bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalies Detection in Chest X-Rays Images Using Faster R-CNN and YOLO
Authors: Nguyen Hai Thanh , Nguyen My N. , Phung Linh Duong , Pham Linh Thuy Thi
Published: June 2023

Lungs are crucial parts of the human body and can be captured as Chest x-ray images for disease diagnosis. Unfortunately, in many countries, hospitals and healthcare centers lack qualified doctors for medical images-based diagnosis. Recent numerous advancements in artificial intelligence have deployed with many medical applications to support doctors for disease diagnosis. In our research, we have leveraged YOLOv5s to identify and extract lungs and performed segmentation tasks with Fast R-CNN and YOLOv5 for comparison. The lung region abnormality detection models have pretty good average precision. For example, the YOLOv5 model outperforms both in terms of training time, prediction, and accuracy, with the AP@.5 and AP@.5:.95 metric values, 0.616 and 0.322 on 2,500 images of 5 abnormalities (aortic enlargement, cardiomegaly, lung opacity, pleural effusion, and pulmonary fibrosis).
Becoming a Crystallographer
Authors: Egli Martin
Published: June 2023

“What do you want to be when you grow up?” is a common question posed to children, and answers such as firefighter, policeman, athlete, doctor, or teacher are probably just as common. Some, like Oliver Sacks, recall an early fascination with metals, the periodic table, and chemical reactions that planted the seeds for the later pursuit of the natural sciences or medicine (neurology in his case). We are familiar with memories of chemists that include their first chemistry set, followed by complaints by parents over strange smells and close calls due to particularly exothermic reactions. For others, including myself, a future in research remained more obscure until a later period in adolescence or perhaps even the undergraduate years. Rather than seeking out a field, the field finds you. In actuality, teachers and mentors with expertise in and enthusiasm for a field exert a force that charts a path toward scientific research throughout life. Here, I stress the importance of terrific teachers and mentors from high school onwards to the undergraduate, Ph.D., and postdoc years for setting me on a track (and on occasion preventing me from derailing) to research in structural chemistry and molecular mechanism using crystallography as the main tool.
Microglial Transcriptional Signatures in the Central Nervous System: Toward A Future of Unraveling Their Function in Health and Disease
Authors: Vecchiarelli Haley A. , Tremblay Marie-Ève
Published: June 2023

Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, throughout health, injury, and disease. Recent transcriptomic studies have identified gene transcript signatures expressed by microglia that may provide the foundation for unprecedented insights into their functions. Microglial gene expression signatures can help distinguish them from macrophage cell types to a reasonable degree of certainty, depending on the context. Microglial expression patterns further suggest a heterogeneous population comprised of many states that vary according to the spatiotemporal context. Microglial diversity is most pronounced during development, when extensive CNS remodeling takes place, and following disease or injury. A next step of importance for the field will be to identify the functional roles performed by these various microglial states, with the perspective of targeting them therapeutically.
Social Protection and Rural Transformation in Africa
Authors: Correa Juan Sebastian , Daidone Silvio , Davis Benjamin , Sitko Nicholas J.
Published: June 2023

This article develops a conceptual framework on pathways through which noncontributory social protection can support resilient and inclusive agricultural growth in rural Africa. It draws insights from a review of rigorous empirical evidence on the impacts of cash transfers and multifaceted cash plus programs on a range of relevant productive outcomes, including accumulation of productive assets, inputs and farm management practices, off-farm labor and nonfarm enterprises, and farm production and income. This review demonstrates an emerging consensus in the literature: that access to social protection programs contributes positively to increasing the productive asset holdings of rural people, increasing the use of improved inputs and farm practices, and shifting away from casual wage labor arrangements. Moreover, there is limited evidence on heterogeneous effects across different baseline characteristics (income, sex, and labor-constrained households, among others). Finally, the article highlights how social protection programs should be considered an integral part of broader rural and agricultural development strategies in order to achieve a more productive, resilient, and equitable rural transformation in Africa.
Immunomodulation by Enteric Viruses
Authors: Bernard-Raichon Lucie , Cadwell Ken
Published: June 2023

Enteric viruses display intricate adaptations to the host mucosal immune system to successfully reproduce in the gastrointestinal tract and cause maladies ranging from gastroenteritis to life-threatening disease upon extraintestinal dissemination. However, many viral infections are asymptomatic, and their presence in the gut is associated with an altered immune landscape that can be beneficial or adverse in certain contexts. Genetic variation in the host and environmental factors including the bacterial microbiota influence how the immune system responds to infections in a remarkably viral strain–specific manner. This immune response, in turn, determines whether a given virus establishes acute versus chronic infection, which may have long-lasting consequences such as susceptibility to inflammatory disease. In this review, we summarize our current understanding of the mechanisms involved in the interaction between enteric viruses and the immune system that underlie the impact of these ubiquitous infectious agents on our health.
Highly Potent Antioxidant/Antibacterial Biogenic ZnO Nanoparticles-Enabled Nano-Scavenger Reinforced by Aegle Marmelos (Linn) Rind’s Extract
Authors: Kumar Ankit , Rustagi Sarvesh , Malik Sumira , Choudhary Priyvart , Khan Zakir Showkat , Allam Ayman Younes , Naik Bindu , Kumar Vijay , Chaudhary Vishal
Published: June 2023

Nano-enabled antioxidant and antibacterial biogenic scavenger is the crucial vector for sustainable and next-generation healthcare/pharmaceuticals. The state-of-the-art biogenic nano-scavenger is concerned with developing metal oxide nanostructures, primarily zinc oxide (ZnO) utilizing bio-extracts owing to their unique physicochemical attributes. This unprecedented study explores the antibacterial/antioxidant scavenging efficacies of green synthesized ZnO nanoparticles (NPs) employing Aegle Marmelos (Linn.) rind extract as multifunctional reagent. The morphological and structural outcomes reveal the formation of irregular biogenic ZnO NPs with all essential characteristic traits with modifications due to Aegle Marmelos (Linn.) rind extract. The as-synthesized biogenic nano-scavenger demonstrated excellent antioxidant potency (DPPH inhibitory activity of 85.13%–91.6%). Besides, it exhibited broadband antibacterial activity against six prominent strains of bacteria including K. Pneumoniae, B. subtilis, S. thalpophilum, P. aeruginosa, S. aureus, and E. coli, which is significant in comparison to medical antibiotics. These exceptional outcomes enable the development of biogenic-antibiotics and antioxidants, which are economic, eco-friendly and high-performing and opens window for next-generation pharmaceutical, bioremediation and healthcare strategies.
An undergraduate laboratory to study exercise thresholds
Authors: Trang Serena , Mattioni Maturana Felipe , Murias Juan M. , Herbert Michael R. , Keir Daniel A.
Published: June 2023

We present a laboratory to study exercise thresholds from gas exchange and ventilatory measures that features the “Exercise Thresholds App,” a free online resource that eliminates postprocessing of data and provides a bank of profiles on which end-users can practice threshold identification skills. In addition to including prelaboratory and postlaboratory recommendations, we present student accounts of understanding, engagement, and satisfaction and introduce a new quiz feature of the app to assist instructors with evaluating learning.
Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions
Authors: Roberts Michael D. , McCarthy John J. , Hornberger Troy A. , Phillips Stuart M. , Mackey Abigail L. , Nader Gustavo A. , Boppart Marni D. , Kavazis Andreas N. , Reidy Paul T. , Ogasawara Riki , Libardi Cleiton A. , Ugrinowitsch Carlos , Booth Frank W. , Esser Karyn A.
Published: June 2023

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of “work-induced hypertrophy” in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.
Abnormal Diagnosis Method of Self-Powered Power Supply System Based on Improved GWO-SVM
Authors: Li Ya jie , Li Shao bing , Li Wei
Published: June 2023

In order to solve the problem of low abnormal diagnosis rate of self-powered power supply system, an improved grey wolf optimization-support vector machine (GWO-SVM) algorithm combined with maximal information coefficient (MIC) are proposed. First, the feature sets of 11 kinds of monitoring data are optimized and selected based on MIC for self-powered power supply system. By eliminating redundant variables and insensitive variables, feature variable sets with great influence on abnormal diagnosis are selected. Second, by upgrading the selection method of control parameter

σ

from linear to nonlinear, an improved GWO-SVM algorithm that can take into account both global and local search capabilities is proposed. Furthermore, the optimal feature set which has great influence on abnormal diagnosis is selected as the input of the proposed algorithm, and then the abnormal diagnosis method combining the improved GWO-SVM with MIC is constructed for self-powered power supply system. The specific algorithm flow and step are given. Finally, compared with other algorithm, the simulation experiments show that the GWO-SVM method has a higher accuracy and a higher recall rate for the abnormal diagnosis in the self-powered power supply system.
Prevalence of Cachexia in Cancer Patients
Authors: Orellana López Cristian , Leyton Estéfane Jose , Ramos Rosales Miguel , Vásquez Ramirez Claudio , Manriquez Arriagada Claudia , Argilés Josep M. , López-Soriano Francisco J. , Ortega González Francisco , Yañez Nicolás , Busquets Silvia
Published: June 2023

Introduction. Cachexia is a syndrome characterized by the loss of musculoskeletal mass, with or without adipose mass, which cannot be reversed by nutritional support. In Chile, there are no data on cachexia in cancer patients that allows for decision making on better interdisciplinary management. In this study, the prevalence of cachexia in inpatient and outpatient cancer patients was investigated. Methods. An observational, descriptive, and cross-sectional study was carried out. Eighty-six inpatients and outpatients were evaluated. Cachexia was evaluated by applying the miniCASCO tool, its weight by bioimpedance, and inflammation by blood parameters. Comparisons and correlations were made considering

p
<
0.05

as the threshold for statistical significance. Results. Forty patients met the inclusion criteria, 35% were men and 65% were women. In all, 27.5% of patients had cachexia secondary to cancer. Of the total number of patients with the syndrome, approximately 45.4% had mild cachexia, 36.3% had severe cachexia, and 18.1% had moderate cachexia. In addition, there was a significant positive correlation

p
=
0.0150

and moderately strong (r = 0.7209) match between the final scores and the stage of cancer. Conclusion. The prevalence of cachectic patients is reported for the first time through the application of the miniCASCO tool. A moderate positive match was detected between the final miniCASCO score and the stages of cancer patients. Finally, an early discovery of cachexia would allow therapeutic interventions aimed at improving the prognosis of cancer patients.
Resting Full-Cycle Ratio versus Fractional Flow Reserve: A SWEDEHEART-Registry-Based Comparison of Two Physiological Indexes for Assessing Coronary Stenosis Severity
Authors: Malmberg Stephen , Lauermann Jörg , Karlström Patric , Gulin Dario , Barmano Neshro
Published: June 2023

The adenosine-requiring physiological index fractional flow reserve (FFR) is the gold-standard method for determining the significance of intermediate lesions, while the resting full-cycle ratio (RFR) is a novel nonhyperaemic index without the need for adenosine administration. The aim of this study was to investigate the degree of concordance between RFR and FFR in indicating the need for revascularisation in patients with intermediate coronary lesions. This was a retrospective, registry-based study utilising data from the SWEDEHEART registry. Patients treated at Ryhov County Hospital in Jönköping, Sweden, between the 1st of January 2020 and the 30th of September 2021, were included. The degree of correlation and concordance between RFR and FFR was determined, both when used with a single cut-off (significant stenosis if RFR ≤0.89) and with a hybrid approach (significant stenosis if RFR ≤0.85, not significant if RFR ≥0.94, and FFR measurement when RFR was in the grey zone 0.86–0.93). The study population consisted of 143 patients with 200 lesions. The overall correlation between FFR and RFR was significant (r = 0.715, R2 = 0.511,

p
≤
0.01

). A strong correlation was seen for lesions in the left anterior descending artery (LAD) and the left circumflex artery (LCX) (r = 0.748 and 0.742, respectively, both

p
≤
0.01

), while the correlation in the right coronary artery (RCA) was moderate (r = 0.524,

p
≤
0.01

). The overall concordance between FFR and RFR using a single cut-off was 79.0%. With a hybrid cut-off approach, the degree of concordance was 91%, with no need of adenosine in 50.5% of the lesions. In conclusion, there was a strong correlation and a high degree of concordance between FFR and RFR in determining the significance of a stenosis. The use of a hybrid approach could improve the identification of physiologically significant stenoses while minimising the use of adenosine.
Inspired by the Black Ghost Knifefish: Bionic Design of Undulatory Fin with 2-DOF Rays and Its Propulsion Performance
Authors: Zhou Jie , Yu Nan , Liu Song , Xin Linbo , Liu Yuhui , Gao Guowei , Na Zhonglai , Hou Xuyan
Published: June 2023

The demand for high-performance underwater thrusters in marine engineering is increasing. The concealed, mobile, and efficient underwater ability of fish provides many directions for research. The black ghost knifefish uses only wavy ventral fins to swim and can hover and roll in the water. Based on the physiological and morphological characteristics of the black ghost knifefish, we explored the structure and movement mode of the ventral fin, so as to establish a two-degree of freedom (2-DOF) structural model and kinematic model. We reveal the motion mechanism of the undulating fin propulsion through the constructed model and computational fluid dynamics. It is found that when the fin surface fluctuates, a pair of vortices with opposite directions will be formed on the concave side of the fin surface. These vortices will produce a central jet on the fin surface, provide a reverse impulse for the ventral fin, and make the fin obtain power. In addition, we found that the propulsive force of the ribbon fin along the body direction is positively correlated with the swing amplitude and frequency of the fin movement, and the propulsive torque of the ribbon fin to realize the maneuvering movement increases first and then decreases with the increase of the torsion angle. The research on the structure and motion mechanism of the ribbon fin of the black ghost knifefish provides a basis for the development of a bionic prototype of multi-DOF motion and the control strategy of high-mobility motion.
Postharvest Fish Processing in the Southwest Region of Cameroon and the Effect of Smoke-Drying on Quality
Authors: Etchutakang Yvonne Nchong , Kewir Fannyuy Veeyee , Nde Divine Bup
Published: June 2023

Fish processing in Cameroon is mostly carried out by untrained individuals using different methods which often produce fish products of poor quality. This study was aimed at identifying the main fish processing technologies used in 5 fishing communities in Limbe Subdivision in the Southwest Region of Cameroon. A total of 120 questionnaires were administered in the study area to identify the most popular unit operation in fish processing and to evaluate its effect under controlled conditions on the quality of fish products. It was found that the main fish technology employed was smoke-drying and that most of the processors dried the Ilisha africana species. Smoke-drying of Ilisha africana was carried out under controlled conditions of temperature and time, and smoked fish samples of different colours ranging from pale brown to dark brown were obtained. Laboratory analysis of the fish samples revealed that the moisture content and microbial content of the fish decreased significantly (

p
<
0.05

), while protein content increased significantly (

p
<
0.05

) with an increase in smoking time and temperature. The optimum moisture content was achieved at temperature ranges of 61-70°C for 18 h (12.3%), 71-80°C for 12 h (10.7%), and 18 h (7.3%). The pH and microbial content of all the samples were within the recommended levels for consumption and safe storage. It was concluded that the best temperature ranges and times for smoke-drying Ilisha africana were 61-70°C for 18 h and 71-80°C for 12 h.
De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna
Published: June 2023

Purpose:

Small-cell lung cancer (SCLC) is a high-grade neuroendocrine tumor with dismal prognosis and limited treatment options. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients, and the overall survival (OS) of those who benefit from it remains very low (∼9.3 months). This finding highlights the need to develop improved mechanistic insight and predictive biomarkers of response.

Experimental Design:

We used human and patient-derived xenograft (PDX)-derived SCLC cell lines to evaluate the effect of lurbinectedin in vitro. We also demonstrate the antitumor effect of lurbinectedin in multiple de novo and transformed SCLC PDX models. Changes in gene and protein expression pre- and post-lurbinectedin treatment was assessed by RNA sequencing and Western blot analysis.

Results:

Lurbinectedin markedly reduced cell viability in the majority of SCLC models with the best response on POU2F3-driven SCLC cells. We further demonstrate that lurbinectedin, either as a single agent or in combination with osimertinib, causes an appreciable antitumor response in multiple models of EGFR-mutant lung adenocarcinoma with histologic transformation to SCLC. Transcriptomic analysis identified induction of apoptosis, repression of epithelial–mesenchymal transition, modulation of PI3K/AKT, NOTCH signaling associated with lurbinectedin response in de novo, and transformed SCLC models.

Conclusions:

Our study provides a mechanistic insight into lurbinectedin response in SCLC and the first demonstration that lurbinectedin is a potential therapeutic target after SCLC transformation.
Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D.
Published: June 2023

Purpose:

The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment.

Patients and Methods:

This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.

Results:

The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged < 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1–Q3) duration of therapy (olaratumab) was 6.0 (3.0–11.9; cohort 1), 14.4 (12.4–20.9; cohort 2), and 14.0 (6.0–21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1–positive tumors.

Conclusions:

Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.
Figure S1 from Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma
Authors: Alden Stephanie L , Lim Mir , Kao Chester , Shu Daniel , Singal Amit G , Noonan Anne , Griffith Paige , Baretti Marina , Ho Won Jin , Kamel Ihab , Yarchoan Mark , Hsiehchen David
Published: June 2023

Figure S1. Survival Characteristics by Response
Supplementary Figure S3 from A Th1-like CD4+ T-cell Cluster that Predicts Disease-free Survival in Early-Stage Lung Cancer
Authors: Yanagihara Akitoshi , Yamasaki Satoshi , Hashimoto Kosuke , Taguchi Ryo , Umesaki Tetsuya , Imai Hisao , Kaira Kyoichi , Nitanda Hiroyuki , Sakaguchi Hirozo , Ishida Hironori , Kobayashi Kunihiko , Horimoto Katsuhisa , Kagamu Hiroshi
Published: June 2023

Fig. S3.
A: CD8+ T cells in peripheral blood collected before surgery were divided into four clusters according to CD62L and CD45RA expression and compared between no recurrence
patients and recurrent patients: CD62LhighCD45RA+ naive, CD62LhighCD45RA- central memory (CM), CD62LlowCD45RA- effector memory (EM), and CD62LlowCD45RA+ effector
memory with CD45RA expression (EMRA).
B: Receiver operating characteristic curve (ROC) analysis was performed to determine if CD8+ T-cell clusters had the ability to discriminate between relapsed and non-relapsed
patients. Then, Kaplan-Meier analysis of disease-free survival (DFS) was performed using the median value was used as a threshold because ROC analysis showed no significance.
Significance was tested by log-rank (Mantel-Cox) test. Hazard ratio (HR) and 95% confidence interval (CI) were obtained by log-rank test.
Supplementary Figure S2 from A Th1-like CD4+ T-cell Cluster that Predicts Disease-free Survival in Early-Stage Lung Cancer
Authors: Yanagihara Akitoshi , Yamasaki Satoshi , Hashimoto Kosuke , Taguchi Ryo , Umesaki Tetsuya , Imai Hisao , Kaira Kyoichi , Nitanda Hiroyuki , Sakaguchi Hirozo , Ishida Hironori , Kobayashi Kunihiko , Horimoto Katsuhisa , Kagamu Hiroshi
Published: June 2023

Fig. S2.
Kaplan-Meier analysis of disease-free survival (DFS) in patients with stage Ⅰ-Ⅱ disease (A), epidermal growth factor
receptor (EGFR) wild-type disease, and EGFR mutations (B) using the threshold of preoperative %Th7R in peripheral
blood obtained by receiver operating characteristic curve analysis. Significance was tested using the log-rank (Mantel-Cox)
test. Hazard ratio (HR) and 95% confidence interval (CI) were obtained by log-rank test.
Supplementary Figure S3 from Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics
Authors: Kazmierski Michal , Welch Mattea , Kim Sejin , McIntosh Chris , Rey-McIntyre Katrina , Huang Shao Hui , Patel Tirth , Tadic Tony , Milosevic Michael , Liu Fei-Fei , Ryczkowski Adam , Kazmierska Joanna , Ye Zezhong , Plana Deborah , Aerts Hugo J.W.L. , Kann Benjamin H. , Bratman Scott V. , Hope Andrew J. , Haibe-Kains Benjamin
Published: June 2023

Model performances across permutations by clinical (EMR) variables.
FIGURE 5 from Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics
Authors: Kazmierski Michal , Welch Mattea , Kim Sejin , McIntosh Chris , Rey-McIntyre Katrina , Huang Shao Hui , Patel Tirth , Tadic Tony , Milosevic Michael , Liu Fei-Fei , Ryczkowski Adam , Kazmierska Joanna , Ye Zezhong , Plana Deborah , Aerts Hugo J.W.L. , Kann Benjamin H. , Bratman Scott V. , Hope Andrew J. , Haibe-Kains Benjamin
Published: June 2023

External validation performance of the top three submissions and the best deep learning submission (number 5): AUROC (A) and C-index (B). The red line indicates the performance achieved by the winning submission in the challenge test set. The performance of tumor volume alone is shown for comparison.
FIGURE 4 from Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics
Authors: Kazmierski Michal , Welch Mattea , Kim Sejin , McIntosh Chris , Rey-McIntyre Katrina , Huang Shao Hui , Patel Tirth , Tadic Tony , Milosevic Michael , Liu Fei-Fei , Ryczkowski Adam , Kazmierska Joanna , Ye Zezhong , Plana Deborah , Aerts Hugo J.W.L. , Kann Benjamin H. , Bratman Scott V. , Hope Andrew J. , Haibe-Kains Benjamin
Published: June 2023

Top performing model. A, Overview of Deep MTLR. The model combines EMR features with tumor volume using a neural network and learns to jointly predict the probability of death at all intervals on the discretized time axis, allowing it to achieve good performance in both the binarized and lifetime risk prediction tasks. A predicted survival curve can be constructed for each individual to determine the survival probability at any timepoint. B, Importance of combined input data for performance on the binary endpoint. Training the deep MTLR on EMR features only led to notably worse performance. Furthermore, using a deep convolutional neural network in place of tumor volume did not improve the 2-year AUROC.
Data from Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma
Authors: Alden Stephanie L , Lim Mir , Kao Chester , Shu Daniel , Singal Amit G , Noonan Anne , Griffith Paige , Baretti Marina , Ho Won Jin , Kamel Ihab , Yarchoan Mark , Hsiehchen David
Published: June 2023

Abstract
Combination anti-PD-(L)1/CTLA-4 blockade is approved in patients with hepatocellular carcinoma (HCC) in the first-line setting or after sorafenib, but whether this treatment has efficacy after prior anti-PD-(L)1 therapy is unknown. We performed a multicenter retrospective review of patients with advanced HCC treated with ipilimumab plus nivolumab after prior anti-PD-(L)1 therapy, excluding patients with prior anti-CTLA-4 treatment. Of the 32 patients who met our inclusion criteria, prior anti-PD-(L)1 regimens included atezolizumab plus bevacizumab (50%, n=16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, n=10), and anti-PD-(L)1 monotherapy (19%, n=6). The median number of prior systemic therapies was two (range 1-8). The objective response rate (ORR) with ipilimumab plus nivolumab by RECIST 1.1 was 22% (1 CR (3%), 6 PR (19%), 8 SD (25%), 16 PD (50%), and 1 NE (3%)), and objective response was associated with improved PFS and OS. Immune related adverse events were reported in 13 patients (41%), with no new safety signals. This study demonstrates that ipilimumab plus nivolumab has efficacy in patients with HCC who have received prior anti-PD-(L)1 therapy, suggesting that failure to respond to prior PD-(L)1 blockade should not preclude treatment with salvage ipilimumab plus nivolumab. Prospective studies are needed to define the optimal sequence of therapies.
Salvage Ipilimumab plus Nivolumab after Anti-PD-1/PD-L1 Therapy in Advanced Hepatocellular Carcinoma
Authors: Alden Stephanie L. , Lim Mir , Kao Chester , Shu Daniel , Singal Amit G. , Noonan Anne , Griffith Paige , Baretti Marina , Ho Won Jin , Kamel Ihab , Yarchoan Mark , Hsiehchen David
Published: June 2023

Combination anti-PD-(L)1/CTLA-4 blockade is approved in patients with hepatocellular carcinoma (HCC) in the first-line setting or after sorafenib, but whether this treatment has efficacy after prior anti-PD-(L)1 therapy is unknown. We performed a multicenter retrospective review of patients with advanced HCC treated with ipilimumab plus nivolumab after prior anti-PD-(L)1 therapy, excluding patients with prior anti-CTLA-4 treatment. Of the 32 patients who met our inclusion criteria, prior anti-PD-(L)1 regimens included atezolizumab plus bevacizumab (50%, n = 16), other anti-VEGF plus anti-PD-(L)1 combinations (31%, n = 10), and anti-PD-(L)1 monotherapy (19%, n = 6). The median number of prior systemic therapies was 2 (range, 1–8). The objective response rate with ipilimumab plus nivolumab by RECIST 1.1 was 22% [1 complete response (3%), 6 partial response (19%), 8 stable disease (25%), 16 progressive disease (50%), and 1 not evaluable (NE) (3%)], and objective response was associated with improved progression-free survival and overall survival. Immune-related adverse events were reported in 13 patients (41%), with no new safety signals. This study demonstrates that ipilimumab plus nivolumab has efficacy in patients with HCC who have received prior anti-PD-(L)1 therapy, suggesting that failure to respond to prior PD-(L)1 blockade should not preclude treatment with salvage ipilimumab plus nivolumab. Prospective studies are needed to define the optimal sequence of therapies.

Significance:

Anti-PD-(L)1 containing regimens are the preferred first-line treatment for advanced HCC, but whether salvage with PD-(L)1/CTLA-4 blockade is effective in patients who have failed prior anti-PD-(L)1 therapy is unknown. Our study demonstrates that ipilimumab plus nivolumab has clinical activity in patients with advanced HCC previously treated with anti-PD-(L)1 therapy, supporting the continued use of this regimen in the late-line setting after prior anti-PD-(L)1 exposure.
Orbital Venous Malformation Excision after Transcaruncular Embolization with Onyx
Authors: Wier Garrison P. , Larochelle Ryan D. , Seinfeld Joshua , Hink Eric M.
Published: June 2023

Orbital venous malformations are low-flow lesions resulting from vascular dysgenesis during development. Patients may present with vision loss, proptosis accentuated by Valsalva, and/or painful spontaneous thrombosis. The preferred treatment for symptomatic lesions is embolization combined with excision. A 34-year-old male presented to our institution from an outside emergency department with a diagnosis of presumed idiopathic orbital inflammation. For the prior month, he had been experiencing left orbital pressure, subjective eye bulging, and both diplopia and blurry vision when in peripheral gaze or when bending over. Despite initial improvement with steroids, his symptoms recurred with tapering. Visual acuity was reduced to 20/25, but pupils and motility remained normal. Biopsy demonstrated a vascular lesion characterized by fibroadipose tissue with histologically unremarkable blood vessels, and cerebral arteriography showed no high-flow components. A diagnosis of orbital venous malformation was made. He then underwent intraoperative angiography and Onyx embolization followed by excision via a transcaruncular approach. Two prior reports have described the use of Onyx in venolymphatic malformations. This report highlights a detailed approach to defining flow characteristics pre- and intraoperatively and expands upon our understanding of the use of Onyx for such cases.
Ultrawide-Field Optical Coherence Tomography in Transvitreal and Subretinal Fibrinoid Syndrome: A Case Report
Authors: Hsu Alan Yun-Hsuan , Chen San-Ni
Published: June 2023

We report a case of fibrinoid reaction after diabetic vitrectomy surgery. Our case report describes a male patient with severe fibrinoid reaction with both intravitreal fibrin bands and subretinal fibrin and fluid following vitrectomy for diabetic retinopathy. He was managed initially with posterior subtenon and suprachoroidal injection of triamcinolone as well as intravitreal injection of tissue plasminogen activator (TPA). Fluid-air exchange and air-fluid exchange were also performed to remove the fibrin degradation product. 1 millimeter of air tamponade was placed in the vitreous cavity to displace the remaining subretinal fibrin. During this patient’s follow-up, the patient’s OCT including ultrawide-field OCT showed transvitreal fibrin bands, subretinal fibrin, as well as subretinal fluid in the right eye. The degradation of intravitreal fibrin bands as well as decrease in subretinal fluid were noted 2 days after intravitreal TPA and suprachoroidal injection of triamcinolone acetonide. The subretinal fibrin was partially reabsorbed and displaced after repeated injection of TPA and air tamponade placement 1 week later. Subsequent follow-up showed complete resolution of the subretinal fibrin and subretinal fluid as well as improved visual acuity. In summary, we describe a case of fibrinoid reaction after vitrectomy for diabetic retinopathy which was successfully treated. Wide-field OCT may also be used to assist in the recognition of this phenomenon.
Hearing Loss and Dementia: A Population-Based Cohort Study
Authors: Kirubalingam Keshinisuthan , Nguyen Paul , Newsted Daniel , Gill Sudeep S. , De La Lis Allison , Beyea Jason A
Published: June 2023

Introduction: Hearing loss (HL) is considered a potentially modifiable risk factor for dementia. We aimed to examine the relationship between HL and incident dementia diagnosis in a province-wide population-based cohort study with matched controls. Methods: Administrative healthcare databases were linked to generate a cohort of patients who were aged ≥40 years at their first claimed hearing amplification devices (HAD) between April 2007 and March 2016 through the Assistive Devices Program (ADP) (257,285 with claims and 1,005,010 controls). The main outcome was incident dementia diagnosis, ascertained using validated algorithms. Dementia incidence was compared between cases and controls using Cox regression. Patient, disease, and other risk factors were examined. Results: Dementia incidence rates (per 1,000 person-years) were 19.51 (95% confidence interval [CI]: 19.26–19.77) and 14.15 (95% CI: 14.04–14.26) for the ADP claimants and matched controls, respectively. In adjusted analyses, risk of dementia was higher in ADP claimants compared with controls (hazard ratio [HR]: 1.10 [95% CI: 1.09–1.12, p < 0.001]). Subgroup analyses showed a dose-response gradient, with risk of dementia higher among patients with bilateral HADs (HR: 1.12 [95% CI: 1.10–1.14, p < 0.001]), and an exposure-response gradient, with increasing risk over time from April 2007-March 2010 (HR: 1.03 [95% CI: 1.01–1.06, p = 0.014]), April 2010-March 2013 (HR: 1.12 [95% CI: 1.09–1.15, p < 0.001]), and April 2013-March 2016 (HR: 1.19 [95% CI: 1.16–1.23, p < 0.001]). Conclusion: In this population-based study, adults with HL had an increased risk of being diagnosed with dementia. Given the implications of HL on dementia risk, understanding the effect of hearing interventions merits further investigation.
Heuristic Approach Uncovering Biological Significance of Gene-Lifestyle Interactions in Cardiometabolic Traits
Authors: San-Cristobal Rodrigo , de Toro-Martín Juan , Vohl Marie-Claude
Published: June 2023

Background: Gene-lifestyle interaction studies using genome-wide association studies (GWAS) data contribute to a better understanding of individual responses to environmental exposures. Objectives: Herein, we aimed at assessing the biological significance of overlapping genes reported in gene-lifestyle interaction studies in cardiometabolic health. Method: A heuristic analysis of genes reporting significant interactions related to cardiometabolic traits was performed to determine the biological pathways common to the different traits. Results: A total of 873 genes were analyzed. Fine and condensed phenotypic solutions were obtained from overlapping genes common to more than one trait. Conclusions: This study revealed significant metabolic pathways associated with the impact of gene-environment interactions on cardiometabolic risk. Graphical Abstract: Publicly available data in cloud-based repositories were used to perform enrichment analyses of genes previously described in GWAS studies that showed interaction with lifestyles. From the enriched pathways, cluster analysis was performed to group enriched metabolic disorders.
Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a
Authors: Caus Maite , Alonso-Montes Cristina , Fernandez-Martin Jose Luis , Marti-Antonio Manuel , Bozic Milica , Valdivielso Jose M.
Published: June 2023

BACKGROUND:

Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC.

METHODS:

We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used.

RESULTS:

CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDR
wt
VSMCs blunted VC and decreased OPN levels.

CONCLUSIONS:

Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process.
Activation of Platelet mTORC2/Akt Pathway by Anti-β2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome
Authors: Tang Zihan , Shi Hui , Chen Changming , Teng Jialin , Dai Jing , Ouyang Xinxing , Liu Honglei , Hu Qiongyi , Cheng Xiaobing , Ye Junna , Su Yutong , Sun Yue , Pan Haoyu , Wang Xuefeng , Liu Junling , Su Bing , Yang Chengde , Xu Yanyan , Liu Tingting
Published: June 2023

BACKGROUND:

Anti-β2GP1 (β2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation.

METHODS:

Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-β2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific
Sin1
(stress-activated protein kinase–interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride–induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-β2GP1 antibodies.

RESULTS:

Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-β2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-β2GP1 antibody on platelet activation. Notably,
Sin1
deficiency suppresses anti-β2GP1 antibody–enhanced platelet activation in vitro and thrombosis in all 3 models.

CONCLUSIONS:

This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-β2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.
Association of Tricuspid Regurgitation With Outcome in Acute Heart Failure
Authors: Cocianni Daniele , Stolfo Davide , Perotto Maria , Contessi Stefano , Barbisan Davide , Savonitto Giulio , Rizzi Jacopo Giulio , Barbati Giulia , Merlo Marco , Altinier Alessandro , Sinagra Gianfranco
Published: June 2023

BACKGROUND:

Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF is lacking. We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for acute HF.

METHODS:

We enrolled 1176 consecutive patients with a primary diagnosis of acute HF and with available noninvasive estimation of TR and pulmonary arterial systolic pressure.

RESULTS:

Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (ie, pulmonary arterial systolic pressure >40 mm Hg), right ventricular dysfunction, and mitral regurgitation was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (pulmonary arterial systolic pressure, left ventricle ejection fraction, right ventricular dysfunction, mitral regurgitation, left and right atrial indexed volumes; hazard ratio, 1.718;
P
=0.009), and the association with outcome was maintained when clinical variables (eg, natriuretic peptides, serum creatinine and urea, systolic blood pressure, atrial fibrillation) were added to the multivariable model (hazard ratio, 1.761;
P
=0.024). The association between moderate-severe TR and outcome was consistent in patients with versus without PH, with versus without right ventricular dysfunction, and with versus without left ventricle ejection fraction <50%. Patients with coexistent moderate-severe TR and PH had 3-fold higher 1-year mortality risk compared with patients with no TR or PH (hazard ratio, 3.024;
P
<0.001).

CONCLUSIONS:

In patients hospitalized for acute HF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. The coexistence of moderate-severe TR and estimated PH was associated with a further increase in mortality risk. Our data must be interpreted in the context of potential underestimation of pulmonary arterial systolic pressure in patients with severe TR.