bluuebunny/crossref_metadata_2025 huggingface dataset:
Open Mitral Comissurotomy for Correction of Isolated Mitral Device
Authors: VV Popov ,   National Institute of Cardiovascular Surgery named after N.M. Amosov AMS of Ukraine, Kyiv, Ukraine, KV Pukas , OO Pankevych , VV Lazoryshynets ,   National Institute of Cardiovascular Surgery named after N.M. Amosov AMS of Ukraine, Kyiv, Ukraine,   National Institute of Cardiovascular Surgery named after N.M. Amosov AMS of Ukraine, Kyiv, Ukraine,   National Institute of Cardiovascular Surgery named after N.M. Amosov AMS of Ukraine, Kyiv, Ukraine
Published: July 2024

Objective: To study the possibilities of open mitral commissurotomy for isolated mitral correction. Methods: A retrospective analysis was conducted on group included 225 patients with MP who were undergoing surgical treatment at the National Institute of Cardiovascular Surgery named after N.M. Amosov of the Academy of Medical Sciences of Ukraine from January 1, 1981 to January 1, 2008. All patients underwent correction of the bladder using OMC (146), as well as in combination with other plastic surgeries on the bladder (79 patients), incl. application of a support ring, suture commissuroplasty, resection of the posterior leaflet. Due to LA thrombosis, thrombectomy was performed in 71 (31.6%) patients. Correction of tricuspid defect in the form of annuloplication according to N.M. Amosov-De Vega was performed in 69 (30.7%) patients. Paraannular plication of the posterior wall of the left atrium using the Kawazoe technique was performed in 2 (0.9%) cases. Results: Of the 225 operated patients in the hospital stage (within 30 days after surgery), none died. Neurological (transient) complications were noted in 3 (1.3%) patients. Stay in the intensive care unit for 38-56 hours. Patients were discharged on average 9-11 days after surgery without clinically significant complications. Conclusion: Open mitral commissurotomy is an adequate method of surgical correction of urinary tract with a minimal risk of fatal complications. The technique is applicable both in isolation and in combination with commissuroplasty and the application of a support ring. The low probability of developing thromboembolic complications in patients with thrombosis of the left atrium allows us to recommend OMC as the operation of choice for massive thrombosis of the left atrium.
Psychosocial Factors in the Safety Level in an Industrial Process: The Case Study of a Cement Producer
Authors: Acabado Romana Fernando ,   Department of Management Sciences, Atlântica University, Oeiras Municipality, Portugal, Valério Sandra Cristina , Gestoso Carlos Guillen , Fernandez , Silvia Gonzalez ,   Department of Health and Safety, CIMPOR, Portugal,   Master in Faculty of Human Motricity, University of Lisbon, Portugal,   Department of Management Sciences, Atlântica University, Oeiras Municipality, Portugal,   Department of Work Sciences, Cadiz University, Cadiz, Spain
Published: July 2024

Psychosocial risk factors are a major concern at European level, being the source of the increase in health complaints by workers, with implications in potential work-related accidents. Against this background, there was a need to study this subject. We propose, in this thesis, an analysis the relationship between working conditions and health and wellness perceived by workers. The study was conducted in three Portuguese cement plants, with a sample of 192 workers in manufacturing and maintenance areas. For data collection, it was used the INSAT inquiry. To process the data, it was used descriptive statistics and regression models to examine the association between working conditions and health and wellness. The results showed that some features of the work - relational and temporal aspects of work - are factors that affect negatively the worker’s health. The implementation of a safety culture, with a strong commitment from the leaders, constitutes a mean to reduce the effects of these factors on the worker’s health and daily lif
Odontogenic Peri-Mandibular Cellulitis in Adults : Clinical Profile and Treatment at Owendo University Hospital (CHUO)
Authors: AP Makungu ,   Department of Stomatology and Maxillofacial Surgery CHUO, Libreville, Gabon, MMSA Moupab , MMF Nimy
Published: July 2024

Introduction: Odontogenic peri-mandibular cellulitis is a serious, life-threatening infection of the celluloid tissues of the mandible. Our aim is to investigate the clinical and therapeutic profile of odontogenic peri-mandibular cellulitis in adults. Materials and methods: This is a retrospective, descriptive, monocentric study conducted at the Department of Stomatology and Maxillofacial Surgery from 2020 to 2022. Patients aged at least 18 years treated for odontogenic circumscribed perimandibular cellulitis were included. The following were excluded: diffuse cellulitis, maxillary cellulitis, records that could not be used. The following parameters were studied: socio-clinical data (age, sex, habits and lifestyle, factors contributing to cellulitis, consultation time, physical examination, puncture fluid); therapeutic data (treatment method, evolution). Results: 98 cases were collected, giving a prevalence of 15%. The mean age was 33.3 years. Men accounted for 54% of patients, with a sex ratio of 1.17. 53.1% of patients brushed their teeth once a day. 81.6% of patients were self-medicating with NSAIDs. 57.1% consumed alcohol and 90.8% consumed sweets. 48.0% of patients consulted between D4 and D7 for swelling. 48.0% of patients had submylohyoid cellulitis. 76% had a purulent collection. 60.2% received medical/surgical treatment compared to 39.8% who received medical treatment only. 60.2% of cases benefited from incisional drainage and 73.5% from mechanotherapy. The course was favourable in 83.7% of cases. Conclusion: Odontogenic peri-mandibular cellulitis is common and affects young male patients. NSAIDs are the main risk factor and swelling is the main mode of onset. Treatment is medical-surgical with a favourable outcome.
An Unusual Case of Cycloheximide-Resistant Aspergillus Candidus Onychomycosis
Authors: Oualhadj Hamza ,   Laboratory of parasitology-mycology, Avicenna hospital, Cadi Ayyad University, Marrakech, Morocco, Nachat Soumia , Mezouari Mustapha , Moutaj Redouane ,   Laboratory of parasitology-mycology, Avicenna hospital, Cadi Ayyad University, Marrakech, Morocco,   Laboratory of parasitology-mycology, Avicenna hospital, Cadi Ayyad University, Marrakech, Morocco,   Laboratory of parasitology-mycology, Avicenna hospital, Cadi Ayyad University, Marrakech, Morocco
Published: July 2024

Background: Onychomycosis, a common fungal infection of the nails, poses significant challenges in diagnosis and management, particularly with emerging opportunistic pathogens like Aspergillus candidus. We present a case of onychomycosis caused by cycloheximide-resistant A. candidus, underscoring the importance of heightened awareness and surveillance among medical mycology teams. Case presentation: A 63-year-old male with a history of chronic smoking and type 2 diabetes mellitus presented with lateral onycholysis of the right big toenail. Microscopic examination and culture revealed A. candidus, resistant to cycloheximide. Treatment involved chemical avulsion of the nail plate, systemic terbinafine, and topical amorolfine nail lacquer. Conclusion: Our report signifies the emergence of A. candidus as a significant causative agent of onychomycosis, particularly in individuals with predisposing comorbidities. Vigilance among medical mycology teams is crucial for tracking evolving epidemic trends and optimizing treatment approaches. Continued surveillance and reporting are essential for advancing our understanding and management of fungal infections in clinical practice.
A Fundamental Problem in Physics - (Mass vs Electric Charge)
Authors: Nguyen Hoa Van ,   Lecturer, School of Electrical Engineering, Computing and Mathematical Sciences, Curtin University, Perth, Australia
Published: July 2024

In modern physics there exist opposite concepts regarding the constancy and the variability of two major properties of the electron: its mass and its electric charge. Section 1: Mainstream physicists consider the mass of the electron as varying with its velocity while its electric charge as a fundamental constant of physics. Section 2: On the other hand, many other physicists maintain the opposite concept: the mass of the electron is invariant in all physical conditions while its electric charge is variable. Section 3: In the case when the mass is invariant, a mathematical expression for the variability of the electric charge of the electron in external fields will be deduced. Section 4: A thought experiment to demonstrate the variability of the electric charge of the electron in a changing magnetic field. Section 5: Discussions i) Why is the electric charge changed in external field? ii) Renormalizing the mass is problematic iii) Renormalizing the electric charge is innovative iv) The mystery of the mass of the muon v) The controversial concept of time dilation
Deep Learning in Drug Discovery: Current Landscape and Future Prospects
Authors: Liu Sensen ,   Washington Univeristy in St. Louis, St.Louis, MO, USA, Lin Yin-Shan ,   Northeastern University, Boston, MA, USA
Published: July 2024

Deep learning (DL) has emerged as a transformative technology in drug discovery, offering the potential to accelerate and optimize various stages of the drug development pipeline. While numerous reviews have summarized the broader landscape of machine learning (ML) in this field, this review focuses specifically on deep learning, highlighting its unique strengths and challenges. We examine the current state-of-the-art deep learning algorithms applied in drug discovery, categorizing them by their architectural designs and applications. We further identify emerging trends and potential areas for future research, emphasizing the need for continued exploration and innovation at the intersection of deep learning and drug discovery
Assessment of the effectiveness of the replacement of hip joints in patients with spondyloarthritis
Authors: Al-Lami M. A. D. ,   Kazan State Medical University of the Ministry of Health of Russia, Kazan, Russia, Akhtyamov I. F. , Nuriakhmetova T.Yu.. , Lapshina S.A. ,   Kazan State Medical University of the Ministry of Health of Russia, Kazan, Russia,   The Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan, Kazan, Russia,   Kazan State Medical University of the Ministry of Health of Russia, Kazan, Russia
Published: July 2024

The lesion of the hip joint with ankylosing spondylitis (AS) is an unfavorable prognostic sign and can lead to the endoprosthetics (EP) of the joint. Objective. to evaluate the results of the EP of the hip joints in patients with AS with joint dynamic observation by a rheumatologist and orthopedist during the first year after surgery. Materials and methods. The results of the EP of the hip joint of 120 patients in three groups of one central study were analyzed. The 1st and 2nd groups consisted of patients with ankylosing spondylarthrosis after endoprosthetics of the hip joint, but with various options for maintenance in terms of basic therapy, and the 3rd group with coxsartrosis after planned replacement of the joint. Dynamic observation by the rheumatologist and orthopedist was carried out before the operation, after the operation, after 6 and 12 months. Results. The effectiveness of arthroplasty of large joints with a reliable (p <0.05) decrease in pain (VAS) in the first month after EP, improving functional capacity (BASFI) and a decrease in ASDAS (ASDAS) after 6 and 12 months after EP. There were no complications after the operation. A clinical example of a patient with a severe course of ankylosing spondylitis and the effectiveness of arthroplasty is presented. Conclusion. EP of the hip joints in patients with spondiloarthritis is effective not only in terms of improving the functional ability and removing pain, but also to reduce the activity of the disease as a whole
Identification of the Effect of Concrete Carbonation on the Strength of Cooling Tower Structures Using the Monte Carlo Simulation Method
Authors: Supiyat Agus , Biantoro Agung Wahyudi
Published: July 2024

Cooling Tower buildings are examples of construction that is directly exposed to adverse weather conditions that cause concrete damage in the form of carbonation. damage such as concrete cover spalling, cracks on the surface of concrete walls, and corrosion of reinforcement, Conditions like this need to be handled seriously because they have an impact on the structural safety factor of the building. This study aims to determine the effect of carbonation on the concrete structure of the Geothermal Power Plant Cooling Tower Building on Mount Salak which has experienced degradation of concrete quality due to carbonation. Concrete Analysis method to determine the relationship of the effect of carbonation on concrete strength in the Cooling Tower structure uses Monte Carlo simulation method based on measurements of concrete cover and carbonation depth. Monte Carlo simulation results to estimate the carbonation rate of concrete showed an average of 2.4 cm per year for a simulation period of 25 years. The average carbonation of concrete obtained from probability is 2.28. By repeating the simulation, an average value close to the estimate will be obtained from the coefficient of determination test results of 48.1%. The effect exerted by concrete quality on concrete carbonation is negative, meaning that better concrete quality will reduce concrete carbonation.
Effectiveness of Using Short Movies to Improve Vocabulary Mastery
Authors: Ail Lailatussholichah , Ria Kamilah Agustina
Published: July 2024

The objective of this research is to find out whether or not the implementation of short movies media effective to improve the students’ vocabulary mastery. The researcher conducted a pre-experimental group design. The population of this research is the seveth-grade students of SMP A. Wahid Hasyim Tebuireng Jombang in the academic year 2023/2024. Total of the population was 9 classes. The sample in this study was class VII H SMP A. Wahid Hasyim Tebuireng Jombang, totaling 32 students. Based on the data normality test that has been carried out by the researcher, it shows that sig. 2-tailed is 0.200 meaning that the data is normally distributed, then it will be continued with a simple paired t-test. based on the Testing of Hypothesis Terms, If the score of t is sig. <0.05, Ha is accepted and H0 is rejected. on the simple paired t-test calculation, the data shows sig. (2-tail) 0.000. The data is smaller than 0.05, meaning that H0 is rejected and Ha is accepted. the students' scores of pre-test was in medium level, while in post-test, the students' score was high. it could be concluded that the short movies was effective to improve students' vocabulary mastery in SMP A. Wahid Hasyim Tebuireng Jombang.
Content Analysis of Character Education in “English for Nusantara” Textbook for Seventh Grade Students
Authors: Sari Fadilla Zulfia , Ma’rifatulloh Sayid
Published: July 2024

The objective of this research is to find out whether character education in the "English for Nusantara" textbook for seventh-grade students is in accordance with the current curriculum. This research analyzed character education contained in the reading and conversational texts of the textbook. The research methodology used a descriptive qualitative approach and content analysis technique. The characters found in the textbook were classified into six dimensions of the Pancasila Student Profile. The results showed that the six dimensions of the Pancasila Student Profile were found. The dimension of having faith, fear of God Almighty, having a noble character 33.2%, global diversity 12.9%, mutual cooperation 16.7%, independent 20.4%, critical reasoning 7.5%, and creative 9.3%. In the six dimensions of the Pancasila Student Profile, which have 20 elements, only 19 were found, while one element that was not found was intercultural communication and interaction. The characters in this book are mostly integrated implicitly. The primary focus dimension of the “English for the Nusantara” textbook was having faith, fear of God Almighty, and having noble character. In addition, the main focus element in this textbook was the manner towards others. Based on the classification of character education stated by Prismarani (2014), this textbook scored 95% and was classified as ‘very high’ quality.
إستراتجة تقديم القصة لترقية مهارة الكلام في المعهد السلفي حملة القرءان جوكوراطا جومبانج
Authors: Maulaya Muhammad Dzikru Alfin , Ubaidillah Burhanuddin
Published: July 2024

Speaking skill is one of the language skills taught to students in learning the Arabic language. Speech is the main tool for building understanding and communication through the means of language. This speech activity is what stimulates the linguistics class, but it is often the opposite. The process of speech does not stimulate the situation and then finally stagnates. This causes students to be weak in mastering vocabulary and beautiful patterns.The method of this research is qualitative research with a qualitative descriptive approach, data obtained through observation, interview, and documentation, so that the data collected is in the form of information that is analyzed through data reduction, data analysis, and drawing conclusions. The results of this research can be summarized as follows: (1) The teaching step is to present the story Telling using the teacher’s direct method in order to enable the students to understand and master the Arabic language to the fullest extent, especially with regard to speaking skills. The goal is for students to master the material provided, including: choose an appropriate story, understand story structure, practice pronunciation and intonation, practice speaking, discuss the story, role-play and entertain, and create their own stories.(2) The Learning strategy of presenting the story is a powerful tool to improve the learning of students of the Boarding School Salafiyah “Hamalatul Qur’an” Jogoroto Jombang for the following reasons: emotional engagement, increased understanding, development of speaking and listening skills, strengthening moral values, stimulating creativity, richer use of language, and thus strengthening cultural connections. Story presentation can be an effective tool to enhance the learning experiences of students at various levels of education.
Do patients with suicidal ideation differ from those with suicidal behavior in sociodemographic and clinical variables?
Authors: Aliño Maria , Sánchez-Reolid Daniel , Montes María Jesús , Fernández-Caballero Antonio , Fernández-Sotos Patricia , Ricarte Jorge Javier
Published: July 2024

This observational, analytical, cross-sectional, and prospective study (n=64) di#erentiates sociode-mographically and clinically between two groups (SI and SB) aiming to establish patient pro!les. Unma-rried women aged 33.39 years (SI) and 28 years (SB), urban residents without children, often students or workers in less specialized roles, identi!ed as midd-le class. More than 60% of the SI and 83% of the SB received psychopharmacological treatment and outpatient care but were never hospitalized. SI pre-sented onset of suicidal ideation at 26, SB at 23, with 62% of SB before the age of 18. 86.4% of SI and 90% of SB lacked family history of suicide, however, 80% of SI had a family history of mental illness versus 36% of SB. Planning and ideation before attempts increa-sed the risk of severity. Our !ndings underscore the need for speci!c prevention and intervention for this population.
"Manual de promoción de la resiliencia infantil y adolescente" Rodríguez Muñoz, M. de la F., Morell, J. M. y Fresneda, J. (2015)
Authors: Martin-Barrado Antonio-David
Published: July 2024

Reseña de manual
¿Es posible seguir viviendo después de situaciones traumáticas? ¿La resiliencia depende de la genética o del aprendizaje social? ¿Se puede educar en resiliencia? Estos y otros muchos interrogantes se resuelven a lo largo de las 344 páginas que componen el Manual de promoción de la resiliencia infantil y adolescente.
Rodríguez Muñoz, M. de la F., Morell, J. M. & Fresneda, J. (2015). Manual de promoción de la resiliencia infantil y adolescente. Pirámide.
Construct Validity Study of the Turkish Form of the Short Beck Depression Inventory
Authors: Ozdemir Hatice Deniz , Dagdeviren Hamdi Nezih
Published: July 2024

Aim: The main purpose of this study is to conduct a structural, and criterion-related validity study of the Short Beck Depression Inventory and to make it available for use by healthcare professionals and individuals conducting research in the field.

Method: Designed as a cross-sectional scale adaptation study, this research utilized the 21-item Beck Depression Inventory, the Short Beck Depression Inventory, and the Self-Compassion Scale. Data of the study were collected through Google Forms using extensions transmitted via email and WhatsApp.

Results: The mean age of the 178 participants was 21.09±2.12. The statistical findings in the confirmatory factor analysis of the Short Beck Depression Inventory, the X2/DF (23.68/13); the ratio was found to be 1.82, Root Mean Square Error of Approximation: 0.068, Standardized Root Mean Square Residual: 0.046, Root Mean Square Residual: 0.027, Normed Fit Index: 0.95, Non-Normed Fit Index: 0.97, Comparative Fit Index: 0.98, Incremental Fit Index: 0.98, Relative Fit Index: 0.93, and Goodness of Fit Index: 0.96. In the criterion-related validity study, a relationship was observed between the Short Beck Depression Inventory and the Beck Depression Inventory and between the Self-Compassion Scale.

Conclusion: Upon examining the outcomes of the inventory's confirmatory factor analysis, it was found that all fit indices were within the excellent fit range. The Turkish adaptation of the Short Beck Depression Inventory was concluded to be a highly valid and reliable scale that can be used in clinical settings and research in the adult Turkish population.

Keywords: depression, factor analysis, self-compassion
A novel polymer platform for endoscopic tattooing with high efficacy and safety
Authors: Zhang Liang , Jiang Mengni , Chen Zheng , Zhang Xinyuan , An Wei , Wang Shige , Zhao Jiulong
Published: July 2024

Endoscopic tattooing plays a pivotal role in modern endoscopic localization of gastrointestinal lesions, facilitating further surgical intervention and aiding in the postoperative identification and repositioning of lesions. However, traditional endoscopic tattoo dyes often suffer from drawbacks such as side effects, short tattoo duration, and high overall costs. In this study, we developed polyvinylpyrrolidone (PVP)-modified polypyrrole (PPy) nanoparticles by oxidizing pyrrole in a PVP aqueous solution to create a PPy/PVP nanoparticle solution. This innovation aims to enhance endoscopic tattooing efficiency and mitigate the limitations associated with current tattooing methods. Both in vitro and in vivo evaluations confirmed the biosafety of PPy/PVP nanoparticles. Endoscopic tattooing experiments conducted in a pig model demonstrated the dye’s stability within the digestive tract. Similarly, subcutaneous tissue tattooing experiments performed in a mouse model revealed the sustained stability of the PPy/PVP tattoo dye for at least 180 days. With its robust stability, safety, and longevity, PPy/PVP nanoparticles hold promise as novel tattoo dyes for marking intestinal lesion sites. This advancement has the potential to enhance the accuracy of lesion localization and long-term tracking.
11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis
Authors: Mahida Rahul Y. , Yuan Zhengqiang , Kolluri Krishna K. , Scott Aaron , Parekh Dhruv , Hardy Rowan S. , Matthay Michael A. , Perkins Gavin D. , Janes Sam M. , Thickett David R.
Published: July 2024

Background

Human bone marrow mesenchymal stem cell (MSC) administration reduces inflammation in pre-clinical models of sepsis and sepsis-related lung injury, however clinical efficacy in patients has not yet been demonstrated. We previously showed that Alveolar Macrophage (AM) 11β-hydroxysteroid dehydrogenase type-1 (HSD-1) autocrine signalling is impaired in critically ill sepsis patients, which promotes inflammatory injury. Administration of transgenic MSCs (tMSCs) which overexpress HSD-1 may enhance the anti-inflammatory effects of local glucocorticoids and be more effective at reducing inflammation in sepsis than cellular therapy alone.

Methods

MSCs were transfected using a recombinant lentiviral vector containing the HSD-1 and GPF transgenes under the control of a tetracycline promoter. Thin layer chromatography assessed HSD-1 reductase activity in tMSCs. Mesenchymal stem cell phenotype was assessed by flow cytometry and bi-lineage differentiation. HSD-1 tMSCs were co-cultured with LPS-stimulated monocyte-derived macrophages (MDMs) from healthy volunteers prior to assessment of pro-inflammatory cytokine release. HSD-1 tMSCs were administered intravenously to mice undergoing caecal ligation and puncture (CLP).

Results

MSCs were transfected with an efficiency of 91.1%, and maintained an MSC phenotype. Functional HSD-1 activity was demonstrated in tMSCs, with predominant reductase cortisol activation (peak 8.23 pM/hour/100,000 cells). HSD-1 tMSC co-culture with LPS-stimulated MDMs suppressed TNFα and IL-6 release. Administration of transgene activated HSD-1 tMSCs in a murine model of CLP attenuated neutrophilic inflammation more effectively than transgene inactive tMSCs (medians 0.403 v 1.36 × 106/ml, p = 0.033).

Conclusion

The synergistic impact of HSD-1 transgene expression and MSC therapy attenuated neutrophilic inflammation in a mouse model of peritoneal sepsis more effectively than MSC therapy alone. Future studies investigating the anti-inflammatory capacity of HSD-1 tMSCs in models of sepsis-related direct lung injury and inflammatory diseases are required.
Implications of lncRNAs in Helicobacter pylori-associated gastrointestinal cancers: underlying mechanisms and future perspectives
Authors: Zhang Lei , Yu Fei , Zhang Yue , Li Peifeng
Published: July 2024

Helicobacter pylori (H. pylori) is a harmful bacterium that is difficult to conveniently diagnose and effectively eradicate. Chronic H. pylori infection increases the risk of gastrointestinal diseases, even cancers. Despite the known findings, more underlying mechanisms are to be deeply explored to facilitate the development of novel prevention and treatment strategies of H. pylori infection. Long noncoding RNAs (lncRNAs) are RNAs with more than 200 nucleotides. They may be implicated in cell proliferation, inflammation and many other signaling pathways of gastrointestinal cancer progression. The dynamic expression of lncRNAs indicates their potential to be diagnostic or prognostic biomarkers. In this paper, we comprehensively summarize the processes of H. pylori infection and the treatment methods, review the known findings of lncRNA classification and functional mechanisms, elucidate the roles of lncRNAs in H. pylori-related gastrointestinal cancer, and discuss the clinical perspectives of lncRNAs.
MDSCs use a complex molecular network to suppress T-cell immunity in a pulmonary model of fungal infection
Authors: Kaminski Valéria Lima , Borges Bruno Montanari , Santos Bianca Vieira , Preite Nycolas Willian , Calich Vera Lucia Garcia , Loures Flávio Vieira
Published: July 2024

Background

Paracoccidioidomycosis (PCM) is a systemic endemic fungal disease prevalent in Latin America. Previous studies revealed that host immunity against PCM is tightly regulated by several suppressive mechanisms mediated by tolerogenic plasmacytoid dendritic cells, the enzyme 2,3 indoleamine dioxygenase (IDO-1), regulatory T-cells (Tregs), and through the recruitment and activation of myeloid-derived suppressor cells (MDSCs). We have recently shown that Dectin-1, TLR2, and TLR4 signaling influence the IDO-1-mediated suppression caused by MDSCs. However, the contribution of these receptors in the production of important immunosuppressive molecules used by MDSCs has not yet been explored in pulmonary PCM.

Methods

We evaluated the expression of PD-L1, IL-10, as well as nitrotyrosine by MDSCs after anti-Dectin-1, anti-TLR2, and anti-TLR4 antibody treatment followed by P. brasiliensis yeasts challenge in vitro. We also investigated the influence of PD-L1, IL-10, and nitrotyrosine in the suppressive activity of lung-infiltrating MDSCs of C57BL/6-WT, Dectin-1KO, TLR2KO, and TLR4KO mice after in vivo fungal infection. The suppressive activity of MDSCs was evaluated in cocultures of isolated MDSCs with activated T-cells.

Results

A reduced expression of IL-10 and nitrotyrosine was observed after in vitro anti-Dectin-1 treatment of MDSCs challenged with fungal cells. This finding was further confirmed in vitro and in vivo by using Dectin-1KO mice. Furthermore, MDSCs derived from Dectin-1KO mice showed a significantly reduced immunosuppressive activity on the proliferation of CD4+ and CD8+ T lymphocytes. Blocking of TLR2 and TLR4 by mAbs and using MDSCs from TLR2KO and TLR4KO mice also reduced the production of suppressive molecules induced by fungal challenge. In vitro, MDSCs from TLR4KO mice presented a reduced suppressive capacity over the proliferation of CD4+ T-cells.

Conclusion

We showed that the pathogen recognition receptors (PRRs) Dectin-1, TLR2, and TLR4 contribute to the suppressive activity of MDSCs by inducing the expression of several immunosuppressive molecules such as PD-L1, IL-10, and nitrotyrosine. This is the first demonstration of a complex network of PRRs signaling in the induction of several suppressive molecules by MDSCs and its contribution to the immunosuppressive mechanisms that control immunity and severity of pulmonary PCM.
The immunoregulatory role of gut microbiota in the incidence, progression, and therapy of breast cancer
Authors: Xue Kaiyang , Li Jiawei , Huang Ruijie
Published: July 2024

Breast cancer (BrCa) is the most prevalent malignant tumor in women and one of the leading causes of female mortality. Its occurrence and progression are influenced by various factors, including genetics, environment, lifestyle, and hormones. In recent years, the gut microbiota has been identified as a significant factor affecting BrCa. The gut microbiota refers to the collective population of various microorganisms in the human gastrointestinal tract. Gut microbiota is closely associated with human health and disease development, participating in crucial physiological functions such as digestion, metabolism, immune response, and neural regulation. It has been found to influence the occurrence and treatment of BrCa through a variety of mechanisms. This article aims to review the immunomodulatory role of the gut microbiota in the development and treatment of BrCa.
Winning space for conservation: the growth of wildlife conservancies in Kenya
Authors: Bashir Munira Anyonge , Wanyonyi Edwin
Published: July 2024

Kenya’s conservation areas consist of national parks and reserves, national forests, and private and community wildlife conservancies. The historically protected areas only account for 10% of Kenya’s land mass (national parks, reserves, and protected forests). Conserving Kenya’s biodiversity referred to as a “national heritage” is at the core of the country’s conservation agenda. The success of Kenya’s model of free-ranging wildlife is based on allowing as much unhindered movement and distribution of wildlife as possible. However, the human population increase, along with the expansion of agriculture into arid lands and the impacts of climate change, has affected the dynamics of pastoralism, where increased competition for natural resources has escalated in some areas. One of the identified measures to mitigate the current challenges is to increase the space for conservation and provide incentives for communities to conserve. The development and growth of the wildlife conservancy movement in Kenya have been a prominent response. As of 2023, there have been 230 wildlife conservancies in Kenya totaling 9.04 million ha and comprising 16% of Kenya’s total land mass (with 195 being members of the Kenya Wildlife Conservancies Association). To contribute to the global target of protecting 30% of lands, freshwaters, and oceans by 2030, the Kenyan Government considers the expansion of the number and area of wildlife conservancies as an important mechanism to achieve these targets. Here, we discuss Kenya’s wildlife conservancies from legal and policy perspectives, the factors that have enabled their growth, the challenges they face, and the opportunities ahead.
Patient-specific in silico 3D coronary model in cardiac catheterisation laboratories
Authors: Lashgari Mojtaba , Choudhury Robin P. , Banerjee Abhirup
Published: July 2024

Coronary artery disease is caused by the buildup of atherosclerotic plaque in the coronary arteries, affecting the blood supply to the heart, one of the leading causes of death around the world. X-ray coronary angiography is the most common procedure for diagnosing coronary artery disease, which uses contrast material and x-rays to observe vascular lesions. With this type of procedure, blood flow in coronary arteries is viewed in real-time, making it possible to detect stenoses precisely and control percutaneous coronary interventions and stent insertions. Angiograms of coronary arteries are used to plan the necessary revascularisation procedures based on the calculation of occlusions and the affected segments. However, their interpretation in cardiac catheterisation laboratories presently relies on sequentially evaluating multiple 2D image projections, which limits measuring lesion severity, identifying the true shape of vessels, and analysing quantitative data. In silico modelling, which involves computational simulations of patient-specific data, can revolutionise interventional cardiology by providing valuable insights and optimising treatment methods. This paper explores the challenges and future directions associated with applying patient-specific in silico models in catheterisation laboratories. We discuss the implications of the lack of patient-specific in silico models and how their absence hinders the ability to accurately predict and assess the behaviour of individual patients during interventional procedures. Then, we introduce the different components of a typical patient-specific in silico model and explore the potential future directions to bridge this gap and promote the development and utilisation of patient-specific in silico models in the catheterisation laboratories.
Change in left ventricular function and outcomes following high-risk percutaneous coronary intervention with Impella-guided hemodynamic support
Authors: Farhan Serdar , Freilich Michael , Giustino Gennaro , Vogel Birgit , Baber Usman , Sartori Samantha , Kamran Haroon , Mehran Roxana , Dangas George , Krishnan Prakash , Kini Annapoorna , Sharma Samin K.
Published: July 2024

Introduction

High-risk percutaneous coronary interventions (HRPCI) are a potential treatment option for patients with reduced left ventricular ejection fraction (LVEF) and coronary artery disease. The extent to which such intervention is coupled with improvement in LVEF and associated with favorable outcomes is unknown.

Methods

We aimed to characterize the incidence and correlates of LVEF improvement after Impella-guided HRPCI, and compare clinical outcomes in patients with versus without LVEF improvement. Data on consecutive patients undergoing Impella-guided HRPCI from a single center registry were analyzed. LVEF-improvement was defined as an absolute increase of LVEF of ≥10% measured at ≥30‐days after intervention. The primary outcome was a composite of all‐cause death, myocardial infarction or target vessel revascularization within 1-year.

Results

Out of 161 consecutive patients undergoing Impella-guided HRPCI from June 2008 to December 2017, 43% (n = 70) demonstrated LVEF-improvement (baseline LVEF of 25.09 ± 6.19 to 33.30 ± 11.98 post intervention). Patients without LVEF-improvement had higher frequency of previous MI (61.5% vs. 37.1%, p = 0.0021), Q-waves on ECG (17.6% vs. 5.7%, p = 0.024) and higher SYNTAX scores (30.8 ± 17.6 vs. 25.2 ± 12.2; p = 0.043). After correction of these confounders by multivariable analysis, no significant differences were found regarding the composite endpoint in patients with versus without LVEF-improvement (34.9% vs. 38.3%; p = 0.48).

Discussion

In this single-center retrospective analysis, we report the following findings. First, LVEF improvement of at least 10% was documented in over 40% of patients undergoing Impella supported high-risk PCI. Second, a history of MI, Q-waves on admission ECG, and higher baseline SYNTAX scores were independent correlates of no LVEF improvement. Third, one year rates of adverse CV events were substantial and did not vary by the presence or absence of LVEF improvement Prospective studies with longer follow-up are needed to elucidate the impact of LVEF improvement on clinical outcomes.
Dormant season warming amplifies daytime CO2 emissions from a temperate urban salt marsh
Authors: Vieillard Amanda M. , Girguis Peter , Fulweiler Robinson W.
Published: July 2024

Salt marshes provide many important ecosystem services, key among them being carbon sequestration. However, a large degree of uncertainty remains in salt marsh carbon budgets, particularly during colder months of the year when salt marsh microbial and vegetative activity is assumed to dormant. We also lack data on urban systems. In this study, we used an easily portable carbon dioxide sensor package to directly measure net carbon dioxide (CO2) fluxes throughout the winter in a temperate, urban salt marsh. We sampled across the dormant season both on normal (cold) temperature days and on days that were anomalously warm (defined here as air temperatures 2.8°C above the long-term average). We demonstrated that median (±mad) daytime CO2 fluxes doubled on the warm days, compared to cold days (1.7 ± 2 mmol m−2 h−1, 0.7 ± 1.3 mmol m−2 h−1, respectively). We also show that net CO2 emissions scaled with soil temperature. The high day-to-day variability, however, implies that infrequent or sparse measurements cannot sufficiently capture the temporal dynamics of dormant season salt marsh net CO2 fluxes. The magnitude of the net CO2 source from our sampling during the dormant season leads us to hypothesize that, as mean annual temperatures continue to increase, dormant season CO2 emissions from salt marshes will increasingly offset growing season carbon dioxide uptake. This change compromises the carbon sequestration capacity, and therefore the climate mitigation potential of these ecosystems. Future studies should focus on quantifying the impact of dormant season CO2, and other greenhouse gases on salt marsh carbon budgets.
Diversity of fungi associated with petroglyph sites in the Negev Desert, Israel, and their potential role in bioweathering
Authors: Rabbachin Laura , Nir Irit , Waldherr Monika , Vassallo Ylenia , Piñar Guadalupe , Graf Alexandra , Kushmaro Ariel , Sterflinger Katja
Published: July 2024

The petroglyphs of the Negev Desert, Israel, are famous and valuable archaeological remains. Previous studies have investigated the microbial communities associated with petroglyphs and their potential role in stone deterioration; nevertheless, the role of fungi remains unclear. In this study, the fungal communities present on the stone and, as a comparison, in the surrounding environment (soil and air) at Negev petroglyph sites were analyzed by means of culture-dependent and -independent (metagenomic) techniques. The metagenomic results showed a high fungal biodiversity in the soil, and both approaches highlighted the prevalence of species producing melanized, large, thick-walled spores (mainly Alternaria spp.). From the air sampling, mostly Cladosporium spp. were retrieved. On the other hand, on the rock, the results seem to indicate a low presence of fungi, but with a rock-specialized mycobiota consisting of extremotolerant microcolonial fungi (MCF) (e.g., Vermiconidia and Coniosporium) and lichens (Flavoplaca). In addition, low proportions of cosmopolitan fungi were detected on the stone, but the comparison of the data clearly indicates that they are transients from the surrounding environment. The ability of the isolated strains to dissolve CaCO3 and therefore be a potential threat to the petroglyphs (limestone substrate) was tested, but only one strain resulted in positive acid production under laboratory conditions. Nevertheless, both lichens and MCF detected in this study are well-known stone deteriogens, which may have a significant impact on the petroglyph’s deterioration.
Single-cell atlas of rainbow trout peripheral blood leukocytes and profiling of their early response to infectious pancreatic necrosis virus
Authors: Perdiguero Pedro , Jiménez-Barrios Pablo , Morel Esther , Abós Beatriz , Tafalla Carolina
Published: July 2024

The recent development of single cell sequencing technologies has revolutionized the state-of-art of cell biology, allowing the simultaneous measurement of thousands of genes in single cells. This technology has been applied to study the transcriptome of single cells in homeostasis and also in response to pathogenic exposure, greatly increasing our knowledge of the immune response to infectious agents. Yet the number of these studies performed in aquacultured fish species is still very limited. Thus, in the current study, we have used the 10x Genomics single cell RNA sequencing technology to study the response of rainbow trout (Oncorhynchus mykiss) peripheral blood leukocytes (PBLs) to infectious pancreatic necrosis virus (IPNV), an important trout pathogen. The study allowed us to obtain a transcriptomic profile of 12 transcriptionally distinct leukocyte cell subpopulations that included four different subsets of B cells, T cells, monocytes, two populations of dendritic-like cells (DCs), hematopoietic progenitor cells, non-specific cytotoxic cells (NCC), neutrophils and thrombocytes. The transcriptional pattern of these leukocyte subpopulations was compared in PBL cultures that had been exposed in vitro to IPNV for 24 h and mock-infected cultures. Our results revealed that monocytes and neutrophils showed the highest number of upregulated protein-coding genes in response to IPNV. Interestingly, IgM+IgD+ and IgT+ B cells also upregulated an important number of genes to the virus, but a much fainter response was observed in ccl4+ or plasma-like cells (irf4+ cells). A substantial number of protein-coding genes and genes coding for ribosomal proteins were also transcriptionally upregulated in response to IPNV in T cells and thrombocytes. Interestingly, although genes coding for ribosomal proteins were regulated in all affected PBL subpopulations, the number of such genes transcriptionally regulated was higher in IgM+IgD+ and IgT+ B cells. A further analysis dissected which of the regulated genes were common and which were specific to the different cell clusters, identifying eight genes that were transcriptionally upregulated in all the affected groups. The data provided constitutes a comprehensive transcriptional perspective of how the different leukocyte populations present in blood respond to an early viral encounter in fish.
First-line treatments for extensive-stage small-cell lung cancer with immune checkpoint inhibitors plus chemotherapy: a China-based cost-effectiveness analysis
Authors: Yi Lidan , Zhou Zhen , Zeng Xiaohui , Tan Chongqing , Liu Qiao
Published: July 2024

Objective

To determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China.

Methods

Using a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model.

Results

In the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model.

Conclusion

In China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective.
Association of the Scottish inflammatory prognostic score with treatment-related adverse events and prognosis in esophageal cancer receiving neoadjuvant immunochemotherapy
Authors: Zhao Qiang , Wang Liang , Yang Xun , Feng Jifeng , Chen Qixun
Published: July 2024

Background

To investigate the relationship between the Scottish inflammatory prognostic score (SIPS), treatment-related adverse events (TRAEs), and prognostication in patients with neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESCC).

Methods

A retrospective investigation was carried out on 208 ESCC patients treated with NICT. The relationships between the SIPS, TRAEs, and prognosis [disease-free survival (DFS) and overall survival (OS)] were analyzed.

Results

The patients, comprising 62 (29.8%) cases of SIPS0, 103 (49.5%) cases of SIPS1, and 43 (20.7%) cases of SIPS2, were categorized into three groups based on SIPS. Among patients with SIPS2, the oldest age (P=0.006), lowest BMI (P=0.001), longest tumor length (P=0.001), most advanced ypT stage (P=0.014), and ypN stage (P<0.001) were identified. Pathological complete response (PCR) rates showed statistically significant variations between the three groups (SIPS0: 45.2%, SIPS1: 27.2%, SIPS2: 16.3%, P=0.004). All TRAEs were found in 63.9% (133 cases) of the cases, with serious TRAEs (grade 3-4) accounting for 13.9% (29 cases). TRAEs themselves were not linked with SIPS (P=0.668), while serious TRAEs had a significant correlation with SIPS (P=0.002). Multivariate logistic analysis showed that SIPS2 seemed to confer serious TRAEs [odds radio (OR)=4.044; 95% CI: 1.395-11.722; P=0.010]. For patients classified as SIPS0, 1, or 2, the 3-year DFS was 83.9%, 58.3%, and 39.5% (P<0.001). The 3-year OS for those with SIPS0, 1, or 2 was 88.7%, 72.8%, and 53.5%, respectively (P<0.001). SIPS was substantially correlated with DFS (but not with OS) and could be utilized as an independent predictor [SIPS2: hazard ratio (HR)=3.743, 95% CI: 1.770-7.914, P=0.001; SIPS1: HR=2.303, 95% CI: 1.149-4.616, P=0.019].

Conclusion

The SIPS is associated with serious TRAEs and can be used as a predictor of serious TRAEs in ESCC receiving NICT. SIPS may be employed for pretreatment assessment since it was found to be substantially correlated with DFS.