bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Thermal, Ultrasonication, and Thermosonication Processes on the Quality Profile of Watermelon-Beetroot Juice Blend: A Comparative Study
Authors: Mukhtar Kinza , Nabi Brera Ghulam , Manzoor Muhammad Faisal , Zia Sania , Bhat Zuhaib F. , Hussain Shahzad , Aadil Rana Muhammad
Published: April 2024

Fruit juices are popular beverages that provide various health benefits due to their rich nutritional profile, but they are prone to microbial spoilage and quality deterioration. Thermal pasteurization is the conventional method to preserve fruit juices, but it causes undesirable changes in the physicochemical and nutritional value of the juices. Therefore, there is a need to develop alternative methods to ensure the microbial safety and quality of fruit juices. The aim of this study was to investigate the impact of thermal (95-100°C for 4 min), ultrasonication (US) (25 kHz for 5 and 10 min), and thermosonication (TS) (25 kHz at 40 and 50°C) processes on the quality profile of watermelon-beetroot juice blend, a novel juice formulation with enhanced nutritional and functional properties with 50 : 50 formulation. The samples were analysed for physicochemical (colour, pH, total soluble solids, and titratable acidity), bioactive (phenolic, flavonoid, antioxidant, and ascorbic acid contents), and microbiological (total plate count and yeast/molds) properties. The results showed that all the processed samples retained high total phenolic (756.33-842.33 μg GAE/g), total flavonoid (435.33-512.67 μg CE/g), and ascorbic acid (45.23-50.34 mg/100 mL) contents along with a high antioxidant potential (total antioxidant capacity (274.14-305.33 μg AAE/g) and DPPH radical scavenging activity (33.05-42.18%)) while preserving the normal physicochemical characteristics and decreasing the microbial counts of all the processed blend juices. In conclusion, the US treatment (10 min) produced the juice blends with the best quality. The findings of this research suggest that thermal, US, and TS processes are promising technologies for the preservation of fruit juices and that watermelon-beetroot juice blend is a novel juice formulation with high nutritional and functional value. The results of this research might be useful to the processed fruit juice industry and the consumers who are looking for healthy and safe fruit juices.
Impact of Indoor Air Quality and Multi‐domain Factors on Human Productivity and Physiological Responses: A Comprehensive Review
Authors: Deng Zhipeng , Dong Bing , Guo Xin , Zhang Jianshun
Published: April 2024

Indoor environmental quality (IEQ) significantly impacts human health, well‐being, and productivity. However, a comprehensive and in‐depth review of the combined effects of IAQ and other multi‐domain factors on human productivity is lacking. There has not been any prior review that encapsulates the impact of multi‐domain factors on productivity and physiological responses of occupants. To address this gap, this review paper investigates and highlights the impact of IAQ and multi‐domain factors (thermal, visual, and acoustic) on human productivity and occupant well‐being in the built environment. The review explores various research methods, including evaluation of human productivity and creativity, data collection, and physiological signal analysis. We also examined the interactions between IAQ and multi‐domain factors, as well as strategies for optimizing productivity through integrated building design and smart systems. The key findings from this review reveal that IAQ significantly impacts human productivity and occupant well‐being, with interactions between IAQ and other IEQ factors further impacting these effects. Despite advances in the field, there are several limitations and gaps in the current research methods and study designs, including small sample sizes, limited and insufficient experimental design and control, reliance on laboratory or simulated environments, lack of follow‐up and long‐term data, and lack of robust performance metrics. The review proposes future research directions, including specific applications, and follow‐up work to address these limitations and further advance the understanding of IAQ and multi‐domain factors in the built environment. The implications of this review for policy and practice include the need for holistic and integrated approaches to IAQ and IEQ management, with a focus on creating healthy and productive indoor environments. This review emphasizes the importance of considering the complex interplay between IAQ and multi‐domain factors, as well as the potentials of adopting smart control systems and sustainable design strategies to optimize productivity and occupant well‐being in the built environment. By addressing these critical issues, we can enhance the overall quality of life for building occupants and contribute to a more sustainable future.
Methicillin-Resistant Staphylococcus aureus Carriage among Neonate Mothers, Healthcare Workers, and Environmental Samples in Neonatal Intensive Care Units: A Systematic Review
Authors: Keneh Nene Kaah , Kenmoe Sebastien , Bowo-Ngandji Arnol , Akoachere Jane-Francis Tatah Kihla , Kamga Hortense Gonsu , Ndip Roland Ndip , Ebogo-Belobo Jean Thierry , Kengne-Ndé Cyprien , Mbaga Donatien Serge , Tendongfor Nicholas , Assam Jean Paul Assam , Ndip Lucy Mande , Esemu Seraphine Nkie
Published: April 2024

Background. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). The MRSA colonization of neonates, attributed to various sources, including mothers, healthcare workers, and environmental surfaces, can lead to severe infection, prolonged hospital stays, and even death, imposing substantial economic burdens. Given the pressing need to mitigate MRSA spread in these vulnerable environments, further examination of the subject is warranted. This systematic review is aimed at synthesizing available evidence on MRSA carriage proportions among mothers of newborns, healthcare workers, and environmental surfaces in NICUs. Methodology. We included observational studies published in English or French from database inception to March 21, 2023. These studies focused on MRSA in nonoutbreak NICU settings, encompassing healthy neonate mothers and healthcare workers, and environmental surfaces. Literature search involved systematic scanning of databases, including Medline, Embase, Web of Science, Global Health, and Global Index Medicus. The quality of the selected studies was assessed using the Hoy et al. critical appraisal scale. The extracted data were summarized to calculate the pooled proportion of MRSA positives, with a 95% confidence interval (CI) based on the DerSimonian and Laird random-effects model. Results. A total of 1891 articles were retrieved from which 16 studies were selected for inclusion. Most of the studies were from high-income countries. The pooled proportion of MRSA carriage among 821 neonate mothers across four countries was found to be 2.1% (95% CI: 0.3-5.1; I2=76.6%, 95% CI: 36.1-91.5). The proportion of MRSA carriage among 909 HCWs in eight countries was determined to be 9.5% (95% CI: 3.1-18.4; I2=91.7%, 95% CI: 87.1-94.6). The proportion of MRSA carriage among HCWs was highest in the Western Pacific Region, at 50.00% (95% CI: 23.71-76.29). In environmental specimens from five countries, a pooled proportion of 16.6% (95% CI: 3.5-36.0; I2=97.7%, 95% CI: 96.6-98.4) was found to be MRSA-positive. Conclusion. With a significant heterogeneity, our systematic review found high MRSA carriage rates in neonate mothers, healthcare workers, and across various environmental surfaces in NICUs, posing a potential risk of nosocomial infections. Urgent interventions, including regular screening and decolonization of MRSA carriers, reinforcing infection control measures, and enhancing cleaning and disinfection procedures within NICUs, are crucial. This trial is registered with CRD42023407114.
Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors
Authors: Magrath Justin W. , Sampath Shruthi Sanjitha , Flinchum Dane A. , Hartono Alifiani B. , Goldberg Ilon N. , Boehling Julia R. , Savkovic Suzana D. , Lee Sean B.
Published: April 2024

Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to a 5-year survival rate of only 15% to 25%. Here, we depleted EWSR1::WT1 in DSRCT and established its essentiality in vivo. Transcriptomic analysis revealed that EWSR1::WT1 induces unique transcriptional alterations compared with WT1 and other fusion oncoproteins and that EWSR1::WT1 binding directly mediates gene upregulation. The E-KTS isoform of EWSR1::WT1 played a dominant role in transcription, and it bound to the CCND1 promoter and stimulated DSRCT growth through the cyclin D–CDK4/6–RB axis. Treatment with the CDK4/6 inhibitor palbociclib successfully reduced growth in two DSRCT xenograft models. As palbociclib has been approved by the FDA for the treatment of breast cancer, these findings demonstrate the sensitivity of DSRCT to palbociclib and support immediate clinical investigation of palbociclib for treating this aggressive pediatric cancer.

Significance:

EWSR1::WT1 is essential for desmoplastic small round cell tumors and upregulates the cyclin D–CDK4/6–RB axis that can be targeted with palbociclib, providing a targeted therapeutic strategy for treating this deadly tumor type.
Racial Disparities in Early-Stage NSCLC Treatment: A Call for Action
Authors: Pellini Bruna , Chaudhuri Aadel A.
Published: April 2024

Non–small cell lung cancer (NSCLC) is associated with a 5-year survival rate of only 28%; however, when caught at an early stage, it can be cured with surgery or stereotactic body radiotherapy (SBRT). Unfortunately, racial disparities may result in limited access to care for some patients. Liu and colleagues analyzed 64,999 cases of early-stage NSCLC treated between 2005 and 2017 from the Florida Cancer Registry and showed that Black patients had 36% lower odds of receiving curative-intent surgery compared with their White counterparts. This study highlights significant racial disparities in treatment patterns that must be addressed urgently.

See related article by Liu and colleagues, Cancer Epidemiol Biomarkers Prev 2024;33:489–99
Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells
Authors: Picco Gabriele , Rao Yanhua , Al Saedi Angham , Lee Yang , Vieira Sara F. , Bhosle Shriram , May Kieron , Herranz-Ors Carmen , Walker Samantha J. , Shenje Raynold , Dincer Cansu , Gibson Freddy , Banerjee Ruby , Hewitson Zoe , Werner Thilo , Cottom Joshua E. , Peng Yang , Deng Nanhua , Zhang Youyou , Nartey Eldridge N. , Nickels Leng , Landis Philip , Conticelli Daniela , McCarten Katrina , Bush Jacob , Sharma Mamta , Lightfoot Howard , House David , Milford Emma , Grant Emma K. , Glogowski Michal P. , Wagner Craig D. , Bantscheff Marcus , Rutkowska-Klute Anna ,   Cell Model Network UK Group, Zappacosta Francesca , Pettinger Jonathan , Barthorpe Syd , Eberl H. Christian , Jones Brian T. , Schneck Jessica L. , Murphy Dennis J. , Voest Emile E. , Taygerly Joshua P. , DeMartino Michael P. , Coelho Matthew A. , Houseley Jonathan , Sharma Geeta , Schwartz Benjamin , Garnett Mathew J.
Published: April 2024

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR–Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth in vitro and in vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic lethal targeting of WRN in MSI cancer and tools to dissect WRN biology.

Significance: We report the discovery and characterization of potent, selective WRN helicase inhibitors for MSI cancer treatment, with biomarker analysis and evaluation of efficacy in vivo and in immunotherapy-refractory preclinical models. These findings pave the way to translate WRN inhibition into MSI cancer therapies and provide tools to investigate WRN biology.

See related commentary by Wainberg, p. 1369
Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity
Authors: Glitza Isabella C. , Seo Yongwoo David , Spencer Christine N. , Wortman Jennifer R. , Burton Elizabeth M. , Alayli Farah A. , Loo Christopher P. , Gautam Shikha , Damania Ashish , Densmore Julie , Fairchild Justin , Cabanski Christopher R. , Wong Matthew C. , Peterson Christine B. , Weiner Brian , Hicks Nathan , Aunins John , McChalicher Christopher , Walsh Emily , Tetzlaff Michael T. , Hamid Omid , Ott Patrick A. , Boland Genevieve M. , Sullivan Ryan J. , Grossmann Kenneth F. , Ajami Nadim J. , LaVallee Theresa , Henn Matthew R. , Tawbi Hussein A. , Wargo Jennifer A.
Published: April 2024

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an overall response rate of 25% in the SER-401 arm and 67% in the placebo arm (though the study was underpowered related to poor accrual during the COVID-19 pandemic). Translational analyses demonstrated that vancomycin preconditioning was associated with the disruption of the gut microbiota and impaired immunity, with incomplete recovery at ICB administration (particularly in patients with high baseline Ruminococcaceae). These results have important implications for future microbiome modulation trials.

Significance: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti–PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials.

See author Yongwoo David Seo discuss this research brief, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932607668/63addff7fc
Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer
Authors: Yaeger Rona , Uboha Nataliya V. , Pelster Meredith S. , Bekaii-Saab Tanios S. , Barve Minal , Saltzman Joel , Sabari Joshua K. , Peguero Julio A. , Paulson Andrew Scott , Jänne Pasi A. , Cruz-Correa Marcia , Anderes Kenna , Velastegui Karen , Yan Xiaohong , Der-Torossian Hirak , Klempner Samuel J. , Kopetz Scott E.
Published: April 2024

Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2–7.6). Median progression-free survival was 6.9 months (95% CI, 5.7–7.4) and median overall survival was 15.9 months (95% CI, 11.8–18.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3–4 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance.

Significance:

Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer.

This article is featured in Selected Articles from This Issue, p. 897

See co-corresponding author Rona Yaeger discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606282/f27a6e46f4
Insights and Opportunity Costs in Applying Spatial Biology to Study the Tumor Microenvironment
Authors: Walker Cameron R. , Angelo Michael
Published: April 2024

The recent development of high-dimensional spatial omics tools has revealed the functional importance of the tumor microenvironment in driving tumor progression. Here, we discuss practical factors to consider when designing a spatial biology cohort and offer perspectives on the future of spatial biology research.
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

Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene–environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.

Significance:

We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.
The Association between Urinary Sodium-Potassium Ratio, Kidney Function, and Blood Pressure in a Cohort from the General Population
Authors: Brobak Karl Marius , Melsom Toralf , Eriksen Bjørn Odvar , Høieggen Aud , Norvik Jon Viljar , Solbu Marit Dahl
Published: April 2024

Introduction: Subclinical kidney dysfunction may contribute to salt-sensitive hypertension. We assessed the association between the urinary sodium-potassium ratio (Na/K ratio) and blood pressure (BP) in a general population cohort without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension. We investigated whether any such association was mediated by the kidney function markers measured glomerular filtration rate (mGFR), urinary albumin-creatinine ratio (ACR), and urinary epidermal growth factor-creatinine ratio (EGF-Cr). Methods: The Tromsø Study is a population-based study of inhabitants of the municipality of Tromsø, Northern Norway. Participants aged 50–62 years, without diabetes, chronic kidney disease, or cardiovascular disease, were invited to the substudy Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6; 2007–09). For the present study, we excluded participants reporting the use of 1 or more antihypertensive agents, leaving 1,311 RENIS-T6 participants for a cross-sectional analysis. We measured office BP, 24-h ambulatory blood pressure (ABP), and mGFR using iohexol clearance. Na/K ratio, ACR, and EGF-Cr were measured in morning urine samples. Results: Urinary Na/K ratio was significantly associated with systolic office BP and ABP independently of cardiovascular risk factors and kidney function markers. A one-standard deviation unit increase in the Na/K ratio was associated with increased systolic ABP by 1.0 (0.3–1.6) mm Hg. Urinary Na/K ratio showed a stronger association with office BP than ABP. EGF-Cr, ACR, and mGFR did not mediate the relationship between urinary Na/K ratio and systolic BP. Conclusions: In a representative sample of the middle-aged North-European population without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension, there was a consistent association between urinary Na/K ratio and BP. The association with BP was not mediated through kidney function measures, suggesting a relationship between a diet with high sodium and low potassium and higher BP regardless of kidney function.
Cross-Sectional Study on Autosomal Recessive Congenital Ichthyoses: Association of Genotype with Disease Severity, Phenotypic, and Ultrastructural Features in 74 Italian Patients
Authors: Diociaiuti Andrea , Corbeddu Marialuisa , Rossi Sabrina , Pisaneschi Elisa , Cesario Claudia , Condorelli Angelo Giuseppe , Samela Tonia , Giancristoforo Simona , Angioni Adriano , Zambruno Giovanna , Novelli Antonio , Alaggio Rita , Abeni Damiano , El Hachem May
Published: April 2024

Background: Autosomal recessive congenital ichthyoses (ARCIs) are a clinically heterogeneous group of keratinization disorders characterized by generalized skin scaling due to mutations in at least 12 genes. The aim of our study was to assess disease severity, phenotypic, and ultrastructural features and to evaluate their association with genetic findings in ARCI patients. Methods: Clinical signs and symptoms, and disease severity were scored in a single-center series of patients with a genetic diagnosis of ARCI. Skin ultrastructural findings were reviewed. Results: Seventy-four consecutive patients (mean age 11.0 years, range 0.1–48.8) affected with lamellar ichthyosis (50/74, 67.5%), congenital ichthyosiform erythroderma (18/74, 24.3%), harlequin ichthyosis (two/74, 2.7%), and other minor ARCI subtypes (four/74, 5.4%) were enrolled. Mutated genes were as follows: TGM1 in 18/74 (24.3%) patients, ALOX12B in 18/74 (24.3%), CYP4F22 in 12/74 (16.2%), ABCA12 in nine/74 (12.2%), ALOXE3 in seven/74 (9.5%), NIPAL4 in seven/74 (9.5%), and CERS3, PNPLA1, and SDR9C7 in 1 patient each (1.4%). Twenty-five previously undescribed mutations in the different ARCI causative genes, as well as two microduplications in TGM1, and two microdeletions in CYP4F22 and NIPAL4 were identified. The mean ichthyosis severity score in TGM1- and ABCA12-mutated patients was significantly higher than in all other mutated genes, while the lowest score was observed in CYP4F22-mutated patients. Alopecia, ectropion, and eclabium were significantly associated with TGM1 and ABCA12 mutations, and large, thick, and brownish scales with TGM1 mutations. Among specific phenotypic features, psoriasis-like lesions as well as a trunk reticulate scale pattern and striated keratoderma were present in NIPAL4-mutated patients. Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients. Conclusion: Our study expands the phenotypic and genetic characterization of ARCI by the description of statistically significant associations between disease severity, specific clinical signs, and different mutated genes. Finally, we highlighted the presence of psoriasis-like lesions in NIPAL4-ARCI patients as a novel phenotypic feature with diagnostic and possible therapeutic implications.
Deliverables from Metabolomics in Kidney Disease: Adenine, New Insights, and Implication for Clinical Decision-Making
Authors: Ragi Nagarjunachary , Sharma Kumar
Published: April 2024

Background: Chronic kidney disease (CKD) presents a persistent global health challenge, characterized by complex pathophysiology and diverse progression patterns. Metabolomics has emerged as a valuable tool in unraveling the intricate molecular mechanisms driving CKD progression. Summary: This comprehensive review provides a summary of recent progress in the field of metabolomics in kidney disease with a focus on spatial metabolomics to shed important insights to enhancing our understanding of CKD progression, emphasizing its transformative potential in early disease detection, refined risk assessment, and the development of targeted interventions to improve patient outcomes. Key Message: Through an extensive analysis of metabolic pathways and small-molecule fluctuations, bulk and spatial metabolomics offers unique insights spanning the entire spectrum of CKD, from early stages to advanced disease states. Recent advances in metabolomics technology have enabled spatial identification of biomarkers to provide breakthrough discoveries in predicting CKD trajectory and enabling personalized risk assessment. Furthermore, metabolomics can help decipher the complex molecular intricacies associated with kidney diseases for exciting novel therapeutic approaches. A recent example is the identification of adenine as a key marker of kidney fibrosis for diabetic kidney disease using both untargeted and targeted bulk and spatial metabolomics. The metabolomics studies were critical to identify a new biomarker for kidney failure and to guide new therapeutics for diabetic kidney disease. Similar approaches are being pursued for acute kidney injury and other kidney diseases to enhance precision medicine decision-making.
Cyanotic Nephropathy in an Adult Patient with Eisenmenger Syndrome: A Case Report and Literature Review
Authors: Zhu Fanyou , Wen Rui , Tan Xiangling , Nie Hongjun , Li Jiali , Wang Qi , Qin Jiao
Published: April 2024

Introduction: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as “pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level.” It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. Case Presentation: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. Conclusion: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.
Showcasing Sustainability Within Dietetics Education – Opportunities and Challenges
Authors: McCullough Fiona
Published: April 2024

Background: Low professional confidence and perceived competence create tangible barriers to integrating sustainable food systems (SFS) and diets into dietetic practice. One opportunity to facilitate more systemic integration into dietetic education and training is to include these concepts in professional standards. To better understand the barrier of low professional confidence and perceived competence for engagement with SFS-related practice, the purpose of this research was to investigate dietetic training standards for SFS content and to highlight opportunities for growth within the profession. Questions posed by this research are: (1) how, if at all, are SFS and diets articulated in dietetic training standards, and (2) to what level of cognitive complexity? Methods: A content analysis of dietetic training standards documents was conducted between 15 April and 15 September 2021. Search terms included 'sustain*' or 'sustainable', 'food systems' and/or 'diets'. Extracted data with applicable SFS content were analysed for level of cognitive complexity requirements. Results: Of 47 National Dietetics Associations, researchers obtained 23 dietetic training standards documents, of which 16 included SFS-related content. The majority of documents used broad descriptors of the concepts, with little granularity and at a lower level of cognitive complexity.
Atopische Dermatitis: Langzeitstudie zeigt positive Ergebnisse für Dupilumab bei Kindern
Authors: Neustädter Irena , Blatt Sophie
Published: April 2024

Background: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. Objectives: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Methods: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. Results: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response. Conclusions: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6-11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit. Trial registration: ClinicalTrials.gov Identifier NCT02612454.
Atopische Dermatitis: Zuverlässigkeit von PROs und deren Bedeutung in klinischer Praxis
Authors: Kirsten Natalia
Published: April 2024

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD. Methods: Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12–75years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm- SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups. Results: Of the 882 participants included in the psychometric analyses, the majority were adults (n¼769, 87.2%), male (n¼536, 60.8%), and white (n¼630, 71.4%). Multi-item scores from the ADerm- SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clin-ically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD.
Potential Drug-Drug Interactions in Outpatient Lung Cancer Patients in a University Hospital
Authors: Jafarova Demirkapu Mahluga , Cavdar Eyyup
Published: April 2024

Introduction: Concomitant use of drugs in the same or different indications can sometimes lead to undesirable interactions. The prevalence of drug interactions is high in cancer patients. In this study, we aimed to determine the frequency and clinical severity of drug interactions in outpatient lung cancer patients. Methods: The drugs used, kidney and liver blood analysis results of 160 outpatient lung cancer patients over the age of 18 years who received chemotherapy between October 2020 and July 2021 were evaluated. The Lexi-Interact online database was used to identify the types of clinically significant drug interactions, frequently interacting drugs, and clinical outcomes predicted by the databases. Results: The average number of drugs per patient was 4.2 ± 2.3. It was determined that there was a relationship between multidrug use and comorbidity, and the number of drugs used increased as the number of diagnoses increased. A relationship was also found between potential drug-drug interactions (pDDIs), which we observed in 52.5% of the patients, and the number of drugs used and age. The most common clinically significant C- (36.9%), D- (16.9%), and X- (10.6%) type pDDIs were detected between conventional paclitaxel-hydrochlorothiazide, conventional paclitaxel-carboplatin, and ipratropium-tiotropium, respectively. Conclusions: The use of frequently interacting drugs in outpatient lung cancer patients can lead to pDDIs. In these patients, the application of therapy by observing the drug-drug interaction may improve the quality of life.
La escritura, una experiencia de paz. Transformación de la comprensión de paz, a través de la producción escrita, en niños y niñas de quinto grado
Authors: Carmona Idárraga María Isabel , Hernández Giraldo Luz Amparo
Published: April 2024

Las pruebas saber se quedan cortas para valorar cómo escriben nuestros niños y niñas en Colombia. De allí, la preocupación por investigar cómo la escritura transforma las comprensiones de paz de 4 niños y 3 niñas de quinto grado de básica primaria, en una institución oficial urbana. Es una investigación de tipo cualitativa, con un diseño metodológico de estudio de caso múltiple. La recolección de la información a través de dos entrevistas semiestructuradas (una inicial y otra final), la aplicación de seis talleres sobre escritura y paz, instrumentos creados por las investigadoras, y los registros en diarios de campo. El análisis e interpretación de la información se desarrolló en cinco etapas: transcripción de la información, categorización natural y categorización axial, elaboración de redes semánticas y confirmación de transformaciones. Los resultados demuestran el carácter epistémico y social de la escritura; se considera como un hallazgo importante para la investigación el identificar la escritura como un asunto emotivo que le permite a los sujetos enunciarse y reconocerse a través de ella y transformadora de la manera como los niños y niñas enfrentan conceptos que les tocan su vida cotidiana.
La acción educativa abordada desde el modelo del texto
Authors: Sánchez José Roberto
Published: April 2024

Este articulo estuvo enmarcado en una investigación sobre la valoración del currículo, el cual muestra la poética de toda obra curricular desde la función narrativa, propuesta por Ricoeur, como fundamento para una hermenéutica del currículo. A partir de esto, toda carrera es una obra discursiva mediada por el texto. Esta mediación permite valorar el proceso de implantación a través de la narratividad de los actores implicados, en la que los perfiles de egreso se incorporan en las estructuras narrativas de docentes y estudiantes, reestructurando los campos semánticos de las acciones educativas, en consecuencia, los currículos concurrentes, establecidos por Posner, son derivados del acto de narrar.
Sistematización del proyecto “Los parques educativos: espacios públicos para el ejercicio ciudadano y la construcción de paz en 18 municipios del suroeste antioqueño”
Authors: Pino Yolanda , Valderrama Leydy
Published: April 2024

En este artículo se presentan los resultados de la sistematización del proyecto: "Los parques educativos: Espacios públicos para el ejercicio ciudadano y la construcción de paz", ejecutado por la Fundación CINDE con el acompañamiento y financiación de las Fundaciones SURA y BANCOLOMBIA. La intención inicial de esta iniciativa fue contribuir al desarrollo de habilidades en los líderes y lideresas para la formulación e implementación de propuestas favorables a la construcción de paz y al ejercicio de la ciudadanía. El proyecto se desarrolló durante diez (10) meses, entre junio de 2015 y abril del 2016, se realizaron encuentros pedagógicos experienciales, formulación de iniciativas comunitarias, acciones de multiplicación de los aprendizajes y construcción de material didáctico, teniendo como eje central el juego y el reconocimiento del contexto. De esta experiencia se desprenden aprendizajes significativos tanto para los participantes como para las entidades involucradas en su desarrollo, que se presentan al final del artículo como lecciones aprendidas y que se convierten en claves importantes para los procesos de formación ciudadana y construcción de paz.
De lo relacional en el arte como recurso imaginativo para la construcción de la paz
Authors: Parra Ospina Astrid Yohana
Published: April 2024

Lo relacional en el arte parte de una estrategia que entrecruza lo estético y lo artístico con un propósito de intervención social, donde el gesto creativo se da desde la problematización de las relaciones humanas y sus contextos. De este modo, con el presente artículo se pretende ampliar la mirada frente a la potencialidad de esta perspectiva contemporánea del arte, y el poder de la imaginación y la creatividad en lo humano, como herramienta que agencia, desde una apuesta ético-estética, la re-significación de la vida en común, la resolución de conflictos y la acciones conscientes en pos de la construcción de paz.
Ciudadanía, una vida posible en sociedad
Authors: Díaz Perdomo María Liliana , Rojas Suarez Nelson Darío
Published: April 2024

El presente artículo tiene como propósito mostrar las diferentes miradas con las que se aborda el tema de la ciudadanía, en relación con otros conceptos en las dinámicas democráticas como ciudadanía un concepto con historia; una mirada a la ciudadanía en Colombia, ciudadanía y escuela; tecnologías, medios de comunicación e impacto en la ciudadanía; Ciudadanía, participación y valores morales. Con base a una revisión documental, expone las diferentes investigaciones que se han realizado en su mayoría a nivel Latinoamericano y precisando el caso colombiano, con el que se pretende ayudar a comprender el concepto de ciudadanía expresada a lo largo de la historia y en diferentes escenarios sociales.
Lenguajes poéticos desde el silencio, un encuentro con la experiencia
Authors: Villada Rendón Paula Andrea
Published: April 2024

Diferentes autores han reflexionado sobre la crisis de la experiencia en la modernidad, época en la cual es concebida como experimento y no como experiencia particular que surge del acontecer y genera sorpresa y novedad. En este sentido, el artículo invita a pensar el concepto de experiencia desde la propuesta hecha por Jorge Larrosa, la experiencia como "eso que nos pasa", que nos permite hacernos conscientes de nosotros, de los otros y del mundo, que genera transformaciones.
Más allá de la saturación de información y de comunicación provocada por el sistema tecnológico actual, del afán, fruto de la competencia y de la incansable búsqueda de una mayor productividad, es necesario volver al silencio, que implica presencia y atención, en el cual la experiencia encuentra la posibilidad de nacer y dar paso a la apertura, al reconocimiento y a la contemplación de aquello que de manera inesperada y singular brinda sentido a la existencia y nos posibilita reconocer el rostro de ese otro que también nos interpela. El asombro, la imaginación y los sueños tienen cabida en el silencio, y para ello, es necesario recuperar otros lenguajes poéticos como el arte.
La belleza revelada del cedro y el yarey: la artesanía nacida de un grupo tradicional de ascendencia haitiana en Cuba
Authors: Pullés Ligia Lavielle , López Diana Liset Pompa
Published: April 2024

Las variopintas artes y oficios populares latinoamericanos son apreciadas por nutrirse de raíces étnicas ancestrales, que cuentan su historia en el tejido o el material de la pieza. Entre ellos, las artesanías distinguen el color mestizo del continente. En Cuba, algunas producciones de este tipo narran el paso de los siglos en manos de artífices alejados del conocimiento académico. Los saberes creativos, transmitidos fundamentalmente de forma generacional, en la comunidad o en la familia, aportan valores históricos a artículos de uso utilitario o no. Precisamente este tema expone a una familia descendiente de inmigrantes haitianos de una zona rural del oriente del país, herederos de una tradición artesanal también procedente de Haití. Su obra resulta interesante en tanto devela cómo las prácticas familiares y comunales rurales de este grupo portador conocido como Los Richard devienen en una producción cultural (artesanal y también musical) que favorece al entorno social donde se enclavan. La perspectiva cualitativa expresa en diversas entrevistas en profundidad y la observación etnográfica nos permitió no solo ahondar en la historia y las formas de hacer artesanía de esta familia creadora, sino también divulgar los valores de su producción y sus logros como grupo familiar portador dentro del mismo municipio y las redes de la cultura de toda la región oriental de la ínsula cubana.
O conceito de relevância na recuperação de informação
Authors: Janaite Neto Jorge , Ferneda Edberto
Published: April 2024

This work aims to present a bibliographical survey on the concept of relevance, its properties and characteristics, as well as systematizing its manifestations and its use in Information Science, particularly in the process of information retrieval. To achieve this, the research was based on a bibliographical survey of several authors who have relevance as an object of study. It found that the concept of relevance has several formal definitions and can be interpreted in different ways. Relevance is also strongly linked to information retrieval systems. In this context, it can be classified under two approaches: user relevance and system relevance. From the results, we conclude that relevance plays a fundamental role in Information Science, with emphasis on the information retrieval process, which often uses this concept as a metric to evaluate the effectiveness of algorithms and systems.