bluuebunny/crossref_metadata_2025 huggingface dataset:
How effective is the BNT162b2 mRNA vaccine against SARS-CoV-2 transmission and infection? A national programme analysis in Monaco, July 2021 to September 2022
Authors: Althaus Thomas , Overton Christopher E. , Devaux Isabelle , House Thomas , Lapouze Arnaud , Troel Alexa , Vanzo Bertrand , Laroche Margaux , Bordero Alexandre , Jorgensen Pernille , Pebody Richard , Voiglio Eric J.
Published: June 2024

Background

We quantified SARS-CoV-2 dynamics in different community settings and the direct and indirect effect of the BNT162b2 mRNA vaccine in Monaco for different variants of concern (VOC).

Methods

Between July 2021 and September 2022, we prospectively investigated 20,443 contacts from 6320 index cases using data from the Monaco COVID-19 Public Health Programme. We calculated secondary attack rates (SARs) in households (n = 13,877), schools (n = 2508) and occupational (n = 6499) settings. We used binomial regression with a complementary log–log link function to measure adjusted hazard ratios (aHR) and vaccine effectiveness (aVE) for index cases to infect contacts and contacts to be infected in households.

Results

In households, the SAR was 55% (95% CI 54–57) and 50% (48–51) among unvaccinated and vaccinated contacts, respectively. The SAR was 32% (28–36) and 12% (10–13) in workplaces, and 7% (6–9) and 6% (3–10) in schools, among unvaccinated and vaccinated contacts respectively. In household, the aHR was lower in contacts than in index cases (aHR 0.68 [0.55–0.83] and 0.93 [0.74–1.1] for delta; aHR 0.73 [0.66–0.81] and 0.89 [0.80–0.99] for omicron BA.1&2, respectively). Vaccination had no significant effect on either direct or indirect aVE for omicron BA.4&5. The direct aVE in contacts was 32% (17, 45) and 27% (19, 34), and for index cases the indirect aVE was 7% (− 17, 26) and 11% (1, 20) for delta and omicron BA.1&2, respectively. The greatest aVE was in contacts with a previous SARS-CoV-2 infection and a single vaccine dose during the omicron BA.1&2 period (45% [27, 59]), while the lowest were found in contacts with either three vaccine doses (aVE − 24% [− 63, 6]) or one single dose and a previous SARS-CoV-2 infection (aVE − 36% [− 198, 38]) during the omicron BA.4&5 period.

Conclusions

Protection conferred by the BNT162b2 mRNA vaccine against transmission and infection was low for delta and omicron BA.1&2, regardless of the number of vaccine doses and previous SARS-CoV-2 infection. There was no significant vaccine effect for omicron BA.4&5. Health authorities carrying out vaccination campaigns should bear in mind that the current generation of COVID-19 vaccines may not represent an effective tool in protecting individuals from either transmitting or acquiring SARS-CoV-2 infection.
Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors
Authors: Lan Ailin , Li Han , Shen Meiying , Li Daxue , Shu Dan , Liu Yang , Tang Haozheng , Li Kang , Peng Yang , Liu Shengchun
Published: June 2024

Background

Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors.

Methods

This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality.

Results

During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27).

Conclusions

Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).
Assessing the impact of extracellular matrix fiber orientation on breast cancer cellular metabolism
Authors: Pickett Madison R. , Chen Yuan-I , Kamra Mohini , Kumar Sachin , Kalkunte Nikhith , Sugerman Gabriella P. , Varodom Kelsey , Rausch Manuel K. , Zoldan Janet , Yeh Hsin-Chin , Parekh Sapun H.
Published: June 2024

The extracellular matrix (ECM) is a dynamic and complex microenvironment that modulates cell behavior and cell fate. Changes in ECM composition and architecture have been correlated with development, differentiation, and disease progression in various pathologies, including breast cancer [1]. Studies have shown that aligned fibers drive a pro-metastatic microenvironment, promoting the transformation of mammary epithelial cells into invasive ductal carcinoma via the epithelial-to-mesenchymal transition (EMT) [2]. The impact of ECM orientation on breast cancer metabolism, however, is largely unknown. Here, we employ two non-invasive imaging techniques, fluorescence-lifetime imaging microscopy (FLIM) and intensity-based multiphoton microscopy, to assess the metabolic states of cancer cells cultured on ECM-mimicking nanofibers in a random and aligned orientation. By tracking the changes in the intrinsic fluorescence of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, as well as expression levels of metastatic markers, we reveal how ECM fiber orientation alters cancer metabolism and EMT progression. Our study indicates that aligned cellular microenvironments play a key role in promoting metastatic phenotypes of breast cancer as evidenced by a more glycolytic metabolic signature on nanofiber scaffolds of aligned orientation compared to scaffolds of random orientation. This finding is particularly relevant for subsets of breast cancer marked by high levels of collagen remodeling (e.g. pregnancy associated breast cancer), and may serve as a platform for predicting clinical outcomes within these subsets [3–6].
Plasmodium falciparum neonatal malaria with atypical presentation: a case series from southwestern Ethiopia
Authors: Tesso Zerubabel Girma , Gossaye Tariku Yigremachew , Bekana Dereje Sileshi , Kebede Molla Asnake , Besir Fikretsion Degemu , Dabe Nikodimos Eshetu
Published: June 2024

Background

Neonatal malaria is defined as the detection of asexual stages of Plasmodium species in the cord blood within the first 28 days of life. It can be congenital or acquired through mosquito bites or blood transfusions. Neonates are generally considered to be relatively protected due to the multiple innate and acquired physiological protective effects present in neonates. However, in areas where malaria is endemic, the prevalence of malaria in neonates is high. The predominant clinical feature of malaria in neonates is fever. Other clinical manifestations of neonatal malaria include respiratory distress, pallor and anaemia, hepatomegaly, refusal to feed, jaundice and diarrhoea. Atypical presentations without fever can lead to inaccurate diagnosis and contribute to neonatal morbidity and mortality. Neonates from endemic areas with any of the above symptoms should be screened for malaria.

Case presentation

We present a series of three cases of neonatal Plasmodium falciparum malaria that presented atypically without febrile episodes and were diagnosed and managed at Mizan-Tepi University Teaching Hospital between July and September 2023. The first patient presented with vomiting, refusal to feed, pallor, severe anaemia, and splenomegaly. The second patient presented with an inconsolable cry, failure to pass feces, abdominal distention, and anaemia. The third patient presented with vomiting and anaemia. All patients received a 7-day course of intravenous artesunate; the first patient also received a blood transfusion. All patients recovered and were discharged.

Conclusions

Partial immunity resulting from repeated malaria infections in endemic regions may result in the transfer of high levels of maternal Immunoglobulin G (IgG) antibodies through the placenta and can produce different atypical clinical presentations. In malaria-endemic areas, neonates presenting with any of the presenting signs and symptoms of malaria, including afebrile presentation, require malaria screening to avoid delays in diagnosis.
Cinnamaldehyde inhibits the NLRP3 inflammasome by preserving mitochondrial integrity and augmenting autophagy in Shigella sonnei-infected macrophages
Authors: Hua Kuo-Feng , Lin Yu-Bei , Chiu Hsiao-Wen , Wong Wei-Ting , Ka Shuk-Man , Wu Chun-Hsien , Lin Wen-Yu , Wang Chien-Chun , Hsu Chung-Hua , Hsu Hsien-Ta , Ho Chen-Lung , Li Lan-Hui
Published: June 2024

Background

Worldwide, more than 125 million people are infected withShigellaeach year and develop shigellosis. In our previous study, we provided evidence thatShigella sonneiinfection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves ofCinnamomum osmophloeumkaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome inS. sonnei-infected macrophages.

Methods

Macrophages were infected withS. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity.

Results

CA inhibited the NLRP3 inflammasome inS. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1β and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages againstS. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection.

Conclusion

CA shows promise as a nutraceutical for mitigatingS. sonneiinfection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages againstS. sonnei.
NK-92 cells labeled with Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer
Authors: Lian Jingge , Li Meng , Duan Meng , Sun Yaqian , Wang Zilin , Guo Xinyu , Li Jingchao , Gao Guo , Li Kangan
Published: June 2024

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.
Landscape assessment of the availability of medical abortion medicines in India
Authors: Karna Priya , Sharma K. Aparna , Grossman Amy , Gupta Madhur , Chatterjee Tapas , Williams Natalie , Prata Ndola , Sorhaindo Annik , Läser Laurence , Rehnström Loi Ulrika , Ganatra Bela , Chaudhary Pushpa
Published: June 2024

Background

Medical abortion with mifepristone and misoprostol can be provided up to 63 days’ gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India.

Methods

We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021.

Results

Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment.

Conclusion

Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed.
Aberrant left coronary artery from the pulmonary artery with patent ductus arteriosus - a case report and review of the literature
Authors: Amer Ahmad , Shai Hanita , Assa Sagi , Mitler Avital , Sternfeld Alona Raucher
Published: June 2024

Background

Aberrant left coronary artery from pulmonary artery (ALCAPA) is a very rare congenital heart defect. Its coexistence with patent ductus arteriosus (PDA) is extremely rare. The high pressures created by the left-to-right shunt in the pulmonary arteries can delay symptoms and create a real challenge in diagnosing ALCAPA. Missing this diagnosis can have severe results, including extensive ischemia and sudden death.

Case presentation

We present a case of an infant born with a large PDA. Initially treated conservatively, however, due to congestive heart failure and lack of weight gain, she underwent surgical ligation of the PDA at the age of four and a half months. Following surgery, she developed pulmonary edema. Echocardiography revealed decreased ventricular function. ECG revealed ST elevations on lateral leads, and serum troponin was significantly increased. The patient underwent cardiac magnetic resonance imaging (MRI), which revealed signs of wall ischemia and decreased function of the left ventricle (LV) with unclear coronary anatomy. Diagnostic catheterization revealed an ALCAPA. She underwent surgical intervention, and the left coronary artery was re-implanted in the aortic sinus. Follow-up revealed slow improvement of cardiac function.

Discussion and literature review

The coexistence of PDA and ALCAPA is a very rare occurrence. We found at least 10 reported cases in the literature. Delayed diagnosis might be detrimental. The prognosis of these patients is variable.

Conclusion

An unusual post-surgical course following PDA repair requires a high index of suspicion and appropriate evaluation for ALCAPA, preferably with angiography.
Delayed management of acute type A aortic dissection with concomitant coronary artery bypass graft
Authors: Khawaja Zohaib R. , Aboutabl Yusuf M. , Cambronero Gabriel E. , Willis Robert G. , Gilani Aaron S. , Imielski Bartlomiej R.
Published: June 2024

Background

Pre-operative coronary angiography and concomitant, planned coronary artery bypass are infrequently performed with type A aortic dissection repair. We present a case in which pre-operative coronary computed tomography angiography was appropriate, and subsequent dissection repair and concomitant coronary artery bypass were successfully performed.

Case Presentation

The patient is a 58-year-old male with heart failure with preserved ejection fraction, renal insufficiency, hypertension, obesity, and smoking history, who presented with a three-to-four-day history of persistent back pain, worsening exertional dyspnea, and orthopnea, as well as a two-to-three month history of dyspnea, lower extremity edema, and intermittent angina. He was diagnosed with an acute type A aortic dissection and anti-impulse control was initiated. However, repair was delayed in order to allow apixaban to metabolize and decrease the risk of bleeding, as the patient was approximately six days post-dissection, without malperfusion, with a well-controlled blood pressure on anti-impulse therapy, and had received five days of anticoagulation. During this time, coronary computed tomography angiography was performed to assess the need for concomitant revascularization and showed coronary artery disease. Ascending aorta hemiarch replacement with aortic valve resuspension, two-vessel coronary artery bypass grafting, and left atrial appendage clipping were performed successfully.

Conclusions

Pre-operative imaging can be considered in a select group of acute type A aortic dissections that present without malperfusion, and with well-controlled blood pressure on anti-impulse/negative inotropic therapy.
Endothelial progenitor cell-derived extracellular vesicles: the world of potential prospects for the treatment of cardiovascular diseases
Authors: Chen De-Xin , Lu Chuang-Hong , Na Na , Yin Rui-Xing , Huang Feng
Published: June 2024

Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular vesicles (EVs) serve as vital mediators in intercellular communication and material exchange. Endothelial progenitor cells (EPCs), recognized as precursors of vascular endothelial cells (ECs), have garnered considerable attention in recent years due to the potential therapeutic value of their derived extracellular vesicles (EPC-EVs) in the context of CVDs. This comprehensive review systematically explores the origins, characteristics, and functions of EPCs, alongside the classification, properties, biogenesis, and extraction techniques of EVs, with particular emphasis on their protective roles in CVDs. Additionally, we delve into the essential bioactive components of EPC-EVs, including microRNAs, long non-coding RNAs, and proteins, analyzing their beneficial effects in promoting angiogenesis, anti-inflammatory and anti-oxidant activities, anti-fibrosis, anti-apoptosis, and myocardial regeneration. Furthermore, this review comprehensively investigates the therapeutic potential of EPC-EVs across various CVDs, encompassing acute myocardial infarction, myocardial ischemia–reperfusion injury, atherosclerosis, non-ischemic cardiomyopathies, and diabetic cardiovascular disease. Lastly, we summarize the potential challenges associated with the clinical application of EPC-EVs and outline future directions, aiming to offer a valuable resource for both theoretical insights and practical applications of EPC-EVs in managing CVDs.
Riemann problem for multiply connected domain in Besov spaces
Authors: Bliev Nazarbay , Yerkinbayev Nurlan
Published: June 2024

In this paper, we obtain conditions of the solvability of the Riemann boundary value problem for sectionally analytic functions in multiply connected domains in Besov spaces embedded into the class of continuous functions. We indicate a new class of Cauchy-type integrals, which are continuous on a closed domain with continuous (not Hölder) density in terms of Besov spaces, and for which the Sokhotski–Plemelj formulas are valid.
Bacteria colonization and gene expression related to immune function in colon mucosa is associated with growth in neonatal calves regardless of live yeast supplementation
Authors: Nishihara Koki , Villot Clothilde , Cangiano Lautaro , Guan Le Luo , Steele Michael
Published: June 2024

Background

As Holstein calves are susceptible to gastrointestinal disorders during the first week of life, understanding how intestinal immune function develops in neonatal calves is important to promote better intestinal health. Feeding probiotics in early life may contribute to host intestinal health by facilitating beneficial bacteria colonization and developing intestinal immune function. The objective of this study was to characterize the impact of early life yeast supplementation and growth on colon mucosa-attached bacteria and host immune function.

Results

Twenty Holstein bull calves received no supplementation (CON) or Saccharomyces cerevisiae boulardii (SCB) from birth to 5 d of life. Colon tissue biopsies were taken within 2 h of life (D0) before the first colostrum feeding and 3 h after the morning feeding at d 5 of age (D5) to analyze mucosa-attached bacteria and colon transcriptome. Metagenome sequencing showed that there was no difference in α and β diversity of mucosa-attached bacteria between day and treatment, but bacteria related to diarrhea were more abundant in the colon mucosa on D0 compared to D5. In addition, qPCR indicated that the absolute abundance of Escherichia coli (E. coli) decreased in the colon mucosa on D5 compared to D0; however, that of Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii, which could competitively exclude E. coli, increased in the colon mucosa on D5 compared to D0. RNA-sequencing showed that there were no differentially expressed genes between CON and SCB, but suggested that pathways related to viral infection such as “Interferon Signaling” were activated in the colon mucosa of D5 compared to D0.

Conclusions

Growth affected mucosa-attached bacteria and host immune function in the colon mucosa during the first 5 d of life in dairy calves independently of SCB supplementation. During early life, opportunistic pathogens may decrease due to intestinal environmental changes by beneficial bacteria and/or host immune function. Predicted activation of immune function-related pathways may be the result of host immune function development or suggest other antigens in the intestine during early life. Further studies focusing on the other antigens and host immune function in the colon mucosa are required to better understand intestinal immune function development.
Synthetic community derived from grafted watermelon rhizosphere provides protection for ungrafted watermelon against Fusarium oxysporum via microbial synergistic effects
Authors: Qiao Yizhu , Wang Zhendong , Sun Hong , Guo Hanyue , Song Yang , Zhang He , Ruan Yang , Xu Qicheng , Huang Qiwei , Shen Qirong , Ling Ning
Published: June 2024

Background

Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community.

Results

Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria.

Conclusions

Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture.
Deep learning-based pathway-centric approach to characterize recurrent hepatocellular carcinoma after liver transplantation
Authors: To Jeffrey , Ghosh Soumita , Zhao Xun , Pasini Elisa , Fischer Sandra , Sapisochin Gonzalo , Ghanekar Anand , Jaeckel Elmar , Bhat Mamatha
Published: June 2024

Background

Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15–20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology.

Materials and methods

We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC.

Results

The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence.

Conclusion

Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence.
Factors associated with incomplete adherence to integrase strand transfer inhibitor-containing single-tablet regimen among Japanese people living with HIV
Authors: Kunimoto Yusuke , Hikasa Shinichi , Ishihara Masashi , Tsukiji Mariko , Nobori Kazuko , Kimura Takeshi , Onishi Kenta , Yamamoto Yuuki , Haruta Kyohei , Kasiwabara Yohei , Fujii Kenji , Fukudo Masahide
Published: June 2024

Background

People living with human immunodeficiency virus (PLWH) require high rates of medication adherence to antiretroviral therapy (ART) for a successful treatment outcome. Understanding the factors associated with incomplete adherence among those receiving integrase strand transfer inhibitor-containing single-tablet regimens (INSTI-STRs) is crucial for improving treatment outcomes. This study aimed to identify the factors contributing to incomplete ART adherence among Japanese PLWH receiving INSTI-STRs.

Methods

This multicenter cross-sectional study was conducted at 11 Japanese institutions as an anonymous survey. ART adherence was assessed using a self-reported questionnaire. We defined incomplete ART adherence as missing ≥ 1 dose of antiretroviral drugs (ARVs) over the past month. The factors associated with incomplete ART adherence were assessed using logistic regression analysis. Additionally, we investigated the associations between patients’ satisfaction score with and need for ARVs and their adherence to ART.

Results

The final analysis included data of 387 patients who were treated with INSTI-STRs. Multivariate logistic regression demonstrated significant association of younger age (adjusted odds ratio [aOR], 0.79; 95%confidence interval [CI]: 0.64–0.99 for each 10-year increment) with incomplete ART adherence. Additionally, female sex (aOR, 3.98; 95%CI: 1.36–11.60); depressive symptoms (mild depression: aOR, 1.68; 95%CI: 1.001–2.82, moderate depression: aOR, 2.98; 95%CI: 1.35–6.53, and severe depression: aOR, 8.73; 95%CI: 1.38–55.00 vs. minimal depression); were also significantly associated with incomplete ART adherence when compared with the reference categories. Concomitant medication usage was significantly associated with a lower rate of incomplete ART adherence (1–4 medications: aOR, 0.53; 95%CI: 0.31–0.89 and ≥ 5 medications: aOR, 0.30; 95%CI: 0.13–0.70 vs. no concomitant medication usage). In the incomplete ART adherence group, satisfaction scores for various aspects were significantly lower. Furthermore, a lower proportion of patients in the incomplete ART adherence group preferred the option of “taking tablets daily and visiting the hospital every 3 months,” compared to those in the complete ART adherence group (p = 0.008).

Conclusions

This study demonstrated that factors associated with incomplete ART adherence include younger age, female sex, no concomitant medication, and depressive symptoms. Despite ART simplification, incomplete adherence among PLWH receiving INSTI-STRs, remains a challenge, requiring additional actions.
The Swedish Stroke Self-Efficacy Questionnaire: translation and cross-cultural adaptation
Authors: Klockar Erika , Kylén Maya , McCarthy Linnea , Koch Lena von , Gustavsson Catharina , Jones Fiona , Elf Marie
Published: June 2024

Objective

To translate and cross-culturally adapt the Stroke Self-Efficacy Questionnaire (SSEQ) from English to Swedish and to evaluate psychometric properties of the questionnaire.

Methods

A cross-sectional study design, where the translation followed a process including initial translation, synthesis, backward translation, expert committee, and pretest. Content validity was assessed using Content validity index (CVI). Psychometric assessments included floor-ceiling effects and internal consistency.

Results

Language and cultural congruence were achieved, and content validity index scores were high (0.923-1). The psychometric evaluations provided acceptable outcomes concerning internal consistency, with Cronbach’s alpha scores for the total scale (0.902), the activities subscale (0.861) and the self-management subscale (0.818) respectively. Ceiling effects were evident, but no floor effects.

Conclusion

This study found the Swedish version of the SSEQ promising as a tool for assessment of self-efficacy in a Swedish stroke care setting, although further psychometric assessments are recommended in future studies.
Patient-reported outcomes and healthcare resource utilization in systemic lupus erythematosus: impact of disease activity
Authors: Touma Zahi , Costenbader Karen H. , Hoskin Ben , Atkinson Christian , Bell David , Pike James , Berry Pamela , Karyekar Chetan S.
Published: June 2024

Background

Limited real-world data exists on clinical outcomes in systemic lupus erythematosus (SLE) patients by SLE Disease Activity Index 2000 (SLEDAI-2 K), hereafter, SLEDAI. We aimed to examine the association between SLEDAI score and clinical, patient-reported and economic outcomes in patients with SLE.

Methods

Rheumatologists from the United States of America and Europe provided real-world demographic, clinical, and healthcare resource utilization (HCRU) data for SLE patients. Patients provided self-reported outcome data, capturing their general health status using the EuroQol 5-dimension 3-level questionnaire (EQ-5D-3 L), health-related quality of life using the Functional Assessment of Chronic Illness Therapy (FACIT) and work productivity using the Work Productivity and Activity Impairment questionnaire (WPAI). Low disease activity was defined as SLEDAI score ≤ 4 and ≤ 7.5 mg/day glucocorticoids; patients not meeting these criteria were considered to have “higher” active disease. Data were compared between patients with low and higher disease activity. Logistic regression estimated a propensity score for SLE based on demographic and clinical characteristics. Propensity score matched analyses compared HCRU, patient-reported outcomes, income loss and treatment satisfaction in patients with low disease activity versus higher active disease.

Results

Data from 296 physicians reporting on 730 patients (46 low disease activity, 684 higher active disease), and from 377 patients’ self-reported questionnaires (24 low disease activity, 353 higher active disease) were analyzed. Flaring in the previous 12 months was 2.6-fold more common among patients with higher versus low active disease. Equation 5D-3 L utility index was 0.79 and 0.88 and FACIT-Fatigue scores were 34.78 and 39.79 in low versus higher active disease patients, respectively, indicating better health and less fatigue, among patients with low versus higher active disease. Absenteeism, presenteeism, overall work impairment, and total activity impairment were 47.0-, 2.0-, 2.6- and 1.5-fold greater in patients with higher versus low disease activity. In the previous 12 months there were 28% more healthcare consultations and 3.4-fold more patients hospitalized in patients with higher versus low disease activity.

Conclusion

Compared to SLE patients with higher active disease, patients with low disease activity experienced better health status, lower HCRU, less fatigue, and lower work productivity impairment, with work absenteeism being substantially lower in these patients.
Severe fetal distress and acute maternal pancreatitis secondary to severe hypertriglyceridemia: a case report
Authors: Garin Charlotte , Bridier-Petit Agathe , Ménard Sophie , Lamy Clotilde
Published: June 2024

Background

Acute pancreatitis (AP) during pregnancy is a rare condition and a potential cause of maternal–fetal mortality. Its diagnosis can be challenging. Hypertriglyceridemia (HTG) is one of the causes. We describe a case of severe fetal distress in the third trimester of pregnancy, associated with severe HTG complicated by AP.

Case presentation

A 35-year-old pregnant patient at 36-week gestation presented to the emergency department with acute epigastric pain. After excluding preeclampsia and initially challenging laboratory analyses, a diagnosis of AP was made based on a lipase level 12 times the normal range. The etiology was HTG at 40 times the normal level. Despite initial conservative management, the patient deteriorated rapidly clinically, and severe fetal distress (SFD) necessitated an emergency cesarean section. Lactescent blood appearance was observed intraoperatively. We suspect that the severe and rapid HTG may have caused acute fetal hypoxia.

Conclusions

AP during pregnancy is a rare condition, with significant maternal–fetal mortality. Early diagnosis remains challenging. A multidisciplinary approach is necessary for optimal management, with special consideration for rapid fetal delivery in cases of AP secondary to HTG due to the increased risk of fetal mortality.
Identification of SSR markers linked to the abscission of cotton boll traits and mining germplasm in Cotton
Authors: Shui Guangling , Lin Hairong , Ma Xiaomei , Zhu Bo , Han Peng , Aini Nurimanguli , Guo Chunping , Wu Yuanlong , Pan Zhenyuan , You Chunyuan , Song Guoli , Nie Xinhui
Published: June 2024

Background

Cotton is an economically important crop. It is crucial to find an effective method to improve cotton yield, and one approach is to decrease the abscission of cotton bolls and buds. However, the lack of knowledge of the genetic and molecular mechanisms underlying cotton boll abscission traits has hindered genetic improvements.

Results

Pearson’s correlation analysis revealed a significant positive correlation between boll abscission rates 1 (AR1) and boll abscission rates 2 (AR2). A genome-wide association study was conducted on 145 loci that exhibited high polymorphism and were uniformly distributed across 26 chromosomes (pair). The study revealed 18, 46, and 62 markers that were significantly associated with boll abscission, fiber quality, and yield traits (P < 0.05), explaining 1.75%–7.13%, 1.16%–9.58%, and 1.40%–5.44% of the phenotypic variation, respectively. Notably, the marker MON_SHIN-1584b was associated with the cotton boll abscission trait, whereas MON_CGR5732a was associated with cotton boll abscission and fiber quality traits. Thirteen of the marker loci identified in this study had been previously reported. Based on phenotypic effects, six typical cultivars with elite alleles related to cotton boll abscission, fiber quality, and yield traits were identified. These cultivars hold great promise for widespread utilization in breeding programs.

Conclusions

These results lay the foundation for understanding the molecular regulatory mechanism of cotton boll abscission and provide data for the future improvement of cotton breeding.
Evaluation of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in patients with inflammatory bowel disease: gene expression of TNF-α as a marker of disease severity
Authors: Zaki Moushira , Orban Hisham A. , Mahmoud Marwa , Youness Eman R. , Booles Hoda F. , Khalil Wagdy K. B. , Wafy Wafaa , El-Atrebi Kamal A. , Hamed Khaled , El-Bassyouni Hala T.
Published: June 2024

Background

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of unknown etiology and unpredictable course. The aim of the work was to assess the levels of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in IBD patients compared to controls and evaluate the gene expression of TNF-α as a marker of disease severity.

Methods

Adropin, fasting serum FGF-1 levels, TLR1, and TNF-α were measured in 60 IBD patients. They were also compared with 58 healthy controls matching age and gender. Moreover, the blood cells cDNA copy number of TNF-α were determined as a marker of severity.

Results

Adropin and TLR1 levels were significantly lower in patients than controls. FGF-1 was reduced but not statistically significant. The expression of TNF-α gene in the IBD patients was significantly increased (42%) in comparison with control samples (P < 0.001).

Conclusions

Adropin, IGF-I, and Toll-like receptor-1 biomarkers may have a role in the intricate pathophysiology of IBD and may possibly operate as predictors of disease activity. Thus, they may be therapeutic targets for IBD. Moreover, the expression of TNF-α gene can be used as a marker of severity.
In silico approach to investigate the potential
HKT
gene responsive to salt stress in rice
Authors: Ullah Mohammad Asad , Abdullah-Zawawi Muhammad-Redha , Sukiran Noor Liyana , Uddin Md. Imtiaz , Ismail Ismanizan , Zainal Zamri
Published: June 2024

Rice is frequently subjected to various environmental stresses, resulting in significant production losses, with drought and salinity are the leading causes of plant damage globally. This study aims to characterize and understand the function of rice high-affinity potassium transporters (
HKTs
) genes in response to salinity stress. Initially, the genome-wide analysis was undertaken to reveal the evolutionarily conserved function of the
OsHKT
in higher plants. To investigate the transcription level of
OsHKT
during the vegetative and reproductive stages, two microarray datasets (GSE19024 and GSE3053) were analyzed, and salt-treated samples were subsequently evaluated using real-time PCR. Differentially expressed genes (
DEGs
) were identified from microarray datasets (GSE41650 and GSE14403), followed by constructing a
DEG
network that highlighted interaction partners of the
OsHKTs
. Genome mining of rice revealed 9
HKT
genes, namely
OsHKT1;1–1;5
and
OsHKT2;1–2;4
. These genes exhibited a well-conserved domain structure called
TrkH
. Comprehensive phylogenetic and motif analyses clustered genes encoding
HKT
proteins into seven monophyletic groups, and the motifs were relatively conserved. Ka/Ks ratios indicated a high degree of purifying selection during evolutionary time. Gene ontology findings suggested the involvement of
OsHKT
in stress response. Besides, several CRE motifs in the promoter regions of
OsHKT
have demonstrated their potential roles in abiotic stress responses. Furthermore, we analyzed the top 250 significant
DEGs
from the two datasets (p-value < 0.05; fold two change ≥ 1 or ≤  − 1) to evaluate the relationship among the
DEGs
and
HKTs
. Three co-expressed
OsHKT
genes were discovered to be upregulated in seedlings under salinity treatment, including
OsP5CS2
,
OsHAK1
, and
OsNHX2
, whereas
OsP5CS1
and
OsHAK27
were downregulated. The transcripts of
OsHKT
were found to be differentially expressed in a tissue-specific manner. Analysis of microarray datasets validated by real-time PCR shows that
OsHKT1;5
had a higher expression level, followed by
OsHKT1;1
,
OsHKT1;3
, and
OsHKT2;1
after salinity treatment. In addition, several micro-RNA targets in rice
HKT
genes regulate their expression in response to stress. This study paves the way for future investigation on genes and miRNA-target interaction in plants under environmental stresses, offering potential strategies to enhance stress tolerance in crops via targeted ion transport modification.
Riedel shear structures reactivation may induce earthquakes through long-term steam injection: A case study of a heavy oil production field in northwestern China
Authors: Xu Rui , Liang Chuntao , KanNi Zhati , Wang Meijie , Li Zhongquan , Wang Chaoliang , Liu Zhijin , Chen Chunmei
Published: June 2024

Conventional heavy oil exploitation methods involve steam stimulation and flooding. An oil field in northwestern China has been producing heavy oil via steam injection for several decades. The production area has been seismically quiet until an increase in seismicity occurred several years ago. An array of 40 seismographs has been deployed between July and October 2021 to monitor seismicity and resolve the possible causes of the recent seismicity. Using an end-to-end machine-learning-based high-precision earthquake location workflow, we analyze a microseismic sequence comprised of 178 events that occurred in the study area. Numerical simulations incorporating Coulomb failure stress suggest that prolonged steam injection can reactivate faults and induce seismic events. Similarly, fluid diffusion through conduits may achieve the same effect. Analysis of the focal mechanism solutions of 21 strike-slip and thrust events with [Formula: see text] in conjunction with the background stress regime ([Formula: see text] azimuth = N15°W) reveal that the stress distribution is compatible with a left-lateral Riedel shear structure (RSS) model. Therefore, we can speculate that steam injection may induce earthquakes by reactivating preexisting RSS fault structures. To conclude, the recent seismic events could have been induced by two possible mechanisms: (1) long-term steam injection may cause the static stress level on the faults beneath the reservoir to build up to critical levels, following which a slight stress disturbance can trigger an earthquake and (2) fluid conduits may transport condensed water to basement faults, weakening the faults through fluid diffusion.
Population-Level Identification of Patients With Lynch Syndrome for Clinical Care, Quality Improvement, and Research
Authors: Sharaf Ravi N. , Udaltsova Natalia , Li Dan , Pai Rish K. , Sinha Soham , Li Zixuan , Corley Douglas A.
Published: June 2024

PURPOSE

Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system.

METHODS

Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively.

RESULTS

Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS.

CONCLUSION

It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.