bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Human Rights Treaties Change Economic Outcomes?
Authors: Gahagan Christopher
Published: August 2023

What are the economic effects of political treaties? International treaties like CEDAW have significant effects on women’s political and health outcomes. However, we know little about CEDAW’s effect on the informal economy. I argue that CEDAW ratification reduces informal economic activity by reducing barriers for women in the formal sector. Using non-parametric matching and difference-in-differences, I show ratification reduced informality by as much as 2.2% of GDP in certain regions. This work contributes to research in both international organizations and informal economies in two ways. First, this is the earliest work that explicitly links a human rights treaty to the size of a country’s informal economy. Thus, shedding light on the effects of international human rights treaties on economic outcomes and generating new insights and avenues for future research. Second, by addressing model dependence and relaxing implausible unconfoundedness assumptions, I draw stronger causal inference than previous research has allowed.
Transcranial magnetic stimulation: the road to clinical therapy for dystonia
Authors: Mulcahey Patrick J. , Peterchev Angel V. , Calakos Nicole , Bukhari-Parlakturk Noreen
Published: August 2023

Despite many research studies, transcranial magnetic stimulation (TMS) is not yet an FDA-approved clinical therapy for dystonia patients. This review describes the four major challenges that have historically hindered the clinical translation of TMS. The four challenges described are limited types of clinical trial designs, limited evidence on objective behavioral measures, variability in the TMS clinical response, and the extensive TMS parameters to optimize for clinical therapy. Progress has been made to diversify the types of clinical trial design available to clinical researchers, identify evidence-based objective behavioral measures, and reduce the variability in TMS clinical response. Future studies should identify objective behavioral measures for other dystonia subtypes and expand the optimal TMS stimulation parameters for clinical therapy. Our review highlights the key progress made to overcome these barriers and gaps that remain for TMS to develop into a long-lasting clinical therapy for dystonia patients.
Correlation between energy and displacement demands for infilled reinforced concrete frames
Authors: Angelucci G. , Mollaioli F. , Quaranta G.
Published: August 2023

Introduction: It is well recognized that masonry infills, even though they are non-structural elements, might offer a significant earthquake resistance and can prevent the collapse of relatively weak reinforced concrete structures.

Methods: The goal of this study is to investigate the energy dissipation contribution of masonry infills in reinforced concrete frames subjected to earthquake ground motion. To this purpose, a sticktype model with and without infills is considered for the evaluation of the inelastic response of representative frame structures. The infills are modeled by means of equivalent strut elements, which can only carry compressive loads. To investigate the influence of their mechanical characteristics, different idealized type of masonry infills are considered, and the weakest one is selected for the dynamic analyses based on the whole strong motions database.

Results: Wide ranges of structural systems and natural periods are taken into account, in such a way to establish response spectra for several significant parameters, including those based on energy. The results of the present investigation demonstrate that the infills significantly contribute to the energy dissipation capacity, provided that they are present in all stories.

Discussion: It is found that the contribution of masonry infills is of great importance in reducing both dissipation and displacement energy demands in frame elements. The effectiveness of their contribution depends on the characteristics of the ground motion, especially for non-seismic frames.
The perspectives of NETosis on the progression of obesity and obesity-related diseases: mechanisms and applications
Authors: Li Jinyu , Yin Lijia , Chen Siyi , Li Zelin , Ding Jiatong , Wu Jiaqiang , Yang Kangping , Xu Jixiong
Published: August 2023

Obesity is a disease commonly associated with urbanization and can also be characterized as a systemic, chronic metabolic condition resulting from an imbalance between energy intake and expenditure. The World Health Organization (WHO) has identified obesity as the most serious chronic disease that is increasingly prevalent in the world population. If left untreated, it can lead to dangerous health issues such as hypertension, hyperglycemia, hyperlipidemia, hyperuricemia, nonalcoholic steatohepatitis, atherosclerosis, and vulnerability to cardiovascular and cerebrovascular events. The specific mechanisms by which obesity affects the development of these diseases can be refined to the effect on immune cells. Existing studies have shown that the development of obesity and its associated diseases is closely related to the balance or lack thereof in the number and function of various immune cells, of which neutrophils are the most abundant immune cells in humans, infiltrating and accumulating in the adipose tissues of obese individuals, whereas NETosis, as a newly discovered type of neutrophil-related cell death, its role in the development of obesity and related diseases is increasingly emphasized. The article reviews the significant role that NETosis plays in the development of obesity and related diseases, such as diabetes and its complications. It discusses the epidemiology and negative impacts of obesity, explains the mechanisms of NETosis, and examines its potential as a targeted drug to treat obesity and associated ailments.
Sex-specific associations of γ-glutamyltransferase to HDL-cholesterol ratio and the incident risk of cardiovascular disease: three Korean longitudinal cohorts from different regions
Authors: Jung Dong Hyuk , Park Byoungjin , Ryu Ha Eun , Lee Yong Jae
Published: August 2023

Background

The combination of gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) (GGT/HDL-C) is a novel noninsulin-based marker for assessing the risk of nonalcoholic fatty liver disease and type 2 diabetes mellitus. However, whether the GGT/HDL-C ratio is related to the risk of incident cardiovascular disease (CVD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of GGT/HDL-C ratio on incident CVD risk in three large cohorts of Korean men and women.

Methods

Data were assessed from 27,643 participants without CVD from the Korean Genome and Epidemiology Study (KoGES), Health Risk Assessment Study (HERAS), and Korea Health Insurance Review and Assessment (HIRA) (HERAS-HIRA) datasets. The participants were divided into four groups according to the GGT/HDL-C quartiles. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD using multivariate Cox proportional-hazard regression models over a 50-month period following the baseline survey.

Results

During the follow-up period, 949 patients (3.4%; 529 men and 420 women) developed CVD. The HRs of CVD for GGT/HDL-C quartiles 2-4 were 1.36 (95% CI, 0.91–2.02), 1.54 (95% CI, 1.05–2.26), and 1.66 (95% CI, 1.12–2.47) after adjusting for metabolic parameters in women, but GGT/HDL-C did not show a trend toward increases in incident CVD in men. Regional discrepancies were evident in the results; the increase in HR in the metropolitan hospital cohort was more pronounced than that in the urban cohort, and the risk was not increased in the rural cohort.

Conclusion

GGT/HDL-C ratio may be a useful predictive marker for CVD in women. Furthermore, the prevalence of CVD was strongly correlated with the GGT/HDL-C ratio in metropolitan areas, and this correlation was more significant than that observed with GGT or HDL-C in isolation.
The time-varying effects of economic policy uncertainty and low-carbon economic transition on enterprise innovation in China
Authors: Zhang Lin , Shao Chonglin , Wang Jia
Published: August 2023

With the increasing concern of all sectors of society about climate change, enterprises have become an important subject to undertake environmental protection. At the same time, enterprises have to seek survival and development under the background of economic policy uncertainty. Therefore, companies need to not only fulfill their environmental responsibilities but also find ways to respond to changes in economic policies through innovation. In the study, a three-variable time-varying vector autoregressive (TVP-VAR) model with stochastic volatility was used to investigate the nonlinear dynamic effects of economic policy uncertainty and low-carbon economic transition on enterprise innovation in China. It is found that the influence of economic policy uncertainty on enterprise innovation is time-varying and asymmetrical, especially with the 2008 financial crisis as the turning point. After the financial crisis, the positive impact of economic policy uncertainty on enterprises has been weakening, and in 2015, the positive impact turned into a negative impact. In general, economic policy uncertainty is not conducive to the transition to low-carbon economic transition, and with the outbreak of the financial crisis in 2008, the negative impact reached a negative peak. The low-carbon economic transition has a significant crowding-out effect on enterprise innovation, while enterprise innovation has a significant spillover effect on low-carbon economic transition. The conclusion can provide the scientific basis for enterprises to adapt to the change in the economic environment to complete low-carbon economic transition and formulate innovation strategies, which is conducive to the sustainable development of the ecological environment and economic society.
Discussing energy volatility and policy in the aftermath of the Russia–Ukraine conflict
Authors: Enescu Adrian-Gabriel , Szeles Monica Răileanu
Published: August 2023

The ongoing Russo–Ukrainian War has highly affected energy markets in the EU and worldwide, with different EU- and country-level emergency policy measures being advanced to tackle high energy prices. Despite the progress in green energy initiatives and the race toward climate neutrality by 2050, high energy prices are a matter of concern for all EU countries in the short-to-medium term. The current study investigates the energy price volatility in the aftermath of the Russia–Ukraine conflict, which is of high interest for designing effective government measures (such as monetary and energy policies) addressing the consequent changes occurring in employment, economic activity, commodity and food prices, and, ultimately, sustainable development. For the empirical analysis, we employed generalized autoregressive conditional heteroskedasticity models to capture the volatility of the following energy commodities: Brent crude oil, TTF natural gas, and UK natural gas. The empirical results reveal an elevated degree of persistence of the volatility, namely, that the generalized autoregressive conditional heteroskedasticity term has a slow decay and pronounced fluctuations for all the energy products. The vulnerability of the EU’s energy policy to geopolitical factors is highlighted, especially for gas, which could be due to its dependence on Russian imports. Moreover, the sanctions imposed by the EU on Russia, namely the sixth package of sanctions, have a minimal immediate effect on stabilizing energy returns. The study offers several policy recommendations to improve the resilience of the EU’s energy sector.
ERFVII transcription factors and their role in the adaptation to hypoxia in Arabidopsis and crops
Authors: Loreti Elena , Perata Pierdomenico
Published: August 2023

In this review, we focus on ethylene transcription factors (ERFs), which are a crucial family of transcription factors that regulate plant development and stress responses. ERFVII transcription factors have been identified and studied in several crop species, including rice, wheat, maize, barley, and soybean. These transcription factors are known to be involved in regulating the plant’s response to low oxygen stress—hypoxia and could thus improve crop yields under suboptimal growing conditions. In rice (Oryza sativa) several ERFVII genes have been identified and characterized, including SUBMERGENCE 1A (SUB1A), which enables rice to tolerate submergence. The SUB1A gene was used in the development of SUB1 rice varieties, which are now widely grown in flood-prone areas and have been shown to improve yields and farmer livelihoods. The oxygen sensor in plants was discovered using the model plant Arabidopsis. The mechanism is based on the destabilization of ERFVII protein via the N-degron pathway under aerobic conditions. During hypoxia, the stabilized ERFVIIs translocate to the nucleus where they activate the transcription of hypoxia-responsive genes (HRGs). In summary, the identification and characterization of ERFVII transcription factors and their mechanism of action could lead to the development of new crop varieties with improved tolerance to low oxygen stress, which could have important implications for global food security.
Integration of transcriptomics and metabolomics reveals the responses of the maternal circulation and maternal-fetal interface to LPS-induced preterm birth in mice
Authors: Cao Xianling , Zhou Xuanyou , Chen Songchang , Xu Chenming
Published: August 2023

Background

Term birth (TB) and preterm birth (PTB) are characterized by uterine contractions, rupture of the chorioamniotic membrane, decidual activation, and other physiological and pathological changes. In this study, we hypothesize that inflammation can cause changes in mRNA expression and metabolic stability in the placenta, decidua, chorioamniotic membrane, uterus and peripheral blood, ultimately leading to PTB.

Methods

To comprehensively assess the effects of inflammation on mRNA expression and metabolite production in different tissues of pregnancy, we used a mouse PTB model by intraperitoneally injecting lipopolysaccharide (LPS) and integrated transcriptomics and metabolomics studies.

Results

Our analysis identified 152 common differentially expressed genes (DEGs) and 8 common differentially expressed metabolites (DEMs) in the placenta, decidua, chorioamniotic membrane, uterus, and peripheral blood, or placenta and uterus after LPS injection, respectively. Our bioinformatics analysis revealed significant enrichment of the NOD-like receptor signaling pathway (mmu04621), TNF signaling pathway (mmu04668), IL-17 signaling pathway (mmu04657), and NF-kappa B signaling pathway in the transcriptomics of different tissues, and Hormone synthesis, Lysosome, NOD-like receptor signaling pathway, and Protein digest and absorption pathway in metabolomics. Moreover, we found that several upstream regulators and master regulators, including STAT1, STAT3, and NFKB1, were altered after exposure to inflammation in the different tissues. Interaction network analysis of transcriptomics and metabolomics DEGs and DEMs also revealed functional changes in mice intraperitoneally injected with LPS.

Conclusions

Overall, our study identified significant and biologically relevant alterations in the placenta, decidua, chorioamniotic membrane, uterus, peripheral blood transcriptome and the placenta and uterus metabolome in mice exposed to LPS. Thus, a comprehensive analysis of different pregnancy tissues in mice intraperitoneally injected with LPS by combining transcriptomics and metabolomics may help to systematically understand the local and systemic changes associated with PTB caused by inflammation.
Incorporating inflammatory biomarkers into a prognostic risk score in patients with non-ischemic heart failure: a machine learning approach
Authors: Feng Jiayu , Zhao Xuemei , Huang Boping , Huang Liyan , Wu Yihang , Wang Jing , Guan Jingyuan , Li Xinqing , Zhang Yuhui , Zhang Jian
Published: August 2023

Objectives

Inflammation is involved in the mechanisms of non-ischemic heart failure (NIHF). We aimed to investigate the prognostic value of 21 inflammatory biomarkers and construct a biomarker risk score to improve risk prediction for patients with NIHF.

Methods

Patients diagnosed with NIHF without infection during hospitalization were included. The primary outcome was defined as all-cause mortality and heart transplantations. We used elastic net Cox regression with cross-validation to select inflammatory biomarkers and construct the best biomarker risk score model. Discrimination, calibration, and reclassification were evaluated to assess the predictive value of the biomarker risk score.

Results

Of 1,250 patients included (median age, 53 years, 31.9% women), 436 patients (34.9%) experienced the primary outcome during a median of 2.8 years of follow-up. The final biomarker risk score included high-sensitivity C-reactive protein-to-albumin ratio (CAR) and red blood cell distribution width-standard deviation (RDW-SD), both of which were 100% selected in 1,000 times cross-validation folds. Incorporating the biomarker risk score into the best basic model improved the discrimination (ΔC-index = 0.012, 95% CI 0.003–0.018) and reclassification (IDI, 2.3%, 95% CI 0.7%–4.9%; NRI, 17.3% 95% CI 6.4%–32.3%) in risk identification. In the cross-validation sets, the mean time-dependent AUC ranged from 0.670 to 0.724 for the biomarker risk score and 0.705 to 0.804 for the basic model with a biomarker risk score, from 1 to 8 years. In multivariable Cox regression, the biomarker risk score was independently associated with the outcome in patients with NIHF (HR 1.76, 95% CI 1.49–2.08, p < 0.001, per 1 score increase).

Conclusions

An inflammatory biomarker-derived risk score significantly improved prognosis prediction and risk stratification, providing potential individualized therapeutic targets for NIHF patients.
Whole exome sequencing of well-differentiated liposarcoma and dedifferentiated liposarcoma in older woman: a case report
Authors: Zhao Zidan , Chen Xiaoyan , Xu Jie , Shi Yuntao , Mak Tsz Kin , Huo Mingyu , Zhang Changhua
Published: August 2023

Background

Common kinds of soft tissue sarcomas (STS) include well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS). In this case, we present a comprehensive clinical profile of a patient who underwent multiple recurrences during the progression from WDLPS to DDLPS.

Case presentation

A 62-year-old Asian female underwent retroperitoneal resection of a large tumor 11 years ago, the initial pathology revealed a fibrolipoma-like lesion. Over the next six years, the patient underwent three resections for recurrence of abdominal tumors. Postoperative histology shows mature adipose tissue with scattered “adipoblast”-like cells with moderate-to-severe heterogeneous spindle cells, pleomorphic cells, or tumor giant cells. Immunohistochemistry (IHC) demonstrated positive staining for MDM2 and CDK4, confirming that the abdominal tumor was WDLPS and gradually progressing to DDLPS. Post-operative targeted sequencing and IHC confirmed the POC1B::ROS1 fusion gene in DDLPS. Whole-exome sequencing (WES) revealed that WDLPS and DDLPS shared similar somatic mutations and copy number variations (CNVs), whereas DDLPS had more mutated genes and a higher and more concentrated amplification of the chromosome 12q region. Furthermore, somatic mutations in DDLPS were significantly reduced after treatment with CDK4 inhibitors, while CNVs remained elevated.

Conclusion

Due to the high likelihood of recurrence of liposarcoma, various effective treatments should be taken into consideration even if surgery is the primary treatment for recurrent liposarcoma. To effectively control the course of the disease following surgery, combination targeted therapy may be a viable alternative to chemotherapy and radiotherapy in the treatment of liposarcoma.
The microbiota of Mozzarella di Bufala Campana PDO cheese: a study across the manufacturing process
Authors: Levante Alessia , Bertani Gaia , Marrella Martina , Mucchetti Germano , Bernini Valentina , Lazzi Camilla , Neviani Erasmo
Published: August 2023

Introduction

Mozzarella di Bufala Campana PDO cheese (MBC) is a globally esteemed Italian cheese. The traditional cheesemaking process of MBC relies on natural whey starter culture, water buffalo's milk, and the local agroecosystem.

Methods

In this study, the microbial ecology of intermediate samples of MBC production, coming from two dairies with slightly different cheesemaking technology (dairy M large producer, and dairy C medium-small), was investigated using 16S rRNA amplicon sequencing. This research aimed to provide insights into the dynamics of microbial consortia involved in various cheesemaking steps.

Results and discussion

All samples, except for raw buffalo milk, exhibited a core microbiome predominantly composed of Streptococcus spp. and Lactobacillus spp., albeit with different ratios between the two genera across the two MBC producers. Notably, the microbiota of the brine from both dairies, analyzed using 16S amplicon sequencing for the first time, was dominated by the Lactobacillus and Streptococcus genera, while only dairy C showed the presence of minor genera such as Pediococcus and Lentilactobacillus. Intriguingly, the final mozzarella samples from both producers displayed an inversion in the dominance of Lactobacillus spp. over Streptococcus spp. in the microbiota compared to curd samples, possibly attributable to the alleviation of thermal stress following the curd stretching step. In conclusion, the different samples from the two production facilities did not exhibit significant differences in terms of the species involved in MBC cheesemaking. This finding confirms that the key role in the MBC cheesemaking process lies with a small-sized microbiome primarily composed of Streptococcus and Lactobacillus spp.
Impact of the carbon flux regulator protein pirC on ethanol production in engineered cyanobacteria
Authors: Böhm Julien , Kauss Karsten , Michl Klaudia , Engelhardt Lisa , Brouwer Eva-Maria , Hagemann Martin
Published: August 2023

Future sustainable energy production can be achieved using mass cultures of photoautotrophic microorganisms such as cyanobacteria, which are engineered to synthesize valuable products directly from CO2 and sunlight. For example, strains of the model organism Synechocystis sp. PCC 6803 have been generated to produce ethanol. Here, we performed a study to prove the hypothesis that carbon flux in the direction of pyruvate is one bottleneck to achieve high ethanol titers in cyanobacteria. Ethanol-producing strains of the cyanobacterium Synechocystis sp. PCC 6803 were generated that bear mutation in the gene pirC aiming to increase carbon flux towards pyruvate. The strains were cultivated at different nitrogen or carbon conditions and the ethanol production was analysed. Generally, a clear correlation between growth rate and ethanol production was found. The mutation of pirC, however, had only a positive impact on ethanol titers under nitrogen depletion. The increase in ethanol was accompanied by elevated pyruvate and lowered glycogen levels indicating that the absence of pirC indeed increased carbon partitioning towards lower glycolysis. Metabolome analysis revealed that this change in carbon flow had also a marked impact on the overall primary metabolism in Synechocystis sp. PCC 6803. Deletion of pirC improved ethanol production under specific conditions supporting the notion that a better understanding of regulatory mechanisms involved in cyanobacterial carbon partitioning is needed to engineer more productive cyanobacterial strains.
Neuromuscular recovery from botulism involves multiple forms of compensatory plasticity
Authors: Machamer James B. , Vazquez-Cintron Edwin J. , Stenslik Mallory J. , Pagarigan Kathleen T. , Bradford Aaron B. , Ondeck Celinia A. , McNutt Patrick M.
Published: August 2023

Introduction

Botulinum neurotoxin (BoNT) causes neuroparalytic disease and death by blocking neuromuscular transmission. There are no specific therapies for clinical botulism and the only treatment option is supportive care until neuromuscular function spontaneously recovers, which can take weeks or months after exposure. The highly specialized neuromuscular junction (NMJ) between phrenic motor neurons and diaphragm muscle fibers is the main clinical target of BoNT. Due to the difficulty in eliciting respiratory paralysis without a high mortality rate, few studies have characterized the neurophysiological mechanisms involved in diaphragm recovery from intoxication. Here, we develop a mouse model of botulism that involves partial paralysis of respiratory muscles with low mortality rates, allowing for longitudinal analysis of recovery.

Methods and results

Mice challenged by systemic administration of 0.7 LD50 BoNT/A developed physiological signs of botulism, such as respiratory depression and reduced voluntary running activity, that persisted for an average of 8–12 d. Studies in isolated hemidiaphragm preparations from intoxicated mice revealed profound reductions in nerve-elicited, tetanic and twitch muscle contraction strengths that recovered to baseline 21 d after intoxication. Despite apparent functional recovery, neurophysiological parameters remained depressed for 28 d, including end plate potential (EPP) amplitude, EPP success rate, quantal content (QC), and miniature EPP (mEPP) frequency. However, QC recovered more quickly than mEPP frequency, which could explain the discrepancy between muscle function studies and neurophysiological recordings. Hypothesizing that differential modulation of voltage-gated calcium channels (VGCC) contributed to the uncoupling of QC from mEPP frequency, pharmacological inhibition studies were used to study the contributions of different VGCCs to neurophysiological function. We found that N-type VGCC and P/Q-type VGCC partially restored QC but not mEPP frequency during recovery from paralysis, potentially explaining the accelerated recovery of evoked release versus spontaneous release. We identified additional changes that presumably compensate for reduced acetylcholine release during recovery, including increased depolarization of muscle fiber resting membrane potential and increased quantal size.

Discussion

In addition to identifying multiple forms of compensatory plasticity that occur in response to reduced NMJ function, it is expected that insights into the molecular mechanisms involved in recovery from neuromuscular paralysis will support new host-targeted treatments for multiple neuromuscular diseases.
Molecular characterization of MAP9 in the photoreceptor sensory cilia as a modifier in canine RPGRIP1-associated cone-rod dystrophy
Authors: Takahashi Kei , Kwok Jennifer C. , Sato Yu , Aguirre Gustavo D. , Miyadera Keiko
Published: August 2023

Photoreceptors possess a highly specialized primary cilium containing expanded ciliary membrane discs called the outer segment. The photoreceptor cilium is essential for the maintenance of the outer segment, and pathogenic variants in more than 50 cilia-related genes have been identified as causing non-syndromic inherited retinal diseases in patients. The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) is a structural protein localized to the photoreceptor cilium and biallelic RPGRIP1 variants have been associated with non-syndromic human inherited retinal diseases. In a canine cone-rod dystrophy model, a naturally occurring 44-bp exonic insertion in RPGRIP1 (RPGRIP1ins44/ins44) is the primary disease locus while an additional homozygous variant in MAP9 (microtubule associated protein 9) (MAP9aff/aff) acts as a modifier associated with early disease onset. MAP9 was originally identified as a microtubule-binding protein stabilizing microtubule structure during both mitosis and interphase in human cell lines. However, the roles of MAP9 in primary cilia, including photoreceptor neurosensory cilia, have not been well understood. Hence, we characterized the pathogenic phenotypes associated with homozygous MAP9 variant, and investigated the molecular function of MAP9 in primary cilia using the RPGRIP1-associated oligogenic canine cone-rod dystrophy model as well as cultured cells. Both functionally and structurally, the RPGRIP1ins44/ins44MAP9aff/aff retina exhibited progressive cone photoreceptor degeneration starting earlier than the retina affected by RPGRIP1ins44/ins44 alone. Based on immunostaining of canine retinal sections and cultured cells, we found that MAP9 is prominently localized in the basal body of primary cilia and played an important role in maintaining the structure of ciliary microtubule axoneme. These findings suggest that the affected MAP9, together with mutant RPGRIP1, is deprived of critical roles in cilia organization and maintenance resulting in altered cilia structure and function giving rise to early onset and accelerated disease progression in the RPGRIP1ins44/ins44MAP9aff/aff double homozygote cone-rod dystrophy canine model.
A clearing in the objectivity of aesthetics?
Authors: Lee Daniel H. , Chikazoe Junichi
Published: August 2023

As subjective experiences go, beauty matters. Although aesthetics has long been a topic of study, research in this area has not resulted in a level of interest and progress commensurate with its import. Here, we briefly discuss two recent advances, one computational and one neuroscientific, and their pertinence to aesthetic processing. First, we hypothesize that deep neural networks provide the capacity to model representations essential to aesthetic experiences. Second, we highlight the principal gradient as an axis of information processing that is potentially key to examining where and how aesthetic processing takes place in the brain. In concert with established neuroimaging tools, we suggest that these advances may cultivate a new frontier in the understanding of our aesthetic experiences.
Decision trees to evaluate the risk of developing multiple sclerosis
Authors: Pasella Manuela , Pisano Fabio , Cannas Barbara , Fanni Alessandra , Cocco Eleonora , Frau Jessica , Lai Francesco , Mocci Stefano , Littera Roberto , Giglio Sabrina Rita
Published: August 2023

Introduction

Multiple sclerosis (MS) is a persistent neurological condition impacting the central nervous system (CNS). The precise cause of multiple sclerosis is still uncertain; however, it is thought to arise from a blend of genetic and environmental factors. MS diagnosis includes assessing medical history, conducting neurological exams, performing magnetic resonance imaging (MRI) scans, and analyzing cerebrospinal fluid. While there is currently no cure for MS, numerous treatments exist to address symptoms, decelerate disease progression, and enhance the quality of life for individuals with MS.

Methods

This paper introduces a novel machine learning (ML) algorithm utilizing decision trees to address a key objective: creating a predictive tool for assessing the likelihood of MS development. It achieves this by combining prevalent demographic risk factors, specifically gender, with crucial immunogenetic risk markers, such as the alleles responsible for human leukocyte antigen (HLA) class I molecules and the killer immunoglobulin-like receptors (KIR) genes responsible for natural killer lymphocyte receptors.

Results

The study included 619 healthy controls and 299 patients affected by MS, all of whom originated from Sardinia. The gender feature has been disregarded due to its substantial bias in influencing the classification outcomes. By solely considering immunogenetic risk markers, the algorithm demonstrates an ability to accurately identify 73.24% of MS patients and 66.07% of individuals without the disease.

Discussion

Given its notable performance, this system has the potential to support clinicians in monitoring the relatives of MS patients and identifying individuals who are at an increased risk of developing the disease.
Non-invasive stimulation reveals ventromedial prefrontal cortex function in reward prediction and reward processing
Authors: Rehbein Maimu Alissa , Kroker Thomas , Winker Constantin , Ziehfreund Lena , Reschke Anna , Bölte Jens , Wyczesany Miroslaw , Roesmann Kati , Wessing Ida , Junghöfer Markus
Published: August 2023

Introduction

Studies suggest an involvement of the ventromedial prefrontal cortex (vmPFC) in reward prediction and processing, with reward-based learning relying on neural activity in response to unpredicted rewards or non-rewards (reward prediction error, RPE). Here, we investigated the causal role of the vmPFC in reward prediction, processing, and RPE signaling by transiently modulating vmPFC excitability using transcranial Direct Current Stimulation (tDCS).

Methods

Participants received excitatory or inhibitory tDCS of the vmPFC before completing a gambling task, in which cues signaled varying reward probabilities and symbols provided feedback on monetary gain or loss. We collected self-reported and evaluative data on reward prediction and processing. In addition, cue-locked and feedback-locked neural activity via magnetoencephalography (MEG) and pupil diameter using eye-tracking were recorded.

Results

Regarding reward prediction (cue-locked analysis), vmPFC excitation (versus inhibition) resulted in increased prefrontal activation preceding loss predictions, increased pupil dilations, and tentatively more optimistic reward predictions. Regarding reward processing (feedback-locked analysis), vmPFC excitation (versus inhibition) resulted in increased pleasantness, increased vmPFC activation, especially for unpredicted gains (i.e., gain RPEs), decreased perseveration in choice behavior after negative feedback, and increased pupil dilations.

Discussion

Our results support the pivotal role of the vmPFC in reward prediction and processing. Furthermore, they suggest that transient vmPFC excitation via tDCS induces a positive bias into the reward system that leads to enhanced anticipation and appraisal of positive outcomes and improves reward-based learning, as indicated by greater behavioral flexibility after losses and unpredicted outcomes, which can be seen as an improved reaction to the received feedback.
Effects of anthocyanin supplementation on blood lipid levels: a systematic review and meta-analysis
Authors: Jang Hwan-Hee , Hwang In-Guk , Lee Young-Min
Published: August 2023

Introduction

Dyslipidemia is a major cardiovascular disease risk factor associated with increased mortality. The intake of plant food-derived bioactive compounds is associated with beneficial cardiovascular effects, including decreased blood lipid levels and cardiovascular risk. We aimed to evaluate the effects of anthocyanin intake on blood lipid levels by analyzing relevant randomized controlled trials.

Methods

We searched the PubMed and Embase databases using the “Patient/Population, Intervention, Comparison, and Outcomes” format to determine whether anthocyanin supplementation intervention affected blood lipid levels compared with placebo supplementation in human participants.

Results

A total of 41 studies with 2,788 participants were included in the meta-analysis. Anthocyanin supplementation significantly reduced triglyceride [standardized mean difference (SMD) = −0.10; 95% confidence interval [CI], −0.18, −0.01) and low-density lipoprotein-cholesterol (SMD = −0.16; 95% CI −0.26, −0.07) levels and increased high-density lipoprotein-cholesterol levels (SMD = 0.42; 95% CI 0.20, 0.65).

Discussion

Anthocyanin supplementation significantly improved blood lipid component levels in the included studies. Larger, well-designed clinical trials are needed to further investigate the effects of anthocyanin intake on blood lipid levels and the safety of anthocyanin supplementation for treating dyslipidemia.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257087, identifier: CRD42021257087.
Priorities, barriers, and facilitators for nutrition-related care for autistic children: a qualitative study comparing interdisciplinary health professional and parent perspectives
Authors: Blaine Rachel E. , Blaine Kevin P. , Cheng Katie , Banuelos Cynthia , Leal Aaron
Published: August 2023

Introduction

Children with autism spectrum disorder often face nutrition-related challenges, such as food selectivity, gastrointestinal issues, overweight and obesity, and inadequate nutrient intake. However, the role of routine nutrition-related screening or care by interdisciplinary health professionals is not well understood. This study aimed to compare the beliefs of health professionals with those of parents of autistic children regarding high-priority nutrition-related challenges, barriers and facilitators to care, and desired education and resources related to nutrition for autistic children.

Participants

Interdisciplinary health professionals (n = 25) (i.e., pediatricians, occupational therapists, speech-language pathologists, board certified behavior analysts, registered dietitians) and parents of autistic children (n = 22).

Methods

The study used semi-structured phone interviews, which were recorded, transcribed, verified, and double-coded using the Framework Method.

Results

Thematic analysis of transcripts revealed that while health professionals and parents of autistic children shared some perspectives on nutrition-related challenges and care, they also had distinct viewpoints. Parents emphasized the importance of addressing food selectivity, behavioral eating challenges, sensory issues, and sleep disturbances affecting appetite. Both groups acknowledged the need for tailored support, access to an interdisciplinary care team, and reasonable expectations. Some health professionals perceived parents as lacking motivation or the ability to make changes. In contrast, many parents felt that health professionals lacked the knowledge and motivation to take nutrition or growth concerns seriously. Health professionals acknowledged that their lack of knowledge or capacity to provide nutrition education or referrals was a common barrier to care, particularly given limited community resources.

Discussion

Health professionals who serve autistic children are motivated to address nutrition-related challenges but lack resources related to nutrition. To promote better health outcomes for autistic children, professionals should identify and support parent motivations around nutrition-related care. Both groups expressed interest in accessing autism-specific resources for education, referral, and screening guidance. Future research could explore the development of healthcare training models that improve the competency of health professionals in providing nutrition care and referral for autistic children.
Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells
Authors: Li Liangge , Geng Jiafeng , Yu Wen , Zhou Feifei , Zheng Zhihuan , Fu Kaiyue , Kong Junjie , Feng Xiujing
Published: August 2023

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.
Aminooxy acetic acid suppresses Th17-mediated psoriasis-like skin inflammation by inhibiting serine metabolism
Authors: Lee Jong Yeong , Lee Ji-Hyun , Lim Hyo Jung , Kim Eonho , Kim Dae-Ki , Choi Jin Kyeong
Published: August 2023

Background: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment.

Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes.

Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments.

Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis.
Contrasting patterns of community-weighted mean traits and functional diversity in driving grassland productivity changes under N and P addition
Authors: Yang Yuting , Chen Zhifei , Xu Bingcheng , Ghanizadeh Hossein , Li Wei , Ding Chengqin , Zhou Ronglei , Wen Zhongming
Published: August 2023

Fertilization could influence ecosystem structure and functioning through species turnover (ST) and intraspecific trait variation (ITV), especially in nutrient limited ecosystems. To quantify the relative importance of ITV and ST in driving community functional structure and productivity changes under nitrogen (N) and phosphorous (P) addition in semiarid grasslands. In this regard, we conducted a four-year fertilizer addition experiment in a semiarid grassland on the Loess Plateau, China. We examined how fertilization affects species-level leaf and root trait plasticity to evaluate the ability of plants to manifest different levels of traits in response to different N and P addition. Also, we assessed how ITV or ST dominated community-weighted mean (CWM) traits and functional diversity variations and evaluated their effects on grassland productivity. The results showed that the patterns of plasticity varied greatly among different plant species, and leaf and root traits showed coordinated variations following fertilization. Increasing the level of N and P increased CWM_specific leaf area (CWM_SLA), CWM_leaf N concentration (CWM_LN) and CWM_maximum plant height (CWM_Hmax) and ITV predominate these CWM traits variations. As a results, increased CWM_Hmax, CWM_LN and CWM_SLA positively influenced grassland productivity. In contrast, functional divergence decreased with increasing N and P and showed negative relationships with grassland productivity. Our results emphasized that CWM traits and functional diversity contrastingly drive changes in grassland productivity under N and P addition.
Integrative transcriptome and metabolome analysis reveals the mechanisms of light-induced pigmentation in purple waxy maize
Authors: Lu Yuan , Yu Yao , Xuan Yanfang , Kari Ayiguli , Yang Caixia , Wang Chenyu , Zhang Chao , Gu Wei , Wang Hui , Hu Yingxiong , Sun Pingdong , Guan Yuan , Si Wenshuai , Bai Bing , Zhang Xuecai , Xu Yunbi , Prasanna Boddupalli M. , Shi Biao , Zheng Hongjian
Published: August 2023

Introduction

Waxy maize, mainly consumed at the immature stage, is a staple and vegetable food in Asia. The pigmentation in the kernel of purple waxy maize enhances its nutritional and market values. Light, a critical environmental factor, affects anthocyanin biosynthesis and results in pigmentation in different parts of plants, including in the kernel. SWL502 is a light-sensitive waxy maize inbred line with purple kernel color, but the regulatory mechanism of pigmentation in the kernel resulting in purple color is still unknown.

Methods

In this study, cyanidin, peonidin, and pelargonidin were identified as the main anthocyanin components in SWL502, evaluated by the ultra-performance liquid chromatography (UPLC) method. Investigation of pigment accumulation in the kernel of SWL502 was performed at 12, 17, and 22 days after pollination (DAP) under both dark and light treatment conditions via transcriptome and metabolome analyses.

Results

Dark treatment affected genes and metabolites associated with metabolic pathways of amino acid, carbohydrate, lipid, and galactose, biosynthesis of phenylpropanoid and terpenoid backbone, and ABC transporters. The expression of anthocyanin biosynthesis genes, such as 4CL2, CHS, F3H, and UGT, was reduced under dark treatment. Dynamic changes were identified in genes and metabolites by time-series analysis. The genes and metabolites involved in photosynthesis and purine metabolism were altered in light treatment, and the expression of genes and metabolites associated with carotenoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, and plant hormone signal transduction pathway were induced by dark treatment. Light treatment increased the expression level of major transcription factors such as LRL1, myc7, bHLH125, PIF1, BH093, PIL5, MYBS1, and BH074 in purple waxy maize kernels, while dark treatment greatly promoted the expression level of transcription factors RVE6, MYB4, MY1R1, and MYB145.

Discussion

This study is the first report to investigate the effects of light on waxy maize kernel pigmentation and the underlying mechanism at both transcriptome and metabolome levels, and the results from this study are valuable for future research to better understand the effects of light on the regulation of plant growth.