bluuebunny/crossref_metadata_2025 huggingface dataset:
Crowding out and impoverishing effect of tobacco in Mexico
Authors: Macías Sánchez Alejandra , García Gómez Adrián
Published: August 2023

Introduction

Tobacco is one of the world’s largest preventable causes of premature death, accounting for more than 8 million deaths and costing the global economy US$1.4 trillion each year. Smoking is a global problem with 1.3 billion people using tobacco worldwide, who will face harmful effects on health and on people’s current and future financial situations and quality of life.

This article aims to be the first study to generate evidence on the effects of smoking on household expenditure and the number of people living under the poverty threshold by studying the crowding out and impoverishing effect in Mexico.

Methods

Through econometric methods and maximising a household utility function we estimate the crowding out and impoverishing effect of tobacco consumption in México based on household's income and spending survey from 2020.

Results

Spending on tobacco crowds out household spending on other goods and services. In Mexico, spending on tobacco results in decreased spending on essential goods and services, like education and healthcare, and increased spending on harmful goods such as alcoholic beverages. These effects are common across all income levels but are more pronounced in low-income households. When spending on tobacco increases, for example, following regular price increases made by the tobacco industry, the crowding out effect is exacerbated.

In addition, smoking has an impoverishing effect on the population. This is because some families find that their remaining income level falls below the poverty line after deducting money spent on tobacco (a concept known as secondary poverty). In Mexico, 909 132 people are left with a disposable income level below the extreme poverty line because of expenditure on tobacco and smoking-related diseases.

Conclusions

Smoking affects individual health and the finances of households in Mexico, particularly those of low-income people. By increasing tobacco taxes, those who quit smoking increase their quality of life and well-being. However, those who continue to smoke and increase their tobacco spending are affected by a shift in their spending on other goods and services.

The increase in tobacco taxes must be accompanied by public policies that help reduce tobacco consumption and compensate the crowding out on goods and services relevant to the development of households.
Field study on installation effects of pre-bored grouted planted pile in deep clayey soil
Authors: Zhou Jia-jin , Yu Jian-lin , Gong Xiao-nan , Zhang Ri-hong
Published: August 2023

This paper presents the results of field tests performed to investigate the installation effects of pre-bored grouted planted (PGP) pile in deep clayey soil. The variation of horizontal soil displacements, excess pore water pressures and lateral soil pressures was measured in the PGP pile installation process. The test results show that the drilling and grouting process induced large horizontal soil displacements in the soil within a radial distance of 2 d ( d is pile diameter), and the maximum horizontal soil displacements induced by the drilling and grouting process were smaller than 15.9 mm when the radial distance reached 4–5 d. Moreover, the horizontal soil displacements decreased along the soil layer depth, as the superficial soil layers were of small deformation modulus and lateral soil pressure. The drilling process brought large excess pore water pressures in the soil when the radial distance was less than 3 d, and the excess pore water pressures induced by the drilling stage were all less than 55 kPa when the radial distance reached 4–6 d. The drilling process also induced some lateral soil pressure increases in the soil within a radial distance of 3 d, while the measured maximum lateral soil pressure increases were smaller than 10.9 kPa when the radial distance increased to 4 d. On the whole, the excess pore water pressures and lateral soil pressure increases induced by the installation of PGP pile were much smaller than that induced by the installation of driven PHC pile. Moreover, the horizontal soil displacements, excess pore water pressures and lateral soil pressure increases induced by the installation of PGP pile all recovered rapidly after the installation of pile, as the cemented soil in the pile hole was in liquid state after the drilling and grouting stage.
Limited effects of biochar application and periodic irrigation on jack pine (Pinus banksiana) seedling growth in northern Minnesota, USA
Authors: Slesak Robert A. , Windmuller-Campione Marcella
Published: August 2023

We tested the effect of biochar application on growth of planted jack pine on a sandy soil in northern Minnesota. Biochar was applied in combination with compost and with or without manual irrigation in a factorial design to isolate possible effects associated with nutrient or water availability. There were no differences among treatments in seedling annual diameter or height growth after 4 years. Watering increased mean needle mass, indicating the treatment was somewhat effective at increasing water availability and seedling performance. Watering increased foliage Mg and K concentrations and content, possibly indicating that these elements are limiting to jack pine growth on sandy soils. Biochar-only application decreased foliage Ca concentration relative to controls, likely due to increased nutrient immobilization when biochar is applied without a nutrient source. These findings and others from the region highlight that biochar does not increase planted jack pine seedling survival or growth on sandy soils.
Cognitive Hybrid Deep Learning-based Multi-modal Sentiment Analysis for Online Product Reviews
Authors: Perti Ashwin , Sinha Amit , Vidyarthi Ankit
Published: August 2023

Recently the field of sentiment analysis has gained a lot of attraction in literature. The idea that a machine can dynamically spot the text’s sentiments is fascinating. In this paper, we propose a method to classify the textual sentiments in Twitter feeds. In particular, we focus on analyzing the tweets of products as either positive or negative. The proposed technique utilizes a deep learning schema to learn and predict the sentiment by extracting features directly from the text. Specifically, we use Convolutional Neural Networks with different convolutional layers. Further, we experiment with LSTMs and try an ensemble of multiple models to get the best results. We employ an n-gram-based word embeddings approach to get the machine-level word representations. Testing of the method is conducted on real-world datasets. We have discovered that the ensemble technique yields the best results after conducting experiments on a huge corpus of more than one million tweets. To be specific, we get an accuracy of 84.95%. The proposed method is also compared with several existing methods. An extensive numerical investigation has revealed the superiority of the proposed work in actual deployment scenarios.
Static Scheduling of Weight Programming for DNN Acceleration with Resource Constrained PIM
Authors: Gao Xin , Wang Hongyue , Chen Yiyan , Zhang Yuhao , Shen Zhaoyan , Ju Lei
Published: August 2023

Most existing architectural studies on ReRAM-based processing-in-memory (PIM) DNN accelerators assume that all weights of the DNN can be mapped to the crossbar at once. However, these studies are over-idealized. ReRAM crossbar resources for calculation are limited because of technological limitations, so multiple weight mapping procedures are required during the inference process. In this article, we propose a static scheduling framework which generates the mapping between DNN weights and ReRAM cells with minimum runtime weight programming cost. We first build a ReRAM crossbar programming latency model by simultaneously considering the DNN weight patterns, ReRAM programming operations, and PIM architecture characteristics. Then, the model is used in the searching process to obtain an optimized weight-to-OU mapping table with minimum online programming latency. Finally, an OU scheduler is used to coordinate the activation sequences of OUs in the crossbars to perform the inference computation correctly. Evaluation results show the proposed framework significantly reduces the weight programming overhead and the overall inference latency for various DNN models with different input datasets.
How Can People Become Happier? A Systematic Review of Preregistered Experiments
Authors: Folk Dunigan , Dunn Elizabeth
Published: August 2023

Can happiness be reliably increased? Thousands of studies speak to this question. However, many of them were conducted during a period in which researchers commonly “ p-hacked,” creating uncertainty about how many discoveries might be false positives. To prevent p-hacking, happiness researchers increasingly preregister their studies, committing to analysis plans before analyzing data. We conducted a systematic literature search to identify preregistered experiments testing strategies for increasing happiness. We found surprisingly little support for many widely recommended strategies (e.g., performing random acts of kindness). However, our review suggests that other strategies—such as being more sociable—may reliably promote happiness. We also found strong evidence that governments and organizations can improve happiness by providing underprivileged individuals with financial support. We conclude that happiness research stands on the brink of an exciting new era, in which modern best practices will be applied to develop theoretically grounded strategies that can produce lasting gains in life satisfaction.
Ductile Iron: A Low-Cost Optimal Anode Material for Electrochemical Generation of Ferrate(VI)
Authors: Mai Thi Thanh Thuy , Nguyen Thi Van Anh , Phan Thi Binh , Le Truong Giang
Published: August 2023

The effects of anode composition and temperature on anode electrochemical properties, the passivation layer’s structure, and ferrate(VI) generation in 14 M NaOH were investigated. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and galvanostatic polarization (GP) were used to analyze the electrochemical processes involving the electrosynthesis of ferrate using some low-cost anode materials: ductile iron, grey cast iron, and mild steel. The results proved that the presence of silicon and graphite with sphere form in the ductile iron anode significantly increased ferrate electro-generation. The optimal temperature for the electro-generation of ferrate was 30 °C–40 °C. The current efficiency using the ductile iron anode was constantly at least about 30% superior to that of the grey cast iron and mild steel electrodes. The ductile iron anode material was the most feasible option because it provides the highest ferrate concentration (1.58 g L−1) with the highest current efficiency of 74% and the lowest specific energy consumption of 1.2 kWh kg−1 ferrate.
An Antibody-Free, Silver-Silver Oxide-Carbon Nanotube Nanocomposite-Based Impedimetric Sensor for the Nanomolar Detection of 25-Hydroxyvitamin D3
Authors: Sana Fathima T. K. , Ramaprabhu Sundara
Published: August 2023

Vitamin D deficiency in the body is a worldwide health concern with major consequences on bone health. It is also related to cardiovascular diseases, depression, infectious diseases, autoimmune disorders, cancer, and recently even to COVID-19. In the present work, we have developed a silver-silver oxide nanoparticles-decorated carbon nanotube-modified glassy carbon electrode (AgCNT/GCE) based sensor for antibody-free, nanomolar detection of 25-hydroxyvitamin D (25OHD). The impedimetric technique was utilized to achieve high sensitivity. The sensor exhibited a linear response in the range of 20–100 nM. A remarkably low limit of detection of 7.9 nM was observed, which is lower than the deficiency level defined at 30 nM for human serum. The sensor exhibited excellent response stability, repeatability, reproducibility, and minimal interference. Excellent recovery of ∼102% was also observed in real serum samples. The sensing mechanism and the AgCNT-25OHD interaction have also been explored by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), Fourier Transform Infrared (FTIR) spectroscopy, and UV–vis spectroscopy.
Microstructure and Properties of Porous Copper Foils with High Specific Surface Area Prepared by Electrodeposition
Authors: Jia Ya-peng , Sun Wan-chang , Bai Zhong-bo , Liu Er-yong , Du Liang-liang , Cai Hui , Zhang Jing-li , Peng Xiao-lin , Wang Li-ping
Published: August 2023

The high surface area porous copper foils are synthesized on commercial copper foils by dynamic hydrogen bubble template electrodeposition method. The electrochemical deposition mechanism of porous copper foils and the current density on the structure formation mechanism are explored. The results show that under the conditions of stable electrolyte, electrodeposition time of 20 s, and current density of 2 A·cm−2, the microporous distribution of the deposited layer is uniform and the adhesion between the pore walls is strong. Compared with the planar copper foil, the porous copper foil possesses the “large on top and small on bottom” porous structure, which significantly improves the specific surface area of the copper foil, and the resistance value decreases by 43.1%. The electrochemical test results show that the performance of the porous collector is significantly better than that of the planar collector. Furthermore, the porous copper collector has a lower charge transfer impedance (150 Ω). The results of this paper provide an innovative strategy for the preparation of porous collectors and for solving the problem of lithium metal batteries.
Selective elevation in external carotid artery flow during acute gravitational transition to microgravity during parabolic flight
Authors: Lanéelle Damien , Ogoh Shigehiko , Trihan Jean-Eudes , Bailey Damian M. , Normand Hervé
Published: August 2023

Our findings demonstrate that in microgravity there is a selective increase in external carotid artery blood flow whereas global and regional cerebral blood flow remained preserved. To what extent this reflects an adaptive, neuroprotective response to counter overperfusion remains to be established.
Adult human cardiomyocyte mechanics in osteogenesis imperfecta
Authors: Lee Benjamin W. , Caporizzo Matthew A. , Chen Christina Y. , Bedi Kenneth C. , Peyster Eliot G. , Prosser Benjamin L. , Margulies Kenneth B. , Vite Alexia
Published: August 2023

In a rare donation of a heart from an individual with osteogenesis imperfecta (OI), we explored cardiomyocyte (CM) adaptations to low stiffness. This represents the first assessment of cardiomyocyte mechanics in OI. The data reveal the hypercontractility of OI CMs with rapid rundown when exposed to acute stiffness challenges, extending our understanding of OI. These data demonstrate that the impact of OI on myocardial mechanics includes cardiomyocyte adaptations beyond known direct effects on the extracellular matrix.
Evidence of impaired functional sympatholysis in patients with heart failure with preserved ejection fraction
Authors: Alpenglow Jeremy K. , Bunsawat Kanokwan , Francisco Michael A. , Craig Jesse C. , Iacovelli Jarred J. , Ryan John J. , Wray D. Walter
Published: August 2023

Data from the current study suggest that functional sympatholysis, or the ability to adequately attenuate sympathetic nervous system (SNS)-mediated vasoconstriction during exercise, is impaired in patients with heart failure with preserved ejection fraction (HFpEF). These observations extend the current understanding of HFpEF pathophysiology by implicating inadequate functional sympatholysis as an important contributor to reduced exercising muscle blood flow in this patient group.
Peripheral Arterial Disease and the Pharmacist’s Role in Management
Authors: Stacy Zachary
Published: August 2023

Purpose. Atherosclerosis of arteries in the legs leads to peripheral arterial disease (PAD), increasing the risk of future cardiovascular events. Worldwide prevalence estimates indicate >200 million people have PAD, but this is likely underestimated given the variability in symptoms and lack of awareness by patients and clinicians. Antiplatelet therapy is recommended to reduce cardiovascular risk, but anticoagulation therapy may also be beneficial. This narrative review examined scientific literature for the burden and medical management of PAD, including use of anticoagulants in this population, and provides perspectives on the role of pharmacists to improve outcomes of PAD. Summary. A variety of antiplatelet therapies has been studied in patients with PAD, and treatment is recommended for those with symptomatic disease. The use of dual antiplatelet therapy is limited to patients with symptomatic PAD after revascularization. Anticoagulation with warfarin in combination with antiplatelet therapy did not improve efficacy over antiplatelet therapy alone and increased bleeding. In contrast, the direct factor Xa inhibitor rivaroxaban, when used in combination with low-dose aspirin, has been shown to significantly reduce the risk of cardiovascular death, myocardial infarction (MI), or stroke by 28% in patients with PAD compared with aspirin alone. Similarly, in patients with PAD who have undergone revascularization, rivaroxaban plus aspirin reduced the risk of acute limb ischemia, major amputation, MI, stroke, or cardiovascular death by 15% versus aspirin alone. Major bleeding was significantly increased with rivaroxaban plus aspirin, but with no differences in fatal bleeding, nonfatal intracranial hemorrhage, or symptomatic bleeding into a critical organ between groups. Pharmacist-led interventions for patients with PAD include identifying at-risk patients through medication reviews and clinical assessments, education and monitoring use of prescription and over-the-counter medications, and appropriate counseling on lifestyle modifications. Conclusion. Rivaroxaban plus aspirin reduces the risk of major cardiovascular events, including major adverse limb events and amputation, in patients with PAD. Pharmacists can play an integral role in identifying, screening, and managing patients with PAD to achieve favorable outcomes.
Bioenergy Production Potential of Available Biomass Residue Resources in Ethiopia
Authors: Tolessa Amsalu
Published: August 2023

The study intends to present the bioenergy potential in Ethiopia using major sources of biomass generation. The study utilized data from secondary sources to generate the potential using the available biomass sources within the country. In order to determine the bioenergy potential, four residue biomass sources, including livestock manure, crop residues, forest residues, and municipal solid waste (MSW) from major cities, were considered. The Food and Agriculture Organization Corporate Statistical (FAOSTAT) Database as well as national and local reports were used to compile information on crops, forests, animals, and human populations. The potential of each source is estimated for 2020-21 as the base year. The total bioenergy potential of the country is estimated to be 2955 petajoule (PJ) per year, with 56.01% of it coming from forest residue, 28.29% from crop residue, 15.36% from livestock waste, and 0.33% from MSW. In addition, it is estimated that 819.7 terawatt hours (TWh) of electricity may be generated from all sources yearly. This is equivalent to around 8, 58, and 89 times Ethiopia’s total primary energy consumption, electricity production, and electricity net consumption in 2020, respectively. Results also demonstrated that the total potential (819.7 TWh·y−1) is roughly 56% greater than the forest residues’ potential alone (459 TWh·y−1). This implies that biomass resources might be crucial in assisting Ethiopia to fulfill its future energy needs. To fully realize the availability of biomass energy, the study suggests performing integrated development research, choosing the best feedstock and value chains for bioenergy, and creating a bioenergy database.
Nighttime Home Care in Sweden: “A Constant Struggle to Manage Unforeseen Events”—Operations Managers’ Perceptions of Organization and Provision of Care for Older People
Authors: Andersson Katarina , Sjölund Maria
Published: August 2023

This article aims at exploring how community home care of older people is provided and organized at night. In times of welfare decline, organizational changes, and an increasing aged population, questions arise about home care and support for older people. In Sweden, as in many other Western countries, “ageing in place” is a guiding principle in care provision for older people, which put increasing pressure on home care services. Still, nighttime care represents a research gap within health and social care research, nationally and internationally. This telephone interview survey examines 41 operations managers’ perceptions of organization and care provision and how they account for the goals and work of home care at nighttime in a selection of 37 Swedish municipalities. The analysis was inspired by thematic content analysis where three central themes were categorized: organizational context of nighttime care, working conditions, and challenges of nighttime care. Our results reveal that organizational context varied depending on the demography and size of the municipality. The work situation was characterized by constantly unforeseen events to manage. Multiple challenges were identified on societal and political levels, as were limited resources and recruitment problems. In conclusion, our analysis has identified unpredictability as a core feature of nighttime care work. The complexity of the provision of nighttime care was not recognized as important for the municipal organization. To provide high-quality care at night in ordinary housing, there is a need both to focus on organizational aspects and to have sufficient resources and time.
Cognitive Contributors of Backward Walking in Persons with Multiple Sclerosis
Authors: Takla Taylor N. , Chargo Alexis N. , Daugherty Ana M. , Fritz Nora E.
Published: August 2023

Purpose. Individuals with multiple sclerosis (MS) are at an increased fall risk due to motor and cognitive dysfunction. Our past studies suggest that backward walking (BW) velocity predicts fall risk; however, specific cognitive domains associated with BW velocity remain understudied. The goal of this study was to determine the specific contributions of cognitive functioning to BW velocity in persons with MS. We hypothesized that better visuospatial memory, verbal immediate recall, and faster information processing speed would contribute to faster BW velocity, and deficits in these domains would partially account for disease severity-related impairment in BW velocity. Methods. Participants completed demographic questionnaires, walking tests, and cognitive assessments. Applied structural equation modeling was used to test our hypothesized model of competing cognitive mediators. Within the model, disease severity was a predictor of BW via three intercorrelated cognitive mediators. Results. Participants included 39 individuals with relapsing-remitting MS. Results indicated that 35.3% of the significant total effect of disease severity on BW was accounted for by specific cognitive deficits. Verbal immediate recall had the largest contribution, followed by visuospatial memory and information processing speed. Conclusions. When examining the unique effects of cognitive domains on disease severity-related deficits in BW, a meaningful source of impairment related to visuospatial memory and verbal immediate recall was demonstrated. Considering the utility of BW velocity as a predictor of falls, these results highlight the importance of assessing cognition when evaluating fall risk in MS. Cognitive-based intervention studies investigating fall prevention may find BW as a more specific and sensitive predictor of fall risk than forward walking.
Influence Factor of Naval Vessel’s Equipment under Optimized Sailing Strategy
Authors: Xiong Zihao , Lv Jianwei , Xie Zongren , Xu Yifan
Published: August 2023

A naval vessel is a large and complex weapon system that can be divided into three hierarchical structures: ship‐subsystem‐equipment. Optimization of the sailing strategy has improved the use of the equipment and thus the success ratio of sailing missions. Still, the contribution of reliability and maintainability of different hierarchical structures to the sailing mission success ratio has not been quantitatively analyzed. To solve this problem, the fundamental principle for optimizing each subsystem is proposed based on mathematical analysis to determine the improvement sequence at the subsystem level; at the equipment level, the reliability maintainability parameters are adjusted to observe the change in the mission success probability, influence factors are calculated as the basis for the improvement of the underlying equipment. In practical engineering applications, technical and economic costs also need to be considered, and difficulty degree is defined. The difficulty degree and influence factor are integrated, and the specific reliability engineering, specific maintainability engineering, and reliability & maintainability integrated engineering are implemented respectively. The improvement sequence of each equipment is determined under the optimized sailing strategy to provide a reference and basis for the implementation of naval equipment improvement projects.
Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative
Authors: Song Mihae , Nelson Rebecca A. , Kruper Laura , Mortimer Joanne , Luo Juhua , Jung Su Yon , Wallace Robert B. , Chlebowski Rowan
Published: August 2023

Background:

The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants.

Methods:

A total of 71,312 postmenopausal women were followed for 22.1 years (median). At enrollment, 55,643 (78%) had intact ovaries and 15,669 (22%) had undergone a bilateral oophorectomy. Colorectal cancers were verified by central medical record review with mortality findings enhanced by National Death Index queries.

Results:

With 1,421 incident colorectal cancers, 450 colorectal cancer-specific mortalities, after controlling for covariates, bilateral oophorectomy was not associated with colorectal cancer incidence or colorectal cancer mortality.

Conclusions:

No significant associations between oophorectomy and colorectal cancer incidence and mortality were seen in a large cohort study with long follow-up.

Impact:

As the oophorectomy and colorectal cancer question remains open, further studies of high quality, even with null findings, should be encouraged.
Supplementary Data from Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial
Authors: Mellinghoff Ingo K. , Penas-Prado Marta , Peters Katherine B. , Burris Howard A. , Maher Elizabeth A. , Janku Filip , Cote Gregory M. , de la Fuente Macarena I. , Clarke Jennifer L. , Ellingson Benjamin M. , Chun Saewon , Young Robert J. , Liu Hua , Choe Sung , Lu Min , Le Kha , Hassan Islam , Steelman Lori , Pandya Shuchi S. , Cloughesy Timothy F. , Wen Patrick Y.
Published: August 2023

Appendix
Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19–9 Reference Ranges
Authors: Dbouk Mohamad , Abe Toshiya , Koi Chiho , Ando Yohei , Saba Helena , Abou Diwan Elizabeth , MacGregor-Das Anne , Blackford Amanda L. , Mocci Evelina , Beierl Katie , Dbouk Ali , He Jin , Burkhart Richard , Lennon Anne Marie , Sokoll Lori , Canto Marcia Irene , Eshleman James R. , Goggins Michael
Published: August 2023

Purpose:

CA19–9 synthesis is influenced by common variants in the fucosyltransferase (FUT) enzymes FUT3 and FUT2. We developed a clinical test to detect FUT variants, and evaluated its diagnostic performance for pancreatic ductal adenocarcinoma (PDAC).

Experimental Design:

A representative set of controls from the Cancer of the Pancreas Screening study was identified for each FUT functional group. Diagnostic sensitivity was determined first in a testing set of 234 PDAC cases, followed by a 134-case validation set, all of whom had undergone resection with curative intent without neoadjuvant therapy. Tumor marker gene testing was performed in the Johns Hopkins Molecular Diagnostics Laboratory. CA19–9 levels were measured in the Hopkins Clinical Chemistry lab. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative ability of CA19–9 alone versus with the gene test.

Results:

Applying the CA19–9 standard cutoff (<36 U/mL) to all 716 subjects yielded a 68.8% sensitivity in the test set of cases, 67.2% in the validation set, at 91.4% specificity. Applying 99th percentile cutoffs according to each individual's FUT group (3, 34.9, 41.8, and 89.2, for the FUT3-null, FUT-low, FUT-intermediate, and FUT-high groups, respectively) yielded a diagnostic sensitivity for CA19–9 in the first set of cases of 66.7%, 65.7% in the validation set, at 98.9% specificity. ROC analysis for CA19–9 alone yielded an AUC of 0.84; with the tumor marker gene test, AUC improved to 0.92 (P < 0.001).

Conclusions:

Using a tumor marker gene test to personalize an individual's CA19–9 reference range significantly improves diagnostic accuracy.
Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial.
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: August 2023

Purpose:

Non-inflamed (cold) tumors such as leiomyosarcoma do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis or PARP inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pretreated patients with leiomyosarcoma.

Patients and Methods:

Patients were randomized to receive durvalumab 1,500 mg IV every 4 weeks with either olaparib 300 mg twice a day orally (Arm A) or cediranib 20 mg every day orally 5 days/week (Arm B) until unacceptable toxicity or disease progression. Paired tumor biopsies, serial radiologic assessments and stool collections were performed. Primary endpoints were safety and immune cell changes in the TME. Objective responses and survival were correlated with transcriptomic, radiomic, and microbiome parameters.

Results:

Among 30 heavily pretreated patients (15 on each arm), grade ≥ 3 toxicity occurred in 3 (20%) and 2 (13%) on Arms A and B, respectively. On Arm A, 1 patient achieved partial response (PR) with increase in CD8 T cells and macrophages in the TME during treatment, while 4 had stable disease (SD) ≥ 6 months. No patients on Arm B achieved PR or SD ≥ 6 months. Transcriptome analysis showed that baseline M1-macrophage and B-cell activity were associated with overall survival.

Conclusions:

Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some patients with leiomyosarcoma. Baseline M1-macrophage and B-cell activity may identify patients with leiomyosarcoma with favorable outcomes on immunotherapy and should be further evaluated.
Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance
Authors: Hanna Glenn J. , Roof Scott A. , Jabalee Jamie , Rettig Eleni M. , Ferrandino Rocco , Chen Sida , Posner Marshall R. , Misiukiewicz Krzysztof J. , Genden Eric M. , Chai Raymond L. , Sims John , Thrash Elaine , Stern Scott J. , Kalman Noah S. , Yarlagadda Sreenija , Raben Adam , Clements Lydia , Mendelsohn Abie , Kaczmar John M. , Pandey Yadav , Bhayani Mihir , Gupta Piyush , Kuperwasser Charlotte , Del Vecchio Fitz Catherine , Berger Barry M.
Published: August 2023

Purpose:

Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance.

Experimental Design:

This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5–154).

Results:

The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5–97.5] and 87.3% (95% CI: 79.1–95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9–99.8) and 98.4% (95% CI: 97.3–99.5), respectively.

Conclusions:

TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.
Supplementary table 2 from FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: August 2023

Supplementary table 2
Supplementary Figure 1, 2 and Table 1,2 from FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: August 2023

Supplementary Figure 1, 2 and Table 1,2
Supplementary Figure 1 from FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: August 2023

Supplementary Figure 1
FOXN Transcription Factors: Regulation and Significant Role in Cancer
Authors: Song Jiali , Li Longshan , Fang Yang , Lin Yue , Wu Luojia , Wan Wei , Wei Gen , Hua Fuzhou , Ying Jun
Published: August 2023

A growing number of studies have demonstrated that cancer development is closely linked to abnormal gene expression, including alterations in the transcriptional activity of transcription factors. The Forkhead box class N (FOXN) proteins FOXN1–6 form a highly conserved class of transcription factors, which have been shown in recent years to be involved in the regulation of malignant progression in a variety of cancers. FOXNs mediate cell proliferation, cell-cycle progression, cell differentiation, metabolic homeostasis, embryonic development, DNA damage repair, tumor angiogenesis, and other critical biological processes. Therefore, transcriptional dysregulation of FOXNs can directly affect cellular physiology and promote cancer development. Numerous studies have demonstrated that the transcriptional activity of FOXNs is regulated by protein–protein interactions, microRNAs (miRNA), and posttranslational modifications (PTM). However, the mechanisms underlying the molecular regulation of FOXNs in cancer development are unclear. Here, we reviewed the molecular regulatory mechanisms of FOXNs expression and activity, their role in the malignant progression of tumors, and their value for clinical applications in cancer therapy. This review may help design experimental studies involving FOXN transcription factors, and enhance their therapeutic potential as antitumor targets.
Supplementary Video 2B from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Video 2B shows representative images of a Sulfasalazine-treated spheroid. Scale bar: 200 µm, number at top left: days post-implantation.
Supplementary Video 2A from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Video 2A shows representative images of a vehicle-treated spheroid. Scale bar: 200 µm, number at top left: days post-implantation.
Supplementary Table 5 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Table 5 shows Differentially expressed genes for epithelial vs. amoeboid analysis
Supplementary Table 3 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Table 3 shows Differentially expressed genes for escaping vs. epithelial analysis
Supplementary Table 2 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Table 2 shows Transcript counts for common housekeeping genes, with cells excluded from the study due to low housekeeping expression highlighted in yellow
Supplementary Figure 6 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Figure 6 shows an Amoeboid cell cohort gallery
Supplementary Figure 4 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Supplementary Figure 4 shows an Epithelial cohort gallery
FIGURE 5 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Inhibition of OPRD1 reduces melanoma spheroid growth and invasion. A, Representative maximum intensity projections of imaged hemispheroids for vehicle- and naltrindole-treated spheroids, scale bar 200 μm. B, Relative spheroid volume over time for vehicle- and naltrindole-treated cells. Shaded areas represent SEM. C, Cumulative number of escaped cells over time normalized to spheroid surface area. B and C, Datapoints represent the mean of eight replicates.
FIGURE 4 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Gene expression analysis for epithelial, escaping, and amoeboid cells. A, Top: 462 genes were DE, 144 for escaping versus epithelial (Esc-v-Epi), 22 for amoeboid versus escaping (Amo-v-Esc), and 422 for amoeboid versus epithelial (Amo-v-Epi). Bottom: Venn diagram of the number of DE genes for the three pairwise comparisons. B, Volcano plot for Esc-v-Epi DE analysis, with genes enriched in “escaping” cells shown as positive on the x-axis. C, Volcano plot for Amo-v-Esc DE analysis, with genes enriched in “amoeboid” cells shown as positive on the x-axis. D, Volcano plot for Amo-v-Epi DE analysis, with genes enriched in “amoeboid” cells shown as positive on the x-axis. For B–D, significantly DE genes with an adjusted P value < 0.05 are shown in light blue, with no minimum value for log2FC. E, Expression of EMT markers for epithelial, leaving, and amoeboid cells shown via dot plot. F, Expression of cancer stem cell markers for epithelial, leaving, and amoeboid cells shown via dot plot.
FIGURE 3 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Clustering of single cells and their gene expression heat map based on 462 DE genes. A, UMAP clustering of 35 cells based on expression of 462 DE genes. B, Unsupervised hierarchical clustering of 35 cells based on the expression of 462 DE genes. Cells initially diverge into two groups, epithelial (L1) and invasive (R1), before further diverging into escaping (R2) and amoeboid (R3). C, Heat map of 462 DE genes for single cells arranged according to the unsupervised clustering in B.
FIGURE 2 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Single-cell tagging and isolation based on morphologic and positional data. A, Sphericity and distance to spheroid values are generated for each invading cell surrounding the spheroid. Left panel depicts maximum intensity projections for three invading cells (Fluo) of different sphericities, following cell surface segmentation (Fluo + Surf), and following surface pseudocoloring according to sphericity value (Surf + Pseudo). Right panels illustrate the smoothed spheroid surface (red) computed to calculate the nearest distance (dashed arrow) to the spheroid edge from individual cells. B, Left: The three photoconverted cell types “Epithelial,” “Escaping,” and “Amoeboid.” Middle: Representative images of the photoconversion of the three cell types and corresponding flow cytometry scatter plots of Dendra2 red versus green fluorescence obtained during single-cell sorting. Right: The number of cells photoconverted and recovered via single-cell sorting for escaping and amoeboid cells. C, Sorting yields expressed as a percentage of photoconverted cells for escaping and amoeboid cells.
FIGURE 1 from Targeted Single-cell Isolation of Spontaneously Escaping Live Melanoma Cells for Comparative Transcriptomics
Authors: Tearle Jacqueline L.E. , Arjunan Satya N.V. , Tay Szun S. , Colakoglu Feyza , Cremasco James , Golo Matteo , Biro Maté
Published: August 2023

Methodologic pipeline for single-cell isolation of live escaping tumor cells. 1, A clonal population of tumor cells are expanded from a single cell. 2, Photoconvertible cells are seeded in ULA plates to generate spheroids. 3, Spheroids are embedded within a 3D collagen matrix and imaged over time by light microscopy. 4, Image analysis and extraction of quantitative metrics can be used to select cells of interest. 5, Single cells of interest are photoconverted using a 405 nm laser. 6, Collagen matrix is enzymatically digested to provide a solution of suspended single cells. 7, Cells are sorted via FACS. 8, Cells can be further cultured or immediately analyzed.
A Meta-Analysis of Neurodevelopmental Outcomes following Intravitreal Bevacizumab for the Treatment of Retinopathy of Prematurity
Authors: Baiad Abed A. , Kherani Imaan Z. , Popovic Marko M. , Katsnelson Glen , Muni Rajeev H. , Mireskandari Kamiar , Tehrani Nasrin N. , Zhou Tianwei Ellen , Kertes Peter J.
Published: August 2023

Background: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC). Objectives: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP. Methods: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment. Results: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = −1.25, 4.27], 2.43 [CI = −1.36, 6.22], and 1.97 [CI = −1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05). Conclusion: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.