bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19
Authors: Owens Cameron D , Bonin Pinto Camila , Detwiler Sam , Olay Lauren , Pinaffi-Langley Ana Clara da C , Mukli Peter , Peterfi Anna , Szarvas Zsofia , James Judith A , Galvan Veronica , Tarantini Stefano , Csiszar Anna , Ungvari Zoltan , Kirkpatrick Angelia C , Prodan Calin I , Yabluchanskiy Andriy
Published: March 2024

Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds and infection) alter cellular structures and physiologic processes within the neurovascular unit and contribute to cognitive dysfunction. COVID-19 has posed significant complications during acute and convalescent stages in multiple organ systems, including the brain. Cognitive impairment is a prevalent complication in COVID-19 patients, irrespective of severity of acute SARS-CoV-2 infection. Moreover, overwhelming evidence from in vitro, preclinical and clinical studies has reported SARS-CoV-2-induced pathologies in components of the neurovascular unit that are associated with cognitive impairment. Neurovascular unit disruption alters the neurovascular coupling response, a critical mechanism that regulates cerebromicrovascular blood flow to meet the energetic demands of locally active neurons. Normal cognitive processing is achieved through the neurovascular coupling response and involves the coordinated action of brain parenchymal cells (i.e. neurons and glia) and cerebrovascular cell types (i.e. endothelia, smooth muscle cells and pericytes). However, current work on COVID-19-induced cognitive impairment has yet to investigate disruption of neurovascular coupling as a causal factor. Hence, in this review, we aim to describe SARS-CoV-2's effects on the neurovascular unit and how they can impact neurovascular coupling and contribute to cognitive decline in acute and convalescent stages of the disease. Additionally, we explore potential therapeutic interventions to mitigate COVID-19-induced cognitive impairment. Given the great impact of cognitive impairment associated with COVID-19 on both individuals and public health, the necessity for a coordinated effort from fundamental scientific research to clinical application becomes imperative. This integrated endeavour is crucial for mitigating the cognitive deficits induced by COVID-19 and its subsequent burden in this especially vulnerable population.
Understanding the determinants of household cooking-fuel choice in sub-Saharan Africa: evidence from Nigeria
Authors: Aminu Raheem Olatunji , Dzudzor Maxwell Adizor , Oyawole Funminiyi Peter , Afolayan Samson Oluwaseyi
Published: March 2024

Overreliance on traditional cooking fuels by agricultural households poses a significant obstacle to achieving the United Nations Sustainable Development Goal 7 by 2030 in Nigeria. Despite the emerging recognition of remittances as a crucial factor influencing cooking-fuel choices in the energy-transition literature, there is a paucity of studies examining this influence in Nigeria. Using data from 4400 agricultural households sourced from the fourth wave of the Nigerian Living Standard Measurement Survey data sets, this study examined the influence of remittances on cooking-fuel choices, among other factors in Nigeria. Employing descriptive statistics and the multinomial logit regression model, the analysis reveals that traditional cooking fuels, including wood, crop residue and animal dung, continue to dominate the cooking-fuel landscape. The empirical result of the multinomial logit model showed that households that receive remittances are more likely to use modern cooking fuels. Furthermore, wealthier, more educated households with access to electricity are more likely to use modern and transitional cooking fuels than traditional cooking fuels. Based on the findings, the study suggests the incentivization of remittances into the country through the reduction in associated transaction costs and accelerated public infrastructural investment in affordable electricity and good road networks to connect rural areas to gas-supply networks to drive the transition to modern cooking energy. Additionally, educational and awareness campaigns about the health risks associated with traditional cooking energy, particularly indoor air pollution, should be encouraged, especially in rural areas.
α2-Antiplasmin is associated with macrophage activation and fibrin deposition in a macrophage activation syndrome mouse model
Authors: Kanno Yosuke , Toyama Kinomi , Shibata Haruna , Matsuo Osamu , Ozaki Kei-ichi
Published: March 2024

Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated the roles of alpha2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by toll-like receptor-9 agonist (CpG) and D-(+)-galactosamine hydrochloride (DG). α2AP deficiency attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. Interferon-γ (IFN-γ) is associated with macrophage activation, including migration, and plays a pivotal role in MAS progression. α2AP enhanced the IFN-γ-induced migration, and tissue factor production. Additionally, we showed that fibrin-induced macrophage activation and tumor necrosis factor-α production. Moreover, the blockade of α2AP by neutralizing antibodies attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. These data suggest that α2AP may regulate IFN-γ-induced responses and be associated with macrophage activation and fibrin deposition in the MAS progression.
Validation of the Klinrisk chronic kidney disease progression model in the FIDELITY population
Authors: Tangri Navdeep , Ferguson Thomas , Leon Silvia J , Anker Stefan D , Filippatos Gerasimos , Pitt Bertram , Rossing Peter , Ruilope Luis M , Farjat Alfredo E , Farag Youssef M K , Schloemer Patrick , Lawatscheck Robert , Rohwedder Katja , Bakris George L
Published: March 2024

Background

Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk.

Methods

The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk.

Results

At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome (P = .31).

Conclusions

Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.
Enhancing systematic reviews in orthodontics: a comparative examination of GPT-3.5 and GPT-4 for generating PICO-based queries with tailored prompts and configurations
Authors: Demir Gizem Boztaş , Süküt Yağızalp , Duran Gökhan Serhat , Topsakal Kübra Gülnur , Görgülü Serkan
Published: March 2024

Objectives

The rapid advancement of Large Language Models (LLMs) has prompted an exploration of their efficacy in generating PICO-based (Patient, Intervention, Comparison, Outcome) queries, especially in the field of orthodontics. This study aimed to assess the usability of Large Language Models (LLMs), in aiding systematic review processes, with a specific focus on comparing the performance of ChatGPT 3.5 and ChatGPT 4 using a specialized prompt tailored for orthodontics.

Materials/Methods

Five databases were perused to curate a sample of 77 systematic reviews and meta-analyses published between 2016 and 2021. Utilizing prompt engineering techniques, the LLMs were directed to formulate PICO questions, Boolean queries, and relevant keywords. The outputs were subsequently evaluated for accuracy and consistency by independent researchers using three-point and six-point Likert scales. Furthermore, the PICO records of 41 studies, which were compatible with the PROSPERO records, were compared with the responses provided by the models.

Results

ChatGPT 3.5 and 4 showcased a consistent ability to craft PICO-based queries. Statistically significant differences in accuracy were observed in specific categories, with GPT-4 often outperforming GPT-3.5.

Limitations

The study’s test set might not encapsulate the full range of LLM application scenarios. Emphasis on specific question types may also not reflect the complete capabilities of the models.

Conclusions/Implications

Both ChatGPT 3.5 and 4 can be pivotal tools for generating PICO-driven queries in orthodontics when optimally configured. However, the precision required in medical research necessitates a judicious and critical evaluation of LLM-generated outputs, advocating for a circumspect integration into scientific investigations.
Strategies to improve atrioventricular synchrony in patients with a Micra AV leadless pacemaker
Authors: Garweg Christophe , Breitenstein Alexander , Clémenty Nicolas , De Asmundis Carlo , Iacopino Saverio , Johansen Jens Brock , Sharman David , Theis Cathrin , Prat Xavier Viñolas , Winter Stefan , Reichlin Tobias
Published: March 2024

The second generation of transcatheter pacing systems, called Micra AV, can provide atrioventricular (AV) synchronous pacing via a new pacing algorithm relying on sensing mechanical atrial contraction. Several novel programming parameters were introduced to enable AV synchronous pacing, including an A3 window and A4 window as well as a conduction mode switch and an activity mode switch. In addition to several automated features, manual programming optimization of some of the novel parameters is key to improving AV synchrony. A solid knowledge of the features and their programming is essential for electrophysiologists implanting or following patients with Micra AV devices. Differences in programming optimization might partially explain the high variability of AV synchrony published in real-world data reports. This article reviews the key programming parameters of Micra AV. Subsequently, optimal programming recommendations for defined patient profiles are presented. Those were established by consensus within an expert panel comprised of 11 European electrophysiologists from high-volume Micra AV centres. The patient profiles were (1) high degree AV block and slow sinus rhythm; (2) high degree AV block and fast sinus rhythm; and (3) intermittent AV block. The panel recommended to evaluate the mechanical atrial activity on transthoracic echocardiography prior to implant. It was also agreed that Auto A3 Threshold and Tracking Check should be turned off in all patients, AV conduction mode switch should be turned off in all patients with high degree AV block, and the lower rate should be programmed to 50 bpm with exceptions based on individual clinical assessment. Future studies will be useful to evaluate the strength of those recommendations to improve the AV synchrony.
Genome-Wide Polygenic Score for Muscle Strength Predicts Risk for Common Diseases and Lifespan: A Prospective Cohort Study
Authors: Herranen Päivi , Koivunen Kaisa , Palviainen Teemu , Kujala Urho M , Ripatti Samuli , Kaprio Jaakko , Sillanpää Elina , FinnGen
Published: March 2024

Background

We used a polygenic score for hand grip strength (PGS HGS) to investigate whether genetic predisposition for higher muscle strength predicts age-related noncommunicable diseases, survival from acute adverse health events, and mortality.

Methods

This study consisted of 342 443 Finnish biobank participants from FinnGen Data Freeze 10 (53% women) aged 40–108 with combined genotype and health registry data. Associations between PGS HGS and a total of 27 clinical endpoints were explored with linear or Cox regression models.

Results

A higher PGS HGS was associated with a reduced risk of selected common noncommunicable diseases and mortality by 2%–10%. The risk for these medical conditions decreased by 5%–23% for participants in the highest PGS HGS quintile compared to those in the lowest PGS HGS quintile. A 1 standard deviation (SD) increase in the PGS HGS predicted a lower body mass index (β = −0.112 kg/m2, standard error [SE] = 0.017, p = 1.69E-11) in women but not in men (β = 0.004 kg/m2, p = .768). PGS HGS was not associated with better survival after acute adverse health events compared to the nondiseased period.

Conclusions

The genotype that supports higher muscle strength appears to protect against future health adversities, albeit with modest effect sizes. Further research is needed to investigate whether or how a favorable lifestyle modifies this intrinsic capacity to resist diseases, and if the impacts of lifestyle behavior on health differs due to genetic predisposition for muscle strength.
Surprising Gendered Age Differences in Rural Malawians’ Early COVID-19 Pandemic Prevention Efforts
Authors: Myroniuk Tyler W , Kohler Hans-Peter , Mwapasa Victor , Mwera James , Kohler Iliana V
Published: March 2024

Objectives

We assess how age, the presence of mature adults aged 45+ years, and recent deaths in rural households are associated with coronavirus disease 2019 (COVID-19) preventative actions and the likelihood of getting vaccinated against the virus in Malawi during early stages of the pandemic.

Methods

We draw upon data from 2,187 rural Malawians who participated in a 2020 COVID-19 Phone Survey. We estimate the log odds of engaging in “low-cost” and “high-cost” COVID-19 preventative actions based on age, gender, household composition, and recent household deaths. Low-cost prevention efforts were washing hands with soap and water frequently, avoiding close contact with people when going out, and avoiding shaking hands. High-cost actions included staying at home and decreasing time spent close to people not living in their household. We also estimate the chances of acquiring the COVID-19 vaccine in early stages of its availability.

Results

Mature women (45+ years) in general and younger men (<45 years)—living with at least one mature adult in the household—were less likely than others to comply with low-cost actions. Mature men were more likely than younger men (<45 years) to take on high-cost actions. To some extent, individuals who experienced a recent family death were more likely to engage in high-cost COVID-19 preventative actions as well as getting vaccinated.

Discussion

Gendered age differences in preventing the transmission of COVID-19 offer hints of larger social norms affecting protective efforts. The analyses also inform future COVID-19 public health outreach efforts in Malawi and other rural SSA contexts.
Representation and interpretation about underwater sound speed gradient field in the GNSS-A observation
Authors: Yokota Yusuke , Ishikawa Tadashi , Watanabe Shun-ichi , Nakamura Yuto , Nagae Koya
Published: March 2024

The Global Navigation Satellite System—Acoustic ranging combination technique (GNSS-A) is a seafloor geodetic observation technique that achieves an accuracy of centimetres by combining high-rate GNSS data with acoustic ranging. The technique determines the seafloor position by acoustic ranging between the sea surface and multiple seafloor stations, using GNSS data from the sea surface station. Here, the gradient state of the underwater sound speed structure (SSS) is a significant source of error. The open-source software GARPOS can reduce the effect from underwater gradient structures by retrieving the underwater disturbance as a parameter projected onto the sea surface and seafloor. To evaluate the effects of underwater disturbances, a quantitative comparison of the model parameters is necessary. In this study, we developed a representation method to evaluate features of the ocean field. Here, the expression method was described in the order of a formulation and an interpretation in the case of a 2-D cross-section and extension to the case of an actual 3-D field. This method makes it possible to evaluate SSS states in the GNSS-A observations. As an example, we showed the correlation between the anomaly of the expressed ocean state and the anomaly of the seafloor station position, showing that this expression method is an effective index for correcting bias errors. Additionally, we used the data from sites located in the Kuroshio area, a strong current near Japan, to show that the ocean state can be quantitatively interpreted using this expression method.
Indirect joint petrophysical inversion of shallow-seismic and multi-offset ground-penetrating radar field data
Authors: Qin Tan , Bohlen Thomas , Pan Yudi
Published: March 2024

In near-surface surveys, shallow-seismic and ground-penetrating radar (GPR) full-waveform inversions (FWIs) have received increasing attention because of their ability to reconstruct high-resolution subsurface models. However, they have different sensitivities to the same targets and thus may yield conflicting geophysical parameter models. To solve this issue, we have developed an indirect joint petrophysical inversion (JPI) integrating shallow-seismic and multi-offset GPR data. These data are used to reconstruct porosity and saturation whereby we use only strong sensitivities between petrophysical and geophysical parameters. To promote its field application, we proposed an input strategy to avoid measuring rock matrix parameters and make indirect JPI more robust. We apply indirect JPI to the field data acquired in Rheinstetten, Germany and find that it reveals the mechanical, electrical and petrophysical properties more reliably than individual inversions. The reconstructed models are assessed by direct-push technology, borehole sample measurements and migrated GPR image. Indirect JPI can fit seismic and GPR observed data simultaneously and provide consistent multiparameter models, which are hard to achieve by FWIs and individual petrophysical inversions. We also find that the method is robust when there are uncertainties in petrophysical a priori information. Overall, the field example proves the great potential of using indirect JPI to solve real-world problems.
On the elastodynamics of rotating planets
Authors: Maitra Matthew , Al-Attar David
Published: March 2024

Equations of motion are derived for (visco)elastic, self-gravitating and variably rotating planets. The equations are written using a decomposition of the elastic motion that separates the body’s elastic deformation from its net translational and rotational motion as far as possible. This separation is achieved by introducing degrees of freedom that represent the body’s rigid motions; it is made precise by imposing constraints that are physically motivated and that should be practically useful. In essence, a Tisserand frame is introduced exactly into the equations of solid mechanics. The necessary concepts are first introduced in the context of a solid body, motivated by symmetries and conservation laws, and the corresponding equations of motion are derived. Next, it is shown how those ideas and equations of motion can readily be extended to describe a layered fluid–solid body. A possibly new conservation law concerning inviscid fluids is then stated. The equilibria and linearization of the fluid–solid equations of motion are discussed thereafter, along with new equations for use within normal-mode coupling calculations and other Galerkin methods. Finally, the extension of these ideas to the description of multiple, interacting fluid–solid planets is qualitatively discussed.
Increasing accuracy of 3-D geomechanical-numerical models
Authors: Ziegler Moritz O , Heidbach Oliver
Published: March 2024

The current crustal stress field is of key importance to understand geodynamic processes and to assess stability aspects during subsurface usage. To provide a 3-D continuous description of the stress state, linear elastic forward geomechanical-numerical models are used. These models solve the equilibrium of forces between gravitational volume forces and surfaces forces imposed mainly by plate tectonics. The latter are responsible for the horizontal stress anisotropy and impose the inverse problem to estimate horizontal displacement boundary conditions that provide a fit best to horizontal stress magnitude data within the model volume. However, horizontal stress magnitude data have high uncertainties and they are sparse, clustered and not necessarily representative for a larger rock volume. Even when Bayesian statistics are incorporated and additional stress information such as borehole failure observations or formation integrity test are used to further constrain the solution space, this approach may result in a low accuracy of the model results, that is the result is not correct. Here, we present an alternative approach that removes the dependence of the solution space based on stress magnitude data to avoid potential low accuracy. Initially, a solution space that contains all stress states that are physically reasonable is defined. Stress magnitude data and the additional stress information are then used in a Bayesian framework to evaluate which solutions are more likely than others. We first show and validate our approach with a generic truth model and then apply it to a case study of the Molasse foreland basin of the Alps in Southern Germany. The results show that the model's ability to predict a reliable stress state is increasing while the number of likely solutions may also increase, and that outlier of stress magnitude data can be identified. This alternative approach results in a substantial increase in computational speed as we perform most of the calculations analytically.
‘You can’t really separate these risks, our environment, our animals and us’: Australian children’s perceptions of the risks of the climate crisis
Authors: Arnot Grace , Pitt Hannah , McCarthy Simone , Warner Elyse , Thomas Samantha
Published: March 2024

Perceptions of the risks associated with the climate crisis are shaped by a range of social and political contexts and information sources. While some have expressed concerns about the impact of the spread of climate misinformation through social media platforms on young people, others have shown that the youth climate movement has played a key role in countering misinformation. Despite this, there has been very limited research with children about how they conceptualize the risks associated with the climate crisis, how they receive climate information, and how they understand and apply this to their own and others’ lives. The following qualitative study used photo-elicitation techniques and in-depth interviews with Australian children to address this gap. A total of n = 28 children (12–16 years) participated, with four themes constructed from the data using a reflexive approach to thematic analysis. Children were concerned about how the climate crisis would continue to harm their futures and the health of planet and people. They recognized that some groups and countries would experience more risks associated with the climate crisis as compared to others. While they received information from a range of different sources (school, family, social media), they mostly used social media to seek out climate information. They recognized that social media sites could be a source of climate misinformation, and argued that a range of strategies were needed to identify and counter false information about the climate crisis. Children's perspectives must be harnessed to improve information about climate risks and action.
Optimization and research of smart grid load forecasting model based on deep learning
Authors: Zhang Dong
Published: March 2024

In order to accurately grasp the power consumption of the market and deeply understand the operation law of the power market, the power grid must achieve accurate power load prediction by studying the supply and demand of the power system and the change law. Therefore, a smart grid load prediction analysis method based on deep learning is proposed. Firstly, DenseNet network is used to extract features, so as to achieve feature reuse and improve efficiency. Then, combining the long short-term memory (LSTM) network based on attention mechanism, a combined model DenseNet–AM–LSTM is proposed to solve the long-term dependence problem of feature extraction. After using batch normalization, the model can use higher learning rate to improve the training speed of the model and obtain the best prediction accuracy of the model. The experimental results show that this method can accurately predict the power load, and the accuracy is higher than the current popular methods, and it is expected to become an important technical support for solving the core problems of smart grid.
MALDI-TOF MS combined with AUC method for tigecycline susceptibility testing in Escherichia coli
Authors: Yan Zelin , Li Jiapin , Hu Yanyan , Zhang Yanyan , Wu Yuchen , Ju Xiaoyang , Cai Chang , Chen Gongxiang , Sun Chengtao , Zhang Rong
Published: March 2024

Objectives

The wide spread of tet(X4) gene orthologues in the environment, food, poultry and humans is causing serious tigecycline resistance. Consequently, developing a fast and universal method to detect tigecycline resistance has become increasingly important.

Methods

During 2019–2022, 116 Escherichia coli isolates were obtained from nine provinces in China. All isolates were tested for their susceptibility to antimicrobial agents by the microdilution broth method and for the tet(X4) gene by PCR. Ten tet(X4)-positive E. coli isolates were used to confirm certain conditions, including the optimal incubation time, the optimal concentration of tigecycline, and the cut-off of the relative growth (RG) value.

Results

The optimal time and concentration of tigecycline for separation of susceptible and resistant isolates was 2 h and 4 mg/L, and the RG cut-off value was 0.4. We validated whether the experiment was feasible using 116 isolates of E. coli. The method yielded a susceptibility of 94.9% (95% CI: 81.4%–99.1%) and a specificity of 96.1% (95% CI: 88.3%–99.0%).

Conclusions

This research has shown that this optical antimicrobial susceptibility testing method can rapidly differentiate between susceptible and resistant phenotypes in isolates of E. coli. In the same range as the current gold-standard methods, the clinical turnaround time is reduced from 48 h to 2.5 h. The above results suggest that the method has splendid specificity and operationality.
Impact of dry density and incomplete saturation on microbial growth in bentonite clay for nuclear waste storage
Authors: Beaver Rachel C , Vachon Melody A , Tully Claire S , Engel Katja , Spasov Emilie , Binns W Jeffrey , Noël James J , Neufeld Josh D
Published: March 2024

Aims

Many countries are in the process of designing a deep geological repository (DGR) for long-term storage of used nuclear fuel. For several designs, used fuel containers will be placed belowground, with emplacement tunnels being backfilled using a combination of highly compacted powdered bentonite clay buffer boxes surrounded by a granulated “gapfill” bentonite. To limit the potential for microbiologically influenced corrosion of used fuel containers, identifying conditions that suppress microbial growth is critical for sustainable DGR design. This study investigated microbial communities in powdered and gapfill bentonite clay incubated in oxic pressure vessels at dry densities between 1.1 g cm−3 (i.e. below repository target) and 1.6 g cm−3 (i.e. at or above repository target) as a 1-year time series.

Results

Our results showed an initial (i.e. 1 month) increase in the abundance of culturable heterotrophs associated with all dry densities <1.6 g cm−3, which reveals growth during transient low-pressure conditions associated with the bentonite saturation process. Following saturation, culturable heterotroph abundances decreased to those of starting material by the 6-month time point for all 1.4 and 1.6 g cm−3 pressure vessels, and the most probable numbers of culturable sulfate-reducing bacteria (SRB) remained constant for all vessels and time points. The 16S rRNA gene sequencing results showed a change in microbial community composition from the starting material to the 1-month time point, after which time most samples were dominated by sequences associated with Pseudomonas, Bacillus, Cupriavidus, and Streptomyces. Similar taxa were identified as dominant members of the culture-based community composition, demonstrating that the dominant members of the clay microbial communities are viable. Members of the spore-forming Desulfosporosinus genus were the dominant SRB for both clay and culture profiles.

Conclusions

After initial microbial growth while bentonite was below target pressure in the early phases of saturation, microbial growth in pressure vessels with dry densities of at least 1.4 g cm−3 was eventually suppressed as bentonite neared saturation.
Effect of citric acid on cell membrane structure and function of Issatchenkia terricola WJL-G4
Authors: Meng Xiangfeng , Liu Xinyi , Bao Yihong , Luo Ting , Wang Jinling
Published: March 2024

Aims

This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis.

Methods and results

The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l−1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l−1.

Conclusions

I. terricola could successfully adjust its membrane structure and function below 60 g l−1 of citric acid. However, for citric acid concentrations above 80 g l−1, its structure and function were dramatically changed, which might result in reduced functionality.
Current status and future perspective of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck
Authors: Kiyota Naomi , Tahara Makoto , Homma Akihiro
Published: March 2024

Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to high-dose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
Randomized trials of multicancer screening tests: augmenting their ability to identify a genuine mortality benefit
Authors: Weiss Noel S
Published: March 2024

Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.
Testing many constraints in possibly irregular models using incomplete U-statistics
Authors: Sturma Nils , Drton Mathias , Leung Dennis
Published: March 2024

We consider the problem of testing a null hypothesis defined by equality and inequality constraints on a statistical parameter. Testing such hypotheses can be challenging because the number of relevant constraints may be on the same order or even larger than the number of observed samples. Moreover, standard distributional approximations may be invalid due to irregularities in the null hypothesis. We propose a general testing methodology that aims to circumvent these difficulties. The constraints are estimated by incomplete U-statistics, and we derive critical values by Gaussian multiplier bootstrap. We show that the bootstrap approximation of incomplete U-statistics is valid for kernels that we call mixed degenerate when the number of combinations used to compute the incomplete U-statistic is of the same order as the sample size. It follows that our test controls type I error even in irregular settings. Furthermore, the bootstrap approximation covers high-dimensional settings making our testing strategy applicable for problems with many constraints. The methodology is applicable, in particular, when the constraints to be tested are polynomials in U-estimable parameters. As an application, we consider goodness-of-fit tests of latent-tree models for multivariate data.
VKH-like syndrome in the setting of Dabrafenib and Trametinib therapy for BRAF mutant metastatic melanoma: a case report
Authors: Gunaratnam Cadric , Muzicenco Olga , Sivagurunathan Premala , Franzco Michael Hogden
Published: March 2024

Dabrafenib and trametinib, approved for the treatment of BRAF-mutant metastatic melanoma, are associated with a spectrum ophthalmic toxicity including pan-uveitis and serous retinopathy. Vogt–Koyanagi–Harada (VKH) is a systemic inflammatory disorder characterized by bilateral granulomatous pan-uveitis, exudative retinal detachments, and often associated with extraocular manifestations such as tinnitus, vitiligo, headaches, or encephalopathy. We present a 49-year-old woman with stage IV metastatic cutaneous melanoma developed bilateral acute pan-uveitis with multifocal serous retinal detachments, 4 months after starting combined dabrafenib and trametinib therapy. Clinical assessment, together with fluorescein angiography, optical coherence tomography, and serology led to the diagnosis of a (VKH)-like uveitis. Prompt systemic corticosteroids and modification of the dosing schedule of the suspected offending agents resulted in the resolution of intraocular inflammation and serous retinal detachments. This case underscores the importance of the prompt recognition of the association between VKH-like uveitis and BRAF/MEK inhibitors, enabling early intervention without compromising metastatic melanoma treatment.
ZmMPK6, a mitogen-activated protein kinase, regulates maize kernel weight
Authors: Li Wenyu , Li Yayong , Shi Huiyue , Wang Han , Ji Kun , Zhang Long , Wang Yan , Dong Yongbin , Li Yuling
Published: March 2024

Kernel weight is a critical agronomic trait in maize production. Many genes are related to kernel weight but only a few of them have been applied to maize breeding and cultivation. Here, we identify a novel function of maize mitogen-activated protein kinase 6 (ZmMPK6) in the regulation of maize kernel weight. Kernel weight was reduced in zmmpk6 mutants and increased in ZmMPK6-overexpressing lines. In addition, starch granules, starch content, protein content, and grain-filling characteristics were also affected by the ZmMPK6 expression level. ZmMPK6 is mainly localized in the nucleus and cytoplasm, widely distributed across various tissues, and is expressed during kernel development, which is consistent with its role in kernel weight. Thus, these results provide new insights into the role of ZmMPK6, a mitogen-activated protein kinase, in maize kernel weight, and could be applied to further molecular breeding for kernel quality and yield in maize.
Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe−/− mice
Authors: Deng Yajuan , Yang Xiaoyu , Ye Xueru , Yuan Youwen , Zhang Yanan , Teng Fei , You Danming , Zhou Xuan , Liu Wenhui , Li Kangli , Luo Shenjian , Yang Zhi , Chen Ruxin , Shi Guojun , Li Jin , Zhang Huijie
Published: March 2024

Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.
Poxviruses
Authors: Smith Geoffrey L.
Published: March 2024

Poxviruses are large, complex DNA viruses that have played several seminal roles in medicine and biological science. Cowpox virus was introduced by Jenner as the first human vaccine in 1796; widespread vaccination with vaccinia virus led to the global eradication of smallpox in 1977, the only human disease to have been eradicated. Smallpox is caused by variola virus, the most infamous poxvirus. Other poxviruses include molluscum contagiosum, which is the only other poxvirus that infects only humans, causing benign skin tumours that may be single or multiple, typically persisting for months before undergoing spontaneous regression. In 2022, there was a worldwide epidemic of monkeypox virus, spread largely by sexual contact. The development of vaccinia virus as an expression vector pioneered the concept of using genetically engineered viruses as live vaccines. Vaccinia virus is also being developed as an oncolytic agent. Poxviruses remain excellent models for studying virus-host interactions and virus immune evasion strategies.
Persistent problems and recovery after critical illness
Authors: Mikkelsen Mark E. , Iwashyna Theodore J.
Published: March 2024

Post-intensive care syndrome is defined as new or worsening impairment in cognition, mental health, or physical function that persists after a critical illness. The complexities of post-intensive care syndrome come from the interactions of the patient’s premorbid mental health and physical function, the acute physiologic derangements and acute organ injury of the critical illness, and the side effects of procedures, treatments, and potential complications incurred during the critical illness. Problems are better described as challenging syndromes rather than specific actionable diagnoses, with the four major functional problems for patients being weakness, cognitive impairment, psychological problems, and new or worsened organ dysfunction. The sequelae of critical illness often extend beyond patients and impact the families of critically ill patients.
Disorders of the synthesis or function of haemoglobin
Authors: Hay Deborah , Weatherall David J.
Published: March 2024

Inherited disorders of haemoglobin are the most common single-gene diseases affecting humans. Caused by disordered production of one or more globin chains or changes in globin structure, thalassaemia and sickle cell disease are responsible for an immense burden of illness across the globe. Thalassaemia describes a heterogeneous group of Mendelian conditions due to reduced synthesis of one or more of the globin chains. According to their clinical manifestations, the thalassaemias are classified into major (a severe transfusion-dependent disease), intermediate (characterized by anaemia and splenomegaly), and minor forms (in most cases, a symptomless carrier state). On account of their high frequency in many populations, and because they cause severe anaemia in their homozygous and compound heterozygous states, the β thalassaemias are the most important. Most countries in which the disease is common are introducing programmes for its prevention (population screening and prenatal diagnosis). Symptomatic management of severe thalassaemia requires regular blood transfusion, judicious use of splenectomy if hypersplenism develops, and chelating agents to reduce iron overload. Sickle cell disease—haemoglobin S differs from haemoglobin A by the substitution of valine for glutamic acid at position 6 in the β globin chain; homozygosity for haemoglobin S causes sickle cell disease. This occurs very frequently in African populations and, sporadically, throughout the Mediterranean region and the Middle East, and in several populations in India. Management of the acute and chronic complications remains largely supportive, with hydroxycarbamide (hydroxyurea) hitherto being the only widely used treatment with proven efficacy—although the whole field is now enriched by clinical trials based on several promising therapeutic discoveries and predicated on decades of intensive medical research.
bilby in space: Bayesian inference for transient gravitational-wave signals observed with LISA
Authors: Hoy C , Nuttall L K
Published: March 2024

The Laser Interferometer Space Antenna (LISA) is scheduled to launch in the mid-2030s, and is expected to observe gravitational-wave candidates from massive black hole binary mergers, extreme mass ratio inspirals, and more. Accurately inferring the source properties from the observed gravitational-wave signals is crucial to maximize the scientific return of the LISA mission. bilby, the user-friendly Bayesian inference library, is regularly used for performing gravitational-wave inference on data from existing ground-based gravitational-wave detectors. Given that Bayesian inference with LISA includes additional subtitles and complexities beyond its ground-based counterpart, in this work we introduce bilby_lisa , a python package that extends bilby to perform parameter estimation with LISA. We show that full nested sampling can be performed to accurately infer the properties of LISA sources from transient gravitational-wave signals in (a) zero noise and (b) idealized instrumental noise. By focusing on massive black hole binary mergers, we demonstrate that higher order multipole waveform models can be used to analyse a year’s worth of simulated LISA data, and discuss the computational cost and performance of full nested sampling compared with techniques for optimizing likelihood calculations, such as the heterodyned likelihood.
The dark balance: quantifying the inner halo response to active galactic nuclei feedback in galaxies
Authors: Arora Nikhil , Courteau Stéphane , Macciò Andrea V , Cho Changhyun , Patel Raj , Stone Connor
Published: March 2024

This paper presents a study of the impact of supermassive black hole (SMBH) feedback on dark matter (DM) haloes in numerical NIHAO (Numerical Investigation of a Hundred Astrophysical Object) simulations of galaxies. In particular, the amount of DM displaced via active galactic nuclei (AGNs) feedback and the physical scale over which AGN feedback affects the DM halo are quantified by comparing NIHAO simulations with and without AGN feedback. NIHAO galaxies with log (M*/M⊙) ≥ 10.0 show a growing central DM suppression of 0.2 dex (∼40  per cent) from z = 1.5 to the present relative to no AGN feedback simulations. The growth of the DM suppression is related to the mass evolution of the SMBH and the gas mass in the central regions. For the most massive NIHAO galaxies with log (M*/M⊙) > 10.5, partially affected by numerical resolution, the central DM suppression peaks at z = 0.5 after which halo contraction overpowers AGN feedback due a shortage of gas and thus, SMBH growth. The spatial scale, or ‘sphere of influence’, over which AGN feedback affects the DM distribution decreases as a function of time for Milky Way-mass galaxies (from ∼16 kpc at z = 1.5 to ∼7.8 kpc at z = 0) as a result of halo contraction due to stellar growth. For the most massive NIHAO galaxies, the size of the sphere of influence remains constant (∼16 kpc) for z > 0.5 owing to the balance between AGN feedback and halo contraction.