bluuebunny/crossref_metadata_2025 huggingface dataset:
ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma
Authors: Lin Sheng , Chen Qi , Tan Canliang , Su Manyi , Min Ling , Ling Lv , Zhou Junhao , Zhu Ting
Published: June 2024

Background

Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown.

Methods

Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration.

Results

It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments.

Conclusions

Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.
Engineering cascade biocatalysis in whole cells for syringic acid bioproduction
Authors: Liu Xin , An Yi , Gao Haijun
Published: June 2024

Background

Syringic acid (SA) is a high-value natural compound with diverse biological activities and wide applications, commonly found in fruits, vegetables, and herbs. SA is primarily produced through chemical synthesis, nonetheless, these chemical methods have many drawbacks, such as considerable equipment requirements, harsh reaction conditions, expensive catalysts, and numerous by-products. Therefore, in this study, a novel biotransformation route for SA production was designed and developed by using engineered whole cells.

Results

An O-methyltransferase from Desulfuromonas acetoxidans (DesAOMT), which preferentially catalyzes a methyl transfer reaction on the meta-hydroxyl group of catechol analogues, was identified. The whole cells expressing DesAOMT can transform gallic acid (GA) into SA when S-adenosyl methionine (SAM) is used as a methyl donor. We constructed a multi-enzyme cascade reaction in Escherichia coli, containing an endogenous shikimate kinase (AroL) and a chorismate lyase (UbiC), along with a p-hydroxybenzoate hydroxylase mutant (PobA**) from Pseudomonas fluorescens, and DesAOMT; SA was biosynthesized from shikimic acid (SHA) by using whole cells catalysis. The metabolic system of chassis cells also affected the efficiency of SA biosynthesis, blocking the chorismate metabolism pathway improved SA production. When the supply of the cofactor NADPH was optimized, the titer of SA reached 133 μM (26.2 mg/L).

Conclusion

Overall, we designed a multi-enzyme cascade in E. coli for SA biosynthesis by using resting or growing whole cells. This work identified an O-methyltransferase (DesAOMT), which can catalyze the methylation of GA to produce SA. The multi-enzyme cascade containing four enzymes expressed in an engineered E. coli for synthesizing of SA from SHA. The metabolic system of the strain and biotransformation conditions influenced catalytic efficiency. This study provides a new green route for SA biosynthesis.

Graphical Abstract
Automatic detection of epilepsy from EEGs using a temporal convolutional network with a self-attention layer
Authors: Huang Leen , Zhou Keying , Chen Siyang , Chen Yanzhao , Zhang Jinxin
Published: June 2024

Background

Over 60% of epilepsy patients globally are children, whose early diagnosis and treatment are critical for their development and can substantially reduce the disease’s burden on both families and society. Numerous algorithms for automated epilepsy detection from EEGs have been proposed. Yet, the occurrence of epileptic seizures during an EEG exam cannot always be guaranteed in clinical practice. Models that exclusively use seizure EEGs for detection risk artificially enhanced performance metrics. Therefore, there is a pressing need for a universally applicable model that can perform automatic epilepsy detection in a variety of complex real-world scenarios.

Method

To address this problem, we have devised a novel technique employing a temporal convolutional neural network with self-attention (TCN-SA). Our model comprises two primary components: a TCN for extracting time-variant features from EEG signals, followed by a self-attention (SA) layer that assigns importance to these features. By focusing on key features, our model achieves heightened classification accuracy for epilepsy detection.

Results

The efficacy of our model was validated on a pediatric epilepsy dataset we collected and on the Bonn dataset, attaining accuracies of 95.50% on our dataset, and 97.37% (A v. E), and 93.50% (B vs E), respectively. When compared with other deep learning architectures (temporal convolutional neural network, self-attention network, and standardized convolutional neural network) using the same datasets, our TCN-SA model demonstrated superior performance in the automated detection of epilepsy.

Conclusion

The proven effectiveness of the TCN-SA approach substantiates its potential as a valuable tool for the automated detection of epilepsy, offering significant benefits in diverse and complex real-world clinical settings.
Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation
Authors: Hou Yu , Zhu Lin , Ye Xiaofeng , Ke Qiaoying , Zhang Qibin , Xie Xiaowei , Piao Ji-gang , Wei Yinghui
Published: June 2024

Background

Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies.

Results

In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats.

Conclusion

In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.

Graphical Abstract
Delayed epistaxis after endoscopic transnasal pituitary tumor resection: clinical characteristics, risk factors, treatment and prevention
Authors: Mu Chengzhi , Song Zhenyu , Yu Shengyuan
Published: June 2024

Background

Delayed epistaxis after endoscopic transnasal pituitary tumor resection (ETPTR) is a critical complication, tending to cause aspiration or hemorrhagic shock. This study assessed clinical characteristics, risk factors, and provide treatment and prevention advice of this complication.

Methods

This was a retrospective monocentric analysis of 862 patients who underwent ETPTR. Statistical analyses of clinical data revealed the incidence, sources and onset time of delayed epistaxis. Univariate analysis and binary logistic regression were used to identify risk factors.

Results

The incidence of delayed epistaxis was 2.78% (24/862), with an average onset time of 20.71 ± 7.39 days. The bleeding sources were: posterior nasal septal artery branch of sphenopalatine artery (12/24), multiple inflammatory mucosae (8/24), sphenopalatine artery trunk (3/24) and sphenoid sinus bone (1/24). Univariate analysis and binary logistic regression analysis confirmed that hypertension, nasal septum deviation, chronic rhinosinusitis and growth hormone pituitary tumor subtype were independent risk factors for delayed epistaxis. Sex, age, history of diabetes, tumor size, tumor invasion and operation time were not associated with delayed epistaxis. All patients with delayed epistaxis were successfully managed through endoscopic transnasal hemostasis without recurrence.

Conclusions

Delayed epistaxis after ETPTR tends to have specific onset periods and risk factors. Prevention of these characteristics may reduce the occurrence of delayed epistaxis. Endoscopic transnasal hemostasis is recommended as the preferred treatment for delayed epistaxis.
Pediatric rheumatology education: the virtual frontier a review
Authors: McColl Jeanine , Mwizerwa Oscar , Scott Christiaan , Tse Shirley ML , Foster Helen E.
Published: June 2024

Background

Many children with rheumatic and musculoskeletal diseases are unrecognized. Identifying these children requires health care provider awareness, knowledge, and skills to recognize disease features and how (and when) to refer to specialist care. The aim of this paper is to highlight the need for better access to health care, review the essential role that education and virtual care play to address unmet need in low resource areas and especially to expand workforce capacity. Using collaborative partnerships, virtual platforms, and innovative assessment methods, musculoskeletal care and education can be delivered to reach a greater audience than ever before. Increased awareness through multiple initiatives and readily available resources are imperative to improve global rheumatology care.

Conclusion

The needs of children with rheumatic diseases and musculoskeletal conditions are vastly underserved around the world resulting in preventable morbidity and mortality. Expanded implementation of virtual education and e-health care platforms provides an opportunity to increase access to care for children globally.
The prevalence of unintended pregnancy and its influence on pregnancy experience in Tabriz, Iran, 2023: a cross-sectional study
Authors: Maghalian Mahsa , Nikanfar Roghayeh , Nabighadim Mahsan , Mirghafourvand Mojgan
Published: June 2024

Background

There is a lack of quantitative studies that specifically measure the association between the experience of pregnancy and unintended pregnancy. The present study aims to address the prevalence of unintended pregnancy and identify its predictors. Additionally, the study explores whether unintended pregnancy is associated with pregnancy uplifts and hassles.

Methods

This cross-sectional study was conducted on 488 pregnant women between 20 to 40 weeks' gestation at the comprehensive health center in Tabriz City from February 2022 to January 2023. A cluster sampling method was used for sampling, and data were collected using socio-demographic questionnaires and the Pregnancy Experience Scale (PES). Descriptive statistics were used to describe the socio-demographic characteristics and the prevalence of unintended pregnancy. Binary logistic regression was employed to identify the predictors of pregnancy desirability. To examine the relationship between unintended pregnancy and pregnancy experience, an independent t-test was used for bivariate analysis, and a general linear model (GLM) was utilized for multivariate analysis, with control for potential confounding variables.

Results

The prevalence of unintended pregnancies was 30.7% (24.3% unwanted pregnancies, and 6.4% mistimed pregnancies). The results of the binary logistic regression indicated that the lower age of both the woman and her spouse were significant predictors for unintended pregnancy (P < 0.05). Based on an independent t-test, the mean score for uplifts in women with unintended pregnancy was significantly lower than in women with intended pregnancy (mean difference (MD): -4.99; 95% confidence interval (CI): -5.96 to -4.02; p < 0.001), While the mean score of hassles in women with unintended pregnancy was significantly higher than women with intended pregnancy (MD: 2.92; 95% CI: 2.03 to 3.80; p < 0.001). The results of GLM showed that women who had unintended pregnancies had significantly lower scores for uplifts (B = -4.99; 95% CI: -5.96 to -4.03; P < 0.001) and higher scores for hassles (B = 2.92; 95% CI: 2.06 to 3.78; P < 0.001).

Conclusions

The high prevalence of unintended pregnancies in Tabriz highlights the importance of targeted interventions to address this issue, considering the policy framework and unique challenges faced by women. Future studies should focus on developing context-specific interventions that effectively meet the needs of women with unintended pregnancies.
Reduced preoperative serum choline esterase levels and fecal peritoneal contamination as potential predictors for the leakage of intestinal sutures after source control in secondary peritonitis
Authors: Amati A. L. , Ebert R. , Maier L. , Panah A. K. , Schwandner T. , Sander M. , Reichert M. , Grau V. , Petzoldt S. , Hecker A.
Published: June 2024

Background

The high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons’ choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis.

Methods

Between January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis.

Results

Length of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p < 0.0001, p = 0.0026 and p =0.0009, respectively). Reduced serum choline esterase (sCHE) levels and a high extent of peritonitis were identified as independent risk factors for insufficiency of enteric sutures placed during emergency laparotomy.

Conclusions

A preoperative sCHE < 4.5 kU/L and generalized fecal peritonitis associate with a significantly higher incidence of enteric suture insufficiency after primary reconstruction of the lower gastro-intestinal tract in a peritonitic abdomen. These parameters may guide surgeons when choosing the optimal surgical procedure in the emergency setting.
Unilateral biportal endoscopic versus microscopic transforaminal lumbar interbody fusion for lumbar degenerative disease: a retrospective study
Authors: Arunakul Rattalerk , Anumas Suthiya , Pattharanitima Pattharawin , Susrivaraput Chananyu , Pholsawatchai Waroot
Published: June 2024

Background

In the past decade, Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) with a microscopic tubular technique has become a surgical procedure that reduces surgical-related morbidity, shortens hospital stays, and expedites early rehabilitation in the treatment of lumbar degenerative diseases (LDD). Unilateral biportal endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) has emerged as a novel surgical technique. The present study aims to compare the clinical outcomes and postoperative complications of MIS-TLIF and Endo-TLIF for treating LDD.

Methods

A retrospective analysis of LLD patients undergoing either Endo-TLIF or MIS-TLIF was performed. Patient demographics, operative data (operation time, estimated blood loss, length of hospitalization), and complications were recorded. The visual analog scale (VAS) score for leg and back pain and the Oswestry Disability Index (ODI) score were used to evaluate the clinical outcomes.

Results

This study involved 80 patients, 56 in the MIS-TLIF group and 34 in the Endo-TLIF group. The Endo-TLIF group showed a more substantial improvement in the VAS for back pain at 3 weeks post-surgery compared to the MIS-TLIF group. However, at the 1-year mark after surgery, there were no significant differences between the groups in the mean VAS for back pain and VAS for leg pain. Interestingly, the ODI at one year demonstrated a significant improvement in the Endo-TLIF group compared to the MIS-TLIF group. Additionally, the MIS-TLIF group exhibited a shorter operative time than the Endo-TLIF group, with no notable differences in estimated blood loss, length of hospitalization, and complications between the two groups.

Conclusion

Endo-TLIF and MIS-TLIF are both safe and effective for LDD. In surgical decision-making, clinicians may consider nuances revealed in this study, such as lower early postoperative back pain with Endo-TLIF and shorter operative time with MIS-TLIF.
Epicardial placement of human placental membrane allografts in coronary artery bypass graft surgery is associated with reduced postoperative atrial fibrillation: a pilot study for a future multi-center randomized controlled trial
Authors: Khalpey Zain , Kumar Ujjawal , Hitscherich Pamela , Aslam Usman , Chnari Evangelia , Long Marc
Published: June 2024

Background

Post-operative atrial fibrillation (POAF) occurs in up to 40% of patients following coronary artery bypass grafting (CABG) and is associated with a higher risk of stroke and mortality. This study investigates how POAF may be mitigated by epicardial placement of aseptically processed human placental membrane allografts (HPMAs) before pericardial closure in CABG surgery. This study was conducted as a pilot feasibility study to collect preliminary for a forthcoming multi-center randomized controlled trial.

Methods

This retrospective observational study of patients undergoing CABG surgery excluded patients with pre-operative heart failure, chronic kidney disease, or a history of atrial fibrillation. The “treatment” group (n = 24) had three HPMAs placed epicardially following cardiopulmonary bypass decannulation but before partial pericardial approximation and chest closure. The only difference in clinical protocol for the control group (n = 54) was that they did not receive HPMA.

Results

HPMA-treated patients saw a significant, greater than four-fold reduction in POAF incidence compared to controls (35.2–8.3%, p = 0.0136). Univariate analysis demonstrated that HPMA treatment was associated with an 83% reduction in POAF (OR = 0.17, p = 0.0248). Multivariable analysis yielded similar results (OR = 0.07, p = 0.0156) after controlling for other covariates. Overall length of stay (LOS) between groups was similar, but ICU LOS trended lower with HPMA treatment (p = 0.0677). Post-operative inotrope and vasopressor requirements were similar among groups. There was no new-onset post-operative heart failure, stroke, or death reported up to thirty days in either group.

Conclusions

Epicardial HPMA placement can be a simple intervention at the end of CABG surgery that may provide a new approach to reduce post-operative atrial fibrillation by modulating local inflammation, possibly reducing ICU and hospital stay, and ultimately improving patient outcomes.
Pediatric trauma patients in Swedish ambulance services -a retrospective observational study of assessments, interventions, and clinical outcomes
Authors: Larsson Glenn , Larsson Sanna , Strand Viktoria , Magnusson Carl , Andersson Hagiwara Magnus
Published: June 2024

Background

Pediatric trauma patients constitute a significant portion of the trauma population treated by Swedish Emergency Medical Services (EMS), and trauma remains a notable cause of death among Swedish children. Previous research has identified potential challenges in prehospital assessments and interventions for pediatric patients. In Sweden, there is limited information available regarding pediatric trauma patients in the EMS. The aim of this study was to investigate the prevalence of pediatric trauma patients within the Swedish EMS and describe the prehospital assessments, interventions, and clinical outcomes.

Methods

This retrospective observational study was conducted in a region of Southwestern Sweden. A random sample from ambulance and hospital records from the year 2019 was selected. Inclusion criteria were children aged 0–16 years who were involved in trauma and assessed by EMS clinicians.

Results

A total of 440 children were included in the study, representing 8.4% of the overall trauma cases. The median age was 9 years (IQR 3–12), and 60.5% were male. The leading causes of injury were low (34.8%) and high energy falls (21%), followed by traffic accidents. The children were assessed as severely injured in 4.5% of cases. A quarter of the children remained at the scene after assessment. Complete vital signs were assessed in 29.3% of children, and 81.8% of children were assessed according to the ABCDE structure. The most common intervention performed by prehospital professionals was the administration of medication. The mortality rate was 0.2%.

Conclusions

Pediatric trauma cases accounted for 8.4% of the overall trauma population with a variations in injury mechanisms and types. Vital sign assessments were incomplete for a significant proportion of children. The adherence to the ABCDE structure, however, was higher. The children remained at the scene after assessment requires further investigation for patient safety.
Gender-transformative school-based sexual health intervention: study protocol for a randomized controlled trial
Authors: Leiva Loreto , Torres-Cortés Betzabé , Antivilo-Bruna Andrés , Zavala-Villalón Gloria
Published: June 2024

Background

There is general agreement that sexuality is a central aspect of human development; it is key in sexual health and reproductive education during adolescence. However, in spite of the existing interventions on this topic and the evidence generated, the inclusion of a gender focus in sexuality is relatively recent and there is little evidence available, thus structured and corroborated interventions with a gender-transforming perspective in sexuality are required.

Methods

We will use a mixed method experimental design with a parallel cluster-randomized trial (GRTs) that will evaluate the effectiveness of a comprehensive gender-transformative intervention of sexual education (ENFOCATE -Focus-on-), which will be complemented with qualitative studies to understand the implementation process. The participants will be 609 10th and 11th-grade students. The randomization will be by grade, and the data will be collected at three moments (pre-intervention, post-intervention, and a 3-month follow-up).

Discussion

Comprehensive, gender-focused, and culturally pertinent interventions in sexuality are needed for adolescents of countries with high, middle, and low incomes. These produce better results in terms of sexual health, and including a gender-transformative focus contributes to equity in health. Focus-on is unique since it uses a comprehensive gender-transformative intervention in sexual education that will allow putting into practice a program based both on international evidence and that which arises from the object population. It also uses a culturally-sensitive focus, since it is designed based on the characteristics of the object population; it will allow adapting some activities to the needs of the context in which it is developed.

Trial registration

The study was prospectively registered on June 6, 2023, at ClinicalTrials.gov ID: NCT05896540. Protocol version number 1.0. May 22, 2023.
Effectiveness of exercise rehabilitation on aplastic anemia patients receiving hematopoietic stem cell transplantation: study protocol for a randomized controlled trial
Authors: Ye Menghua , Liu Ting , Mao Xiaopei , Tan Xiaoxue , Wang Jin , Xu Min
Published: June 2024

Background

Although hematopoietic stem cell transplantation provides the chances of survival for aplastic anemia patients, it is also related to many treatment-related physical and psychological side effects that severely influence the quality of life. Exercise interventions have shown positive results in mixed hematology populations. The study aims to determine the effectiveness of exercise rehabilitation in improving the quality of life, fatigue, and physical function in these patients.

Methods

The study will enroll a total of 82 aplastic anemia patients receiving hematopoietic stem cell transplantation. They will be randomly divided into two groups in a 1:1 ratio. The intervention group will participate in structured exercise rehabilitation (plus usual care), while control group participants will receive usual care. The exercise rehabilitation program will be performed from neutrophil and platelet engraftment until 100 days after transplantation. All outcomes will be measured at the following time points: the neutrophil and platelet engraftment (± 1day, T0), discharge from the transplantation module (± 1 day, T1), hospital discharge (± 1 day, T2), and 100 days post-transplantation (± 5 days, T3).

Discussion

This study aims to assess the effectiveness of exercise rehabilitation for aplastic anemia patients receiving hematopoietic stem cell transplantation in a Chinese single center. It is particularly vital to conduct the studies in this population. Moreover, the evidence obtained from the study will provide evidence for future research and clinical practice to exercise in aplastic anemia patients.

Trial registration

ChiCTR2200060762. Registered on May 2022, www.trialregister.nl/trial/7702.
Nilgai antelope display no signs of infection upon experimental challenge with a virulent Babesia bovis strain
Authors: Johnson Tammi L. , Persinger Kelly A. , Taus Naomi S. , Davis Sara K. , Poh Karen C. , Kappmeyer Lowell S. , Laughery Jacob M. , Capelli-Peixoto Janaína , Lohmeyer Kimberly H. , Ueti Massaro W. , Olafson Pia U.
Published: June 2024

Background

Bovine babesiosis is caused by infection with the protozoal parasite Babesia bovis, which is transmitted by Rhipicephalus (Boophilus) spp. It can cause mortality rates up to 90% in immunologically naive Bos taurus cattle. In south Texas, R. (B.) microplus is known to infest nilgai antelope (Boselaphus tragocamelus); however, their susceptibility to infection with B. bovis and their role in the transmission of the parasite remain unknown. In this study, we challenged nilgai antelope with B. bovis and evaluated their susceptibility to infection.

Methods

Nilgai were needle inoculated with ≈108B. bovis-parasitized erythrocytes (merozoites) or a homogenate of B. bovis-infected larval ticks (sporozoite) delivered intravenously. Bos taurus beef calves were inoculated in parallel, as this strain of B. bovis is lethal to cattle. Temperature and hematocrit were monitored daily over the course of each study, and whole blood was collected for molecular [polymerase chain reaction (PCR)] and serological [indirect enzyme-linked immunosorbent assay (ELISA)] diagnostic evaluation. Histological sections of nilgai cerebral tissue were examined for evidence of infection. Recipient bovine calves were sub-inoculated with blood from nilgai challenged with either stage of the parasite, and they were monitored for clinical signs of infection and evaluated by a PCR diagnostic assay. Red blood cells (RBCs) from prechallenged nilgai and B. taurus beef cattle were cultured with an in vitro B. bovis merozoite culture to examine colonization of the RBCs by the parasite.

Results

Nilgai did not display clinical signs of infection upon inoculation with either the merozoite or sporozoite stage of B. bovis. All nilgai were PCR-negative for the parasite, and they did not develop antibodies to B. bovis. No evidence of infection was detected in histological sections of nilgai tissues, and in vitro culture analysis indicated that the nilgai RBCs were not colonized by B. bovis merozoites. Cattle subinoculated with blood from challenged nilgai did not display clinical signs of infection, and they were PCR-negative up to 45 days after transfer.

Conclusions

Nilgai do not appear to be susceptible to infection with a strain of B. bovis that is lethal to cattle. Tick control on these alternative hosts remains a critical priority, especially given their potential to disseminate ticks over long distances.

Graphical Abstract
The healthcare costs of increased body mass index–evidence from The Trøndelag Health Study
Authors: Hansen Edwards Christina , Håkon Bjørngaard Johan , Minet Kinge Jonas , Åberge Vie Gunnhild , Halsteinli Vidar , Ødegård Rønnaug , Kulseng Bård , Waaler Bjørnelv Gudrun
Published: June 2024

Background

Earlier studies have estimated the impact of increased body mass index (BMI) on healthcare costs. Various methods have been used to avoid potential biases and inconsistencies. Each of these methods measure different local effects and have different strengths and weaknesses.

Methods

In the current study we estimate the impact of increased BMI on healthcare costs using nine common methods from the literature: multivariable regression analyses (ordinary least squares, generalized linear models, and two-part models), and instrumental variable models (using previously measured BMI, offspring BMI, and three different weighted genetic risk scores as instruments for BMI). We stratified by sex, investigated the implications of confounder adjustment, and modelled both linear and non-linear associations.

Results

There was a positive effect of increased BMI in both males and females in each approach. The cost of elevated BMI was higher in models that, to a greater extent, account for endogenous relations.

Conclusion

The study provides solid evidence that there is an association between BMI and healthcare costs, and demonstrates the importance of triangulation.
Machine learning approach as an early warning system to prevent foodborne Salmonella outbreaks in northwestern Italy
Authors: Garcia-Vozmediano Aitor , Maurella Cristiana , Ceballos Leonardo A. , Crescio Elisabetta , Meo Rosa , Martelli Walter , Pitti Monica , Lombardi Daniela , Meloni Daniela , Pasqualini Chiara , Ru Giuseppe
Published: June 2024

Salmonellosis, one of the most common foodborne infections in Europe, is monitored by food safety surveillance programmes, resulting in the generation of extensive databases. By leveraging tree-based machine learning (ML) algorithms, we exploited data from food safety audits to predict spatiotemporal patterns of salmonellosis in northwestern Italy. Data on human cases confirmed in 2015–2018 (n = 1969) and food surveillance data collected in 2014–2018 were used to develop ML algorithms. We integrated the monthly municipal human incidence with 27 potential predictors, including the observed prevalence of Salmonella in food. We applied the tree regression, random forest and gradient boosting algorithms considering different scenarios and evaluated their predictivity in terms of the mean absolute percentage error (MAPE) and R2. Using a similar dataset from the year 2019, spatiotemporal predictions and their relative sensitivities and specificities were obtained. Random forest and gradient boosting (R2 = 0.55, MAPE = 7.5%) outperformed the tree regression algorithm (R2 = 0.42, MAPE = 8.8%). Salmonella prevalence in food; spatial features; and monitoring efforts in ready-to-eat milk, fruits and vegetables, and pig meat products contributed the most to the models’ predictivity, reducing the variance by 90.5%. Conversely, the number of positive samples obtained for specific food matrices minimally influenced the predictions (2.9%). Spatiotemporal predictions for 2019 showed sensitivity and specificity levels of 46.5% (due to the lack of some infection hotspots) and 78.5%, respectively. This study demonstrates the added value of integrating data from human and veterinary health services to develop predictive models of human salmonellosis occurrence, providing early warnings useful for mitigating foodborne disease impacts on public health.
A syrup containing l-arabinose and d-xylose appears superior to PEG-4000 as a bowel cleansing agent
Authors: Wang Dezhi , Liao Xingchen , Zhang Heng , Wang Yilin , Zhang Mingjie , Ren Fangli , Ma Xianzong , Sheng Jianqiu , Jin Peng , Yu Dongliang , Xie Hui , Wang Xin
Published: June 2024

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising l-arabinose and d-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. l-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.
Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews
Authors: Plans-Beriso E , Babb-de-Villiers C , Petrova D , Barahona-López C , Diez-Echave P , Hernández O R , Fernández-Martínez N F , Turner H , García-Ovejero E , Craciun O , Fernández-Navarro P , Fernández-Larrea N , García-Esquinas E , Kuhn I , Jiménez-Planet V , Moreno V , Rodríguez-Artalejo F , Sánchez M J , Pollan-Santamaria M , Blackburn L , Kroese M , Pérez-Gómez B
Published: June 2024

Introduction

Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes.

This review is part of the “Personalised Prevention Roadmap for the future HEalThcare” (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union.

Objective

To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings.

Methods

Three rapid scoping reviews are being conducted in parallel (February–June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map.

Inclusion criteria

Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings.

Systematic review registration

https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).
Genomic deletions in Aureobasidium pullulans by an AMA1 plasmid for gRNA and CRISPR/Cas9 expression
Authors: Masi Audrey , Wögerbauer Klara , Mach Robert L. , Mach-Aigner Astrid R.
Published: June 2024

Background

Aureobasidium pullulans is a generalist polyextremotolerant black yeast fungus. It tolerates temperatures below 0 °C or salt concentrations up to 18%, among other stresses. A. pullulans genome sequencing revealed a high potential for producing bioactive metabolites. Only few molecular tools exist to edit the genome of A. pullulans, hence it is important to make full use of its potential. Two CRISPR/Cas9 methods have been proposed for the protoplast-based transformation of A. pullulans. These methods require the integration of a marker gene into the locus of the gene to be deleted, when the deletion of this gene does not yield a selectable phenotype. We present the adaptation of a plasmid-based CRISPR/Cas9 system developed in Aspergillus niger for A. pullulans to create deletion strains.

Results

The A. niger CRISPR/Cas9 plasmid led to efficient genomic deletions in A. pullulans. In this study, strains with deletions ranging from 30 to 862 bp were obtained by using an AMA1 plasmid-based genome editing strategy.

Conclusion

The CRISPR/Cas9 transformation system presented in this study provides new opportunities for strain engineering of A. pullulans. This system allows expression of Cas9 and antibiotic resistance while being easy to adapt. This strategy could open the path to intensive genomic engineering in A. pullulans.
Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)—an analysis of an administrative health claims database
Authors: Vallabhaneni Srilakshmi , Adusumalli Srinath , Wu Jingyi , Groeneveld Peter W. , Gerson James , O’Quinn Rupal P.
Published: June 2024

Background

First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials.

Objective

Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients.

Methods

We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding.

Results

A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib.

Conclusions

There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.
Development of two multiplex PCR assays for rapid detection of eleven Gram-negative bacteria in children with septicemia
Authors: Miringu Gabriel , Musyoki Abednego , Muriithi Betty , Wandera Ernest , Waithiru Dan , Odoyo Erick , Shoji Hisashi , Menza Nelson , Ichinose Yoshio
Published: June 2024

Aim

This study aimed to develop a multiplex PCR assay for simultaneous detection of major Gram-negative etiologies of septicemia and evaluate its performance.

Methods

Multiplex PCR (mPCR) assays were developed targeting 11 bacterial strains. Species-specific primers were confirmed using known clinical isolates and standard strains. Gradient PCR was performed on each primer against its target bacterial gene to determine its optimal amplification condition. The minimum detectable DNA concentration of the two assays was evaluated by adjusting bacterial DNA concentration to 100 ng/μL and, tenfold serially diluting it up to 10 pg/μL with DNAse-free water. The diagnostic accuracy of mPCR assays was established by subjecting the assays to 60 clinical blood samples.

Results

Two mPCR assays were developed. Optimal primer annealing temperature of 55 °C was established and utilized in the final amplification conditions. The assays detected all targeted bacteria, with a 100 pg minimum detectable DNA concentration. Pathogens were not detected directly from whole blood, but after 4 h and 8 h of incubation, 41% (5/12) and 100% (12/12) of the bacteria were detected in culture fluids, respectively. The assays also identified Salmonella spp. and Klebsiella pneumoniae co-infections and extra pathogens (1 E. coli and 2 K. pneumoniae) compared with culture. The sensitivity and specificity of the mPCR were 100.0% (71.7–100.0) and 98.0% (90.7–99.0), respectively. The area under the ROC curve was 1.00 (1.00–1.00).

Conclusions

The mPCR assays demonstrated substantial potential as a rapid tool for septicemia diagnosis alongside the traditional blood culture method. Notably, it was able to identify additional isolates, detect co-infections, and efficiently detect low bacterial DNA loads with high sensitivity, implying its value in enhancing efficiency of diagnosis of septicemia.
Paisaje semiótico virtual de las enfermedades autoinmunes: el caso del lupus.
Authors: Galloso Camacho María Victoria
Published: June 2024

En este artículo se analiza el paisaje semiótico virtual en la imagen gráfica de las enfermedades autoinmunes, en concreto el lupus. Metodológicamente, partimos de la enfermedad como un proceso sociosanitario y analizamos los modos actuales de visibilización discursiva de este tipo de enfermedades a través de redes sociales para conseguir resultados inmediatos sobre su percepción y aceptación en pacientes, familiares y conjunto de la sociedad. La conclusión es que, aunque los síntomas en términos de medicina no son solo reductibles a los signos físicos, la atenta mirada médica del territorio corporal es vital para el diagnóstico de muchas enfermedades, caso de la mariposa facial del lupus.
El turismo en Huelva a través del paisaje lingüístico urbano.
Authors: Heredia Mantis María
Published: June 2024

La provincia de Huelva presenta unas características sociodemográficas singulares. Al tener amplios terrenos de costa, recibe una considerable cantidad de turistas todos los años. También la dedicación económica de la provincia a la agricultura de exportación supone un flujo migratorio constante de países de Europa del Este y de África. Las instituciones son conocedoras de ello y, por tanto, diseñan su comunicación con estos sectores de la población a través de los signos que emiten e incorporan al paisaje lingüístico urbano onubense. En este estudio cuantificamos, clasificamos y analizamos el paisaje lingüístico de carácter institucional para conocer el tipo de comunicación que establecen las instituciones y evaluar la situación de multilingüismo que este tipo de signos genera en las ciudades de Huelva. Nuestros resultados apuntan a un mayor interés por parte de las instituciones en la población turista y la repercusión económica de sus actividades de ocio que en la población migrada y sus necesidades de comprensión de los mensajes administrativos y de interés general.
Una aproximación al estudio del paisaje lingüístico político en el País Vasco: análisis comparativo entre Vitoria-Gasteiz y Zizurkil.
Authors: Reguero Ugarte Urtzi
Published: June 2024

El presente artículo es una breve aproximación al estudio del paisaje lingüístico político del País Vasco. Para ello se han escogido dos localidades con una realidad sociolingüística diferente: por un lado, un municipio guipuzcoano donde el 60% de los habitantes habla euskera y, por otro lado, Vitoria, capital de la comunidad autónoma, donde el 80% tiene el castellano como lengua materna. En el estudio se analizan las diferentes manifestaciones lingüísticas en los carteles, las pancartas, las pegatinas y otros soportes de contenido político, social o sindical aparecidos en dichas localidades. Desde un enfoque exclusivamente lingüístico, el interés de trabajo se centra en el uso y la elección que se hace de una lengua u otra y en observar si existen diferencias según la realidad sociolingüística. Se concluye que el euskera es la lengua priorizada en los signos de carácter ideológico-reivindicativo