bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient‐Reported Symptoms in the Global Multiple System Atrophy Registry
Authors: Palma Jose‐Alberto , Krismer Florian , Meissner Wassilios G. , Kuijpers Mechteld , Millar‐Vernetti Patricio , Perez Miguel A. , Fanciulli Alessandra , Norcliffe‐Kaufmann Lucy , Bower Pam , Wenning Gregor K. , Kaufmann Horacio
Published: August 2022

Background

The Global Multiple System Atrophy Registry (GLOMSAR) was established in 2013. It is an online patient‐reported contact registry open and free that relies on self‐reported diagnosis by the patient or caregiver.

Objectives

To report the demographics of patients enrolled in GLOMSAR and the results of an ancillary online symptom questionnaire.

Methods

Patients enrolled in GLOMSAR were invited to complete a custom‐designed online questionnaire about disease onset and symptom prevalence.

Results

At the time of writing, there were 1083 participants in GLOMSAR, of which 33% (365) completed the questionnaire. The onset and frequency of most symptoms was similar to those reported in the literature in physician‐reported studies. Some were understudied or not typically associated with multiple system atrophy (MSA), including reduced female sexual sensation (55%), forgetfulness (60%), pseudobulbar affect (37%), olfactory changes (36%), and visual hallucinations (21%).

Conclusions

Patient‐reported studies and ancillary online questionnaires are valid, underused research tools useful to advance our knowledge on understudied MSA features and highlight the patients' voice.
Inverse scattering problem with Levinson formula for eigenparameter‐dependent discrete Sturm–Liouville equation
Authors: Koprubasi Turhan , Mohapatra Ram N.
Published: August 2022

In this paper, an inverse scattering problem for discrete Sturm–Liouville equation with eigenparameter‐dependent boundary condition is investigated. In quest of finding scattering function and the main equation of this problem, the uniqueness of the kernel is proven. Also, an appropriate Levinson‐type formula based on the continuity of scattering function is given.
On new fractional integral inequalities using Marichev–Saigo–Maeda operator
Authors: Singhal Meenakshi , Mittal Ekta
Published: August 2022

Generalizations of fractional integral inequalities were introduced by many authors. The aim of our investigation is to establish some new fractional integral inequalities using Marichev–Saigo–Maeda (MSM) fractional integral operator for convex function. Further, we obtain some more fractional integral inequalities of Grüss type using MSM operator.
An efficient hybrid numerical method based on an additive scheme for solving coupled systems of singularly perturbed linear parabolic problems
Authors: Kumar Sunil , Kuldeep  , Ramos Higinio , Singh Joginder
Published: August 2022

We construct an efficient hybrid numerical method for solving coupled systems of singularly perturbed linear parabolic problems of reaction‐diffusion type. The discretization of the coupled system is based on the use of an additive or splitting scheme on a uniform mesh in time and a hybrid scheme on a layer‐adapted mesh in space. It is proven that the developed numerical method is uniformly convergent of first order in time and third order in space. The purpose of the additive scheme is to decouple the components of the vector approximate solution at each time step and thus make the computation more efficient. The numerical results confirm the theoretical convergence result and illustrate the efficiency of the proposed strategy.
A reciprocal learning strategy for semisupervised medical image segmentation
Authors: Zeng Xiangyun , Huang Rian , Zhong Yuming , Xu Zeyan , Liu Zaiyi , Wang Yi
Published: August 2022

Background

Semisupervised strategy has been utilized to alleviate issues from segmentation applications due to challenges in collecting abundant annotated segmentation masks, which is an essential prerequisite for training high‐performance 3D convolutional neural networks (CNNs) .

Purpose

Existing semisupervised segmentation methods are mainly concerned with how to generate the pseudo labels with regularization but not evaluate the quality of the pseudo labels explicitly. To alleviate this problem, we offer a simple yet effective reciprocal learning strategy for semisupervised volumetric medical image segmentation, which generates more reliable pseudo labels for the unannotated data.

Methods

Our proposed reciprocal learning is achieved through a pair of networks, one as a teacher network and the other as a student network. The student network learns from pseudo labels generated by the teacher network. In addition, the teacher network autonomously optimizes its parameters based on the reciprocal feedback signals from the student's performance on the annotated images. The efficacy of the proposed method is evaluated on three medical image data sets, including 82 pancreas computed tomography (CT) scans (training/testing: 62/20), 100 left atrium gadolinium–enhanced magnetic resonance (MR) scans (training/testing: 80/20), and 200 breast cancer MR scans (training/testing: 68/132). The comparison methods include mean teacher (MT) model, uncertainty‐aware MT (UA‐MT) model, shape‐aware adversarial network (SASSNet), and transformation‐consistent self‐ensembling model (TCSM). The evaluation metrics are Dice similarity coefficient (Dice), Jaccard index (Jaccard), 95% Hausdorff distance (95HD), and average surface distance (ASD). The Wilcoxon signed‐rank test is used to conduct the statistical analyses.

Results

By utilizing 20% labeled data and 80% unlabeled data for training, our proposed method achieves an average Dice of 84.77%/90.46%/78.53%, Jaccard of 73.71%/82.67%/69.00%, ASD of 1.58/1.90/0.57, and 95HD of 6.24/5.97/4.34 on pancreas/left atrium/breast data sets, respectively. These results outperform several cutting‐edge semisupervised approaches, showing the feasibility of our method for the challenging semisupervised segmentation applications.

Conclusions

The proposed reciprocal learning strategy is a general semisupervised solution and has the potential to be applied for other 3D segmentation tasks.
Associations between the ALSFRS‐R score and urate levels during 12 months of edaravone treatment for amyotrophic lateral sclerosis: Post hoc analysis of ALSFRS‐R scores in clinical studies MCI186‐16, MCI186‐17, and MCI186‐19
Authors: Takahashi Fumihiro , Kano Osamu , Nagano Yoshito , Yoneoka Takatomo , Nelson Sally , Ushirogawa Yoshiteru
Published: August 2022

Introduction/Aims

In this study we examined the relationship between urate levels at baseline and functional change measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS‐R) total score after edaravone treatment.

Methods

Data from the edaravone trials MCI186‐16, MCI186‐17, and MCI186‐19 were analyzed, including the following treatment sequence groups: edaravone‐edaravone (EE, n = 113); edaravone‐placebo (EP, n = 45); and placebo‐edaravone (PE, n = 146). Subgroups were defined as low baseline urate (below the median value of 4.8 mg/dL) and high baseline urate (≥4.8 mg/dL). The differences in ALSFRS‐R total score change and urate change were evaluated using the mixed model for repeated measurement for overall population, by urate‐level subgroup, and by trial.

Results

Compared with the PE group, the EE group showed a slower decline in ALSFRS‐R score, regardless of the urate baseline level, and a slower decline in urate level in the higher baseline urate subgroup. Smaller changes in ALSFRS‐R score and urate were observed in patients diagnosed with “probable, laboratory‐supported ALS.” There was a positive correlation between changes from baseline to cycle 12 in urate levels and ALSFRS‐R score.

Discussion

Edaravone treatment in ALS patients diagnosed with “definite ALS” or “probable ALS” showed slowing of disease progression, regardless of baseline urate level. In addition, because edaravone treatment was associated with a slower decline in urate level in the higher baseline urate subgroup and urate‐level changes were associated with changes in ALSFRS‐R score, urate level, and/or change may be one indicator in predicting disease progression after edaravone administration.
Establishment of a new classification system for chronic inflammatory demyelinating polyneuropathy based on unsupervised machine learning
Authors: Chang Chun‐Wei , Ro Long‐Sun , Lyu Rong‐Kuo , Kuo Hung‐Chou , Liao Ming‐Feng , Wu Yih‐Ru , Chen Chiung‐Mei , Chang Hong‐Shiu , Weng Yi‐Ching , Huang Chin‐Chang , Chang Kuo‐Hsuan
Published: August 2022

Introduction/Aims

A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features.

Methods

The clinical, laboratory, and electrophysiological features of 172 treatment‐naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree‐based model.

Results

Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p < .001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p < .001; hypoalbuminemia: 4.09 g/dL, p < .001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p = .043) and 3 (25.0%; p = .014). A tree‐based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%).

Discussion

The established hierarchical clustering with the tree‐based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials.
COVID‐19 infection and vaccination in patients with skeletal muscle channelopathies
Authors: Vivekanandam Vinojini , Jayaseelan Dipa , Hanna Michael G.
Published: August 2022

Introduction/Aims

Although we have gained insight into coronavirus disease‐2019 (COVID‐19) caused by severe acute respiratory syndrome–coronavirus 2 since the beginning of the pandemic, our understanding of the consequences for patients with neuromuscular disorders is evolving. In this study we aimed to study the impact of COVID‐19 and COVID‐19 vaccination on skeletal muscle channelopathies.

Methods

We conducted a survey of patients with genetically confirmed skeletal muscle channelopathies seen at the UK Nationally Commissioned Channelopathy Service.

Results

Thirty‐eight patient responses were received. Six patients had COVID‐19 infection leading to exacerbation of their underlying muscle channelopathy. No major complications were reported. Thirty‐six patients had received one or two COVID‐19 vaccinations and the majority (68%) had no worsening of their underlying channelopathy. Thirty‐two percent reported worsening of their usual symptoms of their muscle channelopathy, but all reported recovery to baseline levels. No serious adverse events were reported.

Discussion

The overall rates of COVID‐19 infection were low in our study and COVID‐19 vaccine uptake rates were high. Our results have been useful to inform patients that a subset of patients have reversible worsening of their channelopathy post–COVID‐19 vaccination. Our study provides information for giving advice to patients with skeletal muscle channelopathies regarding COVID‐19 infection and vaccination.
Conformer Selection Upon Dilution with Water: The Fascinating Case of Liquid Ethylene Glycol Studied via Molecular Dynamics Simulations**
Authors: Gaur Anjali , Balasubramanian Sundaram
Published: August 2022

The aqueous solution of ethylene glycol (EG) is a binary liquid mixture that displays rich conformational and structural behaviour, which has not yet been adequately explored through atomistic molecular dynamics simulations. Herein, employing an accurate force field for EG, several physical properties of this solution are calculated to be in quantitative agreement with experimental data. While 79 % of molecules in neat liquid EG exist with their central OCCO dihedral in the gauche state, this fraction increases to 89 % in the dilute aqueous solution, largely in response to the increase in the static dielectric constant of the solution from that of neat liquid EG. The increase in gauche conformers increases the mean dipole moment of EG molecules in the solution which is additionally contributed by specific conformational states of the two terminal HOCC dihedral angles.
Solubility determination of boehmite nanoparticles and modeling of solution thermodynamics of blend polymeric membranes
Authors: Kumar Anil , Ghosh Uttam Kumar
Published: August 2022

The solubility of boehmite nanoparticles was determined experimentally for 20 different solvents using Hansen solubility parameter method (HSP). The algorithm given by Gharagheizi was optimized using MATLAB. The solubility was found as, δ = 33.08 MPa1/2 with, δD = 16.50 MPa1/2, δP = 15.54 MPa1/2, and δH = 24.09 MPa1/2. Flory‐Huggin's theory was used to model the quarternary system of a blend polymeric membrane. The thermodynamic equations were solved and optimized using MATLAB and ternary phase diagrams were obtained for different filler compositions. Thermodynamic enhancement and kinetic hindrance parameters were obtained to predict the membrane morphologies. The porosity of the membrane was increased with the addition of nanoparticles. Contact angle of the membrane was decreased from 84.45° to 50.2°.
‘I didn't know what was in front of me’—Bereaved parents' experience of adapting to life when a co‐parent of dependent children has died with cancer
Authors: Hanna Jeffrey R. , Semple Cherith J.
Published: August 2022

Objective

It is not clear how the bereaved parent navigates life with the children after a co‐parent has died. The objective of this study is to explore bereaved parents' experience of managing life when a co‐parent of dependent children has died with cancer.

Methods

Twenty‐one in‐depth interviews were conducted with bereaved parents when a co‐parent died with cancer. Data were analysed thematically.

Results

Bereaved parents highlighted how their children was their key focus after the death of a co‐parent with cancer, as they effortfully strived to be a ‘perfect parent’. While some bereaved parents struggled to adapt to the role as a sole parent, others described the importance of maximising social networks to help with the practical aspects of parenting. However, most bereaved parents described intense feelings of loneliness as they navigated parenting alone. To help navigate this post‐bereavement period, parents considered it important for their children to openly talk about the deceased parent. Also, meeting others who have experienced similar situations was helpful for the bereaved parent and children, providing hope for the future. Results are discussed under two themes: (1) adapting to life without the parent, and (2) a desire to keep the memory alive of the parent that died with cancer.

Conclusions

Bereaved parents should be encouraged to practice self‐care when a co‐parent has died from cancer so they can appropriately meet the needs of their children. Bereaved parents should be reassured that showing emotion in front of the children is helpful and could facilitate better grief experiences for the whole family.
Ca2+‐dependent interactions between lipids and the tumor‐targeting peptide pHLIP
Authors: Vasquez‐Montes Victor , Tyagi Vivek , Sikorski Eden , Kyrychenko Alexander , Freites J. Alfredo , Thévenin Damien , Tobias Douglas J. , Ladokhin Alexey S.
Published: August 2022

Cancerous tissues undergo extensive changes to their cellular environments that differentiate them from healthy tissues. These changes include changes in extracellular pH and Ca2+ concentrations, and the exposure of phosphatidylserine (PS) to the extracellular environment, which can modulate the interaction of peptides and proteins with the plasma membrane. Deciphering the molecular mechanisms of such interactions is critical for advancing the knowledge‐based design of cancer‐targeting molecular tools, such as pH‐low insertion peptide (pHLIP). Here, we explore the effects of PS, Ca2+, and peptide protonation state on the interactions of pHLIP with lipid membranes. Cellular studies demonstrate that exposed PS on the plasma membrane promotes pHLIP targeting. The magnitude of this effect is dependent on extracellular Ca2+ concentration, indicating that divalent cations play an important role in pHLIP targeting in vivo. The targeting mechanism is further explored with a combination of fluorescence and circular dichroism experiments in model membranes and microsecond‐timescale all‐atom molecular dynamics simulations. Our results demonstrate that Ca2+ is engaged in coupling peptide‐lipid interactions in the unprotonated transmembrane conformation of pHLIP. The simulations reveal that while the pH‐induced insertion leads to a strong depletion of PS around pHLIP, the Ca2+‐induced insertion has the opposite effect. Thus, extracellular levels of Ca2+ are crucial to linking cellular changes in membrane lipid composition with the selective targeting and insertion of pHLIP. The characterized Ca2+‐dependent coupling between pHLIP sidechains and PS provides atomistic insights into the general mechanism for lipid‐coupled regulation of protein‐membrane insertion by divalent cations.
Depicting the proton relay network in human aromatase: New insights into the role of the alcohol‐acid pair
Authors: Zhang Chao , Gilardi Gianfranco , Di Nardo Giovanna
Published: August 2022

Human aromatase is the cytochrome P450 catalyzing the conversion of androgens into estrogens in a three steps reaction essential to maintain steroid hormones balance. Here we report the capture and spectroscopic characterization of its compound I (Cpd I), the main reactive species in cytochromes P450. The typical spectroscopic transitions indicating the formation of Cpd I are detected within 0.8 s when mixing aromatase with meta‐chloroperoxybenzoic acid. The estrogen product is obtained from the same reaction mixture, demonstrating the involvement of Cpd I in aromatization reaction. Site‐directed mutagenesis is applied to the acid‐alcohol pair D309 and T310 and to R192, predicted to be part of the proton relay network. Mutants D309N and R192Q do not lead to Cpd I with an associated loss of activity, confirming that these residues are involved in proton delivery for Cpd I generation. Cpd I is captured for T310A mutant and shows 2.9‐ and 4.4‐fold faster rates of formation and decay, respectively, compared to wild‐type (WT). However, its activity is lower than the WT and a larger amount of H2O2 is produced during catalysis, indicating that T310 has an essential role in proton gating for generation of Cpd 0 and Cpd I and for their stabilization. The data provide new evidences on the role of threonine belonging to the conserved “acid‐alcohol” pair and known to be crucial for oxygen activation in cytochromes P450.
Effect of Particle Size on the Optical Properties of Silicon‐Vacancy Centers in Nanodiamonds Fabricated by a Detonation Process
Authors: Makino Yuto , Saito Yoshiki , Takehara Hikaru , Tsurui Akihiko , Okuyama Naoto , Ashida Masaaki
Published: August 2022

Nanodiamonds containing silicon‐vacancy centers (SiV‐NDs) are attracting attention as promising fluorescent markers. Recently, the preparation of single‐digit‐nanometer‐sized SiV‐NDs by a detonation process, which can be carried out on a practical scale, has been demonstrated. However, little is known about the effect of these extremely small diamonds fabricated by a detonation process on the electronic state of the SiV centers. In the present study, SiV‐NDs prepared by the detonation process are investigated spectroscopically. It is reported that the extremely small particle size, ≈10 nm, causes an increase of the nonradiative transition probability and an enhancement of the electron–phonon coupling compared with those of typical SiV centers. Because of their electronic states, SiV‐NDs also exhibit a short luminescence lifetime (≈0.56 ns) and a large linewidth (≈14.4 nm) at room temperature. Nevertheless, the fundamental properties of the SiV center, such as the photostability, do not change, irrespective of the particle size.
The IRIS paradox: Imaging findings in a case of PJP‐IRIS
Authors: Reddy Taryn , Bajwa Ramey , Burke Andrew
Published: August 2022

Immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) and Pneumocystis jirovecii pneumonia infection reflects an exaggerated inflammatory response of the host immune system to an antigen, which is temporally related to recovery of the immune system. Clinical manifestations include fever, cough, dyspnoea and hypoxia following the commencement of antiretroviral therapy. Diagnosis is made on clinical and radiological criteria with exclusion of other infective and non‐infective causes. Unrecognized, IRIS may be associated with significant morbidity and mortality. Treatment with corticosteroids often results in prompt recovery. There is limited literature on radiological findings of Pneumocystis jirovecii pneumonia‐associated IRIS. Here we describe cross‐sectional imaging findings of PJP‐IRIS in a patient following commencement of antiretroviral therapy.
Sarcoidosis developing after COVID‐19: A case report
Authors: Somboonviboon Dujrath , Wattanathum Anan , Keorochana Narumon , Wongchansom Kittisak
Published: August 2022

COVID‐19 has been implicated in the development of a range of autoimmune diseases and medical consequences. Sarcoidosis is an inflammatory disease with sustained granulomatous inflammation. The possible main pathogenesis of sarcoidosis is a dysregulation between immune response and certain environmental antigens. We present a case of sarcoidosis as an interesting sequela of COVID‐19. The patient was hospitalized due to SARS‐CoV‐2 without complication. Ten weeks after the illness, his chest computed tomography (CT) showed bilateral hilar, paratracheal and subcarinal lymph node enlargement. Endobronchial ultrasound with transbronchial needle aspiration (EBUS‐TBNA) was performed; pathologic findings were that of well‐formed non‐necrotizing granulomas. Complete eye examination reported panuveitis and papillitis in both eyes. On the basis of these findings, sarcoidosis was diagnosed. Therefore, sarcoidosis developing after COVID‐19 was suggested as a possible link between the viral infection and dysregulation of the inflammation process. However, further studies are needed to confirm this association.
Robust hybrid observer design based on reconstructability conditions for piecewise linear systems
Authors: Mera Manuel , Bejarano Francisco Javier
Published: August 2022

In this article, a robust hybrid observer is proposed to estimate the state of piecewise linear systems (PWL) that fulfill the reconstructability conditions. The design of this observer uses a high order sliding mode differentiator and is based on the reconstructability conditions for the discrete state of PWL systems. Additionally, the design takes into account the case when the differentiator output does not converge exactly to the actual derivatives of the system output. This could be due to the system output being affected by unknown but bounded perturbations or the differentiator being implemented on a digital device. The applicability of the results is illustrated by a numerical example.
Improved Charge Separation and Injection Efficiencies of Bismuth Vanadate Photoanode by Depositing Composite CoOx/CuO Cocatalyst
Authors: Hu Yingfei , Hu Qingyuan , Zhong Qian , Guan Hangmin , Hao Lingyun , Wang Yuanyuan , Zhang Wenyan , Du Hongxiu , Tian Wenjie
Published: August 2022

Exploring cheap and efficient cocatalysts is particularly important for a photoanode during photoelectrochemical (PEC) water splitting. Herein, we demonstrate that composite CoOx/CuO cocatalyst could efficiently enhance the oxygen evolution activity of BiVO4. The onset potential of BiVO4 shifts negatively from 0.42 to 0.38 V vs. the reversible hydrogen electrode (RHE), and the photocurrent of BiVO4 increases from 0.42 mA cm−2 to 1.58 mA cm−2 at 1.23 V vs. RHE, which increases by about 3.76 times. It was confirmed by subsequent electrochemical and physical characterization that the charge separation and injection efficiency were improved, and the IPCE was also improved. Systematic studies indicate that composite CoOx/CuO cocatalyst exhibits better performance than the single CoOx or CuO cocatalyst for promoting the separation of electron‐hole, and accelerating the surface water oxidation reaction.
Experimental Selection of Bases for Colloidal Gold‐Polymer Composite Catalyst in Homocoupling Reactions
Authors: Hou Jian , Egemole Franklin O. , Eyimegwu Faith M. , Yun Jaehan , Jang Wongi , Byun Hongsik , Kim Jun‐Hyun
Published: August 2022

This work describes the empirical screening of base types and amounts on the catalytic property of gold‐polymer composite particles in the aerobic homocoupling of arylboronic acid. As these particles notably improve the yields of biaryl in the presence of bases, various bases and their amounts are systematically tested to experimentally identify an ideal base that can provide high reactivity and recyclability of the composite particles in mild and green conditions. Interestingly, the following conditions ‐ soluble strong bases at sub‐stoichiometric quantities (0.5 eq.) and insoluble weak bases at excess amounts (3.0 eq.) in EtOH ‐ significantly enhance the catalytic activities of the composite particles. Upon screening two ideal bases, overall catalytic properties of the composite particles including reaction rate at three different temperatures, activation energy (51–52 kJ/mole), and recyclability (7 cycles) were compared. Understanding the effect of bases and fine‐tuning reaction conditions can potentially improve overall reactivity and recyclability of the composite particles as a green quasi‐homogenous catalyst.
A Study on Sulfonylation of Cyanohydrins with α‐Functionalized Sulfonyl Chlorides
Authors: Dobrydnev Alexey V. , Vashchenko Bohdan V. , Popova Maria V. , Volovenko Yulian M.
Published: August 2022

Herein we describe the reaction of cyanohydrins with α‐functionalized sulfonyl chlorides and discuss the reactivity of target α‐functionalized β‐enamino γ‐sultones. Depending on electron‐withdrawing activity of α‐functionality of given sulfonyl chlorides the reaction with cyanohydrins either accomplished in one‐pot manner (tandem sulfonylation–CSIC reaction) affording β‐enamino γ‐sultones (α‐functionality=CO2Me, CN, p‐C6H4‐CO2Me) or resulted in sulfonylated cyanohydrins, which can be converted into target β‐enamino γ‐sultones through the t‐BuOK‐mediated CSIC reaction (α‐functionality=Ph). The nature of α‐functionality drastically affects the reactivity of α‐functionalized β‐enamino γ‐sultones. Specifically, α‐CO2Me and α‐CN β‐enamino γ‐sultones are less reactive toward electrophiles and tolerate the nucleophiles. This is the consequence of high degree of conjugation between amino group and EWG within the sultone framework. At the same time, α‐aryl β‐enamino γ‐sultones possess significantly lower degree of conjugation (due to steric hindrance between aryl core and sultone framework) and therefore retain reactivity of the enamine fragment.
Mono‐Acetylenes as New Crosslinkers for All‐Carbon Living Charge Carbon Nanotubide Organogels
Authors: Bayazit Mustafa Kemal , Yau Hin Chun , Leese Hannah , Lee Won Jun , Shaffer Milo S. P.
Published: August 2022

Nanomaterials, such as single‐walled carbon nanotubes (SWCNTs) and graphenes, can be readily gelled using bi‐ or multi‐functional reagents as crosslinkers. This study reports a new reaction of monofunctional acetylenes with negatively charged SWCNTs (nanotubides), prepared by reduction. Mono‐acetylenes (e. g. phenylacetylene (PAc) and diphenyl acetylene (DiPAc)) are introduced as crosslinkers to form all‐carbon SWCNT organogels at room temperature. The resulting isolated SWCNT aerogels have a density of ∼4.5–5.5 mg cm−3. Raman spectroscopy and thermogravimetric analysis suggest a covalent surface modification (∼1 functional group per 110 (PAc) and 712 (DiPAc) SWCNT carbon atoms). Significantly, the acetylene reaction does not consume all available negative charges. The SWCNT organogel is still reactive after crosslinking and can reduce a stable gold complex, chloro(triphenylphosphine)gold (I), to form AuNPs (∼12–14 nm), suggesting the formation of a living nanotubide organogel intermediate, suitable for a range of secondary reactions. Mono‐acetylenes can crosslink other negatively charged molecular systems, and surface decoration of the aerogels with other metal NPs is anticipated.
Incentivizing STEM participation: Evidence from the SMART Grant Program
Authors: Blume‐Kohout Margaret E. , Scott Jacob P.
Published: August 2022

The U.S. National Science and Mathematics Access to Retain Talent (SMART) Grant program provided up to $8000 to high‐achieving, low‐income undergraduates majoring in STEM fields. We evaluate the effects of this financial incentive on college graduates' major fields and subsequent STEM workforce retention using nationally‐representative survey data and a difference‐in‐differences quasi‐experimental approach. The SMART Grant program significantly increased the probability that first‐generation college graduates majored in STEM, by about 7 percentage points. However, this increase is almost entirely offset by affected STEM graduates' significantly lower STEM workforce retention. These program effects also appear to be concentrated among students whose parents had some college experience rather than those who were first in their families to attend college.
A new species of early Cambrian arthropod reconstructed from exceptionally preserved mandibles and associated small carbonaceous fossils (SCFs)
Authors: Harvey Thomas H. P. , Butterfield Nicholas J.
Published: August 2022

Mandibulate arthropods (myriapods, hexapods and crustaceans) account for a major component of extant animal diversity but their origins remain unclear. Here, we re‐examine the record of exceptionally preserved arthropodan microfossils, including mandibles, from the lower Cambrian (Stage 4) Mount Clark Formation, Northwest Territories, Canada. The assemblage comes from a single drillcore horizon and occurs as thousands of small carbonaceous fossils (SCFs) representing disarticulated body parts. The mandibles occur as isolated molar surfaces with an elongate outline, a heavy setal fringe, and a subtle right–left asymmetry. These are sufficiently distinctive to diagnose a new genus and species of arthropod, Masticaris fimbriata. Co‐occurring SCFs include diverse appendage lobes and ventral body fragments, along with spines and setae assignable to 53 morphological categories and occurring either singly or in arrays, including filter plates. Most are plausibly interpreted as belonging to the feeding apparatus of M. fimbriata. The mandibles and filter plates correspond to those in extant pancrustaceans, particularly branchiopods, although the mouthparts of some more basal Cambrian arthropods raise the possibility of convergent feeding adaptations. Overall, anatomical and taphonomic continuity with younger SCFs suggests that M. fimbriata belongs to an early pancrustacean radiation that is still largely cryptic in the fossil record. More generally, the assemblage provides an inventory of fine‐scale cuticular specializations in early Cambrian arthropods that prefigure the trophic versatility and ecological dominance of crustaceans in the modern marine fauna.
Immunomodulation in age‐related disorders and nanotechnology interventions
Authors: Chintapula Uday , Chikate Tanmayee , Sahoo Deepsundar , Kieu Amie , Guerrero Rodriguez Ingrid D. , Nguyen Kytai T. , Trott Daniel
Published: August 2022

Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age‐related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few. Conventional treatment addresses the onset of age‐related diseases by early detection of risk factors, administration of vaccines as preventive care, immunomodulatory treatment, and other dietary supplements. However, these approaches often come with systemic side‐effects, low bioavailability of therapeutic agents, and poor outcomes seen in the elderly. Recent innovations in nanotechnology have led to the development of novel biomaterials/nanomaterials, which explore targeted drug delivery and immunomodulatory interactions in vivo. Current nanotechnology‐based immunomodulatory approaches that have the potential to be used as therapeutic interventions for some prominent age‐related diseases are discussed here. Finally, we explore challenges and future aspects of nanotechnology in the treatments of age‐related disorders to improve quality of life in the elderly.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Associated production of heavy Higgs bosons with a $$ \mathrm{b}\overline{\mathrm{b}} $$ pair in the nonholomorphic MSSM and LHC searches
Authors: Chattopadhyay Utpal , Datta AseshKrishna , Mukherjee Samadrita , Swain Abhaya Kumar
Published: August 2022

Abstract

In the NonHolomorphic Supersymmetric Standard Model (NHSSM), the Yukawa couplings of the bottom quark (yb) and the tau lepton (yτ) might receive substantial supersymmetric (SUSY) radiative corrections which have prominent dependencies on the NHSSM-specific trilinear soft parameters, $$ {A}_b^{\prime } $$

A
b
′

and $$ {A}_{\tau}^{\prime } $$

A
τ
′

, respectively, in addition to their well-known dependence on tan β as is already present in the Minimal SUSY Standard Model (MSSM). We study to what extent these could affect the production cross sections of the heavy Higgs bosons (H and A) in association with a pair of b-quarks and their decay branching ratios, in particular, to a $$ \tau \overline{\tau} $$
τ

τ
¯

pair and compare them with those obtained in the MSSM. Requiring compliance with the recently observed upper bounds on the product of their total cross section and the branching ratio to $$ \tau \overline{\tau} $$
τ

τ
¯

at the 13 TeV run of the Large Hadron Collider (LHC), with data worth 139 fb−1, results in an altered exclusion region in the customary mA− tan β plane in the framework of the NHSSM when compared to what is derived by the LHC experiments within an MSSM setup. Such alterations are estimated to be pronounced only for large tan β (≥ 40) and for large, negative $$ {A}_b^{\prime } $$

A
b
′

when one finds a reinforced exclusion of the mA − tan β plane with an excluded mA value larger by ≈ 200 GeV, compared to the MSSM case, at tan β = 60. On the other hand, the maximum relaxation in mA, for a similarly large but positive $$ {A}_b^{\prime } $$

A
b
′

, barely exceeds ≈ 100 GeV as a result of complementary variations in production cross sections and decay branching fractions of the heavy, neutral Higgs bosons.
Portraying double Higgs at the Large Hadron Collider II
Authors: Huang Li , Kang Su-beom , Kim Jeong Han , Kong Kyoungchul , Pi Jun Seung
Published: August 2022

Abstract

The Higgs potential is vital to understand the electroweak symmetry breaking mechanism, and probing the Higgs self-interaction is arguably one of the most important physics targets at current and upcoming collider experiments. In particular, the triple Higgs coupling may be accessible at the HL-LHC by combining results in multiple channels, which motivates to study all possible decay modes for the double Higgs production. In this paper, we revisit the double Higgs production at the HL-LHC in the final state with two b-tagged jets, two leptons and missing transverse momentum. We focus on the performance of various neural network architectures with different input features: low-level (four momenta), high-level (kinematic variables) and image-based. We find it possible to bring a modest increase in the signal sensitivity over existing results via careful optimization of machine learning algorithms making a full use of novel kinematic variables.
Polyakov model in ’t Hooft flux background: a quantum mechanical reduction with memory
Authors: Pazarbaşı Cihan , Ünsal Mithat
Published: August 2022

Abstract

We construct a compactification of Polyakov model on T2 × ℝ down to quantum mechanics which remembers non-perturbative aspects of field theory even at an arbitrarily small area. Standard compactification on small T2 × ℝ possesses a unique perturbative vacuum (zero magnetic flux state), separated parametrically from higher flux states, and the instanton effects do not survive in the Born-Oppenheimer approximation. By turning on a background magnetic GNO flux in co-weight lattice corresponding to a non-zero ’t Hooft flux, we show that N-degenerate vacua appear at small torus, and there are N − 1 types of flux changing instantons between them. We construct QM instantons starting with QFT instantons using the method of replicas. For example, SU(2) gauge theory with flux reduces to the double-well potential where each well is a fractional flux state. Despite the absence of a mixed anomaly, the vacuum structure of QFT and the one of QM are continuously connected. We also compare the quantum mechanical reduction of the Polyakov model with the deformed Yang-Mills, by coupling both theories to TQFTs. In particular, we compare the mass spectrum for dual photons and energy spectrum in the QM limit. We give a detailed description of critical points at infinity in the semi-classical expansion, and their role in resurgence structure.
Systems spatiotemporal dynamics of traumatic brain injury at single-cell resolution reveals humanin as a therapeutic target
Authors: Arneson Douglas , Zhang Guanglin , Ahn In Sook , Ying Zhe , Diamante Graciel , Cely Ingrid , Palafox-Sanchez Victoria , Gomez-Pinilla Fernando , Yang Xia
Published: August 2022

Background

The etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains.

Methods

We profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24-h) and subacute (7-day) phases of mTBI at single-cell resolution.

Results

We demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling implied astrocytes as a key regulator of the cell–cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, andmt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes.

Conclusions

Our results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.
Correction to: Designing a Winner–Loser Gap for WTA in Subthreshold. Resolution Performance Revisited
Authors: Marinov Corneliu A. , Costea Ruxandra L.
Published: August 2022

A Correction to this paper has been published: 10.1007/s00034-022-02100-9
Numerical tripping of high-speed turbulent boundary layers
Authors: Ceci Alessandro , Palumbo Andrea , Larsson Johan , Pirozzoli Sergio
Published: August 2022

The influence of turbulence inflow generation on direct numerical simulations (DNS) of high-speed turbulent boundary layers at Mach numbers of 2 and 5.84 is investigated. Two main classes of inflow conditions are considered, based on the recycling/rescaling (RR) and the digital filtering (DF) approach, along with suitably modified versions. A series of DNS using very long streamwise domains is first carried out to provide reliable data for the subsequent investigation. A set of diagnostic parameters is then selected to verify achievement of an equilibrium state, and correlation laws for those quantities are obtained based on benchmark cases. Simulations using shorter domains, with extent comparable with that used in the current literature, are then carried out and compared with the benchmark data. Significant deviations from equilibrium conditions are found, to a different extent for the various flow properties, and depending on the inflow turbulence seeding. We find that the RR method yields superior performance in the evaluation of the inner-scaled wall pressure fluctuations and the turbulent shear stress. DF methods instead yield quicker adjustment and better accuracy in the prediction of wall friction and of the streamwise Reynolds stress in supersonic cases. Unrealistically high values of the wall pressure variance are obtained by the baseline DF method, while the proposed DF alternatives recover a closer agreement with respect to the benchmark. The hypersonic test case highlights that similar distribution of wall friction and heat transfer are obtained by both RR and DF baseline methods.

Graphical abstract
A potent virucidal activity of functionalized TiO2 nanoparticles adsorbed with flavonoids against SARS-CoV-2
Authors: León-Gutiérrez Gabriela , Elste James Edward , Cabello-Gutiérrez Carlos , Millán-Pacheco Cesar , Martínez-Gómez Mario H. , Mejía-Alvarez Rafael , Tiwari Vaibhav , Mejía Armando
Published: August 2022

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism.

Key points/Highlights

• Unique TiO2nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity.

• The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro.

• Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

Graphical abstract
Impact of preoperative body mass index and weight loss on morbidity and mortality following colorectal cancer—a retrospective cohort study
Authors: Axt Steffen , Wilhelm Peter , Spahlinger Ricarda , Rolinger Jens , Johannink Jonas , Axt Lena , Kirschniak Andreas , Falch Claudius
Published: August 2022

Purpose

Body weight and preoperative weight loss (WL) are controversially discussed as risk factors for postoperative morbidity and mortality in colorectal cancer surgery. The objective of this study is to determine whether body mass index (BMI) or WL is associated with a higher postoperative complication rate.

Methods

In this retrospective cohort study, data analysis of 1241 consecutive patients undergoing colorectal cancer surgery in an 11-year period was performed. The main outcome measures were wound infections (WI), anastomotic leakages (AL), and in-house mortality.

Results

A total of 697 (56%) patients with colon and 544 (44%) with rectum carcinoma underwent surgery. The rate of WI for each location increased with rising BMI. The threshold value was 28.8 kg/m2. Obese patients developed significantly more WI than normal-weight patients did following rectal resection (18.0% vs. 8.2%, p = 0.018). Patients with preoperative WL developed significantly more AL following colon resections than did patients without preoperative WL (6.2% vs. 2.5%, p = 0.046). In-house mortality was significantly higher in obese patients following colon resections than in overweight patients (4.3% vs. 0.4%, p = 0.012). Regression analysis with reference to postoperative in-house mortality revealed neither increased BMI nor WL as an independent risk factor.

Conclusions

Increased preoperative BMI is associated with a higher WI rate. AL rate after colon resection was significantly higher in patients showing preoperative WL. Preoperative BMI and WL are therefore risk factors for postoperative morbidity in this study. Nevertheless, this has to be further clarified by means of prospective studies.

Trial registration DRKS00025359, 21.05.2021, retrospectively registered.