Selection Of Candidates Research Articles

Genome-wide scan for selection signatures in Mexican Sardo Negro Zebu cattle

The Sardo Negro cattle (SN) is the only zebu cattle breed developed in Mexico. Since its development, the selection could have led to an increase in the homozygosity level in some regions of the genome and made differentiation with other cattle populations. We aimed to identify and characterize selection signatures in SN using medium-density SNP data using four approaches: 1) Runs of homozygosity (ROH) 2) Nucleotide Diversity 3) Tajima’s D and 4) the Wright’s fixation index (FST). A sample of 555 SN animals genotyped for 65k SNPs was used to obtain ROH segments considered regions under selection. The FST values were estimated by comparing the sample of genotyped SN animals with samples of genotyped animals from the Gir, Brahman, and Ongole breeds. Only one region mapped to 35.78–42.51 Mb on BTA6 was considered a selection signature by the ROH method. This selection signature overlapped with the lowest diversity, negative values of Tajima’s D and a diversification region between SN and the other Zebu breeds by FST. We found several candidate genes (LCORL, NCAPG, and SLIT2) related to growth and other economically important productive traits in this common region. Using the FST method, different regions, such as regions on BTA8 (8:93.4–93.9 Mb), BTA11 (11:99.2–99.7), and BTA14 (14: 26.1–26.8) related to growth and milk traits also were defined as candidate selection signatures. The selective signals identified in this study reflected the direction of the selection pressure that primarily involves the increase of live weight traits in the Sardo Negro cattle breeding program.

Justification of the approach to identifying promising managers for project management

The article deals with problems of project management in the context of a shortage of human resources at enterprises in the real sector of the economy as well as with promising areas of development to improve the efficiency of project management. The necessity of conducting work on preliminary analysis and selection of candidates is noted, with consideration to individual characteristics and expected goals. Within the framework of the tasks set for the study, the authors have shown the possibility of a three-factor evaluation of candidates to achieve results sufficient from the practical point of view in terms of choosing the most promising candidate from the available staff, and the possibility of obtaining a reasoned decision on the need to involve an external manager for the project implementation in the absence of the required competencies in the company’s staff of the. A brief overview of the methodological framework of management is given, which allows solving the problem of a reasonable approach to the recruitment for appointment to situational positions. It is shown that based on the developed approach, reasonable and strategically correct management decisions can be made. It can be used at enterprises in the real sector of the economy when making decisions on the appointment of project managers to improve the efficiency of work to achieve the goals stated in the project as well as for educational purposes to form decision-making skills and evaluate candidates for leadership positions.

Revolutionizing new drug discovery: Harnessing AI and machine learning to overcome traditional challenges and accelerate targeted therapies

Designing highly targeted, selective drugs with desirable absorption, distribution, metabolism, excretion, and pharmacokinetic (PK) profiles; single-digit nanomolar efficacy; and a wider therapeutic index are challenging. In the traditional drug discovery process, researchers screen thousands of chemical compounds during pre-clinical development, progressing through hit identification, lead optimization, and candidate selection to shortlist – potential clinical candidates with favorable PK profiles, high tolerability, and manageable toxicity. The selected candidate must demonstrate sufficient efficacy in treating the target disease in humans. Despite these efforts, the success rate of the pre-clinical candidate to sail through Phase I, Phase II, and Phase III in clinical trials remains exceedingly low. Supported by powerful data-driven tools, artificial intelligence (AI) has transformed this traditional drug discovery process by enabling the analysis of large quantities of omics, phenotypic, and expression data to identify the biological mechanisms of pathological conditions and in turn identify druggable proteins or genes. The generative AI-powered toolbox creates novel compounds from scratch, assists scientists in optimizing druggability attributes, and bridges the differences between animal and human physiology and anatomy to predict potential toxicity in humans with high accuracy. This review discusses the bottlenecks in the traditional drug discovery approach, the impact of AI and machine learning (ML) in drug discovery, and potential challenges associated with AI/ML adoption.

Genome-wide selection of potential target candidates for RNAi against Nilaparvata lugens

BackgroundNilaparvata lugens is one of the most destructive pests of rice. RNAi-based N. lugens control offers one alternative strategy to traditional chemical insecticides. However, selection of potential target for RNAi against N. lugens remains a major challenge. Only two target genes for nuclear transgenic N. lugens-resistant plants have been screened. Importantly, only one or few potential target genes against N. lugens were screened every time by knowledge of essential genes from model organisms in previous study.ResultsHere, in silico genome-wide selection of potential target genes against N. lugens through homology comparison was performed. Through genome synteny comparisons, about 3.5% of Drosophila melanogaster genome was found to have conserved genomic synteny with N. lugens genome. By using N. lugens proteins to search D. melanogaster homologs defining lethal or sterile phenotype, 358 N. lugens genes were first screened as putative target genes. Transgenic rice lines expressing dsRNA of randomly selected gene (NlRan or NlSRP54) from 358 putative target genes enhanced resistance to N. lugens. After expression check and safety check, 115 N. lugens genes were screened as potential target candidates.ConclusionThe combined efforts in this study firstly provide one in silico genome-wide homology-based screening approach for RNAi-based target genes against N. lugens, which not only offer one new opportunity to batch select potential target candidates in pests of interest, but also will facilitate the selection of RNAi target in many pest species by providing more than one hundred potential target candidates.

Structure–Tissue Exposure/Selectivity Relationship (STR) on Carbamates of Cannabidiol

The structure–tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics. L2 and L4 had almost same plasma exposure, which was not correlated with their exposure in the brain, while tissue exposure/selectivity was correlated with efficacy/safety. Structural modifications of CBD carbamates not only changed drug plasma exposure, but also altered drug tissue exposure/selectivity. The secondary amine of carbamate can be metabolized into CBD, while the tertiary amine is more stable. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters can be used to predict STR. Therefore, STR can alter drug tissue exposure/selectivity in normal tissues, impacting efficacy/toxicity. The drug optimization process should balance the structure–activity relationship (SAR) and STR of drug candidates for improving clinical trials.

Virtual screening, ADMET prediction, molecular docking, and dynamic simulation studies of natural products as BACE1 inhibitors for the management of Alzheimer’s disease

Alzheimer’s disease (AD) is a degenerative neurological disorder that chronically and irreversibly affects memory, cognitive function, learning ability, and organizational skills. Numerous studies have demonstrated BACE1 as a critical therapeutic target for AD, emphasizing the need for specific inhibition of BACE1 to develop effective therapeutics. However, current BACE1 inhibitors have certain limitations. Therefore, the aim of this study was to identify potential novel candidates derived from natural products that can be utilized for the treatment of AD. To achieve this, 80,617 natural compounds from the ZINC database were subjected to virtual screening and subsequently filtered according to the rule of five (RO5), leading to the identification of 1,200 compounds. Subsequently, the 1,200 compounds underwent molecular docking studies against the BACE1 receptor, utilizing high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) techniques to identify high-affinity ligands. Of the 50 ligands that exhibited the highest G-Scores in HTVS, further analysis was conducted using SP docking and scoring methods. This analysis led to the identification of seven ligands with enhanced binding affinities, which were then subjected to additional screening via XP docking and scoring. Finally, the stability of the most promising ligand in relation to BACE1 was assessed through molecular dynamics (MD) simulations. The computational screening demonstrated that the docking energy values for seven ligands binding to target enzymes ranged between − 6.096 and − 7.626 kcal/mol. Among these, ligand 2 (L2) exhibited the best binding energy at -7.626 kcal/mol with BACE1. MD simulations further confirmed the stability of the BACE1-L2 complex, emphasizing the formation of a robust interaction between L2 and the target enzymes. Additionally, pharmacokinetic and drug-likeness evaluations indicated that L2 is non-carcinogenic and able to permeate the blood-brain barrier (BBB). The findings of this study will contribute to narrowing down the selection of candidates for subsequent in vitro and in vivo testing.

Digital models for the selection of party organs and election candidates in Spanish political parties: the impact of intraparty democracy

Processes for selecting party officials and election candidates are key aspects of the internal democracy of political parties. This is not only because they reveal who is appointed, but also because they provide insight into intra-party dynamics and the levels of internal democracy within the parties. The aim of this article is to offer a general overview of the internal selection models used by Spanish political parties with representation in the Congress of Deputies, in order to determine whether online procedures are as widespread as is often believed, and, whether they have any real impact on intra-party democracy. We look into whether political parties are making widespread use of digital tools to promote new selection processes, whether the establishment of online selection mechanisms impacts the internal democracy of political parties and what types of parties are primarily using these tools. For this purpose we have conducted a taxonomy of the selection processes in Spanish political parties represented in the Congress of Deputies, based on the development of a model of indicators drawing on some previous studies.

Too old to be a diversity hire: Choice bundling shown to increase gender-diverse hiring decisions fails to increase age diversity.

Past research has shown that people are more likely to make the decision to hire candidates whose gender would increase group diversity when making multiple hiring choices in a bundle (i.e., when selecting multiple team members simultaneously) compared to making choices in isolation (i.e., when selecting a single team member). However, it is unclear if this bundling effect extends to age diversity and the selection of older candidates, as older workers are often the target of socially acceptable negative stereotypes and bias in recruitment, leaving them unemployed for longer than their younger counterparts. Across five preregistered experiments (total N = 4,096), we tested if the positive effect of bundling on diversity of selections extends to older candidates in hiring decisions. We found evidence of bias against older job candidates in hiring decisions but found inconsistent effects of choice bundling on the selection of older candidates across experiments. An effect of bundling was found in two of five experiments, with no meta-analytic effect found across the five studies. Making older candidates more competitive and introducing a diversity statement aimed at increasing their selection both significantly increased older candidate selections, but failed to activate the bundling effect. We discuss the theoretical implications for choice bundling interventions and for age as a diversity characteristic to support the design of interventions that meet the challenges of an aging workforce. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The S-PLUS Ultra-Short Survey: First data release

Context. This paper presents the first public data release of the S-PLUS Ultra-Short Survey (USS), a photometric survey with short exposure times, covering approximately 9300 deg2 of the Southern sky. The USS utilizes the Javalambre 12-band magnitude system, including narrow, medium, and broad-band filters targeting prominent stellar spectral features. The primary objective of the USS is to identify bright, extremely metal-poor (EMP; [Fe/H] ≤ −3) and ultra-metal-poor (UMP; [Fe/H] ≤ −4) stars for further analysis using medium- and high-resolution spectroscopy. Aims. This paper provides an overview of the survey observations, calibration method, data quality, and data products. Additionally, it presents the selection of EMP and UMP candidates. Methods. The data from the USS were reduced and calibrated using the same methods as presented in the S-PLUS DR2. An additional step was introduced, accounting for the offset between the observed magnitudes off the USS and the predicted magnitudes from the very low-resolution Gaia XP spectra. Results. This first release contains data for 163 observed fields totaling ~324 deg2 along the Celestial Equator. The magnitudes obtained from the USS are well-calibrated, showing a difference of ~15 mmag compared to the predicted magnitudes by the GaiaXPy toolkit. By combining colors and magnitudes, 140 candidates for EMP or UMP have been identified for follow-up studies. Conclusions. The S-PLUS USS DR1 is an important milestone in the search for bright metal-poor stars, with magnitudes in the range 10 < r ≤ 14. The USS is an ongoing survey; in the near future, it will provide many more bright metal-poor candidate stars for spectroscopic follow-up.

Revisiting Unaddressed Safety Concerns Regarding Intense Pulsed Light Treatment: Past and Present Perspectives.

The light spectrum of intense pulsed light (IPL) comprises visible to near-infrared light. It has been widely employed in the field of aesthetics for approximately 30 years. However, several studies have demonstrated the appearance of various undesirable biomarkers on the skin after IPL irradiation, which remain elucidated. We reviewed the evolving concepts and explored the potentially harmful effects of IPL that may have been neglected in the past. Increased levels of reactive oxidative stress, p53, p16, proliferating cell nuclear antigen, interleukin-6, C-reactive protein, and cleaved caspase 3 and decreased albumin levels in human or mouse skin have been observed after IPL treatment. Visible and infrared light can exert harmful and beneficial effects on human skin. If perform improperly, IPL treatment may lead to cellular senescence, photoaging, photocarcinogenesis, thermal aging, and inflammaging. Further studies are required to verify the significance of the changes in the relevant biomarkers. The selection of treatment candidates, optimal parameters, and standardized protocols for IPL therapy are necessary.

A fast-aware multi-target response prediction approach and its application in aeronautical engineering

Response prediction is a fundamental yet challenging task in aeronautical engineering, requiring an accurate selection of sensor positions correlated with the target responses to achieve precise predictions. Unfortunately, in large-scale structures, the rigorous selection of reliable sensor candidates for multi-target responses remains largely unexplored. In this paper, we propose a flexible and generalized framework for selecting the most relevant sensors to the multi-target response and predicting the target response, referred to as the Fast-aware Multi-Target Response Prediction (FMTRP) approach in the spirit of divide-and-conquer. Specifically, first, a multi-task learning module is designed to predict multi-point response tasks at the same time. Simultaneously, we meticulously devise adaptive mechanisms to facilitate loss-term reweighting and encourage prioritization of challenging tasks in multiple prediction tasks. Second, to ensure ease of interpretation, we introduce a hybrid penalty to select sensors at the group-sparsity, individual-sparsity and element-sparsity levels. Finally, due to the substantial number of candidate sensors posing a significant computational burden, we develop a more efficient search strategy and support computation to make the proposed approach applicable in practice, leading to substantial runtime improvements. Extensive experiments on aircraft standard model response datasets and large airliner test flight datasets validate the effectiveness of the proposed approach in identifying sensor locations and simultaneously predicting responses at multiple points. Compared to state-of-the-art methods, the proposed approach achieves an accuracy of over 99% in sinusoidal excitation and exhibits the shortest runtime (3.514 s).

Risk factors for local recurrence following marginal mandibulectomy in gingival cancer

Surgery is the first line of treatment in gingival cancers of the mandible, and bone resection is necessary in the majority of cases. In the less extensive surgical option, marginal mandibulectomy (MM), the mandibular base is preserved. In contrast, in a segmental mandibulectomy (SM) the mandible is divided and the continuity is not preserved. If MM can be performed with comparable oncological results to SM, it is the preferred method. The aim of the present study was to identify preoperative predictors for local recurrence (LR), to support the selection of candidates for MM. Outcome measures were local recurrence free survival (LRFS) and disease specific survival (DSS). 67 patients treated with MM between 2008 and 2021 were included. Cox regression analyses of LR with hazard ratios and adjustments for postoperative radiotherapy, pathological T-stage (pT) and soft tissue margins were performed. 5-years LRFS was 63% (95% CI 46.9–75.5) and DSS 80.6% (95% CI 64.7–89.9). In conclusion we found that edentulous patients, more advanced pT-stage and positive soft tissue margins had increased risk for LR. Future studies of the correlation between cT and pT would be important to provide more robust preoperative support in the selection between MM and SM.

Survival Outcomes of Radiofrequency Ablation for Intrahepatic Cholangiocarcinoma from the SEER Database: Comparison with Radiotherapy and Resection

To determine effectiveness of radiofrequency ablation for treatment of intrahepatic cholangiocarcinoma (iCCA) using a population-based database. Data was extracted from Surveillance, Epidemiology, and End Results database from 2000 to 2020 to include 194 patients who underwent ablation for iCCA. Patient demographics, overall survival (OS), and cancer-specific survival (CSS) were retrieved. Factors associated with survival were evaluated. Comparison between ablation and surgical resection (n=2653) or external beam radiotherapy (n=1068) were performed. In the ablation group, atients diagnosed and treated after 2010 demonstrated improved OS than the 2000-2009 subgroup (mOS 32 versus 21 months, HR: 0.50 [95%CI: 0.33-0.75], p=0.001). Additional factors associated with OS included tumor size (≤3cm versus >3cm, p=0.049) and tumor stage (p<0.001). For patients diagnosed after 2010, the 1-, 3-, and 5-year OS were 82.8% (95%CI: 74.8-88.4%), 43.5% (95%CI: 33.5-53.1%), and 23.7% (95%CI: 15.3-33.5%), respectively. Patients with local disease (1-year OS: 87.8% [95%CI: 78.6-93.3%]) demonstrated improved OS than regional (1-year OS: 81.3% [95%CI: 52.5-93.5%]) and distant disease (50.2% [95%CI: 34.0-78.8%], p<0.001). For tumors ≤3cm, ablation and surgical resection offered comparable survival benefits (p=0.561), although both were better than radiotherapy (p<0.0001). Survival of iCCA patients who underwent thermal ablation has improved over the last 10 years. For tumors ≤3cm, ablation could be as effective as resection with careful candidate selection, and may be considered as front line compared to radiotherapy in certain patient populations. Patient selection based on tumor size and disease stage could improve survival outcomes.

A Survey of Solid Form Landscape: Trends in Occurrence and Distribution of Various Solid Forms and Challenges in Solid Form Selection

This survey provides a comprehensive analysis of solid form screens for 476 new chemical entities (NCEs) conducted at Pharmaron from 2016 to 2023. The findings from this survey reveal notable trends in polymorphism, salt formation, crystallization behavior and molecular weight (MW) distribution of the NCEs evaluated. Most solid form screens were conducted to select the preferred solid form for Investigational New Drug (IND) enabling projects, others were for candidate selection or late-stage development. Comparison to published historical data was made to show changes in occurrence of counterions/co-formers for salts/co-crystals, polymorphs, and the distribution of MWs over time. Increased complexity in the solid-form landscape and selection of the development form are discussed, including challenges in crystallization and selection of lead forms. The distribution of types of crystal forms and the observation of emerging and disappearing polymorphs are presented. These results highlight the evolving challenges and considerations in solid form screening and form selection and offer insights for future pharmaceutical development and crystallization strategies.

The Zimbabwe political space

Zimbabwe's post-independence election processes have been predominantly male-dominated, with women relegated to the periphery as electorates or party ‘cheerleaders’. Since the Beijing conference in 1995, Zimbabwe enacted several laws to overcome bottlenecks that have impeded women's participation in political processes, with the 2013 Constitution serving as the ultimate template for promoting women's engagement in mainstream electoral systems. Nonetheless, women’s participation as candidates or leaders in electoral processes has declined significantly since the 2013 Constitution. The study brings to the fore, findings to respond to 3 fundamental research questions which are: 1) what is the interlinkage between economic, cultural, social, and physical spaces with the electoral processes, 2) what are the complex social inclusion factors in political spaces, and 3) what recommendations can be proffered to enhance inclusion of women in electoral processes. In answering the questions, the research draws on content analysis of reports from the Project on Preventing Violence Against Women in Politics Project (VAWP/E), face-to-face interviews, and focus group discussions to offer insights and investigate the opportunities provided by various legal frameworks to increase women's engagement in electoral and political processes in Zimbabwe. The article further systematically explores other important factors and elements that impede and contribute to women's full participation in electoral processes as candidates. This study contends that the availability of excellent legal provisions does not result in increased women's participation in electoral politics as candidates unless there is political will. The study further asserts that participation in social, cultural, economic, and physical spaces interacts in a complex manner and influences women's participation in Zimbabwe's electoral political processes as candidates. Because of the country's political polarisation and the impunity of perpetrators of political violence, the political arena is believed to be intimidating and discouraging, thus not ripe, for women to participate as candidates. The study recommends a wholesome approach to dismantling the complex interlinkages between cultural, social, economic, and physical spaces as obstacles affecting the inclusion of women in electoral processes as candidates. Thus, the study further recommends that existing legal instruments should be complemented by progressively dismantling the social, cultural, and physical forces prohibiting women's participation as leaders in electoral processes. Specific provisions in the Electoral Act may further be used to penalise failure by political parties to field a reasonable number of women as candidates in elections.

The Impact of Transactional Politics on Papuan Ethnic Identity Politics in the Dynamics of the 2024 General Election in Manokwari Regency

The objective of this study is to investigate the perspectives of the Papuan ethnic group regarding the dynamics of identity politics in general elections, which frequently encompass aspirations related to identity politics. The term "Papuan ethnicity" refers to an identity within Papuan nationalism, symbolizing the mobilization and unification of Papuans. In the context of elections, the notion of Papuan ethnicity becomes a significant issue for electoral candidates, particularly for those who lack support from their fellow Papuans. Utilizing qualitative research methods and ethnographic approaches, this study explores the impact of transactional politics on the ethnic perspectives and political participation of Papuans during elections. It examines various factors, including the influence of political funding on voter preferences, the mobilization of ethnic groups for political backing, and the dynamics of inter-ethnic interactions within political disputes. The findings of this research aim to provide an in-depth understanding of the patterns of political aspirations in Papua and their implications for the consolidation of democracy in Indonesia.Keywords: identity politics, political aspirations, Papuan ethnicity, general elections

Optimizing patient selection for cardiac resynchronization therapy in a multicenter study of Japanese patients: assessment of the MADIT-ICD benefit group

Abstract Background The MADIT-ICD benefit group, derived from ventricular tachycardia (VT)/ventricular fibrillation (VF) scores and non-arrhythmic mortality scores (Table 1), facilitates the appropriate selection of candidates for implantable cardioverter-defibrillator (ICD) therapy. While the 2021 European Society of Cardiology Guidelines have discussed the advantages and considerations of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT), the optimal selection of CRT with or without a defibrillator remains unclear, particularly in Asian populations. This is especially relevant for primary prevention using ICD, which is characterized by fewer cases of ischemic etiology compared to Western countries. Purpose This study aimed to evaluate the utility of the MADIT-ICD benefit group in Japanese CRT patients and identify key indicators for determining the necessity of CRT with or without a defibrillator. Methods We conducted a retrospective, multicenter evaluation of 505 consecutive Japanese CRT patients enrolled between 2012 and 2020. Among these patients, 76% were male, with a mean age of 65 years and a mean body mass index of 22.5 kg/m2. Ischemic etiology was present in 25% of patients, with 20% undergoing secondary prevention. The study assessed the cumulative incidences of VT/VF and non-arrhythmic mortality based on the MADIT-ICD benefit group (lowest, intermediate, and highest). Predictors for each outcome were explored, and the MADIT-ICD benefit group was validated in the Japanese cohort. Results Of the 400 included patients, 60 (15%) were categorized into the lowest MADIT-ICD benefit group, 279 (70%) into the intermediate group, and 61 (15%) into the highest group. Over a median follow-up period of 34 months, VT/VF occurred in 4 (13%), 68 (24%), and 14 (23%) patients in the lowest, intermediate, and highest benefit groups, respectively (Gray’s test, P = 0.027, Figure 1A). Non-arrhythmic death occurred in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest, intermediate, and highest benefit groups, respectively (Log-rank test, P = 0.025, Figure 1B). Multivariable analysis identified MADIT-ICD VT/VF score (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.12-1.35; P &amp;lt; 0.001) and left bundle branch block (LBBB) (HR 0.48; 95% CI 0.27-0.86; P = 0.014) as significant predictors for VT/VF, while MADIT-ICD non-arrhythmic mortality score (HR 1.16; 95% CI 1.07-1.27; P &amp;lt; 0.001), serum creatinine (Cr) (HR 1.28; 95% CI 1.13-1.45; P &amp;lt; 0.001), and mineral corticoid receptor antagonist (MRA) use (HR 1.84; 95% CI 1.21-2.79; P = 0.004) were significant predictors for non-arrhythmic death (Table 2). Conclusion The MADIT-ICD benefit group, in conjunction with left bundle branch block and renal function, may serve as valuable predictors for determining the necessity of cardioverter-defibrillator therapy in Japanese CRT patients.Table 1 and Figure 1

Impact of left atrial stiffness measurement as a pre-procedural predictor of an extensive left atrial low-voltage area

Abstract Background The presence of a left atrial (LA) low-voltage area (LVA) after pulmonary vein isolation for atrial fibrillation (AF) is a strong predictor of recurrence and LVAs are often an additional ablation target. However, predicting the presence of an LVA before the procedure remains challenging. Purpose To assess the LA stiffness index as a preprocedural predictor of an extensive LVA. Methods We prospectively evaluated 74 patients who underwent catheter ablation for AF and high-density bipolar LA voltage mapping during sinus rhythm or high right atrial pacing. "LVA" was defined as an area with bipolar electrograms (&amp;lt;0.5 mV), while "extensive LVA" was defined as the presence of an LVA that covered more than 15% of the LA surface. Echocardiographic measurements, including the LA volume index (LAVi), E/e' ratio, LA reservoir strain (LASr), and LA stiffness index, calculated as the ratio of E/eʹ to LASr, were performed prior to catheter ablation in all patients. Results Overall, 17 patients (23.0%) had an extensive LVA. Patients with extensive LVAs were older (73 ± 7 vs. 66 ± 8 years; P=0.003), predominantly female (59% vs. 23%; P=0.01), and more frequently showed persistent AF (59% vs. 30%; P=0.04) in comparison to patients without extensive LVAs. According to a receiver operating characteristic curve analysis, the LA stiffness index was more accurate than the LAVi or LASr for predicting extensive LVAs (Figure), allowing using a cutoff value ≥0.6 with 73% sensitivity and 91% specificity. A multivariate logistic regression analysis revealed that the LA stiffness index was an independent predictor of an extensive LVA (odds ratio [OR], 44.11; 95% CI 3.83–507.47, P=0.002). Conclusion The LA stiffness index was a robust predictor of the extent of LVAs in AF patients and thus could be useful for the preprocedural selection of candidates for catheter ablation and to determine the most effective ablation strategies.

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Is extended resection for locally advanced thoracic cancer with cardiopulmonary bypass justified?

BackgroundResection of intrathoracic tumor with cardiopulmonary bypass (CPB) remains a relatively under-reported intervention in literature, and its role in managing locally advanced mediastinal and lung cancers is a topic of ongoing debate. Our aim was to review our experience and assess the role of CPB for treating locally advanced mediastinal and lung cancers.MethodsBetween 2015 and 2020, this study initially included 10 patients with primary locally advanced thoracic malignancies with apparent adjacent cardiovascular invasion demonstrated by thoracic imaging scans. Operation was performed based on a multidisciplinary tumor board consensus. Eventually, 8 patients (3 primary lung cancers and 5 mediastinal cancers) received either salvage or elective resection with CPB; two completed surgery without requiring CPB.ResultsRegarding the extent of adjacent structure involvement, 4 patients presented with involvement of the superior vena cava (SVC), 1 involved the right atrium (RA), 2 involved the SVC and RA, and 1 involved the SVC, the origin of main pulmonary artery, and the ascending aorta. Thirty-day mortality occurred in two of three patients receiving salvage surgery due to respiratory insufficiency. With the long-term follow-up, one patient died of recurrence 25 months postoperatively, one survived with recurrence 30 months postoperatively, and four were alive without recurrence for 35, 36, 49, and 107 months after operations.ConclusionIn certain patients, particularly for elective surgical candidates rather than salvage resection, CPB allows for extended resection of locally advanced thoracic cancers with acceptable perioperative safety and survival.