotrophic factor (BDNF) expression and 5-HT neurotransmission, resulting in a depressive-like phenotype. Intracerebroventricular treatment with an indatraline-conjugated antisense oligonucleotide (IND-ASO) for four weeks induced an effective and safe reduction of h-α-Syn synthesis in 5-HT neurons and its accumulation in the forebrain, alleviating early deficits of 5-HT function and improving the behavioural phenotype. Altogether, our findings show that α-synucleinopathy in 5-HT neurons negatively affects brain circuits that control mood and emotions, resembling the expression of neuropsychiatric symptoms occurring at the onset of PD. Early preservation of 5-HT function by reducing α-Syn synthesis/accumulation may alleviate PD-related depressive symptoms.
Lineage-specific early complete donor chimerism and risk of relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
Authors: Lindahl Hannes , Vonlanthen Sofie , Valentini Davide , Björklund Andreas T. , Sundin Mikael , Mielke Stephan , Hauzenberger Dan
Published: February 2022

Recipient–donor chimerism is routinely analyzed after allogeneic hematopoietic stem cell transplantation (HSCT) to monitor engraftment and graft rejection. For malignancies, chimerism can also be used to screen for disease relapse post-HSCT but methodology and interpretation of results are not standardized and likely depend on underlying diagnosis. We have implemented highly sensitive and accurate methodologies for chimerism analysis for the purpose of improving relapse prediction. Here, we report an exploratory retrospective analysis of clinical routine chimerism results from all 154 HSCTs for acute myeloid leukemia (AML) performed at our center during the years 2015–2020 with the aim of suggesting a clinically useful threshold at which risk of relapse is high. Relapse was not reliably predicted based on single elevated chimerism values obtained before time of overt relapse. However, early complete donor chimerism, here defined as recipient DNA < 0.2% in CD33+ cells in any blood or bone marrow sample taken during the first 60 days after HSCT, correlated inversely with relapse during the observation time (log-rank test P = 0.033). We propose that achievement of complete chimerism determined early after HSCT using sensitive methods can be used for risk-stratification of AML patients.
SUMOylation of PDPK1 Is required to maintain glycolysis-dependent CD4 T-cell homeostasis
Authors: Sun Fei , Wang Fa-Xi , Zhu He , Yue Tian-Tian , Yang Chun-Liang , Luo Jia-Hui , Luo Xi , Zhou Hai-Feng , Rong Shan-Jie , Lu Wan-Ying , Zhou Qing , Yang Ping , Xiong Fei , Liu Yan-Jun , Yan Tong , Liao Yun-Fei , Zhang Shu , Wang Cong-Yi
Published: February 2022

The immune system is finely tuned to fight against infections, eradicate neoplasms, and prevent autoimmunity. Protein posttranslational modification (PTM) constitutes a molecular layer of regulation to guarantee the proper intensity of immune response. Herein, we report that UBC9-mediated protein SUMOylation plays an essential role in peripheral CD4 T-cell proliferation, but without a perceptible impact on T-cell polarization. Both conventional T-cell (Tcon) and regulatory T-cell (Treg) maintenance are differentially affected, which was likely caused by a shared deficit in cell glycolytic metabolism. Mechanistically, PDPK1 (3-phosphoinositide-dependent protein-kinase 1) was identified as a novel SUMOylation substrate, which occurred predominantly at lysine 299 (K299) located within the protein-kinase domain. Loss of PDPK1 SUMOylation impeded its autophosphorylation at serine 241 (S241), thereby leading to hypoactivation of downstream mTORC1 signaling coupled with incompetence of cell proliferation. Altogether, our results revealed a novel regulatory mechanism in peripheral CD4 T-cell homeostatic proliferation, which involves SUMOylation regulation of PDPK1–mTORC1 signaling-mediated glycolytic process.
Single-cell analysis of skin immune cells reveals an Angptl4-ifi20b axis that regulates monocyte differentiation during wound healing
Authors: Wee Wei Kiat Jonathan , Low Zun Siong , Ooi Chin Kiat , Henategala Benjamin Patrana , Lim Zhi Guang Ridley , Yip Yun Sheng , Vos Marcus Ivan Gerard , Tan William Wei Ren , Cheng Hong Sheng , Tan Nguan Soon
Published: February 2022

The persistent inflammatory response at the wound site is a cardinal feature of nonhealing wounds. Prolonged neutrophil presence in the wound site due to failed clearance by reduced monocyte-derived macrophages delays the transition from the inflammatory to the proliferative phase of wound healing. Angiopoietin-like 4 protein (Angptl4) is a matricellular protein that has been implicated in many inflammatory diseases. However, its precise role in the immune cell response during wound healing remains unclear. Therefore, we performed flow cytometry and single-cell RNA sequencing to examine the immune cell landscape of excisional wounds from Angptl4+/+ and Angptl4−/− mice. Chemotactic immune cell recruitment and infiltration were not compromised due to Angptl4 deficiency. However, as wound healing progresses, Angptl4−/− wounds have a prolonged neutrophil presence and fewer monocyte-derived macrophages than Angptl4+/+ and Angptl4LysM−/− wounds. The underlying mechanism involves a novel Angptl4-interferon activated gene 202B (ifi202b) axis that regulates monocyte differentiation to macrophages, coordinating neutrophil removal and inflammation resolution. An unbiased kinase inhibitor screen revealed an Angptl4-mediated kinome signaling network involving S6K, JAK, and CDK, among others, that modulates the expression of ifi202b. Silencing ifi202b in Angptl4−/− monocytes, whose endogenous expression was elevated, rescued the impaired monocyte-to-macrophage transition in the in vitro reconstituted wound microenvironment using wound exudate. GSEA and IPA functional analyses revealed that ifi202b-associated canonical pathways and functions involved in the inflammatory response and monocyte cell fate were enriched. Together, we identified ifi202b as a key gatekeeper of monocyte differentiation. By modulating ifi202b expression, Angptl4 orchestrates the inflammatory state, innate immune landscape, and wound healing process.
Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes
Authors: Chang Hsin-Fang , Schirra Claudia , Ninov Momchil , Hahn Ulrike , Ravichandran Keerthana , Krause Elmar , Becherer Ute , Bálint Štefan , Harkiolaki Maria , Urlaub Henning , Valitutti Salvatore , Baldari Cosima T. , Dustin Michael L. , Jahn Reinhard , Rettig Jens
Published: February 2022

Cytotoxic T lymphocytes (CTL) kill malignant and infected cells through the directed release of cytotoxic proteins into the immunological synapse (IS). The cytotoxic protein granzyme B (GzmB) is released in its soluble form or in supramolecular attack particles (SMAP). We utilize synaptobrevin2-mRFP knock-in mice to isolate fusogenic cytotoxic granules in an unbiased manner and visualize them alone or in degranulating CTLs. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion releases soluble GzmB. MCGs can be labelled with the SMAP marker thrombospondin-1 and their fusion releases intact SMAPs. We propose that CTLs use SCG fusion to fill the synaptic cleft with active cytotoxic proteins instantly and parallel MCG fusion to deliver latent SMAPs for delayed killing of refractory targets.