bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of genotoxic impurities in extracted nicotine vs. synthetic nicotine
Authors: Nisathar Ayesha , Chen Hui , Lei Xiaoli , Zeng Zeyu , Chen Jia
Published: October 2024

Nicotine is a chiral alkaloid; nitrogen-containing organic compound that occurs naturally. (S)-nicotine is extracted from Tobacco plants and used as the key addictive ingredient in many smoking products. Synthetic nicotine has gained the interest of many smoking product manufacturers over the last few decades due to the ease and low cost of manufacturing. Another claimed advantage of synthetic nicotine is the absence of genotoxic impurities that form during the extraction process of nicotine. These impurities are other plant alkaloids, phenolic compounds, and heavy metals. Additionally, the U. S. FDA has implemented new regulations on the quality control of synthetic nicotine. However, only a very few research articles have been published on assessing the complete impurity profile of synthetic nicotine. Therefore, the need to know the composition difference between tobacco-extracted nicotine vs. synthetic nicotine is highly necessary. In this research study, the impurity profile of thirteen different lots of synthetic nicotine was compared with fourteen lots of nicotine extracted from plants using in-house analytical methods. First, the samples were tested for other alkaloids and phenols by reversed-phase High-Performance Liquid Chromatography (HPLC). Second, the chiral purity was analyzed by normal phase HPLC. Third, lead and arsenic content were tested by atomic absorption and fluorescence spectrometry. Fourth, nicotine-specific nitrosamines were tested by LC-MS. The reversed phase HPLC data suggested similar quantities of total impurities in both synthetic and tobacco-extracted nicotine (0.1%). However, synthetic nicotine lacks some impurities such as cotinine, nornicotine, and nicotine-N-oxide. Additionally, the synthetic nicotine lots used in this study have high enantiomeric purity similar to the tobacco-extracted nicotine.
Mycobacterium tuberculosis combine with EBV infection in severe adult meningoencephalitis: a rare case reports and literature review
Authors: Wang Jian , Li Mengjiao , Zhu Junchi , Cheng Lijuan , Kong Ping
Published: October 2024

Background

Tuberculous meningitis (TBM) with adults Epstein-Barr (EB) virus encephalitis is a very rare infectious disease, with a high mortality and disability. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is highly diagnostic. We report on a case of severe meningoencephalitis caused by co-infection with mycobacterium tuberculosis and EB virus. Brain MRI indicated a parenchyma lesion in the brain. mNGS of CSF indicated Mycobacterium tuberculosis and EB virus amplification, positive serum EB virus IgG antibodies, and improved symptoms after anti-tuberculosis and antiviral treatment. A re-examination of the brain MRI revealed that the significantly absorption of the lesions.

Case report

A 49-year-old male patient presented with a chief complaint of headache and fever with consciousness disturbance. The brain magnetic resonance imaging showed a lesions in the right parenchymal brain with uneven enhancement, accompanied by significantly increased intracranial pressure, elevated CSF cell count and protein levels, as well as notably decreased glucose and chloride levels. mNGS of CSF showed the coexistence of Mycobacterium tuberculosis and EBV. The patient was diagnosed as TBM with EBV encephalitis. The patient’s symptoms gradually improved with the active administration of anti-tuberculosis combined with antiviral agents, the use of hormones to reduce inflammatory reaction, dehydration to lower intracranial pressure, and intrathecal injection. Subsequent follow-up brain magnetic resonance imaging indicated significant absorption of the lesions, along with a marked decrease in CSF count and protein levels, as well as obvious increase in glucose and chloride levels.

Conclusion

TBM associated with adult EBV encephalitis is extremely rare. The disease’s early stages are severe and have a high fatality rate. A prompt and accurate diagnosis is particularly important. NGS of CSF is of great value for early diagnosis.
A generic framework for the semantic contextualization of indicators
Authors: Nicholson Nicholas , Štotl Iztok
Published: October 2024

Indicators are quantitative or qualitative measures used to gauge various aspects of society and assess change over time (such as monitoring the progress or effectiveness of a public policy). Ideally, indicators should be precisely defined and measured according to harmonized procedures that may not be feasible in practice, especially in domains such as health, where indicators are often derived from preexisting, heterogeneous datasets. Integrating such data has posed a persistent challenge, but semantic technologies offer advantages by enriching data in a relatively simple, linkable, and non-disruptive way. However, without harmonized frameworks, the difficulties associated with data integration are unlikely to be resolved. In this article, we propose a generic, domain-neutral indicator contextualization framework for structuring and linking distributed datasets with contextual metadata according to a standard model. The framework integrates the concepts of the International Organization for Standardization/International Electrotechnical Commission (ISO/IEC) 11179 metadata registry standard with the common core ontologies (CCO) mid-level ontology suite, and incorporates other semantic technologies to make it adaptable and interoperable within and across domains. Application of the framework to an example indicator illustrates the versatility and adaptability of the approach in a federated data architecture. The contextual information can be dereferenced using standard query tools to provide data users a comprehensive understanding and overview of the indicator. The framework is amenable to deep learning applications via the principles of semantic data models, linked open data, and knowledge organization systems. The ideas are presented to stimulate further reflection and consolidation of standard data contextualization frameworks.
Sedimentary characteristics and reservoir architecture of a lacustrine mixed carbonate/siliciclastic system: the lower member of the ShangGanchaigou Formation, Neogene, in the western Qaidam Basin, China
Authors: Wenjie Feng , Ye Zhang
Published: October 2024

Lacustrine mixed carbonate/siliciclastic sediment is an important type of oil and gas reservoir with significant potential. Although previous studies have investigated the sedimentary characteristics of the mixed depositional system in numerous oil and gas-bearing basins worldwide, a detailed sedimentary architecture model is still lacking for guiding reservoir characterization at the hydrocarbon reservoir scale. In this paper, a typical lacustrine mixed carbonate/siliciclastic sedimentary system, preserved in the lower member of the ShangGanchaigou Formation, Neogene, in the western Qaidam Basin, Western China, was deeply investigated based on well logging data from 640 wells, 438 m of cores from 3 core wells, and outcrop studies. The results demonstrate that 1) seven types of architecture elements, namely, distributary channel, channel mouth bar, distal bar, sheet-like sand, shallow water mud, algal mound, and marl flat characterized by different lithofacies associations, were recognized based on core and well logging data. 2) The lacustrine mixed carbonate/siliciclastic depositional system can be divided into three facies belts. Along the lakeward direction, the proximal facies belt is dominated by delta front deposits and characterized by gradually downstream bifurcating distributary channels and associated lateral amalgamated delta lobes. The middle facies belt is characterized by isolated and small-scale delta lobes and inter-lobe deposits, including sheet-like sand, small-scale algal mounds, and marl flats, and the distal facies belt is a combination of large-scale algal mounds and marl flats. 3) Within a depression, short-term base-level cycles controlled the facies belt transition, and the proximal, middle, and distal facies belts formed under relatively low, middle, and high base-level conditions, respectively. 4) The scale and connectivity of reservoirs gradually decreased from the proximal to the distal belt.
Hydrocarbon charge history of deeply buried clastic reservoirs in the Bozi area of the Kuqa Depression, western China: implications for deep and ultra-deep petroleum exploration
Authors: Yang Peng , Song Yaya , Liu Keyu , Wang Shunyu , Wei Xinzhuo , Liu Jianliang
Published: October 2024

Significant progress has recently been made in deep and ultra-deep oil and gas exploration globally, demonstrating enormous exploration potential of the deep and ultra-deep strata. However, the accumulation and preservation pattern of deep and ultra-deep oil and gas remains poorly understood, greatly impeding further petroleum exploration and development in the deep and ultra-deep strata. By taking the Bozi deep and ultra-deep condensate gas reservoirs in the Kuqa Depression, western China as an example, we attempt to reconstruct the hydrocarbon charge history in such deep reservoirs via an integrated investigation involving quantitative grain fluorescence, fluid inclusion petrography and microthermometry, micro-fluorescence spectroscopy, laser Raman spectroscopy, PVTx modelling, and basin modelling. The results show that: (1) The Bozi deep and ultra-deep reservoirs contain one group of gas inclusion assemblage, and two groups of oil inclusion assemblages, with one being characterized by near yellowish-whitish and blue-whitish diphasic or triphasic oil inclusions, and the other being featured by bright blue diphasic oil inclusions; (2) The first oil charge occurred during the Early Neogene (6.5–5.5 Ma), and the second oil charge occurred during the Late Neogene (4.4–3.5 Ma), under normal hydrostatic pressure or slightly weak overpressure; and (3) The gas charge occurred during the Pleistocene (∼1.6 Ma), with a corresponding reservoir pressure coefficient of approximately 1.7, transforming the reservoir fluid phase state from black oil or volatile oil to condensate gas. Our findings highlight that aside from the present burial depth, a favorable burial history model is crucial for the preservation of liquid hydrocarbons in deep and ultra-deep reservoirs. The occurrence of liquid hydrocarbons in the Bozi deep and ultra-deep condensate gas reservoirs with depths over 7,000 m is benefited from a prolonged period (>100 Ma) of shallow burial and a late-stage (since 10 Ma) rapid subsidence.
Acupoint catgut embedding: a potential intervention strategy for obesity-related precocious puberty
Authors: Liang Yun , Yuan Yuan , Yang Jie
Published: October 2024

Introduction

Obesity-related precocious puberty is induced by obesity, and acupoint catgut embedding (ACE) therapy is known to treat obesity. This study aims to validate the hypothesis that ACE can delay the onset of obesity-related precocious puberty.

Methods

Female Sprague-Dawley rats, 21 days old, were randomly divided into three groups: the high-fat diet combined with ACE treatment group (ACE), the high-fat diet group (HFD), and the normal control diet group (NCD), with 8 rats in each group. The vaginal opening (VO) time was monitored, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total estradiol (E2) were measured, followed by statistical analysis.

Results

Kaplan-Meier survival curves, with VO as the endpoint, showed that vaginal opening was delayed in the ACE group compared to the HFD group, with a statistically significant difference (p < 0.05). The changes in levels of FSH, LH, and E2 indicated that sexual development was delayed in the ACE group compared to the HFD group and was more similar to the NCD group.

Discussion

Combining the vaginal opening time and changes in hormone levels, this study confirms the potential role of ACE in delaying the onset of obesity-related precocious puberty.
Influencing factors and predictions of carbon emissions for the chemical industry in China
Authors: Wang Weiru , Hu Fan , Li Mengzan , Shi Xincong , Liu Xinyuan
Published: October 2024

As global warming increases the frequent occurrences of natural disasters, the reduction of carbon emissions has become an important issue around the world. The chemical industry is an important source of carbon emissions in China. The carbon emissions of the chemical industry are calculated from 2000 to 2019 by using the emission factor method. The logarithmic mean divisia index (LMDI) method is exploited to analyze the factors that influence carbon emissions, and the emissions variations are attributed to the contributions of carbon intensity, energy structure, energy intensity, industrial value-added rate, per capita industrial output value, and industrial scale. The results of decomposition show that per capita industrial output value is the main driving factor, and energy intensity is the main inhibiting factor of the chemical industry’s carbon emissions. In order to quantify the variation of carbon emissions, the extended stochastic impacts by regression on population, affluence, and technology (STIRPAT) model is constructed and examined. Using the STIRPAT model, the basic scenario and energy intensity control scenario are set, and the carbon emissions are predicted, which shows that under a strict energy intensity control scenario, carbon emissions may reach a peak around 2031. The factors influencing the decomposition and prediction of carbon emissions should be helpful in reducing the carbon emissions of the chemical industry in China.
Combination of nitrogen and organic fertilizers reduce N2O emissions while increasing winter wheat grain yields and quality in China
Authors: Jin Yakang , Chen Hong , Tang Xiaoqian , Zhang Lei , Yan Jun , Li Shuangjun , Chen Ya , Li Xinwei , Wu Hongbao , Xiao Xin
Published: October 2024

Wheat grain yields, quality, and nitrous oxide (N2O) emissions were controlled through the type and application rate of nitrogen (N) fertilizer. Here, we investigated the optimal management of N fertilization by examining the combined effects of organic and N fertilizers on wheat yields, quality, and N2O emissions. Field trials under six treatments were located on campus farms at Anhui Science and Technology University, including farmer’s common practice (270 kg N ha-1, N270), 2/3 reduction in N270 (90 kg N ha-1, N90), organic fertilizer with equal N270 (OF270), 2/3 reduction in OF270 (OF90), 4/5 reduction OF270 + 1/5 reduction N270 (20% OF270 + 80% N270), and 4/5 reduction OF90 + 1/5 reduction N90 (20% OF90 + 80% N90) were applied to winter wheat. The plots were arranged in a randomized complete block experimental design. The N2O emissions were quantified under different fertilization measures in the peak wheat growing season during sowing, jointing, and grain filling stages, respectively. Compared with N270 and N90 treatments, N2O emissions were significantly decreased by 18.6% and 27.2%, respectively, under 20% OF270 + 80% N270% and 20% OF90 + 80% N90 (p < 0.05). Further, N2O emissions in N270 were increased by 50.8% relative to N90. Wheat yields increased significantly under 20% OF90 + 80% N90 by 27.6% (N270) and 16.4% (N90), and were considerably enhanced under 20% OF270 + 80% N270 by 40.6% (N270) and 12.7% (N90) in contrast to OF270 and N270 (p < 0.05). Compared with N90, the content of wet gluten, protein and starch under 20% OF90 + 80% N90 treatment significantly increased by 7.7%, 13.8% and 7.9%, and enhanced by 7.6%, 4.8%, 8.0% relative to OF90, respectively (p < 0.05). The starch content increased significantly by 2.0%, whereas the settlement value decreased considerably by 2.9% under 20% OF270 + 80% N270 (p < 0.05), and there was no notable difference in the wet gluten and protein contents (p > 0.05). Our findings indicated that organic fertilizer mixed with N fertilizer can effectively reduce N2O emissions, increase both the grain yields and quality in wheat field compared with N fertilizer alone.
β2-integrins control HIF1α activation in human neutrophils
Authors: Kling Lovis , Eulenberg-Gustavus Claudia , Jerke Uwe , Rousselle Anthony , Eckardt Kai-Uwe , Schreiber Adrian , Kettritz Ralph
Published: October 2024

During inflammation, human neutrophils engage β2-integrins to migrate from the blood circulation to inflammatory sites with high cytokine but low oxygen concentrations. We tested the hypothesis that the inhibition of prolyl hydroxylase domain-containing enzymes (PHDs), cytokines, and β2-integrins cooperates in HIF pathway activation in neutrophils. Using either the PHD inhibitor roxadustat (ROX) (pseudohypoxia) or normobaric hypoxia to stabilize HIF, we observed HIF1α protein accumulation in adherent neutrophils. Several inflammatory mediators did not induce HIF1α protein but provided additive or even synergistic signals (e.g., GM-CSF) under pseudohypoxic and hypoxic conditions. Importantly, and in contrast to adherent neutrophils, HIF1α protein expression was not detected in strictly suspended neutrophils despite PHD enzyme inhibition and the presence of inflammatory mediators. Blocking β2-integrins in adherent and activating β2-integrins in suspension neutrophils established the indispensability of β2-integrins for increasing HIF1α protein. Using GM-CSF as an example, increased HIF1α mRNA transcription via JAK2-STAT3 was necessary but not sufficient for HIF1α protein upregulation. Importantly, we found that β2-integrins led to HIF1α mRNA translation through the phosphorylation of the essential translation initiation factors eIF4E and 4EBP1. Finally, pseudohypoxic and hypoxic conditions inducing HIF1α consistently delayed apoptosis in adherent neutrophils on fibronectin under low serum concentrations. Pharmacological HIF1α inhibition reversed delayed apoptosis, supporting the importance of this pathway for neutrophil survival under conditions mimicking extravascular sites. We describe a novel β2-integrin-controlled mechanism of HIF1α stabilization in human neutrophils. Conceivably, this mechanism restricts HIF1α activation in response to hypoxia and pharmacological PHD enzyme inhibitors to neutrophils migrating toward inflammatory sites.
A new modeling strategy for the predictive model of chub mackerel (Scomber japonicus) central fishing grounds in the Northwest Pacific Ocean based on machine learning and operational characteristics of the light fishing vessels
Authors: Han Haibin , Shang Chen , Jiang Bohui , Wang Yuhan , Li Yang , Xiang Delong , Zhang Heng , Shi Yongchuang , Jiang Keji
Published: October 2024

The chub mackerel (Scomber japonicus) is one of the most influential small pelagic fish in the Northwest Pacific Ocean, and accurate modeling approaches and model selection are critical points in predicting the Scomber japonicus fishing grounds. This study investigated the changes in catches and fishing days on no moonlight and bright moonlight days (2014-2022) and compared the differences in predictive performance between the LightGBM and RF models on three datasets under the two modeling approaches [those based on the light fishing vessels operational characteristics (Approach one) and those not (Approach Two)]. The results were as follows: 1) Stronger moonlight intensity (e.g., full moon) can limit the fishing efficiency of light fishing vessels, with most years showing a trend of a higher percentage of fishing days on bright moonlight days than catches percentage, i.e., no moonlight days resulted in higher catches with lower fishing days; 2) Compared to Modeling Approach Two, under Modeling Approach one, RF model achieved better predictive performance on dataset B, while the LightGBM model achieved better predictive performance on both datasets A and B; 3) Overall, the Approach One achieved more satisfactory prediction performance, with the optimal prediction performance on the complete dataset C improved from 65.02% (F1-score of the RF model, Approach Two) to 66.52% (F1-score of the LightGBM model, Approach Two); 4) Under the optimal modeling approach (Approach One) and the optimal model (LightGBM model), the differences in the importance of the variables on dataset A (no moonlight days) and dataset B (bright moonlight days) were mainly centered on the environmental variables, with CV, SLA, and SSS being the most important in dataset A, and CV, DO, and SLA being the most important in dataset B. This study provides a more scientific and reasonable modeling undertaking for the research of light purse seine fishing vessels, which is conducive to guiding fishermen to select the operating area and operating time of the Scomber japonicus fishery more accurately and comprehensively and realizing the balanced development of fisheries in terms of ecology and economy.
Accumulated subcutaneous fat in abdomen is associated with long COVID-19 symptoms among non-hospitalized patients: a prospective observational study
Authors: Li Tingxin , He Baoming , Liu Yuping , Wang Chen
Published: October 2024

Introduction

Long COVID-19 symptoms may have a variety of potential overlapping causes. In this study, we aimed to investigate the potential correlation between abdominal adipose tissue and long COVID-19 symptoms in non-hospitalized patients in China.

Methods

This is a prospective observational study. 424 subjects, recovered from COVID-19 for 2–4 weeks, were enrolled and 408 subjects were finished the follow-up investigation at baseline, 8th week and 12th week. Physical measurements were collected. Kaplan-Meier analysis and cox regression analysis were carried out to assess the correlation.

Results

A total of 72 subjects reported the long COVID-19 symptoms. The adjusted Kaplan-Meier analysis and Cox regression analysis revealed a significant correlation with accumulated subcutaneous fat (SFA ≥ 2.0 dm2) and the long COVID-19 symptoms (HR = 2.63, P < 0.001 for male, HR = 1.52, P = 0.048 for female). However, overweight and central obesity showed positive correlation only in women.

Discussion

This study suggested that accumulated subcutaneous fat in abdomen (SFA ≥ 2.0 dm2) was an important positive factor associated with long COVID-19 symptoms among Chinese non-hospitalized patients. Large investigation and prospective studies are needed to validate the correlation in the future.
Role of immune cells in mediating the effect of gut microbiota on Hashimoto’s thyroiditis: a 2-sample Mendelian randomization study
Authors: Pei Xiao-Qing , Wang Wen-Hao , Gao Yue-Hua , Zhang Tong-Xin , Liu Jing-Yu , Zhao Zhen-Dan , Zhang Hua-Wei
Published: October 2024

Purpose

Hashimoto’s thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT.

Methods

In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures.

Results

There was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT.

Conclusion

In conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT.
Effect of adapted dance program on gait in adults with cerebral palsy: a pilot study
Authors: Joung Hee Joung , Kim Tae Hoon , Park Moon Seok
Published: October 2024

Background

The gait function in adults with cerebral palsy (CP) deteriorates rapidly with age. Dance has been used as an effective intervention to improve balance, postural control, and gait. This study aimed to investigate the feasibility and effects of an adapted dance program (ADP) on the gait in adults with CP. The ADP, which consists of floor and barre workouts, was designed to be adapted for individuals with CP.

Method

Ten female adults with spastic diplegic CP (mean age 52.3 ± 6.34, Gross Motor Function Classification System level II) participated in this study. Outcome measures, examined using 3D gait analysis, included spatiotemporal gait parameters and the Gait Deviation Index (GDI) based on nine kinematic variables in all planes of motion. To assess feasibility, we conducted post-questionnaires and a group interview. The ADP, each lasting 90 min, was held twice per week for 12 weeks.

Results

A statistically significant improvement was observed in GDI (Δ5.74 points, p = 0.014), with a large effect size (d = 0.76). Foot off (Δ-0.72%), first double support (Δ-0.2%), second double support (Δ1.5%), and single support (Δ0.64%) showed no significant differences. Step length (Δ1.48 cm), cadence (Δ3.95 steps/min), and walking speed (Δ6.41 cm/s) tended to increase, though the differences were not statistically significant. Participants expressed high levels of physical and emotional satisfaction, suggesting a need for early intervention.

Conclusion

The ADP may improve gait patterns in adults with spastic diplegic CP. The feasibility results indicated that the ADP is suitable for adults with spastic diplegic CP. This study provides evidence for improvement in gait patterns through dance, which has not been reported in previous dance studies on individuals with CP, offering additional information on the benefits of dance.
Efgartigimod treatment for generalized myasthenia gravis: a single-center case series of 16 patients
Authors: Nomura Toshiya , Imamura Michie , Imura Masao , Mizutani Hironori , Ueda Mitsuharu
Published: October 2024

Background

Efgartigimod was approved in Japan in January 2022 for the treatment of generalized myasthenia gravis (gMG), regardless of antibody status. This case series describes a real-world experience in Japan of efgartigimod treatment for gMG patients with diverse backgrounds.

Methods

We retrospectively analyzed the medical records of 16 Japanese patients (11 females and five males, mean age 40.4 years) with gMG who received efgartigimod at the Kumamoto University Hospital between August 2022 and September 2023. The outcomes were Quantitative Myasthenia Gravis (QMG) responders (≥ 3 point reduction), IgG levels, and change in prednisolone dose, in the first cycle of efgartigimod.

Results

Fifteen patients completed one cycle of efgartigimod. Of the 14 patients for whom QMG scores were obtained, 10 patients were QMG responders. Four of the five patients with Myasthenia Gravis Foundation of America class V were QMG responders. Improvement in QMG after efgartigimod treatment was observed in one patient with myasthenic crisis and in one refractory patient who had unsuccessful eculizumab treatment. The mean reductions from baseline in IgG levels at weeks 1, 2, 3, and follow-up were 38.3, 56.1, 63.1, and 43.9%, respectively. A decrease in prednisolone dose was observed in seven patients. The most common adverse events were headache (three patients) and diarrhea (two patients). One patient discontinued efgartigimod treatment due to a treatment-related adverse event of rash.

Conclusion

Improvements in the outcomes of patients with gMG, including patients with severe gMG, myasthenic crisis, and refractory to anti-complementary therapy, were observed after the first cycle of efgartigimod treatment. Our real-world experience in Japan suggests the future possibilities for the treatment with efgartigimod for gMG with diverse backgrounds.
Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions
Authors: Naderi Mohammad , Nguyen Thi My Nhi , Pompili Christopher , Kwong Raymond W. M.
Published: October 2024

During postnatal brain development, maintaining a delicate balance between excitation and inhibition (E/I) is essential for the precise formation of neuronal circuits. The K+/cl− cotransporter 2 (KCC2) is instrumental in this process, and its dysregulation is implicated in various neurological disorders. This study utilized zebrafish (Danio rerio) to investigate the socio-cognitive consequences of KCC2 disruption. Through CRISPR-Cas9 technology, biallelic kcc2a knockout zebrafish larvae were generated, revealing behavioral abnormalities, including impaired social interactions and memory deficits. Molecular analyses unveiled alterations in key genes associated with the GABAergic and glutamatergic systems, potentially contributing to E/I imbalance. Additionally, KCC2 disruption influenced the expression of oxytocin and BDNF, crucial regulators of social behaviors, synaptic plasticity, and memory formation. The study also explored the therapeutic potential of KCC2 modulation using pharmaceuticals, showing the rescuing effects of CLP-290 and LIT-001 on social abnormalities. However, the selective impact of LIT-001 on social behaviors, not memory, highlights the complexity of neurobehavioral modulation. In summary, this study sheds light on the pivotal role of KCC2 in shaping socio-cognitive functions and suggests potential therapeutic avenues for KCC2-related neurological disorders.
A Mendelian randomization analysis of inflammatory skin disease risk due to mineral deficiencies
Authors: Wu Ronghui , Tian Hao , Zhao Tianqi , Tian Yangyang , Jin Xianhua , Zhu Mingji
Published: October 2024

Background

Mineral deficiencies, such as iron (Fe), zinc (Zn), and selenium (Se), play crucial roles in inflammation and immune responses and are linked to chronic inflammatory skin diseases. This study used genome-wide association study (GWAS) data and Mendelian randomization (MR) to investigate the genetic causality among serum levels of five minerals (Fe, Cu, Zn, Se, Ca), three iron metabolism indicators (TSAT, TIBC, ferritin), and three chronic inflammatory skin diseases [psoriasis (PS), atopic dermatitis (AD), acne vulgaris (AV)].

Methods

Two-sample MR analyses using the “TwoSample MR” package in R were conducted with aggregate outcome data from the FinnGen database. The inverse-variance-weighted (IVW) method was applied to assess causal relationships between mineral levels and disease outcomes. Robustness was examined via heterogeneity and pleiotropy tests.

Results

IVW analysis showed significant association between blood transferrin saturation (TSAT) and PS (p = 0.004, OR = 1.18). Serum Zn and Se levels showed inverse correlation with AD (p = 0.039, OR = 0.92). However, due to limited SNPs, robustness was reduced.

Conclusion

TSAT is genetically linked to PS, highlighting iron homeostasis in disease development. Zn and Se intake may reduce AD risk.
Risk factors for parastomal hernia after abdominoperineal resection of rectal cancer
Authors: Zhu Lele , Li Shun , Wang Feitong
Published: October 2024

Purpose

To investigate risk factors associated with the formation of parastomal hernia after Miles operation, and to provide scientific evidence for the prevention and treatment of parastomal hernia.

Methods

Clinical data from 205 patients with rectal cancer undergoing Miles operation in the Department of General Surgery, Affiliated Hospital of Xuzhou Medical University between May 2016 and May 2021 were analyzed retrospectively. Fourteen potential factors were selected and analyzed by single factor analysis and two element logistic regression analysis for their potential relationship to incidence of parastomal hernia.

Results

49 cases of parastomal hernia occurred among 194 patients during follow-up (incidence 25.26%). Univariate analysis showed that age, thickness of subcutaneous abdominal fat, BMI, and stoma pathway were related to the formation of post-surgical parastomal hernia (P < 0.05). Two element logistic regression analysis showed that advanced age, thickness of subcutaneous abdominal fat, BMI > 25 kg/m2, and transperitoneal surgical approach were independent risk factors for the formation of parastomal hernia after Miles operation (P < 0.05).

Conclusion

Advanced age, thickness of subcutaneous abdominal fat, BMI > 25 kg/m2, and transperitoneal surgical approach are independent risk factors for the formation of parastomal hernia after Miles.
A young child formula supplemented with a synbiotic mixture of scGOS/lcFOS and Bifidobacterium breve M-16V improves the gut microbiota and iron status in healthy toddlers
Authors: Chew Charmaine , Matsuyama Misa , Davies Peter S. W. , Hill Rebecca J. , Morrison Mark , Martin Rocio , Codoñer Francisco M. , Knol Jan , Roeselers Guus
Published: October 2024

Early-life gut microbiota development depends on a highly synchronized microbial colonization process in which diet is a key regulator. Microbiota transition toward a more adult-like state in toddlerhood goes hand in hand with the transition from a milk-based diet to a family diet. Microbiota development during the first year of life has been extensively researched; however, studies during toddlerhood remain sparse. Young children's requirement for micronutrients, such as dietary iron, is higher than adults. However, their intake is usually sub-optimal based on regular dietary consumption. The Child Health and Residence Microbes (CHaRM) study, conducted as an adjunct to the GUMLi (Growing Up Milk “Lite”) trial, was a double-blind randomized controlled trial to investigate the effects on body composition of toddler milk compared to unfortified standard cow's milk in healthy children between 1 and 2 years of age in Brisbane (Australia). In this trial, fortified milk with reduced protein content and added synbiotics [Bifidobacterium breve M-16V, short-chain galactooligosaccharides, and long-chain fructooligosaccharides (ratio 9:1)] and micronutrients were compared to standard unfortified cow's milk. In the present study, the effects of the intervention on the gut microbiota and its relationship with iron status in toddlers were investigated in a subset of 29 children (18 in the Active group and 11 in the Control group) who completed the CHaRM study. The toddler microbiota consisted mainly of members of the phyla Firmicutes, Bacteroidota, and Actinobacteriota. The abundance of the B. breve species was quantified and was found to be lower in the Control group than in the Active group. Analysis of blood iron markers showed an improved iron status in the Active group. We observed a positive correlation between Bifidobacterium abundance and blood iron status. PICRUSt, a predictive functionality algorithm based on 16S ribosomal gene sequencing, was used to correlate potential microbial functions with iron status measurements. This analysis showed that the abundance of predicted genes encoding for enterobactin, a class of siderophores specific to Enterobacteriaceae, is inversely correlated with the relative abundance of members of the genus Bifidobacterium. These findings suggest that healthy children who consume a young child formula fortified with synbiotics as part of a healthy diet have improved iron availability and absorption in the gut and an increased abundance of Bifidobacterium in their gut microbiome.
Community pharmacists’ role towards preventing abuse or misuse and dependence of codeine-containing analgesic medications in Saudi Arabia: a multicenter cross-sectional study
Authors: Alanazi Muteb , Ansari Mukhtar , Alharby Tareq Nafea
Published: October 2024

Introduction

The misuse or abuse and dependence of medications containing codeine continue to be a major global public health concern. This study aimed to investigate the role of community pharmacists in preventing the abuse or misuse and dependence of codeine-containing analgesic drugs in Saudi Arabia.

Methods

A cross-sectional study involving 226 community pharmacists from various community pharmacies across multiple cities of Saudi Arabia was conducted from 09 May 2023 to 09 October 2023. Study data were collected and managed using Research Electronic Data Capture tool. Fourteen trained data collectors visited randomly selected community pharmacies in different cities, provided pharmacists with an electronic questionnaire link, and collected their responses electronically. The dataset was downloaded in SPSS format, and analyzed for both descriptive and inferential purposes.

Results

The primary indicators that community pharmacists considered when suspecting cases of abuse or misuse and dependence included customers who requested a larger quantity of the medication (88.5%), frequently visited the pharmacy and sought the specific medicine (82.7%), and those who took advantage of the crowd (70.8%). Pharmacists have been instrumental in preventing abuse or misuse and dependence by ensuring that medicines with abuse potential are not easily accessible to consumers (87.6%), providing alternative options (81%), reducing the dose (65%), referring patients to physicians (62.4%), and refusing to sell or denying availability (54.9%). Additionally, pharmacists primarily focused on raising public awareness (85%) as a noteworthy proportion of customers (54.9%) became desperate to obtain the drug after missing a dose. It was also suggested that community pharmacists should receive specialized training in substance abuse or misuse, as 46.9% of them lacked such training.

Discussion

Community pharmacists, being frequently the initial point of contact easily reachable, possess the capability to greatly assist in identifying the patients and averting abuse or misuse and dependence during the dispensing of medication. Further, they can provide valuable guidance to those involved in efforts to reduce drug abuse or misuse and dependence.
Nanomedicine in HNSCC therapy-a challenge to conventional therapy
Authors: Li Chenyu , Fang Yuan , Xu Sanchun , Zhao Jingyuan , Dong Deshi , Li Shuai
Published: October 2024

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field.
Effects of BYL-719 (alpelisib) on human breast cancer stem cells to overcome drug resistance in human breast cancer
Authors: Yu Leinan , Zang Chuanbing , Ye Yuanchun , Liu Hongyu , Eucker Jan
Published: October 2024

Introduction

Breast cancer continues to be a major health concern and is currently the most commonly diagnosed cancer worldwide. Relapse, metastasis, and therapy resistance are major clinical issues that doctors need to address. We believe BYL-719, which is PI3 kinase p110а inhibitor, could also inhibit the breast cancer stem cell phenotype and epithelial-to-mesenchymal transition (EMT). In addition to the PI3K/AKT signaling pathway, BYL-719 can also inhibit essential cancer-related signaling pathways, all of which would ultimately act on the microenvironment of cancer stem cells, which is quite complicated and regulates the characteristics of tumors. These include the stemness and resistance of malignant tumors, plasticity of cancer stem cells, and anti-apoptotic features.

Materials and methods

A three-dimensional (3D) mammosphere culture method was used in vitro to culture and collect breast cancer stem cells (BCSCs). MTT, clonogenic, and cell apoptosis assays were used to detect cell viability, self-renewal, and differentiation abilities. A sphere formation assay under 3D conditions was used to detect the mammophore inhibition rate of BYL-719. The subpopulation of CD44+CD24− was detected using flow cytometry analysis while EMT biomarkers and essential signaling pathways were detected using western blotting. All the data were analyzed using GraphPad Prism 9 software.

Results

BCSC-like cells were obtained by using the 3D cell culture method in vitro. We confirmed that BYL-719 could inhibit BCSC-like cell proliferation in 3D cultures and that the stemness characteristics of BCSC-like cells were inhibited. The PI3K/AKT/mTOR signaling pathway could be inhibited by BYL-719, and the Notch, JAK-STAT and MAPK/ERK signaling pathways which have crosstalk in the tumor microenvironment (TME) are also inhibited. By comparing eribulin-resistant breast cancer cell lines, we confirmed that BYL-719 could effectively overcome drug resistance.

Summary/conclusion

The 3D cell culture is a novel and highly effective method for enriching BCSCs in vitro. Furthermore, the stemness and EMT of BCSCs were inhibited by BYL-719 by acting on various signaling pathways. Finally, we believe that drug resistance can be overcome by targeting the BCSCs. Conjugation of BYL-719 with other anti-neoplastic agents may be a promising treatment for this in clinic.
Identification and experimental validation of hub genes underlying depressive-like behaviors induced by chronic social defeat stress
Authors: Chen Yexiang , Jiang Yunhao , Jiang Xingcong , Zhai Caiyu , Wang Yifei , Xu Chi
Published: October 2024

Introduction: Major depressive disorder (MDD), characterized by severe neuropsychiatric symptoms and significant cognitive deficits, continues to present both etiological and therapeutic challenges. However, the specific underlying mechanisms and therapeutic targets remain unclear.

Methods: We analyzed human postmortem dorsolateral prefrontal cortex (dlPFC) samples from MDD patients using datasets GSE53987 and GSE54568, identifying three key genes: AGA, FBXO38, and RGS5. To model depressive-like behavior, we employed chronic social defeat stress (CSDS) and subsequently measured the expression of AGA, FBXO38, and RGS5 in the dlPFC using qPCR and Western blot analysis following CSDS exposure.

Results: CSDS significantly induced depressive-like behavior, and both the protein and transcriptional expression levels of AGA, FBXO38, and RGS5 in the dlPFC of mice were markedly reduced after stress, consistent with findings from datasets GSE53987 and GSE54568.

Conclusion: Our research suggests that AGA, FBXO38, and RGS5 are potential biomarkers for MDD and could serve as valuable targets for MDD risk prediction.
Capsaicin attenuates the effect of inflammatory cytokines in a HaCaT cell model for basal keratinocytes
Authors: Cervantes Recalde Maria Fernanda , Schmidt Jana , Girardi Cristina , Massironi Marco , Rechl Markus Leo , Hans Joachim , Stuhlmann Dominik , Somoza Veronika , Lieder Barbara
Published: October 2024

Introduction

The resolution of the skin’s inflammatory response is only possible if its barrier function is restored. TRPV1 channel activation plays an important role during inflammation but the effect of this activation on the skin barrier under inflammatory conditions has not been clarified. We hypothesize that it could potentially aid the keratinocyte barrier by reducing inflammatory cytokine release and promoting tight junction development.

Methods

To explore the role of TRPV1 activation in inflammation, we designed and optimized an in vitro model of keratinocytes with basal epidermal layer characteristics using HaCaT cells and TNFα to induce inflammation.

Results

TNFα increased the gene expression of tight junction protein claudin 1 (CLDN1) by at least 2.60 ± 0.16-fold, in a concentration-dependent manner, over a 48 h period. The administration of a capsaicin pre-treatment reduced the CLDN1 expression to 1.51 ± 0.16-fold during the first 6 h after TNFα induction, whereas IL-8 cytokine release was reduced 0.64 ± 0.17-fold. After 48 h, CLDN1 protein levels increased by a factor of 6.57 ± 1.39 compared to cells only treated with TNFα.

Discussion

These results suggest that activation of TRPV1 by capsaicin can potentiate the increase in CLDN1 expression and CLDN1 protein synthesis induced by TNFα in cultured keratinocytes, while reducing the release of IL-8.
Religious references in political campaigning: a comparative analysis of Latin America and Western Europe on social media
Authors: Schwörer Jakob
Published: October 2024

The relationship between religion and politics is receiving increasing attention in political science, although the focus is often on voter attitudes. Despite secularization trends, scholars expect a resurgence of religion in Western European party politics, where Christianity as a native identity is opposed to non-native Islam by populist radical right parties. In this context, it is primarily hostility toward other religious groups that structures religious elements in political communication. In most Latin American societies, religiosity plays a much greater role for individuals, which is reflected in the discourses of political elites who use genuine religious references to appeal to religious voters (“sacralization of politics”). Using data from my own recent research on content analysis of parties’ and candidates’ Facebook profiles, this article compares how political actors in Latin America and Western Europe use religious references in electoral campaigns and how salient these discourses are. The results help to explain the different prominence of religious discourses in different democratic regions and religious markets. The article contributes to the ongoing debate on the role of religion in 21st century politics.