bluuebunny/crossref_metadata_2025 huggingface dataset:
ЭПИДЕМИИ ГРИППА В РОССИИ В КОНТЕКСТЕ РАЗВИТИЯ СИСТЕМЫ ОБЩЕСТВЕННОГО ЗДРАВООХРАНЕНИЯ
Authors: ЕРМОЛАЕВА Е.В.
Published: February 2024

Формирование системы общественного здравоохранения в России способствовало изменению отношения к инфекционным болезням в российском обществе. Парадоксальность ситуации с гриппом состояла в том, что, несмотря на колоссальное количество умерших, гораздо больший страх вызывали другие заболевания, такие как чума, холера, оспа и др. Кажущаяся легкость симптомов приводила к тому, что заболевшие редко обращались за помощью, и врачи узнавали о заболевании, когда оно принимало массовый характер. Неясность происхождения болезни, сходство симптомов с другими заболеваниями, влияние религиозных учений, астрологии на объяснение причин болезни и последующее ее лечение, способствовали развитию эпидемий. Учет заболевших, выздоровевших и умерших от гриппа не производился, поэтому вплоть до XIX в. частота и реальный ущерб от эпидемий гриппа точно неизвестны. Совершенствование механизма государственного управления здравоохранением на губернском уровне, анализ деятельности местных органов медицинского управления, роль медицинской общественности в решении проблем здравоохранения, развитие санитарно-профилактической медицины в конце XIX – начале XX в. изменили ситуацию. Совершенствование знаний в области эпидемиологии, организация специальных эпидемических отрядов и эвакуационных отделений, обеспечение губерний квалифицированным медицинским персоналом и т.п., позволили разработать систему мероприятий, направленных как на снижение смертности от гриппа и борьбу с инфекцией, так и на его профилактику. Изучение возбудителей гриппа позволило установить его вирусную природу. Локализация источников эпидемий гриппа на востоке и их дальнейшее распространение по территории России и Европы позволили ряду исследователей предположить, что родиной инфекционных заболеваний является Китай. Популярности данной теории также способствовал сформировавшийся в европейских государствах стереотип о Китае как источнике различных вирусов.
360° approach to the patient with mite allergy: from scientific evidence to clinical practice
Authors: Nieto-García Antonio , Abel-Fernández Eva , Nieto-Cid María , Pineda de la Losa Fernando
Published: February 2024

In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.
Application of the iPLUS non-coding sequence in improving biopharmaceuticals production
Authors: Reis-Claro Inês , Silva Maria Inês , Moutinho Ana , Garcia Beatriz C. , Pereira-Castro Isabel , Moreira Alexandra
Published: February 2024

The biotechnological landscape has witnessed significant growth in biological therapeutics particularly in the field of recombinant protein production. Here we investigate the function of 3′UTR cis-regulatory elements in increasing mRNA and protein levels in different biological therapeutics and model systems, spanning from monoclonal antibodies to mRNA vaccines. We explore the regulatory function of iPLUS - a universal sequence capable of consistently augmenting recombinant protein levels. By incorporating iPLUS in a vector to express a monoclonal antibody used in immunotherapy, in a mammalian cell line used by the industry (ExpiCHO), trastuzumab production increases by 2-fold. As yeast Pichia pastoris is widely used in the manufacture of industrial enzymes and pharmaceuticals, we then used iPLUS in tandem (3x) and iPLUSv2 (a variant of iPLUS) to provide proof-of-concept data that it increases the production of a reporter protein more than 100-fold. As iPLUS functions by also increasing mRNA levels, we hypothesize that these sequences could be used as an asset in the mRNA vaccine industry. In fact, by including iPLUSv2 downstream of Spike we were able to double its production. Moreover, the same effect was observed when we introduced iPLUSv2 downstream of MAGEC2, a tumor-specific antigen tested for cancer mRNA vaccines. Taken together, our study provides data (TLR4) showing that iPLUS may be used as a valuable asset in a variety of systems used by the biotech and biopharmaceutical industry. Our results underscore the critical role of non-coding sequences in controlling gene expression, offering a promising avenue to accelerate, enhance, and cost-effectively optimize biopharmaceutical production processes.
Proanthocyanidins isolated from the leaves of Ficus glomerata evaluated on the activities of rumen enzymes: in vitro and in silico studies
Authors: Lata Suman , Koli Pushpendra , Singh Sultan , Bhadoria Brijesh Kumar , Chand Umesh , Yadav Dinesh Kumar , Al-Shuwaili Thamer , Ren Yonglin
Published: February 2024

Two new proanthocyanidins (2S:3S)-(−)-epicatechin-(4α→8)4-(2R:3R)-(+)-catechin (Compound 1) and (2R, 3R)-3-O-galloyl-(+)-catechin (4β→8)3-(2R, 3R)-3-O-galloyl-(+)-catechin (Compound 2) were isolated from Ficus glomerata and characterized by ultraviolet spectroscopy (UV), proton nuclear magnetic resonance (1H NMR), 13C NMR, and heteronuclear multiple bond correlation . The bioactivity and drug scores of isolated compounds were predicted using OSIRIS property explorer applications with drug scores of 0.03 (compound 1) and 0.05 (compound 2). Predictive drug scores provided an indication of the compounds’ potential to demonstrate desired biological effects. Furthermore, the newly discovered proanthocyanidins tended to interact with protein due to their chemical structure and molecular conformation. With the aim of maintaining this focus, compounds 1 and 2 were subjected to in vitro testing against ruminal enzymes to further explore their potential impact. Both compounds showed significant inhibition activities (p < 0.01) against glutamic oxaloacetic transaminase in both protozoa and bacterial fractions, with an effective concentration (EC50) of 12.30–18.20 mg/mL. The compounds also exhibited significant inhibition (p < 0.01) of ruminal glutamic pyruvic transaminase activity, with EC50 values ranging from 9.77 to 17.38 mg/mL. Furthermore, the inhibition was recorded in R-cellulase between EC50 values of 15.85 and 23.99 mg/mL by both compounds. Additionally, both compounds led to a decrease in protease activity with increasing incubation time and concentration. In conclusion, the results indicate that these novel proanthocyanidins hold the potential to significantly impact rumen enzyme biology. Furthermore, their promising effects suggest that they could be further explored for drug development and other important applications.
Case Report: Incidental finding of an atresia of the inferior vena cava—a challenge for cardiac surgery
Authors: Buech Joscha , Radner Caroline , Fabry Thomas , Rutkowski Simon , Hagl Christian , Peterss Sven , Pichlmaier Maximilian A.
Published: February 2024

Inferior vena cava atresia is a rare and usually asymptomatic condition. However, when these patients undergo cardiac surgery, it can present an unexpected and challenging situation for the surgeon. Specifically, adequate venous drainage during cardiopulmonary bypass (CPB) is a critical issue here and may require an extension of cannulation strategies. Adequate preoperative diagnostics, ideally with imaging modalities such as CT angiography or MRI, are required for optimal surgical planning. Here, we describe a rare case of thoracic ascending aortic aneurysm with concomitant inferior vena cava atresia that was successfully operated on. With adequate preoperative planning, we were able to perform an operation without unforeseen complications with standard initialization of CPB.
Predicting rock mass rating ahead of the tunnel face with Bayesian estimation
Authors: Li Xiaojun , Chen Ziyang , Tang Li , Chen Chao , Li Tao , Ling Jiaxin , Lu Yanyun , Rui Yi
Published: February 2024

The rock mass rating (RMR) system plays a crucial role in geomechanics assessments for tunnel projects. However, conventional methods combining empirical and geostatistical approaches often yield inaccuracies, particularly in areas with weak strata such as faults and karst caves. To address these uncertainties and errors inherent in empirical techniques, we propose a progressive RMR prediction strategy based on the Bayesian framework. This strategy incorporates three key components: 1) Variogram modeling: utilizing observational data from the excavation face, we construct and update a variogram model to capture the spatial variability of RMR. 2) TSP-RMR statistic model: we integrate a TSP-RMR statistical model into the Bayesian sequential update process. 3) Bayesian maximum entropy (BME) integration: the BME method combines geological information obtained from tunnel surface excavation with tunnel seismic prediction (TSP) data, ultimately enhancing the RMR prediction accuracy. Our methodology is applied to the Laoying rock tunneling project in Yunnan Province, China. Our findings demonstrate that the fusion of soft data and geological interpretation significantly improves the accuracy of RMR predictions. At selected prediction points, the relative error of our method is less than 15% when compared to the traditional Kriging method. This approach holds substantial potential for advancing RMR estimation ahead of tunnel excavation, particularly when advanced geological forecast data are available.
What would it take? Enhancing outcomes for high-ability students with disability
Authors: Townend Geraldine , McGregor Marie , Alonzo Dennis , Nguyen Hoa T. M.
Published: February 2024

A troubling misconception exists that high-ability is enough to ensure positive educational, mental health and well-being outcomes for gifted students. Of course, we want all our students to develop their potential in school, so why are so many of our more able children failing in school and enduring the repercussions of reduced well-being? The notion that a student is not highly able if they are receiving poor grades is a common societal misconception, and this is commonly the case for gifted learners with disability, also known as twice-exceptional students. A considerable number of school students globally have intellectual ability in the gifted range, a high number of those are gifted with co-occurring disability, and many remain unidentified. It is, therefore, likely that a significant percentage of our classrooms have students who may be flying under the radar and are likely to be underachieving or unsupported within the school system. The purpose of this article is to highlight the issues around gifted students with disability that may contribute to their underachievement. Also discussed is how educators, counsellors and other key stakeholders can support this unique population of students.
Interests and personality matter in the choice of teacher education program
Authors: Leichner Nikolas , Ottenstein Charlotte , Weis Susanne , Schmitt Manfred , Lischetzke Tanja
Published: February 2024

In this paper, we examined whether it is possible to predict German teacher students’ study specialization (i.e., type of school) from data on their personality (in terms of the Big Five) and vocational interests (in terms of the RIASEC model) using multinomial logistic regression. Gender and intelligence were included as control variables. Two studies are reported. The first study (N = 1,145 teacher students) took place at a German university, while Study 2 used data from the German National Education Panel Study (NEPS; data from N = 944 teacher students). In both studies, it was found that the model fit increased significantly after adding personality and vocational interests as predictors (compared with a baseline model containing only gender and intelligence as predictors). Findings show that the model of vocational interests and the Big Five personality model can be used to differentiate between teacher students with different specializations. In the long run, results like these could be used in the field of counseling to help clients who are determined to become a teacher but unsure about which specialization might be most appropriate for them.
Proppant distribution characteristics based on the coring well analysis
Authors: Wang Tao , Zhang Jizhuo , Xiang Yuankai , Tang Wei , Yin Shitan , Ye Yiping , Shi Shanzhi , Li Yi
Published: February 2024

It is significant to clarify the proppant distribution pattern under real fracturing conditions to optimize the sand addition process in hydraulic fracturing of the Mahu tight conglomerate reservoir. However, the laboratory experiment is far from the real fracturing condition due to the limitations of scale, pumping scale, and stress conditions. In this paper, the proppant in cuttings and mud was obtained by screening and cleaning samples from the high-deviated coring well of the Mahu conglomerate reservoir in Xinjiang. The sphericity of particles was observed by a continuous variable magnification microscope, and the transparency (TR) of particles and the red-blue difference (RBD) of reflected light were followed by transmitted light. Considering these three factors, the proppant identification method in cuttings was established to obtain the spatial location and distribution of proppant along the whole well section. The effect of proppant transport and placement was evaluated. The results show that: (1) Compared with the formation of mineral particles, the proppant has better sphericity, TR>20%, and RBD > 30. Combined with the surface roughness, luster, and associated minerals, the particle can be evaluated as a proppant. (2) The content of proppant with small particle size (40/70 mesh) is significantly higher than that with large particle size (20/40 mesh), which ranges from 10‰ to 450‰ and 5‰ to 280‰, respectively. (3) Horizontally, 20/40 mesh proppant migrates approximately 10m, and 40/70 mesh proppant migrates approximately 23 m in the hydraulic fracture. (4) In the longitudinal fracture, 20/40 mesh proppant was concentrated at a 12 m vertical distance from the adjacent well, while 40/70 mesh proppant was placed at a larger longitudinal range, approximately 10 m above and 10 m below the adjacent well. The research results have certain reference significance for the improvement measures of the sand-adding process in the Mahu tight conglomerate reservoir.
Research on the impact of water-saving technologies on the agricultural production efficiency of high-quality farmers------taking Jiangxi province and Guangdong province in China as examples
Authors: Lei Xiankai , Yang Dongmei
Published: February 2024

Based on the survey data of 1707 high-quality farmers in Guangdong and Jiangxi provinces in China, this article uses the DEA-tobit model and propensity score matching method to explore the impact of water-saving technology adoption on agricultural production efficiency from a micro perspective. The research results show that the adoption of water-saving technology by high-quality farmers can significantly improve agricultural production efficiency. By comparing the results with the baseline regression using propensity score matching method, the study findings are found to be robust. The mechanism and results of the study indicate that agricultural subsidy policies play a regulatory role between water-saving technology adoption and the agricultural production efficiency of high-quality farmers. Further analysis reveals that the impact of water-saving technology on the production efficiency of different types of high-quality farmers varies. Specifically, water-saving technology has a greater impact on the production efficiency of farmer cooperatives and agricultural enterprises compared to large-scale farming households and family farms. Therefore, policy recommendations are proposed to improve the water-saving agricultural technology system, among other aspects.
The effect of limited access to antenatal care on pregnancy experiences and outcomes among undocumented migrant women in Europe: a systematic review
Authors: Osuide Jennifer Okhianosen , Parsa Ali Davod , Mahmud Ilias , Kabir Russell
Published: February 2024

Women who are undocumented migrants in Europe encounter a variety of challenges while trying to access health services, including restricted access to antenatal care (ANC) despite the importance of ANC to the well-being of mothers and their infants. This study's aim was to examine the effect that limited access to antenatal care has on the pregnancy experiences and outcomes of undocumented migrant (UM) women in Europe. Systematic searches were done on PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL Plus, and BioMed Central. From the search results, only primary research articles that reported on the pregnancy outcomes and experiences of undocumented migrants were selected. A meta-analysis was not possible because this review included information from both qualitative and quantitative studies. The data that was taken from the included publications was organised, analysed, using the Microsoft Excel programme, and then meta-synthesised. Twelve papers from seven different European nations—Belgium, France, Sweden, Denmark, Norway, Finland, and England—were included in this systematic review. Eight of the studies aimed to explore the access to and utilization of ANC by undocumented migrant women and the related pregnancy outcomes. Two of the included studies examined the pregnancy experiences of UMs and two examined the perinatal risks associated with living as a migrant with no legal status. Although heterogeneous in their specific findings most of the studies showed undocumented immigrants are more likely to experience unfavourable pregnancy outcomes and experience greater anxiety and worries due to a variety of factors than documented migrants and registered citizens. This review's conclusions demonstrate the pressing need for policy modifications and healthcare reforms in Europe to address the problems associated with undocumented migrants’ restricted access to antenatal care. It also highlights the urgent need for structural changes that will give this vulnerable population's health and well-being a higher priority. It is not just an issue of health equality but also a humanitarian obligation to address the many obstacles and difficulties undocumented migrant women endure during pregnancy.
Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell
Authors: Yang Nan , Srivastava Kamal , Chen Yujuan , Li Hang , Maskey Anish , Yoo Patrick , Liu Xiaohong , Tiwari Raj K. , Geliebter Jan , Nowak-Wegrzyn Anna , Zhan Jixun , Li Xiu-Min
Published: February 2024

Introduction

Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models.

Methods

Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP.

Results

XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range.

Conclusions

XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.
Effects of a music therapy and music listening intervention for nursing home residents with dementia: a randomized controlled trial
Authors: Prick Anna-Eva J. C. , Zuidema Sytse U. , van Domburg Peter , Verboon Peter , Vink Annemieke C. , Schols Jos M. G. A. , van Hooren Susan
Published: February 2024

Introduction

The aim of the present study was to evaluate the effects of an individual music therapy intervention and an individual music listening intervention on neuropsychiatric symptoms and quality of life in people with dementia living in a nursing home and on professional caregiver’s burden to be able to make statements about their specific value of application in clinical practice.

Methods

A multicenter single blind randomized controlled trial with three groups was performed: an individual music therapy intervention (IMTI) group (n = 49), an individual music listening intervention (IMLI) group (n = 56) and a control group (n = 53) receiving usual care. The interventions were given during three weeks, three times a week on non-consecutive days during 30–45 minutes for in total nine sessions. The endpoint of the study is the difference from baseline to interim (1,5 week), post-intervention (3 weeks) and follow-up (6 weeks) in reported scores of problem behaviour (NPI-NH) and quality of life (Qualidem) in people with dementia and occupational disruptiveness (NPI-NH) in care professionals.

Results

In total 158 people with dementia were randomized to one of the two intervention groups or the control group. Multilevel analyses demonstrated that hyperactive behaviour assessed by the NPI-NH was significantly more reduced for the IMLI group at follow up and that restless behaviour assessed by the Qualidem was significantly more reduced for the IMTI group at post and follow-up measurement compared to the control group. No significant effects between groups were found in other NPI-NH clusters or Qualidem subscales.

Conclusion

In conclusion, because we found no convincing evidence that the IMTI or IMLI is more effective than the other both interventions should be considered in clinical practice. For the future, we advise further research into the sustainability of the effects with alternative designs, like a single case experimental design.
The impact of a modified microbiota-accessible carbohydrate diet on gut microbiome and clinical symptoms in colorectal cancer patients following surgical resection
Authors: Kim Boyeon , Lee Jiwon , Jung Eun Sung , Lee Sunyoung , Suh Dong Ho , Park Yu Jin , Kim Jin , Kwak Jung-Myun , Lee Soohyeon
Published: February 2024

A high-fiber diet is widely recognized for its positive effects on the gut microbiome. However, the specific impact of a high-fiber diet on the gut microbiome and bowel habits of patients with colon cancer remains poorly understood. In this study, we aimed to assess the effects of a modified microbiota-accessible carbohydrate (mMAC) diet on gut microbiota composition and clinical symptoms in colon cancer patients who underwent surgical resection. To achieve this, we enrolled 40 patients in two groups: those who received adjuvant chemotherapy and those who did not. Fecal samples were collected before and after dietary interventions for microbial and metabolite analyses. Each group was randomized in a 1: 1 ratio to follow either a 3-week conventional diet followed by a 3-week mMAC diet, or the reverse sequence. Although there were no significant differences in the microbial diversity data before and after the mMAC diet in both the non-chemotherapy and chemotherapy groups, distinct differences in gut microbial composition were revealed after the mMAC diet. Specifically, the abundance of Prevotella, which is associated with high-fiber diets, was further elevated with increased concentrations of acetate and propionate after the mMAC diet. Additionally, patients who experienced improved diarrhea and constipation after the mMAC diet exhibited an enrichment of beneficial bacteria and notable changes in metabolites. In conclusion, this study provides valuable insights into the potential benefits of the mMAC diet, specifically its impact on the gut microbiome and clinical symptoms in postoperative colorectal cancer (CRC) patients. These findings emphasize the potential role of a high-fiber diet in influencing the gut microbiome, and the clinical symptoms warrant further investigation.
Identifying the oral microbiome of adolescents with and without dental fluorosis based on full-length 16S rRNA gene sequencing
Authors: Luo Shanshan , Shao Ruirui , Hong Yue , Zhang Ting , Zhou Qingshuai , Zhou Qian , Rao Fengqing , Zhao Xingxing , Dong Yangting , Zhu Ruiyu , Ling Ping , Cui Guzhen , Guan Zhizhong , Luo Peng , He Yan , Qi Xiaolan , Liao Jian , Hong Wei
Published: February 2024

Dental fluorosis, resulting from long-term environmental exposure to fluoride, is prevalent among diverse populations worldwide. Severe fluorosis not only compromises the aesthetic appeal of teeth but also impairs their functionality. This study aims to investigate the oral microbiome in dental fluorosis and the health individuals of adolescents living in the endemic fluorosis area of Guizhou, China through full-length 16S rDNA sequencing. Fourty-six individuals meet the sampling criteria, and we divided these samples into the following groups: a healthy group (H = 23) and a dental fluorosis group (F = 23), and two subgroups of Miao ethnicity: a healthy Miao group (Hm = 13) and a dental fluorosis Miao group (Fm = 15). A total of 660,389 high-quality sequences were obtained, and 12,007 Amplicon Sequence Variants (ASVs) were identified, revealing significant variations in oral microbiome between Fm and Hm groups. The composition of oral microbiota was similar between the H and F groups. At the genus level, Pseudopropionibacterium and at the species level, Streptococcus oralis_subsp.dentisani_clade_058 were less abundant in group F than in group H (P < 0.05). Further analysis revealed that the abundance of Capnocytophaga gingivalis and Kingella denitrificans was significantly lower in Fm fluorosis patients than in the Hm group (P < 0.05). Based on the LEfSe analysis, the potential core biomarkers in the oral of Fm fluorosis patients were identified at different taxonomic levels, ranging from phylum to species. These include Gammaproteobacteria, Prevotella sp_HMT_304, Gemella sanguinis, and Gracilibacteria_(GN02). Network analysis revealed that the microbiota in the fluorosis group exhibited more complex interactions with each other than the healthy group. Notably, within the Hm group, the potential biomarkers Capnocytophaga gingivalis and Kingella denitrificans exhibited a positive correlation. Finally, we employed PICRUSt2 analysis to explore the abundance clustering of the top 30 functional units in each sample, and we found that the metabolic pathway compositions of the four groups were similar. In summary, our findings suggest that the microbial composition of plaque in Hm patients with dental fluorosis is significantly altered, and we identified the potential marker microorganisms that contribute to these changes.
Alternative polyadenylation and dynamic 3′ UTR length is associated with polysome recruitment throughout the cardiomyogenic differentiation of hESCs
Authors: Hansel-Frose Aruana F. F. , Allmer Jens , Friedrichs Marcel , dos Santos Hellen Geremias , Dallagiovanna Bruno , Spangenberg Lucía
Published: February 2024

Alternative polyadenylation (APA) increases transcript diversity through the generation of isoforms with varying 3′ untranslated region (3′ UTR) lengths. As the 3′ UTR harbors regulatory element target sites, such as miRNAs or RNA-binding proteins, changes in this region can impact post-transcriptional regulation and translation. Moreover, the APA landscape can change based on the cell type, cell state, or condition. Given that APA events can impact protein expression, investigating translational control is crucial for comprehending the overall cellular regulation process. Revisiting data from polysome profiling followed by RNA sequencing, we investigated the cardiomyogenic differentiation of pluripotent stem cells by identifying the transcripts that show dynamic 3′ UTR lengthening or shortening, which are being actively recruited to ribosome complexes. Our findings indicate that dynamic 3′ UTR lengthening is not exclusively associated with differential expression during cardiomyogenesis but rather with recruitment to polysomes. We confirm that the differentiated state of cardiomyocytes shows a preference for shorter 3′ UTR in comparison to the pluripotent stage although preferences vary during the days of the differentiation process. The most distinct regulatory changes are seen in day 4 of differentiation, which is the mesoderm commitment time point of cardiomyogenesis. After identifying the miRNAs that would target specifically the alternative 3′ UTR region of the isoforms, we constructed a gene regulatory network for the cardiomyogenesis process, in which genes related to the cell cycle were identified. Altogether, our work sheds light on the regulation and dynamic 3′ UTR changes of polysome-recruited transcripts that take place during the cardiomyogenic differentiation of pluripotent stem cells.
Influence of short-term hypoxic exposure on spatial learning and memory function and brain-derived neurotrophic factor in rats—A practical implication to human's lost way
Authors: Kiuchi Masataka , Uno Tadashi , Hasegawa Tatsuya , Koyama Katsuhiro , Horiuchi Masahiro
Published: February 2024

The present study aimed to investigate the effects of a short period of normobaric hypoxic exposure on spatial learning and memory, and brain-derived neurotrophic factor (BDNF) levels in the rat hippocampus. Hypoxic conditions were set at 12.5% O2. We compared all variables between normoxic trials (Norm), after 24 h (Hypo-24 h), and after 72 h of hypoxic exposure (Hypo-72 h). Spatial learning and memory were evaluated by using a water-finding task in an open field. Time to find water drinking fountains was significantly extended in Hypo 24 h (36.2 ± 21.9 s) compared to those in Norm (17.9 ± 12.8 s; P < 0.05), whereas no statistical differences between Norm and Hypo-72 h (22.7 ± 12.3 s). Moreover, hippocampal BDNF level in Hypo-24 h was significantly lower compared to Norm (189.4 ± 28.4 vs. 224.9 ± 47.7 ng/g wet tissue, P < 0.05), whereas no statistically differences in those between Norm and Hypo-72 h (228.1 ± 39.8 ng/g wet tissue). No significant differences in the changes in corticosterone and adrenocorticotropic hormone levels were observed across the three conditions. When data from Hypo-24 h and Hypo-72 h of hypoxia were pooled, there was a marginal negative relationship between the time to find drinking fountains and BDNF (P < 0.1), and was a significant negative relationship between the locomotor activities and BDNF (P < 0.05). These results suggest that acute hypoxic exposure (24 h) may impair spatial learning and memory; however, it recovered after 72 h of hypoxic exposure. These changes in spatial learning and memory may be associated with changes in the hippocampal BDNF levels in rats.
Assessing the association between age at first sexual intercourse and migraine: a Mendelian randomization study
Authors: Zhu Guoliang , Wang Miao , Wang Yawen , Kong Fanyi
Published: February 2024

Background and objectives

As indicated by observational and genetic variation studies, age at first sexual intercourse (AFS) may be associated with migraine attack, but there is a lack of evidence from real-world studies due to ethical concerns. Therefore, we conducted a Mendelian randomization study to determine the causal relationship between AFS and migraine.

Methods

We extracted instrumental variables from summary data of a genome-wide association study (GWAS) on AFS and migraine and then conducted two-sample Mendelian randomization analyses. GWAS data for AFS and migraine were obtained from 397,338 unrelated individuals (214,547 females and 182,791 males) and 306,314 individuals (18,477 patients and 287,837 control individuals), respectively.

Results

There was a causal relationship between AFS and risk for migraine (odds ratio (OR) = 0.73, 95% confidence interval (CI) [0.61 to 0.86]), both for migraine with aura (MWA; OR = 0.72, 95% CI [0.58 to 0.89]) and migraine without aura (MOA; OR = 0.66, 95% CI [0.51 to 0.86]). Stratified analyses provided suggestive evidence of the causal relationship between delayed AFS and a decreased risk of migraine for both males (OR = 0.71, 95% CI [0.59 to 0.84]) and females (OR = 0.73, 95% CI [0.61 to 0.89]). Reverse Mendelian randomization did not reveal any effect of migraine on AFS (p > 0.05). No pleiotropy was detected.

Discussion

A delayed AFS is a protective factor against migraine (for both MWA and MOA) in both males and females. This causal relationship indicates the presence of extracranial regulatory pathways of migraine.
The impact of plant-rich diets on sleep: a mini-review
Authors: Polianovskaia Anastasiia , Jonelis Michelle , Cheung Joseph
Published: February 2024

Plant-rich diets (PRDs), also referred to as plant based diets, have been shown to have beneficial effects on various chronic diseases and all-cause mortality. However, limited data are available on the effect of such diets on sleep and sleep disorders. In this review article, we explore existing evidence and potential mechanisms by which PRDs may impact sleep and sleepiness. High-fat diets are associated with drowsiness, while fiber-rich diets improve sleep quality. Anti-inflammatory diets may benefit patients with sleep disturbances, and diets rich in tryptophan and serotonin precursors may improve sleep quality. Isoflavones and polyphenols present in PRDs may also have a positive impact on sleep. Furthermore, diets rich in plants may reduce the risk of obstructive sleep apnea and associated daytime sleepiness. Overall, the current knowledge about PRDs in sleep and sleep disorders is limited, and further research is needed to explore the potential advantages of this dietary approach in sleep disorders.
Selective inhibition of DNA ligase IV provides additional efficacy to the treatment of anaplastic thyroid cancer
Authors: Sriramareddy Sathya Neelature , Jamakhani Majeed , Vilanova Léa , Brossel Hélène , Staumont Bernard , Hamaidia Malik
Published: February 2024

Background

Although the incidence of anaplastic thyroid carcinoma (ATC) is low (2.5% of thyroid cancer cases), this cancer has a very poor prognosis (survival rates < 5 months) and accounts for 14–39% of deaths. Conventional therapies based on surgery in combination with radiotherapy or chemotherapy showed limited effectiveness primarily due to the robust and protective DNA damage response in thyroid cancer cells.

Methods

We used single-cell transcriptomic data from patients with different subtypes of thyroid cancer to study expression of genes involved in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Then, we investigated the mechanisms of DNA damage and repair in anaplastic (C643 and Hth74) and papillary (TPC-1) thyroid cancer cell lines. The effect of caffeine (inhibitor of ATM and ATR) and UCN-01 (CHK1 inhibitor) was evaluated in cell cycle progression of thyroid cancer cells after γ‐radiation or doxorubicin treatment. The DNA damage response was monitored after staining of phosphorylated γ-H2AX and 53BP1. Reporter plasmids were used to determine the efficacy of double-strand DNA breaks (DSBs) repair by HR and NHEJ in thyroid cancer cells. We evaluated the combination of selective inhibition of the DNA ligase IV by SCR7 and doxorubicin on cellular apoptosis and tumor growth in xenograft murine models of anaplastic thyroid cancer.

Results

Single-cell RNA-Seq showed that NHEJ- and HR-related genes are expressed in ATC and PTC patients. We showed that ATC cells undergo mitosis in the presence of unrepaired DNA damage caused by γ‐radiation and doxorubicin treatment. To proliferate and survive, these cells efficiently repair DNA lesions using homologous recombination (HR) and non-homologous end joining (NHEJ). The combination of SCR7 with doxorubicin, significantly increased apoptosis and impaired ATC tumor growth in a xenograft mouse model compared to doxorubicin monotherapy.

Conclusion

This study shows the therapeutic value of the combination of a DNA ligase IV inhibitor and DNA-damaging agents (doxorubicin and/or γ-radiation) for the treatment of anaplastic thyroid cancer.
Massive extrapancreatic solid pseudopapillary neoplasm misdiagnosed as hepatic tumor: a case report and literature review
Authors: Guo Jixu , Zhao Qingjuan , Qin Liting , Xie Shengjie , Lu Shiliu , Li Baibei , He Meilin , Xie Linhong , Yu Shuiping
Published: February 2024

Background

Solid pseudopapillary neoplasms (SPNs) of the pancreas are uncommon, low-malignancy neoplasms. Moreover, the occurrence of extrapancreatic SPNs is rarely encountered.

Case summary

A 45-year-old female presented with a right upper abdominal mass and abdominal pain for 3 and 1 months as chief complaints, respectively. Initially, the patient was misdiagnosed with hepatocellular carcinoma based on her symptoms and results of physical and imaging examinations. Following multidisciplinary discussion and ruling out surgical contraindications, a decision was taken to proceed with surgical intervention. Interestingly, the tumor was found to originate from the retroperitoneum and had invaded the right half of the liver and the right wall of the inferior vena cava. The operation was uneventful, and the pathological findings confirmed the tumor as an extrapancreatic SPN. The patient remained asymptomatic after 15 months of follow-up.

Conclusion

Surgical treatment remains the preferred option for extrapancreatic SPN. The preoperative misdiagnosis also highlights the importance of accurate diagnosis and the development of appropriate treatment strategies for liver masses.
Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Li Fucheng , Wang Youyu , Dou He , Chen Xingyan , Wang Jianan , Xiao Min
Published: February 2024

Background

The persistence of inflammatory stimulus has a tight relationship with the development of age-related diseases, ultimately resulting in a gradual escalation in the prevalence of tumors, but this phenomenon is rare in young cancer patients. Breast cancer arising in young women is characterized by larger tumor diameters and more aggressive subtypes, so neoadjuvant chemotherapy (NACT) can be especially appropriate for this population. Immune inflammatory biomarkers have been reportedly linked to the prognosis of some malignant tumor types, with varying results. In this study, we investigated the possible predictive value of blood-based markers in young breast cancer patients undergoing NACT, in addition to the association between the clinicopathological features and prognosis.

Methods

From December 2011 to October 2018, a total of 215 young breast cancer patients referred to Harbin Medical University Cancer Hospital received NACT and surgery were registered in this retrospective study. The pretreatment complete blood counts were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV).

Results

NLR, PLR, MLR, and PIV optimal cut-off values were 1.55, 130.66, 0.24, and 243.19, as determined by receiver operating characteristic analysis. Multivariate analysis revealed that PIV, HR status, HER-2 status, and Ki-67 index were all independent predictive factors for pathological complete response. Subgroup analysis revealed that young breast cancer patients in the population characterized by low PIV and HR negative group were more likely to get pCR (P=0.001). The five-year overall survival (OS) rate was 87.9%, and Cox regression models identified PIV as independently related to OS.

Conclusion

In the present study, the pretreatment PIV was found to be a useful prognostic indicator for pCR and long-term survival in young breast cancer patients undergoing NACT. High immune and inflammation levels, MLR and PIV were connected to poor clinical prognosis in young breast cancer patients. PIV is a promising biomarker to guide strategic decisions in treating young breast cancer.
Characterisation of RSV infections in children without chronic diseases aged 0–36 months during the post-COVID-19 winter season 2022/2023
Authors: Meier Katharina , Riepl Angela , Voitl Peter , Lischka Lena , Voitl Julian J. M. , Langer Klara , Kuzio Ulrike , Redlberger-Fritz Monika , Diesner-Treiber Susanne C.
Published: February 2024

Background

Respiratory syncytial virus (RSV) is one of the leading causes of hospitalisation, morbidity, and mortality due to respiratory infection in the first years of life. This longitudinal prospective study outlines the 2022/23 season's viral patterns in Austria after the epidemiological changes determined by public health measures. We aimed to highlight differences within the RSV subtypes and genotypes in 0–36-month-old children without chronic diseases in the outpatient setting.

Methods

From November 2022 to March 2023 children younger than 36 months admitted to Vienna's largest paediatric primary healthcare centre with an acute respiratory infection were enrolled in this study. Nasal swabs and multiplex PCR panels detected 20 viruses including RSV subtypes and genotypes. Clinical presentation, features, and treatment of the participants were documented and analysed using the Modified Tal Score (MTS). Patients were scheduled for a telemedical follow-up one week after the initial appointment. Analysis was done using descriptive statistics, including Cramér V and binominal logarithmic regression.

Results

Among the 345 samples from 329 children, RSV was the most common virus (31.9%), followed by influenza (17.5%) and rhinovirus infections (20.58%). Of the RSV positive samples, only 13 cases were RSV subtype A (11.8%), whereas 97 were of subtype B (87.3%); ON1 and BA9 were the only detectable RSV genotypes (ON1: BA9 = 1:9.25). RSV was the main predictor of hospitalisation (OR: 7.5, 95% CI: (1.46–38.40), and age had a significant but smaller effect (OR: 0.89, 95% CI: (0.81–0.99). Almost all patients' clinical status improved within the first days.

Conclusion

RSV cases showed a rapid onset in late November 2022, and subtype B was predominant throughout the season. RSV infection was associated with higher hospitalisation rates, even after excluding high-risk patients (preterm and severe chronic diseases population).

Further testing in the upcoming winter seasons will improve our knowledge of the dominant subtype and its association with disease severity, especially with the development of novel RSV vaccine candidates.
A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer’s disease, and their co-morbidities
Authors: Pan Yun , Li Jieying , Lin Panjie , Wan Lihua , Qu Yiqian , Cao Lingyong , Wang Lei
Published: February 2024

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid β accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.
Artificial light at night alters progression of cold neuropathy in a sex-dependent manner in a mouse model of type II diabetes mellitus
Authors: Bumgarner Jacob R. , White Rhett C. , Brown Jordan A. , Nelson Randy J.
Published: February 2024

Artificial light at night (ALAN) is a pervasive circadian rhythm disruptor. Exposure to ALAN is associated with detrimental effects on physiology and behavior, including disrupted metabolism, immune function, endocrine function, and pain behavior. Given the detrimental effects of ALAN and other circadian rhythm disruptors on pain, we sought to understand how ALAN may alter the progression and severity of diabetic neuropathy. To do this, we used a previously reported high-fat diet and streptozotocin injection protocol to induce a type II diabetic phenotype in ∼8 week old female and male mice and then exposed the mice to either control or ALAN lighting conditions in 14:10 h light-dark cycles for 4 weeks. Male mice housed in control conditions exhibited reduced responsiveness to cold pain; in contrast, ALAN blunted this effect in male mice. ALAN exposure also elevated blood glucose and altered body mass loss in male mice. These effects were not present in female mice. The results of this study highlight the need to consider and study ALAN exposure and sex as a biological variable as risk factors in the treatment and mitigation of pain.