bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between systemic immune-inflammation index and cardiotoxicity related to 5-Fluorouracil in colorectal cancer
Authors: Liu Xiaoqin , Wang Yan , Wang Wenling , Dong Hongming , Wang Gang , Chen Wanghua , Chen Juan , Chen Weiwei
Published: July 2024

Background and aims

The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort.

Methods

The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted.

Results

Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98).

Conclusion

Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.
Development and validation of a health literacy scale for family caregivers of older people with chronic illness
Authors: Kor Patrick Pui Kin , Yu Clare Tsz Kiu , Li Yaqin , Tsang Alex Pak Lik , Tan Lexi Han Zhi , Lam Simon Ching , Lee Paul Hong , Liu Justina Yat Wa , Leung Angela Yee Man , Lee Ka Ching
Published: July 2024

Background

Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness.

Methods

Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale’s structure. Concurrent validity, internal consistency, and test-retest reliability were also examined.

Results

A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p < 0.01). The Cronbach’s α coefficient of the scale was 0.96, with subscales ranging from 0.84 to 0.91. The two-week test-retest reliability was 0.77 (p < 0.01).

Conclusion

This study developed a conceptual model explaining the concept and factors of health literacy among FCs of older people with chronic illness that could provide the groundwork for future studies in developing relevant evidence-based interventions. A new Health Literacy Scale-Family Caregiver (HLS-FC) with satisfactory psychometric properties was developed in this study, which can be utilized to identify caregivers with insufficient health literacy and facilitate timely interventions by healthcare professionals.
Turkish psychometric characteristics of the humanistic practice ability of nursing scale: differences by education, working year, and professional satisfaction
Authors: Sahin Ayse , Tarsuslu Bedia , Yilmaz Aslı , Kuni Filiz , Durat Gulgun
Published: July 2024

Background

Humanistic nursing practices scientifically improve the knowledge structure of nursing, enrich its theoretical system and support its development. Therefore, it is crucial to evaluate the humanistic practice abilities of nurses.

Objective

This study aimed to test the psycholinguistic features, language and construct validity of the Humanistic Practice Ability of Nursing Scale and to examine it according to nurses’ demographic characteristics.

Design and methods

This study was a methodological type of analytical research conducted with 397 clinical nurses working in a hospital. A questionnaire including demographic information and evaluating empathy and compassion adequacy was used. Data were analyzed using explanatory and confirmatory factor analysis, Cronbach’s alpha, item-total score correlation, split-half analysis, t-test, analysis of variance and correlation analysis.

Results

The scale consists of 29 items and four factors, explaining 61.15% of the total variance. Factor loads were > 0.30. confirmatory factor analysis results were χ2/df: 2.58, GFI: 0.86, TLI: 0.91, IFI: 0.92, CFI: 0.92, RMSEA: 0.06, and SRMR: 0.03. The Cronbach alpha value for the full scale is 0.95. A significant relationship was found between the scale and empathy and compassion proficiency. It was observed that the scale scores differed according to the nurses’ education level, working years and job satisfaction (p < 0.05).

Conclusion

This study shows that the Turkish version of the HPAN scale is valid and reliable for 29 items and four factors. The humanistic practice ability of nurses differ according to postgraduate education, years of working in the profession and professional satisfaction.
Impaired GK-GKRP interaction rather than direct GK activation worsens lipid profiles and contributes to long-term complications: a Mendelian randomization study
Authors: Wang Ke , Shi Mai , Luk Andrea O. Y. , Kong Alice P. S. , Ma Ronald C. W. , Li Changhong , Chen Li , Chow Elaine , Chan Juliana C. N.
Published: July 2024

Background

Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction.

Methods

Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR).

Results

Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57–46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78–4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54–0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results.

Conclusions

Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.
LINC00665 promotes the progression and immune evasion of lung cancer by facilitating the translation of TCF7 protein through dependence on IRES
Authors: Han Chaonan , Su Jinchen , Pei Yue , Su Xiangyu , Zheng Di
Published: July 2024

Objective

To investigate the influence of LINC00665 on the development and immune evasion of lung cancer.

Methods

Tumor tissues and corresponding adjacent tissues were collected from 84 lung cancer patients, categorized into non-metastatic (n = 58) and metastatic (n = 26) groups. LINC00665 expression in lung cancer and metastatic lung cancer tissues was assessed via qRT-PCR. Pearson correlation analysis was conducted to examine the correlation between LINC00665 and immune-modulating cytokines (TGF-β, IL-10, IL-1β, IFN-γ, IL-2, TNF-α). A549 and H1299 cells, with relatively high LINC00665 expression, were used for in vitro studies. Cells were transfected with LINC00665-targeting shRNA, and changes in proliferation, apoptosis, migration, invasion, and NK cell cytotoxicity were assessed. Downstream molecular mechanisms of LINC00665 were investigated using GEO database analysis, highlighting the association with HHLA2. LINC00665’s role in promoting HHLA2 expression via binding with TCF7 was explored. In low LINC00665-expressing A549/H1299 cells, overexpression of HHLA2 was performed to evaluate effects on malignant behavior and NK cell sensitivity. A xenograft model was established for in vivo validation through tumor volume and weight measurements, Ki-67 immunoreactivity analysis, and flow cytometry analysis of CD107a + NK cells.

Results

LINC00665, TCF7 mRNA, and HHLA2 mRNA expression levels were significantly higher in lung cancer tissues than adjacent tissues, with non-metastatic lung cancer showing higher expression than metastatic lung cancer. In metastatic lung cancer, LINC00665 positively correlated with immune-suppressive cytokines (TGF-β, IL-10, IL-1β) and negatively correlated with anti-tumor cytokines (IFN-γ, IL-2, TNF-α). LINC00665 knockdown significantly inhibited lung cancer cell growth and metastasis, promoting sensitivity to NK cells. Further analysis revealed that LINC00665 recruits transcription factor TCF7 to upregulate HHLA2 expression in lung cancer cells, thereby facilitating lung cancer development and immune escape.

Conclusion

LINC00665, through recruitment of TCF7 and upregulation of HHLA2, inhibits NK cell cytotoxicity, promoting the development and immune evasion of lung cancer.
Senescent endothelial cells promote liver metastasis of uveal melanoma in single-cell resolution
Authors: Ma Liang , He Xiaoyu , Fu Yidian , Ge Shengfang , Yang Zhi
Published: July 2024

Background

Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM.

Methods

By using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects.

Results

UM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment.

Conclusion

This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.
A bibliometric study related to the treatment of myocardial ischemia-reperfusion Injury
Authors: Feng Jie , Han Leilei , Liu Yunman , Li Kai , Wu Yanqing
Published: July 2024

Background

Myocardial ischemia-reperfusion injury (MIRI) is defined as the restoration of blood flow to the myocardium after a brief interruption of blood supply, causing more severe damage to the ischemic myocardium. However, currently, reperfusion therapy is the preferred therapy for ischemic cardiomyopathy, which undoubtedly causes MIRI, and thus it has become a challenging issue affecting the prognosis of coronary artery disease.

Methods

A search was conducted in the Web of Science Core Collection database for papers relevant to MIRI therapy published between 1 January 2000 and 1 October 2023. Bibliometric analyses were performed using VOSviewer and CiteSpace to elucidate the progress and hotspots.

Results

3304 papers from 64 countries, 2134 research institutions and 13,228 authors were enrolled in the study. Of these, China contributed the most papers and had the biggest impact, while the United States had the most extensive partnership. The Fourth Military Medical University was the primary research institution. The most valuable authors include Chattipakorn, Nipon, Chattipakorn, Siriporn c, Yang, Jian and Yang, Yang.

Conclusion

Over the past 20 years, research on MIRI therapies has made significant strides. Further studies are necessary to explore the interactions between various therapeutic options. Future investigations will emphasize nanocarriers, cardiac regeneration, and stem cell therapies. Our study identifies MIRI research hotspots from a bibliometric perspective, forecasts future trends, and offers fresh insights into MIRI therapy research.
Biosynthesis of TiO2 nano particles by using Rosemary (Rosmarinus officinalis) leaf extracts and its application for crystal dye degradation under sunlight
Authors: Saka Abel , Jule Leta Tesfaye , Badassa Bayissa , Gudata Lamessa , Nagaprasad N. , Shanmugam R. , Dwarampudi L. Priyanka , Seenivasan Venkatesh , Ramaswamy Krishnaraj
Published: July 2024

Titanium dioxide (TiO2) nanoparticles were prepared through Rosmarinus-officinalis leaf extracts at 90 and 200°C. In this research, the degradations of methylene blues by using TiO2 nanoparticles Sun light radiations were studied. The synthesized materials were characterized using XRDs, UV-Vis, PL, SEM, TEM, EDS and XPS. The results displayed that bio-synthesis temperatures intrude the shapes and sizes of TiO2 nanoparticles. For TiO2-90, micrographs show separable crystalline with irregular morphologies and agglomerate cubic particles. For the other TiO2-200 sample, SEM and TEM micro-imaging shows crumbly agglomerated cubic structures. The XRD shows that the intense peaks observed at angles of 25.37°, 37.19°, 47.81° and 53.89° confirming a highly crystalline oriented as (004), (200), and (105) planes respectively. The optical properties of TiO2 nanoparticles synthesized were conveyed by PL and UV-Vis. The energy band gap calculated was 3.0 eV for both samples; that indicates heating temperature didn’t influence the band gap of the samples. The elemental composition Ti and O2 is shown by EDS and XPS. Photo-catalytic experiments discovered that TiO2-90 nanoparticles were well-organized in photo-degradations of MB, likened to TiO2-200. The great activities of TiO2-90 were because of better physicochemical characteristics associated with TiO2-200 effectively degrading MB under photo-light. Photo-degradations of dye under sunlight as plentifully obtainable energy sources by TiO2, synthesized by simpler techniques, can be hopeful to grow an eco-friendly and economical process.
Diagnostic performance of an ultra-sensitive RDT and a conventional RDT in malaria mass testing, treatment and tracking interventions in southern Ghana
Authors: Amoah Linda Eva , Cheng Ndong Ignatius , Acquah Festus Kojo , Adu-Amankwah Susan , Bredu Dorcas Gyama , Mensah Benedicta A. , Anang Sherik-fa , Abban Bernice Cubson , Busayomi Abena , Kwarpong Sebastian Shine , Tey Prosper Kofi , Cudjoe Elizabeth , Asamoah Alexander , Holden Tobias McKenzie , Gerardin Jaline , Nonvignon Justice , Ahorlu Collins
Published: July 2024

Background

Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite carriers play a key role in sustaining transmission. This study assessed the effectiveness of using the Ultra-sensitive NxTek eliminate RDT (uRDT) and conventional SD Bioline HRP2 RDT (cRDT) in diagnosing asymptomatic parasitaemia while measuring the impact of mass testing, treatment and tracking (MTTT) on the prevalence of asymptomatic malaria over a 1-year period in Ghana.

Methods

A total of 4000 targeted participants from two towns, Obom and Kofi Kwei, with their surrounding villages, were tested for asymptomatic malaria four times over the study period using uRDT (intervention) and the cRDT (control) respectively. Participants carrying malaria parasites were followed by home visit and phone calls for compliance to treatment, and filter paper blood blots collected from participants were used to determine true parasite carriage by PET-PCR. A mathematical model of the study site was developed and used to test the impact of test sensitivity and mass migration on the effect of MTTT.

Results

The start and end point sensitivities of the cRDT were 48.8% and 41.7% and those for the uRDT were 52.9% and 59.9% respectively. After a year of MTTTs, asymptomatic parasite prevalence, as determined by PCR, did not differ statistically in the control site (40.6% to 40.1%,P = 0.730) but decreased at the intervention site (55.9% to 46.4%,P < 0.0001). Parasite prevalence by RDT, however, indicated statistical reduction in the control site (25.3% to 22.3%,P = 0.017) and no change in the intervention site (35.1% to 36.0%,P = 0.614). The model predicted a mild effect of both diagnostic sensitivity and human movement in diminishing the impact of MTTT in the study sites.

Conclusions

Asymptomatic parasite prevalence at the molecular level reduced significantly in the site where the uRDT was used but not where the cRDT was used. Overall, the uRDT exhibited higher sensitivity relative to the cRDT. Highly sensitive molecular techniques such as PET-PCR should be included in parasite prevalence estimation during MTTT exercises.

Graphical Abstract
Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report
Authors: Kerola Anne M. , Eklund Kari K. , Valleala Heikki , Tynninen Olli , Helve Jaakko , Haapamäki Ville , Eriksson Mari
Published: July 2024

Background

Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.

Case presentation

We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3–4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.

Conclusions

Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.
Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages
Authors: Tawfik Marwa Mamdouh , Lorgen-Ritchie Marlene , Król Elżbieta , McMillan Stuart , Norambuena Fernando , Bolnick Daniel I. , Douglas Alex , Tocher Douglas R , Betancor Mónica B. , Martin Samuel A. M.
Published: July 2024

To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.
Integrated preparation and manipulation of high-dimensional flying structured photons
Authors: Zhao Haoqi , Zhang Yichi , Gao Zihe , Yim Jieun , Wu Shuang , Litchinitser Natalia M. , Ge Li , Feng Liang
Published: July 2024

The hope for a futuristic global quantum internet that provides robust and high-capacity quantum information transfer lies largely on qudits, the fundamental quantum information carriers prepared in high-dimensional superposition states. However, preparing and manipulating N-dimensional flying qudits as well as subsequently establishing their entanglement are still challenging tasks, which require precise and simultaneous maneuver of 2 (N-1) parameters across multiple degrees of freedom. Here, using an integrated approach, we explore the synergy from two degrees of freedom of light, spatial mode and polarization, to generate, encode, and manipulate flying structured photons and their formed qudits in a four-dimensional Hilbert space with high quantum fidelity, intrinsically enabling enhanced noise resilience and higher quantum data rates. The four eigen spin–orbit modes of our qudits possess identical spatial–temporal characteristics in terms of intensity distribution and group velocity, thereby preserving long-haul coherence within the entirety of the quantum data transmission link. Judiciously leveraging the bi-photon entanglement, which is well preserved in the integrated manipulation process, we present versatile spin–orbit cluster states in an extensive dimensional Hilbert space. Such cluster states hold the promise for quantum error correction which can further bolster the channel robustness in long-range quantum communication.
2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease
Authors: Shim Chi Young , Kim Eun Kyoung , Cho Dong-Hyuk , Park Jun-Bean , Seo Jeong-Sook , Son Jung-Woo , Kim In-Cheol , Lee Sang-Hyun , Heo Ran , Lee Hyun-Jung , Lee Sahmin , Sun Byung Joo , Yoon Se-Jung , Lee Sun Hwa , Kim Hyung Yoon , Kim Hyue Mee , Park Jae-Hyeong , Hong Geu-Ru , Jung Hae Ok , Kim Yong-Jin , Kim Kye Hun , Kang Duk-Hyun , Ha Jong-Won , Kim Hyungseop , Chung Wook-Jin , Park Chan Seok , Ahn Hyo-Suk , Chung Woo-Baek , Cho Eun Joo , Cho Jung Sun , Ryu Dong Ryeol , Yang Dong Heon , Park Jeong Rang , Kim Woo-Shik , Sohn Il Suk , Na Jin Oh , Park Seong-Mi , Hwang Sun Ho , Choi Ji-Yong , Park Tae-Ho , Park Yong Hyun , Choi Jung Hyun , Kim Hack-Lyoung , Seo Hye Sun , Park Jin-Sun , Choi Eui-Young , Son Jang-Won , Kim Shin-Jae , Rhee Sang Jae , Cho In-Jeong , Byun Young Sup , Shin Sung-Hee , Lee Sun Hwa , Beom Jong Wook , Lee Ju-Hee , Bae Dae-Hwan , Kim Sung-Ai , Park Dae Gyun , Kang Min-Kyung , Hong Kyung-Soon ,   The Korean Valve Survey Investigators
Published: July 2024

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.
Seismic Soundoff: The untapped potential of nonseismic methods
Authors: Geary Andrew
Published: July 2024

In episode 221 of SEG's Seismic Soundoff podcast, Irina Filina discusses a recent special section in The Leading Edge on gravity, electrical, and magnetic methods. Filina unravels misconceptions about nonseismic methods and advocates for their proper use and integration with seismic data. With compelling examples, this episode illustrates how these methods can reduce uncertainty and costs in subsurface exploration.
Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Authors: Nabil Laimon Yasmin , Paul Morgan , Ghandour Fatme , El Ahmar Nourhan , Matar Sayed , Denize Thomas , Bagheri Sheshdeh Aseman , Savla Varunika , Mohanna Razan Assaad , Sun Maxine , Saliby Renee Maria , Saad Eddy , Machaalani Marc , Braun David A. , Aftab Dana T. , Xie Wanling , CHOUEIRI Toni K. , Signoretti Sabina
Published: July 2024

4543

Background: High expression of the receptor tyrosine kinase AXL has been associated with resistance to targeted agents and anti-PD-1 therapy in multiple tumor types, including metastatic clear cell Renal Cell Carcinoma (mccRCC). Cabozantinib (cabo), a multitargeted tyrosine kinase inhibitor (TKI) active against VEGFR, MET, and AXL, is approved for the treatment of mccRCC, but no predictive biomarkers are available. Here, we analyzed tumor samples from the METEOR trial to assess whether AXL expression predicts improved clinical outcomes with cabo relative to everolimus (evero, mTOR inhibitor) in patients (pts) with mccRCC. Methods: Double immunohistochemistry staining for AXL and CD45/CD163 (immune cell/ macrophage markers) was performed on 278 pretreatment tumor tissues from the METEOR trial (cabo=147; evero=131). Image analysis algorithms were used to assess the % of AXL+ tumor cells (TC), % of AXL+ immune cells (IC), and combined % of AXL+ TC and IC (TC/IC). Optimal cutoffs, based on the minimum p-value approach, were determined at the 17th, 30th, and 22nd percentile for TC, IC, and TC/IC, respectively. The association with progression-free survival (PFS) was assessed using Cox regression adjusted for IMDC risk groups, the presence of bone metastases, and the number of previous VEGFR TKI treatments. The association with objective response rate (ORR) (cabo arm only due to low response rate in evero arm) was reported descriptively. Results: We observed a strong correlation between % AXL+ TC and % AXL+ IC (Spearman correlation coefficient 0.85; p-value <0.001). In the evero arm, high % AXL+ TC and high % AXL+ TC/IC were significantly associated with shorter PFS (median 1.9 vs. 4.1 months and 1.9 vs 4.2 months, respectively); a similar trend was observed for % AXL+ IC. In the cabo arm, % AXL+ TC, % AXL+ IC, and % AXL+ TC/IC were not associated with PFS or ORR (Table). The magnitude of increase in PFS for pts receiving cabo versus evero was larger in pts with high % AXL+ TC compared to pts with low % AXL+ TC (HR: 0.30 vs. 0.51, p-interaction=0.18) and in pts with high % AXL+ TC/IC compared to pts with low % AXL+ TC/IC (HR: 0.30 vs 0.53, p-interaction=0.12). Conclusions: Our finding that the improvement in outcome with cabo relative to evero is more evident in pts with high levels of AXL expression supports that the antitumor activity of cabo in mccRCC is mediated, in part, by AXL inhibition. Our work identifies AXL expression as a potential predictive biomarker for cabo-based therapies in mccRCC. [Table: see text]
Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Authors: Zaemes Jacob Peter , Hugaboom Miya , Shah Valisha , Haas Naomi B. , McDermott David F. , Jegede Opeyemi , Bilen Mehmet Asim , Stein Mark N. , Sosman Jeffrey A. , Alter Robert S. , Plimack Elizabeth R. , Hurwitz Michael E. , Wu Catherine J. , Einstein David Johnson , Hammers Hans J. , Signoretti Sabina , West Destiny , Denize Thomas , Atkins Michael B. , Braun David A.
Published: July 2024

4546

Background: Seven molecular subsets of ccRCC have been proposed: 1: Angiogenic/Stromal; 2: Angiogenic; 3: Complement/Ω-oxidation; 4: T-effector/Proliferative; 5: Proliferative; 6: Stromal/Proliferative; and 7: snoRNA (Motzer et al. Can Cell 2020). In an analysis of IMmotion 151, which compared 1L atezolizumab/bevacizumab to sunitinib, combination immune checkpoint blockade (ICB) and anti-VEGF therapy was associated with improved progression-free survival (PFS) and overall survival (OS) in clusters (CLs) 4 and 5, increased PFS in CL 7, and decreased OS in CL 2 (Motzer Can Cell 2020, Motzer JAMA Onc 2022). CL 4 was also associated with higher PFS and objective response rate (ORR) in >1L nivo compared to everolimus in an analysis of CheckMate-025 (Denize CCR 2022). To date, outcomes have not been compared among accRCC subtypes in pts who received 1L pure ICB. Methods: In HCRN GU16-260-Cohort A, pts with accRCC received 1L nivo monotherapy until progressive disease (PD), unacceptable toxicity, or completion of 96 weeks of therapy. Pre-treatment FFPE tumor samples were obtained. A machine learning model (random forest) was trained on annotated transcriptomic data from bulk RNA-seq and used to classify tumors that passed quality control into one of the 7 molecular subtypes. Results: 70 tumor samples contained adequate RNA quality and were classified as outlined in the table. IMDC rates and ORR (40%) for the RNAseq population closely matched those of the whole study (Atkins JCO 2022). No tumors were classified in CL 7 and only 3 in CL 5. Tumors in each IMDC group contained a mix of subtypes. The highest ORR occurred in CL 4 (6/10, 60.0%); CL 4 median PFS was 15.2 months and 1-year PFS was 60%. ORR was also high in CLs 1 and 3 at 52.4% and 40.0%, respectively and lowest in CL 2 (12.5%). PD as best response (5/10, 50.0%) and short PFS (5.1 months) were seen in CL 6. Conclusions: Consistent with prior analyses with combination ICB + anti-VEGF and >1L ICB, CL 4 was associated with robust 1L ICB monotherapy antitumor efficacy. Surprisingly, ORR was also high in CLs 1 and 3. In this small dataset, transcriptomic signatures enriched for but did not fully predict ORR. Future prospective trials are needed to identify more discriminative biomarkers of efficacy for pure ICB therapy.[Table: see text]
A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183).
Authors: Hussain Maha H. A. , Kocherginsky Masha , Singh Parminder , Tan Winston , Myint Zin , Jiang Di (Maria) , Wulff-Burchfield Elizabeth Marie , Ma Yangruijue , Sharon Elad , Piekarz Richard , Meeks Joshua J , VanderWeele David James
Published: July 2024

4574

Background: Mutations of COMPASS-related proteins KMT2D, KMT2C, and KDM6A are observed in 66% of advanced urothelial carcinomas (UC). In vivo, the administration of tazemetostat, an enzymatic EZH2 inhibitor (EZH2i), reduced tumor burden and enhanced the immune response in animal models of UC. We hypothesized that tazemetostat might improve response to immunotherapy in advanced UC. Methods: ETCTN 10183 (NCT03854474) is a multicenter pilot study evaluating the safety and efficacy of tazemetostat 800 mg BID+ pembrolizumab 200 mg given every three weeks for up to two years in patients (pts) with platinum-refractory (Arm A) or cisplatin/chemo-ineligible advanced UC (Arm B). The primary objective was to identify the recommended phase two dose (RP2D) of tazemetostat in combination with pembrolizumab. Secondary objectives included safety, response rate, and progression-free survival. Translational objectives included determining tumor mutational burden in COMPASS-related genes, tumor subtyping, TCR clonality, T cell infiltration, and PDL-1 expression. Results: There were no dose-limiting toxicities in the safety lead-in phase (n=6 pts), and the RP2D for tazemetostat was established at 800 mg BID. Baseline characteristics for Arm A N=12, Arm B N=13: 72% males; 96% white, 4% Black; 88% ECOG PS 0-1; 88% had bladder primary, 20% Stage III, 72% stage IV; 80% had visceral or bone metastases. The median number of cycles was 5 in Arm A (range 1-35) and 4 in Arm B (range 2-12). Treatment related G3/4 adverse events (AEs) were observed in 8 patients, most common were anemia and lymphopenia (n=2 each). Treatment related G1/2 AEs included nausea (n=6); skin and subcutaneous tissue disorders (n=3); anemia, lymphopenia, and thrombocytopenia (n=2 each). Among evaluable patients (n=10 in each arm), partial response rate was: Arm A 30%, Arm B 20%; stable disease: Arm A 30%, Arm B 30%; and progressive disease: Arm A 30%, Arm B 20%. 8 pts were on study treatment for ≥ 9 cycles (5 in Arm A, 3 in Arm B). All pts are off protocol treatment. Median progression-free survival was 3.06 (95% CI: 1.38-7.75) months for Arm A and 3.02 (95%CI: 2.4-5.65) for Arm B. Conclusions: Tazemetostat 800 mg BID and pembrolizumab combination is feasible and well-tolerated in patients with advanced UC. In this pilot study, improvement in efficacy relative to historical controls of pembrolizumab alone appears to be modest. Response in tumors with COMPASS-related mutations and EZH2 activity will be evaluated. Clinical trial information: NCT03854474 .
SOGUG-Vexillum: Phase II non-randomized clinical trial of nivolumab/ipilimumab maintenance following first-line chemotherapy in unresectable locally advanced or metastatic urothelial cancer.
Authors: de Velasco Guillermo , García Carbonero Iciar , Anido Urbano , Virizuela Juan Antonio , Álvarez-Fernández Carlos , Álvarez-Márquez Francisco José , Justo de la Peña Marina , Lozano Rebeca , Gajate Pablo , Reig Oscar , Iranzo Aina , Pujol Eduardo
Published: July 2024

4576

Background: Nivolumab (nivo) 1mg/kg plus ipilimumab (ipi) 3mg/kg achieved the highest ORR (42.4%) in refractory metastatic urothelial carcinoma (mUC) with a manageable safety profile. The addition of nivo and ipi subsequently to first-line chemotherapy (CT) could consolidate the clinical benefit. Methods: This single arm, open-label, multicenter study evaluates the effectiveness of ipi 3 mg/kg and nivo 1 mg/kg (Q3W) for 4 cycles followed by nivo maintenance therapy (Q4W) in delaying disease progression in patients with unresectable urothelial cancer that did not progress after first-line platinum-based CT (at least 4-6 cycles of CT). Autoimmune disease, immune deficiency, and symptomatic brain metastasis were excluded. The primary endpoint is Progression Free Survival (PFS) in intention-to-treat and PD-L1 populations. Secondary endpoints include: objective response rate (ORR), duration of response (DoR), overall survival (OS), overall survival from 1st dose of CT (cOS), progression-free survival from 1st dose of CT (cPFS), safety and translational biomarker analysis. Sample size was estimated using a Simon II stage design for 4-months PFS rate (H0= 40%; H1= 60; α= 0.05; β= 80%; attrition 10%), requiring 25 patients in the 1st stage and up to 66 in total. Here we report the interim analysis for 1st stage. Results: As of January 2024, the 1st accrual stage was completed with 25 evaluable patients. Baseline characteristics are outlined in the table. With a median follow-up of 6.8 months (95% CI: 6.2-10.5), the 4-m PFS rate was 64% (95% CI: 47.7-85.9) and the median PFS was 4.3 months (95% CI: 3.2-NR). The median cPFS was 9.4 months (95% CI: 8-NR). The 6-m OS rate was 76.4% (95% CI: 60-97.2), while median cOS was 15.4 months (95% CI: 15.4-NR). The median duration of treatment was 2.6 months (95% CI: 2.1, 5.7). Nivo and ipi were permanently discontinued due to toxicity in 3 (12%) and 1 (4.2%) patients, respectively. Nivo doses were delayed in 8 (32%) patients and ipi in 3 (12%) for management of toxicity. Grade ≥3 toxicities were reported in 8 (32%) patients, being the most common: Immune-mediated hepatitis (8%), ALT/AST increased (8%) and diarrhea (8%). Conclusions: Maintenance treatment with nivo and ipi showed preliminary efficacy consolidating clinical benefit to CT with a manageable safety profile. The 4-m PFS rate surpassed the futility threshold in the interim analysis and the accrual in Stage II is underway. Final survival results are awaited. Clinical trial information: NCT05219435 . [Table: see text]
Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH)
Authors: Xia Fan , Wang Yaqi , Wang Hui , Shen Lijun , Xiang Zuolin , Zhao Yutian , Zhang Huojun , Wan Juefeng , Zhang Hui , Wang Yan , Wu Ruiyan , Wang Jingwen , Yang Wang , Zhou Menglong , Zhou Shujuan , Chen Yajie , Zhang Zhiyuan , Wu Xian , Xuan Yan , Wang Renjie , Sun Yiqun , Tong Tong , Zhang Xun , Wang Lei , Huang Dan , Sheng Weiqi , Yan Hao , Yang Xu , Shen Yuxin , Xu Yu , Zhao Ruping , Mo Miao , Cai Guoxiang , Cai Sanjun , Xu Ye , Zhang Zhen
Published: July 2024

PURPOSE

To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).

PATIENTS AND METHODS

We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT.

RESULTS

Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (
P
< .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5%
v
35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2%
v
33.9%) during neoadjuvant treatment.

CONCLUSION

The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.
Rossellini beyond Repair
Authors: McGlazer Ramsey
Published: July 2024

This essay analyzes Roberto Rossellini’s Europa ’51 (1952), a film Gilles Deleuze made famous for its way of “seeing convicts” in a range of social institutions, including the factory, the bourgeois family, and the psychiatric hospital. Recent accounts of Rossellini’s career have tended to emphasize his role in manufacturing narratives of postwar national innocence. By contrast, this essay reads Europa ’51 as offering a critique of the carceral state, though one that knows itself to be contained, disempowered, and confined. Mindful of the limits of this critique, the essay brings Rossellini’s film into conversation with ongoing debates about “reparative reading” and its alternatives. Noting that Eve Kosofsky Sedgwick encounters, or rather avoids, a “deinstitutionalized person on the street” in “Paranoid Reading and Reparative Reading,” this essay highlights the film’s very different understanding of institutionalization, which anticipates the demystifying and consistently anticarceral critique of official psychiatry that would emerge in the 1960s and 1970s. Whereas the fantasies sustaining Italian neorealism were reparative, the essay argues, Rossellini’s critical and self-critical turns in Europa ’51 take viewers beyond repair.
The Mismeasure of Sport: Race and the Science of Athletic Performance
Authors: Darda Joseph
Published: July 2024

The dominance of some Black athletes in some sports after civil rights led scientists and journalists to search for explanations in athletes’ culture, geography, psychology, and, increasingly, in their genes—all contributing, whether they landed on culture or biology, to a resurgent race science that invented what it purported to investigate. Science writers could not stop asking whether Kenyans won marathons because of their genes or because of their nation’s running tradition, frequently turning to a more fully naturalized gender binary to justify their pursuit of racial difference in sports. The question itself, no matter how it got answered, legitimized the idea that the Black athlete constituted a scientifically valid category, a category that in a society that privileges the natural above the social sciences (and all sciences above the humanities) ultimately entered the public sphere in biological form.
A expansão internacional da cleantech pioneira no Brasil
Authors: Santos Levindo
Published: July 2024

Caso de ensino sobre uma startup brasileira de base científica e oriunda da academia nacional, pioneira no país na produção de fertilizantes orgânicos e organominerais de alta eficiência, a partir do tratamento de resíduos orgânicos urbanos, industriais e agropecuários (uma cleantech). O caso analisa alternativas de mercados e modelos operacionais para a expansão internacional das operações da startup, provocando uma reflexão mais ampla sobre os principais fatores de risco e os pré-requisitos inerentes à internacionalização de empresas nascentes e com acesso limitado a capital financeiro e humano.
Inteligência Artificial e o Conceito de Função de Produção
Authors: Godoi Alexandra Strommer , Goldbaum Sergio
Published: July 2024

Após o lançamento do ChatGPT em 2023, Marcela Lima, consultora de recursos humanos, tem que preparar um pitch para seus clientes sobre o impacto da disseminação da inteligência artificial sobre o emprego. Para tanto, os alunos, assumindo o papel de Marcela, analisam exemplos de setores com diferentes processos produtivos sob uma perspectiva microeconômica. Capital e trabalho podem se relacionar de forma distinta dependendo do setor, sendo substitutos, complementares ou independentes, o que é determinante para medir o efeito da tecnologia no emprego. Através de 3 funções de produção hipotéticas simples, os alunos aprendem a quantificar estes possíveis efeitos e interpretar os resultados.