bluuebunny/crossref_metadata_2025 huggingface dataset:
Bleeding risk stratification in patients admitted for acute coronary syndrome
Authors: Paula S , Figueiredo M , Coelho M , Santos M , Almeida S , Almeida L
Published: May 2024

Funding Acknowledgements

None.

Introduction

The risk of hemorrhagic events should always be accounted for in patients admitted with acute coronary syndromes (ACS). With the increasing frailty of these patients, it is important to identify them and minimize the risk of such events.

Purpose

Identify high-risk patients admitted for ACS for hemorrhagic events during their hospital stay.

Methods

Multicenter retrospective study, data collected from 1/10/2010 and 31/12/2020 with ACS diagnosis. Patients were divided into 3 groups according to hemoglobin (Hb) and platelet (Plat) levels. Group 1 – Hb <8g/dl, Plat <150x109/L; Group 2 – Hb 8-12g/dl, Plat 150-450x109/L; Group 3 – Hb ≥12g/dl, Plat ≥450x109/L. We further divided these patients according to a composite endpoint. Group A without the composite endpoint; Group B with composite endpoint. This composite endpoint was defined as major hemorrhage, intracranial hemorrhage, need of blood transfusions and a Hb decrease of ≥ 2g/dl.

Results

19409 patients were enrolled, of those 4707 (24.3%) had the composite endpoint. Group B was older (68±13 vs 66±12, p<0.001), had higher rates of arterial hypertension (72.5% vs 68.2%, p<0.001), diabetes mellitus (35.6% vs 30.7%, p< 0.001), stroke (9.0% vs 6.6%, p < 0.001) and previous haemorrhage (p= 0.004). No statistically significant differences regarding previous MI (p= 0.240). Hb levels <8g/dL (8.1% vs 0.6%, p<0.001) were associated with a higher risk of hemorrhagic events but not lower levels of Plat, instead higher levels (> 450x109/L) were event associated (1.8% vs 0.9%, p<0.001). The choice of femoral access was related to an increased risk of hemorrhagic events (p<0.001). Logistic regression confirmed that the Hb levels < 12g/dL when compared with normal levels were related to the composite endpoint proportionally to the degree of anemia, the lower the level of Hb the more likely these events occur, Hb <8g/dL p<0.001, OR 4.02, CI (95%) 2.50-6.47 and Hb 8-12g/dL, p<0.001, OR 0.761, CI (95%) 0.693-0.837. Survival analysis also showed that cardiovascular (CV) mortality and re-admission at 1 year were related to the degree of anemia.

Conclusion

Lower levels of Hb correlated well and proportionally to the occurrence of the composite endpoint as well as cardiovascular (CV) mortality and re-admission at 1 year. Contrarily to expected lower levels of Plat did not correlate with a higher risk of hemorrhagic events but instead thrombocytosis did, as a paradoxical risk of bleeding has been noted in patients with thrombocytosis, especially extreme thrombocytosis.
Impact of clinical frailty scale on short and long term outcome in patients with acute coronary syndrome
Authors: Campanile A , Prota C , Iuliano G , Pompa A , Farace C , Sorrentino R , Vigorito F , Ravera A
Published: May 2024

Funding Acknowledgements

None.

Background

As recently outlined in the European Society of Cardiology (ESC) guidelines on acute coronary syndrome (ACS), scarce data still exits about the prognostic role of frailty to guide clinical decision-making for patients with ACS.

Purpose

To assess the potential predictive value of frailty both for short, and long term all-cause mortality, in a contemporary ACS population.

Methods

All consecutive admissions due to ACS, from 01/01/2019 to 31/12/2021, were retrospectively reviewed from an internal database of a tertiary cardiac center in Salerno (Italy). Logistic and Cox proportional regression analysis were performed in order to assess the contribution of frailty on 30-days and long term mortality. Frailty was assessed using the Clinical Frailty Scale (CFS) and patients were classified as non frail (CFS 1-4), and frail (CFS 5-9). Both logistic and Cox regression analysis were adjusted for age, gender, GRACE risk score, comorbidity burden, defined by the Charlson comorbidity score (CCS), and all other relevant covariates associated with outcomes of interest in the univariate analysis.

In order to estimate the survival rates during the follow-up, a Kaplan Meyer analysis was carried out and differences between the CFS groups were assessed using the log-rank test. Robustness of the results were assessed through an internal validation procedure with bootstrapping. All statistical analyses were performed using SPSS software version 25.0 (SPPS Inc., Chicago, Illinois) and R version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria). A p-value of less than 0.05 was considered significant.

Results

1366 patients were identified. The median age was 68 (58-77). Of these patients, 1087 (79,6%) were classified as non-frail (CFS 1-4), and 279 (20,4%) as frail (CFS 5-9). 120 (8,8%) and 140 (11,2%) deaths occurred, respectively, during the first 30 days from admission, and during long term follow-up (median follow-up time: 15 months; IQR: 10-24). After multivariate regression analysis the CFS was associated with both short and long-term mortality (OR: 1,6, 95% CI: 1,34-1,91; p<0,001 and HR: 1,37, 95% CI: 1,18-1,58; p<0,001, Fig. 1). Patients with CFS ≥ 5 showed significant higher mortality rate during long term follow-up (p<0.001; Fig.2).

Conclusions

The CFS is a strong predictor of both short and long-term mortality in patients affected by ACS also after comprehensive adjustment for baseline differences in other risk factors.Fig. 2
Impact of early administration of beta-blocker and RAS inhibitor during VA-ECMO treatment for cardiogenic shock; the post-hoc study of the EARLY-UNLOAD trial
Authors: Park S , Lim Y W , Kim M C , Jeong I S
Published: May 2024

Funding Acknowledgements

None.

Background/introduction

No data about timing and impact of beta-blocker (BB) or renin-angiotensin-aldosterone system inhibitor (RASi) administration for cardiogenic shock (CS) treated with venoatrial extracorporeal membrane oxygenation (VA-ECMO).

Purpose

To analyze an impact of early administration of BB or RASi during VA-ECMO treatment.

Methods

This study is a post-hoc analysis of the EARLY-UNLOAD trial (NCT04775472), the trial evaluated an impact of an early prophylactic unloading strategy using left atrial cannulation (LAC) performed within 12 hours from the initiation of VA-ECMO treatment for CS.

Among total population (N=116), patients whose lactate was normalized during VA-ECMO and survived more than 2 days were included in this analysis (N=103). Patients were classified whether each medication (BB, RASi or one of BB or RASi) was administered during VA-ECMO or not. The primary endpoint was all-cause mortality. Survival analysis for a primary outcome and landmark analysis for all-cause mortality during different periods (<10 days, 10 to 30 days) were performed.

Results

BB, RASi, and BB or RASi were administered in 71.8%, 72.8%, and 83.5% of patients, respectively, during VA-ECMO treatment. In early treatment groups, Both BB and RASi were initiated on day 1 (as median). Duration of VA-ECMO treatment was longer in a group who treated with BB during VA-ECMO (8.5 days, vs 5.0 days as median, P = 0.003), and for RASi, it was comparable (8.0 days vs 7.0 days, P = 0.609).

Incidence of 30-day all-cause mortality at were statistically comparable between groups (figure 1). The results of survival analysis are described in the figure 2. In Kaplan-Meier analysis, BB, RASi, and BB or RASi during VA-ECMO treatment was not associated with lower probability of 30-day all-cause mortality. Landmark analysis, however, showed lower probability of 10-day mortality in the group treated with BB (P by log-rank test = 0.045), RASi (P = 0.008) and BB or RASi (P=0.005) during VA-ECMO. Multivariate Cox proportional modellings also provided lower risk of 10-day all-cause mortality in groups with BB treatment (Hazard ratio [HR] = 0.26, 95% confidence interval [CI]=0.10-0.69, P = 0.007), RASi treatment (HR = 0.22, 95% CI = 0.08-0.56, P = 0.001) or BB or RASi (HR = 0.15, 95% CI = 0.05-0.41, P < 0.001) during VA-ECMO. RASi (HR = 0.47, 95% CI = 0.22-0.97, P = 0.041) or BB or RASi (HR = 0.37, 95% CI = 0.15-0.93, P = 0.038) treatment during VA-ECMO was also associated with lower risk of 30-day all-cause mortality.

Conclusions

In this post-hoc analysis of the EARLY-UNLOAD trial, administration of BB or RASi during VA-ECMO treatment for CS was associated with lower risk of short-term mortality.
The importance of remnant cholesterol particles.Lipid profile in patients with acute coronary syndrome undergoing cardiac rehabilitation
Authors: Lucas Garcia M , Padilla Rodriguez G , Pelaz Sanchez M , Paez Munoz R , Hidalgo Urbano R J , Martinez Quesada M M
Published: May 2024

Funding Acknowledgements

None. Main funding source(s): Ninguno.

Introduction

Recently it has been shown that not all lipid risk for atherosclerosis is due to LDL cholesterol. Both, remnant and small particles have been proposed as risk factors for the first cardiovascular event and recurrences.

Methods

This is an observational, descriptive, prospective, single-centre, descriptive study. We set out to analyse the lipid profile on admission of patients undergoing a cardiac rehabilitation (CR) program in a tertiary hospital. In addition, we studied the association with other analytical parameters, clinical characteristics and CR results in these patients. For this purpose, data were collected from patients who completed the program between January 2022 and March 2023. We compared analytical variables at hospital admission and at the end of the program, as well as clinical and anthropometric data and stress test results. In our study we defined elevated remnants as >30 mg/dl.

Results

We included 170 patients who had a complete analytical profile at hospital admission. In our cohort, 80.5% were male, with a mean age of 57.9+/-9 yrs. A total of 92.5% were referred after acute coronary syndrome. There were 25.6% diabetic, 56.6% smokers and 38.1% obese patients.

Patients with elevated remnants were more likely to be men (90.3 vs 79.8%, p=0.039). No differences were found in age, presence of DM, smoking, obesity or peripheral arterial disease. Functional capacity, quality of life and improvement in these parameters did not differ either. As for baseline lipid profile, it was associated with higher total Ch (190 vs 152, p=0.0), LDL Ch (109 vs 90, p=0.0), TG (227 vs 104, p=0.0) and TG/HDL ratio (6.8 vs 2.5, p=0.0) and lower HDL Ch (37 vs 45, p=0.0).

66.1% of patients with high remnants have an LDL-Ch greater than 100 mg/dl, compared with 29.6% of those with low remnants.(P=0,000).

Regarding the profile at discharge, we found that 34.4% still had elevated remnants at discharge from the CR program (vs 22.2% of those without elevated remnants, P=0.000) and that 75.9% had TG/HDL greater than 2.

After CR, these patients still had higher TG values (156 vs 93, p=0.000), lower HDL-C (43 vs 50, p=0.003) and higher TG/HDL ratio (4 vs 2, p=0.000), despite a greater decrease in remnants and TG/HDL in this group.

Conclusions

More than one third of patients undergoing a Cardiac Rehabilitation Program in our hospital have elevated cholesterol remnants. These particles predominate in male patients and initially, they have a higher prevalence of small and dense LDL and lower HDL cholesterol. In addition, the effect of the cardiac rehabilitation program on the improvement of lipid risk parameters is lower. More powerful intensive treatments are needed to improve cardiovascular risk in this population.
Unveiling the complexity: coexistence of rheumatic heart disease and pulmonary arteriovenous malformation—a unique case report
Authors: Charaniya Riyaz , Shah Jayal , M Apoorva
Published: May 2024

Background

The coexistence of rheumatic heart disease (RHD) and pulmonary arteriovenous malformation (PAVM) is a rare clinical scenario that poses diagnostic and therapeutic challenges. This case report explores the clinical presentation, diagnostic journey, and multidisciplinary management of a patient presenting with both conditions.

Case summary

A 47-year-old female with a history of RHD presented with symptoms of dyspnoea on exertion and cyanosis, suggestive of both cardiac involvement and pulmonary involvement. Subsequent investigations involving imaging, echocardiography, and invasive pulmonary angiography revealed the coexistence of RHD and multiple PAVM in the patient’s left lower lobe of the lung. The patient underwent a tailored treatment plan, initially involving percutaneous mitral balloon valvuloplasty for RHD, followed by a staged procedure of transcatheter PAVM closure with Amplatzer™ Vascular Plug II performed 1 month later. Her saturation normalized following the intervention. The patient’s progress was monitored closely, with adjustments made to the treatment plan based on evolving clinical scenarios. The patient remained well in short-term follow-up.

Discussion

This case highlights the complexity of managing patients having two diverse conditions RHD and PAVM coexisting together, thus emphasizing the importance of a multidisciplinary approach. The unique intersection of cardiac and pulmonary pathologies necessitates careful consideration of diagnostic nuances and tailored treatment strategies. Lessons learned from this case offer valuable insights for clinicians encountering similar scenarios and underscore the significance of individualized, patient-centred care in optimizing outcomes for those with dual pathologies.
Predicting human epidermal growth factor receptor 2 status of patients with gastric cancer by computed tomography and clinical features
Authors: Li Yin , Dai Wei-Gang , Lin Qingyu , Wang Zeyao , Xu Hai , Chen Yuying , Wang Jifei
Published: May 2024

Background

There have been no studies on predicting human epidermal growth factor receptor 2 (HER2) status in patients with resectable gastric cancer (GC) in the neoadjuvant and perioperative settings. We aimed to investigate the use of preoperative contrast-enhanced computed tomography (CECT) imaging features combined with clinical characteristics for predicting HER2 expression in GC.

Methods

We retrospectively enrolled 301 patients with GC who underwent curative resection and preoperative CECT. HER2 status was confirmed by postoperative immunohistochemical analysis with or without fluorescence in situ hybridization. A prediction model was developed using CECT imaging features and clinical characteristics that were independently associated with HER2 status using multivariate logistic regression analysis. Receiver operating characteristic curves were constructed and the performance of the prediction model was evaluated. The bootstrap method was used for internal validation.

Results

Three CECT imaging features and one serum tumor marker were independently associated with HER2 status in GC: enhancement ratio in the arterial phase (odds ratio [OR] = 4.535; 95% confidence interval [CI], 2.220–9.264), intratumoral necrosis (OR = 2.64; 95% CI, 1.180–5.258), tumor margin (OR = 3.773; 95% CI, 1.968–7.235), and cancer antigen 125 (CA125) level (OR = 5.551; 95% CI, 1.361–22.651). A prediction model derived from these variables showed an area under the receiver operating characteristic curve of 0.802 (95% CI, 0.740–0.864) for predicting HER2 status in GC. The established model was stable, and the parameters were accurately estimated.

Conclusions

Enhancement ratio in the arterial phase, intratumoral necrosis, tumor margin, and CA125 levels were independently associated with HER2 status in GC. The prediction model derived from these factors may be used preoperatively to estimate HER2 status in GC and guide clinical treatment.
Highly homologous miR-135a and miR-135b converting non-small cell lung cancer from suppression to progression via enhancer switching
Authors: Zhou Kaicheng , Li Wenxuan , Chen Lu , Chen Siyue , Liu Mengxing , Yang Zhicong , Mao Zhanrui , Yu Wenqiang
Published: May 2024

microRNAs (miRNAs) are short non-coding RNAs that have been increasingly recognized for their significant roles in the progression of cancer. Distinct miRNAs exhibit diverse functions attributed to variations in their sequences. As a result of possessing highly homologous seed sequences, these miRNAs target overlapping or similar gene sets, thus performing analogous roles. However, different from this sight, our study discovered that miR-135a-5p and miR-135b-5p, despite differing by only one nucleotide, exhibit distinct functional roles. Using non-small cell lung cancer (NSCLC) as a paradigm, our findings unveiled the downregulation of miR-135a-5p and upregulation of miR-135b-5p within NSCLC through TCGA database. Consequently, we further investigated their functional differences in A549 cells. Overexpression of miR-135b-5p enhanced the proliferation and migration capabilities of A549 cells, whereas miR-135a-5p transfection exhibited the opposite effect. We demonstrated that the activation of specific enhancers serves as a crucial mechanism underlying the disparate functions exerted by miR-135a-5p and miR-135b-5p in the context of NSCLC, consequently instigating a shift from inhibition to activation in NSCLC progression. Finally, we validated through animal experiments that miR-135b-5p promoted tumor progression, while miR-135a-5p exerted inhibitory effects on NSCLC development. This study offers a novel perspective for researchers to elucidate functional disparities exhibited by highly homologous miRNAs (miR-135a-5p and miR-135b-5p) in the context of NSCLC, along with the transition from inhibitory to progressive states in NSCLC. This study provides a solid foundation for future investigations into the functional roles of highly homologous miRNAs in pathological situation.
Leader-following consensus of heterogeneous nonlinear multi-agent systems within arbitrary pre-specified time
Authors: Wu Shanggen , Feng Yuanzhen , Wang Ziyang , Wang Zhengxin
Published: May 2024

The leader-following consensus problem of second-order heterogeneous nonlinear multi-agent systems (MASs) is studied in this paper. Based on the free-will arbitrary time (FWAT) theory, a piecewise distributed controller is developed to solve this problem within an arbitrary pre-specified convergence time. It should be noted that the pre-specified convergence time is independent of any system parameters and initial conditions. Furthermore, compared with the existing FWAT methods, consensus can still be maintained after the convergence time under the protocol designed in this work. Finally, numerical examples are given to illustrate the validity of the proposed method.
Annihilating Branching Brownian Motion
Authors: Ahlberg Daniel , Angel Omer , Kolesnik Brett
Published: May 2024

We study an interacting system of competing particles on the real line. Two populations of positive and negative particles evolve according to branching Brownian motion. When opposing particles meet, their charges neutralize and the particles annihilate, as in an inert chemical reaction. We show that, with positive probability, the two populations coexist and that, on this event, the interface is asymptotically linear with a random slope. A variety of generalizations and open problems are discussed.
Modelling the architecture of hazelnut (Corylus avellana) Tonda di Giffoni over two successive years
Authors: Grisafi Francesca , Tombesi Sergio , Farinelli Daniela , Costes Evelyne , Durand Jean-Baptiste , Boudon Frédéric
Published: May 2024

Hazelnut (Corylus avellana) cultivation is increasing worldwide. A 3D model of its structure could improve managerial techniques such as pruning. This study aims to analyse, over two successive years, hazelnut architectural development to implement a functional structural plant model. One hundred and four one-year-old shoots of own-rooted hazelnut trees were selected and analysed in winter 2020 and 2021. Exploratory analyses, generalized linear models and multinomial regression models were used to describe the architectural processes. The existence of sylleptic shoots on hazelnut one-year-old shoots, characterized by the presence of the male inflorescence on apical position, was detected. Along proleptic shoots, the branching pattern was described by (i) blind nodes located in the proximal part (ii) sylleptic shoots and mixed buds in the median part (iii) vegetative buds in the distal part. Apical bud died during the growing season, suggesting that Tonda di Giffoni has a sympodial branching. The models revealed dependencies among buds located at the same node, in the case of proleptic shoots. Especially, the probability of a bud bursting depended on both its type (i.e. mixed or vegetative) and the presence of other buds, either mixed or vegetative. Based on these local models and on a flow diagram, which defines the steps that led to the construction of hazelnut tree architecture, the first functional–structural plant model of hazelnut tree architecture was built. Further experiments will be needed and should be repeated over the following years to extend this study towards the juvenile phase and tree architecture over time.
Practice patterns and survival outcomes for muscle-invasive bladder cancer: real-life experience in a general population setting
Authors: Plouvier Sandrine D , Marcq Gautier , Vankemmel Olivier , Colin Pierre , Bonnal Jean-Louis , Leroy Xavier , Saint Fabien , Pasquier David
Published: May 2024

Bladder cancer (BC) is a common malignancy in Europe and North America. Among BCs, muscle-invasive BCs (MIBCs) are distinguished, as they require aggressive treatment due to their spreading potential and poor prognosis. Despite its clinical relevance, little information on MIBC in a general population setting is available. This study aims to report practice patterns and survival outcomes for MIBC patients in a general population setting. MIBCs among BC incidence in 2011 and 2012 recorded in a French population-based cancer registry (810 000 inhabitants) were included in the study. Data were extracted from the medical files. Individual, tumour-related characteristics and initial management including diagnostic tools, multidisciplinary team meeting (MDT) assessment, and treatment delivered were described. Cystectomy, chemoradiation, radiotherapy, and chemotherapy were considered as specific treatments. Matching between MDT decision and the treatment provided was detailed. Management practices were discussed according to the guideline’s recommendations. Overall survival (using the Kaplan–Meier method) and net survival (using the Pohar-Perme estimator) were calculated. Among 538 incident BC cases, 147 (27.3%) were MIBCs. Diagnostic practices displayed a relevant locoregional assessment of BC. Almost all cases (n = 136, 92.5%) were assessed during an uro-oncological MDT with a median time from diagnosis of 18 days (first quartile:12-third quartile:32). Discrepancies appeared between MDT decisions and treatments delivered: 71 out of 86 subjects received the recommended cystectomy or chemoradiation (with or without neoadjuvant chemotherapy); 6 out of 11 had the recommended radio- or chemotherapy; and 9 patients did not undergo any specific treatment despite the MDT decision. Cystectomy was the most common treatment performed; the time to surgery appeared consistent with the guideline’s recommendations. Forty people only received supportive care. Still, the 5-year overall and net survival was poor, with 19% (13–26) and 22% (14–31), respectively. The 5-year net survival was 35% (23–48) for people who underwent curative-intent treatments. MIBC management remains challenging even for cases assessed during an MDT. Many people did not undergo any specific treatment. Prognosis was poor even when curative-intent therapies were delivered. Efforts to reduce exposure to risk factors such as tobacco smoking and occupational exposures must be maintained.
Clustering techniques performance comparison for predicting the battery state of charge: A hybrid model approach
Authors: Ordás María Teresa , del Blanco David Yeregui Marcos , Aveleira-Mata José , Zayas-Gato Francisco , Jove Esteban , Casteleiro-Roca José-Luis , Quintián Héctor , Luis Calvo-Rolle José , Alaiz-Moreton Héctor
Published: May 2024

Batteries are a fundamental storage component due to its various applications in mobility, renewable energies and consumer electronics among others. Regardless of the battery typology, one key variable from a user’s perspective is the remaining energy in the battery. It is usually presented as the percentage of remaining energy compared to the total energy that can be stored and is labeled State Of Charge (SOC). This work addresses the development of a hybrid model based on a Lithium Iron Phosphate (LiFePO4) power cell, due to its broad implementation. The proposed model calculates the SOC, by means of voltage and electric current as inputs and the latter as the output. Therefore, four models based on k-Means, Agglomerative Clustering, Gaussian Mixture and Spectral Clustering techniques have been tested in order to obtain an optimal solution.
Prevalence of anal cytology screening among persons with HIV and lack of access to high-resolution anoscopy at HIV care facilities
Authors: Rim Sun Hee , Beer Linda , Saraiya Mona , Tie Yunfeng , Yuan Xin , Weiser John
Published: May 2024

Background

People with HIV at highest risk of anal cancer include gay, bisexual, and other men who have sex with men and transgender women aged 35 years or older as well as other people with HIV aged 45 years or older. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed the prevalence of anal cytology and access to high-resolution anoscopy among people with HIV overall and in those individuals at highest risk.

Methods

Data were obtained from the Centers for Disease Control and Prevention’s Medical Monitoring Project, a population-based survey of people with HIV aged 18 years and older, and a supplemental Medical Monitoring Project facility survey. We report weighted percentages of people with HIV receiving anal cytology during the past 12 months, access to high-resolution anoscopy, and characteristics of HIV care facilities by availability of high-resolution anoscopy.

Results

Overall, 4.8% (95% confidence interval [CI] = 3.4% to 6.1%) of people with HIV had undergone anal cytology in the prior 12 months. Only 7.7% (95% CI = 5.1% to 10.6%) of gay, bisexual, and other men who have sex with men as well as transgender women 35 years of age or older and 1.9% (95% CI = 0.9% to 2.9%) of all other people with HIV aged 45 years and older had anal cytology. Prevalence was statistically significantly low among people with HIV with the following characteristics: non-Hispanic or Latino, Black or African American, high school education or less, heterosexual orientation, and living in southern Medical Monitoring Project states. Among people with HIV, 32.8% (95% CI = 28.0% to 37.7%) had no access to high-resolution anoscopy on-site or through referral at their care facility; 22.2% (95% CI = 19.5% to 24.9%) had on-site access; 45.0% (95% CI = 41.5% to 48.5%) had high-resolution anoscopy available through referral. Most facilities that received Ryan White HIV/AIDS Program funding, cared for more than 1000 people with HIV, or provided on-site colposcopy also provided high-resolution anoscopy on-site or through referral.

Conclusions

Rates of anal cytology and access to high-resolution anoscopy were low among people with HIV, including those individuals at highest risk of anal cancer. Our data may inform large-scale implementation of anal cancer prevention efforts.
Temporal logics for compartmental models
Authors: Machado Vitor , Benevides Mario
Published: May 2024

This paper introduces two logic frameworks for the study of SIR (Susceptible-Infected-Recovered) and SIRS compartmental epidemic models, one based on Linear Temporal Logic and the other on Computation Tree Logic. We provide a short literature overview on compartmental models and other related works using logics, and then define our logics with their respective axiomatizations, and demonstrate their soundness and completeness proofs.
Functional Divergence in Orthologous Transcription Factors: Insights from AtCBF2/3/1 and OsDREB1C
Authors: Deng Deyin , Guo Yixin , Guo Liangyu , Li Chengyang , Nie Yuqi , Wang Shuo , Wu Wenwu
Published: May 2024

Despite traditional beliefs of orthologous genes maintaining similar functions across species, growing evidence points to their potential for functional divergence. C-repeat binding factors/dehydration-responsive element binding protein 1s (CBFs/DREB1s) are critical in cold acclimation, with their overexpression enhancing stress tolerance but often constraining plant growth. In contrast, a recent study unveiled a distinctive role of rice OsDREB1C in elevating nitrogen use efficiency (NUE), photosynthesis, and grain yield, implying functional divergence within the CBF/DREB1 orthologs across species. Here, we delve into divergent molecular mechanisms of OsDREB1C and AtCBF2/3/1 by exploring their evolutionary trajectories across rice and Arabidopsis genomes, regulatomes, and transcriptomes. Evolutionary scrutiny shows discrete clades for OsDREB1C and AtCBF2/3/1, with the Poaceae-specific DREB1C clade mediated by a transposon event. Genome-wide binding profiles highlight OsDREB1C's preference for GCCGAC compared to AtCBF2/3/1's preference for A/GCCGAC, a distinction determined by R12 in the OsDREB1C AP2/ERF domain. Cross-species multiomic analyses reveal shared gene orthogroups (OGs) and underscore numerous specific OGs uniquely bound and regulated by OsDREB1C, implicated in NUE, photosynthesis, and early flowering, or by AtCBF2/3/1, engaged in hormone and stress responses. This divergence arises from gene gains/losses (∼16.7% to 25.6%) and expression reprogramming (∼62.3% to 66.2%) of OsDREB1C- and AtCBF2/3/1-regulated OGs during the extensive evolution following the rice–Arabidopsis split. Our findings illustrate the regulatory evolution of OsDREB1C and AtCBF2/3/1 at a genomic scale, providing insights on the functional divergence of orthologous transcription factors following gene duplications across species.
LncRNA SNHG3 discriminates rheumatoid arthritis from healthy individuals and regulates inflammatory response and oxidative stress via modulating miR-128-3p
Authors: Li Kejun , Liu Wei , Zhao Xueru , Lin Weiyi , Zhou Wenhui , Zhang Qi
Published: May 2024

Objectives

This study evaluated the expression and significance of SNHG3 in rheumatoid arthritis (RA), aiming to explore a biomarker and regulator for RA.

Methods

The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using polymerase chain reaction (PCR). The RA animal models were induced by the Porcine Type II collagen in Wistar rats and validated by the foot volume and arthritis index score. The human fibroblast-like synoviocytes were treated with lipopolysaccharide (LPS) to mimic the injury during RA onset, and the cell growth was assessed by cell counting kit-8 (CCK8) assay.

Results

SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine Type II collagen induced increasing foot volume and arthritis index scores of rats, and SNHG3 was downregulated in RA rats. In LPS-induced human fibroblast-like synoviocytes, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation.

Conclusions

Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress by negatively modulating miR-128-3p.
Designer TALEs enable discovery of cell death-inducer genes
Authors: Roeschlin Roxana A , Azad Sepideh M , Grove René P , Chuan Ana , García Lucila , Niñoles Regina , Uviedo Facundo , Villalobos Liara , Massimino Maria E , Marano María R , Boch Jens , Gadea José
Published: May 2024

Transcription activator-like effectors (TALEs) in plant-pathogenic Xanthomonas bacteria activate expression of plant genes and support infection or cause a resistance response. PthA4AT is a TALE with a particularly short DNA-binding domain harboring only 7.5 repeats which triggers cell death in Nicotiana benthamiana; however, the genetic basis for this remains unknown. To identify possible target genes of PthA4AT that mediate cell death in N. benthamiana, we exploited the modularity of TALEs to stepwise enhance their specificity and reduce potential target sites. Substitutions of individual repeats suggested that PthA4AT-dependent cell death is sequence specific. Stepwise addition of repeats to the C-terminal or N-terminal end of the repeat region narrowed the sequence requirements in promoters of target genes. Transcriptome profiling and in silico target prediction allowed the isolation of two cell death inducer genes, which encode a patatin-like protein and a bifunctional monodehydroascorbate reductase/carbonic anhydrase protein. These two proteins are not linked to known TALE-dependent resistance genes. Our results show that the aberrant expression of different endogenous plant genes can cause a cell death reaction, which supports the hypothesis that TALE-dependent executor resistance genes can originate from various plant processes. Our strategy further demonstrates the use of TALEs to scan genomes for genes triggering cell death and other relevant phenotypes.
Crowding in Private Quality: The Equilibrium Effects of Public Spending in Education
Authors: Andrabi Tahir , Bau Natalie , Das Jishnu , Karachiwalla Naureen , Ijaz Khwaja Asim
Published: May 2024

We estimate the equilibrium effects of a public school grant program administered through school councils in Pakistani villages with multiple public and private schools and clearly defined catchment boundaries. The program was randomized at the village level, allowing us to estimate its causal impact on the market. Four years after the start of the program, test scores were 0.2 standard deviations higher in public schools. We find evidence of an education multiplier: test scores in private schools were also 0.2 standard deviations higher in treated markets. Consistent with standard models of product differentiation, the education multiplier is greater for those private schools that faced a greater threat to their market power. Accounting for private sector responses increases the program’s cost-effectiveness by 85% and affects how a policy maker would target spending. Given that markets with several public and private schools are now pervasive in low- and middle-income countries, prudent policy requires us to account for private sector responses to public policy, both in policies’ design and evaluation.
The Genetic Architecture of Arabidopsis thaliana in Response to Native Non-Pathogenic Bacterial Species Revealed by Genome-Wide Association Mapping in Field Conditions
Authors: Ramírez-Sánchez Daniela , Duflos Rémi , Gibelin-Viala Chrystel , Zamar Rémy , Vailleau Fabienne , Roux Fabrice
Published: May 2024

Non-pathogenic bacteria can substantially contribute to plant health by mobilizing and supplying nutrients, providing protection against pathogens, and alleviating abiotic stresses. However, the number of genome-wide association studies reporting the genetic architecture of the response to individual members of the beneficial microbiota remains limited. In this study, we established a genome-wide association study under field conditions to estimate the level of genetic variation and the underlying genetic architecture among 162 accessions of Arabidopsis thaliana originating from 54 natural populations in the southwest of France in response to 13 strains of seven of the most abundant and prevalent non-pathogenic bacterial species isolated from the leaf compartment of A. thaliana in the same geographical region. Using a high-throughput phenotyping methodology to score vegetative growth-related traits, extensive genetic variation was detected among A. thaliana accessions in response to these leaf bacteria, at both the species and strain levels. The presence of crossing reaction norms between each strain and the mock treatment indicates that declaring a strain as a plant growth-promoting bacterium is highly dependent on the host genotype tested. In line with the strong genotype-by-genotype interactions, we detected a complex and highly flexible genetic architecture between the 13 strains. Finally, the candidate genes underlying the quantitative trait loci revealed significant enrichment in several biological pathways, including cell, secondary metabolism, signaling, and transport. Altogether, plant innate immunity appears as a significant source of natural genetic variation in plant–microbiota interactions and opens new avenues for better understanding the ecologically relevant molecular dialog during plant–microbiota interactions.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Identification ofRmg11in Tetraploid Wheat as a New Blast Resistance Gene with Tolerance to High Temperature
Authors: Islam M. Thoihidul , Nago Chika , Yoshioka Motohiro , Vy Trinh Thi Phuong , Tosa Yukio , Asuke Soichiro
Published: May 2024

Wheat blast caused by Pyricularia oryzae pathotype Triticum has spread to Asia (Bangladesh) and Africa (Zambia) from the endemic region of South America. Wheat varieties with durable resistance are needed, but very limited resistance resources are currently available. After screening tetraploid wheat accessions, we found an exceptional accession St19 ( Triticum dicoccum, KU-114). Primary leaves of St19 were resistant not only to Brazilian isolate Br48 (a carrier of Type eI of AVR-Rmg8) but also to Br48ΔA8, an AVR-Rmg8 disruptant of Br48, even at 30°C, suggesting that the resistance of St19 is tolerant to high temperature and controlled by a gene or genes other than Rmg8. When an F2population derived from a cross between St19 and St30 (a susceptible accession of T. paleocolchicum, KU-191) was inoculated with Br48, resistant and susceptible seedlings segregated in a 3:1 ratio, indicating that resistance of St19 is conferred by a single gene. We designated this gene Rmg11. Molecular mapping revealed that the RMG11 locus is located on the short arm of chromosome 7A. Rmg11 is effective not only against other two Brazilian isolates (Br5 and Br116.5) but also against Bangladeshi isolates (T-108 and T-109) at the seedling stage. At the heading stage, lines containing Rmg11 were highly susceptible to the Bangladeshi isolates but moderately resistant to the Brazilian isolates. Stacking of Rmg11 with Rmg8 and the 2NS segment is highly recommended to achieve durable wheat blast resistance.
Understanding the Temporal Dynamics of Invasive Late Blight Populations in India for Improved Management Practices
Authors: Dey Tanmoy , Dwivedi Sanjai K. , Datta Sibnarayan , Cooke David E. L. , Roy Sanjoy Guha
Published: May 2024

The microbial oomycete pathogen Phytophthora infestans causes severe epidemics of potato late blight in crops globally. Disease management benefits from an understanding of the diversity of pathogen populations. In this study, we explore the dynamics of P. infestans populations in the late blight-potato agro-ecosystem across the Indian subcontinent. Investigations of the macroecological observations at the field level and microbial ecological principles provided insights into future pathogen behavior. We use a comprehensive simple sequence repeat allele dataset to demonstrate that an invasive clonal lineage called EU_13_A2 has dominated populations over 14 years across India, Bangladesh, and Pakistan. Increasing levels of subclonal variation were tracked over time and space, and, for the first time, populations in Asia were also compared with the source populations from Europe. Within India, a regional pathogen population structure was observed with evidence for local migration, cross-border movement between surrounding countries, and introductions via imports. There was also evidence of genetic drift and between-season transmission of more strongly pathogenic subclones with a complete displacement of some subclonal types. The limited introduction of novel genotypes and the use of resistant potato cultivars could contribute to the dominance of the 13_A2 lineage. The insights will contribute to the management of the pathogen in these key global potato production regions.
Molecular Cytogenetic Characterization of Novel Wheat-Rye T1RS.1AL Translocation Lines with Resistance to Powdery Mildew and Stripe Rust Derived from the Chinese Rye Landrace Qinling
Authors: Li Zhi , Sun Zixin , Zhao Liqi , Yan Tong , Ren Zhenglong , Ren Tianheng
Published: May 2024

Stripe rust and powdery mildew are serious diseases that severely decrease the yield of wheat. Planting wheat cultivars with powdery mildew and stripe rust resistance genes is the most effective way to control these two diseases. Introducing disease resistance genes from related species into the wheat genome via chromosome translocation is an important way to improve wheat disease resistance. In this study, nine novel T1RS.1AL translocation lines were developed from the cross of wheat cultivar Chuannong25 (CN25) and a Chinese rye Qinling. The results of non-denaturing fluorescence in situ hybridization and PCR showed that all new lines were homozygous for the T1RS.1AL translocation. These new T1RS.1AL translocation lines exhibited strong resistance to stripe rust and powdery mildew. The cytogenetics results indicated that the resistance of the new lines was conferred by the 1RS chromosome arms, which came from Qinling rye. The genetic analysis indicated that there were new dominant resistance genes on the 1RS chromosome arm resistant to stripe rust and powdery mildew, and their resistance patterns were different from those of Yr9, Pm8, and Pm17 genes. In addition, the T1RS.1AL translocation lines generally exhibited better agronomic traits in the field relative to CN25. These T1RS.1AL translocations have great potential in wheat-breeding programs in the future.
Artificial Intelligence in Dermatology: A Systematic Review of Its Applications in Melanoma and Keratinocyte Carcinoma Diagnosis
Authors: Jairath Neil , Pahalyants Vartan , Shah Rohan , Weed Jason , Carucci John A. , Criscito Maressa C.
Published: May 2024

BACKGROUND

Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps.

OBJECTIVE

The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC).

METHODS

Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023.

RESULTS AND DISCUSSION

Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.
Plastin 3 expression in circulating tumor cells as a predictor of cancer status in patients with prostate cancer
Authors: Shih Meng-Hung , Cha Tai-Lung , Wu Sheng-Tang , Meng En , Tsao Chih-Wei , Kao Chien-Chang , Chen Chin-Li , Juho Yu-Ching , Ting Hui-Kung , Sun Guang-Huan , Chang Sun-Yran , Yu Dah-Shyong , Yang Ming-Hsin
Published: May 2024

Background

Prostate cancer (PCa) is the most common cancer among men worldwide. The aim of the study is to identify the role of plastin 3 (PLS3) expression in circulating tumor cells (CTCs) of early stage PCa.

Materials and Methods

CTCs were collected from 23 PCa patients based on cell surface markers targeting PCa by V-BioChip. Condition of Plastin 3 expression and correlations to the PCa were also analyzed.

Results

Of the 23 patients with PCa, total CTCs (CK+ or PLS3+) were found in 11 patients and PLS3+ CTCs were detected in 10 patients. When the cohort was stratified by risk group, 90% of the high-risk patients were found to have PLS3+ circulating tumor cells (9/10 patients). However, only 15.4% of low/intermediate-risk patients had PLS3+ circulating tumor cells (2/13 patients). The number of PLS3+ CTCs was higher in the high-risk group.

Conclusions

The expression of PLS3 in CTCs is associated with PCa risk. Further study of PLS3+ CTCs for prognosis prediction is required for clinical application in PCa patients.
In Silico Pharmacokinetics Evaluation of Forgiveness for Doravirine and Rilpivirine
Authors: Fromage Yeleen , Jamal Najwa , Codde Cyrielle , Monchaud Caroline , Labriffe Marc , Ponthier Laure , Marquet Pierre , Faucher Jean François , Woillard Jean-Baptiste
Published: May 2024

Background:

This study aimed to evaluate the concentrations of rilpivirine (RLP) and doravirine (DOR) after 3 days-off using simulations from population pharmacokinetics models.

Methods:

The authors conducted a series of 500 sets of 10,000 Monte Carlo simulations to examine the steady-state conditions for 2 common dosage levels: 25 mg/d for RLP and 100 mg/d for DOR. These simulations were conducted under 2 scenarios: 1 without drug cessation and another after a 3-day break. The validity of the implementation was established through a comparison of median trough concentrations (C24h) with previously reported data. Subsequently, the proportion of simulated patients with C24h and C72h after 3 days-off (C72h/3do) that exceeded the inhibitory concentration 50 (IC50), 5.2 mcg/L for DOR and 20.5 mcg/L for RLP respectively, was calculated. The inhibitory quotient (IQ) was also computed, which was 6 times IC50 for DOR and 4.5 times IC50 for RLP. Finally, nomograms were constructed to estimate the probability of having C72h/3do > IC50 or > IQ for different ranges of C24h.

Results:

Simulated C24h median ± SD for RLP were 61.8 ± 0.4 mcg/L and for DOR 397 ± 0 mcg/L. For RLP, 99.3 ± 0.1% exceeded IC50 at C24h, 16.4 ± 0.4% at C72h/3do, and none surpassed the IQ threshold. In contrast, DOR had 100% ± 0% above IC50 at C24h, 93.6 ± 0.2% at C72h/3do, and 58.6 ± 0.5% exceeded the IQ.

Conclusions:

These findings suggest that treatment with DOR may offer a more forgiving therapeutic profile than RLP, given the larger proportion of patients achieving effective drug exposure with DOR. However, it is important to acknowledge a significant limitation of this study, namely, the assumption that drug concentration is a perfect surrogate for drug effectiveness.