bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlations between Personality Traits, Patient‐Reported Outcome, and Chronic Prostatitis Symptoms in Men with Different Premature Ejaculation Syndromes
Authors: Gao Jingjing , Gao Rui , Liu Xi , Li Chengfu , Gao Pan , Du Junhua , Zhang Xiansheng
Published: April 2022

Although the personality traits (PT), patient‐reported outcome (PRO), and chronic prostatitis (CP) symptoms in premature ejaculation (PE) have been evaluated, there was no study to assess their correlations in men with different PE syndromes. The purpose of this study was to assess the correlations between the PT, PRO, and CP symptoms in men with different PE syndromes. Between January 2019 and January 2021, a cross‐sectional field study was conducted in our andrology clinic. Men with the complaints of PE were divided into lifelong PE (LPE), acquired PE (APE), variable PE (VPE), and subjective PE (SPE). All subjects were required to complete a verbal questionnaire with the PRO, National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), and Temperament and Character Inventory (TCI‐R). Finally, 479 men with the complaints of PE and 365 without the complaints of PE were enrolled. The incidence of PE syndromes in PE complaint group was as follows: LPE 16.70%, APE 48.85%, VPE 11.27%, and SPE 23.17%. Mean ages in PE complaint group were 42.53 ± 12.25 years. In the PE complaint group, the novelty seeking (NS) scores were strongest correlated with the personal distress and quality of life (QOL). The harm avoidance (HA) scores were strongest correlated with the severity of PE and pain syndromes. The self‐transcendence (ST) scores were strongest correlated with the satisfaction with sexual intercourse and QOL. In addition, strongest association between the total scores of NIH‐CPSI and the NS or ST scores was also found in the APE group. The HA scores were also strongest correlated with the total scores of NIH‐CPSI in SPE. Strongest association between the total scores of NIH‐CPSI and the NS/TI or ST/CI scores was also found in the APE group. The HA/TI scores were also strongest correlated with the total scores of NIH‐CPSI in SPE.
A Study of an IT-Assisted Higher Education Model Based on Distributed Hardware-Assisted Tracking Intervention
Authors: Liu Haijun
Published: April 2022

This paper presents an in-depth study and analysis of the model of higher education using distributed hardware tracking intervention of information technology. The MEC-based dynamic adaptive video stream caching technology model is proposed. The model dynamically adjusts the bit rate by referring to the broadband estimation and cache occupancy data to ensure users have a smooth experience effect. Simulation results show that the model has fewer transcoding times and generates lower latency than the traditional model, which is suitable for dual-teacher classroom scenarios and further improves the quality of the user’s video viewing experience. The model uses an edge cloud collaborative architecture to migrate the rendering technology to an edge server closer to the user side, enabling real-time interaction, computation, and rendering, reducing the time of data transmission as well as computation time. According to the blended learning-based adaptive intervention model, three rounds of teaching practice are conducted to validate the effectiveness of the intervention model in terms of both student process performance and outcome performance, thereby improving learning adaptability and improving learning effect. Teachers’ teaching has a significant impact on learning motivation (

β
=
0.311

,

p
<
0.01

), which in turn affects learning adaptability. Teachers use scientific teaching methods to stimulate students’ learning motivation, mobilize enthusiasm, and improve learning adaptability. Under the communication topology of the system as a directed graph, a multi-intelligent system dynamic model with grouping is established; i.e., the intragroup intelligence has the same dynamics but is different between groups, and all system dynamics are unknown. The proposed novel policy iterative algorithm is used to learn the optimal control protocol and achieve optimal consistency control. The effectiveness of the algorithm is demonstrated by the simulation experimental results. The simulation results show that the model has lower latency and energy consumption compared to the cloud rendering model, which is suitable for the safety education classroom scenario and solves the outstanding problems of network connection rate and cloud service latency.
The Association between Platelet Glycocalicin and High Microsatellite Instability in Colorectal Cancer
Authors: Liu Zeng-yao , Jia Qing-chun , Wang Wen , Liu Yu-xi , Wang Rui-tao , Li Jia-yu
Published: April 2022

Background. Elevated platelet volume is the risk factor for the development and poor overall survival of colorectal cancer (CRC) patients. Both microsatellite status and platelet glycoprotein Ibα (GPIbα) are related to platelet volume in CRC patients. This study aimed to investigate platelet GPIbα ectodomain (termed glycocalicin) levels among CRC patients and the association between the glycocalicin levels and microsatellite status in CRC. Methods. The clinical and laboratory data of 430 CRC patients between January 2018 and December 2018 in Harbin Medical University Cancer Hospital were collected. The microsatellite status was determined with a polymerase chain reaction. The participants were separated into high microsatellite instability (MSI-H) and microsatellite stable (MSS) groups according to microsatellite status. The glycocalicin levels were measured with an enzyme-linked immunosorbent assay, and the cut-off point was determined with the receiver-operating characteristics curve. The clinical and pathological characteristics were collected via electronic medical records. Logistic regression was used to explore the association between glycocalicin and microsatellite status. Results. Among the 430 CRC patients enrolled, 64 patients (14.9%) were identified as MSI-H and others as MSS CRC. Glycocalicin levels were significantly reduced in patients with MSI-H than those with MSS. After controlling for potential confounders, logistic regression analysis revealed that glycocalicin levels were independently associated with MSI-H CRC. Conclusions. Reduced glycocalicin levels are associated with the MSI-H subtype of CRC. Further research is needed to elucidate the mechanisms of the association between glycocalicin and MSI-H in CRC patients.
An Intelligent Hough Transform with Jaya of Multipopulation Cooperation for Diameter Estimation of Red-Hot Workpiece
Authors: Zhang Xinyu , Chen Ke , Mu Rong , Yang Yanxi , Li Jinghua
Published: April 2022

Diameter is a critical metric during producing circular workpieces, but it is always challenging to measure accurately due to the existence of noise. The intelligent Hough transform with Jaya (IHTJ) is developed to solve this issue recently. However, it suffers from some disadvantages including unsatisfactory accuracy and convergence rate caused by the problem of trapping into local optimization in the case of inaccurate priori knowledge. In this paper, an IHTJ of multipopulation cooperation (IHTJMC) is proposed to overcome these disadvantages. Firstly, we analyse the problem of IHTJ in the diameter measurement. Secondly, a ring structure of the multipopulation cooperation is designed. In this structure, the whole population is divided into several subpopulations which evolve independently all the time. This can ensure a few best and worst solutions guide the evolution of the whole population at the same time. Then, we propose a migration strategy to finish the cooperation among the different subpopulations, which selects a few individuals from each subpopulation randomly, and exchange them with each other. This strategy can make the different subpopulations share the information among the entire population and improve the global search ability. Finally, three experiments are introduced to test the effectiveness of the IHTJMC. The experimental results demonstrate that the IHTJMC can restrain the problem of falling into local optimization significantly. Compared with the existing methods, it has superior accuracy and robustness for the diameter measurement of a circular workpiece which is heated to red state.
Structure, Dynamics, and Impact of Replication Stress–Induced Structural Variants in Hepatocellular Carcinoma
Authors: Bayard Quentin , Cordier Pierre , Péneau Camille , Imbeaud Sandrine , Hirsch Theo Z. , Renault Victor , Nault Jean-Charles , Blanc Jean-Frédéric , Calderaro Julien , Desdouets Chantal , Zucman-Rossi Jessica , Letouzé Eric
Published: April 2022

Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole-genome sequencing (WGS) to explore in depth the nature of structural variants (SV) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC displayed frequent intra-chromosomal and interchromosomal templated insertion cycles (TIC), likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are proximal to one another within the 3D genome. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induced continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics, and consequences of SV accumulation in tumors with oncogene-induced replication stress.

Significance:

Optical mapping and whole-genome sequencing integration unravels a unique signature of replication stress–induced structural variants that drive genomic evolution and the acquisition of driver events in CCN-HCC.
Distinct Immune Gene Programs Associated with Host Tumor Immunity, Neoadjuvant Chemotherapy, and Chemoimmunotherapy in Resectable NSCLC
Authors: Rocha Pedro , Zhang Jiexin , Laza-Briviesca Raquel , Cruz-Bermúdez Alberto , Bota-Rabassedas Neus , Sanchez-Espiridon Beatriz , Yoshimura Katsuhiro , Behrens Carmen , Lu Wei , Tang Ximing , Pataer Apar , Parra Edwin R. , Haymaker Cara , Fujimoto Junya , Swisher Stephen G. , Heymach John V. , Gibbons Don L. , Lee J. Jack , Sepesi Boris , Cascone Tina , Solis Luisa M. , Provencio Mariano , Wistuba Ignacio I. , Kadara Humam
Published: April 2022

Purpose:

Our understanding of the immunopathology of resectable non–small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.

Experimental Design:

Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.

Results:

PD-L1–positive tumors exhibited increased signature scores for various lymphoid and myeloid cell subsets (P < 0.05). TIME phenotypes exhibited disparate frequencies by stage, PD-L1 expression, and mutational burden. Inflamed and PD-L1+/TILs+ NSCLCs displayed overall significantly heightened levels of immune signatures, with the excluded group representing an intermediate state. A cytotoxic T-cell signature was associated with favorable survival in neoadjuvant chemotherapy–treated NSCLCs (P < 0.05). Pathologic response to chemoimmunotherapy was positively associated with higher expression of genes involved in immune activation, chemotaxis, as well as T and natural killer cells (P < 0.05 for all). Among the three cohorts, chemoimmunotherapy-treated NSCLCs exhibited the highest scores for various immune cell subsets including T effector and B cells (P < 0.05).

Conclusions:

Our findings highlight immune gene programs that may underlie host tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in resectable NSCLC.
Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma
Authors: Nayak Lakshmi , Standifer Nathan , Dietrich Jorg , Clarke Jennifer L. , Dunn Gavin P. , Lim Michael , Cloughesy Timothy , Gan Hui K. , Flagg Elizabeth , George Elizabeth , Gaffey Sarah , Hayden Julia , Holcroft Christina , Wen Patrick Y. , Macri Mary , Park Andrew J. , Ricciardi Toni , Ryan Aileen , Schwarzenberger Paul , Venhaus Ralph , Reyes Melissa de los , Durham Nicholas M. , Creasy Todd , Huang Raymond Y. , Kaley Thomas , Reardon David A.
Published: April 2022

Purpose:

PD-L1 is upregulated in glioblastoma and supports immunosuppression. We evaluated PD-L1 blockade with durvalumab among glioblastoma cohorts and investigated potential biomarkers.

Patients and Methods:

MGMT unmethylated newly diagnosed patients received radiotherapy plus durvalumab (cohort A; n = 40). Bevacizumab-naïve, recurrent patients received durvalumab alone (cohort B; n = 31) or in combination with standard bevacizumab (cohort B2; n = 33) or low-dose bevacizumab (cohort B3; n = 33). Bevacizumab-refractory patients received durvalumab plus bevacizumab (cohort C; n = 22). Primary endpoints were: OS-12 (A), PFS-6 (B, B2, B3), and OS-6 (C). Exploratory biomarkers included: a systematic, quantitative, and phenotypic evaluation of circulating immune cells; tumor mutational burden (TMB); and tumor immune activation signature (IAS).

Results:

No cohort achieved the primary efficacy endpoint. Outcome was comparable among recurrent, bevacizumab-naïve cohorts. No unexpected toxicities were observed. A widespread reduction of effector immune cell subsets was noted among recurrent patients compared with newly diagnosed patients that was partially due to dexamethasone use. A trend of increased CD8+Ki67+ T cells at day 15 was noted among patients who achieved the primary endpoint and were not on dexamethasone. Neither TMB nor IAS predicted outcome.

Conclusions:

Patients with recurrent glioblastoma have markedly lower baseline levels of multiple circulating immune cell subsets compared with newly diagnosed patients. An early increase in systemic Ki67+CD8+ cells may warrant further evaluation as a potential biomarker of therapeutic benefit among patients with glioblastoma undergoing checkpoint therapy. Dexamethasone decreased immune cell subsets. PD-L1 blockade and combination with standard or reduced dose bevacizumab was ineffective.
Spatial Metabolomics Identifies Distinct Tumor-Specific Subtypes in Gastric Cancer Patients
Authors: Wang Jun , Kunzke Thomas , Prade Verena M. , Shen Jian , Buck Achim , Feuchtinger Annette , Haffner Ivonne , Luber Birgit , Liu Drolaiz H.W. , Langer Rupert , Lordick Florian , Sun Na , Walch Axel
Published: April 2022

Purpose:

Current systems of gastric cancer molecular classification include genomic, molecular, and morphological features. Gastric cancer classification based on tissue metabolomics remains lacking. This study aimed to define metabolically distinct gastric cancer subtypes and identify their clinicopathological and molecular characteristics.

Experimental Design:

Spatial metabolomics by high mass resolution imaging mass spectrometry was performed in 362 patients with gastric cancer. K−means clustering was used to define tumor and stroma-related subtypes based on tissue metabolites. The identified subtypes were linked with clinicopathological characteristics, molecular features, and metabolic signatures. Responses to trastuzumab treatment were investigated across the subtypes by introducing an independent patient cohort with HER2-positive gastric cancer from a multicenter observational study.

Results:

Three tumor- and three stroma-specific subtypes with distinct tissue metabolite patterns were identified. Tumor-specific subtype T1(HER2+MIB+CD3+) positively correlated with HER2, MIB1, DEFA-1, CD3, CD8, FOXP3, but negatively correlated with MMR. Tumor-specific subtype T2(HER2−MIB−CD3−) negatively correlated with HER2, MIB1, CD3, FOXP3, but positively correlated with MMR. Tumor-specific subtype T3(pEGFR+) positively correlated with pEGFR. Patients with tumor subtype T1(HER2+MIB+CD3+) had elevated nucleotide levels, enhanced DNA metabolism, and a better prognosis than T2(HER2−MIB−CD3−) and T3(pEGFR+). An independent validation cohort confirmed that the T1 subtype benefited from trastuzumab therapy. Stroma-specific subtypes had no association with clinicopathological characteristics, however, linked to distinct metabolic pathways and molecular features.

Conclusions:

Patient subtypes derived by tissue-based spatial metabolomics are a valuable addition to existing gastric cancer molecular classification systems. Metabolic differences between the subtypes and their associations with molecular features could provide a valuable tool to aid in selecting specific treatment approaches.
An Ascendant Challenge: Central Nervous System Metastases in ALK+ Lung Cancers
Authors: Murciano-Goroff Yonina R. , Harada Guilherme , Drilon Alexander
Published: April 2022

Central nervous system (CNS) metastases constitute a challenge for the design of anaplastic lymphoma kinase (ALK) fusion–positive lung cancer trials. The ASCEND-7 study of ceritinib demonstrates the feasibility of broadening CNS eligibility criteria to include symptomatic brain and leptomeningeal disease and highlights design features that contemporary trials will need to incorporate.

See related article by Chow et al., p. 2506
The Irreversible FLT3 Inhibitor FF-10101 Is Active Against a Diversity of FLT3 Inhibitor Resistance Mechanisms
Authors: Ferng Timothy T. , Terada Daisuke , Ando Makoto , Tarver Theodore C. , Chaudhary Fihr , Lin Kimberly C. , Logan Aaron C. , Smith Catherine C.
Published: April 2022

Small-molecule FLT3 inhibitors have recently improved clinical outcomes for patients with FLT3-mutant acute myeloid leukemia (AML) after many years of development, but resistance remains an important clinical problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 which has previously shown activity against FLT3 tyrosine kinase inhibitor resistance–causing FLT3 F691L and D835 mutations. We report that FF-10101 is also active against an expanded panel of clinically identified FLT3 mutations associated with resistance to other FLT3 inhibitors. We also demonstrate that FF-10101 can potentially address resistance mechanisms associated with growth factors present in the bone marrow microenvironment but is vulnerable to mutation at C695, the amino acid required for covalent FLT3 binding. These data suggest that FF-10101 possesses a favorable resistance profile that may contribute to improved single-agent efficacy when used in patients with FLT3-mutant AML.
KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer
Authors: Choi Seo-Hyun , Kim Jin K. , Chen Chin-Tung , Wu Chao , Marco Michael R. , Barriga Francisco M. , O'Rourke Kevin , Pelossof Raphael , Qu Xuan , Chang Qing , de Stanchina Elisa , Shia Jinru , Smith J. Joshua , Sanchez-Vega Francisco , Garcia-Aguilar Julio
Published: April 2022

KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6β4 through ERK/MEK signaling. Knocking-out integrin β4 (ITGB4) specifically depleted the expression of integrin α6β4 and this resulted in a reduction in the invasion and migration ability of the cancer cells. We also observed a reduction in the number and area of lung metastatic foci in mice that were injected with ITGB4 knockout KRAS-mutant colorectal cancer cells compared with the mice injected with ITGB4 wild-type KRAS-mutant colorectal cancer cells, while no difference was observed in liver metastases. Inhibiting integrin α6β4 in KRAS-mutant colorectal cancer could be a potential therapeutic target to diminish the KRAS-invasive phenotype and associated pulmonary metastasis rate.

Implications:

Knocking-out ITGB4, which is overexpressed in KRAS-mutant colorectal cancer and promotes tumor aggressiveness, diminishes local invasiveness and rates of pulmonary metastasis.
Poorly Differentiated Neuroendocrine Carcinoma of Unknown Primary with Metastasis to the Testis: A Case Report
Authors: Sano Momoko , Noguchi Masaaki , Kinoshita Akiyoshi , Nakamura Mayo , Koike Kazuhiko , Saruta Masayuki
Published: April 2022

Neuroendocrine neoplasms are rare epithelial neoplasms with neuroendocrine differentiation. Few cases of primary testicular poorly differentiated neuroendocrine carcinomas (PD-NECs) have been reported, and secondary testicular neoplasms are rare. A 61-year-old man with a chief complaint of left testicular swelling was referred to our hospital. An orchiectomy was performed in order to determine the pathological diagnosis. Pathological examination showed diffuse sheets of highly atypical cells that were positive for neuroendocrine markers and a Ki-67 proliferation index of 80%. The patient was diagnosed with poorly differentiated small-cell NEC. Contrast-enhanced computed tomography revealed multiple metastases to the pancreas, adrenal glands, and lymph nodes. Esophagogastroduodenoscopy showed multiple gastric metastases, and biopsy revealed the same histological findings as observed for the testicular tumor. Contrast-enhanced magnetic resonance imaging of the head also revealed multiple brain metastases. The confirmed diagnosis was PD-NEC of unknown primary with metastases to the testis, stomach, pancreas, adrenal glands, brain, and lymph nodes. We started the first-line chemotherapy with etoposide and cisplatin. Stereotactic radiotherapy for the brain metastases was administered between the first and second cycles. After five cycles, a partial response was observed; however, disease progression was observed after seven cycles with recurrence of the brain metastases and enlargement of all tumors. To our knowledge, this is the first report of an unknown primary PD-NEC with metastasis to the testis.
The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy
Authors: Nagasue Tomohiro , Hirano Atsushi , Torisu Takehiro , Umeno Junji , Shibata Hiroki , Moriyama Tomohiko , Kawasaki Keisuke , Fujioka Shin , Fuyuno Yuta , Matsuno Yuichi , Esaki Motohiro , Kitazono Takanari
Published: April 2022

Introduction: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites. Methods: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing. Results: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces. Conclusions: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota.
Welfare Assessment on Healthy and Tumor-Bearing Mice after Repeated Ultrasound Imaging
Authors: Girbig Renée Michèle , Baier Jasmin , Palme Rupert , Tolba René , Rix Anne , Kiessling Fabian
Published: April 2022

Introduction: Ultrasound (US) imaging enables tissue visualization in high spatial resolution with short examination times. Thus, it is often applied in preclinical research. Diagnostic US, including contrast-enhanced US (CEUS), is considered to be well-tolerated by laboratory animals although no systematic study has been performed to confirm this claim. Therefore, the aim of this study was to screen for possible effects of US and CEUS examinations on welfare of healthy mice. Additionally, the potential influence of CEUS and molecular CEUS on well-being and therapy response to regorafenib was investigated in breast cancer-bearing mice. Material and Methods: Forty healthy Balb/c mice were randomly assigned for examination with US or CEUS (3×/week) for 4 weeks. Untreated healthy mice and mice receiving only isoflurane anesthesia served as controls (n = 10/group). Ninety-four 4T1 tumor-bearing Balb/c mice were allocated randomly to the following groups: no imaging, isoflurane anesthesia, CEUS, and molecular CEUS. They either received 10 mg/kg regorafenib or vehicle solution daily by oral gavage. Animals were examined three times within 2 weeks. CEUS measurements were performed using phospholipid microbubbles, and phospholipid microbubbles targeting the vascular endothelial growth factor receptor-2 were applied for molecular CEUS. Welfare evaluation was performed by daily observational score sheets, measuring the heart rate, Rotarod performance, and fecal corticosterone metabolites twice a week. On the last day, pathological changes in serum corticosterone concentrations, hemograms, and organ weights were obtained. Moreover, a potential influence of isoflurane anesthesia, CEUS, and molecular CEUS on regorafenib response in tumor-bearing mice was examined. Analysis of variance and Dunnett’s post hoc test were performed as statistical analyses. Results: Severity parameters were not altered after repeated US and CEUS examinations of healthy mice, but spleen sizes were significantly lower after isoflurane anesthesia. In tumor-bearing mice, no effect on animal welfare after repeated CEUS and molecular CEUS could be observed. However, leukocyte counts and spleen weights of tumor-bearing mice were significantly lower in animals examined with CEUS and molecular CEUS compared to the control groups. This effect was not visible in regorafenib-treated animals. Conclusions: Repeated US and (molecular) CEUS have no detectable impact on animal welfare in healthy and tumor-bearing mice. However, CEUS and molecular CEUS in combination with isoflurane anesthesia might attenuate immunological processes in tumor-bearing animals and may consequently affect responses to antitumor therapy.
Understanding Children’s Attention to Dental Caries through Eye-Tracking
Authors: Cho Vanessa Y. , Hsiao Janet H. , Chan Antoni B. , Ngo Hien C. , King Nigel M. , Anthonappa Robert P.
Published: April 2022

Visual attention is a significant gateway to a child’s mind, and looking is one of the first behaviors young children develop. Untreated caries and the resulting poor dental aesthetics can have adverse emotional and social impacts on children’s oral health-related quality of life due to its detrimental effects on self-esteem and self-concept. Therefore, we explored preschool children’s eye movement patterns and visual attention to images with and without dental caries via eye movement analysis using hidden Markov models (EMHMM). We calibrated a convenience sample of 157 preschool children to the eye-tracker (Tobii Nano Pro) to ensure standardization. Consequently, each participant viewed the same standardized pictures with and without dental caries while an eye-tracking device tracked their eye movements. Subsequently, based on the sequence of viewed regions of interest (ROIs), a transition matrix was developed where the participants’ previously viewed ROI informed their subsequently considered ROI. Hence, an individual’s HMM was estimated from their eye movement data using a variational Bayesian approach to determine the optimal number of ROIs automatically. Consequently, this data-driven approach generated the visual task participants' most representative eye movement patterns. Preschool children exhibited two different eye movement patterns, distributed (78%) and selective (21%), which was statistically significant. Children switched between images with more similar probabilities in the distributed pattern while children remained looking at the same ROI than switching to the other ROI in the selective pattern. Nevertheless, all children exhibited an equal starting fixation on the right or left image and noticed teeth. The study findings reveal that most preschool children did not have an attentional bias to images with and without dental caries. Furthermore, only a few children selectively fixated on images with dental caries. Therefore, selective eye-movement patterns may strongly predict preschool children’s sustained visual attention to dental caries. Nevertheless, future studies are essential to fully understand the developmental origins of differences in visual attention to common oral health presentations in children. Finally, EMHMM is appropriate for assessing inter-individual differences in children’s visual attention.
The Eyebrow Approach for the Management of Pediatric Frontal Epidural Abscesses Secondary to Diffuse Sinusitis
Authors: Hallak Hana , Abou-Al-Shaar Hussam , Mallela Arka N. , McDowell Michael M. , Jabbour Noel , Padia Reema , Greene Stephanie , Pollack Ian F.
Published: April 2022

Background: Minimally invasive approaches to the anterior cranial fossa have evolved over the past few decades. The management of frontal epidural abscesses (EDAs) secondary to diffuse sinusitis in the pediatric population using minimally invasive techniques is scarcely reported in the literature. Herein, we report the utilization of a minimally invasive eyebrow approach for multidisciplinary concurrent evacuation of frontal EDA secondary to diffuse sinusitis and trephination of the frontal sinus in three pediatric patients. Case Reports: Three pediatric patients presented to the emergency room with severe headaches, visual changes, somnolence, and significant facial and periorbital swelling. Imaging revealed diffuse sinusitis with focal frontal epidural extension. In all cases, progressive clinical deterioration along with the radiographic findings mandated urgent surgical intervention. The eyebrow approach allowed for concomitant evacuation of the frontal EDA and trephination of the frontal sinus followed by functional endoscopic sinus surgery in the same setting. All patients tolerated the procedure well with complete resolution of their symptoms at the completion of antibiotic therapy and complete resolution of the EDA. Conclusion: The eyebrow approach is a minimally invasive technique that should be considered as part of the armamentarium in the management of select EDA in the pediatric population. It allows for multidisciplinary collaboration between neurosurgeons and otolaryngologists for concomitant evacuation of the EDA and trephination of the frontal sinus. This approach is a feasible, safe, and effective minimally invasive technique that can be employed for the management of EDA secondary to diffuse sinusitis in the pediatric population.
Is Being a Genus? Syrianus’ Criticism of Aristotle
Authors: Granieri Roberto
Published: April 2022

In Metaphysics B 3 Aristotle sets out a famous argument for the thesis that being is not a genus. In his commentary on Metaphysics B, Syrianus criticizes this argument and explains in what sense being is to be regarded as a genus. I reconstruct both Syrianus’ criticisms and his own view. I bring out ways in which they can help us rethink key assumptions of Aristotle’s ontology and shed light both on Syrianus’ critical attitude towards Aristotle and on some of Syrianus’ main views in metaphysics.
Neo-Triple Helix Model of Innovation Ecosystems: Integrating Triple, Quadruple and Quintuple Helix Models
Authors: Cai Yuzhuo
Published: April 2022

This article proposes the neo-Triple Helix model of innovation ecosystems by integrating the Triple, Quadruple and Quintuple Helix models, inspired by Lewontin’s gene, organism and environment Triple Helix metaphor. The model considers innovation ecosystems evolved through interactions between 1) innovation dynamics (or innovation genes), 2) social structures and 3) the natural environment. The systems include two-layer triple helix interactions (or triads): university, industry and government at the gene level, and innovation genes, social structures and the natural environment at the system level. Innovation dynamics are conceptualised by integrating the neo-institutional and neo-evolutionary perspectives of the Triple Helix model. The dialectical relationships between innovation genes, social structures and the natural environment are primarily explained using aspects of the Quadruple and Quintuple Helix models. The neo-Triple Helix model clarifies debates on different helix innovation models, advances helical approaches through synergy building and can guide empirical research and policy design on innovation ecosystems.
Is the Universe Moral?
Authors: Large William
Published: April 2022

Kant argues against the ontological argument for the existence of God but replaces it with a moral theism. This article analyses Kant’s moral proof with emphasis on the Critique of the Power of Judgement, and his historical and political writings. It argues that at the heart of this argument is the idea of progress. The concrete content of the moral law is the idea of a just world. Such a just world would be impossible without the idea of God, since there would be no harmony between nature and freedom. It contrasts Kant’s concept of time and history with Heidegger’s. The difference between them is a reversal of modality. For Kant, actuality determines possibility. If I cannot imagine a just word as actual, then I would fall into moral despair. The idea of God grounds this actuality. For Heidegger, possibility is higher than actuality. Since history has no teleology, then no idea of God is required.
Lectotypification of Saxifraga yuparensis Nosaka (Saxifragaceae)
Authors: TAMURA SAYA , TAKAHASHI HIDEKI , SHUTOH KOHTAROH , SATO KEN , SATO HIROYUKI , SHIMAMURA TAKASHI , NAKAMURA KOH
Published: April 2022

We discussed the typification of the name Saxifraga yuparensis applicable to an alpine plant described from Hokkaido, northern Japan. The holotype is not found in the cited herbarium and other herbaria related to Nosaka. No isotypes or paratypes were cited in its protologue, and no other uncited specimens are unambiguously deduced to have been used by Nosaka when describing the species and do not comprise the original material (Art. 9.4 of the Botanical Code). Therefore, an illustration (Fig. 11 in Nosaka 1974) published as part of the protologue is the only original material that can be chosen in lectotype designation in conformity with Art. 9.12. The illustration is here designated as the lectotype for the name.
A tribute to resistance: Eugenia quilombola (Myrtaceae), a new species with multilocular anthers from the Atlantic Forest of northeastern Brazil
Authors: AMORIM BRUNO S. , DE SOUZA MARIA ANÁLIA DUARTE , ALBUQUERQUE PATRÍCIA MELCHIONNA , NEGRÃO RAQUEL , GIARETTA AUGUSTO
Published: April 2022

Eugenia quilombola, a new species restricted to the northern portion of the Atlantic Forest is here described. Its sheets were previously misidentified as Eugenia umbrosa and this misquoting name have been used in scientific collections and publications until now. After 10 years of studies and discussions about its identity, Eugenia quilombola was recognized as a new taxon based on its diagnostic features of multilocular anthers and verrucose fruits (vs. rimose anther and smooth fruit in E. umbrosa). Furthermore, Eugenia quilombola has a narrow distribution in northeastern Brazil while E. umbrosa occurs in the southeastern region and in the state of Bahia.
Bulbophyllum guniuensis (Orchidaceae: Epidendroideae; Malaxideae), a new species from Eastern China
Authors: ZHANG SI-YU , ZHU KE-RUN , YAN QI , WU WEI , WANG BO-RUI , NI WEI-YONG , SHAO JIAN-WEN
Published: April 2022

Bulbophyllum guniuensis W.Y. Ni & J.W. Shao, a new species of Orchidaceae from Anhui Province, eastern China, is described and illustrated. This new species is similar to B. henanense in overall plant size and leaf morphology, but differs from the latter by the length of the scape and the morphology of the lateral sepals and lip. B. guniuensis is also similar to B. hirundinis in margin fimbriate-ciliate, 3-veined dorsal sepal and petals, but differs from it in oblique oblong (vs. linear) lateral sepals and pale yellow to orange yellow (vs. purplish-red to yellow) flowers.
Unmasking the Confounder: The Inherent Physiologic Variability of Swine During an Automated Experimental Model of Ischemia-Reperfusion Injury
Authors: Martin Symonne C. , Hauser Nathaniel , Renaldo Antonio C. , Lane Magan , Jordan James E. , Qadri Hisham I. , Mouser Nicholas , Rahbar Elaheh , Williams Timothy K. , Neff Lucas P.
Published: April 2022

Background

We sought to determine the magnitude of the inherent inter-animal physiologic variability by automating a porcine Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) protocol to minimize external influences that might alter physiology and confound experimental results.

Methods

Swine (n = 42) underwent a controlled 30% blood volume hemorrhage followed by 30 minutes of REBOA (ie, ischemic phase). The animals were weaned from REBOA autonomously over 15 minutes, beginning the reperfusion phase, while continuing to provide partial flow balloon support to maintain a target proximal mean arterial pressure (pMAP) of 65 mmHg. Simultaneously, shed blood was re-transfused as part of the resuscitation efforts. Physiologic data were continuously recorded, and serum samples were serially collected. Baseline characteristics, variance in vital signs, and 8-isoprostane levels were quantified during hemorrhage, REBOA, and reperfusion phases.

Results

There was no significant difference in baseline physiology across animals ( P > .05). Hemodynamic variability was highest for pMAP during the ischemic phase ( P = .001) and for distal mean arterial pressure (dMAP) during the weaning/reperfusion phase ( P = .001). The latter finding indicated the variable physiologic response to ischemia-reperfusion injury, as the automated balloon support required by each animal to maintain pMAP was highly variable. Circulating 8-isoprostane variance was significantly higher following the start of reperfusion compared to baseline levels ( P = .001).

Discussion

Despite subjecting animals to a highly consistent ischemia-reperfusion injury through automation, we noted significant variability in the hemodynamic and biochemical response. These findings illustrate the inherent physiologic variability and potential limitations of porcine large animal models for the study of shock.
Changes in Injury Patterns Associated With Elevated Blood Alcohol Level
Authors: Rhodes Heather X. , Moncada Isabella , Biswas Saptarshi
Published: April 2022

Introduction

This study aims to improve public health outreach in a high-risk population.

Methods

This is a single center study of Trauma Registry data, inclusive years January 1, 2016 to March 30, 2021. The study population was stratified into two groups: ETOH ≥ 80 mg/dL and ETOH <80 mg/dL. A total of 1141 were included.

Results

Those above the legal drinking limit had a significantly higher mean ETOH (231 mg/dL; P <.01) and were typically younger men that arrived by ground ambulance. The significant injury patterns of those above the legal limit included full activation and consults who fell from stairs and fell from other or unknown. A higher proportion of intoxicated fall trauma patients above the legal limit were diagnosed with a concussion.

Conclusions

Excess alcohol consumption, particularly during a pandemic year, may lead to a higher incidence of fall from stairs trauma in men who are more likely to be diagnosed with a concussion.
A Reconceptualization of Social Bond Theory to Predict Change Sequences in Offending
Authors: Mears Daniel P. , Stafford Mark C.
Published: April 2022

We argue that reconceptualizing social bond theory (SBT) through incorporation of dual agency and change can identify unique causal change sequences, improve its ability to explain offending, and generate new questions about it. The reconceptualization recognizes that individuals and those with whom they interact play an ongoing role in contributing to the bond. It shows that changes in the bond can contribute to changes in delinquency through three sequences, each with a unique over-time pattern that depends on how bond agents respond to delinquency. We identify implications for SBT—highlighting that theoretical arguments about static effects do not necessarily equate to straightforward predictions about change effects—and, more broadly, efforts to advance theories of offending.
Partition’s orphaned and abandoned children in Pakistan
Authors: Chattha Ilyas
Published: April 2022

Alongside women, children were among the foremost victims of the 1947 Partition violence, and yet this group has been historically neglected by scholars. Countless children became orphaned and were adopted or sent to orphanages. Concomitant with these developments was the growth of an ambitious humanitarian movement to protect the orphaned children. While arguing that these movements spawned the modern benevolent institutions in the early years of Pakistan, this essay also poses the following questions: What was the role of the state and interventions of social workers vis-à-vis the orphaned children? What happened to adolescents after their discharge from charitable institutions? Did their trajectories lead them back into the mainstream of society, or did other fates await them? Drawing on previously untapped and rich archival materials, including the records of relief agencies, unpublished memoirs and government documents, this essay considers the varying circumstances in which children found themselves in orphanages, and explores the motives behind as well as the incidence and social implications of adoptions. It also studies how these charitable orphanages emerged out of a host of needs, expectations, resources and opportunities.
Sleep in an At Risk Adolescent Group: A Qualitative Exploration of the Perspectives, Experiences and Needs of Youth Who Have Been Excluded From Mainstream Education
Authors: Bainton Josie , Hayes Ben
Published: April 2022

The sleep needs, experiences and viewpoints were explored for UK adolescents who have been excluded from mainstream education. Qualitative data was gathered through interviews with 9 participants, aged 11–15 years, who also completed questionnaires. The participants had symptoms of inadequate sleep, poor sleep hygiene behaviours and were not getting the recommended amount of sleep on school nights. Participants described sleep patterns involving often staying up late and having different sleep timing on weekends than weekdays and having difficulties with their sleep. Use of technology and the relevance of family were identified as important and associated with facilitating and hindering factors for sleep. Participants communicated that they lack control over aspects of their sleep and their lives. The experiences and views of the participants can inform professionals’ understanding of how to collaborate with adolescents to improve their sleep and highlight that continued development of sleep education programmes is timely.
The Home Front: World War I, Tenant Activism, and Housing Policy Before the New Deal
Authors: Silber Maia
Published: April 2022

During World War I, mass migration to military manufacturing centers and the suspension of most private construction placed immense pressure on urban rental housing markets. Seeking to address the wartime housing “emergency,” Congress established the nation’s first public housing programs and federal agents based in major cities implemented informal policies to control rents. After the war, national policy shifted away from assisting struggling tenants to promoting homeownership for those who could afford it. However, empowered by the assistance they had received during the war, Philadelphia tenants continued to insist on the need for government action to curtail evictions and rising rents. Though divided by race, ethnicity, income, and political affiliation, struggling tenants shared the belief that the city’s housing problems required collective solutions.
Study on mechanism and improvement technology of Top coal loss in horizontal sublevel fully mechanized caving mining
Authors: Wu Fengfeng , Zhang Shurong , Yue Xin , Liu Changyou , Liu Qiwen , Zhang Jian , Lv Bo , Gao Zhiqiang
Published: April 2022

In view of solving the problems of large top coal loss and low recovery rate in the traditional caving process of horizontal section fully mechanized caving mining, taking the fully mechanized caving face of steeply inclined and extra-thick coal seam in Yimen Coal Mine as the engineering background and the research method of numerical simulation and field measurement was used to study the coal gangue flow characteristics under different coal caving directions and different number of coal caving ports at the bottom plate side, revealing the mechanism of top coal loss and proposing the technology to improve the recovery rate. The results show that the action time of top gangue and the ‘ rotation ‘ of coal gangue flow in the triangle coal area jointly promote the release of triangle coal in the bottom plate, which makes the coal gangue interface steeper and the release rate higher when the coal is released in the lateral direction of the bottom plate; adjusting the number of opening coal mouths when the initial coal caving at the floor side can coordinate the top coal caving speed, gangue down-channeling speed and the closing time of the coal caving mouth. When the first coal caving opens two coal caving mouths, the recovery rate of bottom triangular coal is the highest. Yimen Coal Mine adopted the floor lateral roof side caving and double-mouth caving technology. Compared with the original scheme, the top coal recovery rate of the working face increased by 3%, and the top coal recovery rate of the floor triangle area increased by 7%.