bluuebunny/crossref_metadata_2025 huggingface dataset:
Troglomorphic adaptations on the northern European frontier: the phylogeny of the cave Pseudosinella (Hexapoda, Collembola) in the Western Carpathians
Authors: Kováč Ĺubomír , Žurovcová Martina , Raschmanová Natália , Jureková Nikola , Papáč Vladimír , Parimuchová Andrea
Published: June 2023

Introduction

Using an integrative taxonomic approach, we investigated the morphological and molecular characters to identify the species of the genus Pseudosinella occurring in caves of the Western Carpathians and to clarify their phylogenetic relationships. Based on morphological characters, we hypothesized that Pseudosinella aggtelekiensis (Stach, 1929) and Pseudosinella paclti (Rusek, 1961) originated from different phyletic lineages.

Methods

We used the barcoding fragment of the mtDNA COI gene from 87 individuals from 16 caves to reconstruct the phylogenetic history of the genus Pseudosinella.

Results

The molecular phylogenetic tree revealed two distinct species groups with allopatric distributions. The first group consisted of P. aggtelekiensis populations from the Slovak Karst and three undescribed species from fragmented and isolated karst areas in southeastern Slovakia. The second group, P. paclti populations in the Central Western Carpathians, was merged. This group included Pseudosinellamuranensis, a new species taxonomically described in this work. It is characterized by highly developed troglomorphic features and is restricted to a small karst area, the Muranska planina Plateau. The phylogeny of the genus Pseudosinella from the caves of the Western Carpathians revealed a Miocene diversification. According to molecular calibration, the two distinct Pseudosinella lineages were separated in the Middle Miocene, about 14.51 Mya, followed by further diversification in the P. paclti lineage 10.89 Mya and in the P. aggtelekiensis lineage 11.14 Mya.

Discussion

This phylogeny is consistent with the uplift of Triassic limestones during the early formation of the Western Carpathians in the Paratethys region and the initial development of caves during this period. The study provides further important evidence that the Western Carpathians played a significant role as an independent speciation center of the obligate cave fauna in Europe.
Double whammy: the genetic variants in CECR2 and high Hcy on the development of neural tube defects
Authors: Bai Baoling , Jiang Qian , Liu Lingyun , Liu Changyun , Zhang Qin
Published: June 2023

Introduction: Neural tube defects (NTDs) are serious congenital malformations. The etiology of NTDs involves both genetic and environmental factors. Loss of CECR2 in mice has been shown to result in NTDs. Our previous study indicated that high homocysteine (HHcy) levels could further reduced the expression level of CECR2. This investigation aims to explore the genetic influence of the chromatin remodeling gene, CECR2, in humans and determine if HHcy can have a synergistic effect on protein expression.

Methods: We conducted Next-Generation Sequencing (NGS) of the CECR2 gene in 373 NTD cases and 222 healthy controls, followed by functional assay application to select and evaluate CECR2 missense variants and subsequent Western blotting to identify protein expression levels.

Results: From the analysis, we identified nine rare, NTD-specific mutations within the CECR2 gene. Significantly, four missense variants (p.E327V, p.T521S, p.G701R, and p.G868R) were selected via functional screening. The E9.5 mouse ectodermal stem cell line NE-4C, transfected with plasmids expressing p.E327V, p.T521S, p.G868R variants or a recombinant harboring all four (named as 4Mut), exhibited notable reductions in CECR2 protein expression. Furthermore, exposure to homocysteine thiolactone (HTL), an extremely reactive homocysteine metabolite, amplified the reduction in CECR2 expression, accompanied by a significant increase in the apoptotic molecule Caspase3 activity, a potential NTD inducer. Importantly, folic acid (FA) supplementation effectively counteracted the CECR2 expression decline induced by CECR2 mutation and HTL treatment, leading to reduced apoptosis.

Discussion: Our observations underscore a synergistic relationship between HHcy and genetic variations in CECR2 concerning NTDs, thereby reinforcing the concept of gene-environment interaction phenomena in NTD etiology.
The H2-A Class II molecule α/β-chain cis-mismatch severely affects cell surface expression, selection of conventional CD4+ T cells and protection against TB infection
Authors: Logunova Nadezhda , Kapina Marina , Kondratieva Elena , Apt Alexander
Published: June 2023

Introduction

To dissect the role of the part of the H2 complex comprised of the MHC-II genes in the control of tuberculosis (TB) infection, we previously established a panel of recombinant congenic mouse strains bearing different segments of the H2j haplotype on the B6 (H2b) genetic background. Fine genetic mapping, gene sequencing and assessment of TB phenotypes resulted in identification of the H2-Ab gene as a major factor of TB control.

Methods

We further narrowed the MHC-II H2j interval by spotting a new recombination event, sequencing newly established DNA configuration and establishing a mouse strain B6.I-103 in which j/b recombination occurred within the coding sequence of the H2-Ab gene.

Results

Unexpectedly, a novel H2-Aαb/AβjE0 haplotype provided exclusively high susceptibility to TB challenge. Immunologic analysis revealed an altered CD4+ T-cell selection and maintenance in B6.I-103 mice, as well as seriously impaired expression of the H2-Aαb/Aβj molecule on the surface of antigen presenting cells. Unlike previously reported cases of Class II malfunctioning, the defective phenotype arose not from strong structural mutations, but from regular recombination events within the MHC-II recombination hot spot region.

Discussion

Our findings provide evidence that Class II α/β-chain cis-allelic mismatches created by regular genetic recombination may severely affect immune system functioning. This issue is discussed in the context of the MHC evolution.
B602L-Fc fusion protein enhances the immunogenicity of the B602L protein of the African swine fever virus
Authors: Yang Yang , Xia Qiqi , Zhou Lujia , Zhang Yan , Guan Zhixin , Zhang Junjie , Li Zongjie , Liu Ke , Li Beibei , Shao Donghua , Qiu Yafeng , Ma Zhiyong , Wei Jianchao
Published: June 2023

African swine fever (ASF) is an acute, highly contagious, and deadly infectious disease caused by the African swine fever virus (ASFV) and has a huge impact on the pig industry. A lack of vaccines and effective therapeutic drugs has brought great challenges to the prevention and control of ASF. In this study, insect baculovirus expression system was used to express ASFV B602L protein (B602L) alone and the IgG FC-fused B602L protein (B602L-Fc), and evaluate the immune effect of B602L-Fc in mice model. To be specific, the ASFV B602L protein and B602L-Fc fusion protein were successfully expressed by the insect baculovirus expression system. Then, Functional analysis in vitro revealed that the B602L-Fc fusion protein bound and interacted with the FcRI receptor of antigen-presenting cells and significantly promoted the expression of proteins involved in antigen presentation and various cytokines at mRNA levels in porcine alveolar macrophages. Additionally, immunization using B602L-Fc fusion protein remarkably promoted the Th1-biased cellular immune response and humoral immune response in mice. In conclusion, The B602L-Fc fusion protein could up-regulate the expression of molecules involved in antigen presentation in APCs and enhance the humoral and cellular immune responses in mice. These results suggest that ASFV B602L-Fc recombinant fusion protein may be a promising candidate for subunit vaccine. This study provided useful data for the development of subunit vaccines for ASF.
Nonlocality of scale-dependent eddy mixing at the Kuroshio Extension
Authors: Liu Mingyue , Chen Ru , Guan Wenting , Zhang Hong , Jing Tian
Published: June 2023

Although eddy parameterization schemes are often based on the local assumption, previous studies indicate that the nonlocality of total eddy mixing is prevalent at the Kuroshio Extension (KE). For eddy-permitting climate models, only mixing induced by eddies smaller than the resolvable scale of climate models (L*) needs to be parameterized. Therefore, here we aim to estimate and predict the nonlocality of scale-dependent eddy mixing at the KE region. We consider the separation scale L* ranging from 0.2∘ to 2.5∘, which is comparable to the typical resolution of the ocean component of climate models. Using a submesoscale-permitting model solution (MITgcm llc4320) and Lagrangian particles, we estimate the scale-dependent mixing (SDM) nonlocality ellipses and then diagnose the square root of the ellipse area (Ln,particle). Ln,particle is a metric to quantify the degree of SDM nonlocality. We found that, for all the available L* values we consider, the SDM nonlocality is prevalent in the KE region, and mostly elevated values of Ln,particle occur within the KE jet. As L* decreases from 2.5∘ to 0.2∘, the ratio Ln,particle/L* increases from 0.8 to 8.9. This result indicates that the SDM nonlocality is more non-negligible for smaller L*, which corresponds to climate models with relatively high resolution. As to the SDM nonlocality prediction, we found that compared to the conventional scaling and the curve-fitting methods, the random forest approach can better represent Ln,particle, especially in the coastal regions and within the intense KE jet. The area of the Eulerian momentum ellipses well capture the spatial pattern, but not the magnitude, of Ln,particle. Our efforts suggest that eddy parameterization schemes for eddy-permitting models may be improved by taking into account mixing nonlocality.
Mixed convection and thermal radiation effects on non-Newtonian nanofluid flow with peristalsis and Ohmic heating
Authors: Alrashdi Abdulwahed Muaybid A.
Published: June 2023

Introduction: This investigation explores the heat and mass transfer properties of a non-Newtonian nanofluid containing graphene nano-powder and ethylene glycol during peristalsis. The rheological characteristics of the nanofluid are determined using the Carreau-Yasuda model, and various factors such as viscous dissipation, Lorentz force, Ohmic heating, and Hall effects are taken into account. Mixed convection and thermal radiation effects are also considered in the analysis, and the problem is mathematically described using the long wavelength and low Reynolds number approximations.

Methods: The resulting nonlinear system is solved using numerical methods to obtain the solutions. The dominant effects of mixed convection and thermal radiation are given particular attention, while the influences of other parameters are discussed in relation to these dominant effects.

Results and Discussion: The results demonstrate that increasing the Brinkman number, heat source, and thermal slip parameter leads to higher nanofluid temperatures. However, the heat transfer rate decreases with a higher Hall parameter. The velocity near the center of the channel increases for higher values of the concentration Grashof and Hall parameters. Furthermore, an increase in the Hall and Brownian motion parameters results in a higher concentration of nanoparticles. These findings have practical implications in various fields, including materials science, chemical engineering, and biomedical engineering.
The impact of COVID-19 pandemic on hand hygiene compliance of healthcare workers in a tertiary hospital in East China
Authors: Zhang Xing , Ma Yonghui , Kong Li , Li Yusen , Wang Juan , Li Ning , Xia Yujie , Wang Peng , Zhang Min , Liu Lili , Zhang Dingding , Wen Luhan , Wang Shuangshuang , Liu Zhenghui , Yue Xia , Wang Jixia , Zhang Tong , Meng Xiujuan
Published: June 2023

Introduction

Hand hygiene is a cost-effective measure to reduce healthcare-associated infections (HAIs) in healthcare facilities. The impact of the coronavirus disease 2019 (COVID-19) pandemic on hand hygiene performance (HHP) provided evidence for targeted hand hygiene intervention measures.

Methods

This study evaluated the HHP rate in a tertiary hospital before and after the COVID-19 outbreak. HHP was checked by infection control doctors or nurses every day, and they inputted the HHP rate to the full-time infection control staff every week. A random examination of HHP was conducted by a confidential worker every month. The HHP of healthcare workers (HCWs) was monitored in the outpatient department, inpatient ward, and operating room from January 2017 to October 2022. The influence of COVID-19 prevention and control strategies on HHP was elucidated by analyzing the results of HHP during the study period.

Results

The average HHP rate of HCWs was 86.11% from January 2017 to October 2022. The HHP rate of HCWs after the COVID-19 pandemic was statistically significantly higher than that before the pandemic (P < 0.001). The HHP rate was the highest (93.01%) in September 2022 when the local epidemic occurred. Among the different occupation categories, medical technicians showed the highest HHP rate (89.10%). The HHP rate was the highest after contact with body fluids or blood of patients (94.47%).

Conclusion

The HHP rate of HCWs in our hospital showed an increasing trend in the recent 6 years, especially during the COVID-19 pandemic, and the increase was most obvious during the local epidemic.
Acute mesenteric ischemia following lancehead snakebite: an unusual case report in the Northernmost Brazilian Amazon
Authors: Galan Luis E. B. , Silva Vitória Souza , Silva Vitória Santos , Monte Rommel C. , Jati Sewbert R. , Oliveira Isadora S. , Cerni Felipe A. , Monteiro Wuelton M. , Sachett Jacqueline , Dantas Domingos S. M. , Carbonell Roberto C. C. , Pucca Manuela B.
Published: June 2023

Snakebites have a great impact in the Brazilian Amazon, being the lancehead Bothrops atrox the species responsible for most accidents, disabilities, and deaths. This study shows a case report of an indigenous patient from the Yanomami ethnicity, male, 33 years-old, envenomed by a B. atrox snake. Envenoming caused by B. atrox are characterized by local manifestations (e.g., pain and edema) and systemic manifestations, mainly coagulation disorders. The indigenous victim was admitted in the main hospital of Roraima and evolved with an unusual complication, an ischemia and necrosis of the proximal ileum, requiring segmental enterectomy with posterior side-to-side anastomosis. The victim was discharge after 27 days of hospitalization with no complaints. Snakebite envenomations may evolve with life-threatening complications, which can be treated by the antivenom following access to a healthcare unit, often late in indigenous population. This clinical case shows the need of strategies that aim improvement in the access to the healthcare by indigenous people, as well as demonstrates an unusual complication that may result from lancehead snakebites. The article also discusses the decentralization of snakebites clinical management to indigenous community healthcare centers to mitigate complications.
Leprosy among children in an area without primary health care coverage in Caratateua Island, Brazilian Amazon
Authors: Costa Izabelle Laissa Viana , da Costa Patrícia Fagundes , da Silva Sâmela Miranda , Gobbo Angélica Rita , Pinto Pablo Diego do Carmo , Spencer John Stewart , da Silva Moises Batista , Salgado Claudio Guedes
Published: June 2023

Introduction

The detection of leprosy in children is an important epidemiological marker of the disease, indicating the community’s early exposure to Mycobacterium leprae and active transmission of the infection.

Methods

In order to detect new cases among children by combining clinical evaluation and laboratory tests, we conducted an active case finding among individuals under 15 years old on Caratateua Island, located in the city of Belém, in the Pará state, an endemic region in the Amazon. Dermato-neurological examination, collection of 5 mL of peripheral blood for IgM anti-PGL-I antibody titration, and intradermal scraping for bacilloscopy and amplification of the specific RLEP region by qPCR were performed.

Results

Out of the 56 examined children, 28/56 (50%) new cases were identified. At the time of evaluation, 38/56 (67.8%) children presented one or more clinical alterations. Seropositivity was detected in 7/27 (25.9%) new cases and 5/24 (20.8%) undiagnosed children. DNA amplification of Mycobacterium leprae was observed in 23/28 (82.1%) of new cases and in 5/26 (19.2%) of non-cases. Out of the total cases, 11/28 (39.2%) were exclusively diagnosed by clinical evaluation performed during the active case finding. Seventeen new cases (60.8%) were detected considering the clinical alterations found in addition to positive results for qPCR. In this group, 3/17 (17.6%) qPCR-positive children presented significant clinical changes 5.5 months after the first evaluation.

Discussion

Our research detected a number of cases 5.6 times higher compared to the total number of pediatric cases recorded throughout the year 2021 in the municipality of Belém, which shows a critical scenario of underdiagnosing of leprosy among children under 15 years old in the region. We propose the use of qPCR technique to identify new cases among children with oligosymptomatic or early disease in endemic areas, in addition to the training of Primary Health Care professionals and the implementation of the Family Health Strategy coverage in the visited area.
Quorum sensing gene regulation in Staphylococcus epidermidis reduces the attraction of Aedes aegypti (L.) (Diptera: Culicidae)
Authors: Kim Dongmin , Crippen Tawni L. , Jordan Heather R. , Tomberlin Jeffery K.
Published: June 2023

Introduction

Identifying mechanisms regulating mosquito attraction to hosts is key to suppressing pathogen transmission. Historically, the ecology of the host microbial community and its influence on mosquito attraction, specifically, whether bacterial communication through quorum sensing (QS) modulates VOC production that affects mosquito behavior have not been extensively considered.

Methods

Behavioral choice assays were applied along with volatile collection, followed by GC-MS and RNA transcriptome analyses of bacteria with and without a quorum-sensing inhibitor, furanone C-30.

Results

Utilizing the quorum-sensing inhibitor on a skin-inhabiting bacterium,Staphylococcus epidermidis, we disrupted its interkingdom communication with adultAedes aegyptiand mitigated their attraction to a blood-meal by 55.1%.

Discussion

One potential mechanism suppressing mosquito attraction could be the reduction (31.6% in our study) of bacterial volatiles and their associated concentrations by shiftingS. epidermidismetabolic (12 of 29 up regulated genes) and stress (5 of 36 down regulated genes) responses. Manipulating the quorum-sensing pathways could serve as a mechanism to reduce mosquito attraction to a host. Such manipulations could be developed into novel control methods for pathogen-transmitting mosquitoes and other arthropods.
Dirofilariasis mouse models for heartworm preclinical research
Authors: Marriott A. E. , Dagley J. L. , Hegde S. , Steven A. , Fricks C. , DiCosty U. , Mansour A. , Campbell E. J. , Wilson C. M. , Gusovsky F. , Ward S. A. , Hong W. D. , O'Neill P. , Moorhead A. , McCall S. , McCall J. W. , Taylor M. J. , Turner J. D.
Published: June 2023

Introduction

Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research.

Methods

As a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis.

Results

Non-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc−/− (NSG and NXG) and recombination-activating gene (RAG)2−/−γc−/− mouse strains yielded viable D. immitis larvae at 2–4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%−90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%−88% reduction in L4 larvae at 14–28 days.

Discussion

Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.
Intranasally administered extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells quickly incorporate into neurons and microglia in 5xFAD mice
Authors: Attaluri Sahithi , Jaimes Gonzalez Jenny , Kirmani Maha , Vogel Andrew D. , Upadhya Raghavendra , Kodali Maheedhar , Madhu Leelavathi N. , Rao Shama , Shuai Bing , Babu Roshni S. , Huard Charles , Shetty Ashok K.
Published: June 2023

Introduction

Extracellular vesicles (EVs) released by human-induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs) have robust antiinflammatory and neurogenic properties due to therapeutic miRNAs and proteins in their cargo. Hence, hiPSC-NSC-EVs are potentially an excellent biologic for treating neurodegenerative disorders, including Alzheimer’s disease (AD).

Methods

This study investigated whether intranasally (IN) administered hiPSC-NSC-EVs would quickly target various neural cell types in the forebrain, midbrain, and hindbrain regions of 3-month-old 5xFAD mice, a model of β-amyloidosis and familial AD. We administered a single dose of 25 × 109 hiPSC-NSC-EVs labeled with PKH26, and different cohorts of naïve and 5xFAD mice receiving EVs were euthanized at 45 min or 6 h post-administration.

Results

At 45 min post-administration, EVs were found in virtually all subregions of the forebrain, midbrain, and hindbrain of naïve and 5xFAD mice, with predominant targeting and internalization into neurons, interneurons, and microglia, including plaque-associated microglia in 5xFAD mice. EVs also came in contact with the plasma membranes of astrocytic processes and the soma of oligodendrocytes in white matter regions. Evaluation of CD63/CD81 expression with the neuronal marker confirmed that PKH26 + particles found within neurons were IN administered hiPSC-NSC-EVs. At 6 h post-administration, EVs persisted in all cell types in both groups, with the distribution mostly matching what was observed at 45 min post-administration. Area fraction (AF) analysis revealed that, in both naïve and 5xFAD mice, higher fractions of EVs incorporate into forebrain regions at both time points. However, at 45 min post-IN administration, AFs of EVs within cell layers in forebrain regions and within microglia in midbrain and hindbrain regions were lower in 5xFAD mice than naïve mice, implying that amyloidosis reduces EV penetrance.

Discussion

Collectively, the results provide novel evidence that IN administration of therapeutic hiPSC-NSC-EVs is an efficient avenue for directing such EVs into neurons and glia in all brain regions in the early stage of amyloidosis. As pathological changes in AD are observed in multiple brain areas, the ability to deliver therapeutic EVs into various neural cells in virtually every brain region in the early stage of amyloidosis is attractive for promoting neuroprotective and antiinflammatory effects.
Water drinking during aerobic exercise improves the recovery of non-linear heart rate dynamics in coronary artery disease: crossover clinical trial
Authors: Laurino Maria Júlia Lopez , Silva Anne Kastelianne França da , Santos Lorena Altafin , Vanderlei Luiz Carlos Marques
Published: June 2023

Introduction

The post-exercise recovery is a period of vulnerability of the cardiovascular system in which autonomic nervous system plays a key role in cardiovascular deceleration. It is already known that individuals with coronary artery disease (CAD) are at greater risk due to delayed vagal reactivation in this period. Water ingestion has been studied as a strategy to improve autonomic recovery and mitigate the risks during recovery. However, the results are preliminary and need further confirmation. Therefore, our aim was to investigate the influence of individualized water drinking on the non-linear dynamics of heart rate during and after aerobic exercise in CAD subjects.

Methods

30 males with CAD were submitted to a control protocol composed of initial rest, warming up, treadmill exercise, and passive recovery (60 min). After 48 hours they performed the hydration protocol, composed of the same activities, however, with individualized water drinking proportional to the body mass lost in the control protocol. The non-linear dynamics of heart rate were assessed by indices of heart rate variability extracted from the recurrence plot, detrended fluctuation analysis, and symbolic analysis.

Results and discussion

During exercise, the responses were physiological and similar in both protocols, indicating high sympathetic activity and reduced complexity. During recovery, the responses were also physiological, indicating the rise of parasympathetic activity and the return to a more complex state. However, during hydration protocol, the return to a more complex physiologic state occurred sooner and non-linear HRV indices returned to resting values between the 5th and 20th minutes of recovery. In contrast, during the control protocol, only a few indices returned to resting values within 60 minutes. Despite that, differences between protocols were not found. We conclude that the water drinking strategy accelerated the recovery of non-linear dynamics of heart rate in CAD subjects but did not influence responses during exercise. This is the first study to characterize the non-linear responses during and after exercise in CAD subjects.
Role of vitamin C and SVCT2 in neurogenesis
Authors: Salazar Katterine , Jara Nery , Ramírez Eder , de Lima Isabelle , Smith-Ghigliotto Javiera , Muñoz Valentina , Ferrada Luciano , Nualart Francisco
Published: June 2023

Different studies have established the fundamental role of vitamin C in proliferation, differentiation, and neurogenesis in embryonic and adult brains, as well as in in vitro cell models. To fulfill these functions, the cells of the nervous system regulate the expression and sorting of sodium-dependent vitamin C transporter 2 (SVCT2), as well as the recycling of vitamin C between ascorbic acid (AA) and dehydroascorbic acid (DHA) via a bystander effect. SVCT2 is a transporter preferentially expressed in neurons and in neural precursor cells. In developmental stages, it is concentrated in the apical region of the radial glia, and in adult life, it is expressed preferentially in motor neurons of the cerebral cortex, starting on postnatal day 1. In neurogenic niches, SVCT2 is preferentially expressed in precursors with intermediate proliferation, where a scorbutic condition reduces neuronal differentiation. Vitamin C is a potent epigenetic regulator in stem cells; thus, it can induce the demethylation of DNA and histone H3K27m3 in the promoter region of genes involved in neurogenesis and differentiation, an effect mediated by Tet1 and Jmjd3 demethylases, respectively. In parallel, it has been shown that vitamin C induces the expression of stem cell-specific microRNA, including the Dlk1–Dio3 imprinting region and miR-143, which promotes stem cell self-renewal and suppresses de novo expression of the methyltransferase gene Dnmt3a. The epigenetic action of vitamin C has also been evaluated during gene reprogramming of human fibroblasts to induced pluripotent cells, where it has been shown that vitamin C substantially improves the efficiency and quality of reprogrammed cells. Thus, for a proper effect of vitamin C on neurogenesis and differentiation, its function as an enzymatic cofactor, modulator of gene expression and antioxidant is essential, as is proper recycling from DHA to AA by various supporting cells in the CNS.
Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies
Authors: Angotzi Francesco , Petrella Marco , Berno Tamara , Binotto Gianni , Bonetto Giorgia , Branca Antonio , Carraro Marco , Cavaretta Chiara Adele , Cellini Alessandro , D’Amore Fabio , Forlani Laura , Gianesello Ilaria , Gurrieri Carmela , Imbergamo Silvia , Lessi Federica , Maroccia Antonio , Mazzetto Federica , Pavan Laura , Pezone Sara , Piazza Francesco , Pravato Stefano , Ruocco Valeria , Scapinello Greta , Vianello Fabrizio , Zambello Renato , Zatta Ivan , Zoletto Simone , Padoan Andrea , Trentin Livio , Visentin Andrea
Published: June 2023

The approved combination of Tixagevimab/Cilgavimab has been shown to decrease the rate of symptomatic SARS-CoV-2 infection in patients at increased risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematological malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. We performed a real-life prospective cohort study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab in anti-spike seronegative patients compared to a cohort of seropositive patients who were observed or received a fourth vaccine dose. We recruited 103 patients with a mean age of 67 years: 35 (34%) received Tixagevimab/Cilgavimab and were followed from March 17, 2022, until November 15, 2022. After a median follow-up of 4.24 months, the 3-month cumulative incidence of infection was 20% versus 12% in the Tixagevimab/Cilgavimab and observation/vaccine groups respectively (HR 1.57; 95% CI: 0.65-3.56; p = 0.34). In this study, we report our experience with Tixagevimab/Cilgavimab and a tailored approach to SARS-CoV-2 infection prevention in patients with hematological malignancies during the SARS-CoV-2 omicron surge.
Retention of older veterans with serious mental illness in a clinical exercise program
Authors: Browne Julia , Elbogen Eric B. , Mueser Kim T. , Rudolph James L. , Wu Wen Chih , Philip Noah S. , Mills Whitney L. , Young Alexander S. , Sloane Richard , Hall Katherine S.
Published: June 2023

Older adults with serious mental illness (SMI) have compromised physical function that could be improved with exercise; however, retention in exercise programs is a challenge. This study was a retrospective analysis of retention for the 150 older veterans with SMI that enrolled in Gerofit, a clinical exercise program offered in the Veterans Health Administration. Chi-square and t-tests were conducted to evaluate baseline differences between those that were and were not retained at six and 12 months. Retention was 33% and better health-related quality of life and endurance were related to retention. Future work is needed to improve exercise program retention in this population.
Effectiveness of sleep interventions for rotating night shift workers: a systematic review and meta-analysis
Authors: Jeon Bo Min , Kim Su Hyun , Shin Seung Hwa
Published: June 2023

Background

Sleep disturbance is a common issue among rotating night shift workers and is closely related to health risks. The present study aimed to determine the effectiveness of pharmacological and non-pharmacological sleep interventions for the management of sleep disturbance among rotating night shift workers.

Methods

For this systematic review and meta-analysis, we searched six electronic databases—EMBASE, CINAHL, Cochrane Library, PubMed, Scopus, and Web of Science—for randomized controlled trials and clinical trials published from January 1990 to June 2022. The quality of eligible studies was independently assessed by three authors using the Joanna Briggs Institute Critical Appraisal Checklist for randomized controlled trials and quasi-experimental studies. The meta-analysis was performed based on the random effects model using the Comprehensive Meta-Analysis software. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Of the 1019 studies retrieved, 30 met the inclusion criteria for the systematic review; 25 were selected for the meta-analysis. Sleep interventions were categorized as follows: pharmacological approach (n = 7), light therapy (n = 9), cognitive behavioral approach (n = 7), aroma or alternative therapy (n = 4), and shift schedule modification (n = 3). The overall mean effect size of the interventions was moderate (Hedges' g = 0.59; 95% confidence interval = 0.33–0.84, z = 4.50, p < 0.001).

Conclusion

Sleep interventions were effective in promoting sleep or reducing sleep disturbance among rotating night shift workers. These findings provide evidence of the effectiveness of various pharmacological and non-pharmacological sleep interventions for managing sleep health in the work environment of rotating night shift workers.
Natural experiments for the evaluation of place-based public health interventions: a methodology scoping review
Authors: Albers Patricia N. , Rinaldi Chiara , Brown Heather , Mason Kate E. , d'Apice Katrina , McGill Elizabeth , McQuire Cheryl , Craig Peter , Laverty Anthony A. , Beeson Morgan , Campbell Mhairi , Egan Matt , Gibson Marcia , Fuller Maxwell , Dillon Amy , Taylor-Robinson David , Jago Russell , Tilling Kate , Barr Benjamin , Sniehotta Falko F. , Hickman Matthew , Millett Christopher J. , de Vocht Frank
Published: June 2023

Introduction

Place-based public health evaluations are increasingly making use of natural experiments. This scoping review aimed to provide an overview of the design and use of natural experiment evaluations (NEEs), and an assessment of the plausibility of the as-if randomization assumption.

Methods

A systematic search of three bibliographic databases (Pubmed, Web of Science and Ovid-Medline) was conducted in January 2020 to capture publications that reported a natural experiment of a place-based public health intervention or outcome. For each, study design elements were extracted. An additional evaluation of as-if randomization was conducted by 12 of this paper's authors who evaluated the same set of 20 randomly selected studies and assessed ‘as-if ' randomization for each.

Results

366 NEE studies of place-based public health interventions were identified. The most commonly used NEE approach was a Difference-in-Differences study design (25%), followed by before-after studies (23%) and regression analysis studies. 42% of NEEs had likely or probable as-if randomization of exposure (the intervention), while for 25% this was implausible. An inter-rater agreement exercise indicated poor reliability of as-if randomization assignment. Only about half of NEEs reported some form of sensitivity or falsification analysis to support inferences.

Conclusion

NEEs are conducted using many different designs and statistical methods and encompass various definitions of a natural experiment, while it is questionable whether all evaluations reported as natural experiments should be considered as such. The likelihood of as-if randomization should be specifically reported, and primary analyses should be supported by sensitivity analyses and/or falsification tests. Transparent reporting of NEE designs and evaluation methods will contribute to the optimum use of place-based NEEs.
Localization supervision of chest x-ray classifiers using label-specific eye-tracking annotation
Authors: Bigolin Lanfredi Ricardo , Schroeder Joyce D. , Tasdizen Tolga
Published: June 2023

Convolutional neural networks (CNNs) have been successfully applied to chest x-ray (CXR) images. Moreover, annotated bounding boxes have been shown to improve the interpretability of a CNN in terms of localizing abnormalities. However, only a few relatively small CXR datasets containing bounding boxes are available, and collecting them is very costly. Opportunely, eye-tracking (ET) data can be collected during the clinical workflow of a radiologist. We use ET data recorded from radiologists while dictating CXR reports to train CNNs. We extract snippets from the ET data by associating them with the dictation of keywords and use them to supervise the localization of specific abnormalities. We show that this method can improve a model’s interpretability without impacting its image-level classification.
Postgraduate design education and sustainability—An investigation into the current state of higher education and the challenges of educating for sustainability
Authors: Delaney Emelia , Liu Wei
Published: June 2023

Introduction

Sustainability has remained an important issue within academia and industry, with more recent focus on sustainability education to ensure that future generations are equipped with the knowledge to continue and champion sustainable outcomes. The design and innovation industry has been continuously identified as important by academia, for having high impact on the potential sustainability of products and services during their development. However, little research focuses on the pre-professional education of designers and whether they receive an appropriate education on sustainable issues in relation to their industry.

Methods

This study investigated these issues within the context of United Kingdom-based postgraduate design courses, to determine the current state of sustainability education as well as the impact of government resources and policies on encouraging sustainability education. Courses were identified utilizing online databases and were evaluated using Sterling's model “Levels of Response to Sustainability Education” to understand the current approach to sustainability within design education, including content and pedagogy, offering recommendations for improvement.

Results

Courses were evaluated against Sterling's model “Levels of Response to Sustainability Education”, which enabled the understanding of the current state of higher education and sustainability education with Postgraduate design courses in the UK. Following this review, a model for upgrading sustainability education is proposed.

Discussion

Around 80% of the courses identified throughout this study were ranked as “weak” or “very weak” according to Sterling's model, the proposed model highlights several strategies to aid postgraduate design courses to progress to the “strong” level. The framework model focuses on various sustainability themes to be included within postgraduate design education, teaching methods, as well as the inclusion of a dedicated student reflection period to improve and adapt the sustainability teaching.
Including citizens through co-design in a participatory research project to explore innovative agro-food systems: the case of future dairy livestock systems
Authors: Coeugnet Philippine , Labatut Julie , Duval Julie , Vourc'h Gwenaël
Published: June 2023

Introduction

Livestock farming and its negative impacts are increasingly criticized by society; its evolution toward more sustainable systems is therefore a key aspect of the transition of agro-food systems. It is necessary to rethink livestock systems' research and innovation processes and develop innovative solutions. Including citizens, non-professionals of the sector, who are less influenced by the current organization of the agricultural sector could be an opportunity to generate innovative solutions, but they have been kept away from research and innovation processes so far.

Methods

In this context, we implemented a co-design process involving researchers, livestock professionals, and citizens in a participatory research project aiming at producing knowledge and developing innovative solutions for the future mountain dairy systems. For this, we have adapted the KCP design method known to promote the exploration of innovative solutions, support the agro-ecological transition, and build a common horizon.

Results

The analysis of this collective dynamic and its outputs allowed us to highlight the positive contribution of citizens during the design process, even if they are not livestock experts. The citizens participated in the formulation of new knowledge by questioning the researchers and livestock professionals and were less influenced by the current system. This contributed to the exploration of original and varied solutions for livestock farming systems.

Discussion

This experimentation offers perspectives for including citizens in agro-food systems research and innovation process. It also opens up interesting perspectives for the fields of citizen science and co-design research.
Ocular surface complications following biological therapy for cancer
Authors: Ma Kevin Sheng-Kai , Tsai Ping-Feng , Hsieh Tina Yi-Jin , Chodosh James
Published: June 2023

Novel and highly effective biological agents developed to treat cancer over the past two decades have also been linked to multiple adverse outcomes, including unanticipated consequences for the cornea. This review provides an overview of adverse corneal complications of biological agents currently in use for the treatment of cancer. Epidermal growth factor receptor inhibitors and immune checkpoint inhibitors are the two classes of biological agents most frequently associated with corneal adverse events. Dry eye, Stevens-Johnson syndrome, and corneal transplant rejection have all been reported following the use of immune checkpoint inhibitors. The management of these adverse events requires close collaboration between ophthalmologists, dermatologists, and oncologists. This review focuses in depth on the epidemiology, pathophysiology, and management of ocular surface complications of biological therapies against cancer.
An Acoustoelectric Approach to Neuron Function
Authors: Kotthaus Jörg P.
Published: June 2023

An acoustoelectric approach to neuron function is proposed that combines aspects of the widely accepted electrical-circuit-based Hodgkin–Huxley model for the generation and propagation of action potentials via electric polarization with mechanical models based on propagation via capillary waves. Explaining measured velocities of action potentials quantitatively, it also predicts the electrical tunability of highly anisotropic polarization packages that surf on the dynamic mechanical force field deforming the neuron membrane. It relies substantially on the local motion of dipoles formed by excess charges close to the inside surface of the neuron membrane, which in turn are anisotropically screened by water molecules in their hydration shell, thus modulating the strong electric field at the interface. As demonstrated on acoustic resonators of suspended nanowires fabricated out of amorphous dipolar silicon nitride, high electric fields combined with predominantly axial-strain modulation can cause transverse acoustoelectric polarization waves that propagate soliton-like with extremely low loss. In neurons, the modulation of electric polarization is confined in the nanometer-thin skin of a high electric field inside the neuron membrane and propagates phase-coherent along the axon as a lowest-order one-dimensional breathing mode, similar to transverse polarization pulses studied in nanowire resonators. Some experiments for the further manifestation of the model as well as topological protection of such breathing-mode polarization waves are discussed.
Dynamic Structural Scaling Concept for a Delta Wing Wind Tunnel Configuration Using Additive Manufacturing
Authors: Bantscheff Konstantin , Breitsamter Christian
Published: June 2023

Considering aeroelastic effects plays a vital role in the aircraft design process. The construction of elastic wind tunnel models is a critical element in the investigation of occurring aeroelastic phenomena. However, the structural scaling between full-scale and reduced-scale configurations is a complex design and manufacturing task and is usually avoided in wind tunnel testing. This work proposes a numerical approach for a dynamic aeroelastic scaling technique, which is applied to a fictive delta wing configuration. This scaling methodology is designed to optimise the structural layout of wind tunnel models with an integrated rib and spar structure to meet the behaviour of a realistic full-scale equivalent. For the modelling approach of the wing structure, a beam and shell structure is utilised. The applied scaling laws for the relevant quantities and the applied procedures are described. Computational fluid dynamics (CFD) calculations are performed by solving the Reynolds-averaged Navier–Stokes (RANS) equations for the assumption of a rigid full-scale and down-scaled wing. These calculations are used to verify the aerodynamic scaling assumptions, which are applied to the scaling procedure of the wind tunnel model. Global aerodynamic coefficients are evaluated for a variety of angles of attack. The local flow phenomena of the full-scale and the scaled model are compared in more detail for a medium and a high angle of attack. The pressure coefficient distribution shows a proper accordance for the full-scale and the scaled model. To verify the results of the structural scaling optimisation, a high-fidelity structural full-scale model is compared with the scaled model using the ELFINI FEM solver. Therefore, all structural components are modelled by 2D elements. The results for the reduced eigenfrequencies and according modes of the full-scale and the scaled model show a high level of similarity. A static deformation of the structural grids is performed by applying the aerodynamic loads from the CFD simulations. The results show that the deviation of the nondimensional deformation between the scaled and the full-scale model is negligible. Consequently, the applied scaling methodology proves to be a valuable tool for the conceptual approach of designing aeroelastically scaled wind tunnel models considering 3D-printed material.