bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities and limitations of expanding indications for extensively hydrolyzed protein formulas for in
Authors:   N.F.Filatov Children’s City Clinical Hospital, Moscow, Russian Federation, Chubarova A.I. ,   N.I.Pirogov Russian National Research Medical University, Moscow, Russian Federation
Published: February 2024

Extensively hydrolyzed cow’s milk protein formulas have been created for artificial feeding of children with cow’s milk allergy, and in most of them the carbohydrate and fat components are also significantly modified. This allows us to consider the use of this group of products not only in allergic diseases. For this purpose, it is necessary to reassess the experience of using these products in children with allergic diseases, considering the differences in the hydrolysis substrate, degree of hydrolysis, technology of producing dry powder, as well as the amount and composition of non-protein components, biologically active additives. This article reviews the physiology of protein digestion in infants and the interaction of dietary proteins with the immune system to demonstrate the opportunities and risks of using extensively hydrolyzed cow’s milk protein formulas in nonallergic diseases (short bowel syndrome and other forms of malabsorption, congenital heart disease with intestinal ischemia) and prematurity. Key words: children, hydrolysis, hydrolyzed protein, formulas
Nitrosative stress in adolescents with exogenous constitutional obesity
Authors:   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation, Lesnaya A.S. , Semenova N.V. ,   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation, Darenskaya M.A. ,   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation, Rychkova L.V. ,   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation, Balzhirova D.V. ,   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation, Kolesnikova L.I. ,   Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation
Published: February 2024

Objective. To study the levels of nitric oxide, advanced oxidation protein products and total antioxidant activity in serum and plasma in adolescents with exogenous constitutional obesity. Patients and methods. The study group included 46 adolescents with class I exogenous constitutional obesity (24 girls and 22 boys). The control group included 43 adolescents with normal body weight (23 girls and 20 boys). The levels of nitric oxide, advanced oxidation protein products and total antioxidant activity in serum and plasma were determined by spectrophotometry. Results. There were no statistically significant differences between groups in metabolic indices. In adolescent boys with obesity, a direct correlation was found between the levels of nitric oxide and advanced oxidation protein products, and between the levels of nitric oxide and total antioxidant activity. Conclusion. In the group of adolescent boys with class I exogenous constitutional obesity, the formation of pathogenetic interrelations between the parameters of nitrosative status was observed, which indicates the initial signs of metabolic changes. Key words: obesity, adolescents, free radical oxidation, nitric oxide
Frecuencia y factores asociados a depresión en adultos mayores con antecedente de covid-19 en un Centro de Atención Primaria de Lima Norte
Authors:   , Lopez Valladares Armida Linda
Published: February 2024

La estructura demográfica mundial está cambiando debido al envejecimiento acelerado, se estima que, en el Perú, el número de adultos mayores de 60 años aumente a más del 50% entre 2015 y 2050, lo que plantea desafíos en el sector salud a nivel mundial, tales como el tratamiento de la depresión en los adultos mayores, quienes constituyen el mayor grupo poblacional y el más vulnerable con problemas psiquiátricos. Luego que el COVID-19 llego para quedarse, aumentaron significativamente los casos de depresión a nivel mundial, especialmente en este grupo etario, surgiendo nuevos interrogantes sobre este escenario. Aunque el número de infecciones ha disminuido significativamente en todo el mundo, la COVID-19 sigue siendo una enfermedad crónica para millones de personas. Estos síntomas se denominan "síndrome post-COVID-19”, que son los signos y síntomas clínicos persistentes que ocurren durante o después de la infección por COVID-19, persisten durante más de 12 semanas y no se explican por otros diagnósticos. En este sentido la presente investigación se propone como objetivo a determinar la frecuencia de la depresión y los factores asociados en los adultos mayores con antecedentes de COVID-19 que asisten a un Centro de Salud de Atención Primaria de Lima Norte. El presente estudio se desarrollará bajo un enfoque observacional, descriptivo y transversal. Por lo tanto, es de suma importancia identificar a quienes desarrollan secuelas psiquiátricas como depresión, luego de contraer COVID-19. Para identificar y establecer intervenciones que fortalezcan aspectos como la atención primaria de salud y las políticas de salud mental, promoviendo los beneficios de un enfoque integral, preventivo y multidisciplinario.
Estimación de la edad dental evaluando el volumen pulpar de cinco dientes en imágenes de tomografías computarizadas de haz cónico en una población peruana
Authors:   , Salvatierra Galvez Juliana Magaly
Published: February 2024

La estimación de la edad dental en personas vivas y cadáveres es muy importante para la Odontología Forense, sobre todo en casos de identificación en investigaciones legales y sociales. El objetivo del estudio fue estimación de la edad dental mediante la medición del volumen pulpar de imágenes dentales en tomografía computarizada de haz cónico (TCHC) de pacientes peruanos. Fueron analizadas 231 TCHC de pacientes entre 12 a 60 años a más. [Mujeres (134), hombres (97)] se dividieron en seis grupos de edad (12-19, 20-29, 30-39, 40-49, 50-59, 60 años a más). El análisis volumétrico de la pulpa dental se realizó en un total de 1155 dientes (caninos superiores, incisivos centrales superiores izquierdos, primeros molares superiores izquierdos y primeros premolares inferiores izquierdos), mediante el software Romexis® 5.3.3.5. El análisis de regresión lineal mostró un coeficiente de determinación del 30% que sugiere una correlación débil entre la relación del volumen pulpar de los dientes y la edad. El volumen pulpar de los caninos superiores derecho e izquierdo disminuyó a medida que aumentaba la edad y el volumen pulpar en dientes de personas de 60 años a más fue el más bajo. Sin embargo, se pueden proponer estudios futuros para incluir una gran muestra homogénea de dientes en diferentes categorías y grupos de edad para confirmar la correlación y establecer una ecuación de regresión confiable.
WITHDRAWN: Skin Cells State and its Effect on Visual Perception
Authors: Khalifa Samar
Published: February 2024

The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
WITHDRAWN: Emotional Brain activity Evaluation in Diabetes mellitus type 2: A case report
Authors: Khalifa Samar
Published: February 2024

The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
Developing the Optimal Hybrid Neural Network for Predicting the Factor of Air Pollutants
Authors: S Neduncheliyan , Viswanathan Priya
Published: February 2024

Urban air pollution can be reduced via precise air pollutant forecasts.For that, the air quality index (AQI) quantifies air quality.In this manner, accurate and trustworthy air quality index (AQI) estimates are essential for preserving the natural environment and the general population's health. Using the backpropagation (BP) algorithm, this study describes a method for enhancing the performance of neural networks. Using a network optimized with natural swarm intelligence, a novel optimal-hybrid model approachto Nature Swarm Intelligence (NSI), predicting the Air Quality Index (AQI), is possible. This NSI comprises the optimization algorithms Dove Swarm optimization (DSA) and Bat Algorithm (BA), which aim to optimize the weight of the Backpropagation neural network (BPNN) to promote the air quality prediction. The constructed optimal-hybrid modelcaptured the characteristics of the AQI series and produced a more accurate AQI forecast according to exhaustive comparisons using a set of evaluation indicators. Experiments conducted verify the proposed modelis validfor application when attempting to forecast the AQI. This is because it receives a high RMSE, MAPE, Error Absolute total, and Accuracy value from the simulation. This is because the simulation results suggest that the network model could be a good option for actualization, which is why this is the case.
Exploring Information Security Compliant Behaviors in Healthcare Knowledge Process Outsourcing (KPOs)
Authors: Mahipala Charitha Rakkitha , Perera Pethigamage
Published: February 2024

The healthcare industry increasingly relies on Knowledge Process Outsourcing (KPO) to handle vast amounts of sensitive patient data. This study investigates information security compliance in healthcare KPOs to protect patient privacy and data integrity. Employing a qualitative approach, it analyzes existing security policies, revealing the current state of information security in these organizations and factors influencing compliance. Key themes include employee training, technology, regulatory adherence, and organizational culture. The study uncovers the intricate relationships between these factors and their role in mitigating security risks. Additionally, the research aims to identify best practices to enhance information security compliance in healthcare KPOs. The findings benefit KPO leaders, healthcare providers, and policymakers, enhancing patient data confidentiality while optimizing KPO benefits in healthcare. By contributing insights into information security compliance in healthcare KPOs, this study also enriches discussions on safeguarding sensitive data amid evolving threats and regulations, bolstering trust in healthcare KPO operations.
The Royal College of Ophthalmologists’ National Ophthalmology Database study of cataract surgery: Report 17, A risk factor model for posterior capsule rupture
Authors: Sim Peng Yong , Donachie Paul , Day Alexander , Buchan John
Published: February 2024

Background/ObjectivesTo create a risk factor model for posterior capsule rupture (PCR) during cataract surgery.Subjects/MethodsEligible cataract operations were performed between 01/04/2016 and 31/03/2022 in centres supplying data to the national cataract audit on at least 50 eligible operations with complete data for patients’ gender and age at surgery, anterior chamber depth (ACD) measurement and preoperative visual acuity (VA). A logistic regression model was fitted to identify risk factors for PCR.ResultsThis analysis included 961 208 cataract operations performed on 682 381 patients from 136 participating centres by 3 198 surgeons. The final PCR risk factor model included surgical and patient factors comprising surgeon grade, patients’ gender and age, ability to lie flat and/or cooperate, diabetic status and an interaction between age and gender. Ocular factors were first or second eye surgery, ACD, preoperative VA, previous intravitreal therapy, pupil size, the presence or absence of amblyopia, brunescent / white / mature cataract, diabetic retinopathy, glaucoma, high myopia, previous vitrectomy and pseudoexfoliation / phacodonesis. The highest influencing risk factors were surgery by less experienced trainee surgeon, younger male patients and the presence of pseudoexfoliation / phacodonesis.ConclusionVarious surgical, patient and ocular factors increase the risk of PCR during cataract surgery. Appropriate case allocation should balance the risk to the patient with the requirement for trainee surgeons to gain experience. This risk factor model permits estimation of individualised risks for patients and allows risk-adjustment for surgeons to evaluate their PCR rates based on case complexity.
L-VEIGe: Development of L2 Vocabulary Learning Support System with Suggestibility of Error by Image Generation
Authors: Sugita Kazuki , Gu Wen , Ota Koichi , Hasegawa Shinobu
Published: February 2024

Vocabulary learning has long been taught as a basis for L2 English language learning. The use of visual clues is a widely recognized method in vocabulary learning. Several research have applied automatic image caption generation, invented with computer vision and natural language processing, to English vocabulary learning. However, these vocabulary learning systems mainly use correct answers and their corresponding images. On the other hand, in English vocabulary learning, Fossilization is a problem where errors become difficult to correct and become established through repeated errors by learners. While the use of images has been effective in traditional English vocabulary learning, there has been little research focusing on learners' incorrect answers. In this research, we intentionally created situations where learners are likely to give incorrect answers and constructed an English vocabulary learning support system L-VEIGe (Learning-Vocabulary Error Image Generation) that generates images in response to learners' incorrect answers to promote effective introspection and eliminate repeated errors. An evaluation experiment targeting graduate students who are second language English learners revealed that a proposed method effectively prevents repetitive errors compared to a method without image generation.
Identification of glycosyltransferase genes for diagnosing T-cell mediated rejection and predicting graft loss in kidney transplantation
Authors: Mao Kaifeng , Lin Fenwang , Ye Junli , Li Juan , Ye Junsheng
Published: February 2024

Background Protein glycosylation plays an important role in various biological processes, and abnormal glycosylation is often linked with many diseases. This study aimed to investigate the potential value of glycosyltransferase genes (GTGs) in the diagnosis of T-cell mediated rejection (TCMR) and the prediction of graft loss in kidney transplantation.Methods We downloaded the microarray datasets and GTs from the GEO database and the HUGO Gene Nomenclature Committee (HGNC) database, respectively. Differentially expressed GTGs (DE-GTGs) were obtained by differential expression analysis and Venn analyses. LASSO and XGboost machine learning algorithms were applied to screen hub DE-GTGs, and a TCMR diagnostic model was established based on the hub DE-GTGs. Furthermore, we constructed a long-term graft survival predictive model by univariate Cox analysis and LASSO Cox regression analysis.Results 15 DE-GTGs were obtained. GO and KEGG analyses showed that the DE-GTGs were mainly involved in the glycoprotein biosynthetic process. The TCMR diagnostic model exhibited high diagnostic potential with generally high accuracies (an AUC of 0.833). The immune characteristics analysis revealed that higher levels of immune cell infiltration and immune responses were observed in the high-risk group than in the low-risk group. Furthermore, a predictive model for long‑term graft survival was established. Kaplan-Meier survival analysis suggested that renal grafts in the high-risk group have worse prognostic outcomes than the low-risk group. AUC values of 1-, 2- and 3-year graft survival were 0.76, 0.81, and 0.70, respectively.Conclusion Our results indicate that GTGs not only play an important role in renal graft rejection but also could be used for diagnosing TCMR. Furthermore, GTGs could be applied to predict long-term renal graft outcomes. These results offer novel schemes for assessing kidney transplant diseases and provide a valuable direction for future research.
Usefulness of respiratory-triggered 3D-balanced steady-state free precession in assessing the anatomy of the right adrenal vein for adrenal vein sampling
Authors: Kisohara Masaya , Nakayama Keita , Ohta Kengo , Hatano Motoki , Nakashima Yusuke , Yanagihara Takashi , Shimohira Masashi , Shibamoto Yuta , Kawai Tatsuya
Published: February 2024

Background
Primary aldosteronism (PA) is one of the causes of hypertension. Adrenal vein sampling (AVS) is an interventional radiology procedure used to devise therapeutic strategies for PA. Since catheterization of the right adrenal vein (RAV) is a difficult step in AVS, evaluation of the anatomy of the RAV is essential before AVS.
Purpose
We assessed the confluence of the RAV with the inferior vena cava (IVC) with respiratory-triggered 3D-balanced steady-state free precession magnetic resonance imaging (RT-3D bSSFP) and dynamic contrast-enhanced computed tomography (CECT).
Materials and Methods
Those with RAVs identifiable on RT-3D bSSFP and CECT were included. We evaluated the vertebral level of the confluence of the RAV with the IVC on RT-3D bSSFP and CECT over 10 even divisions of the adjacent intervertebral discs. We also evaluated the highest and lowest levels of the confluence of the RAV with the IVC during AVS procedures on digital angiography to test equivalence.
Results
The confluence of the RAV with the IVC was identified in all modalities in 39 patients which met the inclusion criteria. 95% confidential intervals of the differences in mean showed − 1.00–0.48, -0.01-0.56, -0.21-0.36, -0.71–0.21, and − 0.90–0.41 between RT-3D bSSFP and CECT, RT-3D bSSFP and angiography during spontaneous inspiration (inspiration), RT-3D bSSFP and angiography during spontaneous expiration (expiration), CECT and inspiration, and CECT and expiration, respectively. Equivalence in height was observed between RT-3D bSSFP and expiration (p = 0.0023).
Conclusion
RT-3D bSSFP is helpful in evaluating the height at which the RAV merges into the IVC.
Cell cycle-regulated release of a replication inhibition complex in Vibrio cholerae
Authors: Val Marie-Eve , Niault Theophile , Talavera Ariel , LeCam Eric , Skovgaard Ole , Fournes Florian , Wagner Léa , Tamman Hedvig , Thompson Andrew , Pino Abel Garcia , Mazel Didier
Published: February 2024

Over 10% of bacteria have expanded their genomes through the domestication of megaplasmids, which subsequently evolved into secondary chromosomes encoding core functions. A fundamental challenge of this genomic expansion is coordinating the replication of multiple replicons within a single cell cycle. In Vibrio cholerae, the replication of the secondary chromosome (Chr2) is intricately linked to the replication of the primary chromosome (Chr1) via a unique checkpoint sequence, crtS. This sequence binds to the initiator of Chr2, RctB. While crtS replication on Chr1 triggers Chr2 replication, the specific molecular dynamics remain elusive. To investigate this, we conducted a comprehensive genome-wide analysis of RctB binding patterns in V. cholerae across various cell cycle stages. Our findings show that RctB primarily binds to sites inhibiting replication initiation at the Chr2 origin (ori2). This inhibitory effect is counteracted when crtS replicates on Chr1, causing a shift in RctB binding to sites that activate replication at ori2. Structural analyses support the formation of diverse oligomeric states of RctB, coupled to the allosteric effect of DNA, which determine ori2 accessibility. We propose a synchronization model where, upon replication, crtS locally destabilizes the RctB inhibition complex, releasing the Chr2 replication origin.
Integrated Analysis of Tumor-Associated Macrophages and M2 Macrophages in CRC: Unraveling Molecular Heterogeneity and Developing a Novel Risk Signature
Authors: Shi Lujing , Mao Hongtun , Ma Jie
Published: February 2024

Background: Emerging investigations have increasingly highlighted the critical role of tumor-associated macrophages (TAMs) and M2 macrophages in cancer development, progression, and metastasis, marking them as potential targets in various cancer types. The main objective of this research is to discover new biomarkers associated with TAM-M2 in colorectal cancer (CRC) by combining single-cell RNA sequencing and bulk RNA-seq data. Our objective is to dissect the molecular heterogeneity of CRC and develop a novel risk signature.
Methods: By utilizing weighted gene co-expression network analysis (WGCNA), we acquired TAM-M2-associated genes by intersecting TAM marker genes obtained from scRNA-seq data with module genes of M2 macrophages derived from bulk RNA-seq data. We employed least absolute shrinkage and selection operator (LASSO) Cox analysis to select predictive biomarkers from these TAM-M2-related genes. Quantitative Polymerase Chain Reaction (qPCR) was employed to validate the mRNA expression levels of the genes identified in the screening. This led to the development of the TAM-M2-related signature (TAMM2RS). We also conducted immune landscape analysis across different risk groups.
Results: The combination of scRNA-seq and bulk RNA-seq analyses yielded 377 TAM-M2-related genes. DAPK1, NAGK, and TRAF1 emerged as key prognostic genes in CRC, identified through LASSO Cox analysis. Utilizing these genes, we constructed and validated the TAMM2RS, demonstrating its effectiveness in predicting survival in CRC patients.
Conclusion: Our research offers a thorough investigation into the molecular mechanisms associated with TAM-M2 macrophages in CRC and unveils potential therapeutic targets, offering new insights for treatment strategies in colorectal cancer.
Additive Confirmation of Cavotricuspid Isthmus Conduction Block
Authors: Park Soyoon , Kim Soohyun , Kim Hwajung , Choi Young , Oh Yong-Seog , Kim Tae-Seok , Hwang Youmi , Kim Ji-Hoon , Jang Sung-Won , Kim Sung-Hwan
Published: February 2024

Background
Differential pacing (DP) was generally used to assess the bidirectional conduction block of the cavotricuspid isthmus (CTI) after catheter ablation. The purpose of this study is to evaluate continuous sequence (CS) as a complement to differential pacing.
Methods
Patients who underwent catheter ablation for typical atrial flutter were enrolled. After ablation, the CTI conduction block was evaluated by two maneuvers, DP and CS. With CS, the CTI conduction block was assessed with the recorded sequence of the diagnostic catheter positioned on the CTI lesion.
Results
Both maneuvers were performed in 98 patients. There were ten cases (10/98, 10.2%) where a discrepancy existed between the initial results of CS and DP. Additional ablations were performed, and the CTI bidirectional block was achieved in all patients with two maneuvers. During the median 24 months, there was no recurrence of typical atrial flutter, but it was identified as atrial tachycardia in five cases (5.1%).
Conclusion
DP could not always guarantee the bidirectional block of CTI. In 10.2% of patients with complete block identified by the DP maneuver, incomplete block was confirmed by the CS maneuver. CS, the simple maneuver, could be applied to compensate for the limitation of DP.
Experimental Evaluation of Alternative Water Softening Methods
Authors: Buljubašić Armin , Stuhli Vedran , Odobašić Amra
Published: February 2024

Water hardness and deposition of incrustation is a problem in households and industry. In this regard, several technologies have been developed with purpose of water softening and preventing deposition of incrustation. The ion exchange method is the most commonly used method and is considered a conventional method. However, due to the shortcomings of this method, other methods have predispositions for greater and wider application. A promising alternative approach to water softening is application of sorbents such as synthetic zeolites and biosorbents such as moss Leucobryum glaucum for the purpose of removing water hardness and application of electrochemical methods. In this study, three alternative methods were tested: water softening method with application of biosorbent, electrochemical scale removal method and water softening method with application of natural and artificial adsorbent, and a comparison was made with the conventional method and previously condusted studies on alternative water softening methods.
Comparing the efficacy and safety of cryoablation and microwave ablation in treating paravertebral metastases of rabbit VX2 tumor
Authors: Song Zhenzhen , Zhao Yanfen , Liu Zhu , Li Bing
Published: February 2024

Abstact
We sought to assess and compare the effectiveness and safety of cryoablation (CA) and microwave ablation (MWA) in treating paravertebral metastases of VX2 in rabbits. A rabbit VX2 paravertebral metastases model was established under computed tomography (CT) guidance, with a modeling success rate of 88.23% (60/68). Sixty successfully modeled rabbits were randomly allocated into the MWA group (n = 30) and CA group (n = 30). A comparative analysis between the CA and MWA groups included assessments of the complete ablation rate, operation time, post-ablation pain, and complication rate,.The complete ablation rate in the CA group (86.67%) was higher than that in the MWA group (63.33%) (P < 0.05), and the operation time in the CA group was notably longer than that in the MWA group (P < 0.05).The BRPS ( Bristol Rabbit Pain Scale) scores in both groups decreased at 5 time points after treatment, the post-treatment points scores in the CA group were lower than those in the MWA group (P <0.001). At a followe-up of 21 days postoperatively, the complication rate in the CA group (10.00%) was significantly lower than that in the MWA group (33.33%) (P < 0.05), with 6 rabbits in the MWA group experiencing severe complications. Compared to MWA, CA for paravertebral metastases demonstrates higher efficacy and safety.
A blended learning approach for capacity strengthening to improve the quality of integrated HIV, TB, and Malaria services during antenatal and postnatal care in LMICs: A feasibility study
Authors: Ladur Alice Norah , Egere Uzochukwu , Ravit Marion , Mgawadere Florence , Murray Christopher , White Sarah Ann , Mohammed Hauwa , Mutai Rael , Nyaga Lucy , Shikuku Duncan , Bashir Issak , Ayinde Olubunmi Olufunmilola , Bakar Rukia , Katalambula Leonard , Federici Carlo , Torbica Alexsandra , Furtado Nicholas , Ameh Charles
Published: February 2024

Background The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; 1) self-directed learning (16 hours) 2) facilitated virtual sessions (2.5 hours over 3 days) and 3) 2-day f2f sessions.Methods This study assessed the feasibility, change in healthcare providers' knowledge and costs of the BL package in Nigeria, Tanzania, and Kenya. A mixed methods design was used. A total of 89 healthcare professionals, were purposively selected. Quantitative data was collected through an online questionnaire and skills assessments, analyzed using STATA 12 software. Qualitative data was collected through key informant interviews and focus group discussions, analysed using thematic analysis.Results Majority of participants (86%) accessed the online sessions using a mobile phone from home and health facilities. The median (IQR) time of completing the self-directed component was 16 hours, IQR (8, 30). A multi-disciplinary team comprising of 42% nurse-midwives, 28% doctors, 20% clinical officers and 10% other healthcare professionals completed the BL course. Participants liked the BL approach due to its flexibility in learning, highly educative/relevant content, mixing of health worker cadres and CPD points. Aspects that were noted as challenging were related to personal log-in details and network connectivity issues during the self-directed learning and facilitated virtual sessions respectively.Conclusion The blended learning approach to ANC-PNC in-service training was found to be feasible, cost saving compared to the face-to-face approach and acceptable to health care professionals in LMICs.
Quantifying intratumoral heterogeneity within sub-regions to predict high-grade patterns in clinical stage I solid lung adenocarcinoma
Authors: Zuo Zhichao , Deng Jinqiu , Ge Wu , Zhou Yinjun , Liu Haibo , Zhang Wei , Zeng Ying
Published: February 2024

Background: This study aims to quantify intratumoral heterogeneity(ITH) using preoperative CT scans and evaluate its ability to predict pathological high-grade patterns, specifically micropapillary and/or solid components (MP/S), in patients diagnosed with clinical stage I solid lung adenocarcinoma (LADC).
Methods: In this retrospective study, 457 patients postoperatively diagnosed with clinical stage I solid LADC were included from two medical centers, comprising a training set (center 1, n=304) and a test set (center 2, n=153). Sub-regions within the tumor were identified using the K-means method. Both intratumoral ecological diversity features (hereafter referred to as ITH) and conventional radiomics (hereafter referred to as C-radiomics) were extracted to generate ITH scores and C-radiomics scores. Next, univariate and multivariate logistic regression analyses were employed to identify clinical-radiological (Clin-Rad) features associated with the MP/S (+) group for constructing the Clin-Rad classification. Subsequently, a hybrid model which presented as a nomogram was developed, integrating the Clin-Rad classification and ITH score. The performance of models was assessed using the receiver operating characteristic (ROC) curves, and the area under the curve (AUC), accuracy, sensitivity, and specificity were determined.
Results: The ITH score outperformed both C-radiomics scores and Clin-Rad classification, as indicated by higher AUC values in the training (0.820 versus 0.810 and 0.700) and test sets (0.805 versus 0.771 and 0.732), respectively. Notably, the hybrid model consistently demonstrated robust predictive capabilities in identifying MP/S (+), achieving AUCs of 0.830 in the training set and 0.849 in the test sets.
Conclusion: The ITH of sub-regions within the intratumor has been shown to be a reliable predictor for MP/S (+) in clinical stage I solid LADC. This finding holds the potential to make a significant contribution to clinical decision-making processes.
Markers of low field NMR relaxation features of tissues
Authors: Kołodziejski Karol , Masiewicz Elzbieta , Alamri Amnah , Zampetoulas Vasileios , Samuel Leslie , Murray Graeme , Lurie David J. , Broche Lionel M. , Kruk Danuta
Published: February 2024

This work presents an approach to exploiting Nuclear Magnetic Resonance (NMR) relaxometry data (1H spin-lattice relaxation rates covering the frequency range from below 1 kHz to 10 MHz) for the purpose of differentiating between pathological and reference tissues. Characteristic quantities (markers) that can be obtained in a straightforward manner, not resorting to an advanced analysis of 1H spin-lattice relaxation data, have been identified and compared for pathological and reference colon tissues. Moreover, the relaxation data have been parametrised in terms of Lorentzian spectral densities and the possibility of using the obtained dipolar relaxation constants and correlation times as biomarkers to assess the state of tissues has been discussed. It has also been demonstrated that the relaxation data for the reference and the pathological tissues can be attributed to two groups (for each case). The studies are a step towards exploiting the potential of NMR relaxometry for characterisation of pathological changes in tissues.
Toward a Roadmap for Sustainable Lean Hospital Adoption: A Delphi Study
Authors: Zyl-Cillié Maria M. Van , Dun Desirée H. Van , Meijer Hanneke
Published: February 2024

Background: The benefits of lean adoption in healthcare include improved process efficiency and quality of patient care. Research however indicates that lean implementation in healthcare and specifically hospitals is often not sustained. Furthermore, there is a need for maturity models that guide lean implementation specifically in hospitals. This study develops a prescriptive maturity model named the Sustaining of Lean Adoption in Hospitals Roadmap (SOLAR) that acts as a practical guideline for the sustainable adoption of lean in hospitals.
Methods: The SOLAR is based on three theoretical building blocks, namely the theory of lean implementation success factors in hospitals, implementation science, and change management theory. A systematic literature review was conducted to determine the lean implementation success factors in hospitals as the first building block. For the second building block, practices from implementation science were used to create the action items in the SOLAR. Ten change steps were elicited from change management theory as the third theoretical building block of the roadmap. We refined the roadmap through three Delphi rounds that verified the useability of our model in hospitals.
Results: The final SOLAR consists of four maturity phases (prepare, plan, experiment and learn, and sustain) and includes action items for each phase related to the hospital’s strategy, resources, engaging of people, and culture. The action items and change management steps shown in the SOLAR are notintended as an exhaustive list but provide guidelines on aspects one certainly needs to consider for a hospital that aims to adopt lean sustainably.
Conclusions: The strong theoretical base of the SOLAR enables hospitals to safely experiment and learn which implementation methods are best suited to their unique environment. The SOLAR is, therefore, an actionable guideline that informs both academics and practitioners involved in lean adoption in hospitals. This roadmap can guide future retrospective longitudinal or action research.
Specialized Deep Residual Policy Safe Reinforcement Learning-Based Controller for Complex and Continuous State-Action Spaces
Authors: Abbas Ammar N. , Chasparis Georgios C. , Kelleher John D.
Published: February 2024

Traditional controllers have limitations as they rely on prior knowledge about the physics of the problem, require modeling of dynamics, and struggle to adapt to abnormal situations. Deep reinforcement learning has the potential to address these problems by learning optimal control policies through exploration in an environment. For safety-critical environments, it is impractical to explore randomly, and replacing conventional controllers with black-box models is also undesirable. Also, it is expensive in continuous state and action spaces, unless the search space is constrained. To address these challenges we propose a specialized deep residual policy safe reinforcement learning with a cycle of learning approach adapted for complex and continuous state-action spaces. Residual policy learning allows learning a hybrid control architecture where the reinforcement learning agent acts in synchronous collaboration with the conventional controller. The cycle of learning initiates the policy through the expert trajectory and guides the exploration around it. Further, the specialization through the input-output hidden Markov model helps to optimize policy that lies within the region of interest (such as abnormality), where the reinforcement learning agent is required and is activated. The proposed solution is validated on the Tennessee Eastman process control.
Photoelectrochemical CO2 Reduction Devices Employing A Boundary Layer Flow for Direct Ocean Carbon Capture and Conversion
Authors: Hu Shu , Liu Bin , Qian Zheng , Shi Xiang , Su Haoqing , Zheng Yuze , He Chengxing , Yanagi Rito , Zhang Wentao , Kludze Atsu
Published: February 2024

The capture and utilization of the dissolved inorganic carbon in seawater, e.g., bicarbonates, is a promising strategy for accessing fuels on demand and anywhere. We report unbiased photoelectrochemical (PEC) CO2 reduction (CO2R) devices, which can facilitate sustainable sunlight-to-syngas conversion. However, there have been very few reports on the use of dissolved inorganic carbon for direct light-driven CO2 conversion to produce solar fuels. In this work, we design and implement 3D-printed PEC devices that employ a boundary layer flow. The flow over photoanode-photocathode pairs facilitates the efficient transport of in-situ generated CO2(aq), which is produced upstream at BiVO4 photoanodes, to downstream CO2R Si photocathodes. In flowing seawater, the solar-to-fuels (STF) efficiency improved from 0.4–0.71%, a record for PEC CO2R devices compared with BiVO4-Si systems operating in static bicarbonate electrolytes with continuous CO2 purging. Even in 2.3-mM HCO3− seawater, CO selectivity significantly increased from 3–21% with flow. The boundary layer flow confines the in-situ generated CO2(aq) to the surface of BiVO4 and Si photocathodes. Thus, an optimized flow field can increase the CO2(aq) and proton transport flux and simultaneously reduce the CO2(aq) residence time for its efficient utilization at Si photocathodes. Our process also features a high carbon efficiency: ~ 1 mmol CO2 is additionally released per 4 mmol CO produced.
Identification of TAT, PIC, tPAIC, and TM complex as biomarkers for prognosis and early evaluation of non-severe pneumonia and severe pneumonia diagnosis
Authors: Fan Yanru , Ma Rufei , Zhang Yuan , Hu Biao , Li Gang , Zhang Yujing , Gao Lan
Published: February 2024

Background Pneumonia is a major health problem and the most important causes of mortality in all age groups worldwide. We investigated new automation technology to detect plasma biomarkers, including thrombinantithrombin complex (TAT), α2-plasmininhibitor- plasmin complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC), and evaluated their diagnostic performance and prognostic value for severe pneumonia patients. Methods We collected 414 patients date with pneumonia. sTM, t-PAI·C, TAT, PIC were measured by qualitative chemiluminescence immunoassay performed on HISCL analyzers. Other laboratory tests were evaluated on the day of non-severe pneumonia and severe pneumonia diagnosis. Results There were significant differences in sTM, t-PAI·C, TAT, PIC (P < 0.0001), WBC (P = 0.023), PCT (P = 0.007) and IL-6 (P = 0.002) between the severe pneumonia and non-severe pneumonia groups, Logistic regression analysis showed that sTM (P = 0.001), t-PAI·C(P = 0.001), TAT(P = 0.022), PIC(P = 0.000) and APTT (P = 0.013) were independent risk factors for severe pneumonia. Logistic regression analysis showed that t-PAI·C(P = 0.006)was an independent risk factor for hospital mortality in severe pneumonia.The AUC of sTM combined with t-PAI·C, TAT and PIC on diagnosis of patients with severe pneumonia was 0.868 (95%CI: 0.837,0.899).Kaplan-Meier survival analysis with a log-rank test showed the in-hospital death rate of severe pneumonia was higher in the high TAT(≥ 5.58 ng/ mL) level than in group with low TAT(< 5.58 ng/ mL)level (log rank < 0.029). The same trend with high t-PAI·C was also found in severe pneumonia patients(log rank < 0.021). Conclusions Novel coagulation markers might be potential molecular markers for diagnosing and evaluating prognosis of severe pneumonia.
Electrophysiological Findings in Patients Undergoing Surgical Cryo-ablation for Treatment of Atrial Fibrillation
Authors: Bulava Alan , Mokráček Aleš , Němec Petr , Wichterle Dan , Osmančík Pavel , Budera Petr , Kačer Petr , Vetešková Linda , Skála Tomáš , Šantavý Petr , Chovančík Jan , Branny Piotr , Rizov Vitalii , Kolesár Miroslav , Šafaříková Iva , Rybář Marian
Published: February 2024

Objectives
Current recommendations support surgical treatment of atrial fibrillation (AF) in patients indicated for cardiac surgery. These procedures are referred to as concomitant and may be carried out using radiofrequency energy or cryo-ablation. This study aimed to assess the electrophysiological findings in patients undergoing concomitant cryo-ablation.
Methods
Patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement were included in the trial if concomitant cryo-ablation was part of the treatment plan according to current guidelines. The patients were assigned to undergo radiofrequency catheter ablation (RFCA), i.e., hybrid treatment, as a part of the multicenter trial.
Results
We analyzed 103 patients who underwent RFCA 105±35 days after surgery. Left and right pulmonary veins (PVs) were found isolated in 65 (63.1%) and 63 (61.2%) patients, respectively. The LA posterior wall isolation and mitral isthmus conduction block were found in 38 (36.9%) and 18 (20.0%) patients, respectively. Electrical reconnections (gaps) in the left PVs were more often localized superiorly than inferiorly (57.9% vs. 26.3%, P=0.005) and anteriorly than posteriorly (65.8% vs. 31.6%, P=0.003). Gaps in the right PVs were more equally distributed anteroposteriorly but dominated in superior segments (72.5% vs. 40.0%, P=0.003). There was a higher number of gaps on the roof line compared to the inferior line (131 (67.2%) vs. 67 (42.2%), P <0.001). Compared to epicardial cryo-ablation, endocardial was more effective in creating PVs and LA posterior wall isolation (P <0.05). Cryo-ablation using nitrous oxide (N20) or argon (Ar) gas as cooling agents was similarly effective (P=NS).
Conclusions
The effectiveness of surgical cryo-ablation in achieving transmural and durable lesions in the left atrium is surprisingly low. Gaps are located predominantly in the superior and anterior portions of the PVs and on the roof line. Endocardial cryo-ablation is more effective than epicardial ablation, irrespective of the cooling agent used.
Causal relationships between dietary habits and lung cancer: A two- sample Mendelian randomization study
Authors: Gu Pinchao , Zhu Zheng , Tan Xiaoyan , Deng Langlang , Ma Haitao
Published: February 2024

Background
Several studies have reported that dietary habits are associated with lung cancer (LUCA). However, the causal effects of dietary habits on LUCA incidence are still unclear because of uncontrolled confounding factors.
Methods
We obtained instrumental variables of associated with 5 genetically predicted dietary habits and applied two-sample Mendelian randomization (MR) to explore the causal effects of these variables on LUCA. In this study, inverse-variance weighting (IVW) was the main analysis, which was supplemented by MR‒Egger and the weighted median method.
Results
The IVW method revealed a causal relationship between never eating wheat products and an increased risk of LUCA (odds ratio (OR):1.032, 95% confidence interval (CI):1.005 ~ 1.059, P = 0.002 < 0.05). Eating eggs, dairy, wheat, and sugar was associated with a reduced risk of LUCA (OR = 0.967, 95% CI = 0.967 ~ 0.996, P = 0.014 < 0.05). No causal relationship was found between never eating sugar or foods/drinks containing sugar and LUCA (OR = 1.008, 95% CI = 0.989 ~ 1.027, P = 0.425 > 0.05). In addition, we used IVW and MR‒Egger to assess potential horizontal heterogeneity and pleiotropy, and no heterogeneity or pleiotropy occurred between the dietary variables and LUCA.
Conclusion
We found a positive association between never eating wheat products and LUCA scores. In addition, we found an inverse association between eating eggs, dairy, wheat, and sugar and LUCA scores. However, we found no evidence of a link between never eating sugar or foods/drinks containing sugar and LUCA in our MR results.
Combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma: Differentiation using radiomics based on Multitemporal CT images
Authors: Xu Rong , Guo Le , Chen Guanjun , Qi Rong Rong , Zhang Ling
Published: February 2024

Purpose: To investigate the value of radiomics in differentiating combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and hepatocellular carcinoma (HCC).
Materials and Methods: We retrospectively collected the clinical, serum biomarkers and imaging data of cHCC-CCA (n = 42) and HCC (n = 117) patients. The optimal radiomics features were extracted from CT plain scan, arterial phase, venous phase and delayed phase images for constructing radiomics models. The clinical model, radiomics model and fusion model were constructed by extreme gradient boosting (XGB), and the models were validated with an independent validation cohort. Area under curve (AUC), specificity, sensitivity and decision curve analysis (DCA) were used to evaluate the model efficacy.
Results: The fusion model based on CT radiomics performed the best, with an AUC of 0.969, which was superior to the clinical model (AUC=0.860) and the CT radiomics model (AUC=0.853). DCA showed that the fusion model had the highest clinical net yield compared to the other two models.
Conclusion: The fusion model based on CT radiomics has good performance in distinguishing cHCC-CCA from HCC, which can better assist in individualized clinical decision-making for patients with cHCC-CCA.
Single-cell transcriptomics reveals altered myeloid cell profiles associated with the early establishment of leishmania reservoirs
Authors: Estaquier Jerome , Picard Morgane , Boutrais Steven , Rodrigues Vasco , Fortier Yasmina , Borde Chloé , Soundaramourty Calaiselvy , Clain Julien , Beauparlant Charles Joly , Racine Gina , Zghidi-Abouzid Ouafa , Droit Arnaud , Pruvost Alain , Costi Maria , Silvestre Ricardo , Cordeiro-da-Silva Anabela , MacDougall Jane , André Sónia
Published: February 2024

Current drug regimens to treat visceral leishmaniasis (VL) are associated with a significant frequency of infection relapses, particularly in immunosuppressed patients. Understanding the cellular and tissue-specific persistence of Leishmania infantum post-treatment is crucial for improving therapeutic outcomes. Using a rhesus macaque model of VL, despite the administration of miltefosine (HePC) shortly after infection, L. infantum was detected in various tissues, including the spleen, bone marrow, and peripheral and mesenteric lymph nodes (LNs). Notably, lower HePC penetration in pLNs correlated with persistent parasites, culminating in mLNs relapse three months post-treatment. Our analysis of splenic neutrophils, monocytes/macrophages, and dendritic cells post-HePC treatment revealed parasite reservoirs. Single-cell transcriptomic analysis unveiled myeloid cell heterogeneity and indicated a correlation between the failure to eradicate parasites and incomplete immune cell restoration in the spleen. This study provides valuable insights for developing more effective treatments targeting parasite reservoirs that potentially may reduce relapses.