bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and attitude toward transcranial magnetic stimulation among rehabilitation specialists in Saudi Arabia
Authors: Albishi Alaa M. , Alhadlaq Saja A. , Altowairqi Rahaf T. , Alharbi Mohammed F. , Alsubiheen Abdulrahman M. , Alosaimi Manal H. , Bashir Shahid , Alokaily Ahmad O.
Published: March 2024

Research has demonstrated the benefits of transcranial magnetic stimulation (TMS) in rehabilitation. TMS has been widely used in clinical and research settings for individuals with and without neurological dysfunctions. Therefore, understanding the knowledge and attitudes of rehabilitation specialists regarding TMS is crucial for its application. To our knowledge, no such studies have previously been conducted in the rehabilitation field. Therefore, this study is the first to assess rehabilitation specialists’ knowledge of and attitudes toward TMS. An observational cross-sectional study using a self-administered online survey was conducted among 102 rehabilitation specialists to assess their knowledge and attitudes regarding TMS application in rehabilitation sciences. Descriptive and inferential statistics were used to describe the knowledge and attitudes of rehabilitation specialists toward TMS and examine the impact of different factors such as gender, education level, acceptability, and practice on these outcomes. Rehabilitation specialists who participated in this study showed a limited level of general knowledge of TMS in rehabilitation (7.81 ± 6.20, 37.19%). However, a significant association between educational levels and knowledge was found. Higher knowledge scores were observed for specialists with post-graduate degrees compared to those with only a bachelor’s degree. Moreover, knowledge level, experience, and availability of TMS equipment in the workplace led to a positive attitude toward TMS among rehabilitation specialists. A low knowledge level among rehabilitation specialists was attributed to their level of education. Nevertheless, specialists showed an overall positive attitude toward TMS. Therefore, customized medical education is necessary to incorporate TMS theory and applications into neuroscience and rehabilitation courses for rehabilitation specialists as it holds significant promise as a therapeutic tool.
Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research
Authors: Wang Yingwei , Yao Tao , Lin Yunlu , Ge Hongping , Huang Bixin , Gao Yu , Wu Jianming
Published: March 2024

Background

Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases.

Methods

Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates.

Results

The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10−3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10−3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10−2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10−2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10−3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity.

Conclusion

This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.
Modulatory actions of Echinococcus granulosus antigen B on macrophage inflammatory activation
Authors: Folle Ana Maite , Lagos Magallanes Sofía , Fló Martín , Alvez-Rosado Romina , Carrión Federico , Vallejo Cecilia , Watson David , Julve Josep , González-Sapienza Gualberto , Pristch Otto , González-Techera Andrés , Ferreira Ana María
Published: March 2024

Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1β, IL-6, IL-12p40, IFN-β) secretion and ·NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid’s effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB´s ability to regulate the inflammatory activation of macrophages.
The impact of comorbidities and economic inequality on COVID-19 mortality in Mexico: a machine learning approach
Authors: Méndez-Astudillo Jorge
Published: March 2024

Introduction

Studies from different parts of the world have shown that some comorbidities are associated with fatal cases of COVID-19. However, the prevalence rates of comorbidities are different around the world, therefore, their contribution to COVID-19 mortality is different. Socioeconomic factors may influence the prevalence of comorbidities; therefore, they may also influence COVID-19 mortality.

Methods

This study conducted feature analysis using two supervised machine learning classification algorithms, Random Forest and XGBoost, to examine the comorbidities and level of economic inequalities associated with fatal cases of COVID-19 in Mexico. The dataset used was collected by the National Epidemiology Center from February 2020 to November 2022, and includes more than 20 million observations and 40 variables describing the characteristics of the individuals who underwent COVID-19 testing or treatment. In addition, socioeconomic inequalities were measured using the normalized marginalization index calculated by the National Population Council and the deprivation index calculated by NASA.

Results

The analysis shows that diabetes and hypertension were the main comorbidities defining the mortality of COVID-19, furthermore, socioeconomic inequalities were also important characteristics defining the mortality. Similar features were found with Random Forest and XGBoost.

Discussion

It is imperative to implement programs aimed at reducing inequalities as well as preventable comorbidities to make the population more resilient to future pandemics. The results apply to regions or countries with similar levels of inequality or comorbidity prevalence.
The complex interaction between channel–levee systems and mass transport complexes in the Pliocene–Quaternary Rakhine Basin, offshore Myanmar
Authors: Shao Dali , Fan Guozhang , Ma Hongxia , Wang Haiqiang , Ding Liangbo , Zuo Guoping , Lu Yintao , Xu Xiaoyong
Published: March 2024

Channel–levee systems (CLSs) and mass transport complexes (MTCs) are prevalent in deep-water basins, yet their interplay remains enigmatic. This study uses high-resolution 3D seismic data to investigate the architecture of CLSs and MTCs, aiming to explore how CLSs influence the distribution of MTCs in the Rakhine Basin, Bay of Bengal. Two models are built to illustrate the interaction between CLSs and MTCs. In the first model, large-scale aggradational CLSs created unfilled relief in their overbank environments, which acted as spatially confined topography for subsequent mass-wasting deposits. In this model, the interaction between large-scale CLSs and confined MTCs controls the distribution of confined MTCs. In the second model, laterally migrating CLSs do not create such prominent topographic relief in their overbank environments. This characteristic renders them inconsequential in influencing the distribution of subsequent mass-wasting processes. Consequently, spatially extensive MTCs develop within unconfined settings. This configuration gives rise to lithological traps, which might be common and represent potential drilling targets on continental margins. This study could contribute to a better understanding of the interplay between CLSs and MTCs and have some enlightenment on looking to provide some insight into the search for lithological traps in the Rakhine Basin.
Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer
Authors: McGrath Michael K. , Abolhassani Ali , Guy Luke , Elshazly Ahmed M. , Barrett John T. , Mivechi Nahid F. , Gewirtz David A. , Schoenlein Patricia V.
Published: March 2024

Estrogen receptor positive (ER+) breast cancer is the most common breast cancer diagnosed annually in the US with endocrine-based therapy as standard-of-care for this breast cancer subtype. Endocrine therapy includes treatment with antiestrogens, such as selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). Despite the appreciable remission achievable with these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, and eventual death due to their disease. In these cases, the breast cancer cells have become resistant to endocrine therapy, with endocrine resistance identified as the major obstacle to the medical oncologist and patient. To combat the development of endocrine resistance, the treatment options for ER+, HER2 negative breast cancer now include CDK4/6 inhibitors used as adjuvants to antiestrogen treatment. In addition to the dysregulated activity of CDK4/6, a plethora of genetic and biochemical mechanisms have been identified that contribute to endocrine resistance. These mechanisms, which have been identified by lab-based studies utilizing appropriate cell and animal models of breast cancer, and by clinical studies in which gene expression profiles identify candidate endocrine resistance genes, are the subject of this review. In addition, we will discuss molecular targeting strategies now utilized in conjunction with endocrine therapy to combat the development of resistance or target resistant breast cancer cells. Of approaches currently being explored to improve endocrine treatment efficacy and patient outcome, two adaptive cell survival mechanisms, autophagy, and “reversible” senescence, are considered molecular targets. Autophagy and/or senescence induction have been identified in response to most antiestrogen treatments currently being used for the treatment of ER+ breast cancer and are often induced in response to CDK4/6 inhibitors. Unfortunately, effective strategies to target these cell survival pathways have not yet been successfully developed. Thus, there is an urgent need for the continued interrogation of autophagy and “reversible” senescence in clinically relevant breast cancer models with the long-term goal of identifying new molecular targets for improved treatment of ER+ breast cancer.
Clinical features combined with ultrasound characteristics to predict TERT promoter mutations in papillary thyroid carcinoma: a single-center study over the past 5 years
Authors: Hu Yan , Xu Shangyan , Dong Lei , Pan Zuxian , Zhang Lu , Zhan Weiwei
Published: March 2024

Purpose

Telomerase reverse transcriptase (TERT) has been reported in papillary thyroid carcinoma (PTC). This study aimed to investigate the correlation of TERT promoter mutations with clinical and ultrasound (US) features in PTC and to develop a model to predict TERT promoter mutations.

Methods

Preoperative US images, postoperative pathological features, and TERT promoter mutation information were evaluated in 365 PTC patients confirmed by surgery. Univariate and multivariate factor analyses were performed to identify risk factors for TERT promoter mutations. A predictive model was established to assess the clinical predictive value.

Results

Of the 365 patients with PTC (498 nodules), the number of those with TERT promoter mutations was 67 cases (75 nodules), and the number of those without mutations was 298 cases (423 nodules). The median age was 40 years in the wild-type group and 60 years in the mutant group. Male patients made up 35.82% of the mutant group and 22.82% of the wild-type group. Multivariate analysis revealed that the independent risk factors associated with the occurrence of TERT promoter mutation in PTC were as follows: older age (odds ratio (OR) = 1.07; p = 0.002), maximum diameter of ≥ 10 mm (OR = 3.94; p < 0.0001), unilateral (OR = 4.15; p < 0.0001), multifocal (OR = 7.69; p < 0.0001), adjacent to the thyroid capsule (OR = 1.94; p = 0.044), and accompanied by other benign nodules (OR = 1.94, p = 0.039). A predictive model was established, and the area under the curve (AUC) of the receiver operating characteristic was 0.839. TERT promoter mutations were associated with high-risk US and clinical features compared with the wild-type group.

Conclusion

TERT promoter mutations were associated with older ages. They were also found to be multifocal, with a maximum diameter of ≥ 10 mm, unilateral, adjacent to the thyroid capsule, and accompanied by other benign nodules. The predictive model was of high diagnostic value.
Salivary α-amylase activity is associated with cardiometabolic and inflammatory biomarkers in overweight/obese, non-diabetic Qatari women
Authors: Al Akl Neyla S. , Khalifa Olfa , Habibullah Mohammad , Arredouani Abdelilah
Published: March 2024

Introduction

Obesity, prevalent in approximately 80% of Qatar’s adult population, increases the risk of complications like type 2 diabetes and cardiovascular diseases. Predictive biomarkers are crucial for preventive strategies. Salivary α-amylase activity (sAAa) inversely correlates with obesity and insulin resistance in adults and children. However, the connection between sAAa and cardiometabolic risk factors or chronic low-grade inflammation markers remains unclear. This study explores the association between serum sAAa and adiposity markers related to cardiovascular diseases, as well as markers indicative of chronic low-grade inflammation.

Methods

Serum samples and clinical data of 1500 adult, non-diabetic, Overweight/Obese participants were obtained from Qatar Biobank (QBB). We quantified sAAa and C reactive protein (CRP) levels with an autoanalyzer. Cytokines, adipokines, and adiponectin of a subset of 228 samples were quantified using a bead-based multiplex assay. The associations between the sAAa and the adiposity indices and low-grade inflammatory protein CRP and multiple cytokines were assessed using Pearson’s correlation and adjusted linear regression.

Results

The mean age of the participants was 36 ± 10 years for both sexes of which 76.6% are women. Our analysis revealed a significant linear association between sAAa and adiposity-associated biomarkers, including body mass index β -0.032 [95% CI -0.049 to -0.05], waist circumference β -0.05 [95% CI -0.09 to -0.02], hip circumference β -0.052 [95% CI -0.087 to -0.017], and HDL β 0.002 [95% CI 0.001 to 0.004], albeit only in women. Additionally, sAAa demonstrated a significant positive association with adiponectin β 0.007 [95% CI 0.001 to 0.01]while concurrently displaying significant negative associations with CRP β -0.02 [95% CI -0.044 to -0.0001], TNF-α β -0.105 [95% CI -0.207 to -0.004], IL-6 β [95% CI -0.39 -0.75 to -0.04], and ghrelin β -5.95 [95% CI -11.71 to -0.20], specifically within the female population.

Conclusion

Our findings delineate significant associations between sAAa and markers indicative of cardiovascular disease risk and inflammation among overweight/obese adult Qatari females. Subsequent investigations are warranted to elucidate the nuances of these gender-specific associations comprehensively.
Study on the impact of social capital on the rural residents’ conscious interpersonal waste separation behavior: evidence from Jiangxi province, China
Authors: Teng Yuhua , Li Ning , Yang Jing , Liu Yuan , Liu Changjin
Published: March 2024

Guiding rural residents to implement interpersonal waste separation in their daily lives consciously is crucial for controlling solid waste pollution in developing countries. This paper utilizes survey data from Jiangxi Province which is one of the national pilot zones for ecological conservation in China to analyze the impact of the social capital that includes social networks, social trust, and social norms on the rural residents’ conscious interpersonal waste separation behavior. The empirical results indicate that social capital has a positive effect on the rural residents’ conscious interpersonal waste separation behavior, wherein the effects of social networks and social trust are significant. Among the three dimensions of social capital, social networks and social norms are substitutable, while social trust and social norms have a complementary effect on each other. Moreover, the ecological cognition and subjective norm play a significant mediating role in the relationship between social network, social trust, and social norms and the rural residents’ conscious interpersonal waste separation behavior, while the government policies plays a significant moderating effect.
ISSA-enhanced GRU-Transformer: integrating sports wisdom into the frontier exploration of carbon emission prediction
Authors: Jiang Wei , Liu Changjiang , Qu Qiang , Wang Zhen , Hu Liangnan , Xie Zhaofu , Zhang Bokun , He Jingzhou
Published: March 2024

Introduction

Carbon neutrality has become a key strategy to combat global climate change. However, current methods for predicting carbon emissions are limited and require the development of more effective strategies to meet this challenge. This is especially true in the field of sports and competitions, where the energy intensity of major events and activities means that time series data is crucial for predicting related carbon emissions, as it can detail the emission patterns over a period of time.

Method

In this study, we introduce an artificial intelligence-based method aimed at improving the accuracy and reliability of carbon emission predictions. Specifically, our model integrates an Improved Mahjong Search Algorithm (ISSA) and GRU-Transformer technology, designed to efficiently process and analyze the complex time series data generated by sporting events. These technological components help to capture and parse carbon emission data more accurately.

Results

Experimental results have demonstrated the efficiency of our model, which underwent a comprehensive evaluation involving multiple datasets and was benchmarked against competing models. Our model outperformed others across various performance metrics, including lower RMSE and MAE values and higher R2 scores. This underscores the significant potential of our model in enhancing the accuracy of carbon emission predictions.

Discussion

By introducing this new AI-based method for predicting carbon emissions, this study not only provides more accurate data support for optimizing and implementing carbon neutrality measures in the sports field but also improves the accuracy of time series data predictions. This enables a deeper understanding of carbon emission trends associated with sports activities. It contributes to the development of more effective mitigation strategies, making a significant contribution to global efforts to reduce carbon emissions.
Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan
Authors: Sharip Aigul , Rakhimova Saule , Molkenov Askhat , Ashenova Ainur , Kozhamkulov Ulan , Akhmetollayev Ilyas , Zinovyev Andrei , Zhukov Yuri , Omarov Marat , Tuleutaev Mukhtar , Rakhmetova Venera , Terwilliger Joseph D. , Lee Joseph H. , Zhumadilov Zhaxybay , Akilzhanova Ainur , Kairov Ulykbek
Published: March 2024

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC’s genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.
Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population
Authors: Zacharopoulou Panagiota , Lee Ming , Oliveira Thiago , Thornhill John , Robinson Nicola , Brown Helen , Kinloch Sabine , Goulder Philip , Fox Julie , Fidler Sarah , Ansari M. Azim , Frater John
Published: March 2024

Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants’ viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 B-clade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies.
NVX-CoV2373 induces humoral and cellular immune responses that are functionally comparable to vector and mRNA-based vaccines
Authors: Mai Franz , Kordt Marcel , Bergmann-Ewert Wendy , Reisinger Emil C. , Müller-Hilke Brigitte
Published: March 2024

Background

After licensing of the protein-based vaccine NVX-CoV2373, three technically different vaccines against the SARS-CoV-2 became available for application to the human population - and for comparison of efficacies.

Methods

We here recruited 42 study participants who had obtained one initial dose of NVX-CoV2373 and analyzed their immune responses in contrast to 37 study participants who had obtained either the vector vaccine AZD1222 or the mRNA vaccine BNT162b2 a year earlier. 32 participants also donated blood before first vaccination to serve as a vaccine-naive control. In detail, we investigated and quantified at day 21 and approximately six months after primary immunization the amounts of vaccine-specific antibodies produced, their neutralization capacity, their quality in terms of binding different epitopes and their efficiency in inducing various isotypes. Cellular immunity and intracellular cytokine production following in vitro re-stimulation with BNT162b2 vaccine was analyzed via ELISpot or via flow cytometry.

Results

Our results show that even though vaccination including the mRNA vaccine yielded best results in almost any aspect of antibody levels and binding efficiency, the neutralization capacities against the wild-type Wuhan strain and the Omicron BA.1 variant early and at six months were comparable among all three vaccination groups. As for the T cells, we observed a prevailing CD8 response at three weeks which turned into a predominant CD4 memory at six months which has not yet been observed for AZD1222 and BNT162b2. While additional infection with SARS-CoV-2 resulted in a boost for the humoral response, T cell memory appeared rather unaffected.

Conclusion

Whether any of these differences translate into real world protection from infection, mitigation of severe disease courses and prevention of long/post COVID will need to be investigated in the future.
Universal CAR T cells targeted to HER2 with a biotin-trastuzumab soluble linker penetrate spheroids and large tumor xenografts that are inherently resistant to trastuzumab mediated ADCC
Authors: Nagy Lőrinc , Mezősi-Csaplár Marianna , Rebenku István , Vereb György , Szöőr Árpád
Published: March 2024

CAR T cell therapies face challenges in combating solid tumors due to their single-target approach, which becomes ineffective if the targeted antigen is absent or lost. Universal CAR T cells (UniCAR Ts) provide a promising solution by utilizing molecular tags (linkers), such as biotin conjugated to monoclonal antibodies, enabling them to target a variety of tumor antigens. Recently, we showed that conventional CAR T cells could penetrate the extracellular matrix (ECM) of ADCC-resistant tumors, which forms a barrier to therapeutic antibodies. This finding led us to investigate whether UniCAR T cells, targeted by soluble antibody-derived linkers, could similarly tackle ADCC-resistant tumors where ECM restricts antibody penetration. We engineered UniCAR T cells by incorporating a biotin-binding monomeric streptavidin 2 (mSA2) domain for targeting HER2 via biotinylated trastuzumab (BT). The activation and cytotoxicity of UniCAR T cells in the presence or absence of BT were evaluated in conventional immunoassays. A 3D spheroid coculture was set up to test the capability of UniCAR Ts to access ECM-masked HER2+ cells. For in vivo analysis, we utilized a HER2+ xenograft model in which intravenously administered UniCAR T cells were supplemented with intraperitoneal BT treatments. In vitro, BT-guided UniCAR T cells showed effective activation and distinct anti-tumor response. Upon target recognition, IFNγ secretion correlated with BT concentration. In the presence of BT, UniCAR T cells effectively penetrated HER2+ spheroids and induced cell death in their core regions. In vivo, upon intravenous administration of UniCAR Ts, circulating BT linkers immediately engaged the mSA2 domain and directed effector cells to the HER2+ tumors. However, these co-treated mice died early, possibly due to the lung infiltration of UniCAR T cells that could recognize both native biotin and HER2. Our results suggest that UniCAR T cells guided with soluble linkers present a viable alternative to conventional CAR T cells, especially for patients resistant to antibody therapy and those with solid tumors exhibiting high antigenic variability. Critical to their success, however, is the choice of an appropriate binding domain for the CAR and the corresponding soluble linker, ensuring both efficacy and safety in therapeutic applications.
Extracellular vesicle-mediated communication between CD8+ cytotoxic T cells and tumor cells
Authors: Huang Zeyu , Liu Xuehui , Guo Qinghao , Zhou Yihang , Shi Linlin , Cai Qingjin , Tang Shupei , Ouyang Qin , Zheng Ji
Published: March 2024

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field.
The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma—two sides of the same coin?
Authors: Reschke Robin , Deitert Benjamin , Enk Alex H. , Hassel Jessica C.
Published: March 2024

Tissue-resident memory T cells (TRM cells) have become an interesting subject of study for antitumor immunity in melanoma and other solid tumors. In the initial phases of antitumor immunity, they maintain an immune equilibrium and protect against challenges with tumor cells and the formation of primary melanomas. In metastatic settings, they are a prime target cell population for immune checkpoint inhibition (ICI) because they highly express inhibitory checkpoint molecules such as PD-1, CTLA-4, or LAG-3. Once melanoma patients are treated with ICI, TRM cells residing in the tumor are reactivated and expand. Tumor killing is achieved by secreting effector molecules such as IFN-γ. However, off-target effects are also observed. Immune-related adverse events, such as those affecting barrier organs like the skin, can be mediated by ICI-induced TRM cells. Therefore, a detailed understanding of this memory T-cell type is obligatory to better guide and improve immunotherapy regimens.
Hearing impairment in systemic sclerosis patients—what do we really know?
Authors: Sieśkiewicz Michał , Rębacz Damian , Sieśkiewicz Andrzej
Published: March 2024

Background

Systemic sclerosis (SSc) is a disease of a very heterogeneous clinical picture and immunological profile with progression rate that varies between individuals. Although hearing deterioration is not a complaint that comes to the fore in SSc patients, as it is not life-threatening compared to many other more severe symptoms of this disease, it can significantly impair the quality of life. Medical literature concerning this problem is rather scarce.

Materials and methods

In this article we systematically reviewed the medical publications concerning hearing impairment in patients with systemic sclerosis to evaluate current understanding of this complex problem. Following PRISMA guidelines a total of 19 papers were found and analysed including 11 original studies and 8 case reports.

Results

Although it seems that hearing impairment in SSc patients is relatively more common than in the general population, based on the analysis of available literature, no firm conclusions regarding its frequency and pathomechanism can be drawn yet. Microangiopathy leading to damage to the sensory cells of the inner ear is suspected to be the main mechanism of hearing loss, although damage to the higher levels of the auditory pathway appears to be underestimated due to incomplete audiological diagnosis.

Conclusion

Undoubtedly, the reason for the difficulty in such an evaluation are the complex and still not fully elucidated pathomechanism of SSc, the individually variable dynamics of the disease and the unique heterogeneity of symptoms. Nevertheless, further studies in larger and appropriately selected groups of patients, focused more on the dynamics of microangiopathy and not solely on clinical symptoms could provide answers to many key questions in this regard.
Expression of cellobiose dehydrogenase gene in Aspergillus niger C112 and its effect on lignocellulose degrading enzymes
Authors: Zhong Yanan , Guo Zepan , Li Meiqun , Jia Xiaojiang , Zeng Baiquan
Published: March 2024

Cellobiose dehydrogenase (CDH) is one of the cellulase auxiliary proteins, which is widely used in the field of biomass degradation. However, how to efficiently and cheaply apply it in industrial production still needs further research. Aspergillus niger C112 is a significant producer of cellulase and has a relatively complete lignocellulose degradation system, but its CDH activity was only 3.92 U. To obtain a recombinant strain of A. niger C112 with high cellulases activity, the CDH from the readily available white-rot fungus Grifola frondose had been heterologously expressed in A. niger C112, under the control of the gpdA promoter. After cultivation in the medium with alkali-pretreated poplar fiber as substrate, the enzyme activity of recombinant CDH reached 36.63 U/L. Compared with the original A. niger C112, the recombinant A. niger transformed with Grifola frondosa CDH showed stronger lignocellulase activity, the activities of cellulases, β-1, 4-glucosidase and manganese peroxidase increased by 28.57, 35.07 and 121.69%, respectively. The result showed that the expression of the gcdh gene in A. niger C112 could improve the activity of some lignocellulose degrading enzymes. This work provides a theoretical basis for the further application of gcdh gene in improving biomass conversion efficiency.
Vertical habitat preferences shape the fish gut microbiota in a shallow lake
Authors: Zhang Bowei , Xiao Jiaman , Liu Hongyan , Zhai Dongdong , Wang Ying , Liu Shujun , Xiong Fei , Xia Ming
Published: March 2024

Understanding the interactions between fish gut microbiota and the aquatic environment is a key issue for understanding aquatic microorganisms. Environmental microorganisms enter fish intestines through feeding, and the amount of invasion varies due to different feeding habits. Traditional fish feeding habitat preferences are determined by fish morphology or behavior. However, little is known about how the feeding behavior of fish relative to the vertical structure in a shallow lake influences gut microbiota. In our study, we used nitrogen isotopes to measure the trophic levels of fish. Then high-throughput sequencing was used to describe the composition of environmental microbiota and fish gut microbiota, and FEAST (fast expectation-maximization for microbial source tracking) method was used to trace the source of fish gut microbiota. We investigated the microbial diversity of fish guts and their habitats in Lake Sanjiao and verified that the sediments indeed played an important role in the assembly of fish gut microbiota. Then, the FEAST analysis indicated that microbiota in water and sediments acted as the primary sources in half of the fish gut microbiota respectively. Furthermore, we classified the vertical habitat preferences using microbial data and significant differences in both composition and function of fish gut microbiota were observed between groups with distinct habitat preferences. The performance of supervised and unsupervised machine learning in classifying fish gut microbiota by habitat preferences actually exceeded classification by fish species taxonomy and fish trophic level. Finally, we described the stability of fish co-occurrence networks with different habitat preferences. Interestingly, the co-occurrence network seemed more stable in pelagic fish than in benthic fish. Our results show that the preferences of fish in the vertical structure of habitat was the main factor affecting their gut microbiota. We advocated the use of microbial interactions between fish gut and their surrounding environment to reflect fish preferences in vertical habitat structure. This approach not only offers a novel perspective for understanding the interactions between fish gut microbiota and environmental factors, but also provides new methods and ideas for studying fish habitat selection in aquatic ecosystems.
Empirical phenotyping and genome-wide association study reveal the association of panicle architecture with yield in Chenopodium quinoa
Authors: Habib Zakia , Ijaz Siddra , Haq Imran Ul , Hashem Abeer , Avila-Quezada Graciela Dolores , Abd_Allah Elsayed Fathi , Khan Nasir Ahmad
Published: March 2024

Chenopodium quinoa manifests adaptability to grow under varying agro-climatic scenarios. Assessing quinoa germplasm’s phenotypic and genetic variability is a prerequisite for introducing it as a potential candidate in cropping systems. Adaptability is the basic outcome of ecological genomics of crop plants. Adaptive variation predicted with a genome-wide association study provides a valuable basis for marker-assisted breeding. Hence, a panel of 72 quinoa plants was phenotyped for agro morphological attributes and association-mapping for distinct imperative agronomic traits. Inter simple sequence repeat (ISSR) markers were employed to assess genetic relatedness and population structure. Heatmap analysis showed three genotypes were early maturing, and six genotypes were attributed for highest yield. The SD-121-07 exhibited highest yield per plant possessing green, glomerulate shaped, compact density panicle with less leaves. However, SJrecm-03 yielded less exhibiting pink, intermediate shape, intermediate density panicles with less leaves. The phenotyping revealed strong correlation of panicle architecture with yield in quinoa. A genome-wide association study unraveled the associations between ISSR makers and agro-morphological traits. Mixed linear modes analysis yielded nine markers associated with eight traits at p ≤ 0.01. Moreover, ISSR markers significantly associated with panicle shape and leafiness were also associated with yield per plant. These findings contribute to the provision of authenticity for marker-assisted selection that ultimately would support quinoa breeding programs.
Effects of water stress on nutrients and enzyme activity in rhizosphere soils of greenhouse grape
Authors: Zhang Rui , Zhang Hongjuan , Yang Changyu , Li Hongxia , Wu Jiangqi
Published: March 2024

In grape cultivation, incorrect water regulation will lead to significant water wastage, which in turn will change soil structure and disrupt soil nutrient cycling processes. This study aimed to investigate the effects of different water regulation treatments [by setting moderate water stress (W1), mild water stress (W2), and adequate water availability (CK)] on soil physical–chemical properties and enzyme activity in greenhouse grape during the growing season. The result showed that the W2 treatment had a negative impact on the build-up of dissolved organic carbon (DOC), nitrate nitrogen (NO3-N), and available phosphorus (AP). Throughout the reproductive period, the W1 and W2 treatments decreased the soil’s microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents, and MBC was more vulnerable to water stress. During the growth period, the trends of urease, catalase, and sucrase activities in different soil depth were ranked as 10–20 cm > 0–10 cm > 20–40 cm. The urease activity in 0–10 cm soil was suppressed by both W1 and W2 treatments, while the invertase activity in various soil layers under W1 treatment differed substantially. The W1 treatment also reduced the catalase activity in the 20–40 cm soil layer in the grape growth season. These findings suggested that W2 treatment can conserve water and enhance microbial ecology of greenhouse grape soils. Therefore, W2 treatment was the most effective water regulation measure for local greenhouse grape cultivation.
Altered resting-state functional connectivity and dynamic network properties in cognitive impairment: an independent component and dominant-coactivation pattern analyses study
Authors: Bergamino Maurizio , Burke Anna , Sabbagh Marwan N. , Caselli Richard J. , Baxter Leslie C. , Stokes Ashley M.
Published: March 2024

Introduction

Cognitive impairment (CI) due to Alzheimer’s disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual’s quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia.

Methods

In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined.

Results

Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions.

Discussion

The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD.
Improvement of symptoms in children with autism by TOMATIS training: a cross-sectional and longitudinal study
Authors: Fu Yujia , Tian Mei , Chen Jiaxi , Chen Wenfeng , Li Huang
Published: March 2024

Introduction

Autism spectrum disorder (ASD) is a neurological condition that is marked by deficits in social interaction, difficulty expressing oneself, lack of enthusiasm, and stereotypical conduct. The TOMATIS training method is an effective music therapy for children with ASD for its individually developed programs to improve behavioral deficits.

Methods

The research employed both longitudinal and crosssectional designs.

Results

In the cross-sectional study, the experimental group showed significant improvement in symptoms after TOMATIS training compared to the control group of children with ASD. The results validated the effect of TOMATIS treatment for ASD-related deficits, including perceptual-motor, attentional, social, and emotional issues.

Discussion

ASD’s auditory hypersensitivity hampers social information processing, but TOMATIS enhances cochlear frequency selectivity, aiding in capturing relevant auditory stimuli. In addition, the longitudinal study confirmed these findings, which proved TOMATIS training effective in clinically treating ASD. This study focused on audiometric indicators and behavioural improvement, elucidating the mechanisms behind the training’s success. Behavioral improvements might stem from TOMATIS’ frequency selectivity, reshaping auditory organ-cortical feedback loops to filter interference and focus on valid information.
Relationship between sodium level and in-hospital mortality in traumatic brain injury patients of MIMIC IV database
Authors: Wang Xiaoliang , Li Xin , Sun Jiahao , Wang Mengmeng , Lang Wenjuan , Xu Xin
Published: March 2024

Background

An association between prognosis and high sodium levels in Traumatic Brain Injury (TBI) patients in Intensive Care Units (ICUs) has been noted, but limited research exists on the ideal sodium level in these patients or the impact on early mortality, using the MIMIC-IV database.

Methods

A retrospective survey was conducted on TBI patients from the MIMIC-IV database. Patients were divided into two categories based on their highest serum sodium level within 24 h of admission exceeding 145 mmol/L: those with hypernatremia, and those with moderate-to-low sodium levels. Collected covariates encompasses demographic, clinical, laboratory, and intervention variables. A multivariate logistic regression model was implemented to forecast in-hospital mortality.

Results

The study included 1749 TBI patients, with 209 (11.5%) experiencing in-hospital deaths. A non-linear test exposed an L-shaped correlation between sodium level and in-hospital mortality, with mortality rates increasing after a turning point at 144.1 mmol/L. Compared to the moderate-to-low group’s 9.3% mortality rate, the hypernatremia group had a significantly higher mortality rate of 25.3% (crude odds ratio = 3.32, 95% confidence interval: 2.37 ~ 4.64, p < 0.001). After adjusting for all covariates, the hypernatremia group continued to show a significant correlation with higher mortality risk (adjusted odds ratio = 2.19, 95% confidence interval: 1.38 ~ 3.47, p = 0.001). This trend remained consistent regardless of the analyses stratification.

Conclusion

The study reveals an L-shaped relationship between sodium levels and in-hospital deaths, with a pivotal point at 144.1 mmol/L. TBI patients displaying hypernatremia were independently linked to higher in-hospital mortality, underlining the need for further studies into targeted management of sodium levels in these patients.