bluuebunny/crossref_metadata_2025 huggingface dataset:
Ride comfort investigation of semi-active seat suspension integrated with quarter car model
Authors: Chen Xiaoliang , Song Hao , Zhao Sixia , Xu Liyou
Published: August 2022

A method for parameter identification of the magnetorheological damper (MRD) model with an improved firefly algorithm (IFA) is proposed, and a semi-active seat control system with three-degree-of-freedom (3-DOF) is established by combining with a quarter car model to investigate the ride comfort. The dynamic characteristics of the MRD were analyzed by experimental method. Combined with the IFA, the parameters of the MRD phenomenon model were identified, and the forward model of the MR damper was constructed. The semi-active control model of a 3-DOF seat suspension was established. The MRD controller and suspension system controller were designed. The passive control, PID control, and Fuzzy-PID control on the vibration reduction of the semi-active seat suspension were compared and analyzed, under different road excitation. The simulation results show that the semi-active seat suspension controlled by the PID and Fuzzy-PID can effectively reduce the seat acceleration and dynamic stroke, which significantly improve the ride comfort and operation safety compared to the passive seat suspension.
Vibration energy harvesting on a drone quadcopter based on piezoelectric structures
Authors: Perez Matthias , Billon Kevin , Gerges Tony , Capsal Jean-Fabien , Cabrera Michel , Chesné Simon , Jean-Mistral Claire
Published: August 2022

The aim of this publication is to conclude on the interest of vibratory energy harvesting on classic quadcopter drone for autonomous applications (battery charging in real time, autonomous sensors), monitoring or even vibration control applications. A complete dynamic analysis allows to quantify the amount of electrical power that is possible to produce during the hovering flight of a quadcopter drone. These results have been obtained by substitution of the inert parts of the drone by piezoelectric components. For that purpose, different types of piezoelectric structures have been tested, including some commercial transducers (DuraAct from Piezoelectric Instrument and Murata buzzers) and some home-made such as a piezoelectric paint. Our original piezoelectric smart arms have been able to scavenge up to 5.35 mW during a stationary flight which remains quite enough to supply low-consumption sensors for monitoring applications.
Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials
Authors: Mitchell Lesley G. , Röshammar Daniel , Huang Fenglei , Albisetti Manuela , Brandão Leonardo R. , Bomgaars Lisa , Chalmers Elizabeth , Halton Jacqueline , Luciani Matteo , Joseph David , Tartakovsky Igor , Gropper Savion , Brueckmann Martina
Published: August 2022

Background Dabigatran etexilate, a direct oral thrombin inhibitor, is approved to treat venous thromboembolism (VTE) in both adults and children.

Objectives This population analysis characterized relationships between dabigatran total plasma concentrations and coagulation laboratory parameters (activated partial thromboplastin time [aPTT]; diluted thrombin time [dTT]; ecarin clotting time [ECT]).

Methods Data from three phase 2a and one single-arm and one randomized, comparative phase 2b/3 pediatric studies (measurements: aPTT 2,925 [N = 358]; dTT 2,348 [N = 324]; ECT 2,929 [N = 357]) were compared with adult data (5,740 aPTT, 3,472 dTT, 3,817 ECT measurements; N = 1,978). Population models were fitted using nonlinear mixed-effects modeling. Covariates (e.g., sex, age) were assessed on baseline and drug-effect parameters, using a stepwise covariate model-building procedure.

Results Overall, relationships between dabigatran, aPTT, dTT, and ECT were similar in children and adults. For children aged <6 months, a higher proportion of baseline samples were outside or close to the upper aPTT and ECT adult ranges. No age-related differences were detected for dTT. With increasing dabigatran concentration, aPTT rose nonlinearly (half the maximum effect at 368 ng/mL dabigatran) while dTT and ECT increased linearly (0.37 and 0.73% change per ng/mL dabigatran, respectively). Mean baseline aPTT (45 vs. 36 seconds) and ECT (40 vs. 36 seconds) were slightly increased for those aged <6 months versus older children.

Conclusion The similar relationships of laboratory parameters observed across pediatric age groups suggests that developmental changes in the hemostatic system may have little effect on response to dabigatran.
The Anatomic Features and Role of Superficial Inferior Epigastric Vein in Abdominal Flap
Authors: Park Seong Oh , Imanishi Nobuaki , Chang Hak
Published: August 2022

In lower abdominal flap representing transverse rectus abdominis musculocutaneous (TRAM) flap or deep inferior epigastric perforator (DIEP) flap, superficial inferior epigastric vein (SIEV) exists as superficial and independent venous system from deep system. The superficial venous drainage is dominant despite a dominant deep arterial supply in anterior abdominal wall. As TRAM or DIEP flaps began to be widely used for breast reconstruction, venous congestion issue has been arisen. Many clinical series in regard to venous congestion despite patent microvascular anastomosis site were reported. Venous congestion could be divided in two conditions by the area of venous congestion and each condition is from different anatomical causes. First, if venous congestion was shown in whole flap, it is due to the connection between SIEV and vena comitantes of DIEP. Second, if venous congestion is limited in above midline (Hartrampf zone II), it is due to problem in venous midline crossover. In this article, the authors reviewed the role of SIEV in lower abdominal flap based on the various anatomic and clinical studies. The contents are mainly categorized into four main issues; basic anatomy of SIEV, the two cause of venous congestion, connection between SIEV and vena comitantes of DIEP, and midline crossover of SIEV.
Comparing Seroma Formation at the Deep Inferior Epigastric Perforator, Transverse Musculocutaneous Gracilis, and Superior Gluteal Artery Perforator Flap Donor Sites after Microsurgical Breast Reconstruction
Authors: Merchant Alisha , Speck Nicole E. , Michalak Michal , Schaefer Dirk J. , Farhadi Jian
Published: August 2022

Background Seroma formation is the most common donor site complication following autologous breast reconstruction, along with hematoma. Seroma may lead to patient discomfort and may prolong hospital stay or delay adjuvant treatment. The aim of this study was to compare seroma rates between the deep inferior epigastric perforator (DIEP), transverse musculocutaneous gracilis (TMG), and superior gluteal artery perforator (SGAP) donor sites.

Methods The authors conducted a retrospective single-center cohort study consisting of chart review of all patients who underwent microsurgical breast reconstruction from April 2018 to June 2020. The primary outcome studied was frequency of seroma formation at the different donor sites. The secondary outcome evaluated potential prognostic properties associated with seroma formation. Third, the number of donor site seroma evacuations was compared between the three donor sites.

Results Overall, 242 breast reconstructions were performed in 189 patients. Demographic data were found statistically comparable between the three flap cohorts, except for body mass index (BMI). Frequency of seroma formation was highest at the SGAP donor site (75.0%), followed by the TMG (65.0%), and DIEP (28.6%) donor sites. No association was found between seroma formation and BMI, age at surgery, smoking status, diabetes mellitus, neoadjuvant chemotherapy, or DIEP laterality. The mean number of seroma evacuations was significantly higher in the SGAP and the TMG group compared with the DIEP group.

Conclusion This study provides a single center's experience regarding seroma formation at the donor site after microsurgical breast reconstruction. The observed rate of donor site seroma formation was comparably high, especially in the TMG and SGAP group, necessitating an adaption of the surgical protocol.
Facial Nerve Repair following Acute Nerve Injury
Authors: Fliss Ehud , Yanko Ravit , Zaretski Arik , Tulchinsky Roei , Arad Ehud , Kedar Daniel J. , Fliss Dan M. , Gur Eyal
Published: August 2022

Background Acute facial nerve iatrogenic or traumatic injury warrants rapid management with the goal of reestablishing nerve continuity within 72 hours. However, reconstructive efforts should be performed up to 12 months from the time of injury since facial musculature may still be viable and thus facial tone and function may be salvaged.

Methods Data of all patients who underwent facial nerve repair following iatrogenic or traumatic injury were retrospectively collected and assessed. Paralysis etiology, demographics, operative data, postoperative course, and outcome were examined.

Results Twenty patients underwent facial nerve repair during the years 2004 to 2019. Data were available for 16 of them. Iatrogenic injury was the common category (n = 13, 81%) with parotidectomy due to primary parotid gland malignancy being the common surgery (n = 7, 44%). Nerve repair was most commonly performed during the first 72 hours of injury (n = 12, 75%) and most of the patients underwent nerve graft repair (n = 15, 94%). Outcome was available for 12 patients, all of which remained with some degree of facial paresis. Six patients suffered from complete facial paralysis (50%) and three underwent secondary facial reanimation (25%). There were no major operative or postoperative complications.

Conclusion Iatrogenic and traumatic facial nerve injuries are common etiologies of acquired facial paralysis. In such cases, immediate repair should be performed. For patients presenting with facial paralysis following previous surgery or trauma, nerve repair should be considered up to at least 6 months of injury. Longstanding paralysis is best treated with standard facial reanimation procedures.
Pulses of antibiotics hit microfluidics
Authors: Piccone Ashley
Published: August 2022

Donut-shaped valves and hydrogels combine to isolate bacteria in microfluidic chips, where it can be exposed to transient doses of antibiotics.
Modeling multi-opinion propagation in complex systems with heterogeneous relationships via Potts model on signed networks
Authors: Li Lingbo , Zeng An , Fan Ying , Di Zengru
Published: August 2022

This paper investigates how the heterogenous relationships around us affect the spread of diverse opinions in the population. We apply the Potts model, derived from condensed matter physics on signed networks, to multi-opinion propagation in complex systems with logically contradictory interactions. Signed networks have received increasing attention due to their ability to portray both positive and negative associations simultaneously, while the Potts model depicts the coevolution of multiple states affected by interactions. Analyses and experiments on both synthetic and real signed networks reveal the impact of the topology structure on the emergence of consensus and the evolution of balance in a system. We find that, regardless of the initial opinion distribution, the proportion and location of negative edges in the signed network determine whether a consensus can be formed. The effect of topology on the critical ratio of negative edges reflects two distinct phenomena: consensus and the multiparty situation. Surprisingly, adding a small number of negative edges leads to a sharp breakdown in consensus under certain circumstances. The community structure contributes to the common view within camps and the confrontation (or alliance) between camps. The importance of inter- or intra-community negative relationships varies depending on the diversity of opinions. The results also show that the dynamic process causes an increase in network structural balance and the emergence of dominant high-order structures. Our findings demonstrate the strong effects of logically contradictory interactions on collective behaviors, and could help control multi-opinion propagation and enhance the system balance.
First-principles study on the electronic structure transition of β-UH3 under high pressure
Authors: Wu Juefei , Yue-Chao Wang , Liu Yu , Sun Bo , Zhao Yanhong , Xian Jiawei , Gao Xingyu , Liu Haifeng , Song Haifeng
Published: August 2022

We investigate the electronic properties of stable β-UH3 under high pressure up to 75 GPa within the first-principles DFT + U formalism with pressure-dependent U in a self-consistent calculation, and we find an electronic structure transition at about 20 GPa due to the quantum process of localization and itinerancy for partially filled uranium 5f electrons. The electronic structure transition is examined from four perspectives: magnetization, band structure, density of states, and 5f electron energy. On the basis of the density of states of 5f electrons, we propose an order parameter, namely, the 5f electron energy, to quantify the electronic structure transition under pressure. Analogously to the isostructural transition in 3d systems, β-UH3 retains its magnetic order after the electronic structure transition; however, this is not accompanied by volume collapse at the transition point. Our calculation is helpful for understanding the electronic properties of β-UH3 under high pressure.
Waterlogging priming alleviates the oxidative damage, carbohydrate consumption, and yield loss in soybean (
Authors: Agualongo Darwin Alexis Pomagualli , Da-Silva Cristiane Jovelina , Garcia Natália , de Oliveira Fabiane Kletke , Shimoia Eduardo Pereira , Posso Douglas Antônio , de Oliveira Ana Cláudia Barneche , de Oliveira Denise dos Santos Colares , do Amarante Luciano
Published: August 2022

In this study, we tested whether waterlogging priming at the vegetative stage would mitigate a subsequent waterlogging event at the reproductive stage in soybean [Glycine max (L.) Merr.]. Plants (V3 stage) were subjected to priming for 7 days and then exposed to waterlogging stress for 5 days (R2 stage) with non-primed plants. Roots and leaves were sampled on the fifth day of waterlogging and the second and fifth days of reoxygenation. Overall, priming decreased the H2O2 concentration and lipid peroxidation in roots and leaves during waterlogging and reoxygenation. Priming also decreased the activity of antioxidative enzymes in roots and leaves and increased the foliar concentration of phenols and photosynthetic pigments. Additionally, priming decreased fermentation and alanine aminotransferase activity during waterlogging and reoxygenation. Finally, priming increased the concentration of amino acids, sucrose, and total soluble sugars in roots and leaves during waterlogging and reoxygenation. Thus, primed plants were higher and more productive than non-primed plants. Our study shows that priming alleviates oxidative stress, fermentation, and carbohydrate consumption in parallel to increase the yield of soybean plants exposed to waterlogging and reoxygenation.
Climate Endgame: Exploring catastrophic climate change scenarios
Authors: Kemp Luke , Xu Chi , Depledge Joanna , Ebi Kristie L. , Gibbins Goodwin , Kohler Timothy A. , Rockström Johan , Scheffer Marten , Schellnhuber Hans Joachim , Steffen Will , Lenton Timothy M.
Published: August 2022

Prudent risk management requires consideration of bad-to-worst-case scenarios. Yet, for climate change, such potential futures are poorly understood. Could anthropogenic climate change result in worldwide societal collapse or even eventual human extinction? At present, this is a dangerously underexplored topic. Yet there are ample reasons to suspect that climate change could result in a global catastrophe. Analyzing the mechanisms for these extreme consequences could help galvanize action, improve resilience, and inform policy, including emergency responses. We outline current knowledge about the likelihood of extreme climate change, discuss why understanding bad-to-worst cases is vital, articulate reasons for concern about catastrophic outcomes, define key terms, and put forward a research agenda. The proposed agenda covers four main questions: 1) What is the potential for climate change to drive mass extinction events? 2) What are the mechanisms that could result in human mass mortality and morbidity? 3) What are human societies' vulnerabilities to climate-triggered risk cascades, such as from conflict, political instability, and systemic financial risk? 4) How can these multiple strands of evidence—together with other global dangers—be usefully synthesized into an “integrated catastrophe assessment”? It is time for the scientific community to grapple with the challenge of better understanding catastrophic climate change.
Chemometrics and genome mining reveal an unprecedented family of sugar acid–containing fungal nonribosomal cyclodepsipeptides
Authors: Wang Chen , Xiao Dongliang , Dun Baoqing , Yin Miaomiao , Tsega Adigo Setargie , Xie Linan , Li Wenhua , Yue Qun , Wang Sibao , Gao Han , Lin Min , Zhang Liwen , Molnár István , Xu Yuquan
Published: August 2022

Xylomyrocins, a unique group of nonribosomal peptide secondary metabolites, were discovered in
Paramyrothecium
and
Colletotrichum
spp. fungi by employing a combination of high-resolution tandem mass spectrometry (HRMS/MS)–based chemometrics, comparative genome mining, gene disruption, stable isotope feeding, and chemical complementation techniques. These polyol cyclodepsipeptides all feature an unprecedented
d
-xylonic acid moiety as part of their macrocyclic scaffold. This biosynthon is derived from
d
-xylose supplied by xylooligosaccharide catabolic enzymes encoded in the xylomyrocin biosynthetic gene cluster, revealing a novel link between carbohydrate catabolism and nonribosomal peptide biosynthesis. Xylomyrocins from different fungal isolates differ in the number and nature of their amino acid building blocks that are nevertheless incorporated by orthologous nonribosomal peptide synthetase (NRPS) enzymes. Another source of structural diversity is the variable choice of the nucleophile for intramolecular macrocyclic ester formation during xylomyrocin chain termination. This nucleophile is selected from the multiple available alcohol functionalities of the polyol moiety, revealing a surprising polyspecificity for the NRPS terminal condensation domain. Some xylomyrocin congeners also feature
N-
methylated amino acid residues in positions where the corresponding NRPS modules lack
N-
methyltransferase (M) domains, providing a rare example of promiscuous methylation in the context of an NRPS with an otherwise canonical, collinear biosynthetic program.
In vitro investigation of protein assembly by combined microscopy and infrared spectroscopy at the nanometer scale
Authors: Zhao Xiao , Li Dong , Lu Yi-Hsien , Rad Behzad , Yan Chunsheng , Bechtel Hans A. , Ashby Paul D. , Salmeron Miquel B.
Published: August 2022

The nanoscale structure and dynamics of proteins on surfaces has been extensively studied using various imaging techniques, such as transmission electron microscopy and atomic force microscopy (AFM) in liquid environments. These powerful imaging techniques, however, can potentially damage or perturb delicate biological material and do not provide chemical information, which prevents a fundamental understanding of the dynamic processes underlying their evolution under physiological conditions. Here, we use a platform developed in our laboratory that enables acquisition of infrared (IR) spectroscopy and AFM images of biological material in physiological liquids with nanometer resolution in a cell closed by atomically thin graphene membranes transparent to IR photons. In this work, we studied the self-assembly process of S-layer proteins at the graphene-aqueous solution interface. The graphene acts also as the membrane separating the solution containing the proteins and Ca
2+
ions from the AFM tip, thus eliminating sample damage and contamination effects. The formation of S-layer protein lattices and their structural evolution was monitored by AFM and by recording the amide I and II IR absorption bands, which reveal the noncovalent interaction between proteins and their response to the environment, including ionic strength and solvation. Our measurement platform opens unique opportunities to study biological material and soft materials in general.
Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo
Authors: Ding Xiaokai , Sharko Amanda C. , McDermott Martina S. J. , Schools Gary P. , Chumanevich Alexander , Ji Hao , Li Jing , Zhang Li , Mack Zachary T. , Sikirzhytski Vitali , Shtutman Michael , Ivers Laura , O’Donovan Norma , Crown John , Győrffy Balázs , Chen Mengqian , Roninson Igor B. , Broude Eugenia V.
Published: August 2022

Breast cancers (BrCas) that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2+BrCa have intrinsic resistance and nearly all eventually become resistant to HER2-targeting therapy. Resistance to HER2-targeting drugs frequently involves transcriptional reprogramming associated with constitutive activation of different signaling pathways. We have investigated the role of CDK8/19 Mediator kinase, a regulator of transcriptional reprogramming, in the response of HER2+BrCa to HER2-targeting drugs. CDK8 was in the top 1% of all genes ranked by correlation with shorter relapse-free survival among treated HER2+BrCa patients. Selective CDK8/19 inhibitors (senexin B and SNX631) showed synergistic interactions with lapatinib and trastuzumab in a panel of HER2+BrCa cell lines, overcoming and preventing resistance to HER2-targeting drugs. The synergistic effects were mediated in part through the PI3K/AKT/mTOR pathway and reduced by PI3K inhibition. Combination of HER2- and CDK8/19-targeting agents inhibited STAT1 and STAT3 phosphorylation at S727 and up-regulated tumor suppressor BTG2. The growth of xenograft tumors formed by lapatinib-sensitive or -resistant HER2+breast cancer cells was partially inhibited by SNX631 alone and strongly suppressed by the combination of SNX631 and lapatinib, overcoming lapatinib resistance. These effects were associated with decreased tumor cell proliferation and altered recruitment of stromal components to the xenograft tumors. These results suggest potential clinical benefit of combining HER2- and CDK8/19-targeting drugs in the treatment of metastatic HER2+BrCa.
Tumor-polarized GPX3
+
AT2 lung epithelial cells promote premetastatic niche formation
Authors: Wang Zixin , Zhu Jie , Liu Yanfang , Wang Ziqiao , Cao Xuetao , Gu Yan
Published: August 2022

The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3
+
AT2 cells inhibited CD4
+
T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3
+
AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1α) and promoting HIF-1α-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3
+
AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.
Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA
Authors: Jin Shikai , Bueno Carlos , Lu Wei , Wang Qian , Chen Mingchen , Chen Xun , Wolynes Peter G. , Gao Yang
Published: August 2022

Bacteriophage T7 gp4 helicase has served as a model system for understanding mechanisms of hexameric replicative helicase translocation. The mechanistic basis of how nucleoside 5′-triphosphate hydrolysis and translocation of gp4 helicase are coupled is not fully resolved. Here, we used a thermodynamically benchmarked coarse-grained protein force field, Associative memory, Water mediated, Structure and Energy Model (AWSEM), with the single-stranded DNA (ssDNA) force field 3SPN.2C to investigate gp4 translocation. We found that the adenosine 5′-triphosphate (ATP) at the subunit interface stabilizes the subunit–subunit interaction and inhibits subunit translocation. Hydrolysis of ATP to adenosine 5′-diphosphate enables the translocation of one subunit, and new ATP binding at the new subunit interface finalizes the subunit translocation. The LoopD2 and the N-terminal primase domain provide transient protein–protein and protein–DNA interactions that facilitate the large-scale subunit movement. The simulations of gp4 helicase both validate our coarse-grained protein–ssDNA force field and elucidate the molecular basis of replicative helicase translocation.
Radius measurement via super-resolution microscopy enables the development of a variable radii proximity labeling platform
Authors: Oakley James V. , Buksh Benito F. , Fernández David F. , Oblinsky Daniel G. , Seath Ciaran P. , Geri Jacob B. , Scholes Gregory D. , MacMillan David W. C.
Published: August 2022

The elucidation of protein interaction networks is critical to understanding fundamental biology as well as developing new therapeutics. Proximity labeling platforms (PLPs) are state-of-the-art technologies that enable the discovery and delineation of biomolecular networks through the identification of protein-protein interactions. These platforms work via catalytic generation of reactive probes at a biological region of interest; these probes then diffuse through solution and covalently “tag” proximal biomolecules. The physical distance that the probes diffuse determines the effective labeling radius of the PLP and is a critical parameter that influences the scale and resolution of interactome mapping. As such, by expanding the degrees of labeling resolution offered by PLPs, it is possible to better capture the various size scales of interactomes. At present, however, there is little quantitative understanding of the labeling radii of different PLPs. Here, we report the development of a superresolution microscopy-based assay for the direct quantification of PLP labeling radii. Using this assay, we provide direct extracellular measurements of the labeling radii of state-of-the-art antibody-targeted PLPs, including the peroxidase-based phenoxy radical platform (269 ± 41 nm) and the high-resolution iridium-catalyzed µMap technology (54 ± 12 nm). Last, we apply these insights to the development of a molecular diffusion-based approach to tuning PLP resolution and introduce a new aryl-azide-based µMap platform with an intermediate labeling radius (80 ± 28 nm).
Loss of Ca
V
1.3 RNA editing enhances mouse hippocampal plasticity, learning, and memory
Authors: Zhai Jing , Navakkode Sheeja , Yeow Sean Qing Zhang , Krishna-K Kumar , Liang Mui Cheng , Koh Joanne Huifen , Wong Rui Xiong , Yu Wei Ping , Sajikumar Sreedharan , Huang Hua , Soong Tuck Wah
Published: August 2022

L-type Ca
V
1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate Ca
V
1.3 RNA editing, we demonstrate that unedited Ca
V
1.3
ΔECS
mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of Ca
V
1.3 RNA editing sites slows Ca
2+
-dependent inactivation to increase Ca
2+
influx but reduces channel open probability to decrease Ca
2+
influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited Ca
V
1.3 channels permitted larger Ca
2+
influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the Ca
V
1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the Ca
V
1.3 channel in brain function.
Patient activation reduces effects of implicit bias on doctor–patient interactions
Authors: Gainsburg Izzy , Derricks Veronica , Shields Cleveland , Fiscella Kevin , Epstein Ronald , Yu Veronica , Griggs Jennifer
Published: August 2022

Disparities between Black and White Americans persist in medical treatment and health outcomes. One reason is that physicians sometimes hold implicit racial biases that favor White (over Black) patients. Thus, disrupting the effects of physicians' implicit bias is one route to promoting equitable health outcomes. In the present research, we tested a potential mechanism to short-circuit the effects of doctors’ implicit bias: patient activation, i.e., having patients ask questions and advocate for themselves. Specifically, we trained Black and White standardized patients (SPs) to be “activated” or “typical” during appointments with unsuspecting oncologists and primary care physicians in which SPs claimed to have stage IV lung cancer. Supporting the idea that patient activation can promote equitable doctor–patient interactions, results showed that physicians’ implicit racial bias (as measured by an implicit association test) predicted racially biased interpersonal treatment among typical SPs (but not among activated SPs) across SP ratings of interaction quality and ratings from independent coders who read the interaction transcripts. This research supports prior work showing that implicit attitudes can undermine interpersonal treatment in medical settings and provides a strategy for ensuring equitable doctor–patient interactions.
Very large fluxes of methane measured above Bolivian seasonal wetlands
Authors: France James L. , Lunt Mark F. , Andrade Marcos , Moreno Isabel , Ganesan Anita L. , Lachlan-Cope Thomas , Fisher Rebecca E. , Lowry David , Parker Robert J. , Nisbet Euan G. , Jones Anna E.
Published: August 2022

Methane (CH
4
) mole fractions from the large semiseasonal Llanos de Moxos wetlands (∼70,000 km
2
) in northern Bolivia were measured by aircraft flights and ground sampling during early March 2019 (late wet season). Daily fluxes of CH
4
determined from the measurements using box models and inverse modeling were between 168 (± 50) and 456 (± 145) mg CH
4
⋅m
−2
⋅d
−1
for the areas overflown, very high compared with those of previous Amazon basin studies. If the seasonality of the CH
4
emissions is comparable to other parts of the Amazon Basin, the region could contribute as much as 8% of annual Amazonian CH
4
emissions.
An accurate standardization protocol for heating efficiency determination of 3D printed magnetic bone scaffolds
Authors: Makridis A , Kazeli K , Kyriazopoulos P , Maniotis N , Samaras T , Angelakeris M
Published: August 2022

Last decade, three-dimensional (3D) printing technology has emerged as a useful tool for meticulously fabricated scaffolds with high precision and accuracy, resulting in intricately detailed biomimetic 3D structures. To this end, nowadays, magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability not only to promote bone tissue formation, bone repair, and regeneration, but at the same time allow for nanoscale drug delivery. Although there has been a lot of research effort on the fabrication of bone scaffolds in the last few years, their perspectives as multifunctional magnetic hyperthermia agents remain an open issue. This emerging, uninvestigated research field requires a carefully designed framework to produce reliable results. This work focuses on establishing such a framework by proposing a standardization protocol with certain experimental steps for an accurate evaluation of the heating efficiency of the 3D printed magnetic scaffolds bone phantoms. The specific indexes of specific absorption rate and specific loss power are carefully determined and calculated here to enhance the differences in the heating experimental approaches that have been followed until now between magnetic nanoparticles and magnetic bone scaffolds. Meanwhile, the heating evaluation cases that one can find in magnetic hyperthermia are separately defined and analyzed with their suited experimental protocols. Firstly, 3D printed magnetic scaffolds are designed and fabricated. Secondly, they are evaluated as heating carriers. Agarose is exploited here not only as a tissue mimicking phantom, but also as a heat diffusion medium through the scaffold’s pores. A reliable estimation sequence of the heating efficiency, i.e. the specific absorption rate of the magnetic scaffolds, is introduced, analyzed and discussed in conjunction with the specific loss power, which is the respective quantitative index for evaluating the magnetic nanoparticles’ heating efficacy. Finally, this work proposes how the fabrication procedure of the 3D printed scaffolds can be guided by the magnetic particle hyperthermia literature results, as to increase the scaffolds heating efficiency through printing parameters. Consequently, this work deals with the methodology to create a reproducible and accurate protocol for assessing the heating efficiency of magnetic scaffolds serving as bone implants for deep-seated hyperthermia tumor treatment.
In vivo study of beta-glucan-based biogenic synthesis of silver nanocomposite using Schizophyllum commune for wound dressings in a rat burn model
Authors: Safaee-Ardakani Mohammad Reza , Hatamian-Zarmi Ashrafalsadat , Sadat Seyedeh Mahdieh , Alvandi Hale , Ebrahimi-Hosseinzadeh Bahman , Mokhtari-Hosseini Zahra Beagom , Mohammadi Mehrave
Published: August 2022

Bacterial infection is a significant barrier to the natural wound healing process. Silver nanoparticles have antibacterial activity through the destruction of DNA and bacterial membranes. In the present study, a green method was introduced to synthesize silver nanoparticles produced by the Schizophyllum commune. The antibacterial mat loaded with 0.5, 1, and 3% (w/w) of bioactive silver nanoparticles were produced in polyvinyl alcohol (PVA) and schizophyllan (SPG) solution (20:80) with electrospun (PVA/SPG). Then the physicochemical properties of silver nanoparticles and the mats PVA/SPG containing silver nanoparticles were investigated. An animal model also examined antimicrobial activity, cytotoxicity, adhesion, and grade II burn ulcers. The results showed that spherical silver nanoparticles with a diameter of about 40 nm were produced and completely scattered on the nanofibers according to TEM images. A non-covalent interaction was revealed between SPG and AgNPs; the nanofibers were hydrophilic. Nanofibers containing silver nanoparticles had intense antimicrobial activity against E. coli and S. aureus. This inhibition increases with increasing concentration. The cytotoxicity and adhesion results showed that the PVA/SPG-AgNPs 1% sample had the best effect on fibroblast cells. The 1% sample was tested for the animal model, and after 14 days, it had a practical effect on the control. At 14 days post-treatment, a skinny epithelial layer was formed and covered the wound area, and these nanofibers were suitable for wound dressing. Consequently, PVA/SPG-AgNPs nanofibers could be a good option to cover burn wounds by speeding up the wound healing process and treatment costs.
Comparison of the contact and focus variation measurement methods in the process of surface topography evaluation of additively manufactured models with different geometry complexity
Authors: Bazan Anna , Turek Paweł , Przeszłowski Łukasz
Published: August 2022

One of the key measurement parameters of the surface topography is the measurement area. It influences the possibility of using filters separating components of surface texture and thus determines the reliability of the obtained measurement results. The currently applicable standard does not define the size of the measuring area. To determine its size, fractal analysis was carried out in the article. The paper presents research on two types of geometry: simple geometry in the form of cylindrical and spherical surfaces and more complex geometry represented by free surfaces such as crowns and molars of teeth. In the process of making the research models, four 3D printing techniques were used: Fused Deposition Modeling (FDM), Melted and Extruded Modeling (MEM) Fused Filament Fabrication (FFF) and Material Jetting (MJ). 3D measurements of surface texture were made using a contact profilometer and a focus variation microscope. The analysis of topography images and selected parameters of the surface topography showed that the optical method gave better measurement results than the contact method. In the case of models made with the FDM and MEM techniques, similar values of the Sa parameter were obtained. Slightly smaller values of Sa were recorded for FFF models, while the highest for MJ models. Models made using the FFF method were also characterized by the lowest variability of results. Models made using the MJ method were characterized by relatively deep valleys in comparison with the other models, which was reflected in the Ssk and Svk parameters. The valleys counting from the top surface of the specimen were the shallowest for models made with the FFF method. Surfaces with simpler geometry were characterized by smaller variability of parameters values.
Controlling high-speed dry friction through the geometry of micro-patterned asperities
Authors: Florio Catherine S
Published: August 2022

Advances in manufacturing technologies have provided means to create surface textures with regular patterns of uniform asperities, leading to the potential for improved control of friction. In order to design surface topologies that induce desirable tribological effects, an understanding of the influences of the geometric features of asperities on measures of frictional resistance is required. Dynamic elastic-plastic finite element modeling methods, which included material damage and failure, were used to study the interactions of directly modeled 100 micron rib-like asperities on two deformable aluminum blocks. The relationships between the mechanics of the deformation and failure of five unique asperity geometries, the coefficients of static and kinetic friction, and the system energy stored and dissipated were studied under dry, high-load rate conditions, where motion was initiated in under 1 ms and acceleration approached 100 kG. Influences of the geometric features of the asperities were explored using semi-circular, triangular, and square-shaped cross-sectional profiles and evaluated for complex geometries created by combinations of these basic shapes. Static coefficients of friction were found to vary more than two-fold with asperity geometry based on the contact area normal direction. The study found that it was also possible to maintain the static friction coefficient but more than triple the force to initiation motion simply by changing the asperity shape. While kinetic friction coefficients were less influenced by asperity shape for the high-speed conditions studied, the geometric characteristics directed the way an asperity deformed under load and the extent of the material failure during sliding. A more than four-fold variation in energy stored within the system and over an order of magnitude variation in energy dissipated by the system was found for the geometries examined. This study demonstrates the importance of understanding the mechanical behavior of the asperity when designing surface textures to tailor dry, high-speed friction.
A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies
Authors: Wang Bo , Lin Jun , Hoag Matthew R , Wright Meredith , Ma Mingjun , Cai Wenyan , Gallolu Kankanamalage Sachith , Liu Yue
Published: August 2022

The classical `knob-into-holes' (KIH) strategy (knob(T366Y)/hole (Y407T)) has successfully enhanced the heterodimerization of a bispecific antibody (BsAb) resulting in heterodimer formation up to 92% of protein A (ProA)-purified protein pool. However, it does not show high efficiency for every BsAb. KIH was initially applied to a CD20/CD3 BsAb. After in silico modeling, two additional new mutations, S354Y in knob-heavy chain (HC) and Q347E in hole-HC, together with KIH named `ETYY', were introduced in the Fc. The CD20/CD3 BsAb hybrid only represented ~ 50% of the ProA-purified protein pool when KIH was applied. With ETYY, the percentage of CD20/CD3 hybrid increased to 93.8%. CD20/CD3-v4b (containing ETYY) retains the original activity of the BsAb at both Fab and Fc regions, and also shows good developability. These results indicate that the computer-aided novel ETYY design has the potential to improve the development of next-generation BsAbs with higher yields and simpler purification.
Implementation of an integrated pharmacist collaborative care model in specialty disease state clinics
Authors: Stroedecke Natasha , Lee Jenna , Stutsky Martha , Boothe Kimberly , Tong Kimhouy , Luon Steph , Sawant Vinay , Renauer Marie
Published: August 2022

Purpose

To expand health-system specialty pharmacy (HSSP) clinical continuity by implementing a specialty integrated model for clinical services in target sites.

After evaluation of baseline clinical continuity and institutional goals, select clinics were identified as target sites to which to expand this integrated approach of a medication management clinic (MMC). In this MMC model, the key steps included engaging stakeholders, workflow training, optimization of the electronic health record, service evaluation, compliance with regulatory standards, and development of marketing strategies. The initial focus was development of innovative collaborative practice agreements (CPAs) to expand the scope of ambulatory care pharmacists’ practice. Analysis of existing specialty and ambulatory workflows and technology was completed before development of the integrated workflow. Existing credentialing policies were updated to support expanded practices, and marketing collaterals were developed to support growth of pharmacy referrals. Meetings with stakeholders took place to ensure smooth transitions into integrated areas. Primary endpoints included clinical continuity, as determined by prescription orders placed within the health system sent to the HSSP, and number of signed referrals to MMC. Secondary endpoints included disease state–specific clinical outcomes as well as overall outcomes such as medication adherence, laboratory test adherence, immunization rates, and patient and clinician satisfaction. An MMC model was successfully implemented in 5 target specialty practices. Specialty clinic CPAs were developed for rheumatology and digestive health (including viral hepatitis). Since implementation, clinical continuity increased 23% and referrals exceeded the target at 165%. Data on secondary endpoints are currently being collected to evaluate quality of pharmacy services. Pharmacy services have enhanced patient care and received positive feedback from clinicians.

Conclusion

Expansion of integrated decentralized pharmacists into target practices has increased clinical continuity and the number of pharmacist referrals. Clinicians have regarded pharmacists as vital members of the team. Creation of additional specialty CPAs will be needed to support further growth in other clinics.
Transcriptomic and histochemical analysis reveal the complex regulatory networks in equine chorioallantois during spontaneous term labor
Authors: El-Sheikh Ali Hossam , Scoggin Kirsten , Murase Harutaka , Norris Jamie , Menarim Bruno , Dini Pouya , Ball Barry
Published: August 2022

The equine chorioallantois (CA) undergoes complex physical and biochemical changes during labor. However, the molecular mechanisms controlling these changes are still unclear. Therefore, the current study aimed to characterize the transcriptome of equine CA during spontaneous labor and compare it with that of normal preterm CA. Placental samples were collected postpartum from mares with normal term labor (TL group, n = 4) and from preterm not in labor mares (330 days GA; PTNL group, n = 4). Our study identified 4137 differentially expressed genes (1820 upregulated and 2317 downregulated) in CA during TL as compared with PTNL. TL was associated with the upregulation of several proinflammatory mediators (MHC-I, MHC-II, NLRP3, CXCL8, and MIF). Also, TL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP2, MMP3, and MMP9) with subsequent extracellular matrix degradation and apoptosis, as reflected by upregulation of several apoptosis-related genes (ATF3, ATF4, FAS, FOS, and BIRC3). In addition, TL was associated with downregulation of 21 transcripts coding for collagens. The upregulation of proteases, along with the downregulation of collagens, is believed to be implicated in separation and rupture of the CA during TL. Additionally, TL was associated with downregulation of transcripts coding for proteins essential for progestin synthesis (SRD5A1 and AKR1C1) and angiogenesis (VEGFA and RTL1), as well as upregulation of prostaglandin synthesis-related genes (PTGS2 and PTGES), which could reflect the physiological switch in placental endocrinology and function during TL. In conclusion, our findings revealed the equine CA gene expression signature in spontaneous labor at term, which improves our understanding of the molecular mechanisms triggering labor.
Disrupted dynamic network reconfiguration of the brain functional networks of individuals with autism spectrum disorder
Authors: Wang Min , Wang Lingxiao , Yang Bo , Yuan Lixia , Wang Xiuqin , Potenza Marc N , Dong Guang Heng
Published: August 2022

Human and animal studies on brain functions in subjects with autism spectrum disorder have confirmed the aberrant organization of functional networks. However, little is known about the neural features underlying these impairments. Using community structure analyses (recruitment and integration), the current study explored the functional network features of individuals with autism spectrum disorder from one database (101 individuals with autism spectrum disorder and 120 healthy controls) and tested the replicability in an independent database (50 individuals with autism spectrum disorder and 74 healthy controls). Additionally, the study divided subjects into different age groups and tested the features in different subgroups. As for recruitment, subjects with autism spectrum disorder had lower coefficients in the default mode network and basal ganglia network than healthy controls. The integration results showed that subjects with autism spectrum disorder had a lower coefficient than healthy controls in the default mode network–medial frontal network and basal ganglia network–limbic networks. The results for the default mode network were mostly replicated in the independent database, but the results for the basal ganglia network were not. The results for different age groups were also analysed, and the replicability was tested in different databases. The lower recruitment in subjects with autism spectrum disorder suggests that they are less efficient at engaging these networks when performing relevant tasks. The lower integration results suggest impaired flexibility in cognitive functions in individuals with autism spectrum disorder. All these findings might explain why subjects with autism spectrum disorder show impaired brain networks and have important therapeutic implications for developing potentially effective interventions.