bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Effects on the Prostheses and Vertebrae of Three‐Level Hybrid Surgery: A Finite Element Study
Authors: Huang Kangkang , Wang Qian , Rong Xin , Wu Tingkui , Ding Chen , Meng Yang , Yin Wanhong , Liu Hao , Wang Beiyu
Published: June 2024

Purpose

Three‐level hybrid surgery (HS) consisting of cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) has been partly used for the treatment of multi‐level cervical degenerative disc disease (CDDD). The complications related to the implants and the collapse of the surgical vertebral bodies had been reported in multi‐level anterior cervical spine surgery. Thus, this study aimed to explore the biomechanical effects on the prostheses and vertebrae in three‐level HS.

Methods

A FE model of cervical spine (C0‐T1) was constructed. Five surgical models were developed. They were FAF model (ACDF‐CDA‐ACDF), AFA model (CDA‐ACDF‐CDA), FFF model (three‐level ACDF), SF model (single‐level ACDF), and SA model (single‐level CDA). A 75‐N follower load and 1.0‐N·m moment was applied to produce flexion, extension, lateral bending, and axial rotation.

Results

Compared with the intact model, the range of motion (ROM) of total cervical spine in FAF model decreased by 34.54%, 54.48%, 31.76%, and 27.14%, respectively, in flexion, extension, lateral bending, and axial rotation, which were lower than those in FFF model and higher than those in AFA model. The ROMs of CDA segments in FAF and AFA models were similar to the intact model and SA model. Compared with the intact model, the ROMs at C3/4 segment in FFF model increased from 5.71% to 7.85%, and increased from 5.31% to 6.81% at C7/T1 segment, following by FAF model, then the FAF model. The maximum interface pressures of the Prestige‐LP in FAF model were similar to SA model, however the corresponding values were increased in AFA model. The maximum interface pressures of the Zero‐P were increased in FAF and AFA model compared with those in SF and FFF models. The stress was mainly distributed on the screws. In AFA model, the maximum pressures of the ball and trough articulation in superior and inferior Prestige‐LP were all increased compared with those in SA and FAF model. In FFF model, the maximum pressures of the vertebrae were higher than those in other models. The stress was mainly distributed on the anterior area of the vertebral bodies.

Conclusions

HS seemed to be more suitable than ACDF for the surgical treatment of three‐level CDDD in consideration of the biomechanical effects, especially for the two‐level CDA and one‐level ACDF construct. But a more appropriate CDA prosthesis should be explored in the future.
Six‐year trend of subsequent allergic diseases following Kawasaki disease and its clinical implications: A population‐based matched cohort study of 34,712 patients
Authors: Kim Dongeon , Shin Ji Seong , Kim Sin Young , Kim Jihye
Published: June 2024

Background

It has been suggested that allergic diseases may increase after Kawasaki disease (KD). We aimed to analyze the temporal patterns of allergic disease incidence after KD.

Methods

A nationwide population‐based matched cohort study was conducted using data from the Korean National Health Insurance claims database. Patients aged <5 years diagnosed with KD and their 1:3 propensity score‐matched controls were included. Three cohorts were established: Cohort A, patients with allergies; Cohort B, patients without allergies; and Cohort C, patients without allergies, but excluding patients with birth history and underlying medical conditions. Cumulative incidence rates (%) and associated hospital visits for allergic rhinitis, atopic dermatitis, urticaria, and asthma were compared between the cases and controls during the 6‐year follow‐up period.

Results

The study population comprised 8678 patients diagnosed with KD and 26,034 controls. In Cohort A, although initially, there were intergroup differences in the number of hospital visits for certain allergic diseases, these differences were inconsistent and varied depending on the type of allergic disease. Over time, the differences narrowed, and by the sixth year, the gap had decreased significantly. In Cohorts B and C, the initial incidence rates of the four allergic diseases and associated hospital visits were lower in patients with KD as compared to controls. However, with a faster rate of increase, the incidence rates and number of hospital visits eventually surpassed those of the controls.

Conclusions

The pattern of delayed increase in cumulative incidence rates and hospital visits for allergic diseases after KD suggests the possibility of a shared genetic or immunologic susceptibility between KD and allergic diseases, which becomes evident over time, rather than a direct influence of KD resulting in allergic diseases.
NbPTR1 confers resistance against Pseudomonas syringae pv. actinidiae in kiwifruit
Authors: Yeh Shin‐Mei , Yoon Minsoo , Scott Sidney , Chatterjee Abhishek , Hemara Lauren M. , Chen Ronan K. Y. , Wang Tianchi , Templeton Kerry , Rikkerink Erik H. A. , Jayaraman Jay , Brendolise Cyril
Published: June 2024

Pseudomonas syringae pv. actinidiae biovar 3 (Psa3) causes a devastating canker disease in yellow‐fleshed kiwifruit (Actinidia chinensis). The effector HopZ5, which is present in all isolates of Psa3 causing global outbreaks of pandemic kiwifruit canker disease, triggers immunity in Nicotiana benthamiana and is not recognised in susceptible A. chinensis cultivars. In a search for N. benthamiana nonhost resistance genes against HopZ5, we found that the nucleotide‐binding leucine‐rich repeat receptor NbPTR1 recognised HopZ5. RPM1‐interacting protein 4 orthologues from N. benthamiana and A. chinensis formed a complex with NbPTR1 and HopZ5 activity was able to disrupt this interaction. No functional orthologues of NbPTR1 were found in A. chinensis. NbPTR1 transformed into Psa3‐susceptible A. chinensis var. chinensis ‘Hort16A’ plants introduced HopZ5‐specific resistance against Psa3. Altogether, this study suggested that expressing NbPTR1 in Psa3‐susceptible kiwifruit is a viable approach to acquiring resistance to Psa3 and it provides valuable information for engineering resistance in otherwise susceptible kiwifruit genotypes.
Epidermal nevi and epidermolytic hyperkeratosis: A review of cases, highlighting indications for biopsy and genetics referral
Authors: Nelson Jessie M. , Isaac Jacqueline M. , Mervak Julie E. , Mancuso Jennifer B. , Chan May P. , Arreola Amanda , Cha Kelly B.
Published: June 2024

Epidermal nevi are common benign cutaneous hamartomas that may rarely demonstrate histopathologic evidence of epidermolytic hyperkeratosis (EHK), representing cutaneous mosaicism for pathogenic keratin variants. Rarely, individuals with linear epidermal nevi transmit to their children the inherited form of EHK, also known as epidermolytic ichthyosis, characterized by generalized erythema, blistering, and scaling at birth evolving to widespread hyperkeratosis. We present an updated review of reported cases of linear epidermal nevi with EHK exhibiting transmission of epidermolytic ichthyosis to guide important considerations in the care of individuals with epidermal nevi. Clinical characteristics of linear epidermal nevi do not reliably predict the presence of EHK. All reported cases of transmission to offspring have occurred in individuals with linear epidermal nevi involving more than one anatomic area suggesting increased reproductive risk with involvement of two or more anatomic sites. Therefore, genetics consultation is recommended for these individuals with biopsy‐confirmed EHK. For individuals with smaller areas of epidermal nevus involvement, the implications are less well known, though genetics consultation may still be considered for those interested in further discussion of general reproductive risk.
Genome‐wide identification and characterization of SNW/SKIP domain‐containing proteins in plants
Authors: Silva S. A. , Bezerra V. B. F. , Teixeira F. C. , Roque E. M. S. , do Nascimento J. I. B. , Aguiar A. M. , de Carvalho H. H. , Alves M. S.
Published: June 2024

Sessile organisms, such as plants, developed various ways to sense and respond to external and internal stimuli to maximize their fitness through evolutionary time. Transcripts and protein regulation are, among many, the main mechanisms that plants use to respond to environmental changes. SKIP protein is one such, presenting an SNKW interacting domain, which is highly conserved among eukaryotes, where SKI interacting protein acts in regulating key processes.

In the present work, many bioinformatics tools, such as phylogenetic relationships, gene structure, physical–chemical properties, conserved motifs, prediction of regulatory cis‐elements, chromosomal localization, and protein–protein interaction network, were used to better understand the genome‐wide SNW/SKIP domain‐containing proteins.

In total, 28 proteins containing the SNW/SKIP domain were identified in different plant species, including plants of agronomic interest. Two main protein clusters were formed in phylogenetic analysis, and gene structure analysis revealed that, in general, the coding region had no introns. Also, expression of these genes is possibly induced by abiotic stress stimuli. Primary structure analysis of the proteins revealed the existence of an evolutionarily conserved functional unit. But physicochemical properties show that proteins containing the SNW/SKIP domain are commonly unstable under in vivo conditions.

In addition, the protein network, demonstrated that SKIP homologues could act by modulating plant fitness through gene expression regulation at the transcriptional and post‐transcriptional levels. This could be corroborated by the expression number of gene copies of SKIP proteins in many species, highlighting it's crucial role in plant development and tolerance through the course of evolution.
The efficacy and safety of autologous epidermal cell suspensions for re‐epithelialization of skin lesions: A systematic review and meta‐analysis of randomized trials
Authors: Lou Jiaqi , Xiang Ziyi , Fan Youfen , Song Jingyao , Huang Neng , Li Jiliang , Jin Guoying , Cui Shengyong
Published: June 2024

Background

Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This latest systematic review and meta‐analysis aim to examine the effects of autologous epidermal cell suspensions in re‐epithelialization of skin lesions.

Methods

Relevant articles were retrieved from PubMed, Embase, Cochrane Database, Web of Science, International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, VIP Database for Chinese Technical Periodicals and Wanfang database. The primary output measure was the healing time, and the secondary outputs were effective rate, size of donor site for treatment, size of study treatment area, operation time, pain scores, repigmentation, complications, scar scale scores and satisfaction scores. Data were pooled and expressed as relative risk (RR), mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval (CI).

Results

Thirty‐one studies were included in this systematic review and meta‐analysis, with 914 patients who received autologous epidermal cell suspensions (treatment group) and 883 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced healing time (SMD = −0.86; 95% CI: −1.59–0.14; p = 0.02, I2 = 95%), size of donar site for treatment (MD = −115.41; 95% CI: −128.74–102.09; p<0.001, I2 = 89%), operation time (MD = 25.35; 95% CI: 23.42–27.29; p<0.001, I2 = 100%), pain scores (SMD = −1.88; 95% CI: −2.86–0.90; p = 0.0002, I2 = 89%) and complications (RR = 0.59; 95% CI: 0.36–0.96; p = 0.03, I2 = 66%), as well as significantly increased effective rate (RR = 1.20; 95% CI: 1.01–1.42; p = 0.04, I2 = 77%). There were no significant differences in the size of study treatment area, repigmentation, scar scale scores and satisfaction scores between the two groups.

Conclusion

Our meta‐analysis showed that autologous epidermal cell suspensions is beneficial for re‐epithelialization of skin lesions as they significantly reduce the healing time, size of donar site for treatment, operation time, pain scores and complications, as well as increased effective rate. However, this intervention has minimal impact on size of treatment area, repigmentation, scar scale scores and satisfaction scores.
Film-Cooling Effectiveness on a Turbine Blade Platform With Various Hole Shapes and Layouts
Authors: Hu Jia-Jun , An Bai-Tao
Published: June 2024

This paper reports a film-cooling effectiveness experiment on a turbine blade platform that combines two film hole shapes with three layouts. A linear cascade using the pressure-sensitive paint (PSP) technique was employed to measure the adiabatic film effectiveness and discharge coefficients. Three film hole layouts, including two double-row layouts and one dispersed layout, were designed based on the platform configurations. One double-row layout arranges both rows of holes on the pressure side. Another double-row layout arranges one row on the pressure side and one row on the suction side. The dispersed layout was designed with streamwise multirows using the same number of holes. A fan-shaped hole and a diffusion slot hole were tested and compared. The experiments were conducted at a mainstream Reynolds number of 7 × 105, a mainstream turbulence intensity of 3.6%, and a coolant-to-mainstream density ratio of 1.5. The blowing ratio ranged from 0.5 to 2.5. The results demonstrated that regardless of the hole shape, the dispersed layout performed better than the two double-row layouts. However, the effects of the layout on the film effectiveness and discharge coefficients are smaller for the diffusion slot hole. In the three layouts, the film effectiveness of the diffusion slot holes is remarkably greater than that of the fan-shaped holes, and the superiority increases as the blowing ratio increases. In contrast, the superiority of the diffusion slot hole in double-row layouts surpasses that of a dispersed layout.
Exploring counterclockwise thermodynamic cycles
Authors: Knight Randall D.
Published: June 2024

A common belief is that any closed, counterclockwise cycle on a pV diagram represents a refrigerator or heat pump. It has been established that this is not the case, but previous papers on this topic have made unnecessary assumptions about the temperatures of the energy reservoirs and about how the system exchanges energy with the reservoirs. Relaxing these assumptions leads to a wide array of unexpected behaviors. In some cases, the same pV cycle can be a heat pump, a cold pump, or a Joule pump simply by changing how the system is connected to the reservoirs. This paper explores the strange world of counterclockwise cycles.
Spin coating experiments and theory for undergraduate physics and engineering students—A connection to microfabrication
Authors: Foster M. , Mendoza Cortes J. , Mayer H. C.
Published: June 2024

Spin coating is a process by which thin and uniform layers of liquids are formed on substrates by rotation of the substrate at high speed. Production of these thin liquid layers, specifically using liquids called photoresists, is essential for photolithography in semiconductor and microelectronics processing whereby patterns are transferred and ultimately formed in layers on the substrate. With the surge in interest for increased domestic semiconductor processing capabilities, it makes sense that students in physics and engineering are provided with more knowledge of these processing techniques and how they rely on, among other things, traditional course work, and topics. Spin coating provides an excellent example to connect fluid dynamics with microfabrication. We present detailed experiments that can be performed in a college-level undergraduate laboratory, wherein students can explore both the variables appearing in a known model for spin coating in addition to investigating several of the variables related key assumptions used in the derivation of the model but which do not appear in the resulting equation.
Free-field method for inverse characterization of finite porous acoustic materials using feed forward neural networks
Authors: Müller-Giebeler Mark , Berzborn Marco , Vorländer Michael
Published: June 2024

This paper presents a free-field method for inverse estimation of acoustic porous material parameters from sound pressure measurements above small rectangular samples. The finite sample effect, the spherical propagation of the sound field, and a potential lateral material reaction are considered. Using an extensive series of systematically varied finite element simulations, neural network models are developed to replace computationally expensive simulations as a forward model for the calculation of the complex sound pressure above small samples in the inverse optimization. The method is experimentally validated using various porous material samples. The results show that the influence of the finite sample size is successfully removed and thus, the acoustic properties of the materials can be estimated from the determined porous parameters with high accuracy, even based on a single sound pressure measurement over small samples with pronounced edge diffraction. The poroacoustic parameters hence derived can be used directly, e.g., in simulation applications, or to calculate complex surface impedances or absorption coefficients.
Exploring an Alternative to Record Motor Competence Assessment: Interrater and Intrarater Audio–Video Reliability
Authors: Menescardi Cristina , Carballo-Fazanes Aida , Ortega-Benavent Núria , Estevan Isaac
Published: June 2024

The Canadian Agility and Movement Skill Assessment (CAMSA) is a valid and reliable circuit-based test of motor competence which can be used to assess children’s skills in a live or recorded performance and then coded. We aimed to analyze the intrarater reliability of the CAMSA scores (total, time, and skill score) and time measured, by comparing the live audio with the video assessment method. We also aimed to assess the interrater reliability using both audio- and video coding on a sample of 177 Spanish children. We found moderate-to-excellent inter- and intrarater video–audio intraclass correlation coefficients for the CAMSA score, time measured, time score, and skill score. Nonsignificant differences were found between video and audio recordings in the CAMSA score, time measured, and time score. Our findings support the rationale that different raters and scoring methods can accurately assess the participants’ motor competence level using the CAMSA Spanish version.
Superstars Really Are Scarce: Shohei Ohtani and Baseball Attendance
Authors: Imbrogno Christopher T. , Mills Brian M.
Published: June 2024

We estimate the superstar effects in Major League Baseball, focusing on a particularly unique international athlete, Shohei Ohtani, using a fixed effects panel regression with multiway clustering. Ohtani’s scarce talent as both a pitcher and a hitter provides the potential to have outsized influence on demand at home (superstar effect) and away (superstar externality) games, providing new marketing opportunities for the league. We compare Ohtani’s impact on attendance with other top pitchers, particularly after large attendance drops attributed to the COVID-19 pandemic, suggesting that his superstardom played a key role in bringing fans back to baseball games. Results revealed a large attendance externality, especially after the pandemic, that increased away attendance by up to 40% in 2021 specifically (and up to 20% overall). We propose that Ohtani provides an opportunity for Major League Baseball to leverage a recognizable face of baseball and leverage superstar value that was previously shown to be in decline.
Spin torque–driven electron paramagnetic resonance of a single spin in a pentacene molecule
Authors: Kovarik Stepan , Schlitz Richard , Vishwakarma Aishwarya , Ruckert Dominic , Gambardella Pietro , Stepanow Sebastian
Published: June 2024

Control over quantum systems is typically achieved by time-dependent electric or magnetic fields. Alternatively, electronic spins can be controlled by spin-polarized currents. Here, we demonstrate coherent driving of a single spin by a radiofrequency spin-polarized current injected from the tip of a scanning tunneling microscope into an organic molecule. With the excitation of electron paramagnetic resonance, we established dynamic control of single spins by spin torque using a local electric current. In addition, our work highlights the dissipative action of the spin-transfer torque, in contrast to the nondissipative action of the magnetic field, which allows for the manipulation of individual spins based on controlled decoherence.
Ecological disturbance alters the adaptive benefits of social ties
Authors: Testard C. , Shergold C. , Acevedo-Ithier A. , Hart J. , Bernau A. , Negron-Del Valle J. E. , Phillips D. , Watowich M. M. , Sanguinetti-Scheck J. I. , Montague M. J. , Snyder-Mackler N. , Higham J. P. , Platt M. L. , Brent L. J. N.
Published: June 2024

Extreme weather events radically alter ecosystems. When ecological damage persists, selective pressures on individuals can change, leading to phenotypic adjustments. For group-living animals, social relationships may be a mechanism enabling adaptation to ecosystem disturbance. Yet whether such events alter selection on sociality and whether group-living animals can, as a result, adaptively change their social relationships remain untested. We leveraged 10 years of data collected on rhesus macaques before and after a category 4 hurricane caused persistent deforestation, exacerbating monkeys’ exposure to intense heat. In response, macaques demonstrated persistently increased tolerance and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival after the hurricane, but not before it, revealing a shift in the adaptive function of sociality.
Cryo–electron microscopy reveals hydrogen positions and water networks in photosystem II
Authors: Hussein Rana , Graça André , Forsman Jack , Aydin A. Orkun , Hall Michael , Gaetcke Julia , Chernev Petko , Wendler Petra , Dobbek Holger , Messinger Johannes , Zouni Athina , Schröder Wolfgang P.
Published: June 2024

Photosystem II starts the photosynthetic electron transport chain that converts solar energy into chemical energy and thus sustains life on Earth. It catalyzes two chemical reactions: water oxidation to molecular oxygen and plastoquinone reduction. Coupling of electron and proton transfer is crucial for efficiency; however, the molecular basis of these processes remains speculative owing to uncertain water binding sites and the lack of experimentally determined hydrogen positions. We thus collected high-resolution cryo–electron microscopy data of fully hydrated photosystem II from the thermophilic cyanobacterium
Thermosynechococcus vestitus
to a final resolution of 1.71 angstroms. The structure reveals several previously undetected partially occupied water binding sites and more than half of the hydrogen and proton positions. This clarifies the pathways of substrate water binding and plastoquinone B protonation.
In Other Journals
Authors: Uzogawa Ekeoma E. , Ray L. Bryan , Stern Peter , Grocholski Brent , Osborne Ian S. , Wible Brad , Maroso Mattia
Published: June 2024

Editors’ selections from the current scientific literature
Settlement over China funding puts institutions on notice
Authors: Mervis Jeffrey
Published: June 2024

Cleveland Clinic fined $7.6 million for alleged mismanagement of NIH grants
Ancient earthquake likely rerouted the Ganges
Authors: Kintisch Eli
Published: June 2024

Discovery of new seismic concern stokes flooding fear for densely populated delta region
Characterization of antimalarial activity of artemisinin-based hybrid drugs
Authors: Quadros Helenita Costa , Herrmann Lars , Manaranche Jeanne , Paloque Lucie , Borges-Silva Mariana C. , Dziwornu Godwin Akpeko , D'Alessandro Sarah , Chibale Kelly , Basilico Nicoletta , Benoit-Vical Françoise , Tsogoeva Svetlana B. , Moreira Diogo Rodrigo M.
Published: June 2024

In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive and drug-resistant
Plasmodium falciparum
parasites. Two hybrids were found to display parasite growth reduction, stage-specificity, speed of activity, additivity of activity in drug combinations, and stability in hepatic microsomes of similar levels to those displayed by dihydroartemisinin (DHA). Conversely, the rate of chemical homolysis of the peroxide bonds is slower in hybrids than in DHA. From a mechanistic perspective, heme plays a central role in the chemical homolysis of peroxide, inhibiting heme detoxification and disrupting parasite heme redox homeostasis. The hybrid exhibiting slow homolysis of peroxide bonds was more potent in reducing the viability of ART-resistant parasites in a ring-stage survival assay than the hybrid exhibiting fast homolysis. However, both hybrids showed limited activity against ART-induced quiescent parasites in the quiescent-stage survival assay. Our findings are consistent with previous results showing that slow homolysis of peroxide-containing drugs may retain activity against proliferating ART-resistant parasites. However, our data suggest that this property does not overcome the limited activity of peroxides in killing non-proliferating parasites in a quiescent state.
Pseudomonas aeruginosa
producing FIM-1-metallo-β-lactamase: emergence and cross-transmission in a long-term acute care rehabilitation hospital
Authors: Antonelli Alberto , Coppi Marco , Bonaiuto Chiara , Giovacchini Nicla , Grifoni Camilla , Vaggelli Guendalina , Pupillo Roberto , Vannetti Federica , Farese Alberto , Viaggi Bruno , Pollini Simona , Rossolini Gian Maria
Published: June 2024

FIM-1 metallo-β-lactamase was previously detected in sporadic
Pseudomonas aeruginosa
clinical isolates. Here, we report on FIM-1-positive
P. aeruginosa
from two patients who had shared the same ward in a long-term acute care rehabilitation hospital. Whole-genome sequencing analysis revealed close relatedness of these isolates, which belonged to an ST235 sublineage (clade 8/14) different from those previously reported. Results highlighted the occurrence of clonal diversity among FIM-positive strains and the possibility of their cross-transmission in some healthcare settings.
HIV-associated cancers and lymphoproliferative disorders caused by Kaposi sarcoma herpesvirus and Epstein-Barr virus
Authors: Lurain Kathryn A. , Ramaswami Ramya , Krug Laurie T. , Whitby Denise , Ziegelbauer Joseph M. , Wang Hao-Wei , Yarchoan Robert
Published: June 2024

Within weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS. KSHV was subsequently found to cause several other diseases associated with AIDS and human immunodeficiency virus (HIV) infection. People living with HIV/AIDS continue to have an increased incidence of certain cancers, and many of these cancers are caused by EBV and/or KSHV. In this review, we discuss the epidemiology, virology, pathogenesis, clinical manifestations, and treatment of cancers caused by EBV and KSHV in persons living with HIV.
The atypical antipsychotic aripiprazole alters the outcome of disseminated
Candida albicans
infections
Authors: Reitler Parker , Regan Jessica , DeJarnette Christian , Srivastava Ashish , Carnahan Jen , Tucker Katie M. , Meibohm Bernd , Peters Brian M. , Palmer Glen E.
Published: June 2024

Invasive fungal infections impose an enormous clinical, social, and economic burden on humankind. One of the most common species responsible for invasive fungal infections is
Candida albicans
. More than 30% of patients with disseminated candidiasis fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 medications that antagonize the activity of the azoles on
C. albicans
. Although gain-of-function mutations responsible for antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impacts
C. albicans
physiology, fitness, or virulence. In this study, we examined how exposure to seven azole antagonists affects
C. albicans
phenotype and capacity to cause disease. Most of the azole antagonists appear to have little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact on
C. albicans
hyphal growth and increased cell wall chitin content. It also aggravated the disseminated
C. albicans
infections in mice. This effect was abrogated in immunosuppressed mice, indicating that it is at least in part dependent upon host immune responses. Collectively, these data provide proof of principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.
A BSL-2 compliant mouse model of SARS-CoV-2 infection for efficient and convenient antiviral evaluation
Authors: Chen Zinuo , Cui Qinghua , Ran Yan , Achi Jazmin Galvan , Chen Zhaoyu , Rong Lijun , Du Ruikun
Published: June 2024

Animal models of authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require operation in biosafety level 3 (BSL-3) containment. In the present study, we established a mouse model employing a single-cycle infectious virus replicon particle (VRP) system of SARS-CoV-2 that can be safely handled in BSL-2 laboratories. The VRP [ΔS-VRP(G)-Luc] contains a SARS-CoV-2 genome in which the spike gene was replaced by a firefly luciferase (Fluc) reporter gene (Rep-Luci), and incorporates the vesicular stomatitis virus glycoprotein on the surface. Intranasal inoculation of ΔS-VRP(G)-Luc can successfully transduce the Rep-Luci genome into mouse lungs, initiating self-replication of Rep-Luci and, accordingly, inducing acute lung injury mimicking the authentic SARS-CoV-2 pathology. In addition, the reporter Fluc expression can be monitored using a bioluminescence imaging approach, allowing a rapid and convenient determination of viral replication in ΔS-VRP(G)-Luc-infected mouse lungs. Upon treatment with an approved anti-SARS-CoV-2 drug, VV116, the viral replication in infected mouse lungs was significantly reduced, suggesting that the animal model is feasible for antiviral evaluation. In summary, we have developed a BSL-2-compliant mouse model of SARS-CoV-2 infection, providing an advanced approach to study aspects of the viral pathogenesis, viral-host interactions, as well as the efficacy of antiviral therapeutics in the future.

IMPORTANCE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and pathogenic in humans; thus, research on authentic SARS-CoV-2 has been restricted to biosafety level 3 (BSL-3) laboratories. However, due to the scarcity of BSL-3 facilities and trained personnel, the participation of a broad scientific community in SARS-CoV-2 research had been greatly limited, hindering the advancement of our understanding on the basic virology as well as the urgently necessitated drug development. Previously, our colleagues Jin et al. had generated a SARS-CoV-2 replicon by replacing the essential spike gene in the viral genome with a Fluc reporter (Rep-Luci), which can be safely operated under BSL-2 conditions. By incorporating the Rep-Luci into viral replicon particles carrying vesicular stomatitis virus glycoprotein on their surface, and via intranasal inoculation, we successfully transduced the Rep-Luci into mouse lungs, developing a mouse model mimicking SARS-CoV-2 infection. Our model can serve as a useful platform for SARS-CoV-2 pathological studies and antiviral evaluation under BSL2 containment.
Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice
Authors: Gao Wang , Liu Xingyu , Zhang Shuobo , Wang Jingxia , Qiu Bo , Shao Junhua , Huang Weixin , Huang Yilun , Yao Mingfei , Tang Ling-Ling
Published: June 2024

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as
Enterococcus
and decreased that of
Lachnospiraceae
and
Muribaculaceae
. For moxifloxacin, the significantly high abundance of
Enterococcus
and
Klebsiella
was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1β, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.

IMPORTANCE

Antibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.
Exploring the economic toxicity experiences and coping styles of patients with colorectal cancer fistula in Jiangsu province, China: a qualitative study
Authors: Zhao Weijing , Xu Qin , Zhou Xia , Liu Chunmei , Ding Lingyu
Published: June 2024

Objectives

In recent years, economic toxicity has significantly affected the physical and mental health as well as the quality of life of patients with colorectal cancer. However, this issue has not garnered adequate attention from healthcare professionals. This study aims to investigate the experiences of economic toxicity and coping strategies among patients with colorectal cancer fistula. The findings are intended to inform the development of suitable and effective intervention programmes to address economic toxicity within this patient population.

Design

A descriptive phenomenological approach was employed in this qualitative research, using a semistructured method for data collection and analysis of interview data. Traditional content analysis methods were applied, encompassing coding, categorisation and theme distillation. Data analysis continued until thematic saturation was achieved, with no new themes emerging.

Setting

Nanjing Medical University Lianyungang Clinical Medical College.

Participants

A total of 21 patients with colorectal cancer fistula were selected as interview subjects through purposive sampling. The selection took place from May 2022 to May 2023, involving patients during their stay at a tertiary hospital in Lianyungang city, Jiangsu province, China.

Results

In total, three pieces and eight subthemes were distilled: subjective feelings (worries about treatment costs, concerns about uncertainty about the future, worries about daily life), coping styles (coping alone, unwillingness to help, prepurchased insurance, dealing with illness, giving up treatment, inability to afford costs) and needs and aspirations (need for health policies, need for social support).

Conclusions

Patients with colorectal cancer fistulae experience economic toxicity, leading to significant impairment in both physical and mental health. Despite employing various coping strategies, healthcare professionals must prioritise addressing the economic toxicity issue in patients. Implementing rational and effective interventions can greatly assist patients in effectively managing economic toxicity.
Cohort profile: the ‘Biomarkers of heterogeneity in type 1 diabetes’ study—a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands
Authors: Aanstoot Henk-Jan , Varkevisser Rita D M , Mul Dick , Dekker Pim , Birnie Erwin , Boesten Lianne S M , Brugts Michael P , van Dijk Peter R , Duijvestijn Petronella H L M , Dutta Sanjoy , Fransman Christine , Gonera Rob K , Hoogenberg Klaas , Kooy Adriaan , Latres Esther , Loves Sandra , Nefs Giesje , Sas Theo , Vollenbrock Charlotte E , Vosjan-Noeverman Marleen J , de Vries-Velraeds Martine M C , Veeze Henk J , Wolffenbuttel Bruce H R , van der Klauw Melanie M
Published: June 2024

Purpose

The ‘Biomarkers of heterogeneity in type 1 diabetes’ study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D).

Participants

Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected.

Findings to date

Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia.

Future plans

Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function.

Trial registration number

NCT04977635.
Defoliation level interacts with tree species and soil richness to determine volume increment reduction and recovery from simulated spruce budworm attack
Authors: MacLean David A. , Collier Joe , MacKinnon Wayne E. , Porter Kevin B.
Published: June 2024

Defoliation and tree species determine growth during spruce budworm outbreaks, with site showing inconsistent effects. We determined effects of artificial defoliation treatments (0%, 50%, 100%, 100%+bud) for 3 years on volume increment of 240 balsam fir, black spruce, and white spruce trees, initially 7–10 years old and 2.3–4.1 m tall, on four soil drainage/richness classes. Current annual increment was significantly affected by species × site and site × defoliation interactions, with DBH as covariate. Specific volume increment (SVI) was significantly affected by a species × site × defoliation treatment interaction. Combining species and sites, volume reductions after 3 years were 21%–28%, 43%–51%, and 55%–66% for 50% defoliation, 100% defoliation, and 100%+bud. SVI was negatively, linearly related to cumulative defoliation. Marginal r2 and conditional r2 showed that 64% of variance of SVI was explained by site, species, cumulative defoliation, and DBH, but 90% was explained by fixed and random variables. After 3 years of defoliation, SVI of white spruce was 21%–23% greater than balsam fir and black spruce, and SVI on rich was 55%–79% greater than on poor sites. Cumulative defoliation was a good predictor of growth, and soil richness had a stronger effect on growth after defoliation than in previous studies.
The acute effects of dietary nitrate supplementation on postmenopausal endothelial resistance to ischemia reperfusion injury: a randomized, placebo-controlled, double blind, crossover clinical trial
Authors: Delgado Spicuzza Jocelyn M. , Gosalia Jigar , Studinski Matthew , Armando Chenée , Alipour Elmira , Kim-Shapiro Daniel B. , Flanagan Michael , Somani Yasina B. , Proctor David N.
Published: June 2024

Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO3 −)–nitrite (NO2 −)–nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BRnitrate 600 mg NO3 −/140 mL, BRplacebo ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia–reperfusion (IR) injury to a greater extent in early-postmenopausal (1–6 years following their final menstrual period (FMP), n = 12) compared to late-postmenopausal (6+ years after FMP, n = 12) women. Analyses with general linear models revealed a significant ( p < 0.05) time*treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BRplacebo (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, p < 0.001) and was lower than post-IR with BRnitrate (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, p = 0.014). A single dose of BRnitrate significantly increased resting macrovascular function in the late postmenopausal group only ( p = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.
Ab initio description of monopole resonances in light- and medium-mass nuclei
Authors: Porro A. , Duguet T. , Ebran J.-P. , Frosini M. , Roth R. , Somà V.
Published: June 2024

Giant resonances (GRs) are a striking manifestation of collective motions in atomic nuclei. The present paper is the second in a series of four dedicated to the use of the projected generator coordinate method (PGCM) for the ab initio determination of the isoscalar giant monopole resonance (GMR) in closed- and open-shell mid-mass nuclei. While the first paper was dedicated to quantifying various uncertainty sources, the present paper focuses on the first applications to three doubly-open shell nuclei, namely $$^{46}\hbox {Ti}$$

46

Ti

, $$^{28}\hbox {Si}$$

28

Si

and $$^{24}\hbox {Mg}$$

24

Mg

. In particular, the goal is to investigate, starting from chiral effective field theory nuclear interactions, (i) the coupling of the GMR with the giant quadrupole resonance (GQR) in intrinsically-deformed nuclei, (ii) the possible impact of shape coexistence and shape mixing on the GMR, (iii) the GMR based on shape isomers and (iv) the impact of anharmonic effects on the monopole response. The latter is studied by comparing PGCM results to those obtained via the quasi-particle random phase approximation (QRPA), the traditional many-body approach to giant resonances, performed in a consistent setting. Eventually, PGCM results for sd-shell nuclei are in good agreement with experimental data, which is attributed to the capacity of the PGCM to capture the important fragmentation of the monopole response in light, intrinsically-deformed systems. Still, the comparison to data in $$^{28}\hbox {Si}$$

28

Si

and $$^{24}\hbox {Mg}$$

24

Mg

illustrates the challenge (and the potential benefit) of extracting unambiguous experimental information.
Rich Dynamics in a Hindmarsh–Rose Neuronal Model with Time Delay
Authors: Jiao Xubin , Liu Xiuxiang
Published: June 2024

This paper presents the stability and bifurcation of the Hindmarsh–Rose neuronal model with time delay. First, we discuss the existence and stability of the equilibria, revealing that the system can have a maximum of three equilibria which exhibit always stable, always unstable, and stability switching dynamics, depending on the stability of the equilibria when there is no time delay. Furthermore, an explicit formula for the time delay at which Hopf bifurcation occurs is derived, and the direction and stability of the Hopf bifurcation are also given. Finally, numerical simulations are carried out to support our theoretical results. We find that due to the existence of time delay, our system can exhibit many interesting dynamical behaviors depending on the number of equilibria and the increase in time delay. For instance, with increasing time delay, bistability transitions to the coexistence of a periodic solution and a stable equilibrium, followed by the emergence of quasi-periodic motion alongside stable equilibria, and eventually leading to chaotic motion coexisting with a stable equilibrium.
The Role of Vitamins in Spinal Cord Injury: Mechanisms and Benefits
Authors: Abbaszadeh Fatemeh , Javadpour Pegah , Mousavi Nasab Mohammad Mehdi , Jorjani Masoumeh
Published: June 2024

Spinal cord injury (SCI) is a common neurological disease worldwide, often resulting in a substantial decrease in quality of life, disability, and in severe cases, even death. Unfortunately, there is currently no effective treatment for this disease. Nevertheless, current basic and clinical evidence suggests that vitamins, with their antioxidant properties and biological functions, may play a valuable role in improving the quality of life for individuals with SCI. They can promote overall health and facilitate the healing process. In this review, we discuss the mechanisms and therapeutic potential of vitamins in the treatment of SCI.