bluuebunny/crossref_metadata_2025 huggingface dataset:
The GA and ABA signaling is required for hydrogen-mediated seed germination in wax gourd
Authors: Chang Jingjing , Li Jiawei , Li Jinlong , Chen Xiao , Jiao Jiabin , Li Jing , Song Zhao , Zhang Baige
Published: June 2024

Background

Hydrogen gas (H2), a novel and beneficial gaseous molecule, plays a significant role in plant growth and development processes. Hydrogen-rich water (HRW) is regarded as a safe and easily available way to study the physiological effects of H2 on plants. Several recent research has shown that HRW attenuates stress-induced seed germination inhibition; however, the underlying modes of HRW on seed germination remain obscure under non-stress condition.

Results

In this current study, we investigated the possible roles of gibberellin (GA) and abscisic acid (ABA) in HRW-regulated seed germination in wax gourd (Benincasa hispida) through pharmacological, physiological, and transcriptome approaches. The results showed that HRW application at an optimal dose (50% HRW) significantly promoted seed germination and shortened the average germination time (AGT). Subsequent results suggested that 50% HRW treatment stimulated GA production by regulating GA biosynthesis genes (BhiGA3ox, BhiGA2ox, and BhiKAO), whereas it had no effect on the content of ABA and the expression of its biosynthesis (BhiNCED6) and catabolism genes (BhiCYP707A2) but decreased the expression of ABA receptor gene (BhiPYL). In addition, inhibition of GA production by paclobutrazol (PAC) could block the HRW-mediated germination. Treatment with ABA could hinder HRW-mediated seed germination and the ABA biosynthesis inhibitor sodium tungstate (ST) could recover the function of HRW. Furthermore, RNA-seq analysis revealed that, in the presence of GA or ABA, an abundance of genes involved in GA, ABA, and ethylene signal sensing and transduction might involve in HRW-regulated germination.

Conclusions

This study portrays insights into the mechanism of HRW-mediated seed germination, suggesting that HRW can regulate the balance between GA and ABA to mediate seed germination through ethylene signals in wax gourd.
Plant growth promotion and biocontrol properties of a synthetic community in the control of apple disease
Authors: Qiao Rongye , Xu Mingzhen , Jiang Jihang , Song Zhen , Wang Meibin , Yang Lei , Guo Hui , Mao Zhiquan
Published: June 2024

Background

Apple Replant Disease (ARD) is common in major apple-growing regions worldwide, but the role of rhizosphere microbiota in conferring ARD resistance and promoting plant growth remains unclear.

Results

In this study, a synthetic microbial community (SynCom) was developed to enhance apple plant growth and combat apple pathogens. Eight unique bacteria selected via microbial culture were used to construct the antagonistic synthetic community, which was then inoculated into apple seedlings in greenhouse experiments. Changes in the rhizomicroflora and the growth of aboveground plants were monitored. The eight strains, belonging to the genera Bacillus and Streptomyces, have the ability to antagonize pathogens such as Fusarium oxysporum, Rhizoctonia solani, Botryosphaeria ribis, and Physalospora piricola. Additionally, these eight strains can stably colonize in apple rhizosphere and some of them can produce siderophores, ACC deaminase, and IAA. Greenhouse experiments with Malus hupehensis Rehd indicated that SynCom promotes plant growth (5.23%) and increases the nutrient content of the soil, including soil organic matter (9.25%) and available K (1.99%), P (7.89%), and N (0.19%), and increases bacterial richness and the relative abundance of potentially beneficial bacteria. SynCom also increased the stability of the rhizosphere microbial community, the assembly of which was dominated by deterministic processes (|β NTI| > 2).

Conclusions

Our results provide insights into the contribution of the microbiome to pathogen inhibition and host growth. The formulation and manipulation of similar SynComs may be a beneficial strategy for promoting plant growth and controlling soil-borne disease.
Placental T2WI MRI-based radiomics-clinical nomogram predicts suspicious placenta accreta spectrum in patients with placenta previa
Authors: Yu Hongchang , Yin Hongkun , Zhang Huiling , Zhang Jibin , Yue Yongfei , Lu Yanli
Published: June 2024

Background

The incidence of placenta accreta spectrum (PAS) increases in women with placenta previa (PP). Many radiologists sometimes cannot completely and accurately diagnose PAS through the simple visual feature analysis of images, which can affect later treatment decisions. The study is to develop a T2WI MRI-based radiomics-clinical nomogram and evaluate its performance for non-invasive prediction of suspicious PAS in patients with PP.

Methods

The preoperative MR images and related clinical data of 371 patients with PP were retrospectively collected from our hospital, and the intraoperative examination results were used as the reference standard of the PAS. Radiomics features were extracted from sagittal T2WI MR images and further selected by LASSO regression analysis. The radiomics score (Radscore) was calculated with logistic regression (LR) classifier. A nomogram integrating Radscore and selected clinical factors was also developed. The model performance was assessed with respect to discrimination, calibration and clinical usefulness.

Results

A total of 6 radiomics features and 1 clinical factor were selected for model construction. The Radscore was significantly associated with suspicious PAS in both the training (p < 0.001) and validation (p < 0.001) datasets. The AUC of the nomogram was also higher than that of the Radscore in the training dataset (0.891 vs. 0.803, p < 0.001) and validation dataset (0.897 vs. 0.780, p < 0.001), respectively. The calibration was good, and the decision curve analysis demonstrated the nomogram had higher net benefit than the Radscore.

Conclusions

The T2WI MRI-based radiomics-clinical nomogram showed favorable diagnostic performance for predicting PAS in patients with PP, which could potentially facilitate the obstetricians for making clinical decisions.
Silencing immune-infiltrating biomarker CCDC80 inhibits malignant characterization and tumor formation in gastric cancer
Authors: Yu MeiHong , Peng Jingxuan , Lu Yanxu , Li Sha , Ding Ke
Published: June 2024

Objective

Tumor immune infiltration leads to poor prognosis of gastric cancer patients and seriously affects the life quality of gastric cancer patients. This study was based on bioinformatics to screen prognostic biomarkers in patients with high degree of immune invasion of gastric cancer. Meanwhile, the action of biomarker CCDC80 was explored in gastric cancer by cell and tumorigenesis experiments, to provide reference for the cure of gastric cancer patients.

Methods

Data sets and clinical massage on gastric cancer were collected from TCGA database and GEO database. ConsensusClusterPlus was used to cluster gastric cancer patients based on the 28 immune cells infiltration in ssGSEA. R “Limma” package was applied to analyze differential mRNAs between Cluster 1 and Cluster 2. Differential expression genes were screened by single factor analysis. Stemness markers (SERPINF1, DCN, CCDC80, FBLN5, SPARCL1, CCL14, DPYSL3) were identified for differential expression genes. Prognostic value of CCDC80 was evaluated in gastric cancer. Differences in genomic mutation and tumor microenvironment immune infiltration were assessed between high or low CCDC80. Finally, gastric cancer cells (HGC-27 and MKN-45) were selected to evaluate the action of silencing CCDC80 on malignant characterization, macrophage polarization, and tumor formation.

Results

Bioinformatics analysis showed that CCDC80, as a stemness marker, was significantly overexpressed in gastric cancer. CCDC80 was also related to the degree of gastric cancer immune invasion. CCDC80 was up-expressed in cells of gastric cancer. Silencing CCDC80 inhibited malignant characterization and subcutaneous tumor formation of gastric cancer cells. High expression of CCDC80 was positive correspondence with immune invasion. Silencing CCDC80 inhibited M2 polarization and promoted M1 polarization in tumor tissues. In addition, gastric cancer patients were likely to have mutations in CDH1, ACTRT1, GANAB, and CDH10 genes in the High-CCDC80 group.

Conclusion

Silencing CCDC80, a prognostic biomarker in patients with immune invasion of gastric cancer, could effectively inhibit the malignant characterization, M2 polarization, and tumor formation of gastric cancer.
Exploring the perspectives of older adults who are pre-frail and frail to identify interventions to reduce sedentary behaviour and improve mobility: a thematic content analysis
Authors: Rodrigues Isabel B. , Ching Priscilla , Kalra Mayank , Zheng Rong , Rabinovich Alexander , Papaioannou Alexandra , Leckie Carolyn , Kobsar Dylan , Fang Qiyin , Bray Steven , Adachi Jonathan D.
Published: June 2024

Older adults who are frail are one of the most sedentary and the least physically active age groups. Prolonged sedentary time is associated with increased risk of negative health outcomes. To help design effective and sustainable content and optimize the uptake of sedentary behaviour interventions, an in-depth understanding of older adults’ perceptions of sedentary behaviour is needed; however, most qualitative studies have been conducted in healthy older adults. The aim of this study was to explore perspectives of sedentary behaviour within the context of older adults who are pre-frail and frail after the winter and spring. We included participants if they: (1) spoke English or attended with a translator or caregiver, (2) were ≥ 60 years, and (3) were frail on the Morley Frail Scale. We utilized a qualitative description methodology including a semi-structured in-depth interview and thematic content analysis. Concepts from the COM-B (Capability Opportunity Motivation–Behaviour) model were used to guide the semi-structured interviews and analysis. To ensure credibility of the data, we used an audit trail and analyst triangulation. We recruited 21 older adults (72 ± 7.3 years, 13 females, 13 frail) from southwestern Ontario, Canada. Two individuals were lost to follow-up due to medical mistrust and worse health. We transcribed 39 audio recordings. We identified three salient themes: (1) older adults rationalize their sedentary behaviours through cognitive dissonance (reflective motivation), (2) urban cities in southwestern Ontario may not be “age-friendly” (physical opportunity), and (3) exercise is something people “have to do”, but hobbies are for enjoyment despite medical conditions (psychological capability). Perspectives of sedentary behaviour were different in the winter versus spring, with participants perceiving themselves to be less active in winter. Incorporating dissonance-based interventions as part of an educational program could be used to target the reflective motivation and psychological capability components. Future research should consider interdisciplinary collaborations with environmental gerontology to develop age-friendly communities that promote meaningful mobility to target physical opportunity.
Infant feeding experiences among Indigenous communities in Canada, the United States, Australia, and Aotearoa: a scoping review of the qualitative literature
Authors: Monteith Hiliary , Checholik Carly , Galloway Tracey , Sahak Hosna , Shawanda Amy , Liu Christina , Hanley Anthony J. G.
Published: June 2024

Background

Although exclusive breastfeeding is recommended for the first six months of life, research suggests that breastfeeding initiation rates and duration among Indigenous communities differ from this recommendation. Qualitative studies point to a variety of factors influencing infant feeding decisions; however, there has been no collective review of this literature published to date. Therefore, the objective of this scoping review was to identify and summarize the qualitative literature regarding Indigenous infant feeding experiences within Canada, the United States, Australia, and Aotearoa.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses- Scoping Reviews and the Joanna Briggs Institute Guidelines, in October 2020, Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for relevant papers focusing on Indigenous infant feeding experiences. Screening and full-text review was completed by two independent reviewers. A grey literature search was also conducted using country-specific Google searches and targeted website searching. The protocol is registered with the Open Science Framework and published in BMJ Open.

Results

Forty-six papers from the five databases and grey literature searches were included in the final review and extraction. There were 18 papers from Canada, 11 papers in the US, 9 studies in Australia and 8 studies conducted in Aotearoa. We identified the following themes describing infant feeding experiences through qualitative analysis: colonization, culture and traditionality, social perceptions, family, professional influences, environment, cultural safety, survivance, establishing breastfeeding, autonomy, infant feeding knowledge, and milk substitutes, with family and culture having the most influence on infant feeding experiences based on frequency of themes.

Conclusions

This review highlights key influencers of Indigenous caregivers’ infant feeding experiences, which are often situated within complex social and environmental contexts with the role of family and culture as essential in supporting caregivers. There is a need for long-term follow-up studies that partner with communities to support sustainable policy and program changes that support infant and maternal health.
Parental acceptance of Silver Diamine Fluoride in two lower-middle-income countries: Iran and Tajikistan
Authors: Sabbagh Sedigheh , Moradi Sara , Haghi-Ashtiani Gelareh , Bakhtibekov Gulomnabi , Manaseki-Holland Samira , Ravaghi Vahid
Published: June 2024

Background

Using Silver Diamine Fluoride (SDF) may be an effective public health approach for managing dental caries in children. Parental acceptance of SDF has rarely been investigated in low-income and middle-income countries (LMICs). The aim of this study was to evaluate parental acceptance of SDF to manage dental caries in children aged 2–12 in Iran and Tajikistan.

Methods

This cross-sectional study was conducted in the Kurdistan province of Iran and Khatlon region of Tajikistan, 2022–2023. Parents watched a video about SDF and its weaknesses and strengths as compared to conventional approaches before completing the questionnaire. We also reported Prevalence Ratios with 95% confidence intervals for the relationship between parental acceptance and associated demographic factors as well as dental attitude and experience.

Results

Participants were 245 and 160 parents in Iran and Tajikistan, respectively. In both countries, a majority (Iran: 61.6%, Tajikistan: 77.9%) accepted SDF over conventional treatments for all primary teeth. The majority also accepted SDF only for posterior permanent teeth (Iran: 73.5%, Tajikistan: 78.7%). Black discoloration was the main reason for rejecting SDF. Overall, demographic factors and dental experience and attitude were not significantly associated with SDF acceptance.

Conclusions

SDF was widely accepted by Iranian and Tajik parents. Establishing parental acceptance of SDF is an important step toward its application in LMICs where inexpensive solutions are needed.
Oropharyngeal stenosis in patient with oral submucous fibrosis: a case report with 8-year follow-up
Authors: Al-Aroomi Maged Ali , Chen Jie , Jiang Canhua
Published: June 2024

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture.
Palliative care education in undergraduate medical and nursing programs in Colombia: a cross-sectional analysis
Authors: Sánchez-Cárdenas Miguel Antonio , Tibaquirá Camila Andrea Navarro , Mantilla-Manosalva Nidia , Fonseca David Andrade , Morales Alexandra Marin , Delgado Martha Ximena León
Published: June 2024

Background

The number of people suffering from chronic diseases requiring palliative care (PC) is increasing rapidly. Therefore, PC teaching in undergraduate health science programs is necessary to improve primary PC based on international recommendations and available scientific evidence.

Methods

A descriptive cross-sectional study was conducted. Active undergraduate medical and nursing programs that were approved by the Colombian Ministry of Education and integrated PC teaching into their curricula were included in the study. The total sample consisted of 48 programs: 31 nursing and 17 medical programs.

Results

PC competencies are distributed throughout the curriculum in 41.67% of programs, in elective courses in 31.25%, and in mandatory courses in 27.08% of the programs. The average PC teaching hours is 81 for nursing and 57.6 for medicine. PC clinical rotations are not offered in 75% of the programs. For undergraduate nursing programs, the most frequent competencies taught are the definition and history of PC and identifying common symptoms associated with advanced disease. In undergraduate medicine, the most common competencies are pharmacological and non-pharmacological pain management and identification of PC needs.

Conclusions

PC teaching in undergraduate health science programs mainly addresses the conceptual and theoretical aspects of PC, which are part of the competencies present throughout the programs’ curricula. Low availability of PC clinical rotations was identified. Future studies should assess whether the low availability of clinical rotations in PC limits the ability of students to develop the practical competencies necessary to provide quality PC.

Trial registration

Not applicable.
Online-based survey on health literacy and health situation of school principals and vice principals in Pakistan during the COVID-19 pandemic
Authors: Zakar Rubeena , Shahzad Ruhma , Tariq Fizza , Zakar Muhammad Zakria , Dadaczynski Kevin , Okan Orkan , Fischer Florian
Published: June 2024

Background

This study aimed to evaluate health literacy and general health status among school principals and vice principals in Pakistan, (1) to identify work-related factors associated with them, and (2) to determine their association with physical and mental health, particularly in the context of the COVID-19 pandemic.

Methods

An online-based cross-sectional survey was conducted among 350 school principals and vice principals in Punjab province, Pakistan. The study was conducted under the COVID Global Health Literacy Network. Data related to socio-demographic characteristics, health literacy, general health status, chronic illnesses and impairment, well-being, psychosomatic complaints, and emotional exhaustion were collected. We applied bivariate analyses as well as binary and multivariable logistic regression analyses.

Results

Over half of the respondents (66.6%) had sufficient levels of health literacy. A good general health status was reported by 80.3%. One of the strongest predictors of health literacy and general health status was school position (principals vs. vice principals). Additionally, those with sufficient health literacy were less likely to have frequent emotional exhaustion; while those having good general health status were less likely to report low well-being, frequent emotional exhaustion, and psychosomatic complaints. The study also found that females were less likely to have a good general health status (OR  0.45) and were more likely to have frequent emotional exhaustion (OR  1.75) as well as psychosomatic complaints (OR  1.94) than males.

Conclusions

Limited health literacy in school leaders requires interventions for better decision-making on health matters, emphasizing the need for targeted training programs.
Time synchronization between parietal–frontocentral connectivity with MRCP and gait in post-stroke bipedal tasks
Authors: Phang Chun-Ren , Su Kai-Hsiang , Cheng Yuan-Yang , Chen Chia-Hsin , Ko Li-Wei
Published: June 2024

Background

In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery outcomes. However, the interrelationship between FC, MRCP, gait activities, and bipedal distinguishability have yet to be investigated.

Methods

Ten participants were equipped with EEG devices and inertial measurement units (IMUs) while performing lower limb motor preparation (MP) and motor execution (ME) tasks. MRCP, FCs, and bipedal distinguishability were extracted from the EEG signals, while the change in knee degree during the ME phase was calculated from the gait data. FCs were analyzed with pairwise Pearson’s correlation, and the brain-wide FC was fed into support vector machine (SVM) for bipedal classification.

Results

Parietal–frontocentral connectivity (PFCC) dysconnection and MRCP desynchronization were related to the MP and ME phases, respectively. Hemiplegic limb movement exhibited higher PFCC strength than nonhemiplegic limb movement. Bipedal classification had a short-lived peak of 75.1% in the pre-movement phase. These results contribute to a better understanding of the neurophysiological functions during motor tasks, with respect to localized MRCP and nonlocalized FC activities. The difference in PFCCs between both limbs could be a marker to understand the motor function of the brain of post-stroke patients.

Conclusions

In this study, we discovered that PFCCs are temporally dependent on lower limb gait movement and MRCP. The PFCCs are also related to the lower limb motor performance of post-stroke patients. The detection of motor intentions allows the development of bipedal brain-controlled exoskeletons for lower limb active rehabilitation.
Evaluation of diagnostic techniques for early detection of heartworm in experimentally infected dogs: identification of Dirofilaria immitis-derived microRNA in the initial 28 weeks post-inoculation
Authors: Murillo Daniel Felipe Barrantes , Campbell Elyssa J. , Moorhead Andrew R. , Wang Chengming
Published: June 2024

Background

Dirofilaria immitis, commonly known as heartworm (HW), is a parasitic nematode transmitted by various mosquito species, leading to heartworm disease (HWD) in dogs. Diagnosis of HW typically involves antigen or microfilariae detection, or visualization of adult worms through imaging or post mortem examination. Polymerase chain reaction (PCR) and micro RNA (miRNA) detection have been explored for HW diagnosis.

Methods

Three dogs, previously experimentally infected with HW, underwent blood sampling every 4 weeks for 7 months. Samples were assessed for antigen presence after heat treatment, PCR amplification, and microfilaria examination using Giemsa-stained thick smears. Additionally, whole blood aliquots underwent miRNA deep sequencing and bioinformatic analysis.

Results

Heartworm antigen was detectable after heat treatment at 20 weeks post-inoculation and via PCR at 24 weeks, with microfilariae observed in peripheral blood smears at 28 weeks. However, deep miRNA sequencing revealed that the miRNA candidate sequences are not consistently expressed before 28 weeks of infection.

Conclusions

While ancillary molecular methods such as PCR and miRNA sequencing may be less effective than antigen detection for detecting immature larval stages in an early stage of infection, our experimental findings demonstrate that circulating miRNAs can still be detected in 28 weeks post-infection.

Graphical Abstract
Digital in-line holographic microscopy for label-free identification and tracking of biological cells
Authors: Kim Jihwan , Lee Sang Joon
Published: June 2024

Digital in-line holographic microscopy (DIHM) is a non-invasive, real-time, label-free technique that captures three-dimensional (3D) positional, orientational, and morphological information from digital holographic images of living biological cells. Unlike conventional microscopies, the DIHM technique enables precise measurements of dynamic behaviors exhibited by living cells within a 3D volume. This review outlines the fundamental principles and comprehensive digital image processing procedures employed in DIHM-based cell tracking methods. In addition, recent applications of DIHM technique for label-free identification and digital tracking of various motile biological cells, including human blood cells, spermatozoa, diseased cells, and unicellular microorganisms, are thoroughly examined. Leveraging artificial intelligence has significantly enhanced both the speed and accuracy of digital image processing for cell tracking and identification. The quantitative data on cell morphology and dynamics captured by DIHM can effectively elucidate the underlying mechanisms governing various microbial behaviors and contribute to the accumulation of diagnostic databases and the development of clinical treatments.
Minimally invasive elective gastrectomy after preoperative chemotherapy in a patient with frailty who presented with locally far advanced-stage gastric cancer: a case report
Authors: Shirakami Naoto , Kanaji Shingo , Shimada Atsushi , Mukoyama Tomosuke , Sawada Ryuichiro , Harada Hitoshi , Tanaka Tomonori , Urakawa Naoki , Goto Hironobu , Hasegawa Hiroshi , Yamashita Kimihiro , Matsuda Takeru , Kakeji Yoshihiro
Published: June 2024

Background

Herein, we report a case of gastric antrum cancer with multiple invasions to other organs that was completely cured with laparoscopic distal gastrectomy after preoperative chemotherapy in a patient with poor general condition.

Case presentation

An 80-year-old male patient was diagnosed with anemia during follow-up for cerebral lacunar infarction at another hospital. He was diagnosed with advanced-stage gastric antrum cancer and was referred to our hospital. On esophagogastroduodenoscopy, type 2 advanced-stage gastric cancer was detected at the greater curvature of the antrum, and the biopsy results revealed tubular adenocarcinoma. Contrast-enhanced computed tomography scan revealed multiple invasions to other organs, thick gastric wall with contrast effect, and superior mesenteric vein tumor thrombus. However, there was no evidence of distant metastasis on positron emission tomography/computed tomography scan. The clinical diagnosis was stage IVA gastric cancer. Pancreatoduodenectomy with portal vein resection could be important at this point. However, preoperative chemotherapy with S-1 and oxaliplatin was administered instead of performing extended surgery because the patient had poor general condition (performance status score of 3). The patient received three cycles of preoperative chemotherapy at the hospital along with rehabilitation and nutritional management with oral nutritional supplements. After treatment, the performance status score of the patient improved from 3 to 1. Furthermore, in terms of clinical therapeutic effect, the patient achieved partial response. Hence, laparoscopic distal gastrectomy with D2 lymph node dissection and partial transverse colectomy was performed. After surgery, the patient was admitted for oral intake on postoperative day 6 and was discharged on postoperative day 21. Based on the histopathological examination, gastric cancer had disappeared, and there were no evident malignant findings. Therefore, gastric cancer was classified as grade 3 according to the histological treatment efficacy criteria. The patient did not present with recurrence at 2 years after surgery.

Conclusions

By actively administering preoperative chemotherapy, minimally invasive radical surgery with maximum preservation of the surrounding organs can be performed for locally far advanced-stage gastric cancer in older patients with poor general condition.
Charting the cascade of physical activities: implications for reducing sitting time and obesity in children
Authors: Esmaeilzadeh Samad , Hakala Pirjo , Berg Päivi , Salmon Jo , Rinne Tiina , Pesola Arto J
Published: June 2024

Objective

Traditional intensity-based physical activity measures and variable-centered statistics may not fully capture the complex associations between sitting time, physical activity, and obesity indices. This study investigates the associations between device-measured sitting, standing and different modes of physical activity (i.e., slow walking, brisk-walking, cycling and high-intensity activity) and measured body mass index (BMI) in children using person-based latent profile analyses and Partial Least Squared-structural equation modeling (PLS-SEM).

Methods

A total of 344 children (11.5 ± 0.81 years, boys n = 139) wore a triaxial accelerometer (Fibion®) on their thigh for eight days, and their weight and height were measured at school. Latent profile analysis formed profiles including BMI, total sitting time, and physical activities, and their associations were further studied with PLS-SEM.

Results

The latent profile analysis indicates that high levels of physical activity always coincide with low sitting time. Both normal weight and overweight/obesity can coexist with low physical activity and prolonged sitting. The PLS-SEM results highlight a cascade-like sequence in the relationship between various types of physical activity, sitting time, and BMI. This sequence begins with light-intensity activities, such as standing, progresses to higher-intensity activities, and ultimately through reduced sitting time (sample mean= -0.01; effect size = 0.0001; p = 0.02), mediates a decline in BMI (sample mean= -0.06; effect size = 0.0036; p = 0.01). The most positive effects on sitting time and BMI occur when this pattern is adhered to consistently, suggesting that omitting steps could negatively impact the associations.

Conclusion

These findings suggest that persuading children to increase physical activity incrementally, starting from low-intensity activities such as standing and slow walking to activity types with higher intensities, possibly influence BMI by mediating reduced sitting time. This approach is particularly inclusive for overweight and obese children, taking into account the potential challenges they may encounter when performing activity types with high intensity. These cross-sectional associations need to be verified with longitudinal and experimental designs.
Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma.
Authors: Qiu Haibo , Zhou Zhi-wei , Zhou Ye , Chen Jie , Wan Xiangbin , Li Ning , Tao Kaixiong , Li Yong , Wu Xin , Chen Zi , Liu Lihui , Yang Chen , Men Lichuang , Wang Hengbang , Liang Eric , Wang Cunlin , Jiang Lixin , Yang Dajun , Zhai Yifan , Xu Rui-Hua
Published: June 2024

11502

Background: SDH-deficient GIST is a rare type of GIST, mainly observed in the stomach of children and adolescents or young adults < 30 years of age. No active targeted therapies have been identified in this subset of GIST. Olverembatinib, approved in China for treatment of patients with chronic myeloid leukemia, has shown promising clinical efficacy in SDH-deficient GIST. We report here updated efficacy data in SDH-deficient GIST and preliminary efficacy data in paraganglioma, which is an SDH-deficient–related tumor. Methods: The aim of this study was to evaluate the safety and efficacy (per RECIST v1.1) of olverembatinib in patients with TKI-resistant SDH-deficient GIST and other solid tumors. Olverembatinib was administered orally once every other day (QOD) in 28-day cycles. Results: As of December 27, 2023, 26 patients with SDH-deficient GIST (confirmed by IHC) had received ≥ 1 dose of olverembatinib (median [range] age, 30 [13-56] years), and 25 had received 1 to 4 TKIs (42.3% of patients, ≥ 3; Table 1). Olverembatinib was administered QOD in doses ranging from 30 to 50 mg (30 mg [n = 6]; 40 mg [n = 14]; 50 mg [n = 6]). The median (range) treatment duration was 15.6 (1.8-42.3) months. A total of 6 of 26patients experienced partial response (PR) as the best response. A further 18 patients had stable disease (SD) lasting > 4 cycles. The clinical benefit rate (CBR; complete response [CR] + PR + SD > 4 cycles) was hence 92.3% (24/26) and the longest treatment duration was 40 months. After a median follow-up of 17.0 (4.1-57.5) months, the median progression-free survival (PFS) was 25.7 months (12.1-not reached [NR]). Among the 6 patients with paraganglioma enrolled in this study, best responses were observed in 5, with SD lasting > 4 cycles (CBR, 83.3%), and the median PFS was 8.25 (1.87-NR) months. The adverse event profile was the same as previously reported (Qiu H et al, J Clin Oncol 41:11540), with no newly emergent safety issues observed. Conclusions: Olverembatinib was well tolerated. The CBR exceeded 90%, and the estimated median PFS was significantly prolonged, indicating potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GIST. Clinical trial registration: NCT03594422; internal study identifier: SJ-0003. Clinical trial information: NCT03594422 .[Table: see text]
A phase II study of anlotinib and an anti-PDL1 antibody in patients with alveolar soft part sarcoma: Results of expansion cohorts.
Authors: Tan Zhichao , Wu Yan , Fan Zhengfu , Liu Jiayong , Gao Tian , Bai Chujie , Xue Ruifeng , Li Shu , Zhang Lu , Wang Xinyu
Published: June 2024

11515

Background: The combination of the anti-angiogenesis tyrosine kinase inhibitor (TKI), anlotinib, with the anti-programmed death-ligand 1 (PDL1) antibody (TQB2450) demonstrated commendable antitumor efficacy in a phase II clinical trial for pan-sarcoma patients, particularly within the alveolar soft part sarcoma (ASPS) cohorts (Liu et al., 2022, PMID: 35675031). An expansion of the ASPS cohort has been underway since 2019. Herein, we present the observed efficacy within this ASPS-specific expansion cohort. Methods: ASPS patients naïve to TKIs or immunotherapy received TQB2450 (1200mg) intravenously on day 1, in combination with oral administration of anlotinib (12mg) from day 1 to 14, repeated every 3 weeks. The primary endpoint was best objective response rate (ORR, per RECIST v1.1). Secondary endpoints comprised median progression free survival (PFS), median overall survival (OS), duration of response (DOR), and adverse events (AEs). Formalin-fixed paraffin-embedded (FFPE) slides were taken for immunohistochemistry and examined for lymphocyte marker expression. Results: Twenty-nine patients were enrolled in the phase II trial. The median age was 29 years (range: 19-46), with female 48.3%. A subset of patients (20.7%) had undergone prior lines of chemotherapy. Twenty-eight patients were evaluable for efficacy (one withdrew). The ORR for evaluable patients reached 79.3%, characterized by 3 complete responses and 20 partial responses. The median PFS (months) was not reached (95%CI: 20.7, not-reached). The median DOR (months) for responders was not reached (95%CI: 18.0, not-reached). No mortalities occurred during the follow-up. Treatment demonstrated favorable tolerability, with predominant grade 1 and 2 AEs. Thirteen patients (44.83%) experienced grade ≥3 AEs, principally hypertriglyceridemia (13.79%), lipase elevation (6.90%), amylase elevation (3.45%), and hypertension (3.45%). A detailed analysis of the tumor microenvironment in 7 patients, including 3 good responders and 4 poor responders, revealed a significant discrepancy in the presence of tertiary lymphoid structures (TLS) between the two groups (refer to Table). Conclusions: The combination of anlotinib and TQB2450 exhibits promising efficacy in ASPS patients, markedly enhancing ORR and extending PFS with favorable tolerability. Notably, TLS emerges as a potential predictive indicator of immunotherapeutic efficacy in ASPS. Clinical trial information: CTR20190938 . [Table: see text]
Use of histologic and immunologic factors in sarcoma to predict response rates to immunotherapy.
Authors: Lee Alex Qiang , Hao Clara , Pan Minggui , Ganjoo Kristen N. , Bui Nam
Published: June 2024

11569

Background: Sarcomas are rare mesenchymal neoplasms with substantial histologic and tumor microenvironment heterogeneity, leading to varied treatment responses, particularly to immunotherapy. Because of the heterogeneity of response rates and high risk of disease progression, further determinations of which patients are most likely to benefit from immunotherapy are crucial. In this study, we aim to characterize factors associated with response to immune checkpoint inhibitors (ICIs). Methods: 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care were analyzed. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtype, ICI regimen, tumor mutational burden (TMB), and PD-L1. Results: The most common histologic subtypes analyzed were leiomyosarcoma (LMS, n=48), liposarcoma (LPS, n=27), and undifferentiated pleomorphic sarcoma (UPS, n=18). Immunotherapy regimens primarily consisted of ipilimumab and nivolumab (77.8%), pembrolizumab (14.8%), and nivolumab monotherapy (6.0%). Median OS for all patients was 12.8 months. Response rates across all sarcomas were complete response (CR) 3.2%, partial response (PR) 13.4%, stable disease (SD) 30%, and progression of disease (PD) 53.2%. The ORR was higher in patients treated with pembrolizumab (21.9%) than with ipilimumab and nivolumab (14.3%). The histologic subtypes with the highest ORR were Kaposi sarcoma (KS, 66.7%), alveolar soft part sarcoma (ASPS, 50%), angiosarcoma (AS, 33.3%), myxofibrosarcoma (MFS, 28.6%), and UPS (27.8%). The subtypes with the lowest ORR were osteosarcoma (OS, 0%), synovial sarcoma (SS, 0%), and LPS (3.7%). The subtypes with the highest median PFS were KS (median not reached, NR), ASPS (NR), MFS (27.3 mo), and UPS (11.3 mo). Overall TMB (n=118) was low with a median of 2 mut/MB. Only 4 patients (3.3%) had a TMB ≥10, with a corresponding ORR of 25%. Overall PD-L1 expression (n=93 with TPS or CPS) was also low with a median of 0%. However, positive PD-L1 (n=36/93, > 1%) was associated with better ORR (27.8%, 10/36). 16.2% of patients discontinued immunotherapy due to autoimmune adverse effects; the most common were pneumonitis (18.4%), colitis (15.8%), arthritis (13.2%), and hepatitis (13.2%). Conclusions: Response and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the best ORR and longest PFS while OS, SS, and LPS were the lowest. TMB ≥10 and PD-L1 expression also correlated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs. [Table: see text]
Development and validation of a deep learning–based cardiovascular disease risk prediction model for long-term breast cancer survivors.
Authors: Oh Sinae , Shim Jae Yong
Published: June 2024

12023

Background: Previous efforts in predicting cardiotoxicity risk among patients with breast cancer have mostly focused on preventing and monitoring of cardiovascular complications during cancer therapy. We aimed to develop prediction models for the risk of chronic cardiovascular complications in breast cancer survivors during long-term follow-up. Methods: We used the Korean National Health Insurance Service databases between 2005 and 2021, including 5,131 5-year female breast cancer survivors diagnosed in 2006. The study cohort was randomized on a 4:1 ratio into the derivation and validation cohort. The primary outcome was the occurrence of major adverse cardiovascular events (MACEs), a composite of acute myocardial infarction, congestive heart failure, and stroke, at any time before the final follow-up at 10 years. We used the Cox proportional hazards model (CoxPH) with the least absolute shrinkage and selection operator penalty to determine the order of clinical factors based on their absolute coefficient value. We developed a deep learning survival model (DeepSurv) and compared its performance with traditional models such as CoxPH and random survival forest (RSF) using the same dataset. Model performance was assessed by discrimination and calibration. Results: During the 48054.1 person-years of follow-up, 325 (6.3%) patients developed MACE. We identified 18 relevant clinical factors without zero coefficients, including age, hypertension, atrial fibrillation, stroke, diabetes mellitus, myocardial infarction, household income, congestive heart failure, hemoglobin level, systolic blood pressure, peripheral arterial occlusive disease, chronic kidney disease, aromatase inhibitor use, alcohol consumption, cigarette smoking, tamoxifen use, radiotherapy, and total cholesterol level. The CoxPH, RSF, and DeepSurv model yielded time-dependent concordance index values of 0.713, 0.721, and 0.729, respectively, in the validation cohort. all models demonstrated good integrated Brier scores of 0.031 or less. Conclusions: We developed and validated a deep learning survival model that predict MACEs in individual 5-year breast cancer survivors, incorporating both conventional and breast cancer treatment-related cardiovascular risk factors, and demonstrated good calibration and discrimination. These models can assist breast cancer survivors and clinicians in optimally selecting risk-reducing strategies based on individual MACEs risk.
The impact of glucagon-like peptide 1 agonists on anthracycline or human epidermal growth factor receptor 2 inhibitor-associated cardiotoxicity in patients with breast cancer and diabetes mellitus.
Authors: Chiang Cho Han , Chang Yu-Cheng , Tang Zhiting , See Xin Ya , Chi Kuan-Yu , Chang Yu , Chiang Cho Hung , Ghamari Azin , Curtis Lauren Mary , Neilan Tomas G.
Published: June 2024

12026

Background: Anthracyclines or human epidermal growth factor receptor 2 (HER-2) inhibitors are associated with the potential for major adverse cardiovascular outcomes (MACE) among patients with breast cancer. Diabetes mellitus (DM) further increases the risk of MACE. Glucagon-like peptide 1 agonists (GLP1a) have been shown to improve MACE in the non-cancer population; however, there are no data testing whether GLP1a reduce the risk for MACE associated with anthracyclines or HER-2 inhibitors. Therefore, we hypothesized that GLP1a may decrease the risk for MACE among patients with breast cancer and DM receiving anthracycline or HER-2 inhibitors. Methods: We performed a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult breast cancer patients with type 2 DM who were treated with an anthracycline or HER-2 inhibitor therapy. We matched patients receiving a GLP1a with patients receiving non-GLP1a second-line diabetes medication based on the following variables: age, sex, pre-existing cardiac disease, the use of radiation, metastatic disease, cancer therapy, underlying comorbidities, and use of cardiovascular and diabetes medications. The primary outcome of interest, MACE, was defined as a composite of heart failure, myocardial infarction, and atrial fibrillation/flutter. Secondary outcomes included a composite of heart failure hospitalization and incident heart failure. Safety outcomes included all-cause mortality within 5 years of therapy initiation. Results: We matched 724 patients receiving a GLP1a treatment with patients receiving non-GLP1a treatment. The median age was 60 years for both cohorts. The prevalence of hypertension (81%), metastatic disease (61%), and radiation therapy (42%) was similar between cohorts, as was the use of anthracyclines and HER-2 inhibitors. In Cox proportional hazard analyses, the group receiving GLP1a treatment was associated with a lower risk of MACE (Hazard ratio (HR), 0.59 [95% CI: 0.41-0.86]), and heart failure hospitalization (HR, 0.56 [95% CI: 0.37-0.83]), and all-cause mortality (HR, 0.67 [95% CI: 0.48-0.93]) compared with non-GLP1a. Conclusions: GLP1a were associated with a reduction in major adverse cardiovascular events, incident heart failure and heart failure hospitalization, and all-cause mortality among anthracycline or HER-2 inhibitor-treated patients with breast cancer and DM. [Table: see text]
Experience of young patients with cancer discussing cannabis with their providers.
Authors: Baral Amrit , Diggs Bria-Necole A. , Marrakchi El Fellah Ranya , Hernandez Ortega Nicolas , Islam Jessica Yasmine , Camacho-Rivera Marlene , Penedo Frank J. , Vidot Denise Christina
Published: June 2024

12061

Background: Although cannabis use among cancer patients to manage cancer treatment-related symptoms continues to grow, little is known about patterns in patient-provider communication regarding cannabis use. We examined demographic differences in cannabis communication among cancer patients and providers at a National Cancer Institute designated cancer center. Methods: We used data of 495 cancer patients via an anonymous electronic survey administered at the University of Miami via REDCap. Participants with consent to contact notations in their electronic medical record were recruited via phone calls and personalized messages in their MyUCHART portal. Self-reported responses on patients' disclosure of cannabis use to healthcare providers and their comfort on discussing cannabis with cancer doctors were analyzed. Age was categorized as: 20-39y, 40-59y and ≥60y. Chi-squared/Fisher’s exact tests and logistic regression analyses were conducted adjusting for age, sex, and ethnicity. Results: The sample was 51.8% male, 39.4% Hispanic, and mean age was 45.9y (SD=15.1) (41.1% were between 20-39y); 43.8% were undergoing treatment and 35.4% were in follow-up/finished treatment. Almost half (45.5%) reported current (past 30-days) cannabis use. Younger (20-39y) patients had higher prevalence of not disclosing cannabis use than older (>60y) patients (36.8% vs 23.9% p<0.01). There were no sex or ethnicity statistical differences. Majority (67.7%) of current cannabis users reported comfort discussing cannabis use with their provider. However, among individuals aged 20-39y, 40.8% reported feeling uncomfortable discussing cannabis with their cancer doctor. In the 40-59y age group, 21.0% expressed discomfort, while only 5.6% of those over 60 years reported similar unease. After adjusting for age, sex, and ethnicity, newly diagnosed cancer patients had lower odds (aOR:0.41, 95% CI:0.17-0.99) of feeling comfortable discussing cannabis use compared to those in follow-up/finished treatment group. Conclusions: Age was a significant factor in disclosing cannabis use to healthcare providers, with disparities noted by age group. These insights highlight the importance of considering age-related factors and treatment status when addressing cannabis use discussions within the oncology setting.