bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncogene-Driven Non–Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations
Authors: Huang Chen-Yang , Jiang Nanhai , Shen Meixin , Lai Gillianne G. , Tan Aaron C. , Jain Amit , Saw Stephanie P. , Ang Mei Kim , Ng Quan Sing , Lim Darren W. , Kanesvaran Ravindran , Tan Eng Huat , Tan Wan Ling , Ong Boon-Hean , Chua Kevin L. , Anantham Devanand , Takano Angela M. , Lim Kiat Hon , Tam Wai Leong , Sim Ngak Leng , Skanderup Anders J. , Tan Daniel S. , Rozen Steven G.
Published: April 2024

Non–small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these “nonsmoking-related oncogenes” (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations.

Significance:

Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic.
Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy
Authors: Murphy Sean , Rahmy Sharif , Gan Dailin , Liu Guoqiang , Zhu Yini , Manyak Maxim , Duong Loan , He Jianping , Schofield James H. , Schafer Zachary T. , Li Jun , Lu Xuemin , Lu Xin
Published: April 2024

Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body β-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell–intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer.

Significance:

Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy.
How Artificial Intelligence Unravels the Complex Web of Cancer Drug Response
Authors: Elemento Olivier
Published: April 2024

The intersection of precision medicine and artificial intelligence (AI) holds profound implications for cancer treatment, with the potential to significantly advance our understanding of drug responses based on the intricate architecture of tumor cells. A recent study by Park and colleagues titled “A Deep Learning Model of Tumor Cell Architecture Elucidates Response and Resistance to CDK4/6 Inhibitors” epitomizes this intersection by leveraging an interpretable deep learning model grounded in a comprehensive map of multiprotein assemblies in cancer, known as Nested Systems in Tumors. This study not only elucidates mechanisms underlying the response to CDK4/6 inhibitors in breast cancer therapy but also highlights the critical role of model interpretability leading to new mechanistic insights.
TABLE 1 from Actívatexto: Feasibility and Acceptability of a Mobile Intervention That Promotes Smoking Cessation and Physical Activity among Latinos
Authors: Lara Daimarelys , Alaniz-Cantú Edgar I. , Siddalingaiaha Simran , Oliveira Igor , Chávez-Iñiguez Arlette , DeJesus Elisa , Fuller Daniel , Marquez David X. , Vásquez Elizabeth , Li Dongmei , McIntosh Scott , Ossip Deborah J. , Cupertino Ana Paula , Cartujano-Barrera Francisco
Published: April 2024

Baseline characteristics of participants
Supplementary Table S1 from Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment
Authors: Kadariya Yuwaraj , Sementino Eleonora , Ruan Maggie , Cheung Mitchell , Hadikhani Parham , Osmanbeyoglu Hatice U. , Klein-Szanto Andres J. , Cai Kathy , Testa Joseph R.
Published: April 2024

Primary antibodies used for IHC, IF, and immunoblot analyses
Efficacy of Siltuximab and 1,927 nm Fractional Laser for the Treatment of Cutaneous Manifestations in Castleman’s Disease: The Role of Dermoscopy and Reflectance Confocal Microscopy for Lesion Evaluation
Authors: Paolino Giovanni , Ardigò Marco , Della-Torre Emanuel , Moroni Luca , Rizzo Nathalie , Nicola Matteo Riccardo Di , Bianchi Vittoria Giulia , Dagna Lorenzo , Ramirez Giuseppe Alvise , Mercuri Santo Raffaele
Published: April 2024

Introduction: Multicentric Castleman’s disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman’s disease (CD) is usually a challenge, especially in case of cutaneous involvement. Case Presentation: We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. Conclusion: We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings.
Acute and Chronic Kidney Dysfunction and Prognosis following Thrombectomy for Ischemic Stroke
Authors: Bobot Mickaël , Hak Jean-François , Casolla Barbara , Dehondt Jean-Daniel , Burtey Stéphane , Doche Emilie , Suissa Laurent
Published: April 2024

Introduction: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy. Methods: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS). Results: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3–6: 50.0% vs. 41.7%, p = 0.262) but higher mortality (24.2% versus 9.5%, p = 0.004). In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas score: 1.7 ± 0.8 vs. 1.0 ± 0.8, p = 0.002), lower initial infarct volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p = 0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3–6: 63.8% vs. 49.0%, p = 0.002) and mortality (23.4% versus 7.7%, p = 0.002). In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3–6: adjOR 2.79 [1.11–7.02], p = 0.029) and mortality (adjOR 2.52 [1.03–6.18], p = 0.043) at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome. Conclusions: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis.
Luteolin Is More Potent than Cromolyn in Their Ability to Inhibit Mediator Release from Cultured Human Mast Cells
Authors: Tsilioni Irene , Theoharides Theoharis
Published: April 2024

Introduction: Mast cells are known for their involvement in allergic reactions but also in inflammatory reactions via secretion of numerous pro-inflammatory chemokines, cytokines, and enzymes. Drug development has focused on antiproliferative therapy for systemic mastocytosis and not on inhibitors of mast cell activation. The only drug available as a “mast cell blocker” is disodium cromoglycate (cromolyn), but it is poorly absorbed after oral administration, is a weak inhibitor of histamine release from human mast cells, and it develops rapid anaphylaxis. Instead, certain natural flavonoids, especially luteolin, can inhibit mast cell activation. Methods: Here, we compared pretreatment (0–120 min) with equimolar concentration (effective dose for 50% inhibition = 100 mm for inhibition of histamine release by cromolyn) of cromolyn and luteolin on release of mediators from the cultured human LADR mast cell line stimulated either by immunoglobulin E (IgE) and anti-IgE or with IL-33. Results: We show that luteolin is significantly more potent than cromolyn inhibiting release of histamine, tryptase, metalloproteinase-9, and vascular endothelial growth factor. Moreover, while luteolin also significantly inhibited release of IL-1β, IL-6, and IL-8 (CXCL8) and TNF, cromolyn had no effect. Conclusion: These findings support the use of luteolin, especially in liposomal form to increase oral absorption, may be a useful alternative to cromolyn.
Indicated Stress Prevention Addressing Adolescents with High Stress Levels Based on Principles of Acceptance and Commitment Therapy: A Randomized Controlled Trial
Authors: Binder Franziska , Koenig Julian , Resch Franz , Kaess Michael
Published: April 2024

Introduction: Stress affects many adolescents and is associated with physical and mental health symptoms that can have a negative impact on normative development. However, there are very few evidence-based, specific treatment approaches. The aim of the study was to investigate an eight-session group intervention using components of Acceptance and Commitment Therapy (ACT) enriched with elements of CBT (psychoeducation, problem solving) and art therapy, compared to a waitlist control (WLC) group, regarding its efficacy in reducing stress and associated symptoms. Methods: We conducted a randomized controlled trial in eight cohorts. Eligible participants were 13–18 years old with elevated stress levels. Via block-randomization (n = 70), participants were allocated to receive ACT (n = 38) or WLC (n = 32) and subsequent ACT. We used a multimodal assessment (self-reports, interviews, ecological momentary assessment, physiological markers) before treatment (T1), after the training of the ACT group (T2) and after subsequent training in the WLC group (T3). Primary outcome was perceived stress at T2 assessed with the Perceived Stress Scale. The trial was preregistered at the German Clinical Trials Register (ID: DRKS00012778). Results: Results showed significantly lower levels of perceived stress in the ACT group at T2, illustrating superiority of ACT compared to WLC with a medium to large effect size (d = 0.77). Furthermore, the training was effective in the reduction of symptoms of school burnout and physical symptoms associated with stress. Conclusion: Indicated prevention, especially when based on the principles of ACT and CBT, seems efficient in significantly decreasing stress in adolescents with increased stress.
Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein 7 (IGFBP7) for the prediction of acute kidney injury following cardiac surgery
Authors: Xie Yun , Guo Qin , Yang Bo , Xie Pan , Zhang Jingxiao , Lu Wei , Ronco Claudio , Jiang Gengru
Published: April 2024

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinases-2 • insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2•IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2•IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery.
Methods: In the prospective cohort study, blood and urine samples were collected 6–12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes.
Results: A total of 557 patients were enrolled, 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland clinical score, and simplified renal index than those without AKI. Urinary TIMP-2•IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2•IGFBP7 value of 0.265 (ng/ml)2/1,000. The TIMP-2•IGFBP7 values, simplified renal index (SRI) Score and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint, the percentage of patients who reached the composite end-point in the TIMP-2•IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/ml)2/1,000 group.
Conclusions: Postoperative implementation of TIMP-2•IGFBP7 improved prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/ml))2/1,000 for the prediction of CSA-AKI among all AKI patients.
The Influence of Vitamin D on Pregnancy and Outcomes: Current Knowledge and Future Perspectives
Authors: Kurmangali Zhanar , Abdykalykova Bibigul , Kurmangali Aimen , Zhantagulov Danat , Terzic Milan
Published: April 2024

Introduction: The purpose of the research was to explore the relationship between pathology and pregnancy outcomes with serum 25-hydroxycholecalciferol levels and vitamin D supplementation. Methods: A literature search was performed for systematic literature reviews published between January 2018 and February 2023. Forty-two publications were selected for further analysis. Results: This study demonstrates that elevated maternal serum 25(OH)D levels are associated with a decreased risk of preterm labour and various pregnancy-related health issues, highlighting the protective benefits of adequate vitamin D during pregnancy. Conclusion: Vitamin D supplementation during pregnancy at a dose of 2,000 IU or higher is preventive for pre-eclampsia, insulin resistance, and the development of bronchial asthma in early childhood. Vitamin D screening is indicated for all pregnant women. Dosages of vitamin D preparations should be determined individually, considering laboratory tests and risk factors.
Implementation Evaluation of an Early Notification Care Bundle for Patients with Hip Fracture (eHIP)
Authors: Curtis Kate , McKenzie John , Melville Geoffrey , Moules Peter , Wylie Cayce , Tyler Alexandra , Mulholland Bridie
Published: April 2024

Introduction: Hip fracture in older adults results in significant mortality and is one of the costliest fall-related injuries. The Australian Commission for Quality and Safety in Health Care hip fracture clinical care standards consolidate the best available evidence for managing this patient group; however, uptake is variable. The aim of this study was to evaluate the implementation and effectiveness of a multidisciplinary early activation mechanism and bundle of care (eHIP) on patient and health service outcomes. Methods: This controlled pre- and post-test study was conducted from June 2019–June 2021 at a large regional hospital in Australia. We hypothesised that eHIP would result in at least 50% of hip fracture patients receiving six or more components of the ACSQHC Hip Fracture Clinical Care Standard. Secondary outcomes include hospital-acquired complication rates and acute treatment costs. Results: There were 565 cases included for analysis. After implementation of eHIP (the post-period), 88% of patients received a correct activation of the eHIP pathway, sustained over 12 months. The proportion of patients receiving the primary outcome of six or more components increased from 36% to 49%. Care at presentation (pain and cognitive assessment) increased by 23%, and unrestricted mobilisation within 24 h improved by 10%. Prescription of appropriate analgesia improved 10-fold (5.2–57%), and patients receiving the gold standard fascia iliaca block increased from 68% to 88%. Acute treatment costs did not significantly change. Discussion/Conclusion: eHIP, a hip fracture care program incorporating evidence-based behaviour change theory, resulted in sustained improvements to patient care as recommended by the ACSQHC Hip Fracture Clinical Care Standard.
Obstructive Jaundice Caused by Metastatic Neuroendocrine Tumor of the Ampulla of Vater in a Young Adult: A Case Report
Authors: Alsalman Jaafar , Alquorain Abdulaziz , Alyousef Mohammed , Aldandan Omran , Alzahrani Ibrahim
Published: April 2024

Introduction: Ampullary neuroendocrine tumors (NETs) are usually diagnosed in the 5th–6th decades of life, and no cases were reported in <20 years of age. We report a rare case, presenting at a very young age, of well-differentiated NET involving the ampulla of Vater with lymph node metastasis. Case Presentation: An 18-year-old man presented with a 3-month history of upper abdominal pain and jaundice. Abdominal ultrasound showed a dilated common bile duct, and endoscopic retrograde cholangiopancreatography revealed two duodenal polypoid lesions, one of them overlying the ampulla of Vater, with an erythematous and ulcerated surface. Histopathological examination confirmed the diagnosis of NET grade 1. Octreotide scan revealed 2 para-aortic lymph nodes with intense radiotracer uptake. The patient had undergone Whipple surgery with para-aortic lymph node dissection. Histopathological examination of the surgical specimens was confirmatory of NET grade 2 and paraganglioma in a few of the dissected lymph nodes. Postoperatively, the patient was kept on monthly intramuscular octreotide. Follow-up gallium-68 DOTATATE is unremarkable apart from an avid left para-aortic lymph node which is showing stability over 12 months of follow-up. Conclusion: This case demonstrates that NETs of the ampulla of Vater can present at a very young age. Radical surgical excision with extended lymph node dissection and postoperative octreotide is associated with better patient outcomes and survival.
Nourishing Neurons: Exploring the Role of Plant-Based Diets in Parkinson’s Disease Prevention
Authors: Poulia Kalliopi Anna
Published: April 2024

Background: Plant-based diets have been associated with a lower risk of several chronic diseases, but the relationship with PD is unknown. Objectives: We examined the association of three different plant-based diets with PD incidence in the UK Biobank cohort. Methods: We conducted a prospective study among 126,283 participants from the UK Biobank cohort. Three plant-based diet indices (overall plant-based diet index, PDI; healthful plant-based diet index, hPDI; and unhealthful plant-based diet index, uPDI) were derived from 24-hour dietary recalls based on 17 food groups. Multivariable Cox regression models were used to estimate the risk of PD across quartiles of the PDIs and for each of the food groups that constituted the score. Further analyses were carried out to assess potential heterogeneity in associations between hPDI and PD across strata of some hypothesized effect modifiers. Results: During 11.8 years of follow-up (1,490,139 person-years), 577 cases of PD incidence were reported. After multivariable adjustment, participants in the highest hPDI and overall PDI quartile had lower risk of PD (22% and 18%, respectively), whereas a higher uPDI was associated with a 38% higher PD risk. In food-based analyses, higher intakes of vegetables, nuts, and tea were associated with a lower risk of PD (28%, 31% and 25%, respectively). Stratifying by Polygenic Risk Score (PRS), results were significant only for those with a lower PRS for PD.
Cartografia da invasão, conquista e ocupação de territórios indígenas em Minas Gerais
Authors: Dornela Bernardo de Pinho Tavares , Costa Antônio Gilberto
Published: April 2024

Contrapondo-se ao que ocorreu no centro-oeste do território mineiro — onde a descoberta aurífera levou à intensa ocupação e exploração, bem como à dizimação dos povos nativos —, que se consolidou como um distrito minerador nas Minas Gerais, a porção leste do território permaneceu, por considerável período de tempo, ainda mais distante das “mãos” do poder colonizador. Isso fez com que ali se concentrasse a maior parte da presença e da resistência dos povos indígenas da capitania mineira, sobreviventes daquele ímpeto. A partir da segunda metade do século XVIII, no entanto, os novos rumos da dinâmica econômica da capitania fazem esse quadro se alterar, colocando o “sertão leste” nas vistas governamentais como alternativa para a dinamização da economia. O avanço da invasão e da ocupação de terras indígenas na região, baseado em processos de guerra e suposta pacificação, é observado por meio de diversos documentos cartográficos históricos, produzidos entre a segunda metade dos Setecentos e dos Oitocentos joaninos. Analisados à luz dos acontecimentos interpretados por diversos autores, esses documentos tornam-se importantes fontes de pesquisa e entendimento do que ocorreu aos indígenas do leste mineiro.
Consumo de drogas sintéticas por graduandos de uma universidade pública: prevalência e fatores associados
Authors: Barbosa Gabriel Ghossain , Dos Santos Júnior Amilton , Dalgalarrondo Paulo , Azevedo Renata Cruz Soares de
Published: April 2024

Objective: to present the prevalence of synthetic drug use (lysergic acid diethylamide – LSD, andecstasy) and associated factors among university students. Methodology: a quantitative and crosssectionalstudy, part of a research on sociodemographic profile, university life, mental health andpsychosocial identity. An anonymous, face-to-face questionnaire was applied to undergraduate studentsat a Brazilian public university. Use of synthetics in the past year was analyzed in relation to gender,sexuality, socioeconomic status, academic performance, interpersonal/sexual violence, mental health,use of psychoactive substances and quality of life. Bivariate and multivariate analysis methods wereused, employing the Statistical Package for the Social Sciences and R software packages. Results:6,906 students participated in the study, of whom 8.3% used LSD, 7.9% ecstasy, and 10.8% LSD and/or ecstasy in the past year. Synthetic drug use was associated with cocaine use (OR 4.90), frequentmarijuana use (OR 6.83) and solvent use (OR 8.11). There was an association with belonging tosexual minority groups, higher socioeconomic status, poorer academic performance, sexual violencewhile intoxicated and higher scores on the quality of life scale. There was a weaker association withmale gender and poorer mental health. Conclusion: high synthetic drug use rates were observedin this population, and the associated factors may assist in the development of targeted interventionstrategies within the university context.
Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry
Authors: Patel Siddharth M. , Berg David D. , Bohula Erin A. , Baird-Zars Vivian M. , Barsness Gregory W. , Chaudhry Sunit-Preet , Chonde Meshe D. , Cooper Howard A. , Ginder Curtis , Jentzer Jacob C. , Kontos Michael C. , Miller P. Elliott , Newby L. Kristin , O’Brien Connor G. , Park Jeong-Gun , Pierce Matthew J. , Pisani Barbara A. , Potter Brian J. , Shah Kevin S. , Teuteberg Jeffrey J. , Katz Jason N. , van Diepen Sean , Morrow David A.
Published: April 2024

BACKGROUND:

Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined.

METHODS:

The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018–2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status.

RESULTS:

Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%–45% and 11%–73% for VIS <10 to ≥40, respectively;
P
trend
<0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS (
P
trend
<0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70–0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69–0.74] to 0.76 [95% CI, 0.74–0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70–0.74] to 0.77 [95% CI, 0.75–0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23–1.49] versus 1.84 [95% CI, 1.69–2.01];
P
interaction
<0.0001).

CONCLUSIONS:

Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.
Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation
Authors: Zhu Yike , Ackers-Johnson Matthew , Shanmugam Muthu K. , Pakkiri Leroy Sivappiragasam , Drum Chester Lee , Chen Yanpu , Kim Johnny , Paltzer Wyatt G. , Mahmoud Ahmed I. , Tan Wilson Lek Wen , Lee Mick Chang Jie , Jiang Jianming , Luu Danh Anh Tuan , Ng Shi Ling , Li Peter Yi Qing , Wang Anhui , Qi Rong , Ong Gabriel Jing Xiang , Ng Timothy Yu , Haigh Jody J. , Tiang Zenia , Richards A. Mark , Foo Roger S.Y.
Published: April 2024

BACKGROUND:

Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

METHODS:

Here, we leveraged 2 models of in vitro cultured adult mouse cardiomyocytes and in vivo adeno-associated virus serotype 9 cardiomyocyte–targeted delivery of reprogramming factors (
Oct4
,
Sox2
,
Klf4
, and
Myc
) in adult mice to study CMDD. We profiled their transcriptomes using RNA sequencing, in combination with multiple published data sets, with the aim of identifying a common denominator for tracking CMDD.

RESULTS:

RNA sequencing and integrated analysis identified
Asparagine Synthetase
(
Asns
) as a unique molecular marker gene well correlated with CMDD, required for increased asparagine and also for distinct fluxes in other amino acids. Although
Asns
overexpression in
Oct4
,
Sox2
,
Klf4
, and
Myc
cardiomyocytes augmented hallmarks of CMDD,
Asns
deficiency led to defective regeneration in the neonatal mouse myocardial infarction model, increased cell death of cultured adult cardiomyocytes, and reduced cell cycle in
Oct4
,
Sox2
,
Klf4
, and
Myc
cardiomyocytes, at least in part through disrupting the mammalian target of rapamycin complex 1 pathway.

CONCLUSIONS:

We discovered a novel gene
Asns
as both a molecular marker and an essential mediator, marking a distinct threshold that appears in common for at least 4 models of CMDD, and revealing an
Asns
/mammalian target of rapamycin complex 1 axis dependency for dedifferentiating cardiomyocytes. Further study will be needed to extrapolate and assess its relevance to other cell state transitions as well as in heart regeneration.
Recommendations for the Use of Dietary Fiber to Improve Blood Pressure Control
Authors: Jama Hamdi A. , Snelson Matthew , Schutte Aletta E. , Muir Jane , Marques Francine Z.
Published: April 2024

According to several international, regional, and national guidelines on hypertension, lifestyle interventions are the first-line treatment to lower blood pressure (BP). Although diet is one of the major lifestyle modifications described in hypertension guidelines, dietary fiber is not specified. Suboptimal intake of foods high in fiber, such as in Westernized diets, is a major contributing factor to mortality and morbidity of noncommunicable diseases due to higher BP and cardiovascular disease. In this review, we address this deficiency by examining and advocating for the incorporation of dietary fiber as a key lifestyle modification to manage elevated BP. We explain what dietary fiber is, review the existing literature that supports its use to lower BP and prevent cardiovascular disease, describe the mechanisms involved, propose evidence-based target levels of fiber intake, provide examples of how patients can achieve the recommended targets, and discuss outstanding questions in the field. According to the evidence reviewed here, the minimum daily dietary fiber for adults with hypertension should be >28 g/day for women and >38 g/day for men, with each extra 5 g/day estimated to reduce systolic BP by 2.8 mm Hg and diastolic BP by 2.1 mm Hg. This would support a healthy gut microbiota and the production of gut microbiota-derived metabolites called short-chain fatty acids that lower BP. Awareness about dietary fiber targets and how to achieve them will guide medical teams on better educating patients and empowering them to increase their fiber intake and, as a result, lower their BP and cardiovascular disease risk.
Trends and Disparities in Valvular Heart Disease Mortality in the United States From 1999 to 2020
Authors: Tan Min Choon , Yeo Yong Hao , San Boon Jian , Suleiman Addi , Lee Justin Z. , Chatterjee Arka , Sell‐Dottin Kristen A. , Sweeney John P. , Fortuin F. David , Lee Kwan S.
Published: April 2024

Background

Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real‐world mortality data on valvular heart disease (VHD) in the United States remain limited.

Methods and Results

We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age‐adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22‐year study, there were 446 096 VHD deaths, accounting for 0.80% of all‐cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD‐related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2–8.5) to 6.6 (95% CI, 6.5–6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR.

Conclusions

The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.
British Values, Hong Kong Voices: Tracing Hong Kong’s Britishness and Its Influences on British Immigration Policies
Authors: Yu Andrew
Published: April 2024

This article examines the rationale behind the United Kingdom’s decision to offer Hongkongers new immigration routes and assess whether Britishness constitutes part of Hong Kong’s identity, influencing this policy choice. It explores the concept of Britishness and how Hong Kong developed a distinct identity through its colonial history and experiences under British rule. Perspectives from the British administration, Hongkongers, and Chinese government on Hong Kong’s Britishness are considered. The article argues the United Kingdom action stems from two factors – perceiving a shared Britishness between Hongkongers and Britons mitigating public backlash, and viewing Hongkongers’ Britishness as crucial to their integration. Ultimately, Britishness remains integral to Hong Kong due to shared social and political values with Britain from over 150 years of colonial rule.
Three species of the family Aoridae Stebbing, 1899 (Crustacea: Amphipoda) collected from remote islands in southern Japan, with a key to all Japanese species of the family
Authors: ARIYAMA HIROYUKI , KODAMA MASAFUMI
Published: April 2024

Three species of the aorid amphipod were collected from remote islands in southern Japan. Protolembos ryukyuensis sp. nov. was collected from Ishigaki Island in Okinawa Prefecture and Tanegashima Island in Kagoshima Prefecture, and characterized by the dense plumose setae on the male gnathopods 1 and 2. Tethylembos cavatus sp. nov. and T. japonicus Ariyama, 2004 were collected from Miyake Island and the Ogasawara Islands in Tokyo Prefecture, respectively. Both species share the male gnathopod 1 propodus heavily setose medially; however, Tethylembos cavatus can be distinguished from T. japonicus in the excavated basis of the male pereopod 5. Keys to species of Protolembos Myers, 1988 and Tethylembos Myers, 1988 in the world and a key to all Japanese species of the family Aoridae are provided. Number of aorid species in Japan stands at 34.
Two New Species of Oak Gall Wasp (Hymenoptera: Cynipidae, Cynipini) from Türkiye
Authors: TATAROĞLU MUSA , KATILMIŞ YUSUF
Published: April 2024

Two new species of the genus Andricus Hartig, 1840 (Cynipidae: Cynipini), Andricus ismaili Tataroğlu & Katılmış sp. n. asexual generation on Quercus infectoria Olivier and Andricus musaazmazi Tataroğlu & Katılmış sp. n. sexual generation on Quercus trojana Webb are described from Türkiye. SEM images, gall photos, and data on the diagnosis, distribution, and biology of the two new species are provided.
Introduction
Authors: Tortell Philippe D.
Published: April 2024

This introduction sets the stage for the volume’s comprehensive exploration of the global mineral resource sector, intertwining personal narrative with discussion of the broader societal implications of minerals and mining. The challenges and opportunities facing mineral resource extraction are placed against the backdrop of climate change and the necessary transition to renewable energy. This introduction outlines how a diverse group of authors came together to explore the future of Earth’s minerals from a wide range of perspectives, including Indigenous rights, economics, science and engineering, law and geopolitics.
Ocean Minerals
Authors: Wiltshire John
Published: April 2024

The oceans cover 71% of the planet, and the seafloor contains the largest source of new minerals yet to be exploited, including manganese nodules and crusts, and polymetallic sulfides. These ocean floor deposits could provide a vast source of critical metals for the coming green economy, including cobalt, nickel, copper and rare-earth elements. However, the environmental effects of large-scale seafloor mining are not well known, and hotly debated between mining companies eager to profit, and environmental groups seeking to impose moratoria on seabed mining pending better documentation of potential impacts. Seabed mining, presently in limbo, could start as early as 2025.
Aura Tenebris (Radiant Darkness)
Authors: Read Thomas Augusta
Published: April 2024

This piece reflects on the composition of the ‘Gold’ movement.
Mine Waste
Authors: Beckie Roger
Published: April 2024

To a large extent, mining is a waste management business. In most mining operations, metal resources are found in host rocks at concentrations of a few percent or less, resulting in the production of large quantities of wastes during metal extraction and processing. These wastes can occur in the form of bulk waste rock, and fine-grained material (tailings) that remain after the ore is ground and processed. The two principal mine-waste management challenges are the containment of tailings, and the management of contamination leaching from tailings and waste rock. Over the past decade, several high-profile, catastrophic tailings-dam failures have led to a significant change in the way mine wastes are treated. New global standards have significantly improved industry tailing-management practices, with the potential to significantly reduce, if not eliminate, the environmental impacts of mine wastes. This essay reviews the complex problem of mine waste management, and discusses emerging new approaches—both technical and regulatory—to help ensure that mine waste storage facilities are safe from catastrophic failure, and non-polluting in perpetuity. More work is needed to ensure that these new approaches become cost-effective so that they can be widely adopted by the global mining sector.
El correo electrónico como medio de aprendizaje lingüístico
Authors: Casanovas Montserrat
Published: April 2024

Se analizan las características que presenta el correo electrónico y las peculiaridades de las interacciones que se producen a través de este canal frente a otros tipos de comunicación electrónica, así como sus potencialidades como medio didáctico en la enseñanza/aprendizaje de lenguas. Se revisan algunas experiencias didácticas basadas en el uso de este medio y se propone una tipología de aplicaciones didácticas que se ejemplifica con algunas de las experiencias pedagógicas realizadas en el ámbito de la didáctica de las lenguas.
Trabajando con chat en cursos de postgrado en línea
Authors: Campuzano Laura
Published: April 2024

En este artículo se analiza una experiencia llevada a cabo de 1998 a 2000 con el chat como único medio de comunicación sincrónica en los seis cursos en línea de la Especialidad en Lingüística Aplicada que ofrece la Maestría en Educación con Especialidades de la Universidad Virtual del Instituto Tecnológico y de Estudios Superiores de Monterrey (MEE-UV-ITESM) en México. Como muestra, se toman tres tipos de chats diferentes por su finalidad y por las restricciones impuestas (temática establecida/no establecida), cuyos fragmentos se comentan. A la luz de ese análisis, se destacan las ventajas del uso del chat en educación universitaria.
Prophylactic Cholecystectomy is Safe in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy
Authors: Hanna David N. , Khajoueinejad Nazanin , Ghani Muhammad O. , Hermina Andrew , Mina Alexander , Bailey Christina E. , Cohen Noah , Labow Daniel , Golas Benjamin , Sarpel Umut , Idrees Kamran , Magge Deepa
Published: April 2024

Background

While cholecystectomy is one of the most common operations performed in the United States, there is a continued debate regarding its prophylactic role in elective surgery. Particularly among patients with peritoneal carcinomatosis who undergo cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), further abdominal operations may pose increasing morbidity due to intraabdominal adhesions and potential recurrence. This bi-institutional retrospective study aims to assess postoperative morbidity associated with prophylactic cholecystectomy at the time of CRS-HIPEC.

Methods

We performed a bi-institutional retrospective analysis of 578 patients who underwent CRS-HIPEC from 2011 to 2021. Postoperative outcomes among patients who underwent prophylactic cholecystectomy at the time of CRS-HIPEC were compared to patients who did not, particularly rate of bile leak, hospital length of stay, rate of Clavien-Dindo classification morbidity grade III or greater, and number of hospital re-admissions within 30 days.

Results

Of the 535 patients available for analysis, 206 patients (38.3%) underwent a prophylactic cholecystectomy. Of the 3 bile leaks (1.5%) that occurred among patients who underwent prophylactic cholecystectomy, all 3 occurred in patients who underwent a concomitant liver resection. There were no significant differences in hospital length of stay, postoperative morbidity, and number of hospital re-admissions among patients who underwent prophylactic cholecystectomy compared to those who did not.

Conclusion

Prophylactic cholecystectomy in patients undergoing CRS-HIPEC is not associated with increased morbidity or increased bile leak risk compared to historical data. While the benefits of prophylactic cholecystectomy are not yet elucidated, it may be considered to avoid potential future morbid operations for biliary disease.
Is Minimally Invasive Resection of Large Thymoma Appropriate?
Authors: Manyak Grigory A. , Bassiri Aria , Alvarado Christine E. , Sarnaik Kunaal S. , Sinopoli Jilian , Tapias Leonidas , Linden Philip A. , Towe Christopher W.
Published: April 2024

Background

Current practice patterns suggest open rather than minimally invasive (MIS) approaches for thymomas >4 cm. We hypothesized there would be similar perioperative outcomes and overall survival between open and MIS approaches for large (>4 cm) thymoma resection.

Methods

The National Cancer Database was queried for patients who underwent thymectomy from 2010 to 2020. Surgical approach was characterized as either open or MIS. The primary outcome was overall survival and secondary outcomes were margin status, and length of stay (LOS). Differences between approach cohorts were compared after a 1:1 propensity match.

Results

Among 4121 thymectomies, 2474 (60%) were open and 1647 (40%) were MIS. Patients undergoing MIS were older, had fewer comorbidities, and had smaller tumors (median; 4.6 vs 6 cm, P < .001). In the unmatched cohort, MIS and open had similar 90-day mortality (1.1% vs 1.8%, P = .158) and rate of positive margin (25.1% vs 27.9%, P = .109). MIS thymectomy was associated with shorter LOS (2 (1-4) vs 4 (3-6) days, P < .001). Propensity matching reduced the bias between the groups. In this cohort, overall survival was similar between the groups by log-rank test ( P = .462) and multivariate cox hazard analysis (HR .882, P = .472). Multivariable regression showed shorter LOS with MIS approach (Coef −1.139, P < .001), and similar odds of positive margin (OR 1.130, P = .150).

Discussion

MIS has equivalent oncologic benefit to open resection for large thymomas, but is associated with shorter LOS. When clinically appropriate, MIS thymectomy may be considered a safe alternative to open resection for large thymomas.
The Mitigating Effects of Water Sound Attributes on Stress Responses to Traffic Noise
Authors: Deng Li , Rising Hope Hui , Gu Chao , Bimal Anju
Published: April 2024

Traffic noise is a significant risk factor for adverse health outcomes. Despite burgeoning interest in reducing the harmful health effects of traffic noise, research on the influence of physical and psychoacoustic attributes has been sparse. Consequently, this study examines the impacts of various acoustic attributes on mitigating stress response to traffic noise using dependent variables derived from electrodermal activity. The results indicate that: (a) mixing water sound (noise) at a low signal-to-noise ratio effectively mitigated stress response to traffic noise (signal), whereas mixing white noise with high fractal complexity (noise) significantly induced stress; and (b) sound pressure and acoustic sharpness significantly reduced stress response to traffic noise. Conversely, attributes such as high fractal complexity, moderate and high signal-to-noise ratios, acoustic loudness, and mean frequency significantly increased stress. This research offers a viable blueprint for creating evidence-based noise mitigation strategies that focus on intervention sound attributes.
“We Out Here”: Black Women, Well-Being, and #blackgirlsrun on Instagram
Authors: Cameron Shanice Jones
Published: April 2024

This study explores the meanings that Black women associate with long-distance running and how these meanings informed their digital practice, specifically the content they distributed through #blackgirlsrun on Instagram. Drawing from 12 semi-structured phone interviews and participant observation data, this project exemplifies how Black women in the United States utilize social media to create knowledges and cultivate communities that center their health and well-being. The participants regarded long-distance running as an anchor practice, or an activity that simultaneously enriches multiple dimensions of one’s well-being and prompts additional healthy behaviors. The thematic analysis revealed that the participants distributed posts through #blackgirlsrun on Instagram to: (a) invite Black women Instagram users to identify as runners; (b) disrupt running stereotypes; and (c) facilitate generational well-being. The significance of these findings as they relate to Black women’s well-being and digital practice are also discussed.