bluuebunny/crossref_metadata_2025 huggingface dataset:
Video support for prehospital stroke consultation: implications for system design and clinical implementation from prehospital simulations
Authors: Candefjord Stefan , Andersson Hagiwara Magnus , Sjöqvist Bengt Arne , Karlsson Jan-Erik , Nordanstig Annika , Rosengren Lars , Söderholm Hanna Maurin
Published: May 2024

Background

Video consultations between hospital-based neurologists and Emergency Medical Services (EMS) have potential to increase precision of decisions regarding stroke patient assessment, management and transport. In this study we explored the use of real-time video streaming for neurologist–EMS consultation from the ambulance, using highly realistic full-scale prehospital simulations including role-play between on-scene EMS teams, simulated patients (actors), and neurologists specialized in stroke and reperfusion located at the remote regional stroke center.

Methods

Video streams from three angles were used for collaborative assessment of stroke using the National Institutes of Health Stroke Scale (NIHSS) to assess symptoms affecting patient’s legs, arms, language, and facial expressions. The aim of the assessment was to determine appropriate management and transport destination based on the combination of geographical location and severity of stroke symptoms. Two realistic patient scenarios were created, with severe and moderate stroke symptoms, respectively. Each scenario was simulated using a neurologist acting as stroke patient and an ambulance team performing patient assessment. Four ambulance teams with two nurses each all performed both scenarios, for a total of eight cases. All scenarios were video recorded using handheld and fixed cameras. The audio from the video consultations was transcribed. Each team participated in a semi-structured interview, and neurologists and actors were also interviewed. Interviews were audio recorded and transcribed.

Results

Analysis of video-recordings and post-interviews (n = 7) show a more thorough prehospital patient assessment, but longer total on-scene time, compared to a baseline scenario not using video consultation. Both ambulance nurses and neurologists deem that video consultation has potential to provide improved precision of assessment of stroke patients. Interviews verify the system design effectiveness and suggest minor modifications.

Conclusions

The results indicate potential patient benefit based on a more effective assessment of the patient’s condition, which could lead to increased precision in decisions and more patients receiving optimal care. The findings outline requirements for pilot implementation and future clinical tests.
Paramedics’ experiences of barriers to, and enablers of, responding to suspected or confirmed COVID-19 cases: a qualitative study
Authors: Howarth Ursula , Zimmerman Peta-Anne , van de Mortel Thea F. , Barr Nigel
Published: May 2024

Background

Paramedics’ work, even pre-pandemic, can be confronting and dangerous. As pandemics add extra stressors, the study explored paramedics’ lived experience of the barriers to, and enablers of, responding to suspected or confirmed Coronavirus Disease 2019 (COVID-19) cases.

Methods

This exploratory-descriptive qualitative study used semi-structured interviews to investigate Queensland metropolitan paramedics’ experiences of responding to cases during the COVID-19 pandemic. Interview transcripts were analysed using thematic analysis. Registered Paramedics were recruited by criterion sampling of staff who experienced the COVID-19 pandemic as active officers.

Results

Nine registered paramedics participated. Five themes emerged: communication, fear and risk, work-related protective factors, leadership, and change. Unique barriers included impacts on effective communication due to the mobile nature of paramedicine, inconsistent policies/procedures between different healthcare facilities, dispatch of incorrect information to paramedics, assisting people to navigate the changing healthcare system, and wearing personal protective equipment in hot, humid environments. A lower perceived risk from COVID-19, and increased empathy after recovering from COVID-19 were unique enablers.

Conclusions

This study uncovered barriers and enablers to attending suspected or confirmed COVID-19 cases unique to paramedicine, often stemming from the mobile nature of prehospital care, and identifies the need for further research in paramedicine post-pandemic to better understand how paramedics can be supported during public health emergencies to ensure uninterrupted ambulance service delivery.
Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: “INSIST” study
Authors: Mohammedi Kamel , Fauchier Laurent , Quignot Nadia , Khachatryan Artak , Banon Tamar , Kapnang Raissa , Kikuchi Kazue , Ren Hongye , Massien Christine , Vigié Lucile , Larsen Sara , Sibon Igor
Published: May 2024

Background

People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France.

Methods

We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs.

Results

Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47–7.15] versus 1.38 [1.24–1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7–159.0] versus 126.4 [117.2–136.4]; stroke recurrence: 86.7 [66.4–113.4] versus 66.5 [59.2–74.6]; mortality 291.5 [259.1–327.9] versus 144.1 [134.3–154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66–2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378).

Conclusions

The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.
Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study
Authors: Elhadad Mohamed A. , del C. Gómez-Alonso Mónica , Chen Chien-Wei , Neumeyer Sonja , Delerue Thomas , Rathmann Wolfgang , Näbauer Michael , Meisinger Christa , Kääb Stefan , Seissler Jochen , Graumann Johannes , Koenig Wolfgang , Suhre Karsten , Gieger Christian , Völker Uwe , Peters Annette , Hammer Elke , Waldenberger Melanie
Published: May 2024

Background and aims

Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.

Methods

The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model.

Results

In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30–1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09–1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways.

Conclusions

Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.
Importance of on-farm research for validating process-based models of climate-smart agriculture
Authors: Ellis Elizabeth , Paustian Keith
Published: May 2024

Climate-smart agriculture can be used to build soil carbon stocks, decrease agricultural greenhouse gas (GHG) emissions, and increase agronomic resilience to climate pressures. The US recently declared its commitment to include the agricultural sector as part of an overall climate-mitigation strategy, and with this comes the need for robust, scientifically valid tools for agricultural GHG flux measurements and modeling. If agriculture is to contribute significantly to climate mitigation, practice adoption should be incentivized on as much land area as possible and mitigation benefits should be accurately quantified. Process-based models are parameterized on data from a limited number of long-term agricultural experiments, which may not fully reflect outcomes on working farms. Space-for-time substitution, paired studies, and long-term monitoring of SOC stocks and GHG emissions on commercial farms using a variety of climate-smart management systems can validate findings from long-term agricultural experiments and provide data for process-based model improvements. Here, we describe a project that worked collaboratively with commercial producers in the Midwest to directly measure and model the soil organic carbon (SOC) stocks of their farms at the field scale. We describe this study, and several unexpected challenges encountered, to facilitate further on-farm data collection and the creation of a secure database of on-farm SOC stock measurements.
Lysine-specific methyltransferase Set7/9 in stemness, differentiation, and development
Authors: Daks Alexandra , Parfenyev Sergey , Shuvalov Oleg , Fedorova Olga , Nazarov Alexander , Melino Gerry , Barlev Nickolai A.
Published: May 2024

The enzymes performing protein post-translational modifications (PTMs) form a critical post-translational regulatory circuitry that orchestrates literally all cellular processes in the organism. In particular, the balance between cellular stemness and differentiation is crucial for the development of multicellular organisms. Importantly, the fine-tuning of this balance on the genetic level is largely mediated by specific PTMs of histones including lysine methylation. Lysine methylation is carried out by special enzymes (lysine methyltransferases) that transfer the methyl group from S-adenosyl-L-methionine to the lysine residues of protein substrates. Set7/9 is one of the exemplary protein methyltransferases that however, has not been fully studied yet. It was originally discovered as histone H3 lysine 4-specific methyltransferase, which later was shown to methylate a number of non-histone proteins that are crucial regulators of stemness and differentiation, including p53, pRb, YAP, DNMT1, SOX2, FOXO3, and others. In this review we summarize the information available to date on the role of Set7/9 in cellular differentiation and tissue development during embryogenesis and in adult organisms. Finally, we highlight and discuss the role of Set7/9 in pathological processes associated with aberrant cellular differentiation and self-renewal, including the formation of cancer stem cells.
Hemodynamic instability caused by pneumorrachis and pneumomediastinum following epidural analgesia: a case report
Authors: Fountoulaki Maria , Kapetanakis Emmanouil I. , Kouna Niki , Papagiannis Nikolaos , Sidiropoulou Tatiana
Published: May 2024

Background

Pneumomediastinum and pneumorrachis are rare complications following epidural analgesia, that can either be asymptomatic or rarely can produce mild to moderate severity symptoms. Most reported cases regarding the presentation of these two entities with epidural analgesia concern asymptomatic patients, however there are cases reporting post-dural puncture headache and respiratory manifestations.

Case presentation

We present a case where a combined lumbar epidural and spinal anesthesia was performed using the loss of resistance to air technique (LOR), on a 78-year-old Greek (Caucasian) male undergoing a total hip replacement. Despite being hemodynamically stable throughout the operation, two hours following epidural analgesia the patient manifested a sudden drop in blood pressure and heart rate that required the administration of adrenaline to counter. Pneumomediastinum, pneumorrachis and paravertebral soft tissue emphysema were demonstrated in a Computed Tomography scan. We believe that injected air from the epidural space and surrounding tissues slowly moved towards the mediastinum, stimulating the para-aortic ganglia causing parasympathetic stimulation and therefore hypotension and bradycardia.

Conclusion

Anesthesiologists should be aware that epidural analgesia using the LOR to technique injecting air could produce a pneumomediastinum and pneumorrachis, which in turn could produce hemodynamic instability via parasympathetic stimulation.
Eradication of Klebsiella pneumoniae pulmonary infection by silver oxytetracycline nano-structure
Authors: Mosallam Farag M. , Elshimy Rana
Published: May 2024

Targeted bactericidal nanosystems hold significant promise to improve the efficacy of existing antimicrobials for treatment of severe bacterial infections by minimizing the side effects and lowering the risk of antibiotic resistance development. In this work, Silver Oxytetracycline Nano-structure (Ag-OTC-Ns) was developed for selective and effective eradication of Klebsiella pneumoniae pulmonary infection. Ag-OTC-Ns were prepared by simple homogenization-ultrasonication method and were characterized by DLS, Zeta potential, TEM and FT-IR. The antimicrobial activity of Ag-OTC-Ns was evaluated in vitro using broth micro-dilution technique and time-kill methods. Our study showed that MICs of AgNO3, OTC, AgNPs and Ag-OTC-Ns were 100, 100, 50 and 6.25 µg/ml, respectively. Ag-OTC-Ns demonstrated higher bactericidal efficacy against the targeted Klebsiella pneumoniae at 12.5 µg/ml compared to the free Oxytetracycline, AgNO3 and AgNPs. In vivo results confirmed that, Ag-OTC-Ns could significantly eradicate K. pneumoniae from mice lung in compare with free Oxytetracycline, AgNO3 and AgNPs. In addition, Ag-OTC-Ns could effectually diminish the inflammatory biomarkers levels of Interferon Gamma and IL-12, and as a result it could effectively lower lung damage in K. pneumoniae infected mice. Ag-OTC-Ns has no significant toxicity on tested mice along the experimental period, there was no sign of behavioral abnormality in the surviving mice indicating that the Ag-OTC-Ns is safe at the used concentration. Furthermore, capability of 5 kGy Gamma ray to sterilize Ag-OTC-Ns solution without affecting it stability was proven.
BHLHE41 inhibits bladder cancer progression via regulation of PYCR1 stability and thus inactivating PI3K/AKT signaling pathway
Authors: Xiao Shuai , Chen Junjie , Wei Yongbao , Song Wei
Published: May 2024

Background

The basic helix-loop-helix family member e41 (BHLHE41) is frequently dysregulated in tumors and plays a crucial role in malignant progression of various cancers. Nevertheless, its specific function and underlying mechanism in bladder cancer (BCa) remain largely unexplored.

Methods

The expression levels of BHLHE41 in BCa tissues and cells were examined by qRT-PCR and western blot assays. BCa cells stably knocking down or overexpressing BHLHE41 were constructed through lentivirus infection. The changes of cell proliferation, cell cycle distribution, migration, and invasion were detected by CCK-8, flow cytometry, wound healing, transwell invasion assays, respectively. The expression levels of related proteins were detected by western blot assay. The interaction between BHLHE41 and PYCR1 was explored by co-immunoprecipitation analysis.

Results

In this study, we found that BHLHE41 was lowly expressed in bladder cancer tissues and cell lines, and lower expression of BHLHE41 was associated with poor overall survival in bladder cancer patients. Functionally, by manipulating the expression of BHLHE41, we demonstrated that overexpression of BHLHE41 significantly retarded cell proliferation, migration, invasion, and induced cell cycle arrest in bladder cancer through various in vitro and in vivo experiments, while silence of BHLHE41 caused the opposite effect. Mechanistically, we showed that BHLHE41 directly interacted with PYCR1, decreased its stability and resulted in the ubiquitination and degradation of PYCR1, thus inactivating PI3K/AKT signaling pathway. Rescue experiments showed that the effects induced by BHLHE41 overexpression could be attenuated by further upregulating PYCR1.

Conclusion

BHLHE41 might be a useful prognostic biomarker and a tumor suppressor in bladder cancer. The BHLHE41/PYCR1/PI3K/AKT axis might be a potential therapeutic target for bladder cancer intervention.
Applying LASSO logistic regression for the prediction of biliary complications after ex vivo liver resection and autotransplantation in patients with end-stage hepatic alveolar echinococcosis
Authors: Lin Xin , Shao Ying-Mei , Zhang Rui-Qing , Aji Tuerganaili
Published: May 2024

Background

The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model.

Methods

This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method.

Results

The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417–0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit.

Conclusions

A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.
Rethinking students’ mental health assessment through GHQ-12: evidence from the IRT approach
Authors: Comotti Anna , Barnini Teresa , Fattori Alice , Paladino Maria Emilia , Riva Michele Augusto , Bonzini Matteo , Belingheri Michael
Published: May 2024

Background

The General Health Questionnaire-12 (GHQ-12) is a widely used screening tool for mental health assessment however its traditional scoring methods and cutoffs may not adequately capture the mental health complexities of younger populations.

Methods

This study explores GHQ-12 responses from a sample of university students. Possible differences in means scores considering gender, age, academic field and degree course were assessed through t-test or one-way ANOVA as appropriate. To deeper understanding different levels of severity and individual item impact on general distress measurement, we applied Item-Response-Theory (IRT) techniques (two-parameters logistic model). We compared students’ population with a population of workers who underwent a similar psychological evaluation.

Results

A total of 3834 university students participated in the study. Results showed that a significant proportion (79%) of students reported psychological distress. Females and younger students obtained significantly higher average scores compared to others. IRT analysis found item-specific variations in mental distress levels, with more indicative items for short-term fluctuations and potential severe mental health concerns. Latent class analysis identified three distinct subgroups among students (including 20%, 37%, 43% of the participants respectively) with different levels of psychological distress severity. Comparison with a population of adults showed that students reported significantly higher scores with differences in the scale behavior.

Conclusion

Our results highlighted the unique mental health challenges faced by students, suggesting a reevaluation of GHQ-12 applicability and cutoff scores for younger populations, emphasizing the need for accurate instruments in mental health evaluation.
Monitoring of ground subsidence using PS-InSAR technique in the Southeast Texas (SETX) Region
Authors: Nur Arip Syaripudin , Nam Boo Hyun , Choi Shinwoo , Kim Yong Je
Published: May 2024

The southeast Texas (SETX) coastal area, owing to its unique geographical location and geological attributes, is facing a spectrum of geological challenges, such as ground subsidence, flooding, and coastal erosion. This study endeavors to evaluate the recent instances of ground subsidence and their associated rates, focusing on comprehending their implications for flooding within SETX. Employing the Persistence Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) technique, this study employs Sentinel-1 SAR satellite data with descending orbit observations spanning from January 2020 to March 2023. Our findings indicate that both the northwestern and eastern regions of Houston have been settled with rates up to 2 cm/year. This settlement trend is consistent with data derived from GPS and groundwater level measurements. This investigation explicitly shows the substantial temporal and spatial variations in subsidence rates, predominantly influenced by localized groundwater extraction due to urbanization (e.g., population growth, land development, etc.). By advocating for the integration of InSAR, GPS, and groundwater measurements, this research aspires to make valuable contributions toward the mitigation of subsidence and flood-related hazards in the SETX area.
A pediatric case of Burkitt’s lymphoma with bile duct obstruction requiring surgical biliary reconstruction
Authors: Watanabe Shun , Suzuki Kan , Ogino Kei , Irie Sumiko , Kamata Yuko , Matsudera Shotaro , Hatanaka Masahiro , Kurosaki Kazunori , Ishikawa Makoto , Okuya Mayuko , Sato Yuya , Yamamiya Akira , Irisawa Atsushi , Ishida Kazuyuki , Yoshihara Shigemi , Kojima Kazuyuki
Published: May 2024

Background

Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt’s lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery.

Case presentation

A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed.

Conclusions

Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue.
Interpretable machine learning decodes soil microbiome’s response to drought stress
Authors: Hagen Michelle , Dass Rupashree , Westhues Cathy , Blom Jochen , Schultheiss Sebastian J. , Patz Sascha
Published: May 2024

Background

Extreme weather events induced by climate change, particularly droughts, have detrimental consequences for crop yields and food security. Concurrently, these conditions provoke substantial changes in the soil bacterial microbiota and affect plant health. Early recognition of soil affected by drought enables farmers to implement appropriate agricultural management practices. In this context, interpretable machine learning holds immense potential for drought stress classification of soil based on marker taxa.

Results

This study demonstrates that the 16S rRNA-based metagenomic approach of Differential Abundance Analysis methods and machine learning-based Shapley Additive Explanation values provide similar information. They exhibit their potential as complementary approaches for identifying marker taxa and investigating their enrichment or depletion under drought stress in grass lineages. Additionally, the Random Forest Classifier trained on a diverse range of relative abundance data from the soil bacterial micobiome of various plant species achieves a high accuracy of 92.3 % at the genus rank for drought stress prediction. It demonstrates its generalization capacity for the lineages tested.

Conclusions

In the detection of drought stress in soil bacterial microbiota, this study emphasizes the potential of an optimized and generalized location-based ML classifier. By identifying marker taxa, this approach holds promising implications for microbe-assisted plant breeding programs and contributes to the development of sustainable agriculture practices. These findings are crucial for preserving global food security in the face of climate change.
Quality of life in individuals with neurofibromatosis type 1 associated cutaneous neurofibromas: validation of the Dutch cNF-Skindex
Authors: Dhaenens Britt A. E. , van Dijk Sarah A. , Fertitta Laura , Taal Walter , Wolkenstein Pierre , Oostenbrink Rianne
Published: May 2024

Background

Almost all patients with Neurofibromatosis type 1 (NF1) develop cutaneous neurofibroma (cNF), benign dermal tumours that have a large impact on the patient’s Quality of Life (QoL). The French cNF-Skindex is the first questionnaire to specifically assess cNF-related QoL in patients with NF1. We aimed to adapt and validate a Dutch version of the cNF-Skindex.

Methods

The questionnaire was translated using forward and backwards translation, and subsequently administered to a sample of 59 patients on two separate occasions. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating internal consistency and test-retest reliability, by calculating Cronbach’s alpha and Spearman’s rank correlation coefficients. The EQ-5D-5L and SF-36 were used to evaluate convergent validity, using Spearman’s rank correlation coefficients. An exploratory factor analysis was performed to study the data’s internal structure. Multivariable linear regression was used to model the relationship between patient characteristics and the cNF-Skindex.

Results

The Dutch cNF-Skindex demonstrated excellent feasibility and reliability (Cronbach’s alpha 0.96, test-retest correlation coefficient 0.88). Convergent validity was confirmed for the EQ-5D-5L and relevant SF-36 scales. All items and subdomains from the original questionnaire were confirmed following exploratory factor analysis. The patient characteristics included in the multivariable linear regression were not significantly associated with the cNF-Skindex score.

Conclusions

The Dutch cNF-Skindex displayed excellent psychometric properties, enabling use in the Netherlands.
Alterations of the hormones follitropin and lutropin in the blood of young mice dosed with lindane
Authors: Pérez-González Ernestina , Flores-Flores Frida Ariadna , Lugo-Martínez Perla Yareli , Herrera-Moreno María Nancy , Llanes-Cárdenas Omar , González-Ocampo Héctor Abelardo , Solis-Carrasco Jesús Daniel , Barraza-Tizoc Claudia Leonor , Enríquez-Verdugo Idalia , Almanza-Peñuelas Juan Francisco , Ramos-Beltrán Daniela Esmeralda , Salomón-Soto Víctor Manuel
Published: May 2024

Background

The gonadotropins lutropin and follitropin stimulate steroid synthesis in the gonads during gonadal maturation by promoting oogenesis and spermatogenesis. Endocrine disruptors such as lindane (γHCH) can alter the reproductive stage so and could alter puberty by interfering with lutropin and follitropin signaling. γHCH was classified by World Health Organization as “moderately restricted”, and in 2009 it is production and agricultural use was prohibited, under the Stockholm Convention, however, its use as a pharmaceutical treatment against lice and scabies is still allowed (and mainly, for use by the health sector). This study aimed to examine the effects of single-dose exposure to γHCH in young mice (Mus musculus) on lutropin and follitropin concentration, and to correlate gonadal maturity status and phenotypic characteristics.

Methods

Young γHCH-treated mice (16 females and 16 males) received a single dose of 25, 10, 5, or 0 µg/ml γHCH per gram of body weight, ocular route. Once secondary sexual characteristics were observed, the gonads were dissected and examined using histological techniques and the ovarian follicles were classified as dependent and independent of gonadotropins; the testicles were classified as inactive, early and late spermatogenesis; and the blood was processed with the lutropin and follitropin ELISA kit.

Results

The results indicate significant differences in the concentration of lutropin and follitropin between males and females (Fisher p < 0.05). The lutropin and follitropin levels showed a tendency to decrease in females, whereas, in males they tended to increase as the dose of γHCH increased. In females, it was observed that at the follitropin and lutropin decreased 42.3% and 83.7%, respectively at dose of 25 µg/ml; while in males, follitropin increased 51.9% at the dose of 25 µg/ml, and at the dose of 10 µg/ml lutropin increased by 242.5%. Contrary to that, gonadal maturity increased in females and decreased in males with increasing γHCH dose, disagreeing with the idea that gonadotropins coincide with the onset of puberty and gonadal maturity.

Conclusions

The results allow us to infer that exposure to γHCH could promote non-monotonic responses; however, this does not seem to alter puberty in the doses and conditions of the present experiment.
Bilateral simultaneous total knee arthroplasty with and without patellar resurfacing. A prospective single surgeon series with a minimum follow-up of 7 years
Authors: Alamino Leonel Perez , Garabano German , Pesciallo Cesar Ángel , Del Sel Hernán
Published: May 2024

Background

Total knee arthroplasty (TKA) is the most effective treatment for end-stage adult knee osteoarthritis, but it has been reported that patient satisfaction may vary. A malfunction of the patellofemoral joint may produce anterior knee pain (AKP) for several reasons. While some surgeons systematically resurface the patella despite the risk of potential complications such as fracture, loosening, or wear of the patella, others prefer to preserve it to reduce AKP and revision rates. This study aimed to evaluate whether patellar resurfacing had better clinical and functional outcomes, complications, and revision rates in patients undergoing simultaneous bilateral total knee arthroplasty.

Methods

We conducted a prospective cohort study, including patients who underwent bilateral simultaneous TKA in which the patella was replaced in one knee and preserved in the other, with a minimum follow-up of 7 years. We assessed clinical and functional outcomes with the Knee Society Score (KSS) and Visual Analogue Scale (VAS); complications and revision rates were also registered.

Results

The final series consisted of 43 patients with 86 knee arthroplasties. After a mean of 7.6 years of follow-up, no significant differences were found regarding KSS (clinical: 82.8 ± 7.4 versus 83.2 ± 3.4, p = 0.92; functional 89.1 ± 8.2: versus 90.4 ± 6.8; p = 0.99), VAS (2.0 ± 0.9 versus 1.8 ± 1.0; p = 0.84), complications (10.5% versus 8.1%; p = 0.57), or revision rates (2.3% versus 2.3%; p = 0.99) when comparing patellar resurfacing versus retention.

Conclusion

In the context of total knee arthroplasty, patellar replacement did not demonstrate statistically significant differences concerning patellar retention in clinical nor functional outcomes, AKP, complications, or revision rates after a minimum of 7 years of follow-up.
First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses.
Authors: Juric Dejan , Kalinsky Kevin , Turner Nicholas C. , Jhaveri Komal L. , Schmid Peter , Loi Sherene , Saura Cristina , Im Seock-Ah , Sunpaweravong Patrapim , Li Huiping , Musolino Antonino , Zhang Qingyuan , Nowecki Zbigniew , Leung Roland Ching-Yu , Thanopoulou Eirini , Shankar Noopur , Lei Guiyuan , Devine Jacob , Stout Thomas J , Loibl Sibylle
Published: May 2024

1003

Background: INAVO120 (NCT04191499) showed significantly and meaningfully improved investigator-assessed progression-free survival (PFS; stratified hazard ratio 0.43) with Inavo+Palbo+Fulv v Pbo+Palbo+Fulv, and manageable safety and tolerability. To further characterize the substantial benefit/risk of the Inavo triplet, we assessed additional clinically relevant efficacy endpoints, detailed safety data of key adverse events (AEs) for Inavo (hyperglycemia [HG], diarrhea, rash, stomatitis), and pt-reported outcomes (PROs). Methods: Efficacy endpoints includedtime from randomization to end of next-line treatment (tx; proxy for PFS2) and to first chemotherapy (TTFC). Key AEs were reported by grouped terms. PROs were assessed by PRO-CTCAE, an overall bother item, BPI-SF, and EORTC QLQ-C30. Results: Increases in median “PFS2” (24.0 v 15.1 mo; unstratified hazard ratio: 0.59 [95% CI, 0.42–0.83]) and TTFC (NE v 15.0 mo; unstratified hazard ratio: 0.53 [95% CI, 0.37–0.78]) were observed in the Inavo v Pbo arm (median follow-up: 21.3 mo; Table). Key AEs were mostly G1–2 and had resolved (Table). No key AEs were G4–5. In the Inavo arm, among pts who experienced key AEs (HG, diarrhea, rash, stomatitis), median time to first onset was 7, 15, 29, and 13 days, respectively. The key AEs were managed with standard supportive care and Inavo dose interruptions/reductions. One pt discontinued Inavo due to HG; one, due to stomatitis. Pts receiving Inavo experienced a longer duration of time without worsening pain severity and maintained their day-to-day functioning and health-related quality of life on tx. Most pts in both arms reported levels of selected symptomatic AEs from the PRO-CTCAE and overall tx bother as moderate or less, indicating that Inavo does not contribute additional tx burden. Conclusions: Inavo+Palbo+Fulv was associated with sustained benefit beyond disease progression, delaying chemotherapy administration, with manageable safety and tolerability that was reflected in PROs; hence, supporting it as a new standard of care. Clinical trial information: NCT04191499 . [Table: see text]
Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202.
Authors: Giordano Antonio , Awan Arif Ali Ali , Yang Bruce Justine , Rugo Hope S. , Diamond Jennifer Robinson , Novik Yelena , Baranda Joaquina Celebre , Muro Kei , Ono Makiko , Nanda Rita , Kaplan Jason , Gorla Seema Rao , Liu Shubin , Wozniak Michele , Lee Anthony , Traina Tiffany A.
Published: May 2024

1005

Background: EV, a Nectin-4–directed antibody–drug conjugate, is approved for use in urothelial cancer. Nectin-4 is expressed in several solid tumors, including BC. EV monotherapy was evaluated in TNBC and HR+/HER2- BC in EV-202 (NCT04225117). Methods: In this open-label, multicohort, phase 2 trial, eligible adults had locally advanced or metastatic (la/m) solid tumors, measurable disease, and ECOG PS 0–1. In BC cohorts, patients (pts) had prior taxanes or anthracyclines, ≥1 standard-of-care cytotoxic regimen and ≤2 lines (L) of cytotoxic therapy for la/mBC, and prior PD-1/L1 inhibitor (TNBC) or endocrine treatment (tx) with a CDK4/6 inhibitor (HR+/HER2- BC). Nectin-4 expression was not required but was assessed retrospectively. Pts received EV 1.25 mg/kg intravenously days 1, 8, and 15 of each 28-d cycle until discontinuation criteria (eg, disease progression, unacceptable toxicity) were met. Primary endpoint was confirmed objective response rate (ORR); ≥10 (TNBC) or ≥12 (HR+/HER2- BC) responders out of 40 evaluable pts were needed to claim promising antitumor activity. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Antitumor activity was investigator-assessed per RECIST v1.1. Results: In the TNBC cohort, 42 female pts received EV as of Mar 3, 2023 (median follow-up, 11.8 mo). Median age was 53 y, 64% had ≥2L systemic tx for metastatic BC, and 33% had prior sacituzumab govitecan. ORR was 19.0%. Grade ≥3 tx-related adverse events (TRAEs) in >1 pt were decreased neutrophil count (n=3, 7%), decreased white blood cell count (n=2, 5%), and increased aspartate aminotransferase (n=2, 5%). Selected TRAEs of special interest were skin reactions (n=25, 60%), peripheral neuropathy (n=11, 26%), and hyperglycemia (n=2, 5%). In the HR+/HER2- BC cohort (median age, 57.0 y), 45 female pts received EV as of Dec 3, 2022 (median follow-up, 11.2 mo). Most (73%) had ≥3L systemic tx for metastatic BC. ORR was 15.6%. Grade ≥3 TRAEs in >1 pt were maculopapular rash (n=7, 16%), pruritus and increased aspartate aminotransferase (both n=3, 7%), and abdominal pain and erythema (both n=2, 4%). Selected TRAEs of special interest were skin reactions (n=28, 62%), peripheral neuropathy (n=12, 27%), and hyperglycemia (n=5, 11%). Additional efficacy data for both cohorts are in the table. Conclusions: EV showed antitumor activity in heavily pretreated TNBC. Safety in both cohorts was manageable and consistent with previous reports. Clinical trial information: NCT04225117 . [Table: see text]
Role of social determinants burden on outcomes and survival for AYAs with cancer.
Authors: Daunov Michael , Perez Jamie Abraham , Cullen Jennifer , Egler Rachel A. , Daunov Kate
Published: May 2024

1610

Background: Health care utilization and survival are correlated with social determinants of health (SDoH). Minimal data exists on the impact of SDoH within AYA Oncology. Methods: TriNetX, a de-identified healthcare research database retrospectively examined presence of SDoH billing codes among AYA cancer patients at various time points. Three cohorts were evaluated: ages <15, 15-39, >39. Cox proportional hazards regression was used to assess predictors of SDoH burden and survival in AYAs. Results: Baseline demographics were similar across cohorts. AYAs had higher baseline SDoH (25811, 5.2%) compared to <15 (3913, 2.9%) and >39 (58237, 1.8%). After diagnosis, AYAs had greater incidence of SDoH burden at 1y (OR 1.86 vs <15, 2.71 vs >39), 3y (OR 1.79 vs <15, 2.63 vs >39), and 5y (OR 1.8 vs <15, 2.5 vs >39). AYAs with any SDoH had higher occurrences of ED (OR 2.51) and ICU visits (OR 1.94). Within AYAs, baseline SDoH code was most prevalent in 30-39 age group, males, Hawaiian/Pacific Islanders, and lung cancers. The most common SDoH code in AYAs at diagnosis was homelessness at 57.8%. In a multivariate analysis examining incidence of SDoH in AYAs, positive associations were age 30-39; 1.95 (1.61-2.37), males; 1.49 (1.36-1.63), American Indian/Alaska Native; 4.44 (3.12-6.31), and presence of SDoH at diagnosis; 83.0 (71.6-96.3). Mortality in AYAs was associated with age 30-39; 1.81 (1.72-1.91), males; 1.58 (1.54-1.63), unknown race; 1.53 (1.48-1.58), and CNS tumors; 1.15 (1.06-1.25). Conclusions: AYAs with cancer have a high prevalence of SDoH burden at diagnosis and acquired. Within AYAs, age 30-39, males, and minority populations were most likely to acquire a SDoH code and have worse survival. The strongest association with both incidence of SDoH burden and mortality was a SDoH code at diagnosis. [Table: see text]
Challenges and solutions to recruiting diverse populations to oncology clinical trials: A mixed-methods study of clinical research coordinators.
Authors: Velazquez Manana Ana I. , Trejo Evelin , Piawah Sorbarikor , Kaplan Celia
Published: May 2024

1619

Background: Multiple barriers limit the enrollment of diverse populations in oncology clinical trials (CTs). A review of our institutional CTs recruitment dashboard identified underrepresentation of Black and Latinx adults among thoracic and gastrointestinal (GI) oncology CTs participants compared to demographics of our catchment area and patient population. We conducted a mixed-methods study to identify barriers and potential solutions to the enrollment of diverse populations in oncology CTs in our institution. Methods: We conducted a mixed methods study enrolling clinical investigators and clinical research coordinators’ (CRCs) at an NCI-designated CCC in Northern California. Data from CRCs is presented. All CRCs supporting CTs in the thoracic and GI medical oncology were invited to participate in qualitative, one-on-one, semi-structured interviews. Participants completed 60-90 minutes interview and a short survey. Data were analyzed using a thematic inductive approach. Results: Of 14 CRCs, the majority were female (78.6%), with primary focus on thoracic (50.0%) and GI (35.7%) oncology CTs. 64.3% of CRCs reported >80% of their work was dedicated to coordinating and managing therapeutic cancer CTs. In survey responses CRCs identified inability to take time away from work/family (64.3%), inadequate insurance coverage (42.9%), lack of transportation (35.7%), and language barriers (35.7%) as major barriers to enrollment of diverse patients in CTs. In qualitative interviews CRCs expressed the need of culturally and language appropriate materials for CT recruitment, establishing a sense of connection between clinical research staff/PI and patients, accommodating socioeconomic concerns, and resources to respond to potential participants’ mistrust of medical research. Main obstacles faced by CRCs during patient enrollment in CTs included lack of time, low patient awareness, resistance from colleagues, lack of multilingual staff, and inadequate logistical support. CRCs identified in-person interpretation as beneficial and identified a strong rapport between the clinical provider and the potential participant as the most important component to boost recruitment of minorities. Lastly, CRCs highlighted that institutional efforts are needed to increase CT participation among all populations. Conclusions: Lack of representation of diverse populations in CTs remains a complex challenge. Our study of CRCs’ perceptions highlights access to in-person translators, culturally and language concordant materials, education resources, and increased rapport as key areas for intervention to facilitate patient enrollment of diverse populations. Analysis into practice-specific patterns within our cancer centers can help identify areas for interventions to support the recruitment and enrollment of diverse populations in oncology CTs.