bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2
Authors: Niu Chao , Liang Tingting , Chen Yongchong , Zhu Shan , Zhou Lei , Chen Naifei , Qian Lei , Wang Yufeng , Li Min , Zhou Xin , Cui Jiuwei 
Published: September 2024

IntroductionCytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague.MethodsUsing spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed.ResultsThis study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB–dependent transcription of CRS-related inflammatory cytokines.DiscussionTargeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
Identifying immune checkpoints on dysregulated T-cells as prognostic biomarkers for multiple myeloma patients with COVID-19
Authors: Li Ziping , He Huiwen , Zhang Fujing , Li Haolong , Jin Xianghong , Song Yuhang , Liu Shuangjiao , Wang Xuan , Zhuang Junling 
Published: September 2024

BackgroundBroad T cell phenotypic alterations and potential dysfunctions were prominent in COVID-19. There are few and inconclusive data about the role of immune checkpoints for T cell exhaustion/activation during SARS-CoV-2 infection in multiple myeloma (MM) patients.MethodsWe tested T cell subsets and immune checkpoints in 177 MM patients with COVID-19, as well as in 32 healthy infected controls and 42 uninfected MM patients. The percentage of CD4+ and CD8+ subpopulation and immune checkpoints (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4, OX40, and 4-1BB) were evaluated by flow cytometry.ResultsWe have found that pronounced lymphopenia and inverted CD4/CD8 ratio in severe COVID-19 patients were especially developed within the first month after infection. And T cell subset dysregulation was persistent in severe patients recovering from SARS-CoV-2 infection. Immune checkpoints on CD4+ T cells were variable and uncorrelated with the level of adaptive immunity, while the proportion of CD4+ T cells was positively correlated with humoral immune response. PD-1 and TIGIT on CD8+ T cells were significantly elevated in severe patients and sustained for more than 2 months, which was associated with impaired cellular immune function. Moreover, exhausted molecules PD-1 and TIGIT on T cells were reduced in immunotherapy patients.ConclusionThe prolonged T cell dysregulation after severe SARS-CoV-2 infection highlights the close surveillance from reinfection in MM patients even during convalescence. PD-1 and TIGIT on CD8+ T cells could be important prognostic factors to stratify prognosis in MM patients with COVID-19. Moreover, immunotherapy may downregulate the expression of exhausted checkpoints PD-1 and TIGIT, leading to T cell overactivation and severe COVID-19.
Abundance and diversity of cotton insect pests under repeatedly cultivated cotton fields of Tanzania
Authors: Benjamin Madama , Rwegasira Gration M. 
Published: September 2024

IntroductionCotton production in Tanzania is facing significant challenges due to insect pests that cause extensive damages to the crop. The most notable pests include the African bollworm (Heliothis armigera Hubner), Spiny bollworm (Earias biplaga Walker), Cotton stainers (Dysdercus sidae (Herrich-Schaeffer), Cotton Aphids (Aphis gossypii Glover), Thrips (Thrips tabaci Lindeman), Jassids (Amrasca biguttula, Bigutula), Leafhoppers (Cicadellidae jassidae), and Whiteflies (Bemisia tabaci Genn). If left uncontrolled, these pests can cause up to 60% damage to the crop. Despite the importance of cotton and the fact that most of these pests are endemic, there are scanty knowledge on the dynamics and distribution of cotton pests across the seasons of the year and crop’s phenological growth stages (germination, vegetative growth, flowering and boll formation) in areas under repeated cultivation of the crop in Tanzania. Here we report on the influence of seasons and cotton’s phenological stages on the abundance, diversity, distribution and richness of cotton insect pests.MethodsThe study was conducted in the Misungwi district for two cotton-growing seasons, using the UKM08 cotton variety. Stick traps and handpicking methods were deployed in catching the cotton insect pests.ResultsOn average, a total of 8,500 insect specimen of diverse families and species were collected every season. The four dominant species among the collected were Aphis gossypii (17.37%), Amrasca biguttula (11.42%), Nezara viridura (10.7%), and Bemisia tabacci (10.68%). Both cotton phenological growth stages and seasons significantly (p&lt;0.05) influenced the abundance, diversity, distribution and richness of cotton insect pests. In particular, the phenological growth stage 3 exhibited greater diversity of insect pests. The pests’ distribution patterns remained relatively uniform across the crop growth stages.DiscussionFindings from the present study could contribute to developing sustainable pest management strategies in areas under repeated cotton production in Tanzania and elsewhere.
Dry eye disease and spondyloarthritis: expanding the spectrum of systemic inflammatory disorders associated with ocular surface disease. Data from the international AIDA Network Spondyloarthritis Registry
Authors: Vitale Antonio , Caggiano Valeria , Martín-Nares Eduardo , Di Meglio Nunzia , Sica Cristian , Hinojosa-Azaola Andrea , Perfetti Maria Orsetta , Pagliara Alessandra , Guidetti Giorgia , Fonollosa Alex , Lopez Roberta , Sbalchiero Jessica , Sota Jurgen , Carreño Ester , Kawakami-Campos Perla Ayumi , Gentileschi Stefano , de-la-Torre Alejandra , Tosi Gian Marco , Mazzei Maria Antonietta , Balistreri Alberto , Frediani Bruno , Cantarini Luca , Fabiani Claudia 
Published: September 2024

ObjectiveDry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED.MethodsA total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients.ResultsDED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72–42.52, p = 0.001). The Schirmer test values of &lt; 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of &lt;5 s was observed in 34 (47.9%) patients with axial-SpA and six (31.6%) healthy controls. The median OSDI score was found to be 22.9 (IQR = 29.35) among the patients with axial-SpA and 0.0 (IQR = 4.69) among the healthy controls (p = 0.009). The fluorescein and lissamine green staining of the ocular surface indicated a significantly higher Oxford Grading Scale in the patients with axial-SpA than in the healthy controls.ConclusionPatients with axial-SpA often complain of eye dryness, which may be quantified with the self-administered OSDI questionnaire and objectively assessed through the tests commonly used for the diagnosis of DED. Patients suspected of having axial-SpA should routinely be asked about dry eye symptoms and evaluated for potential corneal and conjunctival damage.
Evaluation of the review models and approval timelines of authorities participating in the East African Medicine Regulatory Harmonisation initiative: alignment and strategies for moving forward
Authors: Ngum Nancy , Ndomondo-Sigonda Margareth , Habonimana Rémy , Siyoi Fred , Irasabwa Clarisse , Ojukwu Julia , Apolinary Felchism , Okello Andrew , Ahmada Sabrina , Walker Stuart , Salek Sam 
Published: September 2024

IntroductionMedicines regulatory harmonisation has been embraced by many national regulatory authorities (NRAs) to improve public health through faster availability of safe, high-quality, and effective medical products to patients and enhanced standardisation of technical guidelines and work sharing, leading to reduced cost to pharmaceutical companies. After ten years of implementing regulatory harmonisation by the East African Community Medicines Registration Harmonization (EAC-MRH) initiative, it is now imperative for participating NRAs to rely on each other to minimise duplication of use of limited resources. Major challenges in implementing reliance are the lack of clear registration processes and delays in the approval. The aim of this study was to compare review models, target timelines and data requirements used in assessing applications by EAC-MRH NRAs so as to align and propose strategies for improvement.MethodsA validated questionnaire that standardises and captures review processes was completed by the head of the medicine’s registration division in each of the seven EAC-MRH NRAs. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities.ResultsMost applications received by all countries were for generics except Kenya, which received a significant number of new active substance applications (55 and 53 in 2020 and 2021). Mean approval times for generics using full review varied, with Tanzania’s time declining for the three years. Target timelines for full review for the five countries ranged between 180 calendar days (Tanzania) to the highest 330 days (Zanzibar). The three countries (Kenya, Rwanda and Uganda) utilising the verification review model had a target timeline of 90 days. All six authorities conducted abridged reviews and fast-track assessments through a priority review track. The common technical document format was mandatory for applications in all authorities. The target timeline for key milestones in the review process varied for each country with a few similarities.DiscussionThe study has provided a baseline for review models, target timelines and data requirements utilised in assessing applications for registration by EAC-MRH NRAs. Implementing the recommendations from this study will enable the NRAs to align and improve their registration processes.
Refractive errors in Tianjin youth aged 6–18 years: exploring urban–rural variations and contributing factors
Authors: Fang Xin-He , Song De-Sheng , Jin Nan , Du Bei , Wei Rui-Hua 
Published: September 2024

PurposeRefractive errors, particularly myopia, constitute a significant global public health concern, contributing to morbidity and disability. A more comprehensive understanding of the determinants of refractive errors and the differences between urban and rural areas is essential to develop effective preventive measures for youth. This study aimed to compare the prevalence and risk factors of refractive errors among youth in urban and rural Tianjin, China.MethodsThis school-based cross-sectional study was conducted in 2022. Elementary, middle, and high school students aged 6–18 years from both urban and rural areas of Tianjin were included. All participants underwent visual acuity testing and refractive measurement and completed comprehensive questionnaires.ResultsA total of 346,146 participants (176,628 boys) were included in this investigation (50.36% for urban and 49.64% for rural, respectively). Myopia, hyperopia, astigmatism, and anisometropia were present in 56.8, 9.7, 56.64, and 21.3% of urban students, respectively. Similarly, rural students had a prevalence of 57.6, 11.5, 56.48, and 22.0% for the respective conditions. Compared to rural students, after adjusting for age, sex, and other significant variables, urban students were 1.05 times more likely to have myopia (95% CI: 1.03–1.07, p &lt; 0.0001), 0.71 times less likely to have hyperopia (95% CI: 0.69–0.73, p &lt; 0.0001), and 1.02 times more likely to have astigmatism (95% CI: 0.69–0.73, p &lt; 0.0001). There was no significant association between anisometropia and residence (OR: 1.00, 95% CI: 0.98–1.02, p = 0.9850). Sociodemographic and physiological factors contribute to the disparities in the prevalence of refractive errors between urban and rural areas. Age, increased near-work activities, and Decreased outdoor time were identified as risk factors for myopia, astigmatism, and anisometropia. Conversely, the absence of a parental history of refractive errors emerged as a protective factor for myopia and astigmatism among students. Lower parental education levels were negatively correlated with the risk of myopia and anisometropia in their children. Specifically, the lower the parental education, the greater the risk of myopia in their offspring. For urban students only, lower parental education was associated with an increased risk of astigmatism.ConclusionCrude prevalence estimates May not accurately reflect the true burden of refractive error due to confounding factors such as age and sex. Accounting for these factors revealed that urban students were more likely to have myopia and astigmatism but less likely to have hyperopia compared to their rural counterparts. These disparities highlight the importance of considering geographical variations when implementing strategies for myopia control and prevention.
The impact of carvacrol on the larval gut bacterial structure and function of Lymantria dispar
Authors: Yang Jing , Chen Yun-Ze , Zhang Guo-Cai 
Published: September 2024

IntroductionThe gut bacteria of insects play an important role in regulating their metabolism, immune system and metabolizing pesticides. Our previous results indicate that carvacrol has certain gastric toxic activity on Lymantria dispar larvae and affects their detoxification metabolism at the mRNA level. However, the impact of carvacrol on the gut bacteria of L. dispar larvae has been unclear.MethodsIn this study, the 16S rRNA sequencing technology was used to sequence and analyze the gut bacteria of the larvae which were exposed with sublethal concentration (0.297 mg/mL) and median lethal concentration (1.120 mg/mL), respectively.ResultsA total of 10 phyla, 16 classes, 47 orders, 72 families, 103 genera, and 135 species were obtained by using a 97% similarity cutoff level. The dominant bacterial phyla in the gut of the L. dispar larvae are Firmicutes and Proteobacteria. The treatment with carvacrol can significantly affect the structure of gut bacteria in the larvae of the L. dispar. At both doses, carvacrol can shift the dominant gut bacteria of the larvae from Proteobacteria to Firmicutes. At the genus level, two doses of carvacrol can significantly enhance the relative abundance of probiotic Lactobacillus in the gut of L. dispar larvae (p ≤ 0.01). Additionally, significant differences were observed among the five bacterial genera Burkholderia-Caballeronia-Paraburkholderia, Anoxybacillus, Pelomonas, Mesorhizobium (p ≤ 0.05). The analysis of α-diversity and β-diversity indicates that the treatment with carvacrol at two doses significantly affect the bacterial richness and diversity in the larvae. However, the results of functional classification prediction (PICRUSt) indicate that carvacrol significantly down-regulate 7 functions, including Energy metabolism, Cell growth and death, and up-regulate 2 functions, including Carbohydrate metabolism and Membrane transport. The network analysis indicates that the correlation between gut bacteria also has been changed. In addition, the insecticidal activity results of carvacrol against L. dispar larvae with gut bacteria elimination showed that gut bacteria can reduce the insecticidal activity of carvacrol against L. dispar larvae.DiscussionThis study provides a theoretical foundation for understanding the role of gut bacteria in detoxifying plant toxins and conferring pesticide resistance.
Discovery of anti-infective compounds against Mycobacterium marinum after biotransformation of simple natural stilbenes by a fungal secretome
Authors: Nitschke Jahn , Huber Robin , Vossio Stefania , Moreau Dimitri , Marcourt Laurence , Gindro Katia , Queiroz Emerson F. , Soldati Thierry , Hanna Nabil 
Published: September 2024

IntroductionMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, remains a serious threat to human health worldwide and the quest for new anti-tubercular drugs is an enduring and demanding journey. Natural products (NPs) have played a significant role in advancing drug therapy of infectious diseases.MethodsThis study evaluated the suitability of a high-throughput infection system composed of the host amoeba Dictyostelium discoideum (Dd) and Mycobacterium marinum (Mm), a close relative of Mtb, to identify anti-infective compounds. Growth of Dd and intracellular Mm were quantified by using luminescence and fluorescence readouts in phenotypic assays. The system was first benchmarked with a set of therapeutic anti-Mtb antibiotics and then used to screen a library of biotransformed stilbenes.ResultsThe study confirmed both efficacy of established antibiotics such as rifampicin and bedaquiline, with activities below defined anti-mycobacterium susceptibility breakpoints, and the lack of activity of pyrazinamide against Mm. The screening revealed the promising anti-infective activities of trans-δ-viniferins and in particular of two compounds 17 and 19 with an IC50 of 18.1 μM, 9 μM, respectively. Both compounds had no activity on Mm in broth. Subsequent exploration via halogenation and structure-activity relationship studies led to the identification of derivatives with improved selectivity and potency. The modes of action of the anti-infective compounds may involve inhibition of mycobacterial virulence factors or boosting of host defense.DiscussionThe study highlights the potential of biotransformation and NP-inspired derivatization approaches for drug discovery and underscores the utility of the Dd-Mm infection system in identifying novel anti-infective compounds.
Effects of Phaffia rhodozyma on microbial community dynamics and tobacco quality during tobacco fermentation
Authors: Mai Jing , Zhu Ming-Jun , Hu Bin-Bin , Zhang Hong , Liu Zhong-Hua , Sun Jian-Feng , Hu Yang , Zhao Lu 
Published: September 2024

IntroductionCarotenoids are important precursors of various aroma components in tobacco and play an important role in the sensory quality of tobacco. Phaffia rhodozyma is a species of Xanthophyllomyces capable of synthesizing a highly valuable carotenoid-astaxanthin, but has not yet been used in improving tobacco quality.MethodsThe dynamic changes of microbial community and metabolites during tobacco fermentation were analyzed in combination with microbiome and metabolome, and the quality of tobacco after fermentation was evaluated by sensory scores.ResultsP. rhodozyma could grow and produce carotenoids in tobacco extract, with a maximum biomass of 6.50 g/L and a maximum carotenoid production of 36.13 mg/L at 100 g/L tobacco extract. Meanwhile, the correlation analysis combined with microbiome and metabolomics showed that P. rhodozyma was significantly positively correlated with 11 metabolites such as 6-hydroxyluteolin and quercetin. Furthermore, the contents of alcohols, ketones and esters, which were important aromatic components in fermented tobacco, reached 77.57 μg/g, 58.28 μg/g and 73.51 μg/g, increasing 37.39%, 265.39% and 266.27% compared to the control group, respectively. Therefore, the aroma and flavor, and taste scores of fermented tobacco increased by 0.5 and 1.0 points respectively.DiscussionThis study confirmed that P. rhodozyma fermentation could effectively improve the sensory evaluation of tobacco, and provided a novel microbial fermentation method to improve tobacco quality.
Congenital deafness and vestibular disorders: a systematic literature review
Authors: Genovese Elisabetta , Segato Erika , Liberale Carlotta , Zampieri Erica , Monzani Daniele , Apa Enrico , Palma Silvia , Nocini Riccardo 
Published: September 2024

IntroductionCongenital deafness is a pathological entity that represents an economical and social burden, affecting up to 0.2% of newborns in Europe. Sensorineural hearing loss (SHL) is caused by a variety of factors, including congenital abnormalities, perinatal infectious diseases and genetic syndromes. The inner ear’s vestibular system, nestled alongside the auditory organs, is crucial for balance maintenance. Its close connection with the auditory system means that disturbances in one often coincide with disturbances in the other, highlighting their intertwined functions. With this review we aim to describe objective vestibular tests found in literature and to study their use for diagnosis of vestibular disturbances in patients affected by congenital deafness.MethodsThe review is conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. The search string used was: [(congenital deafness) OR (congenital hearing loss) OR (congenital hypoacusia)] AND [(vestibular disorders) OR (vertigo)]. An initial abstract reading selection was made, and a subsequent comprehensive full-text reading. For each article, we identified the type of vestibular test utilized and its corresponding outcome.ResultsOut of the initial—papers identified through the search string—articles met the eligibility criteria for further analysis through abstract and full-text reading. After further selection—articles were chosen for detailed examination, focusing on the data of patients.ConclusionCongenital hearing loss profoundly affects a child’s development, especially in language and communication skills, and it is frequently associated with a pathological vestibular system. Early identification allows timely intervention with personalized therapies. In current literature, there is still no gold standard test to identify balance disorders in patients with congenital hearing loss. There is considerable variability on the subject due to the inclusion of diverse patients with various diagnoses, alongside a wide range of available technologies. Managing such conditions necessitates collaboration among healthcare providers, ensuring comprehensive care through prompt diagnosis and personalized treatment plans. Ongoing research aims to further improve screening methods and develop precision medicine approaches tailored to individual needs.