bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoid receptor type 1 in the aging gut regulates the mucosal permeability via miR-191-5p
Authors: Lee Yunna , Kim Yuju , Park Soyeong , Heo Gwangbeom , Chung Hae Young , Im Eunok
Published: August 2023

Background

Aging is associated with a broad loss of function throughout the body, and gastrointestinal (GI) dysfunction can occur with aging. The endocannabinoid (eCB) system plays a pivotal role in various GI diseases, and alterations in the eCB system have been observed during brain and skin aging. Therefore, we investigated the putative role of the eCB system in aging-related changes in the intestine.

Methods

The expression of cannabinoid receptor type 1 (CB1) was investigated in rat intestinal tissues using quantitative real-time PCR. Cellular senescence was induced by hydrogen peroxide (H2O2) and hydroxyurea (HU) in rat and human intestinal epithelial cells. Cellular permeability was evaluated by transepithelial electrical resistance (TEER) measurement.

Results and Discussion

The expression of CB1 was decreased in the small intestine of aged rats compared to that of young rats. Senescent cells showed reduced TEER values and decreased expression of ZO-1, indicating increased intestinal permeability, which is tightly regulated by the CB1 signaling. In silico miRNA analysis suggested that ZO-1 was a direct target gene of miR-191-5p. Increased expression of miR-191-5p by HU was restored by CB1 agonist ACEA co-treatment. Moreover, NF-κB p65 activation was associated with CB1-related miR-191-5p signaling. In conclusion, aging-induced CB1 reduction leads to increased intestinal permeability and decreased ZO-1 expression via upregulation of miR-191-5p and NF-κB p65 activation. Taken together, these results suggest that CB1 signaling may be a useful strategy to reduce intestinal permeability in aging-related and other inflammatory conditions in the gut.
Development and evaluation of a risk prediction model for diabetes mellitus type 2 patients with vision-threatening diabetic retinopathy
Authors: Gong Di , Fang Lyujie , Cai Yixian , Chong Ieng , Guo Junhong , Yan Zhichao , Shen Xiaoli , Yang Weihua , Wang Jiantao
Published: August 2023

Objective

This study aims to develop and evaluate a non-imaging clinical data-based nomogram for predicting the risk of vision-threatening diabetic retinopathy (VTDR) in diabetes mellitus type 2 (T2DM) patients.

Methods

Based on the baseline data of the Guangdong Shaoguan Diabetes Cohort Study conducted by the Zhongshan Ophthalmic Center (ZOC) in 2019, 2294 complete data of T2DM patients were randomly divided into a training set (n=1605) and a testing set (n=689). Independent risk factors were selected through univariate and multivariate logistic regression analysis on the training dataset, and a nomogram was constructed for predicting the risk of VTDR in T2DM patients. The model was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC) in the training and testing datasets to assess discrimination, and Hosmer-Lemeshow test and calibration curves to assess calibration.

Results

The results of the multivariate logistic regression analysis showed that Age (OR = 0.954, 95% CI: 0.940-0.969, p = 0.000), BMI (OR = 0.942, 95% CI: 0.902-0.984, p = 0.007), systolic blood pressure (SBP) (OR =1.014, 95% CI: 1.007-1.022, p = 0.000), diabetes duration (10-15y: OR =3.126, 95% CI: 2.087-4.682, p = 0.000; >15y: OR =3.750, 95% CI: 2.362-5.954, p = 0.000), and glycated hemoglobin (HbA1C) (OR = 1.325, 95% CI: 1.221-1.438, p = 0.000) were independent risk factors for T2DM patients with VTDR. A nomogram was constructed using these variables. The model discrimination results showed an AUC of 0.7193 for the training set and 0.6897 for the testing set. The Hosmer-Lemeshow test results showed a high consistency between the predicted and observed probabilities for both the training set (Chi-square=2.2029, P=0.9742) and the testing set (Chi-square=7.6628, P=0.4671).

Conclusion

The introduction of Age, BMI, SBP, Duration, and HbA1C as variables helps to stratify the risk of T2DM patients with VTDR.
Going beyond frontiers in household energy transition in Poland—a perspective
Authors: Kubiczek Jakub , Hadasik Bartłomiej , Krawczyńska Dominika , Przedworska Kornelia , Ryczko Aleksandra
Published: August 2023

Transition towards a cleaner and more sustainable environment is mainly driven by co-participation of households, whereas the residents’ transformation willingness is determined by various factors, including an environmentally-friendly attitude and greater public awareness. Simultaneously, the global push for a climate-neutral economy fuels the increasing emphasis on eco-consciousness and promotion of green investments. However, Poland still heavily relies on coal for energy production, despite the opportunities provided by the EU. Poland faces challenges in transitioning its households to cleaner energy sources, particularly due to historical conditions and the dominance of solid fuel boilers. This article shed light on the inefficiency of the energy transition process in Poland, presenting legal, economic, and social aspects. Despite multiple efforts, energy transition in Poland is not as buoyant as in other EU countries. Among the reasons for this phenomenon are the adverse behavior of residents, or government policies that favor the carbon-centric nature of the economy resulting in the low use of EU and state funds. This may lead to a continuation of the slower pace of change and eventually reaching the Frontier of development in Poland’s energy transition. The multitude of campaigns and initiatives encouraging Poles to switch to green energy should be underscored, but due to their scant ecological awareness and orientation towards economic rather than ecological considerations, existing measures should be reviewed. In view of the above, to ensure an effective transition, it is necessary to recognize and clearly define the incentives that would induce Polish households to use climate-neutral energy sources.

Foreword: Monetary data has been standardized and, in view of this, the paper uses the euro (EUR) currency, including in places where the original data was given in a different currency. The exchange rate as of 12 June 2023 was used.
Efficient DNA knock-in using AAV-mediated delivery with 2-cell embryo CRISPR-Cas9 electroporation
Authors: Davis Daniel J. , McNew James F. , Maresca-Fichter Hailey , Chen Kaiwen , Telugu Bhanu P. , Bryda Elizabeth C.
Published: August 2023

Recent advances in CRISPR-Cas genome editing technology have been instrumental in improving the efficiency to produce genetically modified animal models. In this study we have combined four very promising approaches to come up with a highly effective pipeline to produce knock-in mouse and rat models. The four combined methods include: AAV-mediated DNA delivery, single-stranded DNA donor templates, 2-cell embryo modification, and CRISPR-Cas ribonucleoprotein (RNP) electroporation. Using this new combined approach, we were able to produce successfully targeted knock-in rat models containing either Cre or Flp recombinase sequences with knock-in efficiencies over 90%. Furthermore, we were able to produce a knock-in mouse model containing a Cre recombinase targeted insertion with over 50% knock-in efficiency directly comparing efficiencies to other commonly used approaches. Our modified AAV-mediated DNA delivery with 2-cell embryo CRISPR-Cas9 RNP electroporation technique has proven to be highly effective for generating both knock-in mouse and knock-in rat models.
Functional analysis of a novel nonsense variant c.91A>T of the TRAPPC2 gene in a Chinese family with X-linked recessive autosomal spondyloepiphyseal dysplasia tarda
Authors: Lou Guiyu , Zhao Yuanyin , Zhao Huiru , Zhang Yuwei , Hao Bingtao , Qin Litao , Liu Hongyan , Liao Shixiu
Published: August 2023

Spondyloepiphyseal dysplasia tarda (SEDT) is a condition involving late-onset, X-linked recessive skeletal dysplasia caused by mutations in the TRAPPC2 gene. In this paper, we identified a novel nonsense variant in a SEDT pedigree and analyzed the function of the variant in an attempt to explain the new pathogenesis of the TRAPPC2 protein in SEDT. Briefly, DNA and RNA samples from the peripheral blood of SEDT individuals were prepared. The causative variant in the Chinese SEDT family was identified by clinic whole-exome sequencing analysis. Then, we observed the mRNA expression of TRAPPC2 in patients and the mutant TRAPPC2 level in vitro and analyzed the protein stability and subcellular distribution by cell fluorescence and Western blotting. We also investigated the effect of TRAPPC2 knockdown on the expression and secretion of COL2A1 in SW1353 cells or primary human chondrocytes. Herein, we found a nonsense variant, c.91A>T, of the TRAPPC2 gene in the pedigree. TRAPPC2 mRNA expression levels were significantly decreased in the available peripheral blood cell samples of two affected patients. An in vitro study showed that the mutant plasmid exhibited significantly lower mRNA and protein of TRAPPC2, and the mutant protein changed its membrane distribution. TRAPPC2 knockdown resulted in decreased COL2A1 expression and collagen II secretions. Our data indicate that the novel nonsense variant, c.91A>T, of the TRAPPC2 gene is the cause of SEDT in this pedigree. The variant results in a lowered expression of TRAPPC2 and then affects the COL2A1 expression and collagen II secretions, which may explain the mechanism of loss of function of the variant.
Methylation-related genes involved in renal carcinoma progression
Authors: Zamora-Fuentes Jose María , Hernández-Lemus Enrique , Espinal-Enríquez Jesús
Published: August 2023

Renal carcinomas are a group of malignant tumors often originating in the cells lining the small tubes in the kidney responsible for filtering waste from the blood and urine production. Kidney tumors arise from the uncontrolled growth of cells in the kidneys and are responsible for a large share of global cancer-related morbidity and mortality. Understanding the molecular mechanisms driving renal carcinoma progression results crucial for the development of targeted therapies leading to an improvement of patient outcomes. Epigenetic mechanisms such as DNA methylation are known factors underlying the development of several cancer types. There is solid experimental evidence of relevant biological functions modulated by methylation-related genes, associated with the progression of different carcinomas. Those mechanisms can often be associated to different epigenetic marks, such as DNA methylation sites or chromatin conformation patterns. Currently, there is no definitive method to establish clear relations between genetic and epigenetic factors that influence the progression of cancer. Here, we developed a data-driven method to find methylation-related genes, so we could find relevant bonds between gene co-expression and methylation-wide-genome regulation patterns able to drive biological processes during the progression of clear cell renal carcinoma (ccRC). With this approach, we found out genes such as ITK oncogene that appear hypomethylated during all four stages of ccRC progression and are strongly involved in immune response functions. Also, we found out relevant tumor suppressor genes such as RAB25 hypermethylated, thus potentially avoiding repressed functions in the AKT signaling pathway during the evolution of ccRC. Our results have relevant implications to further understand some epigenetic–genetic-affected roles underlying the progression of renal cancer.
Irreversible electroporation combined with chemotherapy and PD-1/PD-L1 blockade enhanced antitumor immunity for locally advanced pancreatic cancer
Authors: Ma Yangyang , Xing Yanli , Li Hongmei , Yuan Ting , Liang Bing , Li Rongrong , Li Jianyu , Li Zhonghai , Li Shuying , Niu Lizhi
Published: August 2023

Background

Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.

Methods

A retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.

Results

A total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0–38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.

Conclusion

The addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.
Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability
Authors: Graydon Elizabeth K. , Conner Tonia L. , Dunham Kim , Olsen Cara , Goguet Emilie , Coggins Si’Ana A. , Rekedal Marana , Samuels Emily , Jackson-Thompson Belinda , Moser Matthew , Lindrose Alyssa , Hollis-Perry Monique , Wang Gregory , Maiolatesi Santina , Alcorta Yolanda , Reyes Anatalio , Wong Mimi , Ramsey Kathy , Davies Julian , Parmelee Edward , Ortega Orlando , Sanchez Mimi , Moller Sydney , Inglefield Jon , Tribble David , Burgess Timothy , O’Connell Robert , Malloy Allison M. W. , Pollett Simon , Broder Christopher C. , Laing Eric D. , Anderson Stephen K. , Mitre Edward
Published: August 2023

Introduction

Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2).

Methods

We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores.

Results

Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination.

Discussion

These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.
Cohesive bond strength of marine aggregates and its role in fragmentation
Authors: Hayashi Yasuhito , Wada Shigeki , Seto Mayumi , Adachi Yasuhisa
Published: August 2023

Marine aggregates are one of the main contributors to carbon sequestration in the deep sea through the gravitational settling of biogenic particles formed from the photosynthetic products of phytoplankton. The formation of large particles due to aggregation processes has been the focus of studies in the past, but recent findings on the spatio-temporal distribution of particles suggests that the fragmentation of aggregates plays an important role in aggregate dynamics. Here, we assessed the yield strength of aggregates derived from natural planktonic communities in order to analyze the cohesive bond strength and further understand fragmentation. The experimental approach was designed around the use of a Couette device, which produces a constant laminar shear flow of water. Aggregates were found to have a higher yield strength (~289 ± 64 nN) during phases of nutrient depletion than those of mineral particles such as montmorillonite. Based on an estimated cohesive bond strength of 96 nN a numerical model to predict the temporal variation of aggregate size was created. The output of this model indicates that cohesive bond strength is a major determinant of the size of aggregates in motion. Our findings suggest that the dynamics of marine aggregates are greatly influenced by cohesive bond strength and the role in fragmentation.
Modeling particulate waste assimilation by blue mussels within the spatial constraints of a commercial fish farm: implications for multitrophic aquaculture
Authors: á Norði Gunnvør , Lund Ivar , Andreasen Birgitta , Taylor Daniel , Johannesen Tróndur T. , Jacobsen Bjartur , Hughes Adam D.
Published: August 2023

Commercial salmonid farming is typically performed in open-water net cages where interactions between the environment and production unit might be widespread and not easily predicted or controlled. Integrated multi-trophic aquaculture (IMTA) has been suggested to mitigate some of the environmental impacts. Based on empirical data, the assimilation of particulate waste from a commercial fish farm was modeled by two approaches to salmon/blue mussel IMTA: a system with mussels at the surface next to the fish farm and an alternative setup with mussels submerged under the farm. According to the model, 15% of the feed was defecated and assumed available to the mussels and the submerged mussel farm could assimilate 14.6% of the feces. Sensitivity analysis showed that the current speed, the mussel filtration rate, and the proportion of the material that settles slowly had an impact on this assimilation estimate, which could be significantly higher. However, the model did not include assimilation limitations due to particle size, which may contribute significantly to the submerged farm. The mussel farm at the surface mainly received small slow settling particles, and according to the model, only 0.4% of the fish farm waste was assimilated. The maximum obtainable assimilation was 5.5%. The fraction of slowly settling waste had the most pronounced influence on waste assimilation in the mussel farm at the surface. This is also among the most uncertain parameters, since the relative portion of different settling velocities of fish feces is highly variable, and more information on the size distribution of waste is needed.
Comprehensive studies on the stability of yogurt-type fermented soy beverages during refrigerated storage using dairy starter cultures
Authors: Ziarno Małgorzata , Zaręba Dorota , Ścibisz Iwona , Kozłowska Mariola
Published: August 2023

Introduction

This study aimed to assess the feasibility of utilizing commercially available dairy starter cultures to produce yogurt-type fermented soy beverages and evaluate the fundamental properties of the resulting products.

Methods

Sixteen different starter cultures commonly used in the dairy industry for producing fermented milks, such as yogurt, were employed in the study. The study investigated the acidification curves, acidification kinetics, live cell population of starter microflora during refrigerated storage, pH changes, water-holding capacity, texture analysis, carbohydrates content, and fatty acid profile of the yogurt-type fermented soy beverage.

Results and Discussion

The results demonstrated that the starter cultures exhibited distinct pH changes during the fermentation process, and these changes were statistically significant among the cultures. The acidification kinetics of different cultures of lactic acid bacteria showed characteristic patterns, which can be used to select the most suitable cultures for specific product production. The study also revealed that the choice of starter culture significantly influenced the starter microorganisms population in the yogurt-type fermented soy beverage. Additionally, the pH values and water-holding capacity of the beverages were affected by both the starter cultures and the duration of refrigerated storage. Texture analysis indicated that storage time had a significant impact on hardness and adhesiveness, with stabilization of these parameters observed after 7–21 days of storage. Furthermore, the fermentation process resulted in changes in the carbohydrate content of the soy beverages, which varied depending on the starter culture used.
2bRAD-M reveals the difference in microbial distribution between cancerous and benign ovarian tissues
Authors: Wang Xiaogang , Zheng Yaojun , Chen Xiang , Peng Chen , Zhou Shizhen , Shen Sunan , Zhao Shuli , Wang Tingting
Published: August 2023

The development of ovarian cancer is closely related to various factors, such as environmental, genetic and microbiological factors. In previous research, bacteria were identified in human tumors by 16S rRNA sequencing. However, the microbial biomass in tumor tissue is too low and cannot be accurately identified by 16S rRNA sequencing. In our study, we employ 2bRAD sequencing for Microbiome (2bRAD-M), a new sequencing technology capable of accurately characterizing the low biomass microbiome (bacteria, fungi and archaea) at species resolution. Here we surveyed 20 ovarian samples, including 10 ovarian cancer samples and 10 benign ovarian samples. The sequencing results showed that a total of 373 microbial species were identified in both two groups, of which 90 species shared in the two groups. The Meta statistic indicated that Chlamydophila_abortus and CAG-873_sp900550395 were increased in the ovarian cancer tissues, while Lawsonella_clevelandensis_A, Ralstonia_sp001078575, Brevundimonas_aurantiaca, Ralstonia_sp900115545, Ralstonia_pickettii, Corynebacterium_kefirresidentii, Corynebacterium_sp000478175, Brevibacillus_D_fluminis, Ralstonia_sp000620465, and Ralstonia_mannitolilytica were more abundant in the benign ovarian tissues. This is the first use of 2bRAD-M technique to provide an important hint for better understanding of the ovarian cancer microbiome.
The causal relationship between genetically determined telomere length and meningiomas risk
Authors: Yu Weijie , Mei Yunyun , Lu Zhenwei , Zhou Liwei , Jia Fang , Chen Sifang , Wang Zhanxiang
Published: August 2023

Background

Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors.

Methods

We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR).

Results

In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14, p = 1.04 × 10−5], benign (OR = 4.81, p < 0.05), benign cerebral (OR = 5.36, p < 0.05), and benign unspecified meningioma (OR = 8.26, p < 0.05). The same results were obtained for the LTL-9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR = 4.94, p < 0.05), benign (OR = 3.14, p < 0.05), and benign cerebral meningioma (OR = 3.59, p < 0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR = 1.01, p < 0.05). No heterogeneity or horizontal pleiotropy was detected.

Conclusion

In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations.
Reliability of a telephone interview for the classification of headache disorders
Authors: Angermaier Anselm , Koennecke Andy , Kloetzer Christine , Strauss Sebastian , Fleischmann Robert
Published: August 2023

Objective

The study aimed to test the reliability of a semi-structured telephone interview for the classification of headache disorders according to the ICHD-3.

Background

Questionnaire-based screening tools are often optimized for single primary headache diagnoses [e.g., migraine (MIG) and tension headache (TTH)] and therefore insufficiently represent the diagnostic precision of the ICHD-3, which limits epidemiological research of rare headache disorders. Brief semi-structured telephone interviews could be an effective alternative to improve classification.

Methods

A patient population representative of different primary and secondary headache disorders (n = 60) was recruited from the outpatient clinic (HSA) of a tertiary care headache center. These patients completed an established population-based questionnaire for the classification of MIG, TTH, or trigeminal autonomic cephalalgia (TAC). In addition, they received a semi-structured telephone interview call from three blinded headache specialists individually. The agreement of diagnoses made either using the questionnaires or interviews with the HSA diagnoses was evaluated.

Results

Of the 59 patients (n = 1 dropout), 24% had a second-order and 5% had a third-order headache disorder. The main diagnoses were as follows: frequent primary headaches with 61% MIG, 10% TAC, 9% TTH, and 5% rare primary and 16% secondary headaches. Second-order diagnosis was chronic migraine throughout, and third-order diagnoses were medication overuse headache and TTH. Agreement between main headaches from the HSA was significantly better for the telephone interview than for the questionnaire (questionnaire: κ = 0.330; interview: κ = 0.822; p < 0.001). Second-order diagnoses were not adequately captured by questionnaires, while there was a trend for good agreement with the telephone interview (κ = 0.433; p = 0.074). Headache frequency and psychiatric comorbidities were independent predictors of HSA and telephone interview agreement. Male sex, headache frequency, severity, and depressive disorders were independently predictive for agreement between the questionnaire and HSA. The telephone interview showed high sensitivity (≥71%) and specificity (≥92%) for all primary headache disorders, whereas the questionnaire was below 50% in either sensitivity or specificity.

Conclusion

The semi-structured telephone interview appears to be a more reliable tool for accurate diagnosis of headache disorders than self-report questionnaires. This offers the potential to improve epidemiological headache research and care even in underserved areas.
Impact of 4-week of a restricted Mediterranean diet on taste perception, anthropometric, and blood parameters in subjects with severe obesity
Authors: Cattaneo Camilla , Mambrini Sara Paola , Gilardini Luisa , Scacchi Massimo , Pagliarini Ella , Bertoli Simona
Published: August 2023

Introduction

The study of taste functionality and its relation to human health is receiving growing attention. Obesity has been reported to cause alterations in sensory perception regarding system functionality and preferences. However, a small body of research addresses tastes perception and its modification with the achievement of body mass reduction through surgical intervention. Much fewer efforts have been made to evaluate the impact of mild restrictive nutritional intervention on gustatory functions. Thus, the objectives of this study were to determine if a dietary intervention of 4 weeks following a restricted balanced Mediterranean diet would affect the sweet and salty taste thresholds of subjects with severe obesity and could influence their anthropometric and blood parameters.

Methods

Fifty-one patients with severe obesity (F: 31; age: 43.7 ± 12.5; BMI = 47.6 ± 1.0) were enrolled in the study. The recognition threshold for sweet and salty taste and anthropometric and blood parameters were assessed before and after the 4-week weight loss program.

Results and Discussion

The Mediterranean diet has proven to be an effective treatment, significantly improving all anthropometric and blood parameters (p < 0.05) after 4 weeks of intervention. Moreover, the hypo-sodium treatment associated with the diet significantly improved the salty threshold (p < 0.001). No changes were detected for the sweet threshold. Collectively, these data highlight that dietary treatment might impact taste perception differently. Therefore, a taste-oriented nutritional intervention could represent a novel approach to developing more individualized, taste-oriented follow-up interventions to maintain sustainable and long-term weight loss.
A novel homozygous HES7 splicing variant causing spondylocostal dysostosis 4: a case report
Authors: Lv Shaoguang , Wu Yuanyuan , Liu Fang , Jiao Baoquan
Published: August 2023

Background

Spondylocostal dysostosis 4 (SCDO4) is characterized by short stature (mainly short trunk), dyspnea, brain meningocele, and spina bifida occulta, which is caused by homozygous or compound heterozygous HES7 (HES family bHLH transcription factor 7) variants. The incidence of SCDO4 remains unknown due to the extremely low number of cases. This study reveals a novel homozygous HES7 splicing variant causing SCDO4 and reviews all the previously reported HES7 variants and corresponding symptoms, providing a comprehensive overview of the phenotypes and genotypes of HES7 variants.

Case presentation

This case report focuses on a Chinese neonate who was first hospitalized for tachypnea, cleft palate, and short trunk. After a series of auxiliary examinations, the patient was also found to have deformities of vertebrae and rib, left hydronephrosis, and patent foramen ovale. He underwent surgery for congenital hydronephrosis at 5 months old and underwent cleft palate repair when he was 1 year old. After two and half years of follow-up, the boy developed normally. A novel homozygous HES7 splicing variant (c.226+1G>A, NM_001165967.2) was identified in the proband by whole-exome sequencing and verified by Sanger sequencing. The variant was inherited from both parents and minigene assays demonstrated that this variant resulted in the retention of intron3 in the HES7 transcript. Including this case, a total of six HES7 variants and 13 patients with SCDO4 have been reported.

Conclusions

Our findings expand the genotype-phenotype knowledge of SCDO4 and provide new evidence for genetic counseling.
Mapping the regulatory landscape of AI in healthcare in Africa
Authors: Townsend Beverley Alice , Sihlahla Irvine , Naidoo Meshandren , Naidoo Shiniel , Donnelly Dusty-Lee , Thaldar Donrich Willem
Published: August 2023

Introduction: Artificial intelligence (AI)-enhanced technology has seen unprecedented expansion in the recent past. This growth brings with it huge opportunities for the positive transformation of the economy, business, healthcare, and society. However, a critical question is whether, and to what extent, regulatory measures and mechanisms have been implemented to safeguard its design, development, and deployment. This paper offers a scoping exercise that maps the regulatory landscape of AI in healthcare (including health research) in certain African countries.

Methods: This research is conducted across 12 African countries: Botswana, Cameroon, The Gambia, Ghana, Kenya, Malawi, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. As limited specific AI legislation is found in these African countries, and because AI is informed by ancillary regulatory frameworks, we include data protection, digital health, consumer protection, and intellectual property in our research. A scoping review method was applied with a manual search of digital libraries with search terms customised for each repository consisting of core search terms for the various topics, including, among others, “law,” “regulation,” “artificial intelligence,” “data protection,” “intellectual property,” and “digital health”.

Results and discussion: Analysis of the data demonstrated that while in the African countries under investigation there is no sui generis AI regulation, recent developments were found in areas that inform AI adoption, including in digital health, data protection, consumer protection, and intellectual property. Our findings highlight the fragmentation of the African AI regulatory landscape and illustrate the importance of continued AI regulatory development to ensure that Africa is well positioned for future AI adoption in health.
Lomerizine attenuates LPS-induced acute lung injury by inhibiting the macrophage activation through reducing Ca2+ influx
Authors: Song Yunduan , Gou Yusen , Gao Jiameng , Chen Dongxin , Zhang Haibo , Zhao Wenjuan , Qian Feng , Xu Ajing , Shen Yao
Published: August 2023

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS.
Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis
Authors: Zheng Zeyi , Lu Ziyu , Song Yani
Published: August 2023

Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk.

Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model.

Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71).

Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).
The identification and expression pattern of the sex determination genes and their sex-specific variants in the egg parasitoid Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae)
Authors: Ning Su-Fang , Huo Liang-Xiao , Lv Lin , Wang Ying , Zhang Li-Sheng , Che Wu-Nan , Dong Hui , Zhou Jin-Cheng
Published: August 2023

Introduction:Trichogramma wasps are egg parasitoids of agricultural lepidopteran pests. The sex of Trichogramma is determined by its ploidy as well as certain sex ratio distorters, such as the endosymbiotic bacteria Wolbachia spp. and the paternal sex ratio (PSR) chromosome. The sex determination systems of hymenopterans, such as Trichogramma spp., involve cascades of the genes transformer (tra), transformer-2 (tra2), and doublesex (dsx) and are associated with sex-specific tra and dsx splicing. First, these genes and their sex-specific variants must be identified to elucidate the interactions between the sex ratio disorders and the sex determination mechanism of Trichogramma.

Methods: Here, we characterized the sex determination genes tra, tra2, and dsx in Trichogramma dendrolimi. Sex-specific tra and dsx variants were detected in cDNA samples obtained from both male and female Trichogramma wasps. They were observed in the early embryos (1–10 h), late embryos (12–20 h), larvae (32 h and 48 h), pre-pupae (96 h), and pupae (144 h, 168 h, 192 h, and 216 h) of both male and female T. dendrolimi offspring.

Results: We detected female-specific tra variants throughout the entire early female offspring stage. The male-specific variant began to express at 9–10 h as the egg was not fertilized. However, we did not find any maternally derived, female-specific tra variant in the early male embryo. This observation suggests that the female-specific tra variant expressed in the female embryo at 1–9 h may not have originated from the maternal female wasp.

Discussion: The present study might be the first to identify the sex determination genes and sex-specific gene splicing in Trichogramma wasps. The findings of this study lay the foundation for investigating the sex determination mechanisms of Trichogramma and other wasps. They also facilitate sex identification in immature T. dendrolimi and the application of this important egg parasitoid in biological insect pest control programs.
Development of effective model for non-destructive detection of defective kiwifruit based on graded lines
Authors: Wang Feiyun , Lv Chengxu , Dong Lizhong , Li Xilong , Guo Pengfei , Zhao Bo
Published: August 2023

The accurate detection of external defects in kiwifruit is an important part of postharvest quality assessment. Previous studies have not considered the problems posed by the actual grading environment. In this study, we designed a novel approach based on improved Yolov5 to achieve real-time and efficient non-destructive detection of multiple defect categories in kiwifruit. First, a kiwifruit image acquisition device based on grading lines was developed to enhance the image acquisition. Subsequently, a kiwifruit dataset was constructed based on the external defect characteristics and a new data enhancement method was proposed to augment the kiwifruit samples. Thereafter, the SPD-Conv and DW-Conv modules were combined to improve Yolov5s, with EIOU as the loss calculation function. The results demonstrated that the improved model training loss value was 0.013 lower, the convergence was accelerated, the number of parameters was reduced, and the computational effort was increased. The detection accuracies of the samples in the test set, which included healthy, leaf-rubbing damaged, healed cuts or scarred, and sunburned samples, were 98.8%, 98.7%, 97.6%, and 95.9%, respectively, with an overall detection accuracy of 97.7%. The detection time was 8.0 ms, thereby meeting real-time sorting demands. The average detection accuracy and model size of SSD, Yolov5s, Yolov7, and Yolov5-Ours were compared. When the confidence threshold was 0.5, the detection accuracy of Yolov5-Ours was 10% and 6.4% higher than that of SSD and Yolov5s, respectively. In terms of the model size, Yolov5-Ours was approximately 6.5- and 4-fold smaller than SSD and Yolov7, respectively. Thus, Yolov5-Ours achieved the highest accuracy, adaptability, and robustness for the detection of all kiwifruit categories as well as a small volume and portability. These results can provide technical support for the non-destructive detection and grading of agricultural products in the future.
Comparative analysis of wild-type and chloroplast MCU-deficient plants reveals multiple consequences of chloroplast calcium handling under drought stress
Authors: Corti Francesca , Festa Margherita , Stein Frank , Stevanato Piergiorgio , Siroka Jitka , Navazio Lorella , Vothknecht Ute C. , Alboresi Alessandro , Novák Ondřej , Formentin Elide , Szabò Ildikò
Published: August 2023

Introduction

Chloroplast calcium homeostasis plays an important role in modulating the response of plants to abiotic and biotic stresses. One of the greatest challenges is to understand how chloroplast calcium-permeable pathways and sensors are regulated in a concerted manner to translate specific information into a calcium signature and to elucidate the downstream effects of specific chloroplast calcium dynamics. One of the six homologs of the mitochondrial calcium uniporter (MCU) was found to be located in chloroplasts in the leaves and to crucially contribute to drought- and oxidative stress-triggered uptake of calcium into this organelle.

Methods

In the present study we integrated comparative proteomic analysis with biochemical, genetic, cellular, ionomic and hormone analysis in order to gain an insight into how chloroplast calcium channels are integrated into signaling circuits under watered condition and under drought stress.

Results

Altogether, our results indicate for the first time a link between chloroplast calcium channels and hormone levels, showing an enhanced ABA level in the cmcu mutant already in well-watered condition. Furthermore, we show that the lack of cMCU results in an upregulation of the calcium sensor CAS and of enzymes of chlorophyll synthesis, which are also involved in retrograde signaling upon drought stress, in two independent KO lines generated in Col-0 and Col-4 ecotypes.

Conclusions

These observations point to chloroplasts as important signaling hubs linked to their calcium dynamics. Our results obtained in the model plant Arabidopsis thaliana are discussed also in light of our limited knowledge regarding organellar calcium signaling in crops and raise the possibility of an involvement of such signaling in response to drought stress also in crops.
How do teacher support trajectories influence primary and lower-secondary school students’ study well-being
Authors: Ulmanen Sanna , Rautanen Pihla , Soini Tiina , Pietarinen Janne , Pyhältö Kirsi
Published: August 2023

Effective long term teacher support is key to promoting and sustaining students’ study well-being at school. However, little is known about individual variations in the development of perceived teacher support and how such variations are associated with study engagement and study-related burnout. Also, understanding of the differences between age cohorts across school levels is still limited. To address this limitation, we used latent growth mixture (LGM) modeling to study whether teacher support trajectories influenced study engagement and study-related burnout among Finnish primary and lower-secondary school students. Two cohorts of students, namely primary school students from the 4th to 6th grades (N = 2,204) and lower-secondary school students from the 7th to 9th grades (N = 1,411), were followed for three years. LGM revealed four latent trajectories for teacher support, which were labeled high stable (72%), low stable (12%), decreasing (11%) and increasing (5%). The teacher support trajectories were strongly associated with students’ study engagement and study burnout. Moreover, heightened study-related burnout symptoms and decreased study engagement were associated with a decline in perceived teacher support, while higher levels of study engagement and low levels of study burnout symptoms were associated with a continuum of positive teacher support experience. Primary school students were more likely to employ stable and high levels of teacher support, compared with lower-secondary school students, highlighting the importance of improving conditions in lower-secondary school so that the teacher support will better reach all their students.
The impact of social support and emotion dysregulation on COVID-19 depressive symptoms
Authors: Dhruve Deepali M. , Russo Jenna E. , Oliveros Arazais D.
Published: August 2023

Introduction

Stress resulting from the global COVID-19 pandemic has been linked to psychological consequences, such as depressive symptoms, for individuals worldwide. Outbreaks and pandemics are known to accentuate stressors or generate new ones owing to health-related worries, reduced mobility, and social activity due to quarantine, and sudden life changes. Although post-lockdown U.S. research findings suggest a greater risk of depression among 18- to 25-year-olds, familiarity with technology and virtual socializing may offer college students some protective effect, warranting research with such groups.

Methods

The current study thus explored emotion dysregulation (ED) and perceived social support (PSS) as potential mechanisms for the relationship between COVID-19 stress and depressive symptoms among students at a southern university in the United States. Participants (N = 489) completed a cross-sectional survey assessing their current levels of COVID-19 stress, ED, PSS, and depressive symptoms.

Results

Path analysis showed that PSS buffered the effect of ED on depressive symptoms. The results support the explanatory role of ED in the relationship between COVID-19 stress and depressive symptoms.

Discussion

The perceived social connection may be an essential factor for psychological outcomes during periods of stress and isolation, particularly for those reporting high ED.