bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Antara Tuberkulosis Paru dengan Terjadinya Kelainan pada Jaringan Lunak Rongga Mulut Berdasarkan Lama Pengobatan
Authors: Parmasari Wahyuni Dyah
Published: May 2024

Pendahuluan: Tuberkulosis adalah penyakit infeksi utama tertinggi penyebab kematian, yaitu kurang lebih tiga juta kasus setiap tahunnya. Penyakit tuberkulosis paru dikarenakan bakteri Mycobacterium tuberculosis. Penderita tuberculosis dapat menunjukkan gejala klinis di rongga mulut, merupakan manifestasi sekunder dari tuberkulosis paru. Manifestasinya berupa ulcer, gingival enlargement dan glossitis tuberkulosa. Tujuan Penelitian: untuk mengetahui apakah ada hubungan tuberkulosis paru dengan terjadinya kelainan pada jaringan lunak rongga mulut berdasarkan lama pengobatan. Bahan dan Metode: Penelitian ini menggunakan metode observatif analitik dengan populasi pasien tuberkulosis (TBA positif) rawat jalan di Puskesmas Sukasada II, Buleleng Bali. Berjumlah total yaitu 30 orang. Pasien diobservasi berdasarkan lama pengobatan dari terdiagnosis awal yaitu kelompok hari ke-1 sampai hari ke-30, kelompok hari ke-31 sampai hari ke-60 hari dan kelompok hari ke-61 sampai hari ke-90 setelah mengkonsumsi obat. Hasil: Didapatkan kasus manifestasi oral yaitu ulcer 40%, enlargement gingiva 20% dan glossitis tuberkulosa 13 % pada kelompok dengan lama pengobatan 1-30 hari. Sedangkan pada kelompok hari ke-31 sampai hari ke-60 hari dan hari ke-61 sampai hari ke-90 hari tidak ditemukan manifestasi oral sekunder pada tuberculosis paru. Kesimpulan: Terdapat hubungan antara tuberkulosis paru dengan terjadinya kelainan pada jaringan lunak rongga mulut berdasarkan lama pengobatan.
ΛCDM is alive and well
Authors: Blanchard Alain , Héloret Jean-Yves , Ilić Stéphane , Lamine Brahim , Tutusaus Isaac
Published: May 2024

Despite its successes, the ΛCDM model faces several tensions with recent cosmological data and their increased accuracy. The mismatch between the values of the Hubble constant H0 obtained from {some} direct distance ladder measurements and from the cosmic microwave background (CMB) is the most statistically significant, but the amplitude of the matter fluctuations is also regarded as a serious concern, leading to the investigation of a plethora of {alternative} models. Here, we examine the situation from a different perspective. We first show that the combination of several recent measurements from local probes leads to a tight constraint on the present-day matter density Ωm as well as on the amplitude of the matter fluctuations, both acceptably consistent with the values inferred from the CMB. Secondly, we address the Hubble tension by assuming that some determinations of the value of H0 are possibly biased. We treat such a bias as a nuisance parameter within ΛCDM and we examine such `` ΛCDM + H0 bias’’ models on the same statistical grounds as alternative cosmological models. A bias in Planck or in SH0ES produces similar improvements. However we show that a bias in the Cepheids calibration produces improvements in terms of ΔAIC that supersede existing extended models proposed up to now. In a third step, we show that the value of Ωm we obtained from our RSD, Pantheon+ and 3×2pt from DES, combined with SH0ES determination of H0, leads to a precise determination of the density parameter of the Universe ωm=0.1753±0.0069. This measurement provides an additional low-redshift test for cosmological models by comparing it to the preferred value derived from the CMB. From this test, most ΛCDM extensions seem to be confronted with a new tension as many of them cluster around ωm=0.14, while there is no tension with a local $H_0 67 $ km/s/Mpc. We conclude that a standard ΛCDM model with an unknown bias in the Cepheids distance calibration represents a model that reaches a remarkable agreement, statistically better than previously proposed extensions without bias for which such a comparison can be performed.
Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism
Authors: Huang Wei , Zou Yan , Zhang Kun , Yao Shi , Tang Shi-Hao , Wu Hao , Wang Peng-Fei , Xue Han-Zhong , Yang Tie-Lin , Zhang Kun , Guo Yan
Published: May 2024

Venous Thromboembolism (VTE) is a complex disease that can be classified into two subtypes: Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (Ratio of bis-allylic bonds to double bonds in lipids, and Ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (OR [95% CI]: 1.21 [1.15-1.27]; 1.21 [1.13-1.30]), DVT (OR [95%CI]: 1.24 [1.16-1.33]; 1.26 [1.16-1.36]) and PE (OR [95%CI]: 1.18 [1.08-1.29]; 1.18 [1.09-1.27]). Phosphatidylcholines exhibit potential causal effects on VTE and PE. Phosphatidylcholine acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR [95% CI]: 0.79 [0.73-0.86]), while phosphatidylcholine diacyl C42:6 (PC aa C42:6) and phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR [95%CI]: 1.44 [1.20-1.72]; 1.22 [1.10-1.35]). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of phosphatidylcholine have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.
Análisis del discurso: seguridad interna por los candidatos Guillermo Lasso y Andrés Arauz, elecciones 2021
Authors: Lomas Badillo Raúl Edison , Yungán Pazmiño Marlon Andrés
Published: May 2024

Introducción: el análisis del discurso de las propuestas de campaña electoral presentadas en los planes de trabajo de los candidatos finalistas a la presidencia en las elecciones del 2021, enfocadas hacia el tema de seguridad interna y principalmente al carcelario en el Ecuador, escenario de motines, masacres, violencia y asesinatos de personas privadas de libertad como guías penitenciarios. Objetivos: a) Definir los elementos del discurso político en los planes de gobierno de los candidatos finalistas Guillermo Lasso y Andrés Arauz. b) Analizar el discurso de los presidenciables sobre el tema de seguridad interna en las cárceles del país. Metodología: el estudio es de carácter cuali-cuantitativo, en donde se hace una recopilación de estudios acerca de la situación carcelaria del país y los planes de gobiernos de los candidatos, apoyados en teorías de la comunicación enfocadas en el análisis del discurso y técnicas como la entrevista a expertos en el tema. Resultados: los planes programáticos de campaña poseen recursos lingüísticos del discurso político que estructuran propuestas técnicas o poco llamativas para el votante, lo que contribuye que sus ofertas tiendan a ser divergentes hacía el problema de la seguridad. Conclusiones: al candidato Andrés Arauz, le faltó el componente didáctico en su discurso político enfocado a un conocimiento histórico de la realidad carcelaria en el país. Guillermo Lasso demostró una organización lingüística eficiente y fundamentada, uso de recursos del lenguaje apropiados como una intencionalidad macro social, conceptos relacionados a la seguridad, en un tono persuasivo y ponderado. Área de estudio general: Comunicación. Área de estudio Específico: Análisis del discurso.
AJARAN AGAMA HINDU DALAM ERA DIGITAL: MENDORONG PERILAKU PROSOSIAL ANAK USIA DINI DENGAN TEKNOLOGI
Authors: Indrayasa Kadek Bayu
Published: May 2024

Era digital telah membawa transformasi mendalam dalam cara kita berkomunikasi, belajar, dan berinteraksi. Ini memengaruhi juga bagaimana agama dan nilai-nilai prososial dapat disampaikan dan dipahami oleh anak-anak usia dini. Dalam konteks ini, penelitian ini bertujuan untuk mengeksplorasi peran teknologi dalam menyebarkan ajaran agama Hindu kepada anak-anak usia dini dan sejauh mana hal ini dapat mendorong perilaku prososial. Studi ini menggunakan pendekatan kualitatif dengan metode wawancara dan observasi terhadap kelompok anak usia dini yang mendapatkan ajaran agama Hindu melalui aplikasi dan platform digital. Hasil penelitian menunjukkan bahwa teknologi memiliki potensi besar dalam membantu anak-anak usia dini memahami ajaran agama Hindu dan menginternalisasi nilai-nilai prososial yang terkandung didalamnya.Melalui aplikasi dan platform digital, anak-anak dapat belajar dengan cara yang lebih menarik dan interaktif. Mereka dapat mengakses cerita, gambar, dan video yang memperjelas konsep-konsep agama Hindu. Selain itu, teknologi memungkinkan anak-anak untuk terlibat dalam aktivitas kolaboratif, seperti diskusi kelompok daring, yang mendorong mereka untuk berbagi pengalaman dan merenungkan nilai-nilai agama.Namun, penelitian ini juga menyoroti tantangan dan risiko yang terkait dengan penggunaan teknologi dalam menyebarkan ajaran agama Hindu kepada anak-anak. Oleh karena itu, peran orang tua dan pendidik sangat penting dalam mengawasi dan membimbing anak-anak dalam penggunaan teknologi.Dengan demikian, penelitian ini menyimpulkan bahwa teknologi dapat menjadi alat yang efektif dalam mendukung pembelajaran ajaran agama Hindu dan mendorong perilaku prososial pada anak usia dini. Namun, perlu ada pendekatan yang seimbang antara teknologi dan interaksi sosial dalam pendidikan agama Hindu untuk memastikan bahwa nilai-nilai agama dan prososial dapat diterapkan dalam kehidupan sehari-hari anak-anak.
Development of Guided Inquiry-Based Learner Worksheets to Improve Higher Level Thinking Skills of Learners on Redox Reaction Material
Authors: Br Tarigan Endah Putri , Sugiharti Gulmah
Published: May 2024

This research aims to: (1) knowing the level of need for guided inquiry-based Learner Worksheets (LKPD) at Imelda Medan Private High School. (2) to know the design of LKPD based on guided inquiry on redox material. (3) knowing the feasibility of LKPD according to BSNP standards. (4) knowing the improvement of students' higher-level thinking skills and. (5) knowing the students' response to the guided inquiry-based LKPD on redox reaction material that has been developed. This development was carried out using the R&D method with the 4D development model (Define, Design, Develop, Disseminate). The instruments used are interview guidelines, LKPD validation sheets by validators, questionnaire sheets for students' responses to the developed LKPD. The results of this study indicate that the LKPD prepared has met the eligibility criteria according to BSNP standards validated by material experts and media experts who are UNIMED chemistry lecturers by obtaining a percentage value of 88.46% with the criteria "very feasible needs revision". The average value of students' higher order thinking skills after being taught using the developed LKPD was 83.48 with an n-gain value of 0.79 and the results of students' responses were 85.14% with "very good" criteria. So that overall the guided inquiry-based Learner Worksheet to improve students' higher-level thinking skills is feasible to use in the learning process, especially in redox reaction material.
The Contribution Percentage of Some Biomechanical Variables to the First 10 Meters in the Achievement of Men's 100-Meter Sprint
Authors: Husseın Eman Sabeeh
Published: May 2024

The study aimed to identify the contribution percentage of certain variables to the technical performance of the 100-meter sprint. To achieve this goal, the researcher filmed the runners during the competition period using two motion analysis cameras operating at a speed of 120 frames per second. The research population comprised (45) attempts taken from 9 runners, with (5) attempts for each runner who participated in the second round of the Iraq Clubs Championship in Al-Jadriya on 3/3/2023. The researcher hypothesized that there is variability in the contribution percentages of the biomechanical variables to performance. The researcher identified 12 biomechanical variables after reviewing numerous scientific sources and considering the opinions of experts and specialists in this field. Relevant specific tests were conducted, and after the motion analysis, the researcher used correlational relationships to determine which variables contributed most significantly to the performance. Several conclusions were reached, including that the variables (acceleration in the first 10 meters, average speed for 10 meters, and time for the first 10 meters) achieved the highest correlation with performance, registering values of -0.698, -0.626, and -0.623, respectively. The acceleration for the first 10 meters is identified as the most influential independent biomechanical variable in performance, with a contribution percentage of 0.994. Increasing variables such as contact time, step frequency, and reaction time enhance performance. The researcher suggests prioritizing training to develop these biomechanical variables with the highest impact on performance and incorporating study findings into training programs to address weaknesses in both physical and technical aspects.
The effect of using teaching plans according to the Van Hiele method in learning the dribbling skill in basketball for students
Authors: Saleh Oday Tariq Saleh , Almgdmee Yasser Mahmoud Wahib
Published: May 2024

The study aimed to prepare teaching plans according to the Van Hiele method in learning the basketball dribbling skill, and to identify its effectiveness for intermediate school students. The researchers assumed that there is an effectiveness for the Van Hiele method in performing the basketball dribbling skill for second intermediate school students, and there are statistical differences in favor of the experimental group. The researchers used an experimental approach in the style of two equal groups. The researchers defined their research population as students from Al-Intisar Intermediate School for the academic year (2023-2024), who numbered (564) students. The study sample was deliberately determined to be represented by second-year students, whose number was (90) students, and their percentage was (15.95%). from the research community, and the research sample (45) students, representing (50%) of the total second-year students, was selected in an intentional manner. They were divided into two experimental and control groups, represented by (20) students each, and (5) students were selected for the exploratory experiment. The researchers prepared teaching plans for eight weeks on Monday, 16/10/2023, and the last lesson was on December 4, 2023. As for the control group, the teacher used his usual method, after which a pre-test was conducted for the sample, then the teaching plans were implemented on Sample on Monday 16/10/2023, and the last lesson was on 25/12/2023. As for the control group, the teacher used his usual research method. After that, the two researchers analyzed the results statistically, and by analyzing the data for the test results, it was found that the values of the means The arithmetic mean, the standard deviations, the calculated (t) value, and the error rate for the post-test for the experimental and control groups for the low dribbling skill in basketball, where the arithmetic mean value for the low dribbling skill in the post-test for the experimental group reached (20,594) with a standard deviation of (1,889), while for the control group the arithmetic mean reached (22,447). with a standard deviation of (1.834) and the calculated (t), value was (3.672), while the standard error percentage was (0.01). Since the value of the standard error percentage is smaller than the significance level at (0.05), this indicates the presence of significant differences in the test. Dimension between the experimental and control groups and in favor of the experimental group. The researchers concluded, with the results of the research, that using the Van Hiele method is effective in learning the skill of dribbling in basketball. The researchers came out with several recommendations, including the necessity of using a modern method in physical education lessons and moving away from the traditional methods followed
Netrin-1 Promotes M2 Type Activation and Inhibits Pyroptosis of Microglial Cells by Depressing RAC1/Nf-κB Pathway to Alleviate Inflammatory Pain
Authors: Yin Y , Yan Y , Jin X , Fu Y , Chen Y
Published: May 2024

Netrin-1 (NTN-1) plays a vital role in the progress of nervous system development and inflammatory diseases. However, the role and underlying mechanism of NTN-1 in inflammatory pain (IP) are unclear. BV2 microglia were treated with LPS to mimic the cell status under IP. Adeno-associated virus carrying the NTN-1 gene (AAV-NTN-1) was used to overexpress NTN-1. Complete Freund’s Adjuvant (CFA)-induced mouse was recruited as an in vivo model. MTT and commercial kits were utilized to evaluate cell viability and cell death of BV2 cells. The mRNA expressions and secretions of cytokines were measured using the ELISA method. Also, the pyroptosis and activation of BV2 cells were investigated based on western blotting. To verify the role of Rac1/NF-κB signaling, isochamaejasmin (ISO) and AAV-Rac1 were presented. The results showed that NTN-1 expression was decreased in LPS-treated BV2 microglia and spinal cord tissues of CFA-injected mice. Overexpressing NTN-1 dramatically reversed cell viability and decreased cell death rate of BV2 microglia under lipopolysaccharide (LPS) stimulation, while the level of pyroptosis was inhibited. Besides, AAV-NTN-1 rescued the activation of microglia and inflammatory injury induced by LPS, decreasing IBA-1 expression, as well as iNOS, IL-1β and IL-6 secretions. Meanwhile AAV-NTN-1 promoted the anti-inflammation response, including increases in Arg-1, IL-4 and IL-10 levels. In addition, the LPS-induced activation of Rac1/NF-κB signaling was depressed by NTN-1 overexpression. The same results were verified in a CFA-induced mouse model. In conclusion, NTN-1 alleviated IP by suppressing pyroptosis and promoting M2 type activation of microglia via inhibiting Rac1/NF-κB signaling, suggesting the protective role of NTN-1 in IP.
Keywords: Netrin-1 • Inflammatory pain • Pyroptosis • Microglia M2 activation • Rac1/NF-κB
Physiological and Pathogenesis Significance of Chorein in Health and Disease
Authors: Alkahtani S , Alkahtane AA , Alarifi S
Published: May 2024

This comprehensive review explores the physiological and pathophysiological significance of VPS13A, a protein encoded by the VPS13A gene. The VPS13A gene is associated with Chorea-acanthocytosis (ChAc), a rare hereditary neurodegenerative disorder. The review covers essential aspects, beginning with the genetics of VPS13A, highlighting its role in the pathogenesis of ChAc, and addressing the spectrum of genetic variants involved. It delves into the structure and function of the VPS13A protein, emphasizing its presence in various tissues and its potential involvement in protein trafficking and lipid homeostasis. Molecular functions of VPS13A in the brain tissue and other cell types or tissues with respect to their role in cytoskeletal regulation and autophagy are explored. Finally, it explores the intriguing link between VPS13A mutations, lipid imbalances, and neurodegeneration, shedding light on future research directions. Overall, this review serves as a comprehensive resource for understanding the pivotal role of VPS13A in health and disease, particularly in the context of ChAc.
Key words: Chorein • Tumor • Actin • Microfilament • Gene expression • Chorea-acanthocytosis
Notched Tensile Fracture of a Fe-15Mn-0.6C-2Al Twinning Induced Plasticity Steel at Room Temperature
Authors: Yoo Sang Hyup , Chung Ki-Chae , Moon Hee-Beom , Lee Kyung Hoon , Park Kyung-Tae
Published: May 2024

The tensile fracture behavior of an Al-bearing TWIP steel was investigated by conducting a series of tensile tests on smooth and notched specimens with different notch geometries, focusing on the effects of evolution of the stress triaxiality and the effective strain during deformation. The flow curve and digital image correlation (DIC) analysis evidenced suppression of dynamic strain aging due to Al addition, and therefore, the effects of local inhomogeneous deformation associated with Portevin-Le Chatelier (PLC) band on fracture could be excluded. The smooth specimen fractured with negligible necking despite the absence of PLC bands. As a result, the effective strain was uniform through the gage section and the stress triaxiality (η) of ~0.33 was nearly unchanged over the entire cross-section up to the maximum load. This led to the fracture surface of the smooth specimen being entirely covered with fine equiaxed dimples. For notched specimens, the fracture strain was drastically reduced with decreasing notch radius, indicating the high notch susceptibility of the steel. The effective strain of the notched specimens was the highest at the edge of the notch root, regardless of the notch radius, so cracks first developed at the surface of the notch root. Although the η at the center of the notched specimens (0.40~0.48 depending on the notch radius) was higher than that of the smooth one, the center of the fracture surface of all notched specimens exhibited dimple features that were very similar to the smooth one, even in size. In contrast, in spite of the same η of ~0.33, fractography at the edge of the notched specimens revealed a fracture mode transition from dimple fracture to void sheet fracture to quasi-cleavage fracture as the notch radius decreased. The present results were rationalized in terms of the local evolution of stress triaxiality and effective strain during deformation, which were analyzed using the finite elemental method and DIC technique. It can be said that the fracture mode of TWIP steel, showing limited necking, was more influenced by the distribution and/or gradient of stress traiaxiality and effective strain rather than their local absolute values - that is, the severer their gradient is, the easier the quasi-cleavage fracture occurs.
Perceptions of Mental Health in the LGBTQ+ Student Community: Needs, Barriers, and Access
Authors: Hampton Martavius L. , Beck J. Gayle , Lewis Phillis
Published: May 2024

In 2020, the COVID-19 pandemic devasted health outcomes and economies globally. As a result, many suffered financial hardships, childcare challenges, and poor mental health due to the pandemic’s negative effects. Young people were particularly affected by the pandemic as it pertained to education, social isolation, and access to essential resources and services. Additionally, the U.S. experienced a rise in anti-LGBTQ+ proposals and laws were introduced or passed in various states across the country, particularly in the South. LGBTQ+ youth and young adults are more likely to experience and report poor mental health compared to their straight counterparts. As a result, my two research collaborators (Dr. Gayle Beck and Phillis Lewis) and I proposed to examine the perceptions of mental health services, access, and availability among the LGBTQ+ student community and LGBTQ+ identifying faculty and staff on the University of Memphis campus. As a result of the pending or enacted anti-LGBTQ+ legislation and the effects of the pandemic, a needs assessment was conducted. Three methodological approaches were used to capture student, faculty, and staff insights; an online survey, focus groups, and interviews. The results of the needs assessment suggest that efforts could be used to improve access and reduce barriers for LGBTQ+ students on campus to improve overall mental health by facilitating the provision of counseling services, improving the campus atmosphere for students via training, and supporting LGBTQ mental health on campus.
Qualitative analysis of solutions for a degenerate partial differential equations model of epidemic spread dynamics
Authors: Taranets Roman , Vasylyeva Nataliya , Al-Azem Belgacem
Published: May 2024

Compartmental models are widely used in mathematical epidemiology to describe the dynamics of infectious diseases or in mathematical models of population genetics. In this study, we study a time-dependent Susceptible-Infectious-Susceptible (SIS) Partial Differential Equation (PDE) model that is based on a diffusion-drift approximation of a probability density from a well-known discrete-time Markov chain model. This SIS-PDE model is conservative due to the degeneracy of the diffusion term at the origin. The main results of this article are the qualitative behavior of weak solutions, the dependence of the local asymptotic property of these solutions on initial data, and the existence of Dirac delta function type solutions. Moreover, we study the long-term behavior of solutions and confirm our analysis with numerical computations.
Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes
Authors: Moghaddam Mehrdad Moosazadeh , Behzadi Elham , Sedighian Hamid , Goleij Zoleikha , Kachuei Reza , Heiat Mohammad , Fooladi Abbas Ali Imani
Published: May 2024

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host’s defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.
Lymphomonocytic inflammatory infiltrate with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient: a case report
Authors: Placidi Silvia , Francalanci Paola , Adorisio Rachele , Girardi Katia , Vinti Luciana , Panebianco Mario , Rebonato Micol , Amodeo Antonio , Grutter Giorgia
Published: May 2024

Findings of eosinophilic and lymphomonocytic inflammatory infiltrates in endomyocardial biopsies (EMBs) may help in myocardial disease diagnosis identification. Eosinophilic myocarditis (EM), a rare condition, is fatal if left untreated and has rarely been described in heart transplant recipients. An extensive work up is necessary to achieve an early etiological diagnosis; however, the underlying cause remains unexplained in nearly one-third of the patients. The cornerstone of treatment is corticosteroids, comprehensive therapy and heart failure management (including advanced mechanical support for fulminant myocarditis). We have described the case of a 17-year-old heart transplant recipient who presented with a cardiogenic shock. He was admitted to our intensive care unit and treated with inotropic drugs, such as milrinone, adrenaline, vasopressin, and levosimendan; the doses of these drugs were in accordance with our internal protocol. The patient underwent cardiac catheterization, coronarography, and right ventricular EMB. EMB revealed inflammatory lymphomonocytic and eosinophil granulocyte infiltrates; thus, steroid therapy was initiated, with complete recovery achieved after 15 days. Performing an early differential diagnosis among eosinophilic infiltration, acute cellular rejection (ACR), and possible chemotherapeutic damage is emerging as an important challenge. To our knowledge, this is the first reported case of a lymphomonocytic inflammatory infiltration with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient.
Students’ metacognitive knowledge of learning-strategy effectiveness and their recall of teachers’ strategy instructions
Authors: Olop Joosep , Granström Mikk , Kikas Eve
Published: May 2024

This study aimed to investigate students’ metacognitive knowledge and reported use of surface and deep learning strategies. It also explored the extent to which students recall their teachers’ recommendations for learning strategies and the relationship between these recollections and students’ knowledge and reported use of strategies. A scenario-based questionnaire was used to set a learning goal in the area of biology. Students’ metacognitive knowledge was assessed through perceived effectiveness and reported use of learning strategies. Additionally, open-ended questions allowed students to recall and report recommendations given by their teachers. We used person-centered methods to explore whether different types of recollections were related to reported strategy use. Among students who recollected that their teachers have recommended deep learning strategies, it was typical to value deep strategies higher than surface strategies and report using deep strategies. Also, it was atypical among those students to value surface level strategies and not use deep strategies.
The aging lung: microenvironment, mechanisms, and diseases
Authors: Wang Yanmei , Huang Xuewen , Luo Guofeng , Xu Yunying , Deng Xiqian , Lin Yumeng , Wang Zhanzhan , Zhou Shuwei , Wang Siyu , Chen Haoran , Tao Tao , He Lei , Yang Luchuan , Yang Li , Chen Yutong , Jin Zi , He Chengshi , Han Zhongyu , Zhang Xiaohong
Published: May 2024

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.
Poor immune response to inactivated COVID-19 vaccine in patients with hypertension
Authors: Yang Lei , Zeng TingTing , Li Yang , Guo Qiao , Jiang DePeng
Published: May 2024

Purpose

The safety and efficacy of vaccination in people with hypertension (HTN) is important. There are currently a few data on the immunogenicity and safety of inactivated SARS-CoV-2 vaccinations in hypertension patients.

Methods

After receiving a two-dose immunization, 94 hypertension adult patients and 74 healthy controls (HCs) in this study, the evaluation included looking at antibodies (Abs) against receptor binding domain (RBD) IgG, SARS-CoV-2 neutralizing antibodies (NAbs), RBD-specific B cells, and memory B cells (MBCs).

Results

There was no discernible difference in the overall adverse events (AEs) over the course of 7 or 30 days between HTN patients and HCs. HTN patients had lower frequencies of RBD-specific memory B cells and the seropositivity rates and titers of Abs compared with HCs (all, p < 0.05). HTN patients with cardiovascular and cerebrovascular conditions (CCVD) have lower titers of CoV-2 NAb than in HCs. The titers of both Abs in HTN declined gradually over time.

Conclusion

Inactivated COVID-19 vaccinations were safe in hypertension patients; however humoral immune was limited, especially merged CCVD and declined gradually over time.
Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts
Authors: Lin Duoru , Zhu Qiaolin , Zhang Shuyi , Zhou Fengqi , Zhao Lanqin , Wang Qiwei , Chen Wan , Chen Hui , Lin Xiaoshan , Feng Huanling , Zhong Qiuping , Chen Jingjing , Lin Zhuoling , Li Xiaoyan , Xiao Wei , Zhou Yue , Wang Jinghui , Li Jing , Chen Weirong
Published: May 2024

Background

This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs).

Methods

Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2–3, 3–4, 4–5, and 5–6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed.

Results

A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2–6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson’s correlation test).

Conclusion

Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2–6 years may benefit visual acuity rehabilitation.
Hemodynamics of the VenusP Valve System™—an in vitro study
Authors: Chen Huang , Samaee Milad , Tree Michael , Dasi Lakshmi , Yoganathan Ajit
Published: May 2024

This study aims to evaluate the fluid dynamic characteristics of the VenusP Valve System™ under varying cardiac outputs in vitro. A thorough hemodynamic study of the valve under physiological cardiac conditions was conducted and served as an independent assessment of the performance of the valve. Flow fields downstream of the valve near the pulmonary bifurcation were quantitatively studied by two-dimensional Particle Image Velocimetry (PIV). The obtained flow field was analyzed for potential regions of flow stasis and recirculation, and elevated shear stress and turbulence. High-speed en face imaging capturing the leaflet motion provided data for leaflet kinematic modeling. The experimental conditions for PIV studies were in accordance with ISO 5840-1:2021 standard, and two valves with different lengths and different orientations were studied. Results show good hemodynamics performance for the tested valves according to ISO 5840 standard without significant regions of flow stasis. Observed shear stress values are all well below established hemolysis limits.
Continuous year-round isolation of giant viruses from brackish shoreline soils
Authors: Akashi Motohiro , Takemura Masaharu , Suzuki Seiichi
Published: May 2024

Giant viruses, categorized under Nucleocytoviricota, are believed to exist ubiquitously in natural environments. However, comprehensive reports on isolated giant viruses remain scarce, with limited information available on unrecoverable strains, viral proliferation sites, and natural hosts. Previously, the author highlighted Pandoravirus hades, Pandoravirus persephone, and Mimivirus sp. styx, isolated from brackish water soil, as potential hotspots for giant virus multiplication. This study presents findings from nearly a year of monthly sampling within the same brackish water region after isolating the three aforementioned strains. This report details the recurrent isolation of a wide range of giant viruses. Each month, four soil samples were randomly collected from an approximately 5 × 10 m plot, comprising three soil samples and one water sample containing sediment from the riverbed. Acanthamoeba castellanii was used as a host for virus isolation. These efforts consistently yielded at least one viral species per month, culminating in a total of 55 giant virus isolates. The most frequently isolated species was Mimiviridae (24 isolates), followed by Marseilleviridae (23 isolates), Pandoravirus (6 isolates), and singular isolates of Pithovirus and Cedratvirus. Notably, viruses were not consistently isolated from any of the four samples every month, with certain sites yielding no viruses. Cluster analysis based on isolate numbers revealed that soil samples from May and water and sediment samples from January produced the highest number of viral strains. These findings underscore brackish coastal soil as a significant site for isolating numerous giant viruses, highlighting the non-uniform distribution along coastlines.
Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis
Authors: Chaganti Joga , Poudel Govinda , Cysique Lucette Adeline , Dore Gregory J. , Kelleher Anthony , Matthews Gael , Darley David , Byrne Anthony , Jakabek David , Zhang Xin , Lewis Marrissa , Jha Nikhil , Brew Bruce James
Published: May 2024

Objective

To investigate the association between blood–brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC).

Methods

In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores.

Results

At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans).

Interpretation

PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.
Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia
Authors: Brkušanin Miloš , Kosać Ana , Branković-Srećković Vesna , Jovanović Kristina , Perić Stojan , Karanović Jelena , Matijašević Joković Suzana , Garai Nemanja , Pešović Jovan , Nikolić Dimitrije , Stević Zorica , Brajušković Goran , Milić-Rašić Vedrana , Savić-Pavićević Dušanka
Published: May 2024

Introduction

Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise.

Methods

We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3).

Results

SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment.

Conclusion

Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration.
Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study
Authors: Gao Yining , Zhang Yizongheng , Chunyu Hangxing , Xu Yongfeng , Wang Ying , Liu Suzhi , Chang Jie , Tang Bo , Xu Congying , Lu Yi , Zhou Jian , Kong Xiangyong , Zhu Xiaoying , Chen Sheng , Zhou Qinming , Meng Huanyu
Published: May 2024

Objective

Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease.

Methods

We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes.

Results

The average age at diagnosis was 45.93 ± 4.62 years (range: 11–72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up.

Conclusion

The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.
Effects of selenium and iodine on Kashin-Beck disease: an updated review
Authors: Liu Lin , Luo Pan , Wen Pengfei , Xu Peng
Published: May 2024

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.
KRAS G12C inhibitor combination therapies: current evidence and challenge
Authors: Miyashita Hirotaka , Kato Shumei , Hong David S.
Published: May 2024

Although KRAS G12C inhibitors have proven that KRAS is a “druggable” target of cancer, KRAS G12C inhibitor monotherapies have demonstrated limited clinical efficacy due to primary and acquired resistance mechanisms. Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer. Many clinical trials of combinations of KRAS G12C inhibitors with other targeted therapies, such as SOS1, ERK, CDK4/6, and wild-type RAS, are ongoing. Furthermore, preclinical data have suggested additional promising KRAS G12C combinations with YAP/TAZ-TEAD inhibitors, FAK inhibitors, and farnesyltransferase inhibitors. The combinations of KRAS G12C inhibitors with immunotherapies and chemotherapies have also been investigated, and the preliminary results were reported. More recently, KRAS-targeted therapies not limited to KRAS G12C are being developed, potentially broadening the treatment landscape of KRAS-mutated cancers. Rationally combining KRAS inhibitors with other therapeutics is likely to play a significant role in future treatment for KRAS-mutated solid tumors.