bluuebunny/crossref_metadata_2025 huggingface dataset:
Core issues, case studies, and the need for expanded Legacy African American genomics
Authors: Jackson Fatimah , Clinton Carter , Caldwell Jennifer
Published: June 2023

Introduction: Genomic studies of Legacy African Americans have a tangled and convoluted history in western science. In this review paper, core issues affecting African American genomic studies are addressed and two case studies, the New York African Burial Ground and the Gullah Geechee peoples, are presented to highlight the current status of genomic research among Africa Americans.

Methods: To investigate our target population’s core issues, a metadatabase derived from 22 publicly accessible databases were reviewed, evaluated, and synthesized to identify the core bioethical issues prevalent during the centuries of the African American presence in North America. The sequence of metadatabase development included 5 steps: identification of information, record screening and retention of topic relevant information, identification of eligibility via synthesis for concept identifications, and inclusion of studies used for conceptual summaries and studies used for genetic and genomic summaries. To these data we added our emic perspectives and specific insights from our case studies.

Results: Overall, there is a paucity of existing research on underrepresent African American genomic diversity. In every category of genomic testing (i.e., diagnostic, clinical predictive, pharmacogenomic, direct-to-consumer, and tumor testing), African Americans are disproportionately underrepresented compared to European Americans. The first of our case studies is from the New York African Burial Ground Project where genomic studies of grave soil derived aDNA yields insights into the causes of death of 17th and 18th Century African Americans. In the second of our case studies, research among the Gullah Geechee people of the Carolina Lowcountry reveals a connection between genomic studies and health disparities.

Discussion: African Americans have historically borne the brunt of the earliest biomedical studies used to generate and refine primitive concepts in genetics. As exploited victims these investigations, African American men, women, and children were subjected to an ethics-free western science. Now that bioethical safeguards have been added, underrepresented and marginalized people who were once the convenient targets of western science, are now excluded from its health-related benefits. Recommendations to enhance the inclusion of African Americans in global genomic databases and clinical trials should include the following: emphasis on the connection of inclusion to advances in precision medicine, emphasis on the relevance of inclusion to fundamental questions in human evolutionary biology, emphasis on the historical relevance of inclusion for Legacy African Americans, emphasis on the ability of inclusion to foster expanded scientific expertise in the target population, ethical engagement with their descendants, and increase the number of science researchers from these communities.
Glyco engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues
Authors: Kallolimath Somanath , Palt Roman , Föderl-Höbenreich Esther , Sun Lin , Chen Qiang , Pruckner Florian , Eidenberger Lukas , Strasser Richard , Zatloukal Kurt , Steinkellner Herta
Published: June 2023

Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of IgMs, composed of 21 human protein subunits correctly assembled into pentamers. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications.
Investigating the causal relationship between ankylosing spondylitis and osteoporosis in the European population: a bidirectional Mendelian randomization study
Authors: Mei Jian , Hu Hongxin , Ding Haiqi , Huang Ying , Zhang Wenming , Chen Xiaoqing , Fang Xinyu
Published: June 2023

Background

Ankylosing Spondylitis (AS) is an inflammatory condition affecting the spine, which may lead to complications such as osteoporosis (OP). Many observational studies have demonstrated a close relationship with strong evidence between OP and AS. The combination of AS and OP is already an indisputable fact, but the exact mechanism of AS complicated with OP is unclear. To better prevent and treat OP in patients with AS, it is necessary to understand the specific mechanism of OP in these patients. In addition, there is a study showing that OP is a risk factor for AS, but the causal relationship between them is not yet clear. Therefore, we conducted a bidirectional Mendelian randomization (MR) analysis to determine whether there is a direct causal effect between AS and OP and to investigate the co-inherited genetic information between the two.

Methods

Bone mineral density (BMD) was used as a phenotype for OP. The AS dataset was taken from the IGAS consortium and included people of European ancestry (9,069 cases and 13,578 controls). BMD datasets were obtained from the GEFOS consortium, a large GWAS meta-analysis study, and the UK Biobank and were categorized based on site (total body (TB): 56,284 cases; lumbar spine (LS): 28,498 cases; femoral neck (FN): 32,735 cases; forearm (FA): 8,143 cases; and heel: 265,627 cases) and age (0-15: 11,807 cases; 15-30: 4,180 cases; 30-45: 10,062 cases; 45-60: 18,062 cases; and over 60: 22,504 cases).To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used due to its good statistical power and robustness. The presence of heterogeneity was evaluated using Cochran’s Q test. Pleiotropy was assessed utilizing MR-Egger regression and MR-pleiotropy residual sum and outlier (MR-PRESSO).

Results

Generally, there were no significant causal associations between genetically predicted AS and decreased BMD levels. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. However, there was a sign of a connection between genetically elevated BMD levels and a decreased risk of AS (Heel-BMD: OR = 0.879, 95% CI: 0.795-0.971, P = 0.012; Total-BMD: OR = 0.948, 95% CI: 0.907-0.990, P = 0.017; LS-BMD: OR = 0.919, 95% CI: 0.861-0.980, P = 0.010). The results were confirmed to be reliable by sensitivity analysis.

Conclusion

This MR study found that the causal association between genetic liability to AS and the risk of OP or lower BMD in the European population was not evident, which highlights the second effect (e.g., mechanical reasons such as limited movement) of AS on OP. However, genetically predicted decreased BMD/OP is a risk factor for AS with a causal relationship, implying that patients with OP should be aware of the potential risk of developing AS. Moreover, OP and AS share similar pathogenesis and pathways.
Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages
Authors: Wilton Joana , de Mendonça Filipa Lopes , Pereira-Castro Isabel , Tellier Michael , Nojima Takayuki , Costa Angela M. , Freitas Jaime , Murphy Shona , Oliveira Maria Jose , Proudfoot Nicholas J. , Moreira Alexandra
Published: June 2023

Introduction

Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3’UTR (3’UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3’UTR-APA and IPA in primary human macrophages was unclear.

Methods

In this study, we isolated primary human monocytes from healthy donors, differentiated and polarized them into a pro-inflammatory state and performed indirect co-cultures with CRC cells. ChrRNA-Seq and 3’RNA-Seq was performed to quantify gene expression and characterize new 3’UTR-APA and IPA mRNA isoforms.

Results

Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase of proximal polyA site selection in the 3’UTR and IPA events in genes relevant to macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3’UTR-APA and IPA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro-tumoral genes and induces 3’UTR-APA alterations. Notably, some of these gene expression differences were also found in tumor-associated macrophages of CRC patients, indicating that they are physiologically relevant. Upon macrophage pro-inflammatory polarization, SRSF12 is the pre-mRNA processing gene that is most upregulated. After SRSF12 knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses.

Discussion

Our results reveal new 3’UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools. Furthermore, our results highlight a function for SRSF12 in pro-inflammatory macrophages, key cells in the tumor response.
Protective RNA nanovaccines against Mycobacterium avium subspecies hominissuis
Authors: Touray Bubacarr J.B. , Hanafy Mostafa , Phanse Yashdeep , Hildebrand Rachel , Talaat Adel M.
Published: June 2023

The induction of an effective immune response is critical for the success of mRNA-based therapeutics. Here, we developed a nanoadjuvant system compromised of Quil-A and DOTAP (dioleoyl 3 trimethylammonium propane), hence named QTAP, for the efficient delivery of mRNA vaccine constructs into cells. Electron microscopy indicated that the complexation of mRNA with QTAP forms nanoparticles with an average size of 75 nm and which have ~90% encapsulation efficiency. The incorporation of pseudouridine-modified mRNA resulted in higher transfection efficiency and protein translation with low cytotoxicity than unmodified mRNA. When QTAP-mRNA or QTAP alone transfected macrophages, pro-inflammatory pathways (e.g., NLRP3, NF-kb, and MyD88) were upregulated, an indication of macrophage activation. In C57Bl/6 mice, QTAP nanovaccines encoding Ag85B and Hsp70 transcripts (QTAP-85B+H70) were able to elicit robust IgG antibody and IFN- ɣ, TNF-α, IL-2, and IL-17 cytokines responses. Following aerosol challenge with a clinical isolate of M. avium ss. hominissuis (M.ah), a significant reduction of mycobacterial counts was observed in lungs and spleens of only immunized animals at both 4- and 8-weeks post-challenge. As expected, reduced levels of M. ah were associated with diminished histological lesions and robust cell-mediated immunity. Interestingly, polyfunctional T-cells expressing IFN- ɣ, IL-2, and TNF- α were detected at 8 but not 4 weeks post-challenge. Overall, our analysis indicated that QTAP is a highly efficient transfection agent and could improve the immunogenicity of mRNA vaccines against pulmonary M. ah, an infection of significant public health importance, especially to the elderly and to those who are immune compromised.
IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing
Authors: Gorman Hayley , Moreau France , Dufour Antoine , Chadee Kris
Published: June 2023

The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited MUC2 KO cells. Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. However, FCGBP interacted with other mucus-associated proteins. FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. In MUC2 KO, cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. In DSS colitis, restitution and healed lesions in Muc2+/+ but not Muc2-/- littermates, were accompanied by a rapid increase in Fcgbp mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function.
Clinical utility of ultra-widefield fluorescein angiography and optical coherence tomography angiography for retinal vein occlusions
Authors: Tan Tien-En , Ibrahim Farah , Chandrasekaran Priya R. , Teo Kelvin Yi Chong
Published: June 2023

Retinal vein occlusions (RVOs) are the second most common retinal vascular disease after diabetic retinopathy, and are a significant cause of visual impairment, especially in the elderly population. RVOs result in visual loss due to macular ischemia, cystoid macular edema (CME), and complications related to neovascularization. Vascular assessment in RVOs traditionally relies on standard fluorescein angiography (FA) for assessment of macular and retinal ischemia, which aids in prognostication and guides intervention. Standard FA has significant limitations—it is time-consuming, requires invasive dye administration, allows for limited assessment of the peripheral retina, and is usually evaluated semi-qualitatively, by ophthalmologists with tertiary expertise. More recently, the introduction of ultra-widefield FA (UWF FA) and optical coherence tomography angiography (OCTA) into clinical practice has changed the tools available for vascular evaluation in RVOs. UWF FA allows for evaluation of peripheral retinal perfusion, and OCTA is non-invasive, rapidly-acquired, and provides more information on capillary perfusion. Both modalities can be used to provide more quantitative parameters related to retinal perfusion. In this article, we review the clinical utility and impact of UWF FA and OCTA in the evaluation and management of patients with RVOs.
How does Nogo receptor influence demyelination and remyelination in the context of multiple sclerosis?
Authors: Rashidbenam Zahra , Ozturk Ezgi , Pagnin Maurice , Theotokis Paschalis , Grigoriadis Nikolaos , Petratos Steven
Published: June 2023

Multiple sclerosis (MS) can progress with neurodegeneration as a consequence of chronic inflammatory mechanisms that drive neural cell loss and/or neuroaxonal dystrophy in the central nervous system. Immune-mediated mechanisms can accumulate myelin debris in the disease extracellular milieu during chronic-active demyelination that can limit neurorepair/plasticity and experimental evidence suggests that potentiated removal of myelin debris can promote neurorepair in models of MS. The myelin-associated inhibitory factors (MAIFs) are integral contributors to neurodegenerative processes in models of trauma and experimental MS-like disease that can be targeted to promote neurorepair. This review highlights the molecular and cellular mechanisms that drive neurodegeneration as a consequence of chronic-active inflammation and outlines plausible therapeutic approaches to antagonize the MAIFs during the evolution of neuroinflammatory lesions. Moreover, investigative lines for translation of targeted therapies against these myelin inhibitors are defined with an emphasis on the chief MAIF, Nogo-A, that may demonstrate clinical efficacy of neurorepair during progressive MS.
Case report: Flow changes in routes of collateral circulation in patients with LVO and low NIHSS: a point favor to treat
Authors: Santos Neto Elizeu Pereira dos , de Sousa Ícaro Araújo , Veras Arthur de Oliveira , Barros-Araújo Marx Lima de , Ricarte Irapuá Ferreira , Pontes-Neto Octávio Marques
Published: June 2023

The effectiveness of endovascular thrombectomy in patients presenting low National Institutes of Health Stroke Scale (NIHSS) scores remains controversial, and the acquisition of additional evidence is required to refine the selection of candidates who may benefit the most from this therapeutic modality. In this study, we present the case of a 62-year-old individual, with left internal carotid occlusion stroke and low NIHSS, who had compensatory collateral flow from Willis polygon via the anterior communicating artery. The patient subsequently exhibited neurological deterioration and collateral flow failure from Willis polygon, indicating the need for urgent intervention. The study of collaterals in patients with large vessel occlusion stroke has garnered considerable attention, with research suggesting that individuals with low NIHSS scores and poor collateral profiles may be at a heightened risk of early neurological deterioration. We postulate that such patients may derive significant benefits from endovascular thrombectomy, and may posit that an intensive transcranial Doppler monitoring protocol could facilitate the identification of suitable candidates for such intervention.
Disparities in brain health comorbidity management in intracerebral hemorrhage
Authors: Mayerhofer Ernst , Zaba Natalie O. , Parodi Livia , Ganbold Alena S. , Biffi Alessandro , Rosand Jonathan , Yechoor Nirupama , Anderson Christopher D.
Published: June 2023

Background

Intracerebral hemorrhage (ICH) disproportionally affects underserved populations, and coincides with risk factors for cardiovascular events and cognitive decline after ICH. We investigated associations between social determinants of health and management of blood pressure (BP), hyperlipidemia, diabetes, obstructive sleep apnea (OSA), and hearing impairment before and after ICH hospitalization.

Methods

Survivors of the Massachusetts General Hospital longitudinal ICH study between 2016 and 2019 who received healthcare at least 6 months after ICH were analyzed. Measurements of BP, LDL and HbA1c and their management in the year surrounding ICH and referrals for sleep studies and audiology up to 6 months after ICH were gathered from electronic health records. The US-wide area deprivation index (ADI) was used as proxy for social determinants of health.

Results

The study included 234 patients (mean 71 years, 42% female). BP measurements were performed in 109 (47%) before ICH, LDL measurements were performed in 165 (71%), and HbA1c measurements in 154 (66%) patients before or after ICH. 27/59 (46%) with off-target LDL and 3/12 (25%) with off-target HbA1c were managed appropriately. Of those without history of OSA or hearing impairment before ICH, 47/207 (23%) were referred for sleep studies and 16/212 (8%) to audiology. Higher ADI was associated with lower odds of BP, LDL, and HbA1c measurement prior to ICH [OR 0.94 (0.90–0.99), 0.96 (0.93–0.99), and 0.96 (0.93–0.99), respectively, per decile] but not with management during or after hospitalization.

Conclusion

Social determinants of health are associated with pre-ICH management of cerebrovascular risk factors. More than 25% of patients were not assessed for hyperlipidemia and diabetes in the year surrounding ICH hospitalization, and less than half of those with off-target values received treatment intensification. Few patients were evaluated for OSA and hearing impairment, both common among ICH survivors. Future trials should evaluate whether using the ICH hospitalization to systematically address co-morbidities can improve long-term outcomes.
Be aware of the sodium intake outside student canteens: development and validation of a sodium food frequency questionnaire in Chinese undergraduates
Authors: Xi Yue , Xiang Caihong , Liang Jiajing , Huo Jiaqi , Yong Cuiting , Zou Hanshuang , Pan Yunfeng , Wu Minchan , Xie Qingqing , Deng Jing , Yang Lina , Chen Jihua , Qi Yufei , Li Ying , Lin Qian
Published: June 2023

Background

Chinese college students used to eat in student canteens, making dietary consumption outside the cafeterias the main reason for the difference in sodium intake. This study aims to develop and validate a food frequency questionnaire (Sodium-FFQ) targeting dietary sodium intake outside the canteens among undergraduates in China.

Methods

This cross-sectional study included 124 and 81 college students from comprehensive universities in the development and validation stage. A 24 h dietary recall and a food frequency questionnaire were used to develop the Sodium-FFQ. Food items were selected according to the foods that contributed more to the total sodium intake. Test–retest correlation coefficients with an interval of 14 days were employed to evaluate reproducibility. Validity was assessed against a single 24 h urine collection and a 3-day dietary record using correlation coefficients, Bland–Altman analyses, and cross-classification analysis of Kappa coefficients.

Results

The Sodium-FFQ consists of 12 groups of foods with 48 items. The Spearman correlation coefficient of test–retest on sodium intake was 0.654 (p < 0.05), and that between the Sodium-FFQ, 3 × 24 h dietary record, and 24-h urinary sodium were 0.393 (p < 0.05) and 0.342 (p < 0.05), respectively. The Sodium-FFQ was correlated to 24 h urinary sodium-to-potassium ratio, with a Spearman coefficient of 0.370 (p < 0.05). The classification agreement of the Sodium-FFQ and 24 h urinary sodium was 68.4%, and the Kappa coefficient was 0.371 (p < 0.001).

Conclusion

The Sodium-FFQ developed in this study presented an acceptable reproducibility, validity, and classification agreement. It indicates that the Sodium-FFQ could be a potential tool for promoting sodium restriction in college students.
Associations of specific dietary unsaturated fatty acids with risk of overweight/obesity: population-based cohort study
Authors: Chen Weiming , Ao Yang , Lan Xiaochun , Tong Wenzhou , Liu Xiaohui , Zhang Xia , Ye Qiang , Li Yin , Liu Linfen , Ye Hao , Zhuang Pan , Zhang Yu , Zheng Weifang , Jiao Jingjing
Published: June 2023

Background

The role of specific unsaturated fatty acids (FAs) in the development of overweight/obesity remains unclear in the general population. Here, we aimed to explore the associations of different types of unsaturated FAs with overweight/obesity risk among the Chinese population.

Methods

Eight thousand seven hundred forty-two subjects free of overweight/obesity at entry in the China Health and Nutrition Survey (CHNS) were followed up until 2015. Dietary unsaturated FAs were assessed by 3-day 24-h recalls with a weighing method in each wave. Cox regression models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for overweight/obesity risk associated with unsaturated FAs.

Results

During a median follow-up of 7 years, 2,753 subjects (1,350 males and 1,403 females) developed overweight/obesity. Consuming more monounsaturated FAs (MUFAs) was associated with a lower risk of overweight/obesity (highest vs. lowest quartile: HR 0.80, 95% CI 0.67–0.96; P-trend = 0.010). Similar inverse associations were observed for plant-MUFAs (HRQ4vsQ1 0.83, 95% CI: 0.73–0.94; P-trend = 0.003) and animal-MUFAs (HRQ4vsQ1 0.77, 95% CI: 0.64–0.94; P-trend = 0.004), total dietary oleic acid (OA) (HRQ4vsQ1 0.66, 95% CI: 0.55–0.79; P-trend <0.001), plant-OA (HRQ4vsQ1 0.73, 95% CI: 0.64–0.83; P-trend <0.001) and animal-OA (HRQ4vsQ1 0.68, 95% CI: 0.55–0.84; P-trend <0.001). In addition, the intakes of n-3 polyunsaturated FAs (PUFAs) (HRQ4vsQ1 1.24, 95% CI: 1.09–1.42; P-trend = 0.017) and α-linolenic acid (ALA) (HRQ4vsQ1 1.22, 95% CI: 1.07–1.39; P-trend = 0.039) but not marine n-3 PUFAs were positively linked to overweight/obesity risk. Consumption of n-6 PUFAs (HRQ4vsQ1 1.13, 95% CI: 0.99–1.28; P-trend = 0.014) and linoleic acid (LA) (HRQ4vsQ1 1.11, 95% CI: 0.98–1.26; P-trend = 0.020) had marginal and positive relationships with the incidence of overweight/obesity. N-6/n-3 PUFA ratio ranging from 5.7 to 12.6 was related to higher risk of overweight/obesity.

Conclusion

Higher dietary intake of MUFAs was associated with lower overweight/obesity risk, which was mainly driven by dietary OA from either plant or animal sources. Intakes of ALA, n-6 PUFAs and LA were related to higher risk of overweight/obesity. These results support consuming more MUFAs for maintaining a healthy body weight among the Chinese population.
Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis
Authors: Lian Ying , Wang Gang-Pu , Chen Guo-Qiang , Chen Hua-Nan , Zhang Guang-Yong
Published: June 2023

Background

Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies.

Methods

A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023. To pool data, fixed-effects or random-effects models were used where appropriate. Subgroup analyses, sensitivity analyses, and publication bias tests were performed.

Results

A total of 13 studies (4 cohort studies and 9 case–control studies) were included in the analysis, with a total of 625,738 participants. The highest UPFs consumption was associated with increased risk of colorectal cancer (OR = 1.23, 95% CI: 1.10–1.38), colon cancer (OR = 1.25, 95% CI: 1.14–1.36), and breast cancer (OR = 1.10, 95% CI: 1.00–1.20) but not rectal cancer (OR = 1.18, 95% CI: 0.97–1.43) and prostate cancer (OR = 1.03, 95% CI: 0.93–1.12). In addition, the subgroup analyses showed that a positive association between UPFs consumption and colorectal cancer was observed among men (OR = 1.31, 95% CI: 1.15–1.50), whereas no significant association was observed among women (OR = 1.10, 95% CI: 0.94–1.29).

Conclusion

The present meta-analysis suggests that high UPFs consumption is associated with a significantly increased risk of certain site-specific cancers, especially the digestive tract and some hormone-related cancers. However, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.
Exploring the adoption of less restricted criteria for respiratory syncytial virus prophylaxis in late preterm infants: insights from a retrospective analysis
Authors: Mondì Vito , Paolillo Piermichele , Bedetta Manuela , Lucangeli Natalia , Picone Simonetta
Published: June 2023

Background

Preterm infants born between 33 and 35 weeks of gestational age (wGA) have been considered a “major underserved population” and ineligible to receive palivizumab (PLV), the only drug authorized to date for respiratory syncytial virus (RSV) prophylaxis, by current international guidelines. In Italy, such a vulnerable population is currently eligible for prophylaxis, and, in our region, specific risk factors are taken into consideration (SINLazio score) to target prophylaxis for those at highest risk. Whether the adoption of less or more restrictive eligibility criteria for PLV prophylaxis would translate into differences in bronchiolitis and hospitalization incidence is not known.

Materials and methods

A retrospective analysis was conducted in 296 moderate-to-late preterm infants (born between 33 and 35+6 weeks) who were being considered for prophylaxis in two epidemic seasons: 2018–2019 and 2019–2020. The study participants were categorized according to both the SINLazio score and the Blanken risk scoring tool (BRST), which was found to reliably predict RSV-associated hospitalization in preterm infants on the basis of three risk factor variables.

Results

Based on the SINLazio score, approximately 40% of infants (123/296) would meet the criteria to be eligible for PLV prophylaxis. In contrast, none of the analyzed infants would be considered eligible for RSV prophylaxis on the basis of the BRST. A total of 45 (15.2%) bronchiolitis diagnoses were recorded on average at 5 months of age in the overall population. Almost seven out of 10 (84/123) patients exhibiting ≥3 risk factors to be eligible for RSV prophylaxis according to SINLazio criteria would not be receiving PLV if they were categorized on the basis of the BRST. Bronchiolitis occurrence in patients with a SINLazio score ≥3 was approximately 2.2 times more likely than that in patients with a SINLazio score <3. PLV prophylaxis has been associated with a 91% lower risk of requiring a nasal cannula.

Conclusion

Our work further supports the need for targeting late preterm infants for RSV prophylaxis and calls for an appraisal of the current eligibility criteria for PLV treatment. Therefore, adopting less restrictive criteria may ensure a comprehensive prophylaxis of the eligible subjects, thus sparing them from avoidable short- and long-term consequences of RSV infection.
The impact of CYP2C19 genotype on phenoconversion by concomitant medication
Authors: de Jong Laura M. , Boussallami Soukayna , Sánchez-López Elena , Giera Martin , Tushuizen Maarten E. , Hoekstra Menno , Hawinkels Lukas J. A. C. , Rissmann Robert , Swen Jesse J. , Manson Martijn L.
Published: June 2023

Introduction: Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test results, whereupon dosage or drugs are adjusted. Drug-drug-interactions (DDIs) caused by concomitant medication can however cause mismatches between predicted and observed phenotypes (phenoconversion). Here we investigated the impact of CYP2C19 genotype on the outcome of CYP2C19-dependent DDIs in human liver microsomes.

Methods: Liver samples from 40 patients were included, and genotyped for CYP2C19*2, *3 and *17 variants. S-mephenytoin metabolism in microsomal fractions was used as proxy for CYP2C19 activity, and concordance between genotype-predicted and observed CYP2C19 phenotype was examined. Individual microsomes were subsequently co-exposed to fluvoxamine, voriconazole, omeprazole or pantoprazole to simulate DDIs.

Results: Maximal CYP2C19 activity (Vmax) in genotype-predicted intermediate metabolizers (IMs; *1/*2 or *2/*17), rapid metabolizers (RMs; *1/*17) and ultrarapid metabolizers (UMs; *17/*17) was not different from Vmax of predicted normal metabolizers (NMs; *1/*1). Conversely, CYP2C19*2/*2 genotyped-donors exhibited Vmax rates ∼9% of NMs, confirming the genotype-predicted poor metabolizer (PM) phenotype. Categorizing CYP2C19 activity, we found a 40% concordance between genetically-predicted CYP2C19 phenotypes and measured phenotypes, indicating substantial phenoconversion. Eight patients (20%) exhibited CYP2C19 IM/PM phenotypes that were not predicted by their CYP2C19 genotype, of which six could be linked to the presence of diabetes or liver disease. In subsequent DDI experiments, CYP2C19 activity was inhibited by omeprazole (−37% ± 8%), voriconazole (−59% ± 4%) and fluvoxamine (−85% ± 2%), but not by pantoprazole (−2 ± 4%). The strength of CYP2C19 inhibitors remained unaffected by CYP2C19 genotype, as similar percental declines in CYP2C19 activity and comparable metabolism-dependent inhibitory constants (Kinact/KI) of omeprazole were observed between CYP2C19 genotypes. However, the consequences of CYP2C19 inhibitor-mediated phenoconversion were different between CYP2C19 genotypes. In example, voriconazole converted 50% of *1/*1 donors to a IM/PM phenotype, but only 14% of *1/*17 donors. Fluvoxamine converted all donors to phenotypic IMs/PMs, but *1/*17 (14%) were less likely to become PMs than *1/*1 (50%) or *1/*2 and *2/*17 (57%).

Conclusion: This study suggests that the differential outcome of CYP2C19-mediated DDIs between genotypes are primarily dictated by basal CYP2C19 activity, that may in part be predicted by CYP2C19 genotype but likely also depends on disease-related factors.
Natural products modulate cell apoptosis: a promising way for treating endometrial cancer
Authors: Zhou Xin , Zeng Yiwei , Zheng Runchen , Wang Yuemei , Li Tao , Song Shanshan , Zhang Su , Huang Jinzhu , Ren Yulan
Published: June 2023

Endometrial cancer (EC) is a prevalent epithelial malignancy in the uterine corpus’s endometrium and myometrium. Regulating apoptosis of endometrial cancer cells has been a promising approach for treating EC. Recent in-vitro and in-vivo studies show that numerous extracts and monomers from natural products have pro-apoptotic properties in EC. Therefore, we have reviewed the current studies regarding natural products in modulating the apoptosis of EC cells and summarized their potential mechanisms. The potential signaling pathways include the mitochondria-dependent apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, the mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, NF-κB-mediated apoptotic pathway, PI3K/AKT/mTOR mediated apoptotic pathway, the p21-mediated apoptotic pathway, and other reported pathways. This review focuses on the importance of natural products in treating EC and provides a foundation for developing natural products-based anti-EC agents.
A steady flow of MHD Maxwell viscoelastic fluid on a flat porous plate with the outcome of radiation and heat generation
Authors: Sudarmozhi K. , Iranian D. , Khan Ilyas
Published: June 2023

Maxwell fluids display viscous flow on a long timescale but exhibit additional elastic resistance during rapid deformations. Among various types of rate-type fluids, the Maxwell fluid has achieved prominence in numerous study fields. This viscoelastic fluid has viscous and elastic properties. Due to their reduced complexity, this Maxwell fluid is utilized used in the polymeric industries. We have established a mathematical model based on the applications. This article examines the mathematical and graphical analysis for steady-state magnetohydrodynamic flow in a horizontal flat plate of Maxwell viscoelastic fluid for a permeable medium with heat and thermal radiation. The non-dimensional and similarity transformation used to frame the partial differential equations with restored ordinary differential equations. The shooting technique is originated to find solutions to nonlinear boundary value problems with the help of MATLAB software via the Runge-Kutta Fehlberg method. The primary idea behind this strategy is to change the boundary conditions of boundary value problems into initial value problems. Several plots illustrate the leading parameters such as Prandtl number (Pr), Deborah number (De), Eckert number (Ec), heat generation (Q), radiation (Rd), Lewis number (Le), magnetic parameter (M), and thermal slip condition (β) on the velocity profile and energy transfer behaviour. We validated our results with published work. The most significant impact of this study is that the Nusselt number drops as the Eckert number rises and climbs when heat radiation increases. The skin friction coefficient increases as Deborah number increases.
Fast strain mapping in abdominal aortic aneurysm wall reveals heterogeneous patterns
Authors: Bracco Marta Irene , Broda Magdalena , Lorenzen Ulver Spangsberg , Florkow Mateusz Cezary , Somphone Oudom , Avril Stephane , Biancolini Marco Evangelos , Rouet Laurence
Published: June 2023

Abdominal aortic aneurysm patients are regularly monitored to assess aneurysm development and risk of rupture. A preventive surgical procedure is recommended when the maximum aortic antero-posterior diameter, periodically assessed on two-dimensional abdominal ultrasound scans, reaches 5.5 mm. Although the maximum diameter criterion has limited ability to predict aneurysm rupture, no clinically relevant tool that could complement the current guidelines has emerged so far. In vivo cyclic strains in the aneurysm wall are related to the wall response to blood pressure pulse, and therefore, they can be linked to wall mechanical properties, which in turn contribute to determining the risk of rupture. This work aimed to enable biomechanical estimations in the aneurysm wall by providing a fast and semi-automatic method to post-process dynamic clinical ultrasound sequences and by mapping the cross-sectional strains on the B-mode image. Specifically, the Sparse Demons algorithm was employed to track the wall motion throughout multiple cardiac cycles. Then, the cyclic strains were mapped by means of radial basis function interpolation and differentiation. We applied our method to two-dimensional sequences from eight patients. The automatic part of the analysis took under 1.5 min per cardiac cycle. The tracking method was validated against simulated ultrasound sequences, and a maximum root mean square error of 0.22 mm was found. The strain was calculated both with our method and with the established finite-element method, and a very good agreement was found, with mean differences of one order of magnitude smaller than the image spatial resolution. Most patients exhibited a strain pattern that suggests interaction with the spine. To conclude, our method is a promising tool for investigating abdominal aortic aneurysm wall biomechanics as it can provide a fast and accurate measurement of the cyclic wall strains from clinical ultrasound sequences.
Effects of aerobic exercise on cardiac function and gene expression of NADPH oxidases in diaphragm muscle of rats with aortic stenosis-induced heart failure
Authors: Janini Gomes Mariana , Sabela Ana Karenina , Ferreira Isabele Tiburcio Pecin , de Souza Sérgio Luiz Borges , Mota Gustavo Augusto Ferreira , da Silva Vitor Loureiro , de Campos Dijon Henrique Salomé , Lima Aline Regina Ruiz , Carvalho Marianna Rabelo , Bazan Silmeia Garcia Zanati , Corrêa Camila Renata , Cicogna Antônio Carlos , Okoshi Marina Politi , Pacagnelli Francis Lopes
Published: June 2023

We evaluated the influence of aerobic physical exercise (EX) on gene-encoding proteins associated with oxidative stress in diaphragm muscle of rats with aortic stenosis-induced heart failure (HF). Wistar male rats were divided into four groups: Control sedentary (C); Control exercise (C-Ex); Sedentary aortic stenosis (AS); Aortic stenosis exercise (AS-Ex). Exercised rats trained 5 times a week for 10 weeks on a treadmill. Statistical analysis was performed by ANOVA or Kruskal–Wallis test. In the final echocardiogram, animals with aortic stenosis subjected to exercise demonstrated improvement in systolic function compared to the sedentary aortic stenosis group. In diaphragm muscle, the activity of antioxidant enzymes, malondialdehyde malondialdehyde concentration, protein carbonylation, and protein expression of p65 and its inhibitor IκB did not differ between groups. Alterations in gene expression of sources that generate reactive species of oxygen were observed in AS-Ex group, which showed decreased mRNA abundance of NOX2 and NOX4 compared to the aortic stenosis group (p < 0.05). We concluded that aerobic exercise has a positive impact during heart failure, ameliorating systolic dysfunction and biomarkers of oxidative stress in diaphragm muscle of rats with aortic stenosis-induced heart failure.
Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice
Authors: Pan Shiyue , Karey Emma , Nieves-Cintron Madeline , Chen Yi-Je , Hwang Sung Hee , Hammock Bruce D. , Pinkerton Kent E. , Chen Chao-Yin
Published: June 2023

Background: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality with an estimated 80% of SHS-related deaths attributed to cardiovascular causes. Public health measures and smoking bans have been successful both in reducing SHS exposure and improving cardiovascular outcomes in non-smokers. Soluble epoxide hydrolase (sEH) inhibitors have been shown to attenuate tobacco exposure-induced lung inflammatory responses, making them a promising target for mitigating SHS exposure-induced cardiovascular outcomes.

Objectives: The objectives of this study were to determine 1) effects of environmentally relevant SHS exposure on cardiac autonomic function and blood pressure (BP) regulation and 2) whether prophylactic administration of an sEH inhibitor (TPPU) can reduce the adverse cardiovascular effects of SHS exposure.

Methods: Male C57BL/6J mice (11 weeks old) implanted with BP/electrocardiogram (ECG) telemetry devices were exposed to filtered air or 3 mg/m3 of SHS (6 hr/d, 5 d/wk) for 12 weeks, followed by 4 weeks of recovery in filtered air. Some mice received TPPU in drinking water (15 mg/L) throughout SHS exposure. BP, heart rate (HR), HR variability (HRV), baroreflex sensitivity (BRS), and BP variability were determined monthly.

Results: SHS exposure significantly decreased 1) short-term HRV by ∼20% (p < 0.05) within 4 weeks; 2) overall HRV with maximum effect at 12 weeks (−15%, p < 0.05); 3) pulse pressure (−8%, p < 0.05) as early as week 4; and 4) BRS with maximum effect at 12 weeks (−11%, p < 0.05). Four weeks of recovery following 12 weeks of SHS ameliorated all SHS-induced cardiovascular detriments. Importantly, mice exposed to TPPU in drinking water during SHS-related exposure were protected from SHS cardiovascular consequences.

Discussion: The data suggest that 1) environmental relevant SHS exposure significantly alters cardiac autonomic function and BP regulation; 2) cardiovascular consequences from SHS can be reversed by discontinuing SHS exposure; and 3) inhibiting sEH can prevent SHS-induced cardiovascular consequences.
Influence of long-term fertilization on soil aggregates stability and organic carbon occurrence characteristics in karst yellow soil of Southwest China
Authors: Liu Yanling , Zhang Meng , Xiong Han , Li Yu , Zhang Yarong , Huang Xingcheng , Yang Yehua , Zhu Huaqing , Jiang Taiming
Published: June 2023

Current research has long focused on soil organic carbon and soil aggregates stability. However, the effects of different long-term fertilization on the composition of yellow soil aggregates and the characteristics of the occurrence of organic carbon in the karst region of Southwest China are still unclear. Based on a 25-year long-term located experiment on yellow soil, soil samples from the 0–20 cm soil layer were collected and treated with different fertilizers (CK: unfertilized control; NPK: chemical fertilizer; 1/4 M + 3/4 NP: 25% chemical fertilizer replaced by 25% organic fertilizer; 1/2 M + 1/2 NP: 50% chemical fertilizer replaced by organic fertilizer; and M: organic fertilizer). In water-stable aggregates, soil aggregates stability, total organic carbon (TOC), easily oxidized organic carbon (EOC), carbon preservation capacity (CPC), and carbon pool management index (CPMI) were analyzed. The findings demonstrated that the order of the average weight diameter (MWD), geometric mean diameter (GWD), and macro-aggregate content (R0.25) of stable water aggregates was M > CK > 1/2M +1/2NP > 1/4M +3/4NP> NPK. The MWD, GWD, and R0.25 of NPK treatment significantly decreased by 32.6%, 43.2%, and 7.0 percentage points, respectively, compared to CK treatment. The order of TOC and EOC content in aggregates of different particle sizes was M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, and it increased as the rate of organic fertilizer increased. In macro-aggregates and bulk soil, the CPC of TOC (TOPC) and EOC (EOPC), as well as CPMI, were arranged as M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, but the opposite was true for micro-aggregates. In bulk soil treated with organic fertilizer, the TOPC, EOPC, and CPMI significantly increased by 27.4%–53.8%, 29.7%–78.1%, 29.7–82.2 percentage points, respectively, compared to NPK treatment. Redundancy analysis and stepwise regression analysis show that TOC was the main physical and chemical factor affecting the aggregates stability, and the TOPC in micro-aggregates has the most direct impact. In conclusion, the primary cause of the decrease in SOC caused by the long-term application of chemical fertilizer was the loss of organic carbon in macro-aggregates. An essential method to increase soil nutrient supply and improve yellow soil productivity was to apply an organic fertilizer to increase aggregates stability, storage and activity of SOC in macro-aggregates.
Fungal effectors versus defense-related genes of B. juncea and the status of resistant transgenics against fungal pathogens
Authors: Rai Prajjwal , Prasad Laxman , Rai Pramod Kumar
Published: June 2023

Oilseed brassica has become instrumental in securing global food and nutritional security. B. juncea, colloquially known as Indian mustard, is cultivated across tropics and subtropics including Indian subcontinent. The production of Indian mustard is severely hampered by fungal pathogens which necessitates human interventions. Chemicals are often resorted to as they are quick and effective, but due to their economic and ecological unsustainability, there is a need to explore their alternatives. The B. juncea-fungal pathosystem is quite diverse as it covers broad-host range necrotrophs (Sclerotinia sclerotiorum), narrow-host range necrotrophs (Alternaria brassicae and A. brassicicola) and biotrophic oomycetes (Albugo candida and Hyaloperonospora brassica). Plants ward off fungal pathogens through two-step resistance mechanism; PTI which involves recognition of elicitors and ETI where the resistance gene (R gene) interacts with the fungal effectors. The hormonal signalling is also found to play a vital role in defense as the JA/ET pathway is initiated at the time of necrotroph infection and SA pathway is induced when the biotrophs attack plants. The review discuss the prevalence of fungal pathogens of Indian mustard and the studies conducted on effectoromics. It covers both pathogenicity conferring genes and host-specific toxins (HSTs) that can be used for a variety of purposes such as identifying cognate R genes, understanding pathogenicity and virulence mechanisms, and establishing the phylogeny of fungal pathogens. It further encompasses the studies on identifying resistant sources and characterisation of R genes/quantitative trait loci and defense-related genes identified in Brassicaceae and unrelated species which, upon introgression or overexpression, confer resistance. Finally, the studies conducted on developing resistant transgenics in Brassicaceae have been covered in which chitinase and glucanase genes are mostly used. The knowledge gained from this review can further be used for imparting resistance against major fungal pathogens.