bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of SKA Complex Is Associated With Poor Prognosis in Gliomas
Authors: Yu Shoukai
Published: January 2022

The spindle and kinetochore-associated complex is composed of three members: SKA1, SKA2, and SKA3. It is necessary for stabilizing spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis. The SKA complex is associated with poor prognosis in several human cancers. However, the role of SKA complex in rare malignant diseases, such as gliomas, has not been fully investigated. We investigated several databases, including Oncomine, UALCAN, and cBioPortal to explore the expression profile and prognostic significance of SKA complex in patients with gliomas. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathways were used to analyze the potential enriched pathways. The genes co-expressed with SKA complex were identified and used for developing a protein-protein interaction (PPI) network using the STRING database. We found a significant overexpression of the mRNA levels of SKA1, SKA2, and SKA3 in patients with glioma patients. Higher expression of SKA1 and SKA3, but not SKA2, was significantly correlated with shorter overall survival of patients with glioma. In glioma, SKA complex was found to be involved in nuclear division, chromosome segregation, and DNA replication. The results of PPI network identified 10 hub genes (CCNB2, UBE2C, BUB1B, TPX2, CCNA2, CCNB1, MELK, TOP2A, PBK, and KIF11), all of which were overexpressed and negatively associated with prognosis of patients with glioma. In conclusion, our study sheds new insights into the biological role and prognostic significance of SKA complex in glioma.
Hemodynamic Differences Between Basilar Artery Fenestration and Normal Vertebrobasilar Artery: A Pilot Study
Authors: Dong Jia , Mei Yuqian , Bai Xuesong , Tong Xinyu , Dmytriw Adam A. , Yang Bin , Wang Tao , Patel Aman B. , Yang Xiaoyan , Li Mengyue , Yang Renjie , Chen Duanduan , Jiao Liqun
Published: January 2022

Background: Basilar artery fenestration has been proposed as a contributor to ischemic stroke, as unique flow patterns induced by fenestration may be related to thrombus formation or insufficiency. This study aimed to evaluate the hemodynamics of basilar artery fenestration (BAF) using computational fluid dynamics (CFD).

Methods: Patients with BAF and normal vertebrobasilar system were recruited and separately evaluated using CFD. Specific geometric vascular models were reconstructed based on 3D-rotational angiography (3D-RA). Patients were divided into the BAF group and control group (i.e., patients with the normal vertebrobasilar system). Hemodynamic and geometric variables were calculated and compared between groups using Student's t-test or Wilcoxon rank-sum test.

Results: Overall, 24 patients were included, with 12 patients each in the BAF group and the control group. The BAF group had a significantly smaller basilar artery diameter than the control group (3.1 ± 0.51 vs. 3.76 ± 0.4, p = 0.002). Compared to the control group, the BAF group had higher values of maxOSI (median, 0.3 vs. 0.09, p = 0.028), TAWSSG (median, 983.42 vs. 565.39, p = 0.038) in the flow confluence, higher SAR-TAWSSG in bifurcation (median, 70.22 vs. 27.65, p = 0.002) and higher SAR-TAWSSG in basilar artery (median, 48.75 vs. 16.17, p < 0.001) of the vertebrobasilar artery.

Conclusions: This pilot study suggested that hemodynamic differences between BAF and normal vertebrobasilar artery across multiple shear flow parameters. The disturbed flow in the BAF may increase the risk of thrombus formation, plaque instability, and subsequent ischemic cerebrovascular events. These should be confirmed by future studies.
Minimally Invasive Surgery in Patients With Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Authors: Hou Duanlu , Lu Ying , Wu Danhong , Tang Yuping , Dong Qiang
Published: January 2022

Background: Minimally invasive surgery for intracerebral hemorrhage (ICH) has been evaluated in clinical trials. Although meta-analyses on this topic have been performed in the past, recent trials have added important information to the results of the comparison. However, little work has been done to compare the effect of MIS and conventional treatment on patient prognosis, especially mortality.

Methods: PubMed, EMBASE, Web of Science, Ovid, China National Knowledge Infrastructure, and ClinicalTrials.gov were searched on May 1, 2021, for randomized controlled trials of MIS for spontaneous ICH. The primary outcome was defined as death at follow-up, while the secondary outcome was defined as death in different comparisons between MIS and craniotomy (CT) or medication (Me).

Results: The initial search yielded 12 high-quality randomized controlled trials involving 2,100 patients. We analyzed the odds ratios (ORs) for MIS compared with conventional treatment, including Me and conventional CT. The OR and confidence intervals (CIs) of the primary and secondary outcomes were 0.62 (0.45–0.85) for MIS vs. conventional treatment. We also conducted subgroup analyses and found that the ORs and CIs for MIS compared with that of conventional treatment in the short-term follow-up were 0.58 (0.42–0.80), and, in the long-term follow-up, was 0.67 (0.46–0.98); and found that ORs were 0.68 (0.48–0.98) for MIS vs. CT and 0.57 (0.41–0.79) for MIS vs. Me.

Conclusions: This meta-analysis demonstrates that certain patients with ICH benefit in short- and long-term follow-up from MIS over other treatments, including open surgery and conventional Me.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/.
Elevated Glucose-Potassium Ratio Predicts Preoperative Rebleeding in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Wang Jiayin , Feng Qiangqiang , Zhang Yinbin , Qiu Weizhi , Gao Hongzhi
Published: January 2022

Introduction: Recent reports revealed that higher serum glucose-potassium ratio (GPR) levels at admission were significantly associated with poor outcomes at 3 months following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the association between GPR and the risk of rebleeding following aSAH.

Methods: This single-center retrospective study of patients with aSAH was conducted in our hospital between January 2008 and December 2020. Patients meeting the inclusion criteria were divided into the rebleed group and the non-rebleed group. Univariate and multivariate analyses were implemented to assess the association between risk factors of rebleeding and outcomes.

Results: A total of 1,367 patients experiencing aSAH, 744 patients who met the entry criteria in the study [mean age (54.89 ± 11.30) years; 60.50% female patients], of whom 45 (6.05%) developed rebleeding. The patients in the rebleed group had significantly higher GPR levels than those of patients without rebleeding [2.13 (1.56–3.20) vs. 1.49 (1.23–1.87); p < 0.001]. Multivariable analysis revealed that higher mFisher grade and GPR were associated with rebleeding [mFisher grade, odds ratios (OR) 0.361, 95% CI 0.166–0.783, p = 0.01; GPR, OR 0.254, 95% CI 0.13–0.495, p < 0.001]. The receiver operating characteristics (ROCs) analysis described that the suitable cut-off value for GPR as a predictor for rebleeding in patients with aSAH was determined as 2.09 (the area under the curve [AUC] was 0.729, 95% CI 0.696–0.761, p < 0.0001; the sensitivity was 53.33%, and the specificity was 83.98%). Pearson correlation analysis showed a significant positive correlation between GPR and mFisher grade, between GPR and Hunt–Hess grade (mFisher grade r = 0.4271, OR 0.1824, 95% CI 0.3665–0.4842, p < 0.001; Hunt–Hess grade r = 0.4248, OR 0.1836, 95% CI 0.3697–0.4854, p < 0.001). The patients in the poor outcome had significantly higher GPR levels than those of patients in the good outcome [1.87 (1.53–2.42) vs. 1.45 (1.20–1.80); p < 0.001]. Multivariable analysis demonstrated that GPR was an independent predictor for poor prognosis. The AUC of GPR was 0.709 (95% CI 0.675–0.741; p < 0.0001) (sensitivity = 77.70%; specificity = 55.54%) for poor prognosis.

Conclusion: Higher preoperative serum GPR level was associated with Hunt–Hess grade, mFisher grade, rebleeding, and unfunctional outcome, and that they predicted preoperative rebleeding and the 90-days outcome of non-diabetic patients with aSAH, who had potentially relevant clinical implications in patients with aSAH.
Leukoaraiosis and Gray Matter Volume Alteration in Older Adults: The PROOF Study
Authors: Celle Sébastien , Boutet Claire , Annweiler Cédric , Ceresetti Romain , Pichot Vincent , Barthélémy Jean-Claude , Roche Frédéric
Published: January 2022

Background and Purpose: Leukoaraiosis, also called white matter hyperintensities (WMH), is frequently encountered in the brain of older adults. During aging, gray matter structure is also highly affected. WMH or gray matter defects are commonly associated with a higher prevalence of mild cognitive impairment. However, little is known about the relationship between WMH and gray matter. Our aim was thus to explore the relationship between leukoaraiosis severity and gray matter volume in a cohort of healthy older adults.

Methods: Leukoaraiosis was rated in participants from the PROOF cohort using the Fazekas scale. Voxel-based morphometry was performed on brain scans to examine the potential link between WMH and changes of local brain volume. A neuropsychological evaluation including attentional, executive, and memory tests was also performed to explore cognition.

Results: Out of 315 75-year-old subjects, 228 had punctuate foci of leukoaraiosis and 62 had begun the confluence of foci. Leukoaraiosis was associated with a decrease of gray matter in the middle temporal gyrus, in the right medial frontal gyrus, and in the left parahippocampal gyrus. It was also associated with decreased performances in memory recall, executive functioning, and depression.

Conclusion: In a population of healthy older adults, leukoaraiosis was associated with gray matter defects and reduced cognitive performance. Controlling vascular risk factors and detecting early cerebrovascular disease may prevent, at least in part, dementia onset and progression.
Temporal and Isoform-Specific Expression of CTBP2 Is Evolutionarily Conserved Between the Developing Chick and Human Retina
Authors: Gage Elizabeth , Agarwal Devansh , Chenault Calvin , Washington-Brown Kameron , Szvetecz Sarah , Jahan Nusrat , Wang Zixiao , Jones Melissa K. , Zack Donald J. , Enke Ray A. , Wahlin Karl J.
Published: January 2022

Complex transcriptional gene regulation allows for multifaceted isoform production during retinogenesis, and novel isoforms transcribed from a single locus can have unlimited potential to code for diverse proteins with different functions. In this study, we explored the CTBP2/RIBEYE gene locus and its unique repertoire of transcripts that are conserved among vertebrates. We studied the transcriptional coregulator (CTBP2) and ribbon synapse-specific structural protein (RIBEYE) in the chicken retina by performing comprehensive histochemical and sequencing analyses to pinpoint cell and developmental stage-specific expression of CTBP2/RIBEYE in the developing chicken retina. We demonstrated that CTBP2 is widely expressed in retinal progenitors beginning in early retinogenesis but becomes limited to GABAergic amacrine cells in the mature retina. Inversely, RIBEYE is initially epigenetically silenced in progenitors and later expressed in photoreceptor and bipolar cells where they localize to ribbon synapses. Finally, we compared CTBP2/RIBEYE regulation in the developing human retina using a pluripotent stem cell derived retinal organoid culture system. These analyses demonstrate that similar regulation of the CTBP2/RIBEYE locus during chick and human retinal development is regulated by different members of the K50 homeodomain transcription factor family.
Encapsulation of Docosahexaenoic Acid Oil Substantially Improves the Oxylipin Profile of Rat Tissues
Authors: Wang Jun , Ossemond Jordane , Le Gouar Yann , Boissel Françoise , Dupont Didier , Pédrono Frédérique
Published: January 2022

Docosahexaenoic acid (DHA) is a major n-3 polyunsaturated fatty acid (PUFA) particularly involved in cognitive and cardiovascular functions. Due to the high unsaturation index, its dietary intake form has been considered to improve oxidation status and to favor bioaccessibility and bioavailability as well. This study aimed at investigating the effect of DHA encapsulated with natural whey protein. DHA was dietary provided as triacylglycerols to achieve 2.3% over total fatty acids. It was daily supplied to weanling rats for four weeks in omelet as food matrix, consecutively to a 6-hour fasting. First, when DHA oil was encapsulated, consumption of chow diet was enhanced leading to promote animal growth. Second, the brain exhibited a high accretion of 22.8% DHA, which was not improved by dietary supplementation of DHA. Encapsulation of DHA oil did not greatly affect the fatty acid proportions in tissues, but remarkably modified the profile of oxidized metabolites of fatty acids in plasma, heart, and even brain. Specific oxylipins derived from DHA were upgraded, such as Protectin Dx in heart and 14-HDoHE in brain, whereas those generated from n-6 PUFAs were mainly mitigated. This effect did not result from oxylipins measured in DHA oil since DHA and EPA derivatives were undetected after food processing. Collectively, these data suggested that dietary encapsulation of DHA oil triggered a more efficient absorption of DHA, the metabolism of which was enhanced more than its own accretion in our experimental conditions. Incorporating DHA oil in functional food may finally improve the global health status by generating precursors of protectins and maresins.
Therapeutic Role of Retroperitoneal Lymphadenectomy in 170 Patients With Ovarian Clear Cell Cancer
Authors: Gao Wen , Shi Peipei , Sun Haiyan , Xi Meili , Tang Wenbin , Yin Sheng , Zhang Jiarong
Published: January 2022

Introduction

We evaluated the therapeutic role of retroperitoneal lymphadenectomy in patients with ovarian clear cell cancer (OCCC).

Materials and Methods

We retrospectively reviewed 170 OCCC patients diagnosed at two hospitals in China between April 2010 and August 2020. Clinical data were abstracted, and patients were followed until February 2021. Patients were divided into retroperitoneal lymphadenectomy and no lymphadenectomy groups. The Kaplan–Meier method was used to compare progression-free (PFS) and overall survival (OS) between the two groups. Statistical differences were determined by the log-rank test. The COX proportional hazards regression model was applied to identify predictors of tumor recurrence.

Results

The median age was 52 years; 90 (52.9%) and 80 (47.1%) patients were diagnosed as early and advanced stage, respectively. Clinically positive and negative nodes was found in 40 (23.5%) and 119 (70.0%) patients, respectively. Of all the 170 patients, 124 (72.9%) patients underwent retroperitoneal lymphadenectomy, while 46 (27.1%) did not. The estimated 2-year PFS and 5-year OS rates were 71.4% and 65.9% in the lymphadenectomy group, and 72.0% and 73.7% in no lymphadenectomy group (p = 0.566 and 0.669, respectively). There was also no difference in survival between the two groups when subgroup analysis was performed stratified by early and advanced stage, or in patients with clinically negative nodes. Multivariate analysis showed that retroperitoneal lymphadenectomy were not an independent predictor of tumor recurrence.

Conclusion

Retroperitoneal lymphadenectomy provided no survival benefit in patients diagnosed with OCCC. A prospective clinical trial is needed to confirm the present results.
Case Report: Favorable Response and Manageable Toxicity to the Combination of Camrelizumab, Oxaliplatin, and Oral S-1 in a Patient With Advanced Epstein–Barr Virus-Associated Gastric Cancer
Authors: Lv Wanrui , Cheng Ke , Li Xiaofen , Feng Lusi , Li Hancong , Li Jia , Chang Chen , Cao Dan
Published: January 2022

Some pertinent studies have demonstrated that Epstein–Barr virus-associated gastric cancer (EBVaGC) patients showed a favorable clinical outcome to immunotherapy and Epstein–Barr virus (EBV)-positive status might be a potential biomarker for immunotherapy in gastric cancer (GC). However, knowledge of given exposure to EBVaGC to the first-line immunotherapy is largely inadequate. Moreover, whether camrelizumab can be as effective as other PD-1 inhibitors in the treatment of advanced EBVaGC has not been reported. We report a case of advanced EBVaGC patient with a positive expression of PD-L1, enriched PD-L1+CD68+macrophages, and high TMB who had a long-term partial response and manageable toxicity to the combined approach of camrelizumab (a novel PD-1 inhibitor) and oxaliplatin plus oral S-1 (SOX). As the first-line treatment of advanced EBVaGC patients, camrelizumab combined with SOX regimen may provide a novel combined approach with favorable response and manageable safety. Combination of multiple biomarkers could have a higher effective predictive capacity to immunotherapy. Integrated treatment (chemo-immunotherapy and radiotherapy) might be the optimal strategy for patients with oligometastasis. It deserves prospective research to further validate the efficacy.
Screening and Identification of Novel Potential Biomarkers for Breast Cancer Brain Metastases
Authors: Wang Lulu , Zeng Dan , Wang Qi , Liu Li , Lu Tao , Gao Yan
Published: January 2022

Brain metastases represent a major cause of mortality among patients with breast cancer, and few effective targeted treatment options are currently available. Development of new biomarkers and therapeutic targets for breast cancer brain metastases (BCBM) is therefore urgently needed. In this study, we compared the gene expression profiles of the brain metastatic cell line MDA-MB-231-BR (231-BR) and its parental MDA-MB-231, and identified a total of 84 genes in the primary screening through a series of bioinformatic analyses, including construction of protein-protein interaction (PPI) networks by STRING database, identification of hub genes by applying of MCODE and Cytohubba algorithms, identification of leading-edge subsets of Gene Set Enrichment Analysis (GSEA), and identification of most up-regulated genes. Eight genes were identified as candidate genes due to their elevated expression in brain metastatic 231-BR cells and prognostic values in patients with BCBM. Then we knocked down the eight individual candidate genes in 231-BR cells and evaluated their impact on cell migration through a wound-healing assay, and four of them (KRT19, FKBP10, GSK3B and SPANXB1) were finally identified as key genes. Furthermore, the expression of individual key genes showed a correlation with the infiltration of major immune cells in the brain tumor microenvironment (TME) as analyzed by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), suggesting possible roles of them in regulation of the tumor immune response in TME. Therefore, the present work may provide new potential biomarkers for BCBM. Additionally, using GSEA, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis, we determined the top enriched cellular functions or pathways in 231-BR cells, which may help better understand the biology governing the development and progression of BCBM.
Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations
Authors: Qu Rirong , Ye Fan , Tu Dehao , Cai Yixin , Fu Xiangning
Published: January 2022

Background

With the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.

Methods

Medical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.

Results

A total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions >20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.

Conclusions

A high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.
Targeting KRAS in Lung Cancer Beyond KRAS G12C Inhibitors: The Immune Regulatory Role of KRAS and Novel Therapeutic Strategies
Authors: Cucurull Marc , Notario Lucia , Sanchez-Cespedes Montse , Hierro Cinta , Estival Anna , Carcereny Enric , Saigí Maria
Published: January 2022

Approximately 20% of lung adenocarcinomas harbor KRAS mutations, an oncogene that drives tumorigenesis and has the ability to alter the immune system and the tumor immune microenvironment. While KRAS was considered “undruggable” for decades, specific KRAS G12C covalent inhibitors have recently emerged, although their promising results are limited to a subset of patients. Several other drugs targeting KRAS activation and downstream signaling pathways are currently under investigation in early-phase clinical trials. In addition, KRAS mutations can co-exist with other mutations in significant genes in cancer (e.g., STK11 and KEAP1) which induces tumor heterogeneity and promotes different responses to therapies. This review describes the molecular characterization of KRAS mutant lung cancers from a biologic perspective to its clinical implications. We aim to summarize the tumor heterogeneity of KRAS mutant lung cancers and its immune-regulatory role, to report the efficacy achieved with current immunotherapies, and to overview the therapeutic approaches targeting KRAS mutations besides KRAS G12C inhibitors.
Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer
Authors: Itami Jun , Murakami Naoya , Watanabe Miho , Sekii Shuhei , Kasamatsu Takahiro , Kato Shingo , Hirowatari Hisako , Ikushima Hitoshi , Ando Ken , Ohno Tatsuya , Okamoto Hiroyuki , Okuma Kae , Igaki Hiroshi
Published: January 2022

High-dose-rate brachytherapy by remote afterloading is now performed under three-dimensional image guidance by CT or MRI. Three-dimensional image-guided brachytherapy in cervical cancer disclosed that the traditional intracavitary brachytherapy by Manchester method cannot deliver an adequate dose to the large tumor with resulting local recurrence. To improve the local control rate, combined interstitial and intracavitary (hybrid) brachytherapy can increase the dose to the large parametrial involvement without increasing the dose to the rectum and bladder. Whether hybrid brachytherapy can be performed safely on a multi-institutional basis remains to be studied. From 2015, phase I/II study of hybrid brachytherapy was launched in Japan, and it was revealed that hybrid brachytherapy can be performed safely and with a high quality of radiation dose distribution in a multi-institutional study. In Japan, the number of patients undergoing hybrid brachytherapy in cervical cancer is rapidly rising. Education and clinical trial are very important to establish hybrid brachytherapy in the management of cervical cancer.
FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification
Authors: Wei Shouyi , Lin Haibo , Choi J. Isabelle , Press Robert H. , Lazarev Stanislav , Kabarriti Rafi , Hajj Carla , Hasan Shaakir , Chhabra Arpit M. , Simone Charles B. , Kang Minglei
Published: January 2022

Purpose

This work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.

Methods and Materials

An in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).

Results

All plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/swas increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/sof select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.

Conclusion

This is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.
Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice
Authors: Wang Zhenqing , Xie Yun , Chen Haicheng , Yao Jiahui , Lv Linyan , Li Yanqing , Deng Chunhua , Zhang Min , Sun Xiangzhou , Liu Guihua
Published: January 2022

Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Oxidative stress (OS) is one of the main causes of male infertility, which is characterized by excessive reactive oxygen species (ROS) or lack of antioxidants. Meanwhile, it is reported that oxidative stress plays an important role in the spermatogenic impairment in Inner mitochondrial membrane peptidase 2-like (Immp2l) mutant mice. In this study, we focused on the potential mechanism of Guilingji in protecting the spermatogenic functions in Immp2l mutant mice. The results revealed that Immp2l mutant mice exhibit impaired spermatogenesis and histology shows seminiferous tubules with reduced spermatogenic cells. After administration of Guilingji [150 mg/kg per day intragastric gavage], however, alleviated spermatogenesis impairment and reversed testis histopathological damage and reduced apoptosis. What’s more, western blotting and the levels of redox classic markers revealed that Guilingji can markedly reduce reactive oxygen species. Moreover, Guilingji treatment led to inhibition of the phosphorylation of mitogen-activated protein kinase (MAPK), regulated apoptosis in the cells. In summary, Guilingji can improve spermatogenesis in Immp2l mutant mice by regulating oxidation-antioxidant balance and MAPK pathway. Our data suggests that Guilingji may be a promising and effective antioxidant candidate for the treatment of male infertility.
Effects of Running on Sand vs. Stable Ground on Kinetics and Muscle Activities in Individuals With Over-Pronated Feet
Authors: Jafarnezhadgero AmirAli , Amirzadeh Nasrin , Fatollahi Amir , Siahkouhian Marefat , Oliveira Anderson S. , Granacher Urs
Published: January 2022

Background: In terms of physiological and biomechanical characteristics, over-pronation of the feet has been associated with distinct muscle recruitment patterns and ground reaction forces during running.

Objective: The aim of this study was to evaluate the effects of running on sand vs. stable ground on ground-reaction-forces (GRFs) and electromyographic (EMG) activity of lower limb muscles in individuals with over-pronated feet (OPF) compared with healthy controls.

Methods: Thirty-three OPF individuals and 33 controls ran at preferred speed and in randomized-order over level-ground and sand. A force-plate was embedded in an 18-m runway to collect GRFs. Muscle activities were recorded using an EMG-system. Data were adjusted for surface-related differences in running speed.

Results: Running on sand resulted in lower speed compared with stable ground running (p < 0.001; d = 0.83). Results demonstrated that running on sand produced higher tibialis anterior activity (p = 0.024; d = 0.28). Also, findings indicated larger loading rates (p = 0.004; d = 0.72) and greater vastus medialis (p < 0.001; d = 0.89) and rectus femoris (p = 0.001; d = 0.61) activities in OPF individuals. Controls but not OPF showed significantly lower gluteus-medius activity (p = 0.022; d = 0.63) when running on sand.

Conclusion: Running on sand resulted in lower running speed and higher tibialis anterior activity during the loading phase. This may indicate alterations in neuromuscular demands in the distal part of the lower limbs when running on sand. In OPF individuals, higher loading rates together with greater quadriceps activity may constitute a proximal compensatory mechanism for distal surface instability.
The Cell Wall Proteome of Marchantia polymorpha Reveals Specificities Compared to Those of Flowering Plants
Authors: Kolkas Hasan , Balliau Thierry , Chourré Josiane , Zivy Michel , Canut Hervé , Jamet Elisabeth
Published: January 2022

Primary plant cell walls are composite extracellular structures composed of three major classes of polysaccharides (pectins, hemicelluloses, and cellulose) and of proteins. The cell wall proteins (CWPs) play multiple roles during plant development and in response to environmental stresses by remodeling the polysaccharide and protein networks and acting in signaling processes. To date, the cell wall proteome has been mostly described in flowering plants and has revealed the diversity of the CWP families. In this article, we describe the cell wall proteome of an early divergent plant, Marchantia polymorpha, a Bryophyte which belong to one of the first plant species colonizing lands. It has been possible to identify 410 different CWPs from three development stages of the haploid gametophyte and they could be classified in the same functional classes as the CWPs of flowering plants. This result underlied the ability of M. polymorpha to sustain cell wall dynamics. However, some specificities of the M. polymorpha cell wall proteome could be highlighted, in particular the importance of oxido-reductases such as class III peroxidases and polyphenol oxidases, D-mannose binding lectins, and dirigent-like proteins. These proteins families could be related to the presence of specific compounds in the M. polymorpha cell walls, like mannans or phenolics. This work paves the way for functional studies to unravel the role of CWPs during M. polymorpha development and in response to environmental cues.
Kinase Function of Brassinosteroid Receptor Specified by Two Allosterically Regulated Subdomains
Authors: Ali Khawar , Li Wenjuan , Qin Yaopeng , Wang Shanshan , Feng Lijie , Wei Qiang , Bai Qunwei , Zheng Bowen , Li Guishuang , Ren Hongyan , Wu Guang
Published: January 2022

Plants acquire the ability to adapt to the environment using transmembrane receptor-like kinases (RLKs) to sense the challenges from their surroundings and respond appropriately. RLKs perceive a variety of ligands through their variable extracellular domains (ECDs) that activate the highly conserved intracellular kinase domains (KDs) to control distinct biological functions through a well-developed downstream signaling cascade. A new study has emerged that brassinosteroid-insensitive 1 (BRI1) family and excess microsporocytes 1 (EMS1) but not GASSHO1 (GSO1) and other RLKs control distinct biological functions through the same signaling pathway, raising a question how the signaling pathway represented by BRI1 is specified. Here, we confirm that BRI1-KD is not functionally replaceable by GSO1-KD since the chimeric BRI1-GSO1 cannot rescue bri1 mutants. We then identify two subdomains S1 and S2. BRI1 with its S1 and S2 substituted by that of GSO1 cannot rescue bri1 mutants. Conversely, chimeric BRI1-GSO1 with its S1 and S2 substituted by that of BRI1 can rescue bri1 mutants, suggesting that S1 and S2 are the sufficient requirements to specify the signaling function of BRI1. Consequently, all the other subdomains in the KD of BRI1 are functionally replaceable by that of GSO1 although the in vitro kinase activities vary after replacements, suggesting their functional robustness and mutational plasticity with diverse kinase activity. Interestingly, S1 contains αC-β4 loop as an allosteric hotspot and S2 includes kinase activation loop, proposedly regulating kinase activities. Further analysis reveals that this specific function requires β4 and β5 in addition to αC-β4 loop in S1. We, therefore, suggest that BRI1 specifies its kinase function through an allosteric regulation of these two subdomains to control its distinct biological functions, providing a new insight into the kinase evolution.
Harnessing Large-Scale Herbarium Image Datasets Through Representation Learning
Authors: Walker Barnaby E. , Tucker Allan , Nicolson Nicky
Published: January 2022

The mobilization of large-scale datasets of specimen images and metadata through herbarium digitization provide a rich environment for the application and development of machine learning techniques. However, limited access to computational resources and uneven progress in digitization, especially for small herbaria, still present barriers to the wide adoption of these new technologies. Using deep learning to extract representations of herbarium specimens useful for a wide variety of applications, so-called “representation learning,” could help remove these barriers. Despite its recent popularity for camera trap and natural world images, representation learning is not yet as popular for herbarium specimen images. We investigated the potential of representation learning with specimen images by building three neural networks using a publicly available dataset of over 2 million specimen images spanning multiple continents and institutions. We compared the extracted representations and tested their performance in application tasks relevant to research carried out with herbarium specimens. We found a triplet network, a type of neural network that learns distances between images, produced representations that transferred the best across all applications investigated. Our results demonstrate that it is possible to learn representations of specimen images useful in different applications, and we identify some further steps that we believe are necessary for representation learning to harness the rich information held in the worlds’ herbaria.
Self-Efficacy Beliefs of University Students: Examining Factor Validity and Measurement Invariance of the New Academic Self-Efficacy Scale
Authors: Greco Andrea , Annovazzi Chiara , Palena Nicola , Camussi Elisabetta , Rossi Germano , Steca Patrizia
Published: January 2022

Academic self-efficacy beliefs influence students’ academic and career choices, as well as motivational factors and learning strategies promoting effective academic success. Nevertheless, few studies have focused on the academic self-efficacy of university students in comparison to students at other levels. Furthermore, extant measures present several limitations. The first aim of this study was to develop a reliable and valid scale assessing university students’ self-efficacy beliefs in managing academic tasks. The second aim was to investigate differences in academic self-efficacy due to gender, years of enrollment, and student status. The study involved 831 students (age M = 21.09 years; SD = 1.34 years; 66.3% women) enrolled in undergraduate programs. Indicators of academic experiences and performance (i.e., number of exams passed and average exam rating) were collected. A new scale measuring students’ academic self-efficacy beliefs was administered. Results from a preliminary Exploratory Factor Analysis were consistently supported by findings from a Confirmatory Factor Analysis. Multigroup CFA supported the presence of measurement invariance. Analyses revealed that the new scale has eight factors: “Planning Academic Activities,” “Learning Strategies,” “Information Retrieval,” “Working in Groups,” “Management of Relationships with Teachers,” “Managing Lessons,” “Stress Management,” and “Thesis Work.” Self-efficacy dimensions showed significant relations with academic experiences and students’ performance indicators, as well as differences due to gender, years of enrollment, and student status. Findings are discussed in terms of practical implications for the implementation of intervention programs aimed at fostering self-efficacy beliefs and academic success.
The Effects of Employees’ Perceived Intrinsic Motivation on Knowledge Sharing and Creative Self-Efficacy
Authors: Sun Yu , Hong Jon-Chao , Ye Jian-Hong
Published: January 2022

Knowledge sharing is the major driving force to maintain enterprises’ competitiveness. This study extends the current knowledge-sharing research by considering knowledge sharing as comprising four types: automatic response, rational reflection, ridiculed reflection, and deprived reflection, based on Kahneman’s (2011) types of system thinking. Drawing on the motivation-action-outcome model, this study explored how individuals’ intrinsic motivation can guide the action of knowledge sharing and reflect the outcome of creative self-efficacy in intelligent transportation jobs. By snowball sampling in intelligent transportation companies, a total of 232 effective questionnaires were collected, and confirmatory factor analysis with structural equation modeling was performed. The research results showed that: intrinsic motivation was positively related to the four types of knowledge sharing tendencies; automatic response was not significantly related to creative self-efficacy; rational reflection was positively associated with creative self-efficacy; but ridiculed and deprived reflection were negatively related to creative self-efficacy. These results can be applied to encourage employees to practice rational reflection in knowledge sharing to enhance their creative self-efficacy in intelligent transportation jobs.
“Caring for a Crisis”: Care and Control in Community Mental Health
Authors: Muusse Christien , Kroon Hans , Mulder Cornelis Lambert , Pols Jeannette
Published: January 2022

In the debate on coercion in psychiatry, care and control are often juxtaposed. In this article we argue that this dichotomy is not useful to describe the more complex ways service users, care professionals and the specific care setting interrelate in a community mental health team (CMHT). Using the ethnographic approach of empirical ethics, we contrast the ways in which control and care go together in situations of a psychiatric crisis in two CMHT's: one in Trieste (Italy) and one in Utrecht (the Netherlands). The Dutch and Italian CMHT's are interesting to compare, because they differ with regard to the way community care is organized, the amount of coercive measures, the number of psychiatric beds, and the fact that Trieste applies an open door policy in all care settings. Contrasting the two teams can teach us how in situations of psychiatric crisis control and care interrelate in different choreographies. We use the term choreography as a metaphor to encapsulate the idea of a crisis situation as a set of coordinated actions from different actors in time and space. This provides two choreographies of handling a crisis in different ways. We argue that applying a strict boundary between care and control hinders the use of the relationship between caregiver and patient in care.
The Present State of Existential Interventions Within Palliative Care
Authors: Terao Takeshi , Satoh Moriaki
Published: January 2022

Existential psychotherapy is rooted in the European tradition of existential philosophy. Existential philosophers include Husserl and Heidegger, who were German, and Camus, Sartre, de Beauvoir, and Merleau-Ponty, who were French. Their works contain existentially ultimate themes such as death, freedom, meaninglessness, and isolation. Based on their knowledge of existential philosophy, Binswanger, Frankl, and Boss developed the earlier existential psychotherapies such as Dasein-analysis and Logotherapy, while May, Laing, Yalom, May, and Wong started later existential psychotherapies in the British and American culture. Focusing on patients with advanced cancer and/or terminal care, we found nine types of existential psychotherapies which were investigated using randomized controlled trials (RCTs): Meaning-Centered Group Psychotherapy (MCGP), Individual Meaning-Centered Psychotherapy (IMCP), Meaning-Making intervention (MMi), Meaning of Life Intervention, Managing Cancer and Living Meaningfully (CALM), Hope Intervention, Cognitive and Existential Intervention, Dignity Therapy, and Life-Review Interviews, from 19 relevant RCTs. All deal with death, meaninglessness, isolation, and freedom. Particularly, MCGP, IMCP, MMi, Meaning of Life intervention, and CALM emphasize finding and/or making meaning in the individual's life. The effects on existential or spiritual well-being were confirmed in MCGP, IMCP, Meaning of Life intervention, and Life-Review intervention although the number of studies were very few. In the other interventions, there were heterogenous findings and again the number of studies was very small. Further studies are required to investigate the effects of existential psychotherapy on patients with advanced cancer.
No Alteration Between Intrinsic Connectivity Networks by a Pilot Study on Localized Exposure to the Fourth-Generation Wireless Communication Signals
Authors: Yang Lei , Liu Qingmeng , Zhou Yu , Wang Xing , Wu Tongning , Chen Zhiye
Published: January 2022

Neurophysiological effect of human exposure to radiofrequency signals has attracted considerable attention, which was claimed to have an association with a series of clinical symptoms. A few investigations have been conducted on alteration of brain functions, yet no known research focused on intrinsic connectivity networks, an attribute that may relate to some behavioral functions. To investigate the exposure effect on functional connectivity between intrinsic connectivity networks, we conducted experiments with seventeen participants experiencing localized head exposure to real and sham time-division long-term evolution signal for 30 min. The resting-state functional magnetic resonance imaging data were collected before and after exposure, respectively. Group-level independent component analysis was used to decompose networks of interest. Three states were clustered, which can reflect different cognitive conditions. Dynamic connectivity as well as conventional connectivity between networks per state were computed and followed by paired sample t-tests. Results showed that there was no statistical difference in static or dynamic functional network connectivity in both real and sham exposure conditions, and pointed out that the impact of short-term electromagnetic exposure was undetected at the ICNs level. The specific brain parcellations and metrics used in the study may lead to different results on brain modulation.
Obesity Accelerates Age-Associated Defects in Human B Cells Through a Metabolic Reprogramming Induced by the Fatty Acid Palmitate
Authors: Frasca Daniela , Romero Maria , Garcia Denisse , Diaz Alain , Blomberg Bonnie B.
Published: January 2022

We have measured the secretion of autoimmune antibodies in plasma samples and in culture supernatants of blood-derived B cells from four groups of individuals: young lean (YL), elderly lean (EL), young obese (YO) and elderly obese (EO). We found secretion comparable in YO and EL individuals, suggesting that obesity accelerates age-associated defects in circulating B cells. To define at least one possible molecular pathway involved, we used an in vitro model in which B cells from YL and EL individuals have been stimulated with the Fatty Acid (FA) palmitate, the most common saturated FA in the human body. The rationale to use palmitate is that there is a chronic increase in circulating levels of palmitate, due to increased spontaneous lipolysis occurring during aging and obesity, and this may induce autoimmune B cells. Results herein show that in vitro incubation of B cells from YL and EL individuals with the FA palmitate induces mRNA expression of T-bet, the transcription factor for autoimmune antibodies, as well as secretion of autoimmune IgG antibodies, with B cells from YL individuals looking similar to B cells from EL individuals, confirming our initial hypothesis. The generation of autoimmune B cells in the presence of the FA palmitate was found to be associated with a metabolic reprogramming of B cells from both YL and EL individuals. These results altogether show the critical role of the FA palmitate in inducing human B cell immunosenescence and show for the first time the importance of metabolic pathways in this process.
The Sexual and Reproductive Health Context of an Internally Displaced Persons' Camp in Northeastern Nigeria: Narratives of Girls and Young Women
Authors: Marlow Heather M. , Kunnuji Michael , Esiet Adenike , Bukoye Funsho , Izugbara Chimaraoke
Published: January 2022

In humanitarian settings, ~35 million girls and young women of reproductive age (15–24) are in urgent need of sexual and reproductive health (SRH) information and services. Young women and girls in humanitarian contexts are particularly vulnerable to unwanted pregnancies, unsafe abortion, gender-based violence, and early and forced marriage. We sought to understand girls' and young women's experiences with unwanted pregnancy, abortion, contraception, sexually transmitted infections (STIs), gender-based violence (GBV), and forced marriage in an IDP camp in Northeastern Nigeria. We conducted 25 in-depth interviews with girls aged 15–19 (N = 13; 8 single and 5 married) and young women aged 20–24 (N = 12; 3 single and 9 married). All interviews were audiotaped, transcribed, translated, computer recorded and coded for analysis. The participants in our study fled from and witnessed violence to arrive in the IDP camp with little material support. Lack of necessities, especially food, has driven many to sex in exchange for goods or into forced marriages. This, in turn, leads to increased unwanted pregnancies and unsafe abortions. Participants had limited knowledge about contraception, and some information about SRH services available in the camp, but overall, knowledge and utilization of SRH services was low.