bluuebunny/crossref_metadata_2025 huggingface dataset:
Mississippi, USA's local landscapes: geoheritage value and educational benefits within college palaeontology classrooms
Authors: Clary Renee M.
Published: January 2024

In Mississippi, USA, exposures of fossiliferous Cretaceous and Paleogene strata contributed to geological investigations for more than 200 years. Since 2012, four Mississippi fossiliferous field sites were regularly integrated within university palaeontology classrooms, with community engaged learning (CEL) introduced in 2018. Through CEL projects, the students assisted local organizations with optimizing and/or protecting local fossiliferous sites. Analysis of student surveys demonstrated that students were overwhelmingly positive toward local field sites and CEL inclusion in the palaeontology courses. Students acknowledged ‘real-world’ interdisciplinary CEL experiences moved them beyond the palaeontology content and made them stakeholders in modern issues. While these four sites contain landscapes that qualify as local geoheritage sites because of their educational and potential geotourism value, only one site, W.M. Browning Cretaceous Fossil Park, is preserved for future generations. The other sites (Blue Springs, Osborn Prairie, Smith County) face challenges in their long-term sustainability.
Ultrasound Communication Using the Nonlinearity Effect of Microphone Circuits in Smart Devices
Authors: Zhang Guoming , Ji Xiaoyu , Zhou Xinyan , Qi Donglian , Xu Wenyuan
Published: January 2024

Acoustic communication has become a research focus without requiring extra hardware and facilitates numerous near-field applications such as mobile payment. To communicate, existing researchers use either an audible frequency band or an inaudible one. The former gains a high throughput but endures being audible, which can be annoying to users. The latter, although inaudible, falls short in throughput due to the available (near) ultrasonic bandwidth. In this article, we achieve both high speed and inaudibility for acoustic communication by utilizing the nonlinearity effect on microphones. We theoretically prove the maximum throughput of inaudible acoustic communication by modulating an audible signal onto an ultrasonic band. Then, we design and implementUltraComm, which utilizes a specially designed OFDM scheme. The scheme takes into account the characteristics of the nonlinear speaker-to-microphone channel, aiming to mitigate the effects of signal distortion. We evaluateUltraCommon different mobile devices and achieve throughput as high as 16.24 kbps.
Tensor-Based Viterbi Algorithms for Collaborative Cloud-Edge Cyber-Physical-Social Activity Prediction
Authors: Zhang Shunli , Yang Laurence T. , Zhang Yue , Lu Zhixing , Cui Zongmin
Published: January 2024

With the rapid development and application of smart city, Cyber-Physical-Social Systems (CPSS) as its superset is becoming increasingly important, and attracts extensive attentions. For satisfying the smart requirements of CPSS design, a cloud-edge collaborative CPSS framework is first proposed in this paper. Then Coupled-Hidden-Markov-Model (CHMM) and tensor algebra are used to improve existing activity prediction methods for providing CPSS with more intelligent decision support. There are three key features (timing, periodicity and correlation) implied in CPSS data from multi-edge, which affects the accuracy of activity prediction. Thus, these features are synthetically integrated into improved Tensor-based CHMMs (T-CHMMs) to enhance the prediction accuracy. Based on the multi-edge CPSS data, three Tensor-based Viterbi Algorithms (TVA) are correspondingly proposed to solve the prediction problem for T-CHMMs. Compared with traditional matrix-based methods, the proposed TVA could more accurately compute the optimal hidden state sequences under given observation sequences. Finally, the comprehensive performances of proposed models and algorithms are validated on three open datasets by self-comparison and other-comparison. The experimental results show that the proposed methods is superior to the compared three classical methods in terms of F1 measure, average precision and average recall.
A Reconfigurable Framework for Neural Network Based Video In-Loop Filtering
Authors: Zhang Yichi , Ding Dandan , Ma Zhan , Li Zhu
Published: January 2024

This article proposes a reconfigurable framework for neural network based video in-loop filtering to guide large-scale models for content-aware processing. Specifically, the backbone neural model is decomposed into several convolutional groups and the encoder systematically traverses all candidate configurations combined by these groups to find the best one. The selected configuration index is then encapsulated as side information and passed to the decoder, enabling dynamic model reconfiguration during the decoding stage. The preceding reconfiguration process is only deployed in the inference stage on top of a pre-trained backbone model. Furthermore, we devise
WMSPFormer
, a wavelet multi-scale Poolformer, as the backbone network structure.
WMSPFormer
utilizes a wavelet-based multi-scale structure to losslessly decompose the input into multiple scales for spatial-spectral features aggregation. Moreover, it uses multi-scale pooling operations (
MSPoolformer
) instead of complicated matrix calculations to substitute the attention process. We also extend
MSPoolformer
to a large-scale version using more parameters, referred to as
MSPoolformerExt
. Extensive experiments demonstrate that the proposed
WMSPFormer+Reconfig.
and
WMSPFormerExt+Reconfig.
achieve a remarkable 7.13% and 7.92% BD-Rate reduction over the anchor H.266/VVC, outperforming most existing methods evaluated under the same training and testing conditions. In addition, the low-complexity nature of the
WMSPFormer
series makes it attractive for practical applications.
A Review on Medicinal and Ethnomedicinal Uses, Biological Features, and Phytochemical Constituents of Sesbania sesban L. Merr., A Nitrogen-Fixing Plant Native to the Republic of Chad
Authors: Brahim Mahamat Ousman , Younes Saoud , Otchom Brahim Boy , Franzel Steven , Ouchar Mahamat Hidjazi Al-Djazouli , Soumaya El ismaili
Published: January 2024

This study reports on a literature review of the leguminous tree Sesbania sesban (L.) Merr which is found in the N'djamena region, the Republic of Chad. The study focused on S. sesban’s medicinal and ethnomedicinal uses, biological features, and phytochemical constituents to assist in future evaluations. A literature review was conducted using academic websites, such as Science Direct and Springer, online international plant databases, and data from national herbaria. S. sesban is a perennial shrub or tree that measures 3-4 m in height. This species is becoming rare in N'djamena but can be found in the rainy season, while in winter, it occurs mainly in ponds (called the Chadian dialect “Bouta”) and on the shores of the Chari and Logone rivers. The local inhabitants in Chad use the species as medicine, livestock feed, and fuelwood and for improving soil fertility and repelling desert encroachment. Traditional healers use its leaves to treat breast cancer and edema. S. sesban is an essential species native to the Republic of Chad that needs conservation and valorization. Viewing its importance and rarity in N’djamena , a strategy for replanting the species in gardens, homes, and fields around N'djamena and other regions of Chad is recommended.
A Rare Association: Hereditary Hemorrhagic Telangiectasia with Liver Cirrhosis Causing Portal Hypertension
Authors: Morales-Tovar Denisse , Martínez-Sánchez Froylan D. , Gabutti-Thomas Alejandro , Rivera-Martínez Rodolfo , Córdova-Gallardo Jacqueline
Published: January 2024

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome, is a vascular disorder of autosomal dominant etiology. The hallmark clinical feature is the presence of recurrent episodes of epistaxis in patients with vascular malformations and a tendency to bleed. We present the case of a 71-year-old woman who presented to the emergency department with upper gastrointestinal bleeding caused by esophageal varices, in conjunction with gastric angiodysplasias. The presence of oronasopharyngeal telangiectasias and hepatomegaly raised suspicion of HHT. The diagnostic workup confirmed the presence of angiodysplasia in the gastric region, portal arteriovenous malformation, and a pulmonary shunt.
Investigation of Roughness, Morphology, and Wettability Characteristics of Biopolymer Composite Coating on SS 316L for Biomedical Applications
Authors: Al-Kaisy Hanaa A. , Al-Tamimi Basma H. , Hamad Qahtan A. , Abed Mayyadah S.
Published: January 2024

This project aims to create a 316L stainless steel coated with a biocomposite based on chitosan for use in the biomedical industry. To completely coat the material, the dip-coating technique was used to apply plain chitosan, chitosan nanosilver, chitosan biotin, and chitosan-nanosilver-biotin in that order. This coating’s surface morphology was investigated with field emission scanning electron microscopy (FESEM). Surface roughness, average size distribution, and 2D and 3D surface tomography were all investigated using scanning probe microscopy and atomic force microscopy (SPM and AFM). The Fourier transform infrared (FTIR) spectroscopy technique was used to quantify changes in functional groups. To evaluate the coated samples’ wettability, contact angle measurements were also performed. The chitosan (CS) + nanosilver, CS + biotin, and CS + biotin + nanosilver-coated 316L stainless steel showed roughness values of about 8.68, 4.21, and 3.3 nm, respectively, compared with the neat chitosan coating, which exhibits 12 nm roughness, indicating a strong effect of biotin and nanosilver on surface topography whereas the coating layers were homogenous, measuring around 33 nm in thickness. For CS + nanosilver and CS + biotin, the average size of agglomerates was approximately 444 nm and 355 nm, respectively. The coatings showed adequate wettability for biomedical applications, were homogeneous, and had no cracks. Their contact angles were around 51–75 degrees. All of these results point to the composite coating’s intriguing potential for use in biological applications.
Pembrolizumab Therapy Leading to Complete Remission for Recurrence of Pulmonary Metastases after their Resection and Radical Cystectomy following Gemcitabine and Cisplatin Therapy
Authors: Ishida Kyohei , Hasegawa Go , Hashimoto Takehisa , Ikeda Yohei , Hara Noboru , Nishiyama Tsutomu
Published: January 2024

A 64-year-old man was diagnosed with invasive bladder and right lower ureteral urothelial cancer with right pelvic lymph node and lung metastases. He received four courses of gemcitabine and cisplatin therapy. He underwent lung metastasectomy and radical cystoprostatectomy, with not only primary lesions but also metastatic lesions showing a complete response. New multiple lung metastases were revealed five months after adjuvant chemotherapy. On starting pembrolizumab therapy, the metastatic lesions are notably reduced in size. He is currently receiving pembrolizumab therapy, and no recurrence has been observed for over one year.
Accommodation and Binocular Vision in Children with Myopic Anisometropia
Authors: Zhuang Chu-chu , Zhang Ling , Pan Shan-shan , Wang Yi-ning , Guo Jian-xin
Published: January 2024

Purpose. To assess the differences in accommodation and binocular vision in children with myopic anisometropia and determine the correlation with anisometropia. Method. A total of 110 patients with myopia aged 8–15 years were recruited from June 2021 to February 2022 from the Affiliated Hospital of Xuzhou Medical University. Based on the interocular differences of spherical equivalent refraction, patients were divided into the isometropia (35 children), low anisometropia (LA group, 42 children), and high anisometropia (HA group, 33 children). The variables assessed were refraction, heterophoria, amplitude of accommodation (AMP), accommodative response (AR), gradient AC/A, positive and negative relative accommodation (PRA/NRA), and near stereopsis in the three groups. Pearson’s correlation coefficient tests were used to investigate the possible association between each parameter and interocular differences (IODs). Results. Among 110 subjects, there were 49 males and 61 females with a mean age of 11.39 ± 2.28 years. Compared with those in the isometropia group, AMP was lower and near stereopsis was higher in the LA group, and the distance and near heterophoria, PRA, AR, and near stereopsis were higher, and PRA, AMP, and gradient AC/A were lower in the HA group (all P<0.05). Compared with those in the LA group, the near stereopsis, AR, and the near stereopsis were higher in the HA group, and the gradient AC/A was lower (all P<0.05). However, no significant differences existed in the negative relative accommodation (P>0.05). The distance and near heterophoria, AR, AMP, and near stereopsis were observed to be correlated with IODs, respectively (r = −0.259, p=0.006; r = −0.201, p=0.036; r = 0.306, p=0.001; r = −0.315, p=0.001; r = 0.535, p<0.001). Conclusion. Our results suggested that with the increase of anisometropia, distance and near heterophoria, AR, AMP, and near stereopsis had a tendency to get worse in children with myopic anisometropia.
Genome Resequencing of the Honeybee Apis mellifera jemenetica (Hymenoptera: Apidae): A Key Tool towards Characterization, Conservation, and Genomic Selection
Authors: Alghamdi Ahmad , Alattal Yehya
Published: January 2024

We report the whole-genome sequence of the Arabian honeybee (Apis mellifera jemenetica). Seven A. m. jemenetica samples were sequenced representing three distinct subpopulations. Generated sequence reads were mapped to the reference honeybee Apis mellifera genome (Amel_HAv3.1). Data revealed genome-wide patterns of genetic variation which can be useful in the characterization and assessment of positive selection of the Arabian honeybee using different genetic markers. In total, 75.16 Gb of clean bases were generated, and the GC content of samples ranged between 31.9 and 35.3%. The effective reference genome size is 223,937,270 bp. The mapping rate of samples varied from 88.97% to 96.19%, and the effective mapping depth was between 41.80 and 48.84X. Single-nucleotide polymorphisms (SNPs) among sequenced individuals ranged between 2379499 and 2396116 with respect to the reference A. mellifera genome (Amel_HAv3.1), and 2% of the SNPs were nonsynonymous. Genome Analysis Toolkit (GATK) detected 1097962–1109829 InDels and 10090–11962 structural variations (SV) from which 22.1 to 33.8% were in the form of deletions. Copy number variation (CNV) ranged between 550 and 2824, and 45–91% of them were downregulated. These variations among interbreeding individuals or groups of the same species may reflect an adaptive environmental response and fitness among different subpopulations and can be very useful for subspecies characterization, conservation, and selection of the Arabian honeybee.
Experimental and Numerical Simulation Study of Water Infiltration Impact on Soil-Pile Interaction in Expansive Soil
Authors: Awadalseed Waleed , Zhang Xingli , Ji Yunpeng , Wang XiangJin , Bai Yuntian , Zhao Honghua
Published: January 2024

A laboratory model of a single pile embedded in Nanyang expansive soil and subjected to water infiltration is applied in this study to examine the interaction between the expansive soil and pile foundation upon water infiltration. The soil matric suction decreases as a result of the rising soil-water content. The amount of soil ground heave reaches its peak of 10.7 mm after 200 hours of water infiltration. As matric suction decreases, pile shaft friction also declines, which causes more of the load at the pile head to be carried by the pile base resulting in more pile settlements. A new numerical simulation method is provided to simulate this issue by coupling the subsurface flow, soil deformation, and hygroscopic swelling to investigate the expansive soil-pile response upon water infiltration. From the numerical simulation model, hygroscopic strain arises as a result of elevated moisture levels resulting from the entry of water, and due to ground heave and the mobilization of lateral soil swelling, the shear stress at the interface between the soil and the pile gradually increases over time. It reaches its maximum value of 4420 Pa at upper depths around 200 hours after the infiltration. The comparison between the lab model testing data and the numerical model results demonstrates a good level of concurrence.
Magnetorheological Fluid Dampers: A Close Look at Efficient Parametric Models
Authors: Bahar Arash , Pozo Francesc , Meybodi Mehdi Rashidi , Karami Saeed
Published: January 2024

The reasonable efficiency, high reliability, and minimal maintenance requirements of the semiactive control algorithms make this form of structural control the most successful method from a practical point of view. In addition, significant progress has been made in structural control devices. Magnetorheological (MR) dampers have been the subject of extensive research. In order to develop and implement a successful structural control algorithm, a deep understanding of their operation is required. Therefore, many efforts have been made to classify MR dampers as efficient tools; however, their complicated behavior has also been noted. Various relations have been proposed to describe the highly nonlinear behavior of MR dampers. To develop an efficient control algorithm, one must first properly understand the seismic behavior of the structure and the control device as well as its handling. The handling of the device will be efficient if there is a description for its control, a so‐called inverse model. This model is an answer to the question of whether the proposed device model can be written in a form that practically brings the generated damping force as close as possible to the desired force. In the identification process, the selection of a basic mathematical model is critical. In this review article, we have compiled successful parametric models that accurately replicate the behavior of MR dampers. Since the primary functionality of the device is crucial for the development of a competent control algorithm, we have endeavored to investigate and present the reversibility of the proposed models. We also delved at the characteristics of the parameters that enable precise communication between the central control unit and the device. These parameters, which enable the dialog between the processing unit and the control devices, will play an important role in the development of the inverse model in its simplicity and efficiency.
Symptomatic Liver Cyst Successfully Treated with Transgastric Drainage and Sclerotherapy Using Minocycline Hydrochloride
Authors: Yoshitomi Kengo , Koya Yudai , Miyagawa Koichiro , Maruno Yuki , Yamaguchi Koki , Taniguchi Ryuta , Onitsuka Koji , Sakamoto Yoshitaka , Oe Shinji , Harada Masaru
Published: January 2024

A liver cyst is hepatic fluid-filled cavities often detected in clinical surveillances such as a health examination. Although the liver cyst is usually asymptomatic and observed without any therapeutic intervention, it can be symptomatic and needs treatment due to its enlargement, hemorrhage, and infection. A 74-year-old woman presented with upper abdominal pain and a huge liver cyst in the left lobe. Several examinations including image findings revealed that the symptom could be derived from the liver cyst. Although there is no definite guideline of treatment for symptomatic liver cysts, percutaneous ultrasound-guided drainage with sclerotherapy or surgery is often selected. Because of anatomical accessibility to the liver cyst and the patient’s wish, we performed endoscopic transgastric drainage with insertion of both an internal stent and an external nasocystic tube. Sclerotherapy with minocycline hydrochloride was performed through the nasocystic tube, and the liver cyst shrunk completely without any complications. This is the first reported method of administering minocycline hydrochloride through a nasocystic tube, which can be a therapeutic option for patients with symptomatic liver cysts.
Is eGFR Slope a Novel Predictor of Chronic Complications of Type 2 Diabetes Mellitus? A Systematic Review and Meta‐Analysis
Authors: Sartore Giovanni , Ragazzi Eugenio , Deppieri Elena , Lapolla Annunziata
Published: January 2024

Background. Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end‐stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta‐analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM. Methods. The review and meta‐analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria. Results. Fifteen studies were selected for meta‐analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all‐cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all‐cause mortality, 2.31 (1.70‐3.15); for CV events, 1.73 (1.43‐2.08); for ESKD, 1.54 (1.45‐1.64); and for microvascular events, 2.07 (1.57‐2.73). Overall HR was 1.82 (1.72‐1.92). Conclusions. An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.
The Occupational Therapy Profession in Saudi Arabia
Authors: Aljabri Naif Qasem , Bulkeley Kim , Cusick Anne
Published: January 2024

Objective. To provide an evidence‐based description of how the occupational therapy profession operates in Saudi Arabia. Methods. A case study methodology set out an evidence‐based description of occupational therapy in Saudi Arabia. Three procedures were used: (1) a structured narrative review of publications on occupational therapy in Saudi Arabia based on searches of seven healthcare databases; (2) an audit of “grey literature” about or referring to occupational therapy education, practice, research, or the profession in Saudi Arabia using Google Scholar, Google search, official documents and websites, and relevant global organisation such as the WFOT website and documents; and (3) consultation with occupational therapists to further discuss emerging evidence from peer‐reviewed articles and grey literature about occupational therapy in Saudi Arabia. Data were collected in Arabic and English. Findings. Occupational therapy in Saudi Arabia is a rapidly growing and emerging profession primarily focused on rehabilitation practice. Between 2010 and 2019, seven academic organisations commenced bachelor’s degree programmes. Occupational therapy services in Saudi Arabia are concentrated in city‐based secondary and tertiary healthcare services targeting rehabilitation and disability support. The practice aims to promote the reduction in impairment and increase activity performance and participation in valued life roles. Despite the increasing demand for occupational therapy services, there needs to be more access to and availability of their services. Enhancement of the awareness of occupational therapy among the public and other healthcare professionals is needed. A consistent definition of occupational therapy in Saudi Arabia would strengthen the profession, along with a national scope of practice, practice guidelines, increased workforce and development, and professional education information. Conclusion. Occupational therapy in Saudi Arabia is growing regarding the size of the workforce and the number of programmes and services provided, thus contributing to the health and well‐being of the population primarily through rehabilitation. Further development of the profession is necessary.
Foretinib Is Effective in Acute Myeloid Leukemia by Inhibiting FLT3 and Overcoming Secondary Mutations That Drive Resistance to Quizartinib and Gilteritinib
Authors: Wang Peihong , Zhang Yvyin , Xiang Rufang , Yang Jie , Xu Yanli , Deng Tingfen , Zhou Wei , Wang Caixia , Xiao Xinhua , Wang Shunqing
Published: January 2024

FLT3 internal tandem duplication (FLT3-ITD) mutations are one of the most prevalent somatic alterations associated with poor prognosis in patients with acute myeloid leukemia (AML). The clinically approved FLT3 kinase inhibitors gilteritinib and quizartinib improve the survival of patients with AML with FLT3-ITD mutations, but their long-term efficacy is limited by acquisition of secondary drug-resistant mutations. In this study, we conducted virtual screening of a library of 60,411 small molecules and identified foretinib as a potent FLT3 inhibitor. An integrated analysis of the BeatAML database showed that foretinib had a lower IC50 value than other existing FLT3 inhibitors in patients with FLT3-ITD AML. Foretinib directly bound to FLT3 and effectively inhibited FLT3 signaling. Foretinib potently inhibited proliferation and promoted apoptosis in human AML cell lines and primary AML cells with FLT3-ITD mutations. Foretinib also significantly extended the survival of mice bearing cell-derived and patient-derived FLT3-ITD xenografts, exhibiting stronger efficacy than clinically approved FLT3 inhibitors in treating FLT3-ITD AML. Moreover, foretinib showed potent activity against secondary mutations of FLT3-ITD that confer resistance to quizartinib and gilteritinib. These findings support the potential of foretinib for treating patients with AML with FLT3-ITD mutations, especially for those carrying secondary mutations after treatment failure with other FLT3 inhibitors.

Significance:

Foretinib exhibits superior efficacy to approved drugs in AML with FLT3-ITD mutations and retains activity in AML with secondary FLT3 mutations that mediate resistance to clinical FLT3 inhibitors.
Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis
Authors: Sasine Joshua P. , Kozlova Natalia Y. , Valicente Lisa , Dukov Jennifer , Tran Dana H. , Himburg Heather A. , Kumar Sanjeev , Khorsandi Sarah , Chan Aldi , Grohe Samantha , Li Michelle , Kan Jenny , Sehl Mary E. , Schiller Gary J. , Reinhardt Bryanna , Singh Brijesh Kumar , Ho Ritchie , Yue Peibin , Pasquale Elena B. , Chute John P.
Published: January 2024

Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma–supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in multiple myeloma cells. Silencing EPHB1 or EPHB4 in ECs suppressed multiple myeloma growth in coculture. Similarly, loss of EFNB2 in multiple myeloma cells blocked multiple myeloma proliferation and survival in vitro, abrogated multiple myeloma engraftment in immune-deficient mice, and increased multiple myeloma sensitivity to chemotherapy. Administration of an EFNB2-targeted single-chain variable fragment also suppressed multiple myeloma growth in vivo. In contrast, overexpression of EFNB2 in multiple myeloma cells increased STAT5 activation, increased multiple myeloma cell survival and proliferation, and decreased multiple myeloma sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in multiple myeloma cells increased multiple myeloma cell death and sensitivity to chemotherapy and abolished multiple myeloma growth in vivo. Complementary analysis of multiple myeloma patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls multiple myeloma pathogenesis and can be therapeutically targeted to improve multiple myeloma outcomes.

Significance:

Ephrin B2 reverse signaling mediated by endothelial cells directly regulates multiple myeloma progression and treatment resistance, which can be overcome through targeted inhibition of ephrin B2 to abolish myeloma.
Post-translational Modification of PD-1: Potential Targets for Cancer Immunotherapy
Authors: Lee Te-An , Tsai En-Yun , Liu Shou-Hou , Hsu Hung Shih-Duo , Chang Shing-Jyh , Chao Chi-Hong , Lai Yun-Ju , Yamaguchi Hirohito , Li Chia-Wei
Published: January 2024

Activation of effector T cells leads to upregulation of PD-1, which can inhibit T-cell activity following engagement with its ligand PD-L1. Post-translational modifications (PTM), including glycosylation, phosphorylation, ubiquitination, and palmitoylation, play a significant role in regulating PD-1 protein stability, localization, and interprotein interactions. Targeting PTM of PD-1 in T cells has emerged as a potential strategy to overcome PD-1–mediated immunosuppression in cancer and enhances antitumor immunity. The regulatory signaling pathways that induce PTM of PD-1 can be suppressed with small-molecule inhibitors, and mAbs can directly target PD-1 PTMs. Preliminary outcomes from exploratory studies suggest that focusing on the PTM of PD-1 has strong therapeutic potential and can enhance the response to anti-PD-1.
Rural–Urban Differences in Sun Exposure and Protection Behaviors in the United States
Authors: Dona Allison C. , Jewett Patricia I. , Henning-Smith Carrie , Ahmed Rehana L. , Wei Maria L. , Lazovich DeAnn , Vogel Rachel I.
Published: January 2024

Background:

Evidence regarding whether rural residence is a risk factor for skin cancer is mixed. We compared sun exposure and protection behaviors between rural and urban residents by ethno-racial group in the United States.

Methods:

We analyzed data from three (2013–2018) National Health and Nutrition Examination Survey cycles. We compared self-reported sun exposure and protection measures (sunburn, time spent outside, sunscreen use, wearing long sleeves, staying in shade) by rural–urban residential status using survey-weighted logistic regression models stratified by ethno-racial group, adjusting for age, sex, income, education, body mass index, and smoking.

Results:

Hispanic rural versus urban residents more often reported sunburns in the past year [41.6% vs. 31.2%, adjusted OR (aOR): 1.46 (1.15–1.86)]. White rural versus urban residents more often spent 2+ hours outside on workdays [42.9% vs. 29.1%, aOR: 1.60 (1.27–2.01)] and non-workdays [72.2% vs. 64.8%, aOR: 1.45 (1.12–1.88)] and less often used sunscreen [26.0% vs. 35.1%, aOR: 0.74 (0.59–0.93)] and stayed in the shade [21.7% vs. 26.7%, aOR: 0.72 (0.57–0.89)]. Black rural versus urban residents stayed in the shade less often [31.6% vs. 43.9%, aOR: 0.60 (0.39–0.91)] but less often spent 2+ hours outside on non-workdays [47.6% vs. 56.8%, aOR: 0.67 (0.51–0.90)].

Conclusions:

Across all ethno-racial groups included, rural residents reported greater sun risk behaviors than urban residents, with some nuances by ethno-racial identity, suggesting rural residence is a potential risk factor for skin cancer.

Impact:

Sun protection promotion programs should consider rural–urban settings while also accounting for ethno-racial identities.
Supplementary Table S2 from SAR-096: Phase II Clinical Trial of Ribociclib in Combination with Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)
Authors: Movva Sujana , Matloob Sahar , Handorf Elizabeth A. , Choy Edwin , Merriam Priscilla , Flieder Douglas B. , Cai Kathy Q. , Zhou Yan , Tetzlaff Eric D. , Pagan Cheyenne , Barker Emma , Veggeberg Rosanna , Zumpano Delia , Rink Lori , von Mehren Margaret , George Suzanne
Published: January 2024

Supplementary Table S2: Rb status by IHC vs. NGS in LMS archival tissue
Supplementary Figure S4 from Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study
Authors: Randon Giovanni , Nakamura Yoshiaki , Yaeger Rona , Lonardi Sara , Cremolini Chiara , Elez Elena , Nichetti Federico , Ghelardi Filippo , Nasca Vincenzo , Bergamo Francesca , Conca Veronica , Ros Javier , Bando Hideaki , Maddalena Giulia , Oldani Simone , Prisciandaro Michele , Raimondi Alessandra , Schrock Alexa B. , Agnelli Luca , Walch Henry , Yoshino Takayuki , Pietrantonio Filippo
Published: January 2024

Restricted cubic spline plot showing the association of HER2 CNV and PFS (panel A) and OS (panel B).
Figure S1 from Sex-dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma
Authors: Pan Minggui , Zhou Maggie Yuxi , Jiang Chen , Zhang Zheyang , Bui Nam Q. , Bien Jeffrey , Siy Amanda , Achacoso Ninah , Solorzano Aleyda V. , Tse Pamela , Chung Elaine , Thomas Sachdev , Habel Laurel A. , Ganjoo Kristen N.
Published: January 2024

OS comparison between Stanford and KPNC cohort
Table S6 from Phase I/IIa Trial in Advanced Pancreatic Ductal Adenocarcinoma Treated with Cytotoxic Drug-Packaged, EGFR-Targeted Nanocells and Glycolipid-Packaged Nanocells
Authors: Ganju Vinod , Marx Gavin , Pattison Scott , Amaro-Mugridge Nancy B. , Zhao Jing-Ting , Williams Bryan R.G. , MacDiarmid Jennifer A. , Brahmbhatt Himanshu
Published: January 2024

Table S6: Representativeness of Study Participants
Supplementary Figure S8 from Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer
Authors: Murray Joseph C. , Sivapalan Lavanya , Hummelink Karlijn , Balan Archana , White James R. , Niknafs Noushin , Rhymee Lamia , Pereira Gavin , Rao Nisha , Weksler Benny , Bahary Nathan , Phallen Jillian , Leal Alessandro , Bartlett David L. , Marrone Kristen A. , Naidoo Jarushka , Goel Akul , Levy Benjamin , Rosner Samuel , Hann Christine L. , Scott Susan C. , Feliciano Josephine , Lam Vincent K. , Ettinger David S. , Li Qing Kay , Illei Peter B. , Monkhorst Kim , Scharpf Robert B. , Brahmer Julie R. , Velculescu Victor E. , Zaidi Ali H. , Forde Patrick M. , Anagnostou Valsamo
Published: January 2024

Supplementary Fig.S8 Overview of peripheral blood TCR dynamics in patients with immunotherapy-related pneumonitis. (A) Swimmer plot showing treatment duration for 17 patients with immune-related
toxicity and paired baseline and on-treatment blood samples available for analysis. The time to identification of significant TCR clonotypic expansions and regressions in first on-treatment blood samples is
shown alongside the time to clinical diagnosis of toxicity. Overall, TCR clonotype dynamics were identified on average 20 weeks prior to the clinical presentation of immune-related toxicity in these patients.
(B-E) Logo plots showing global TCR clusters identified using GLIPH2 that were significantly expanded in
on-therapy peripheral blood samples from patients who developed pneumonitis compared to individuals
who developed other immune-related adverse events (irAEs) and individuals who did not develop
immune-related toxicity. The size of each cluster, defined by the number of distinct CDR3 member
sequences, is indicated alongside each panel. Enriched clusters with a minimum motif length of 5 are
shown. (F-G) Boxplots showing the differential abundance of TCR clusters shown in (C-E) from baseline
to on-treatment samples across patient groups.
Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study
Authors: Ahn Daniel H. , Barzi Afsaneh , Ridinger Maya , Samuëlsz Errin , Subramanian Ramanand A. , Croucher Peter J.P. , Smeal Tod , Kabbinavar Fairooz F. , Lenz Heinz-Josef
Published: January 2024

Purpose:

Onvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer.

Patients and Methods:

Preclinical activity of onvansertib was assessed (i) in vitro in KRAS wild-type and -mutant isogenic colorectal cancer cells and (ii) in vivo, in combination with irinotecan, in a KRAS-mutant xenograft model. Clinically, a phase Ib trial was conducted to investigate onvansertib at doses 12, 15, and 18 mg/m2 (days 1–5 and 14–19 of a 28-day cycle) in combination with FOLFIRI/bevacizumab (days 1 and 15) in patients with KRAS-mutant metastatic colorectal cancer who had prior oxaliplatin exposure. Safety, efficacy, and changes in circulating tumor DNA (ctDNA) were assessed.

Results:

In preclinical models, onvansertib displayed superior activity in KRAS-mutant than wild-type isogenic colorectal cancer cells and demonstrated potent antitumor activity in combination with irinotecan in vivo. Eighteen patients enrolled in the phase Ib study. Onvansertib recommended phase II dose was established at 15 mg/m2. Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common. Partial responses were observed in 44% of patients, with a median duration of response of 9.5 months. Early ctDNA dynamics were predictive of treatment efficacy.

Conclusions:

Onvansertib combined with FOLIFRI/bevacizumab exhibited manageable safety and promising efficacy in second-line treatment of patients with KRAS-mutant metastatic colorectal cancer. Further exploration of this combination therapy is ongoing.

See related commentary by Stebbing and Bullock, p. 2005
Mass Spectrometry–Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer
Authors: Huang Yufeng , Gong Ming , Chen Hongmin , Deng Chuangzhong , Zhu Xiaojun , Lin Jiaming , Huang Anfei , Xu Yanyang , Tai Yi , Song Guohui , Xu Huaiyuan , Hu Jinxin , Feng Huixiong , Tang Qinglian , Lu Jinchang , Wang Jin
Published: January 2024

Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry–based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell–dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM.

Implications:

SB9 as a therapeutic target for LCBM.
Role of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in inflammation and pathogen-associated interactions
Authors: Truthe Sarah , Klassert Tilman E. , Schmelz Stefan , Jonigk Danny , Blankenfeldt Wulf , Slevogt Hortense
Published: January 2024

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.
Summary: This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologues across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.
Key messages: The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes, but also identify potential targets for immunomodulatory approaches.
Harnessing Speech-Derived Digital Biomarkers to Detect and Quantify Cognitive Decline Severity in Older Adults
Authors: Cay Gozde , Pfeifer Valeria A. , Lee Myeounggon , Rouzi Mohammad Dehghan , Nunes Adonay S. , El-Refaei Nesreen , Momin Anmol Salim , Atique Md Moin Uddin , Mehl Matthias R. , Vaziri Ashkan , Najafi Bijan
Published: January 2024

Introduction: Current cognitive assessments suffer from floor/ceiling and practice effects, poor psychometric performance in mild cases, and repeated assessment effects. This study explores the use of digital speech analysis as an alternative tool for determining cognitive impairment. The study specifically focuses on identifying the digital speech biomarkers associated with cognitive impairment and its severity. Methods: We recruited older adults with varying cognitive health. Their speech data, recorded via a wearable microphone during the reading aloud of a standard passage, were processed to derive digital biomarkers such as timing, pitch, and loudness. Cohen’s d effect size highlighted group differences, and correlations were drawn to the Montreal Cognitive Assessment (MoCA). A stepwise approach using a Random Forest model was implemented to distinguish cognitive states using speech data and predict MoCA scores based on highly correlated features. Results: The study comprised 59 participants, with 36 demonstrating cognitive impairment and 23 serving as cognitively intact controls. Among all assessed parameters, similarity, as determined by Dynamic Time Warping (DTW), exhibited the most substantial positive correlation (rho = 0.529, p < 0.001), while timing parameters, specifically the ratio of extra words, revealed the strongest negative correlation (rho = −0.441, p < 0.001) with MoCA scores. Optimal discriminative performance was achieved with a combination of four speech parameters: total pause time, speech-to-pause ratio, similarity via DTW, and intelligibility via DTW. Precision and balanced accuracy scores were found to be 88.1 ± 1.2% and 76.3 ± 1.3%, respectively. Discussion: Our research proposes that reading-derived speech data facilitates the differentiation between cognitively impaired individuals and cognitively intact, age-matched older adults. Specifically, parameters based on timing and similarity within speech data provide an effective gauge of cognitive impairment severity. These results suggest speech analysis as a viable digital biomarker for early detection and monitoring of cognitive impairment, offering novel approaches in dementia care.
Identification and Functional Study of Enhancers of EYA1: The Causative Gene of Branchio-Oto-Renal Syndrome
Authors: Wang Feng , Zhang Ruizhi , Jian Jing , Sun Yanhe , Li Qiang
Published: January 2024

Introduction: Branchio-oto-renal syndrome (BOR syndrome) is a rare genetic disorder with an incidence of 1 in 40,000, affecting the development of multiple organs, including the branchio, ear, and kidney. It is responsible for 2% of childhood deafness. Currently, variants in the coding regions of the main causative genes, such as EYA1, SIX1, and SIX5, explain only half of the disease’s etiology. Therefore, there is a need to explore the non-coding regions, which constitute the majority of the genome, especially the regulatory regions, as potential new causative factors. Method: In this study, we focused on the EYA1 gene, which accounts for over 40% of BOR syndrome cases, and conducted a screening of candidate enhancers within a 250-kb region upstream and downstream of the gene using comparative genomics. We characterized the enhancer activities of these candidates in zebrafish using the Tol2 transposon system. Results: Our findings revealed that out of the 11 conserved non-coding elements (CNEs) examined, four exhibited enhancer activity. Notably, CNE16.39 and CNE16.45 displayed tissue-specific enhancer activity in the ear. CNE16.39 required the full-length 206 bp sequence for inner-ear-specific expression, while the core functional region of CNE16.45 was identified as 136 bp. Confocal microscopy results demonstrated that both CNE16.39 and CNE16.45 drove the expression of GFP in the sensory region of the crista of the inner ear in zebrafish, consistent with the expression pattern of eya1. Conclusion: This study contributes to the understanding of the regulatory network governing EYA1 expression and offers new insights to further clarify the pathogenic role of EYA1 in BOR syndrome.