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As one of the latest emerging HVAC technologies, the Variable Refrigerant Flow (VRF) system with heat recovery (HR) configurations has obtained extensive attention from both the academia and industry. Compared with the conventional VRF systems with heat pump (HP) configurations, VRF-HR is capable of recovering heat from cooling zones to heating zones and providing simultaneous cooling and heating operations. This can further lead to substantial energy saving potential and more flexible zonal control. In this paper, a novel model is developed to simulate the energy performance of VRF-HR systems. It adheres to a more physics-based development with the ability to simulate the refrigerant loop performance and consider the dynamics of more operational parameters, which is essential for representing more advanced control logics. Another key feature of the model is the introduction of component-level curves for indoor units and outdoor units instead of overall performance curves for the entire system, and thus it requires much fewer user-specified performance curves as model inputs. The validation study shows good agreements between the simulated energy use from the new VRF-HR model and the laboratory measurement data across all operational modes at sub-hourly time steps. The model has been adopted in the official release of the EnergyPlus simulation program since Version 8.6, which enables more accurate and robust assessments of VRF-HR systems to support their applications in energy retrofit of existing buildings or design of zero-net-energy buildings.

Objective: Hypothalamic signals potently stimulate energy expenditure by engaging peripheral mechanisms to restore energy homeostasis. Previous studies have identified several critical hypothalamic sites (e.g. preoptic area (POA) and ventromedial hypothalamic nucleus (VMN)) that could be part of an interconnected neurocircuit that controls tissue thermogenesis and essential for body weight control. However, the key neurocircuit that can stimulate energy expenditure has not yet been established. Methods: Here, we investigated the downstream mechanisms by which VMN neurons stimulate adipose tissue thermogenesis. We manipulated subsets of VMN neurons acutely as well as chronically and studied its effect on tissue thermogenesis and body weight control, using Sf1Cre and Adcyap1Cre mice and measured physiological parameters under both high-fat diet and standard chow diet conditions. To determine the node efferent to these VMN neurons, that is involved in modulating energy expenditure, we employed electrophysiology and optogenetics experiments combined with measurements using tissue-implantable temperature microchips. Results: Activation of the VMN neurons that express the steroidogenic factor 1 (Sf1; VMNSf1 neurons) reduced body weight, adiposity and increased energy expenditure in diet-induced obese mice. This function is likely mediated, at least in part, by the release of the pituitary adenylate cyclase-activating polypeptide (PACAP; encoded by the Adcyap1 gene) by the VMN neurons, since we previously demonstrated that PACAP, at the VMN, plays a key role in energy expenditure control. Thus, we then shifted focus to the subpopulation of VMNSf1 neurons that contain the neuropeptide PACAP (VMNPACAP neurons). Since the VMN neurons do not directly project to the peripheral tissues, we traced the location of the VMNPACAP neurons' efferents. We identified that VMNPACAP neurons project to and activate neurons in the caudal regions of the POA whereby these projections stimulate tissue thermogenesis in brown and beige adipose tissue. We demonstrated that selective activation of caudal POA projections from VMNPACAP neurons induces tissue thermogenesis, most potently in negative energy balance and activating these projections lead to some similar, but mostly unique, patterns of gene expression in brown and beige tissue. Finally, we demonstrated that the activation of the VMNPACAP neurons' efferents that lie at the caudal POA are necessary for inducing tissue thermogenesis in brown and beige adipose tissue. Conclusions: These data indicate that VMNPACAP connections with the caudal POA neurons impact adipose tissue function and are important for induction of tissue thermogenesis. Our data suggests that the VMNPACAP → caudal POA neurocircuit and its components are critical for controlling energy balance by activating energy expenditure and body weight control.

O objetivo deste estudo de caso foi analisar as percepções de alunos(as) de um curso de Ciências do Esporte no Brasil quanto à importância atribuída e o domínio percebido sobre os conhecimentos e competências do(a) treinador(a) esportivo(a). Utilizamos o questionário de Quinaud et al. (2018), com 192 alunos(as) do primeiro ao quinto ano do curso. Fizemos o uso da estatística descritiva e, após constatarmos a distribuição não normal, recorremos ao teste Kruskal-Wallis para a comparação da importância atribuída e do domínio percebido dentro dos grupos. Nos casos com diferenças significativas utilizamos o teste U de Mann-Whitney, correção de Dun-Bonferroni (p≤0,05) e tamanho de efeito pelo Eta² parcial (Cohen, 1973). Não constatamos diferenças significativas acerca da importância atribuída aos conhecimentos e observamos diferenças em duas competências. Sobre o domínio percebido, constatamos diferenças significativas acerca de todos os conhecimentos e competências, principalmente entre alunos(as) dos primeiros anos comparados aos de 3º, 4º e 5º. Diferentes vivências ao longo do curso parecem auxiliar no desenvolvimento do domínio de conhecimentos e competências dos(as) alunos(as). Considerando que no Brasil há a obrigatoriedade do diploma de graduação para atuar como treinador(a), torna-se importante que os cursos de Educação Física e Esporte prezem pelo desenvolvimento de conhecimentos e competências específicos desta profissão.

Resumo A variabilidade e beleza das ações técnicas individuais do basquetebol são decorrentes das necessidades táticas impostas aos jogadores durante o jogo e fazem parte importante do espetáculo, impactando positivamente os espectadores e mídia. Entre várias formas de fintas, arremessos, passes e bandejas, destacam-se as enterradas, enquanto momento de grande notoriedade no jogo, bem como tema de eventos específicos dedicados a ela no basquetebol masculino. Visando a realização do 1º Torneio de Enterradas no Jogo das Estrelas LBF 2018, o objetivo do estudo foi qual altura do aro necessária para que as jogadoras brasileiras pudessem realizar enterradas. Foi utilizada a altura alcançada no teste de impulsão vertical em progressão de 91 jogadoras participantes das nove equipes na temporada 2018. Verificamos que 25 % dos jogadores masculinos brasileiros de elite enterram em jogos oficiais. Assim, o critério para definir a altura do aro foi que a mesma porcentagem de jogadoras femininas pudessem enterrar, considerando a altura alcançada no teste e a necessidade de passar a bola sobre o aro. Foi determinada a altura de 2.75 m do aro em relação ao solo. Oito jogadoras participaram do evento, sendo quatro brasileiras e quatro argentinas, sendo que cinco delas conseguiram realizar enterradas. Deve-se ressaltar que a altura do aro não foi alterada para os jogos da temporada, e considerar que essa mudança pode não implicar no surgimento de enterradas em partidas oficiais, dado que a dinâmica do jogo é diferente da dinâmica no Torneio de Enterradas e que as jogadoras necessitam de um tempo de adaptação. Palavras-chave: Aro; rendimiento; impulsão; Capacidade Física. Abstract The variability and beauty of basketball's individual technical actions arise from the tactical needs imposed on players during the game, as an important part of the spectacle that positively impacts spectators and media. Among the many feints, throws, passes and layups, are the slam dunks, a notorious moment in the game, and also theme of specific events in men's basketball. In view of the realization of the 1st Slam Dunk Tournament during the 2018 LBF All Stars Games, the aim of the study was to determine the ideal hoop height for Brazilian female players to be able to slam dunk. We analyzed the height achieved in the progressive vertical jump test of 91 female players participating in the nine teams in the 2018 season. Findings suggest that 25% of the elite Brazilian male players slam dunk in official games. Thus, the criteria for defining the hoop height was that the same percentage of female players could slam dunk, considering the height reached on the test and the need to take the ball over the hoop. This resulted in 2.75 m as the height of the rim from the ground. Eight players participated in the event, four Brazilian and four Argentinian, and five of them managed to dunk. It should benoted that the height of the rim has not changed for the regular games of the season, and that this change may not imply the emergence of dunks in official matches, as the game dynamics are different from the dynamics in the Dunk Tournament and that the players need some time to adapt. Keywords: Aro; Performance; Impulsion; Physical Ability. Resumen La variabilidad y hermosura de las acciones técnicas individuales del baloncesto se derivan de las necesidades tácticas impuestas a los jugadores durante el juego y son una parte importante del espectáculo, que impacta positivamente a los espectadores y a la prensa. Entre las muchas maneras de fintas, tiros, pases y entradas, están los mates, como un momento de gran notoriedad en el juego en el baloncesto masculino. Con el objetivo de celebrar el primer “Torneo de mates LBF 2018”, el objetivo del estudio fue determinar la altura del aro necesario para que las jugadoras brasileñas pudieran concretizar los mates. Utilizamos la altura alcanzada en la prueba de salto vertical progresivo de 91 jugadoras de los nueve equipos de la temporada 2018. Encontramos que el 25% de los jugadores masculinos brasileños de élite son capaces de hacer mates en los juegos oficiales. Por lo tanto, el criterio para definir la altura del aro fue que el mismo porcentaje de jugadoras femeninas pudiera concluye mates, considerando la altura alcanzada en la prueba de salto y la necesidad de pasar la pelota sobre el aro. Así, llegamos a la altura del aro desde 2,75 m del suelo. Ocho jugadoras participaron en el evento, cuatro brasileñas y cuatro argentinas, cinco de ellas lograron actuar mates. Cabe señalar que la altura del aro no fue cambiada para los partidos de la temporada, con lo cual esta altura puede no implicar la aparición de mates en esta condición, ya que la dinámica del juego es diferente de la dinámica en el Torneo de mates. Palabras clave: Aro; rendimiento; empuje; Capacidad Física.

Os jogos de ataque por conceitos (JAC) visam estimular jogadores a compreenderem o jogo, solucionarem problemas e criarem vantagens sobre o adversário. O objetivo foi aplicar os JAC para o ensino da fase ofensiva do basquetebol no esporte de participação brasileiro, descrevendo as opiniões dos atletas e seu treinador. Participaram oito atletas do sexo masculino (média de 16,8 ± 1,0 anos), com tempo médio de experiência com o basquetebol de 3,0 ± 1,4 anos, com métodos tradicionais de ensino, e um treinador de 32 anos com oito anos de experiência profissional. Elaboramos os JAC a partir dos conceitos: dividir e passar, passar e cortar, e jogo ao poste. Aplicamos oito sessões de treino, com duração de 90 minutos cada. Realizamos entrevista semiestruturada com o treinador e grupos focais com os atletas, analisadas por análise temática. Nos resultados estabelecemos as categorias opiniões positivas (temas: compreensão da lógica do jogo; aspectos pessoais; e aspectos interpessoais), e negativas (temas: confronto com o novo e tempo de implementação do método). Os JAC foram compreendidos como prazerosos e facilitaram a compreensão da lógica do jogo. Concluimos que os JAC podem ser utilizados para ensino do basquetebol no contexto de participação, com vantagens sobre abordagens pedagógicas tradicionais.

Basketball performance analysis using technical indicators dissociated from the moment they occurred in the game seems to no longer respond to emerging issues of the game as it does not identify the periods when a team’s offensive efficiency has increased or decreased. The aim was to characterize and compare the technical indicators in the positive and negative periods and in the whole game of winning and losing teams in men’s professional basketball. Fourteen games of professional men’s teams of the “Novo Basquete Brasil” Championship in the regular 2011/2012 season were filmed and analyzed. The Kolmogorov-Smirnov test was used to verify data normality. The independent T test was used for variables with normal distribution and the Mann-Whitney test for variables that did not present normal distribution, in order to compare teams’ performance. Analysis in the whole game showed that winning teams had significantly higher averages in successful 3-point field goals but in the positive periods, they showed higher averages for successful free throws, successful layups, defensive rebounds and defensive fouls, and in negative periods, losing teams made more defensive and offensive fouls. The teams’ performance in the whole game may not elucidate the determinant indicators for building the difference in the scoreboard. It is suggested that coaches should identify the periods of best and worst teams’ performance in the game and the indicators involved, preparing teams to overcome the negative periods and obtain more positive periods in the game.

Purpose: This study aimed to develop a stroke effectiveness test in table tennis based on the temporal game structure to assess the ball speed and ball placement of the players, with a purpose to analyze its reproducibility and validity.Methods: Nineteen male table tennis players participated in this study. The test was performed twice during the first session and once during the second session to assess the intrasession and intersession reproducibility, respectively. Moreover, the test was examined on its ability to discriminate between regional (n = 10) and local performance-level (n = 9) players and on the relationship between the test results and the table tennis performance to assess the discriminant and concurrent validity, respectively. In general, the test consisted of 11 simulated rallies of 2–5 balls with the effort and rest ratio of 0.5, and focused on attack with offensive strokes at defensive balls delivered by a robot randomly between the left and right positions on the table.Results: Ball speed, ball placement, and ball speed-ball placement index showed satisfactory reliability (ICC range 0.78–0.96, P < 0.05) and agreement (CV range 2.7–16.2%) outcomes. Additionally, the Bland–Altman plots show the systematic error of the analyses closer to 0, and that most values were within the limits of agreements. Concerning validity analyses, regional players had higher scores of ball placement (+51.3%; P = 0.01, ES = 1.33) and ball speed-ball placement index (+56.1%; P = 0.0009, ES = 1.87) as well as made fewer errors (-25.4%; P = 0.017, ES = 1.20) than local players. Moreover, ball placement (r = -0.79, P = 0.04), ball speed-ball placement index (r = -0.78, P = 0.04), and percentage error (r = 0.88, P = 0.01) presented a strong and significant correlation with table tennis performance. However, ball speed was slightly different between the regional than local players (+1.7%; P = 0.78, ES = 0.13) and this variable was not related to table tennis performance (r = 0.32, P = 0.49).Conclusion: Our findings show evidences that the test is reproducible. Moreover, discriminant and concurrent validity are confirmed for ball placement and ball speed-ball placement index.

Lymphatic leakage, manifesting as chylothorax or chylous ascites, arises from traumatic or nontraumatic causes and poses severe risks such as malnutrition and increased infection susceptibility. Accurate diagnosis and an effective treatment strategy necessitate comprehensive lymphatic imaging. Conventional lymphangiography and dynamic contrast-enhanced MR lymphangiography (DCMRL) have been widely used and studied as effective lymphatic imaging methods. Recently, CT lymphangiography (CTL) has been successfully implemented in animal studies and some patients, and the authors' institution now prioritizes CTL over DCMRL. Contrast-enhanced CTL offers a promising alternative, with advantages such as better accessibility and faster imaging. These advantages of CTL over traditional methods highlight its superior accessibility and fast acquisition time. Moreover, to reduce and optimize radiation dose, the stepwise propagation scanning method in CTL could be used, which is especially beneficial in pediatric patients. In this review, the authors suggest the protocol for CTL and interpretation methods for evaluation and therapeutic planning of central lymphatic disorders, focusing on the condition of lymphatic leakage. © RSNA, 2024 The slide presentation from the RSNA Annual Meeting is available for this article.

Na + -K + -2Cl - cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes. In the present study, we investigated the effect of ET-1 on NKCC1 expression in astrocytes. ET-1 (100 nM)-treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET-1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 μM), an ET B antagonist, but not by FR139317 (1 μM), an ET A antagonist. The involvement of ET-1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI-induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI-induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET-1-treated cultured astrocytes showed increased mRNA and protein expression of hypoxia-inducible factor-1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co-localization of HIF1α with GFAP-positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 μM) and HIF1α siRNA suppressed ET-induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET-1 increases NKCC1 expression in astrocytes through the activation of HIF1α., (© 2024 Wiley Periodicals LLC.)

Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of protein kinase activity plays a significant role in the pathogenesis of cardiac systolic dysfunction. While cardiac contraction mechanisms are well documented, the mechanisms underlying cardiac diastole remain elusive. This gap persists owing to the historical focus on systolic dysfunction in heart failure research. Recently, heart failure with preserved ejection fraction (HFpEF), an age-related disease characterized by cardiac diastolic dysfunction, has emerged as a major public health concern. However, its underlying mechanism remains unclear. In this study, we investigated cardiac protein kinases by analyzing the gene expression of 518 protein kinases in human tissues. We identified alpha-kinase 2 (ALPK2) as a novel cardiac-specific atypical kinase and generated tamoxifen-inducible, cardiomyocyte-specific Alpk2-knockout mice and Alpk2-overexpressing mice. Alpk2 deficiency did not affect cardiac systolic dysfunction in the myocardial infarction model or the pressure-overload-induced heart failure model. Notably, cardiomyocyte-specific Alpk2 deficiency exacerbated cardiac diastolic dysfunction induced by aging and in the HFpEF model. Conversely, Alpk2 overexpression increased the phosphorylation of tropomyosin 1, a major regulator that binds myosin to actin, and mitigated cardiac stiffness in HFpEF. This study provides novel evidence that ALPK2 represents a potential therapeutic target for cardiac diastolic dysfunction in HFpEF and age-related cardiac impairments., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes., (© 2024 the author(s), published by De Gruyter.)

Diffuse pediatric-type high-grade gliomas (pedHGG), H3- and IDH-wildtype, encompass three main DNA-methylation-based subtypes: pedHGG-MYCN, pedHGG-RTK1A/B/C, and pedHGG-RTK2A/B. Since their first description in 2017 tumors of pedHGG-RTK2A/B have not been comprehensively characterized and clinical correlates remain elusive. In a recent series of pedHGG with a Gliomatosis cerebri (GC) growth pattern, an increased incidence of pedHGG-RTK2A/B (n = 18) was observed. We added 14 epigenetically defined pedHGG-RTK2A/B tumors to this GC series and provided centrally reviewed radiological, histological, and molecular characterization. The final cohort of 32 pedHGG-RTK2A/B tumors consisted of 25 pedHGG-RTK2A (78%) and seven pedHGG-RTK2B (22%) cases. The median age was 11.6 years (range, 4-17) with a median overall survival of 16.0 months (range 10.9-28.2). Seven of 11 of the newly added cases with imaging available showed a GC phenotype at diagnosis or follow-up. PedHGG-RTK2B tumors exhibited frequent bithalamic involvement (6/7, 86%). Central neuropathology review confirmed a diffuse glial neoplasm in all tumors with prominent angiocentric features in both subclasses. Most tumors (24/27 with available data, 89%) diffusely expressed EGFR with focal angiocentric enhancement. PedHGG-RTK2A tumors lacked OLIG2 expression, whereas 43% (3/7) of pedHGG-RTK2B expressed this glial transcription factor. ATRX loss occurred in 3/6 pedHGG-RTK2B samples with available data (50%). DNA sequencing (pedHGG-RTK2A: n = 18, pedHGG-RTK2B: n = 5) found EGFR alterations (15/23, 65%; predominantly point mutations) in both subclasses. Mutations in BCOR (14/18, 78%), SETD2 (7/18, 39%), and the hTERT promoter (7/19, 37%) occurred exclusively in pedHGG-RTK2A tumors, while pedHGG-RTK2B tumors were enriched for TP53 alterations (4/5, 80%). In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical University of Graz (35–085 ex 22/23). Consent for publication Not applicable. Competing interests The authors declare that they have no conflicts of interest directly related to the topic of this article., (© 2024. The Author(s).)

Introduction: The adoption of tethered mobile personal health records provides not only medical information to patients but also various convenience functions related to hospital use, thereby increasing accessibility to healthcare services and promoting patient engagement. We analyse the tethered mobile personal health records app's usage logs to determine how it can contribute to improving medical service accessibility and patient engagement., Methods: Log data, that comprised menu type, log time, and date, were collected from the mobile personal health records app of a tertiary referral hospital. Clinical information, including patients' demographics and visit type, was collected from the clinical research warehouse system. The usage log was analysed in terms of the type of visit, service function, and time period., Results: Outpatients accounted for 34% of the total app usage and was the most app-accessed visit type. The most utilized menu functions were lab test and visit schedule for visits or non-visits. For Inpatient and Health check-ups, menu usage patterns showed a focus on lab test results. While investigations and other menu usage showed double peaks in the morning and afternoon, peak usage of lab test results correlated with inpatient blood sampling times, which was around 9 am., Discussion: App menus to access health information, particularly blood tests, emerged as the most accessed menu. Hence, when compared with blood sampling times and hospital information system usage patterns, encounters occurring in the hospital majorly impacted patient app use. For improved patient engagement, improving lab test function should be the priority., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board (IRB) of the Asan Medical Center, South Korea (approval No. 2022 − 0603). MCMH is a service designed to assist in medical treatment. The notice and consent for the use of personal information are disclosed in the terms and conditions of the application. The data analyzed in this study were collected retrospectively and processed under pseudonymization. Consequently, explicit consent from the participants was not obtained. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The present study was designed to identify the preoperative clinical and imaging findings influencing adverse clinical outcomes in patients with chronic constrictive pericarditis after pericardiectomy. Patients with constrictive pericarditis who underwent pericardiectomy between January 2009 and September 2023 were retrospectively analyzed. Preoperative evaluations included assessments of clinical symptoms, comorbidities, laboratory tests, cardiac computed tomography (CT), and transthoracic echocardiography. The volume of pericardial calcifications was quantified on calcium scoring CT. Adverse clinical events were defined as cardiovascular death or hospitalization due to cardiac causes, and all-cause mortality was assessed. Univariable and multivariable Cox proportional hazard model analysis were performed to find factors associated with adverse clinical events. Among the 91 patients with available preoperative CT scans, 26 (28.6%) experienced adverse clinical events after pericardiectomy, with 19 (20.9%) experiencing cardiovascular deaths. On multivariable Cox analysis, larger pericardial calcium volume hazard ratio [HR], 1.004 (95% confidence interval [CI], 1.001-1.006) per 1cm 3 increase; p = 0.005), higher E/E' ratio (HR, 1.059, 95% CI, 1.015-1.105, p = 0.008), and lower albumin level (HR, 0.476, 95% CI, 0.229-0.986, p = 0.046) were significant factors associated with the adverse clinical events after pericardiectomy. The amount of pericardial calcification could be associated with the efficacy of pericardiectomy and potentially have implications for postoperative outcomes. Additionally, a high E/E ratio on echocardiography is indicative of unfavorable postoperative prognosis., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate This retrospective study was approved by the institutional review board of Asan Medical Center. Patients’ informed consent was waived due to retrospective nature of the study., (© 2024. The Author(s).)

Photopolymerization-based three-dimensional (3D) printing techniques such as stereolithography (SLA) attract considerable attention owing to their superior resolution, low cost, and relatively high printing speed. However, the lack of studies on improving the mechanical properties of 3D materials highlights the importance of delving deeper into additive manufacturing research. These materials possess considerable potential in the medical field, particularly for applications such as anatomical models, medical devices, and implants. In this study, we investigated the enhancement of mechanical strength in 3D-printed photopolymers through the incorporation of potassium titanate powder (K 2 Ti 8 O 17 ), with a particular focus on potential applications in medical devices. The mechanical strength of the photopolymer containing potassium titanate was analyzed by measuring its flexural strength, hardness, and tensile strength. Additionally, poly(ethylene glycol) (PEG) was used as a stabilizer to optimize the dispersion of potassium titanate in the photopolymer. The flexural strengths of the printed specimens were in the range of 15-39 MPa (Megapascals), while the measured surface hardness and tensile strength were in the range of 41-80 HDD (Hardness shore D) and 2.3-15 MPa, respectively. Furthermore, the output resolution was investigated by testing it with a line-patterned structure. The 3D-printing photopolymer without PEG stabilizers produced line patterns with a thickness of 0.3 mm, whereas the 3D-printed resin containing a PEG stabilizer produced line patterns with a thickness of 0.2 mm. These findings demonstrate that the composite materials not only exhibit improved mechanical performance but also allow for high-resolution printing. Furthermore, this composite material was successfully utilized to print implants for pre-surgical inspection. This process ensures the precision and quality of medical device production, emphasizing the material's practical value in advanced medical applications.

Stem cells (SCs) and not progenitors (Ps) act as cells of origin of Basal Cell Carcinoma (BCC). The mechanisms promoting BCC formation in SCs or restricting tumour development in Ps are currently unknown. In this study, we transcriptionally profiled SCs and Ps and found that Survivin, a pleiotropic factor that promotes cell division and inhibits apoptosis was preferentially expressed in SCs. Using genetic gain and loss of function mouse models, we showed that Survivin deletion in oncogene-expressing SCs prevents BCC formation. Survivin overexpression renders Ps competent to BCC formation by promoting cell survival and division while preventing apoptosis and differentiation. We identified SGK1, as a key downstream factor of Survivin, and its inhibition prevents BCC formation. This study uncovers the role and mechanisms by which Survivin regulates the competence of SCs to initiate BCC formation promoting the survival of oncogene-expressing SCs and self-renewing division while restricting differentiation and apoptosis.

Photoresist polymers containing cycloaliphatic acrylic monomers have been synthesized for use in the microcircuits of semiconductors. Although cycloaliphatic acrylic monomers exhibit a high etch resistance and excellent thermal properties, their large size increases the distance between the main chains of the resulting polymers. This increased distance facilitates the penetration of a developer between the main chains, which leads to swelling and thus pattern collapse, distortion, and delamination, thereby complicating the fabrication of microcircuits. To solve this problem, various large developers were used in previous studies to reduce the swelling effect. However, these developers could not easily dissolve the unexposed regions of the resist. To overcome this issue, we designed photoresist polymers with smaller functional groups to decrease the degree of swelling. Specifically, ArF photoresist polymers were synthesized from monomers with various sizes of functional groups. We confirmed that the polymer synthesized using cyclohexyl methacrylate (CHMA), which had the smallest functional group, exhibited the shortest distance between the main chains. Consequently, this polymer showed the least swelling, with a swelling ratio of 109%. In contrast, the polymers synthesized using isobornyl acrylate (IBOA) and dicyclopentanyl methacrylate (TCDMA), which have large functional groups, exhibited greater distances between the main chains, resulting in swelling ratios of 114% and 112%, respectively. The polymer with a swelling ratio of 109% showed excellent patterning properties, while those with swelling ratios of 114% and 112% were delaminated by the developer. Our work introduces a novel approach to help reduce the swelling effect and achieve high-quality patterns in negative photoresists.

The liver regenerates after injury; however, prolonged injury can lead to chronic inflammation, fatty liver disease, fibrosis, and cancer. The mechanism involving the complex pathogenesis of the progression of liver injury to chronic liver disease remains unclear. In this study, we investigated the dynamics of gene expression associated with the progression of liver disease. We analyzed changes in gene expression over time in a mouse model of carbon tetrachloride (CCl 4 )-induced fibrosis using high-throughput RNA sequencing. Prolonged CCl 4 -induced liver injury increased the expression levels of genes associated with the unfolded protein response (UPR), which correlated with the duration of injury, with substantial, progressive upregulation of muscle, intestine, and stomach expression 1 (Mist1, bhlha15) in the mouse fibrosis model and other liver-damaged tissues. Knockdown of MIST1 in HepG2 cells decreased tribbles pseudokinase 3 (TRIB3) levels and increased apoptosis, consistent with the patterns detected in Mist1-knockout mice. MIST1 expression was confirmed in liver tissues from patients with metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis (MASH) and correlated with disease progression. In conclusion, MIST1 is expressed in hepatocytes in response to damage, suggesting a new indicator of liver disease progression. Our results suggest that MIST1 plays a key role in the regulation of apoptosis and TRIB3 expression contributing to progressive liver disease after injury., (© 2024. The Author(s).)

Rationale and Objectives: To establish a quantitative CT threshold for radiological disease progression of progressive pulmonary fibrosis (PPF) and evaluate its feasibility in patients with connective tissue disease-related interstitial lung disease (CTD-ILD)., Materials and Methods: Between April 2007 and October 2022, patients diagnosed with CTD-ILD retrospectively evaluated. CT quantification was conducted using a commercial software by summing the percentages of ground-glass opacity, consolidation, reticular opacity, and honeycombing. The quantitative threshold for radiological progression was determined based on the highest discrimination on overall survival (OS). Two thoracic radiologists independently evaluated visual radiological progression, and the senior radiologist's assessment was used as the final result. Cox regression was used to assess prognosis of PPF based on the visual assessment and quantitative threshold., Results: 97 patients were included and followed up for a median of 30.3 months (range, 4.7-198.1 months). For defining radiological disease progression, the optimal quantitative CT threshold was 4%. Using this threshold, 12 patients were diagnosed with PPF, while 14 patients were diagnosed with PPF based on the visual assessment, with an agreement rate of 97.9% (95/97). Worsening respiratory symptoms (hazard ratio [HR], 12.73; P < .001), PPF based on the visual assessment (HR, 8.86; P = .002) and based on the quantitative threshold (HR, 6.72; P = .009) were independent risk factors for poor OS., Conclusion: The quantitative CT threshold for radiological disease progression (4%) was feasible in defining PPF in terms of its agreement with PPF grouping and prognostic performance when compared to visual assessment., Competing Interests: Declaration of Competing Interest Joon Beom Seo owns stocks of Coreline Soft, Co. Ltd., a medical software company in Republic of Korea. The remaining authors declare that they have no conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Preparing appropriate red blood cells (RBCs) before surgery is crucial for improving both the efficacy of perioperative workflow and patient safety. In particular, thoracic surgery (TS) is a procedure that requires massive transfusion with high variability for each patient. Hence, the precise prediction of RBC requirements for individual patients is becoming increasingly important. This study aimed to 1) develop and validate a machine learning algorithm for personalized RBC predictions for TS patients and 2) assess the usability of a clinical decision support system (CDSS) integrating this artificial intelligence model., Methods: Adult patients who underwent TS between January 2016 and October 2021 were included in this study. Multiple models were developed by employing both traditional statistical- and machine-learning approaches. The primary outcome evaluated the model's performance in predicting RBC requirements through root mean square error and adjusted R 2 . Surgeons and informaticians determined the precision MSBOS-Thoracic Surgery (pMSBOS-TS) algorithm through a consensus process. The usability of the pMSBOS-TS was assessed using the System Usability Scale (SUS) survey with 60 clinicians., Results: We identified 7,843 cases (6,200 for training and 1,643 for test sets) of TSs. Among the models with variable performance indices, the extreme gradient boosting model was selected as the pMSBOS-TS algorithm. The pMSBOS-TS model showed statistically significant lower root mean square error (mean: 3.203 and 95% confidence interval [CI]: 3.186-3.220) compared to the calculated Maximum Surgical Blood Ordering Schedule (MSBOS) and a higher adjusted R 2 (mean: 0.399 and 95% CI: 0.395-0.403) compared to the calculated MSBOS, while requiring approximately 200 fewer packs for RBC preparation compared to the calculated MSBOS. The SUS score of the pMSBOS-TS CDSS was 72.5 points, indicating good acceptability., Conclusions: We successfully developed the pMSBOS-TS capable of predicting personalized RBC transfusion requirements for perioperative patients undergoing TS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Financial support for this study was provided entirely by a grant from the Ministry of Health & Welfare, Republic of Korea. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Coronary artery calcium (CAC) scoring CT is a useful tool for screening coronary artery disease and for cardiovascular risk stratification. However, its efficacy in patients with coronary stents, who had pre-existing coronary artery disease, remains uncertain. Historically, CAC CT scans of these patients have been manually excluded from the CAC scoring process, even though most of the CAC scoring process is now fully automated. Therefore, we hypothesized that automating the filtering of patients with coronary stents using artificial intelligence could streamline the entire CAC workflow, eliminating the need for manual intervention. Consequently, we aimed to develop and evaluate a deep learning-based coronary stent filtering algorithm (StentFilter) in CAC scoring CT scans using a multicenter CAC dataset. We developed StentFilter comprising two main processes: stent identification and false-positive reduction. Development utilized 108 non-enhanced echocardiography-gated CAC scans (including 74 with manually labeled stents), and for false positive reduction, 2063 CAC scans with significant coronary calcium (average Agatston score: 523.8) but no stents were utilized. StentFilter's performance was evaluated on two independent internal test sets (Asan cohort- and 2; n = 355 and 396; one without coronary stents) and two external test sets from different institutions (n = 105 and 62), each with manually labeled stents. We calculated the per-patient sensitivity, specificity, and false-positive rate of StentFilter. StentFilter demonstrated a high overall per-patient sensitivity of 98.8% (511/517 cases with stents) and a false-positive rate of 0.022 (20/918). Notably, the false-positive ratio was significantly lower in the dataset containing stents (Asan cohort-1; 0.008 [3/355]) compared with the dataset without stents (Asan cohort-2; 0.043 [17/396], p = 0.008). All false-positive identifications were attributed to dense coronary calcifications, with no false positives identified in extracoronary locations. The automated StentFilter accurately distinguished coronary stents from pre-existing coronary calcifications. This approach holds potential as a filter within a fully automated CAC scoring workflow, streamlining the process efficiently., (© 2024. The Author(s).)

Background: Air pollutants, such as diesel exhaust particles (DEPs), induce respiratory disease exacerbation with neutrophilic infiltration. Progranulin (PGRN), an epithelial cell and macrophage-derived secretory protein, is associated with neutrophilic inflammation. PGRN is digested into various derivatives at inflammatory sites and is involved in several inflammatory processes. PGRN and its derivatives likely regulate responses to DEP exposure in allergic airway inflammation., Aim: To investigate the role of PGRN and its derivatives in the regulation of responses to DEP exposure in allergic airway inflammation., Methods: A murine model of allergic airway inflammation was generated in PGRN-deficient mice, and they were simultaneously exposed to DEP followed by intranasal administration of full-length recombinant PGRN (PGRN-FL) and a PGRN-derived fragment (FBAC). Inflammatory status was evaluated by bronchoalveolar lavage fluid and histopathologic analyses. Human bronchial epithelial cells were stimulated with DEPs and house dust mites (HDMs), and the effect of FBAC treatment was evaluated by assessing various intracellular signaling molecules, autophagy markers, inflammatory cytokines, and intracellular oxidative stress., Results: DEP exposure exaggerated neutrophilic inflammation, enhanced IL-6 and CXCL15 secretions, and increased oxidative stress in the murine model; this effect was greater in PGRN-deficient mice than in wild-type mice. The DEP-exposed mice with PGRN-FL treatment revealed no change in neutrophil infiltration and higher oxidative stress status in the lungs. On the contrary, FBAC administration inhibited neutrophilic infiltration and reduced oxidative stress. In human bronchial epithelial cells, DEP and HDM exposure increased intracellular oxidative stress and IL-6 and IL-8 secretion. Decreased nuclear factor erythroid 2-related factor 2 (Nrf2) expression and increased phosphor-p62 and LC3B expression were also observed. FBAC treatment attenuated oxidative stress from DEP and HDM exposure., Conclusions: FBAC reduced neutrophilic inflammation exaggerated by DEP exposure in a mouse model of allergic airway inflammation by reducing oxidative stress. PGRN and PGRN-derived proteins may be novel therapeutic agents in attenuating asthma exacerbation induced by air pollutant exposure., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Bladder cancer treatments are highly aggressive and have strong side effects. Safer and more effective treatments are needed. In this study, Dibenzolium (DIB), a potent NADPH oxidase inhibitor, was evaluated for its anti-tumor effects. KK-47 (non-invasive), T24 and 5637 (invasive) cells were used in experiments. Cell proliferation, apoptosis and wound healing assays and western blotting were conducted. In addition, DIB was intratumorally administered to mice bearing KK-47, T24 and 5637 tumors, and tumor size and weight were observed over time. After removing tumors, immunohistochemistry (IHC) staining was conducted. Cell proliferation was significantly suppressed in all cell lines, and apoptotic cells increased in the KK-47 and T24 cell lines after DIB. Wound healing was suppressed in all cell lines by DIB. In KK-47 and T24, DIB increased the protein expression of the epithelial marker E-cadherin. In vivo, DIB safely suppressed tumor growth in all cell lines-bearing mice. Cleaved-Caspase-3 and E-cadherin expression increased in KK-47 and T24 tumors after DIB. In conclusion, DIB inhibited tumor growth by inducing apoptosis through the Caspase-3 pathway and reduced migration and invasion by suppressing epithelial mesenchymal transition (EMT) in bladder cancer similarly shown as our previous study of prostate cancer., (© 2024. The Author(s).)

Background: Episodic angioedema with eosinophilia, also known as Gleich's syndrome, is a differential diagnosis in patients with recurrent angioedema with higher blood eosinophils. Meanwhile, less has been elucidated regarding non-episodic angioedema with eosinophilia (NEAE). This study aimed to examine the prevalence, clinical characteristics, and disease course of NEAE., Methods: By reviewing the electronic medical records, we identified patients with NEAE among those referred to allergy clinics due to eosinophilia from January 2021 to December 2023 at Asan Medical Center., Results: Among 687 patients with eosinophilia, 58 (8.4%) were diagnosed with and treated for NEAE. All patients were females, with a mean age of 31.79 years. The mean absolute blood eosinophil count was 4468.76 cells/μL. All patients reported symmetric angioedema of the lower legs, and 37 (63.8%) had additional angioedema of the upper arms. Twenty-five (43.1%) patients reported a preceding event prior to onset of angioedema. Systemic corticosteroids (mean total dose 1745 ± 508.49 mg) were prescribed to all patients, with a treatment duration of approximately 40 days to achieve resolution. Following the resolution of angioedema, 6 patients experienced persistent arthralgia, 1 developed chronic spontaneous urticaria, and 1 developed hypereosinophilic syndrome., Conclusions: NEAE is an essential differential diagnosis in young female patients with eosinophilia, particularly those presenting with symmetric peripheral angioedema., Competing Interests: The authors declare that there is no conflict of interest to declare., (© 2024 The Author(s).)

Background: Probiotics, which are live microorganisms that, when given in sufficient quantities, promote the host's health, have drawn a lot of interest for their ability to enhance gut health. Enterococcus faecalis , a member of the human gut microbiota, has shown promise as a probiotic candidate due to its functional attributes. However, safety concerns associated with certain strains warrant comprehensive evaluation before therapeutic application., Materials and Methods: In this study, E. faecalis EF-2001, originally isolated from fecal samples of a healthy human infant, was subjected to a multi-faceted assessment for its safety and probiotic potential. In silico analysis, CAZyme, biosynthetic, and stress-responsive proteins were identified., Results: The genome lacked biogenic amine genes but contained some essential amino acid and vitamin synthetic genes, and carbohydrate-related enzymes essential for probiotic properties. The negligible difference of 0.03% between the 1 st and 25 th generations indicates that the genetic information of the E. faecalis EF-2001 genome remained stable. The live E. faecalis EF-2001 ( E. faecalis EF-2001L) demonstrated low or no virulence potential, minimal D-Lactate production, and susceptibility to most antibiotics except some aminoglycosides. No bile salt deconjugation or biogenic amine production was observed in an in vitro assay. Hemolytic activity assessment showed a β-hemolytic pattern, indicating no red blood cell lysis. Furthermore, the EF-2001L did not produce gelatinase and tolerated simulated gastric and intestinal fluids in an in vitro study. Similarly, heat-killed E. faecalis EF-2001 ( E. faecalis EF-2001HK) exhibits tolerance in both acid and base conditions in vitro. Further, no cytotoxicity of postbiotic EF-2001HK was observed in human colorectal adenocarcinoma HT-29 cells., Conclusions: These potential properties suggest that probiotic and postbiotic E. faecalis EF-2001 could be considered safe and retain metabolic activity suitable for human consumption.

Background: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions., Methods: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared., Results: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement., Conclusion: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

A bioinformatic analysis is a promising approach to understand the relationship between the vast tumor microbiome and cancer development. In the present study, we studied the relationships between the intratumoral microbiome and classical clinical risk factors using bioinformatics analysis of the Cancer Genome Atlas (TCGA) and the Cancer Microbiome Atlas (TCMA) datasets. We used TCMA database and investigated the abundance of microbes at the genus level in solid normal tissue (n = 22) and the primary tumors of patients with head and neck squamous cell carcinoma (HNSCC) (n = 154) and identified three major tumor microbiomes, Fusobacterium , Prevotella , and Streptococcus . The tissue level of Fusobacterium was higher in primary tumors than in solid normal tissue. However, univariate and multivariate analyses of these 3 microbes showed no significant effects on patient survival. We then extracted 43, 55, or 59 genes that were differentially expressed between the over and under the median groups for Fusobacterium , Prevotella , or Streptococcus using the criteria of >2.5, >1.5, or >2.0 fold and p  < 0.05 in the Mann-Whitney U test. The results of a pathway analysis revealed the association of Fusobacterium- and Streptococcus -related genes with the IL-17 signaling pathway and Staphylococcus aureus infection, while Prevotella -associated pathways were not extracted. A protein-protein interaction analysis revealed a dense network in the order of Fusobacterium , Streptococcus , and Prevotella . An investigation of the relationships between the intratumoral microbiome and classical clinical risk factors showed that high levels of Fusobacterium were associated with a good prognosis in the absence of alcohol consumption and smoking, while high levels of Streptococcus were associated with a poor prognosis in the absence of alcohol consumption. In conclusion, intratumoral Fusobacterium and Streptococcus may affect the prognosis of patients with HNSCC, and their effects on HNSCC are modulated by the impact of drinking and smoking., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Hypertension incidence increases with age and represents one of the most prevalent risk factors for cardiovascular disease. Clonal events in the hematopoietic system resulting from somatic mutations in driver genes are prevalent in elderly individuals who lack overt hematologic disorders. This condition is referred to as age-related clonal hematopoiesis (CH), and it is a newly recognized risk factor for cardiovascular disease. It is not known whether CH and hypertension in the elderly are causally related and, if so, what are the mechanistic features., Methods: A murine model of adoptive bone marrow transplantation was employed to examine the interplay between Tet2 (ten-eleven translocation methylcytosine dioxygenase 2) clonal hematopoiesis and hypertension., Results: In this model, a subpressor dose of Ang II (angiotensin II) resulted in elevated systolic and diastolic blood pressure as early as 1 day after challenge. These conditions led to the expansion of Tet2-deficient proinflammatory monocytes and bone marrow progenitor populations. Tet2 deficiency promoted renal CCL5 (C-C motif ligand 5) chemokine expression and macrophage infiltration into the kidney. Consistent with macrophage involvement, Tet2 deficiency in myeloid cells promoted hypertension when mice were treated with a subpressor dose of Ang II. The hematopoietic Tet2 -/- condition led to sodium retention, renal inflammasome activation, and elevated levels of IL (interleukin)-1β and IL-18. Analysis of the sodium transporters indicated NCC (sodium-chloride symporter) and NKCC2 (Na + -K + -Cl - cotransporter 2) activation at residues Thr53 and Ser105, respectively. Administration of the NLRP3 (NLR family pyrin domain containing 3) inflammasome inhibitor MCC950 reversed the hypertensive state, sodium retention, and renal transporter activation., Conclusions: Tet2-mediated CH sensitizes mice to a hypertensive stimulus. Mechanistically, the expansion of hematopoietic Tet2-deficient cells promotes hypertension due to elevated renal immune cell infiltration and activation of the NLRP3 inflammasome, with consequences on sodium retention. These data indicate that carriers of TET2 CH could be at elevated risk for the development of hypertension and that immune modulators could be useful in treating hypertension in this patient population., Competing Interests: None.

Four previously undescribed compounds talaromyester A ( 1 ) and purpuresters C-E ( 2 - 4 ), together with known purpurester A ( 5 ) and purpuride G ( 6 ), were isolated from the metabolites produced by the Mariana Trench sediment-derived fungus Talaromyces sp. SY2250. Compounds 2 - 5 , two pairs of racemates, were separated on a chiral HPLC column. Structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and optical rotation calculations. Purpuride G ( 6 ) showed antiproliferative activity against glioma cells and may be the main active compound responsible for the activity of the crude extract prepared from the culture of Talaromyces sp. SY2250 in rice medium.

Background Sublobar resection for lung cancer is usually guided by cutoff values for consolidation size (maximal diameter of the solid tumor component) and consolidation-to-tumor ratio (CTR). The effects of these factors as continuous variables and the reason for established cutoffs are, to the knowledge of the authors, unexplored. Purpose To quantitatively assess the predictive value of CTR and consolidation size for cancer recurrence risk after sublobar resection in clinical stage IA lung adenocarcinoma. Materials and Methods This retrospective study reviewed sublobar resection for clinical stage IA lung adenocarcinoma performed between January 2010 and December 2019. A restricted cubic spline function verified linearity by estimating recurrence probabilities using CTR and consolidation size obtained on preoperative CT scans. Statistical analyses included a Cox proportional hazards model to identify risk factors for cancer recurrence and the Cochran-Armitage trend test for the association between CTR and consolidation size. Results Of 1032 enrolled patients (age, 63.9 years ± 9.9 [SD]; 464 male patients), 523 (50.7%) and 509 (49.3%) underwent wedge resection and segmentectomy, respectively. Among patients with a CTR between 1% and 50% ( n = 201), 187 (93.0%) had a consolidation size of less than or equal to 10 mm ( P < .001). There was a positive association between the risk of recurrence with CTR and consolidation size ( r 2 = 0.727; P < .001). The recurrence rate showed the greatest increase when CTR was greater than 50% or consolidation size was greater than 10 mm. Specifically, the recurrence rate increased from 2.1% (three of 146) at 26%-50% CTR to 8.3% (nine of 108) at 51%-75% CTR, and from 4.4% (eight of 183) for 6-10-mm consolidation size to 11.9% (23 of 194) for 11-15-mm consolidation size. The probability of recurrence exhibited linearity and increased with CTR and consolidation size. Conclusion Cancer recurrence risk after sublobar resection for stage IA adenocarcinoma consistently rises with CTR and consolidation size. Current guideline cutoffs for sublobar resection remain clinically relevant given observed recurrence rates. © RSNA, 2024 Supplemental material is available for this article.

Purpose: Our study explores how attitudes of patients with cancer toward smartphone-based commercial health care apps affect their use and identifies the influencing factors., Materials and Methods: Of the 960 patients with cancer who participated in a randomized controlled trial for a smartphone-based commercial health care app, only 264 participants, who completed a survey on app usage experiences conducted between May and August 2022, were included in this study. Participants were categorized into three groups: Positive Persistence (PP), Negative Nonpersistence (NN), and Neutral (NE) on the basis of their attitude and willingness to use smartphone-based commercial health care apps. The Health-Related Quality of Life (QOL) Instrument (8 Items), European QOL (5 Dimensions; 5 Levels), The Human Interaction and Motivation questionnaire, and open-ended questionnaires were used to examine factors potentially influencing extended utilization of digital interventions., Results: Despite demographic similarities among the three groups, only the PP and NE groups showed similar app usage compared with the NN group. The combined group (positive persistence and neutral) exhibited significant improvement in depression ( P = .02), anxiety ( P = .03), and visual analog scale scores ( P = .02) compared with the NN group. In addition, patient interaction ( P < .01) and the presence of a chatbot/information feature on the app ( P < .01) demonstrated a significant difference across the three groups, with the most favorable response observed among the PP group. Patients were primarily motivated to use the app owing to its health management functions, while the personal challenges they encountered during app usage acted as deterrents., Conclusion: These findings suggest that maintaining a non-negative attitude toward smartphone-based commercial health care apps could lead to an improvement in psychological distress. In addition, the social aspect of apps could contribute to extending patient's utilization of digital interventions.

The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC-CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC-CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC- FHC OE ) and hiPSC-CMs overexpressing FHC (hiPSC-CM-FHC OE ) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC-CM-Control. Furthermore, hiPSC-CM-FHC OE presented robust contrast and lower T 2 * values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC-CM-FHC OE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC-CM-FHC OE cells exhibited clear signals in the hearts with lower T 2 * and rapid signal decay. Collectively, data from this proof-of-concept study demonstrated that endogenous labeling with FHC in hiPSC-CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC-CMs in the hearts of live animals., (© 2024 Wiley‐VCH GmbH.)

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder often misdiagnosed as Parkinson's Disease (PD) due to shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, leading to loss of balance, gaze impairment, and dementia. Diagnosing PSP is challenging, and there is a significant demand for reliable biomarkers. Existing biomarkers, including tau protein and neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF), show inconsistencies in distinguishing PSP from other neurodegenerative disorders. Therefore, the development of new biomarkers for PSP is imperative., Methods: We conducted an extensive proteome analysis of CSF samples from 40 PSP patients, 40 PD patients, and 40 healthy controls (HC) using tandem mass tag-based quantification. Mass spectrometry analysis of 120 CSF samples was performed across 13 batches of 11-plex TMT experiments, with data normalization to reduce batch effects. Pathway, interactome, cell-type-specific enrichment, and bootstrap receiver operating characteristic analyses were performed to identify key candidate biomarkers., Results: We identified a total of 3,653 unique proteins. Our analysis revealed 190, 152, and 247 differentially expressed proteins in comparisons of PSP vs. HC, PSP vs. PD, and PSP vs. both PD and HC, respectively. Gene set enrichment and interactome analysis of the differentially expressed proteins in PSP CSF showed their involvement in cell adhesion, cholesterol metabolism, and glycan biosynthesis. Cell-type enrichment analysis indicated a predominance of neuronally-derived proteins among the differentially expressed proteins. The potential biomarker classification performance demonstrated that ATP6AP2 (reduced in PSP) had the highest AUC (0.922), followed by NEFM, EFEMP2, LAMP2, CHST12, FAT2, B4GALT1, LCAT, CBLN3, FSTL5, ATP6AP1, and GGH., Conclusion: Biomarker candidate proteins ATP6AP2, NEFM, and CHI3L1 were identified as key differentiators of PSP from the other groups. This study represents the first large-scale use of mass spectrometry-based proteome analysis to identify cerebrospinal fluid (CSF) biomarkers specific to progressive supranuclear palsy (PSP) that can differentiate it from Parkinson's disease (PD) and healthy controls. Our findings lay a crucial foundation for the development and validation of reliable biomarkers, which will enhance diagnostic accuracy and facilitate early detection of PSP., (© 2024. The Author(s).)

Studyholism (or obsession with studying) is a new potential clinical condition introduced in the literature in 2017. Since then, growing research has supported its conceptualization as a clinical disorder and highlighted some potential intervention targets, namely trait worry, social anxiety, negative interpretation bias, and defense mechanisms. The present study aims to extend the literature concerning psychodynamic-related constructs that might constitute targets for interventions aimed at reducing Studyholism by investigating the role of attachment in 1073 students ( M age = 23.48 ± 3.77), balanced concerning civil status (i.e., currently being single or involved in a relationship/non-single). Among the main findings, we found that insecure attachment-mainly preoccupied attachment-is a positive predictor of Studyholism in both non-single and single students. However, there are also some differences depending on the civil status. Finally, (single) disengaged studyholics have a statistically significant lower level of secure attachment than (single) engaged studyholics. In conclusion, this study showed the value of distinguishing between non-single and single students when investigating the role of attachment. Regarding problematic overstudying specifically, the study provided support for its definition as a clinical disorder, also with evidence of the appropriateness of its OCD-related conceptualization. Finally, it suggests preoccupied (insecure) attachment as a target to reduce Studyholism by fostering in students the feeling of being loved and deserving of being loved in their current adult relationships.

Background: Professionals with expertise in health informatics play a crucial role in the digital health sector. Despite efforts to train experts in this field, the specific impact of such training, especially for individuals from diverse academic backgrounds, remains undetermined., Objective: This study therefore aims to evaluate the effectiveness of an intensive health informatics training program on graduates with respect to their job roles, transitions, and competencies and to provide insights for curriculum design and future research., Methods: A survey was conducted among 206 students who completed the Advanced Health Informatics Analyst program between 2018 and 2022. The questionnaire comprised four categories: (1) general information about the respondent, (2) changes before and after program completion, (3) the impact of the program on professional practice, and (4) continuing education requirements., Results: The study received 161 (78.2%) responses from the 206 students. Graduates of the program had diverse academic backgrounds and consequently undertook various informatics tasks after their training. Most graduates (117/161, 72.7%) are now involved in tasks such as data preprocessing, visualizing results for better understanding, and report writing for data processing and analysis. Program participation significantly improved job performance (P=.03), especially for those with a master's degree or higher (odds ratio 2.74, 95% CI 1.08-6.95) and those from regions other than Seoul or Gyeonggi-do (odds ratio 10.95, 95% CI 1.08-6.95). A substantial number of respondents indicated that the training had a substantial influence on their career transitions, primarily by providing a better understanding of job roles and generating intrinsic interest in the field., Conclusions: The integrated practical education program was effective in addressing the diverse needs of trainees from various fields, enhancing their capabilities, and preparing them for the evolving industry demands. This study emphasizes the value of providing specialized training in health informatics for graduates regardless of their discipline., (© Kye Hwa Lee, Jae Ho Lee, Yura Lee, Hyunna Lee, Ji Sung Lee, Hye Jeon Jang, Kun Hee Lee, Jeong Hyun Han, SuJung Jang. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodeling during repair, as predicted by a minimal mathematical modeling of the spatiotemporal dynamics and fate behavior of basal cells. The basal cell layer progressively returns to a solid-like state with re-epithelialization. Bulk, single-cell RNA, and epigenetic profiling of SCs, together with functional experiments, uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting in poor quality of life. Beyond the cardiomyocyte-centric view of heart failure, it is now accepted that alterations in the interstitial extracellular matrix (ECM) also play a major role in the development of heart failure. Here, we show that protein kinase N (PKN) is expressed in cardiac fibroblasts. Furthermore, PKN mediates the conversion of fibroblasts into myofibroblasts, which plays a central role in secreting large amounts of ECM proteins via p38 phosphorylation signaling. Fibroblast-specific deletion of PKN led to a reduction of myocardial fibrotic changes and cardiac dysfunction in mice models of ischemia-reperfusion or heart failure with preserved ejection fraction. Our results indicate that PKN is a therapeutic target for cardiac fibrosis in heart failure., (© 2024. The Author(s).)

We aimed to evaluate the ability of deep learning (DL) models to identify patients from a paired chest radiograph (CXR) and compare their performance with that of human experts. In this retrospective study, patient identification DL models were developed using 240,004 CXRs. The models were validated using multiple datasets, namely, internal validation, CheXpert, and Chest ImaGenome (CIG), which include different populations. Model performance was analyzed in terms of disease change status. The performance of the models to identify patients from paired CXRs was compared with three junior radiology residents (group I), two senior radiology residents (group II), and two board-certified expert radiologists (group III). For the reader study, 240 patients (age, 56.617 ± 13.690 years, 113 females, 160 same pairs) were evaluated. A one-sided non-inferiority test was performed with a one-sided margin of 0.05. SimChest, our similarity-based DL model, demonstrated the best patient identification performance across multiple datasets, regardless of disease change status (internal validation [area under the receiver operating characteristic curve range: 0.992-0.999], CheXpert [0.933-0.948], and CIG [0.949-0.951]). The radiologists identified patients from the paired CXRs with a mean accuracy of 0.900 (95% confidence interval: 0.852-0.948), with performance increasing with experience (mean accuracy:group I [0.874], group II [0.904], group III [0.935], and SimChest [0.904]). SimChest achieved non-inferior performance compared to the radiologists (P for non-inferiority: 0.015). The findings of this diagnostic study indicate that DL models can screen for patient misidentification using a pair of CXRs non-inferiorly to human experts., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background: Digital health care apps, including digital therapeutics, have the potential to increase accessibility and improve patient engagement by overcoming the limitations of traditional facility-based medical treatments. However, there are no established tools capable of quantitatively measuring long-term engagement at present., Objective: This study aimed to evaluate an existing engagement index (EI) in a commercial health management app for long-term use and compare it with a newly developed EI., Methods: Participants were recruited from cancer survivors enrolled in a randomized controlled trial that evaluated the impact of mobile health apps on recovery. Of these patients, 240 were included in the study and randomly assigned to the Noom app (Noom Inc). The newly developed EI was compared with the existing EI, and a long-term use analysis was conducted. Furthermore, the new EI was evaluated based on adapted measurements from the Web Matrix Visitor Index, focusing on click depth, recency, and loyalty indices., Results: The newly developed EI model outperformed the existing EI model in terms of predicting EI of a 6- to 9-month period based on the EI of a 3- to 6-month period. The existing model had a mean squared error of 0.096, a root mean squared error of 0.310, and an R 2 of 0.053. Meanwhile, the newly developed EI models showed improved performance, with the best one achieving a mean squared error of 0.025, root mean squared error of 0.157, and R 2 of 0.610. The existing EI exhibited significant associations: the click depth index (hazard ratio [HR] 0.49, 95% CI 0.29-0.84; P<.001) and loyalty index (HR 0.17, 95% CI 0.09-0.31; P<.001) were significantly associated with improved survival, whereas the recency index exhibited no significant association (HR 1.30, 95% CI 1.70-2.42; P=.41). Among the new EI models, the EI with a menu combination of menus available in the app's free version yielded the most promising result. Furthermore, it exhibited significant associations with the loyalty index (HR 0.32, 95% CI 0.16-0.62; P<.001) and the recency index (HR 0.47, 95% CI 0.30-0.75; P<.001)., Conclusions: The newly developed EI model outperformed the existing model in terms of the prediction of long-term user engagement and compliance in a mobile health app context. We emphasized the importance of log data and suggested avenues for future research to address the subjectivity of the EI and incorporate a broader range of indices for comprehensive evaluation., (©Yae Won Tak, Jong Won Lee, Junetae Kim, Yura Lee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.09.2024.)

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established., Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization., Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG&#95;RTK2 (n = 19), pedHGG&#95;A/B (n = 6), and pedHGG&#95;MYCN (n = 5), but only one pedHGG&#95;RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS., Conclusions: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG&#95;RTK2, pedHGG&#95;A/B, EGFR and BCOR mutations, chromosome 6 rearrangements)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objectives: Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan., Methods: A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database., Results: Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death., Conclusions: The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Improvements in therapies for heart failure with preserved ejection fraction (HFpEF) are crucial for improving patient outcomes and quality of life. Although HFpEF is the predominant heart failure type among older individuals, its prognosis is often poor owing to the lack of effective therapies. The roles of the spleen and bone marrow are often overlooked in the context of HFpEF. Recent studies suggest that the spleen and bone marrow could play key roles in HFpEF, especially in relation to inflammation and immune responses. The bone marrow can increase production of certain immune cells that can migrate to the heart and contribute to disease. The spleen can contribute to immune responses that either protect or exacerbate heart failure. Extramedullary hematopoiesis in the spleen could play a crucial role in HFpEF. Increased metabolic activity in the spleen, immune cell production and mobilization to the heart, and concomitant cytokine production may occur in heart failure. This leads to systemic chronic inflammation, along with an imbalance of immune cells (macrophages) in the heart, resulting in chronic inflammation and progressive fibrosis, potentially leading to decreased cardiac function. The bone marrow and spleen are involved in altered iron metabolism and anemia, which also contribute to HFpEF. This review presents the concept of an interplay between the heart, spleen, and bone marrow in the setting of HFpEF, with a particular focus on extramedullary hematopoiesis in the spleen. The aim of this review is to discern whether the spleen can serve as a new therapeutic target for HFpEF., (© 2024. The Author(s).)

Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target., Competing Interests: Declaration of interests M.G.F. is a consultant for Twentyeight-Seven Therapeutics and Blueprint Medicines. M.M. is an SAB member for Cygnal Therapeutics. K.L.L. is founder and equity holder of Travera Inc. and receives consulting fees from BMS, Integragen, and Rarecyte, and research support from Lilly, BMS, and Amgen. D.H. has acted as an advisor for Novartis in relation to ribociclib., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)