bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the prediction of the suitable distribution of Polygonatum kingianum under different climatic conditions based on the MaxEnt model
Authors: Guo Yixin , Zhang Shiyan , Tang Shicheng , Pan Jianying , Ren Linghui , Tian Xin , Sun Zhirong , Zhang Zilong
Published: January 2023

Introduction: Environmental changes have led to changes in the suitable areas for growing certain medicinal plants, which might lead to changes in cultivation areas and quality of medicinal materials. Polygonatum kingianum is a commonly used medicinal plant and, with its growing demand, the sustainable development of P. kingianum is particularly important.

Methods: Therefore, this study comprehensively considered environmental variables, such as climate, soil, and topography, collected 181 valid distribution records, and used the MaxEnt to predict and evaluate the changes and potential distribution of P. kingianum.

Results: The results showed that the current high-suitability areas (31,534.60 km2) for this medicinal plant are mainly distributed in the Southern part of Yunnan Province, western part of Guangxi Province, and Southwestern part of southwestern Guizhou Province. Under a future climate change scenario, the area of suitable habitats showed a trend of first expansion and then contraction, but the overall trend still expanded. The medicinal plant’s migration trend to the northwest of Guizhou Province and northeast of Yunnan Province was more clear. At the Chinese scale, temperature and precipitation were the important factors affecting the medicinal plant’s distribution. At the national scale, Bio7, Bio12, Bio17, Bio11, S_USDA_TEX_CLASS, and Elevation were key variables affecting P. kingianum distribution, whose cumulative value of percent contribution was 93.6%. At a more precise scale, precipitation, soil variables, and altitude became the key factors affecting its distribution. Among them, S_USDA_TEX_CLASS has the highest contribution rate.

Discussion: Overall, the results of this study provided a reference for the determination of suitable planting areas of P. kingianum in China.
Predictors for pharmacological therapy and perinatal outcomes with metformin treatment in women with gestational diabetes
Authors: Brzozowska Malgorzata M. , Puvanendran Anita , Bliuc Dana , Zuschmann Andrew , Piotrowicz Agata K. , O’Sullivan Anthony
Published: January 2023

Background

The prevalence of gestational diabetes mellitus (GDM) has been increasing in Australia and worldwide. The study aims were to examine, in comparison with dietary intervention, perinatal outcomes for women with gestational diabetes who were attending a single hospital clinic and to identify predictors for their pharmacological GDM treatment.

Methods

A prospective, observational study of women with GDM, treated with “Diet, N= 50”, “Metformin, N = 35”, “Metformin and Insulin, N = 46” or “Insulin, N = 20”.

Findings

The mean BMI for the whole cohort was 25.8 ± 4.7 kg/m2. The Metformin group, compared to the Diet group, had OR=3.1 (95% CI:1.13 to 8.25) for caesarean section birth (LSCS) compared to normal vaginal birth mode with no longer such a significant association after controlling for the number of their elective LSCS. The insulin treated group had the highest number of small for gestational age neonates (20%, p<0.05) with neonatal hypoglycaemia (25%, p< 0.05). Fasting glucose value on oral GTT (glucose tolerance test) was the strongest predictor for a pharmacological intervention requirement with OR = 2.77 (95CI%: 1.16 to 6.61), followed by timing of OGTT with OR=0.90 (95% CI: 0.83 to 0.97) and previous pregnancy loss with OR=0.28 (95% CI:0.10 to 0.74).

Interpretation

These data suggest that metformin may be a safe alternative treatment to insulin treatment in GDM. Raised fasting glucose on oral GTT was the strongest indicator that GDM women with BMI < 35 kg/m2 may require pharmacological therapy. Further studies are needed to identify the most effective and safe management of gestational diabetes within the public hospital setting.

Australian New Zealand Clinical Trial Registry ANZCTR Trial Id

ACTRN12620000397910.
Carbon emission and financial development under the “double carbon” goal: Considering the upgrade of industrial structure
Authors: Yang Wen-Jie , Tan Meng-Zhuo , Chu Shun-Ho , Chen Zhen
Published: January 2023

Economic growth is fueled by financial development, which also takes the initiative in attaining green development and a low-carbon economy. The advanced industrial constitution is used as a moderator and mediator variable in this article to investigate whether there is a moderating effect and mediating effect between financial development and carbon emissions. This article chooses panel data from 283 Chinese cities from 2006 to 2019 to empirically analyze the impact of financial development on carbon emissions. The consequences indicate that financial development wields an evident active influence over carbon emissions. Additionally, the upgrading of industrial structures wields an evident positive impact on carbon emissions. There exists a medium impact of industrial structure upgrading. Results show that, first, when estimating carbon emissions demand, China’s financial expansion should be taken into consideration as a significant driver of rising carbon emissions. Second, although the extent of financial intermediation has a greater impact on carbon emissions than other financial development indicators, its effectiveness appears to have far less impact, even if it statistically has the potential to affect carbon emissions. Third, although the size of China’s stock market has a substantially greater impact on carbon emissions, the impact of its efficiency is quite little.
Modelling a tradable transport permit scheme using system dynamics
Authors: Harrison Gillian , Shepherd Simon
Published: January 2023

Introduction: In this paper we consider system dynamics (SD) modelling of tradable transport permit schemes (TTPS). TTPS are complex and uncertain, having not yet been implemented beyond experimental trials anywhere in the world, yet have for some time been suggested as an efficient and equitable policy response to reducing car-based travel and its associated externalities.

Method: Although there is a large number of econometric models that explore the potential of TTPS, there have been none published (to our knowledge) that have used the SD approach. SD is an appropriate method for developing our understanding of TTPS efficiency and equity as it captures feedbacks and tracks the influence of the TTPS over a period of time. Thus, we have developed an SD model of TTPS, drawing from the literature that already exists. It is a micro-level model that considers heterogeneity within a population on a daily basis over a matter of months. We carry out sensitivity testing of price sensitivity, initial permit price, daily preference and permit allocation and develop combined scenarios of these attributes.

Results: Our modelling results suggest a sensitivity of TTPS to heterogeneity across the population, which will influence the final equilibrium price. Trading encourages a redistribution of wealth across the population but may also mean that some travel needs are not met, which may require some allocation according to need or a certain portion of protected permits. The inclusion of non-car users within the allocation further encourages trading behaviours and allows for compensation for externalities of car use.

Discussion: Through an analysis of outputs we are able to bring new insights into the governance frameworks required for a successful TTPS. In particular we have shown the importance of allocation considerations in the design of a TTPS when issues of fairness across the population are considered. Although there is no data of existing schemes available for us to calibrate our models, we compare the trends with data from an in-the-field TTPS experiment.
Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA
Authors: Stolovich-Rain Miri , Kumari Sujata , Friedman Ahuva , Kirillov Saveliy , Socol Yakov , Billan Maria , Pal Ritesh Ranjan , Das Kathakali , Golding Peretz , Oiknine-Djian Esther , Sirhan Salim , Sagie Michal Bejerano , Cohen-Kfir Einav , Gold Naama , Fahoum Jamal , Kumar Manoj , Elgrably-Weiss Maya , Zhou Bing , Ravins Miriam , Gatt Yair E. , Bhattacharya Saurabh , Zelig Orly , Wiener Reuven , Wolf Dana G. , Elinav Hila , Strahilevitz Jacob , Padawer Dan , Baraz Leah , Rouvinski Alexander
Published: January 2023

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.
Understanding the squamous cell carcinoma immune microenvironment
Authors: Saeidi Vahide , Doudican Nicole , Carucci John A.
Published: January 2023

Primary cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with a rising incidence of about 1.8 million in the United States annually. Primary cSCC is usually curable by surgery; however, in some cases, cSCC eventuates in nodal metastasis and death from disease specific death. cSCC results in up to 15,000 deaths each year in the United States. Until recently, non-surgical options for treatment of locally advanced or metastatic cSCC were largely ineffective. With the advent of checkpoint inhibitor immunotherapy, including cemiplimab and pembrolizumab, response rates climbed to 50%, representing a vast improvement over chemotherapeutic agents used previously. Herein, we discuss the phenotype and function of SCC associated Langerhans cells, dendritic cells, macrophages, myeloid derived suppressor cells and T cells as well as SCC-associated lymphatics and blood vessels. Possible role(s) of SCC-associated cytokines in progression and invasion are reviewed. We also discuss the SCC immune microenvironment in the context of currently available and pipeline therapeutics.
Immune regulation based on sex differences in ischemic stroke pathology
Authors: Niu Pingping , Li Liqin , Zhang Yonggang , Su Zhongzhou , Wang Binghao , Liu He , Zhang Shehong , Qiu Sheng , Li Yuntao
Published: January 2023

Ischemic stroke is one of the world’s leading causes of death and disability. It has been established that gender differences in stroke outcomes prevail, and the immune response after stroke is an important factor affecting patient outcomes. However, gender disparities lead to different immune metabolic tendencies closely related to immune regulation after stroke. The present review provides a comprehensive overview of the role and mechanism of immune regulation based on sex differences in ischemic stroke pathology.
Nano selenium-enriched probiotic Lactobacillus enhances alum adjuvanticity and promotes antigen-specific systemic and mucosal immunity
Authors: Liu Runhang , Sun Weijiao , Sun Tianzhi , Zhang Wenzhi , Nan Yongchao , Zhang Zheng , Xiang Kongrui , Yang Hongliang , Wang Fang , Ge Junwei
Published: January 2023

Nano selenium-enriched probiotics have been identified to improve immune responses, such as alleviating inflammation, antioxidant function, treatment of tumors, anticancer activity, and regulating intestinal flora. However, so far, there is little information on improving the immune effect of the vaccine. Here, we prepared nano selenium-enriched Levilactobacillus brevis 23017 (SeL) and heat-inactivated nano selenium-enriched L. brevis 23017 (HiSeL) and evaluated their immune enhancing functions on the alum-adjuvanted, inactivated Clostridium perfringens type A vaccine in mouse and rabbit models, respectively. We found that SeL enhanced immune responses of the vaccine by inducing a more rapid antibody production, eliciting higher immunoglobulin G (IgG) antibody titers, improving secretory immunoglobulin A (SIgA) antibody level and cellular immune response, and regulating Th1/Th2 immune response, thus helping to induce better protective efficacy after challenge. Moreover, we confirmed that the immunoenhancement effects are related to regulating oxidative stress, cytokine secretion, and selenoprotein expression. Meanwhile, similar effects were observed in HiSeL. In addition, they show enhanced humoral immune response at 1/2 and 1/4 standard vaccine doses, which confirms their prominent immune enhancement effect. Finally, the effect of improving vaccine immune responses was further confirmed in rabbits, which shows that SeL stimulates the production of IgG antibodies, generates α toxin–neutralizing antibodies rapidly, and reduces the pathological damage to intestine tissue. Our study demonstrates that nano selenium-enriched probiotics improve the immune effect of the alum adjuvants vaccine and highlight its potential usage in remedying the disadvantages of alum adjuvants.
Efficacy of lure mixtures in baited traps to attract different fruit fly species in guava and vegetable fields
Authors: Ahmad Shakil , Jaworski Coline C. , Ullah Farman , Jamil Momana , Badshah Hayat , Ullah Farman , Luo Yanping
Published: January 2023

Fruit flies (Diptera: Tephritidae) are major pests of fruits and vegetables worldwide. We measured the efficacy of attractive lure mixtures in baited traps on naturally-occurring fruit flies in commercial mosaic guava and vegetables fields in Pakistan. We tested three mixtures (methyl-eugenol [ME] and cue lure [CL]; GF-120 and methyl eugenol; and GF-120 and cue lure) in eleven ratios: 0:100, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, and 100:0. We recorded three fruit fly species: Bactrocera zonata was the most abundant in baited traps, followed by Bactrocera dorsalis, while Zeugodacus cucurbitae was significantly less attracted to baited traps. We also found that the most attractive mixture and ratio varied among species: B. dorsalis was most attracted by 40CL:60ME, while B. zonata was most and equally attracted by 100ME, 10CL:90ME, 20CL:80ME, 30CL:70ME, and 40CL:60ME. Finally, Z. cucurbitae was most attracted by 10CL:90ME, which resulted in the highest total number of flies counted in 10CL:90ME-baited traps. Mixtures with GF-120 were less attractive to all three species. Our results suggest that lure mixtures in baited traps influence the attraction of fruit flies in a species-specific way. This needs to be considered in the integrated pest management of multiple species of fruit flies simultaneously. If Bactrocera species are most damaging and abundant, a 40CL:60ME mixture in baited traps will likely be most effective to reduce pest abundance and crop damage. However, if Z. cucurbitae is the main pest target causing most crop damage and yield loss, 10CL:90ME-baited traps will be a more effective in their monitoring and management.
Meta-analysis of genetic diversity and intercolony relatedness among reproductives in commercial honey bee populations
Authors: Tarpy David R. , Caren Joel R. , Delaney Deborah A.
Published: January 2023

Honey bee colonies are large kin groups, each with a single mother queen and thousands of female workers. Queen bees are highly polyandrous, each mating with an average of approximately 12 drones from other colonies. We used a meta-analysis approach to compare the pedigree relationships of honey bee reproductives (queens and their mates) across five different studies and to quantify the overall genetic diversity of breeding populations. We compared the inferred genotypes of queens and their mates from microsatellite analyses of worker offspring from a feral Africanized honey bee population (which served as a negative control for inbreeding), an experimentally derived population of sister queens (which served as a positive control for inbreeding), and three separate commercially managed populations. We then compared the relatedness of all drones mated to each queen (mate-mate), all queens within each population (queen-queen), each queen with each of her mates (queen-mate), and all drones within each population (drone-drone). We found, as expected, the lowest levels of genetic similarity in the outcrossed population and highest levels of genetic similarity in the inbred population. Levels of genetic similarity among the managed honey bee populations were intermediate but closer to that of the inbred population. Genetic structuring of the entire breeding population resulted in two major subpopulations, likely deriving from breeders on the east and west coast. The effects that these findings have on the overall population genetic diversity of managed honey bees is discussed.
Analysis of international shipping emissions reduction policy and China’s participation
Authors: Liu Huirong , Mao Zhengkai , Li Xiaohan
Published: January 2023

In addressing climate change, the shipping industry, which is regarded as one sector that cannot be ignored in controlling greenhouse gas emissions, has become a key area of concern for the international community to achieve emissions reduction targets. The International Maritime Organization—the body that regulates international shipping—as well as the European Union and other international entities have adopted a series of emissions reduction policies, beginning a new era of shipping emissions reduction. In view of the urgency and complexity of this issue, the future policy direction of shipping emissions reduction and whether or not existing policies can achieve the emissions reduction targets have become the focus of attention in the global shipping industry. In addition, China’s dual identity as a shipping magnate and a developing country plays a crucial role in the development of shipping emissions reduction trends, and reducing shipping emissions is necessary for China to achieve the “double carbon” commitment. In view of the above, this study endeavours to compare the current major shipping emission reduction policies from the perspective of international law and the perspective of macro policies, and analyze the future direction of international shipping emissions reduction policy. At the same time, the study identify China as one of the key countries to influence future policy making and proposes the position and path for China's participation in international shipping emissions reduction, which provided valuable contributions for China to participate in accelerating energy transformation, exploring participation in the carbon emission market, and promoting international unified shipping policy.
Seasonal drivers of productivity and calcification in the coral Platygyra carnosa in a subtropical reef
Authors: Dellisanti Walter , Chung Jeffery T. H. , Yiu Sam K. F. , Tsang Ryan Ho Leung , Ang Put , Yeung Yip Hung , Qiu Jian-Wen , McIlroy Shelby E. , Wells Mark L. , Wu Jiajun , Chan Leo Lei
Published: January 2023

Scleractinian corals are increasingly subjected to local stressors combined with global changes. In subtropical areas, corals exhibit metabolic plasticity and resilience in response to variability and extremes in local temperature, salinity, and light; however, the physiological mechanisms by which corals acclimate or adapt to these changing conditions remain disputed. We assessed the physiological status of the coral Platygyra carnosa during a two-year in situ monitoring survey. To obtain metabolic rates (respiration and photosynthesis), photochemical efficiency (Fv / Fm), and biocalcification measurements, non-invasive techniques such as underwater respirometry, Pulse Amplitude Modulated (PAM) fluorometry, total alkalinity measurements, and digital photography were used. Our findings show clear seasonality in water quality parameters, which affected coral health. Elevated temperatures during the summer were below the maximum monthly mean < 31°C) but reduced the energetic productivity of corals (-44% relative to winter). Fluctuations in salinity (25–38 ppt) and pH (7.65–8.44) were linked to rainfall and reduced calcification rates. The conditions during the spring were favorable for coral metabolism and calcification (+20% relative to summer). Overall, our research demonstrates that the metabolic plasticity of P. carnosa in response to shifts in seawater quality allows this species to survive ongoing environmental change. Our in situ observations provide fundamental insights into coral response mechanisms under changing environmental conditions and contribute to projections of coral health under future scenarios of global change.
Effect of Ca doping on the arbitrary canting of magnetic exchange interactions in La1-xCaxMnO3 nanoparticles
Authors: Ali Akhtar , Shah Wiqar H. , Safeen Akif , Ali Liaqat , Tufail Muhammad , Ullah Zakir , Safeen Kashif , Eldin Sayed M. , R. Ali Mohamed , Sohail Muhammad , Imran Naveed
Published: January 2023

La1-xCaxMnO3 nanoparticles (x = 0.1, 0.2, 0.3) (LCMO NPs) were synthesized using the coprecipitation method. The prepared samples were investigated using x-ray diffraction (XRD), which confirmed the single-phase structure. The nanoparticle’s crystallite size was determined using Debye–Scherrer’s formula. Scanning electron microscopy showed that the size of the nanoparticles was between 33 nm and 55 nm. Energy-dispersive x-ray spectroscopy (EDX) was used to determine the elemental composition of samples. The four-probe method was used to measure the temperature-dependent electrical resistivity. Magnetic properties, such as hysteresis loop, magnetoresistance, and magnetization versus temperature, were measured using a vibrating sample magnetometer. The study of magnetization versus applied magnetic field M(H) showed that, at 77 K, all the loops exhibit ferromagnetism. DC magnetization versus temperature at a 70-Oe-applied field for all samples showed a paramagnetic-ferromagnetic phase transition. A decrease in Curie temperature Tc after increasing the concentration of x was observed. The real and imaginary parts of temperature-dependent ac magnetic susceptibility were measured and revealed a transition from the ferromagnetic to the paramagnetic phase at a particular temperature Tc, with DC magnetization behavior.
The domestication of the African Union model law on medical products regulation: Perceived benefits, enabling factors, and challenges
Authors: Ncube Bakani Mark , Dube Admire , Ward Kim
Published: January 2023

Introduction

In 2016, the African Union (AU) Model Law on Medical Products Regulation was endorsed by AU Heads of State and Government. The aims of the legislation include harmonisation of regulatory systems, increasing collaboration across countries, and providing a conducive regulatory environment for medical product/health technology development and scale-up. A target was set to have at least 25 African countries domesticating the model law by 2020. However, this target has not yet been met. This research aimed to apply the Consolidated Framework for Implementation Research (CFIR) in analysing the rationale, perceived benefits, enabling factors, and challenges of AU Model Law domestication and implementation by AU Member States.

Methods

This study was a qualitative, cross-sectional, census survey of the national medicines regulatory authorities (NRAs) of Anglophone and Francophone AU Member States. The heads of NRAs and a senior competent person were contacted to complete self-administered questionnaires.

Results

The perceived benefits of model law implementation include enabling the establishment of an NRA, improving NRA governance and decision-making autonomy, strengthening the institutional framework, having streamlined activities which attract support from donors, as well as enabling harmonisation, reliance, and mutual recognition mechanisms. The factors enabling domestication and implementation are the presence of political will, leadership, and advocates, facilitators, or champions for the cause. Additionally, participation in regulatory harmonisation initiatives and the desire to have legal provisions at the national level that allow for regional harmonisation and international collaboration are enabling factors. The challenges encountered in the process of domesticating and implementing the model law are the lack of human and financial resources, competing priorities at the national level, overlapping roles of government institutions, and the process of amending/repealing laws being slow and lengthy.

Conclusion

This study has enabled an improved understanding of the AU Model Law process, the perceived benefits of its domestication, and the enabling factors for its adoption from the perspective of African NRAs. NRAs have also highlighted the challenges encountered in the process. Addressing these challenges will result in a harmonised legal environment for medicines regulation in Africa and be an important enabler for the effective operation of the African Medicines Agency.
Detection and quantification of viable but non-culturable Legionella pneumophila from water samples using flow cytometry-cell sorting and quantitative PCR
Authors: Nisar Muhammad Atif , Ross Kirstin E. , Brown Melissa H. , Bentham Richard , Best Giles , Whiley Harriet
Published: January 2023

Legionella pneumophila is a waterborne pathogen and, as the causative agent of Legionnaires’ disease, a significant public health concern. Exposure to environmental stresses, and disinfection treatments, promotes the formation of resistant and potentially infectious viable but non-culturable (VBNC) Legionella. The management of engineered water systems to prevent Legionnaires’ disease is hindered by the presence of VBNC Legionella that cannot be detected using the standard culture (ISO11731:2017-05) and quantitative polymerase reaction (ISO/TS12869:2019) methods. This study describes a novel method to quantify VBNC Legionella from environmental water samples using a “viability based flow cytometry-cell sorting and qPCR” (VFC + qPCR) assay. This protocol was then validated by quantifying the VBNC Legionella genomic load from hospital water samples. The VBNC cells were unable to be cultured on Buffered Charcoal Yeast Extract (BCYE) agar; however, their viability was confirmed through their ATP activity and ability to infect amoeba hosts. Subsequently, an assessment of the ISO11731:2017-05 pre-treatment procedure demonstrated that acid or heat treatment cause underestimation of alive Legionella population. Our results showed that these pre-treatment procedures induce culturable cells to enter a VBNC state. This may explain the observed insensitivity and lack of reproducibility often observed with the Legionella culture method. This study represents the first time that flow cytometry-cell sorting in conjunction with a qPCR assay has been used as a rapid and direct method to quantify VBNC Legionella from environmental sources. This will significantly improve future research evaluating Legionella risk management approaches for the control of Legionnaires’ disease.
New protocol for kinetic assay seeding ability recovery “KASAR” from formalin-fixed paraffin-embedded tissues
Authors: Hepker Monica , Clabaugh Griffin , Jin Huajun , Kanthasamy Anumantha G.
Published: January 2023

The real-time quaking-induced conversion (RT-QuIC) alpha-synuclein (aSyn) protein kinetic seeding assay has been very useful for detecting pathological aggregates in various synucleinopathies including Parkinson’s disease (PD). This biomarker assay relies on fresh frozen tissue to effectively seed and amplify aSyn aggregating protein. With vast repositories of formalin-fixed paraffin-embedded (FFPE) tissues, it is paramount to harness the power of kinetic assays to unlock the diagnostic potential of archived FFPE biospecimens. However, the major challenge posed by significantly reduced amplification of formalin-fixed tissues in the assay suggests that formalin fixation deterred monomer interaction with the sample seed and depressed subsequent protein aggregation. To overcome this challenge, we developed a kinetic assay seeding ability recovery (KASAR) protocol to maintain the integrity of the tissue and seeding protein. For this, we implemented a series of heating steps with the brain tissue suspended in a buffer composed of 500 mM tris-HCl (pH 7.5) and 0.02% SDS after the standard deparaffinization of the tissue sections. Initially, samples from seven human brain samples, including four samples from patients diagnosed with dementia with Lewy bodies (DLB) and three samples from healthy controls without DLB, were compared to fresh frozen samples under three different, but clinically common sample storage conditions: formalin-fixed, FFPE, and FFPE slices cut 5 µm thick. The KASAR protocol was able to recover seeding activity for all positive samples in all storage conditions. Next, 28 FFPE samples from the submandibular gland (SMG) of patients diagnosed with PD, incidental Lewy body disease (ILBD), or healthy controls were tested with 93% of results replicating when blinded. With samples of only a few milligrams, this protocol recovered the same quality of seeding in formalin-fixed tissue as fresh frozen tissue. Moving forward, protein aggregate kinetic assays, in conjunction with the KASAR protocol, can be used to understand and diagnose neurodegenerative diseases more comprehensively. Overall, our KASAR protocol unlocks and restores the seeding ability of formalin-fixed paraffin-embedded tissues for the amplification of biomarker protein aggregates in kinetic assays.
Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse
Authors: Fuller Margaret J. , Gupta Subhash C. , Fan Rong , Taugher-Hebl Rebecca J. , Wang Grace Z. , Andrys Noah R. R. , Bera Amal K. , Radley Jason J. , Wemmie John A.
Published: January 2023

Drugs of abuse produce rearrangements at glutamatergic synapses thought to contribute to drug-reinforced behaviors. Acid-Sensing Ion Channels (ASICs) have been suggested to oppose these effects, largely due to observations in mice lacking the ASIC1A subunit. However, the ASIC2A and ASIC2B subunits are known to interact with ASIC1A, and their potential roles in drugs of abuse have not yet been investigated. Therefore, we tested the effects of disrupting ASIC2 subunits in mice exposed to drugs of abuse. We found conditioned place preference (CPP) to both cocaine and morphine were increased in Asic2−/− mice, which is similar to what was observed in Asic1a−/− mice. Because nucleus accumbens core (NAcc) is an important site of ASIC1A action, we examined expression of ASIC2 subunits there. By western blot ASIC2A was readily detected in wild-type mice, while ASIC2B was not, suggesting ASIC2A is the predominant subunit in nucleus accumbens core. An adeno-associated virus vector (AAV) was used to drive recombinant ASIC2A expression in nucleus accumbens core of Asic2−/− mice, resulting in near normal protein levels. Moreover, recombinant ASIC2A integrated with endogenous ASIC1A subunits to form functional channels in medium spiny neurons (MSNs). However, unlike ASIC1A, region-restricted restoration of ASIC2A in nucleus accumbens core was not sufficient to affect cocaine or morphine conditioned place preference, suggesting effects of ASIC2 differ from those of ASIC1A. Supporting this contrast, we found that AMPA receptor subunit composition and the ratio of AMPA receptor-mediated current to NMDA receptor-mediated current (AMPAR/NMDAR) were normal in Asic2−/− mice and responded to cocaine withdrawal similarly to wild-type animals. However, disruption of ASIC2 significantly altered dendritic spine morphology, and these effects differed from those reported previously in mice lacking ASIC1A. We conclude that ASIC2 plays an important role in drug-reinforced behavior, and that its mechanisms of action may differ from ASIC1A.
Endothelial cell TRPA1 activity exacerbates cerebral hemorrhage during severe hypertension
Authors: Sullivan Michelle N. , Thakore Pratish , Krishnan Vivek , Alphonsa Sushma , Li Wencheng , Feng Earley Yumei , Earley Scott
Published: January 2023

Introduction: Hypoxia-induced dilation of cerebral arteries orchestrated by Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) cation channels on endothelial cells is neuroprotective during ischemic stroke, but it is unknown if the channel has a similar impact during hemorrhagic stroke. TRPA1 channels are endogenously activated by lipid peroxide metabolites generated by reactive oxygen species (ROS). Uncontrolled hypertension, a primary risk factor for the development of hemorrhagic stroke, is associated with increased ROS production and oxidative stress. Therefore, we hypothesized that TRPA1 channel activity is increased during hemorrhagic stroke.

Methods: Severe, chronic hypertension was induced in control (Trpa1fl/fl) and endothelial cell-specific TRPA1 knockout (Trpa1-ecKO) mice using a combination of chronic angiotensin II administration, a high-salt diet, and the addition of a nitric oxide synthase inhibitor to drinking water. Blood pressure was measured in awake, freely-moving mice using surgically placed radiotelemetry transmitters. TRPA1-dependent cerebral artery dilation was evaluated with pressure myography, and expression of TRPA1 and NADPH oxidase (NOX) isoforms in arteries from both groups was determined using PCR and Western blotting techniques. In addition, ROS generation capacity was evaluated using a lucigenin assay. Histology was performed to examine intracerebral hemorrhage lesion size and location.

Results: All animals became hypertensive, and a majority developed intracerebral hemorrhages or died of unknown causes. Baseline blood pressure and responses to the hypertensive stimulus did not differ between groups. Expression of TRPA1 in cerebral arteries from control mice was not altered after 28 days of treatment, but expression of three NOX isoforms and the capacity for ROS generation was increased in hypertensive animals. NOX-dependent activation of TRPA1 channels dilated cerebral arteries from hypertensive animals to a greater extent compared with controls. The number of intracerebral hemorrhage lesions in hypertensive animals did not differ between control and Trpa1-ecKO animals but were significantly smaller in Trpa1-ecKO mice. Morbidity and mortality did not differ between groups.

Discussion: We conclude that endothelial cell TRPA1 channel activity increases cerebral blood flow during hypertension resulting in increased extravasation of blood during intracerebral hemorrhage events; however, this effect does not impact overall survival. Our data suggest that blocking TRPA1 channels may not be helpful for treating hypertension-associated hemorrhagic stroke in a clinical setting.
High frequency deep brain stimulation can mitigate the acute effects of cocaine administration on tonic dopamine levels in the rat nucleus accumbens
Authors: Yuen Jason , Goyal Abhinav , Rusheen Aaron E. , Kouzani Abbas Z. , Berk Michael , Kim Jee Hyun , Tye Susannah J. , Blaha Charles D. , Bennet Kevin E. , Lee Kendall H. , Shin Hojin , Oh Yoonbae
Published: January 2023

Cocaine’s addictive properties stem from its capacity to increase tonic extracellular dopamine levels in the nucleus accumbens (NAc). The ventral tegmental area (VTA) is a principal source of NAc dopamine. To investigate how high frequency stimulation (HFS) of the rodent VTA or nucleus accumbens core (NAcc) modulates the acute effects of cocaine administration on NAcc tonic dopamine levels multiple-cyclic square wave voltammetry (M-CSWV) was used. VTA HFS alone decreased NAcc tonic dopamine levels by 42%. NAcc HFS alone resulted in an initial decrease in tonic dopamine levels followed by a return to baseline. VTA or NAcc HFS following cocaine administration prevented the cocaine-induced increase in NAcc tonic dopamine. The present results suggest a possible underlying mechanism of NAc deep brain stimulation (DBS) in the treatment of substance use disorders (SUDs) and the possibility of treating SUD by abolishing dopamine release elicited by cocaine and other drugs of abuse by DBS in VTA, although further studies with chronic addiction models are required to confirm that. Furthermore, we demonstrated the use of M-CSWV can reliably measure tonic dopamine levelsin vivowith both drug administration and DBS with minimal artifacts.
Thoracic dorsal root ganglion stimulation reduces acute myocardial ischemia induced ventricular arrhythmias
Authors: Kuwabara Yuki , Howard-Quijano Kimberly , Salavatian Siamak , Yamaguchi Tomoki , Saba Samir , Mahajan Aman
Published: January 2023

Background

Dorsal root ganglion stimulation (DRGS) may serve as a novel neuromodulation strategy to reduce cardiac sympathoexcitation and ventricular excitability.

Objective

In this pre-clinical study, we investigated the effectiveness of DRGS on reducing ventricular arrhythmias and modulating cardiac sympathetic hyperactivity caused by myocardial ischemia.

Methods

Twenty-three Yorkshire pigs were randomized to two groups, which was control LAD ischemia-reperfusion (CONTROL) or LAD ischemia-reperfusion + DRGS (DRGS) group. In the DRGS group (n = 10), high-frequency stimulation (1 kHz) at the second thoracic level (T2) was initiated 30 min before ischemia and continued throughout 1 h of ischemia and 2 h of reperfusion. Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were assessed, along with evaluation of cFos expression and apoptosis in the T2 spinal cord and DRG.

Results

DRGS decreased the magnitude of activation recovery interval (ARI) shortening in the ischemic region (CONTROL: −201 ± 9.8 ms, DRGS: −170 ± 9.4 ms, p = 0.0373) and decreased global dispersion of repolarization (DOR) at 30 min of myocardial ischemia (CONTROL: 9546 ± 763 ms2, DRGS: 6491 ± 636 ms2, p = 0.0076). DRGS also decreased ventricular arrhythmias (VAS–CONTROL: 8.9 ± 1.1, DRGS: 6.3 ± 1.0, p = 0.038). Immunohistochemistry studies showed that DRGS decreased % cFos with NeuN expression in the T2 spinal cord (p = 0.048) and the number of apoptotic cells in the DRG (p = 0.0084).

Conclusion

DRGS reduced the burden of myocardial ischemia-induced cardiac sympathoexcitation and has a potential to be a novel treatment option to reduce arrhythmogenesis.
The role of miR-128 in cancer development, prevention, drug resistance, and immunotherapy
Authors: Budi Hendrik Setia , Younus Laith A. , Lafta Methaq Hadi , Parveen Sameena , Mohammad Hawraa Jabbar , Al-qaim Zahraa Haleem , Jawad Mohammed Abed , Parra Rosario Mireya Romero , Mustafa Yasser Fakri , Alhachami Firas Rahi , Karampoor Sajad , Mirzaei Rasoul
Published: January 2023

A growing body of evidence has revealed that microRNA (miRNA) expression is dysregulated in cancer, and they can act as either oncogenes or suppressors under certain conditions. Furthermore, some studies have discovered that miRNAs play a role in cancer cell drug resistance by targeting drug-resistance-related genes or influencing genes involved in cell proliferation, cell cycle, and apoptosis. In this regard, the abnormal expression of miRNA-128 (miR-128) has been found in various human malignancies, and its verified target genes are essential in cancer-related processes, including apoptosis, cell propagation, and differentiation. This review will discuss the functions and processes of miR-128 in multiple cancer types. Furthermore, the possible involvement of miR-128 in cancer drug resistance and tumor immunotherapeutic will be addressed.
Challenges and future of HER2-positive gastric cancer therapy
Authors: Ma Chenzhe , Wang Xiao , Guo Jiwu , Yang Bo , Li Yumin
Published: January 2023

Gastric cancer is the fifth most common cancer worldwide, and the treatment of advanced gastric cancer has relatively little progress. With the continuous development of molecularly targeted therapy for tumors, it has been discovered that human epidermal growth factor receptor 2 (HER2) contributes to the poor prognosis and pathogenesis of various cancers. In order to treat HER2-positive advanced gastric cancer, Trastuzumab has emerged as the first first-line targeted medication used in conjunction with chemotherapy. The consequent trastuzumab resistance has become an important issue, and various new HER2-targeted gastric cancer drugs are emerging to address this challenge. This review’s primary concern is the drug mechanism of various HER2-positive gastric cancer targeted therapy and fresh techniques of detection.
Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors
Authors: Li Xingzhi , Chen Jie , Wang Xiaobo , Bai Tao , Lu Shaolong , Wei Tao , Tang Zhihong , Huang Chengwen , Zhang Bin , Liu Bowen , Li Lequn , Wu Feixiang
Published: January 2023

Purpose

To evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC).

Methods

Data on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4–6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS).

Results

Early tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076–51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p<0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171–0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099–0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039–0.554; p=0.005).

Conclusions

Early tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.
Sex hormone influence on female-biased autoimmune diseases hints at puberty as an important factor in pathogenesis
Authors: Yang Qianfan , Kennicott Kameron , Zhu Runqi , Kim Jooyong , Wakefield Hunter , Studener Katelyn , Liang Yun
Published: January 2023

The majority of autoimmune diseases affect more women than men, suggesting an important role for sex hormones in regulating immune response. Current research supports this idea, highlighting the importance of sex hormones in both immune and metabolic regulation. Puberty is characterized by drastic changes in sex hormone levels and metabolism. These pubertal changes may be what forms the gulf between men and women in sex bias towards autoimmunity. In this review, a current perspective on pubertal immunometabolic changes and their impact on the pathogenesis of a select group of autoimmune diseases is presented. SLE, RA, JIA, SS, and ATD were focused on in this review for their notable sex bias and prevalence. Due to both the scarcity of pubertal autoimmune data and the differences in mechanism or age-of-onset in juvenile analogues often beginning prior to pubertal changes, data on the connection between the specific adult autoimmune diseases and puberty often relies on sex hormone influence in pathogenesis and established sex differences in immunity that begin during puberty.
Childhood vaccination practices and associated factors among mothers/caregivers in Debre Tabor town, Northwest Ethiopia: A cross-sectional study
Authors: Simegn Wudneh , Diress Mengistie , Gela Yibeltal Yismaw , Belay Daniel Gashaneh , Ayelign Kibret Anteneh , Chilot Dagmawi , Sinamaw Deresse , Abdu Seid Mohammed , Andualem Amare Agmas , Anmut Bitew Desalegn , Eshetu Habitu Birhan , Mohammed Seid Abdulwase
Published: January 2023

Background

Incomplete immunization and non-immunization increase the risk of disease and death among children. This study aims to assess childhood vaccination practices and associated factors among mothers and caregivers in Debre Tabor town, Amhara region, Ethiopia.

Methods

A community-based cross-sectional study design was conducted between February 30 and April 30, 2022. The study participants were proportionally allocated to all six kebeles found in the town. A systematic random sampling technique was used to select the study participants. The collected data were checked and coded and then entered into EpiData Version 3.1 and exported into SPSS Version 26. The results were organized using frequency tables, graphs, and charts, and bivariate and multivariable logistic regression were used to test the association of covariates with childhood vaccination practices.

Result

Approximately 422 study mothers and caregivers participated in the study, with a response rate of 100%. The mean age was 30.63 years (11.74), which ranged from 18 to 58 years. More than half of the study participants (56.4%) expressed fears about the side effects of vaccination. A majority (78.4%) of the study participants availed of counseling services about vaccination, and 71.1% of them received regular antenatal care. This study found that approximately 280 [66.4%, 95% confidence interval (CI): 61.8–70.6] mothers/caregivers had a history of good childhood vaccination practices. The factors of the fear of side effects [adjusted odds ratio (AOR) = 3.34; 95% CI: 1.72–6.49], no workload (AOR = 6.08; 95% CI: 1.74–21.22), medium workload (AOR = 4.80; 95% CI: 1.57–14.71), being a mother of child/children (AOR = 2.55; 95% CI: 1.27–5.13), positive attitude (AOR = 2.25; 95% CI: 1.32–3.82), and sound knowledge (AOR = 3.88; 95% CI: 2.26–6.68) were significantly associated with childhood vaccination practices.

Conclusion

More than half of the study participants had a history of good childhood vaccination practices. However, the rate of such practices was low among mothers and caregivers. The fear of side effects, workload, motherhood, attitude, and knowledge were all factors associated with childhood vaccination practices. Awareness creation and a consideration of the workload of mothers would be helpful in dispelling fears and increasing the rate of good practices among mothers and caregivers.