bluuebunny/crossref_metadata_2025 huggingface dataset:
Eight-Year Outcomes of Implantation of Posterior Chamber Phakic Intraocular Lens With a Central Port for Moderate to High Ametropia
Authors: Kamiya Kazutaka , Shimizu Kimiya , Takahashi Masahide , Ando Wakako , Hayakawa Hideki , Shoji Nobuyuki
Published: December 2021

Purpose: To assess the 8-year clinical outcomes of implantation of an implantable collamer lens (ICL) with a central port (KS-Aquaport; EVO-ICL) for moderate to high myopia and myopic astigmatism.

Methods: This retrospective study comprised a total of 177 eyes of 106 patients with spherical equivalents of −7.99 ± 3.33 D [mean ± standard deviation], who underwent EVO-ICL implantation. We evaluated the safety, efficacy, predictability, stability, and adverse events of the surgery, at 1 month, and 1, 2, 4, 6, and 8 years postoperatively.

Results: The logarithm of the minimal angle of resolution (LogMAR) uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) were −0.07 ± 0.17 and −0.20 ± 0.09, respectively, at 8 years postoperatively. The safety and efficacy indices were 1.18 ± 0.24 and 0.89 ± 0.28, respectively. At 8 years, 83 and 93% eyes were within ± 0.5 D and ± 1.0 D of the targeted correction, respectively. Change in manifest refraction from 1 month to 8 years postoperatively was −0.13 ± 0.30 D. Three eyes (1.7%) that developed cataracts had a slight pre-existing peripheral anterior subcapsular cataract formation required simultaneous ICL extraction and cataract surgery at 2 or 3 years or ICL size change (1 size up) at 7 years postoperatively. We found that neither significant intraocular pressure (IOP) rise (including pupillary block) nor significant endothelial cell loss occurred in any case throughout the 8-year observation period.

Conclusions: Current ICL implantation with central port technology offered good continuous outcomes for all measures of safety, efficacy, predictability, and stability for correcting moderate to high myopic errors over a long period, thereby suggesting its long-term viability as a surgical approach for the treatment of such eyes.
Characterizing the Core Internal Gene Pool of H9N2 Responsible for Continuous Reassortment With Other Influenza A Viruses
Authors: Yang Haoyi , Hu Mingda , Wang Boqian , Jin Yuan , Gong Xingfei , Liang Long , Yue Junjie , Chen Wei , Ren Hongguang
Published: December 2021

Reassortment among avian influenza viruses is the main source of novel avian influenza virus subtypes. Studies have shown that the H9N2 virus often donates internal segments to generate novel reassortant avian influenza viruses, acting as a reassortment template. However, the characteristics of the internal pattern of reassortment remain unclear. In this article, we first defined the core gene pool of the internal segments of the H9N2 virus that provide templates for reassortment. We used genetic distance and sequence similarity to define typical clusters in the core gene pool. Then, we analyzed the phylogenetic relationships, feature vector distances, geographic distributions and mutation sites of strains related to the core gene pool. Strains in the same typical clusters have close phylogenetic relationships and feature vector distances. We also found that these typical clusters can be divided into three categories according to their main geographic distribution area. Furthermore, typical clusters in the same geographic area contain some common mutation patterns. Our results suggest that typical clusters in the core gene pool affect the reassortment events of the H9N2 virus in many respects, such as geographic distribution and amino acid mutation sites.
Non-tuberculous Mycobacterial Infection of the Musculoskeletal System Detected at Two Tertiary Medical Centres in Henan, China, 2016–2020
Authors: Ma Qiong , Chen Rende , Yang Enhui , Yuan Youhua , Tian Yongfu , Han Yongguang , Wang Shanmei , Wang Baoya , Yan Wenjuan , Zhang Qi , Jing Nan , Ma Bing , Wang Zhen , Li Yi , Li Yongjun
Published: December 2021

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal system is rare but poses a grave threat to public health. These infections yield non-specific symptoms that remain undetected until the development of the later stages of the disease. In this study, we performed a retrospective review of 25 cases of musculoskeletal NTM infection at two tertiary medical centres over a 5-year period to determine the clinical features and improve the current clinical diagnosis and treatment. The most common mycobacterial species detected were Mycobacterium fortuitum in eleven patients, Mycobacterium abscessus in eight patients, Mycobacterium houstonense in three patients, Mycobacterium avium in two patients, and Mycobacterium smegmatis in one patient. The sites of infection included the limbs and joints, most commonly the knee (ten patients) and foot (six patients). The median duration from the onset of symptoms to diagnosis was 2.5 months (0.8–13.5 months). Deep sinus tracts extending to the surgical site were observed in 60% of the patients (15/25), and granulomatous inflammation and granulomatous inflammation with necrosis occurred in 60% of the patients (15/25). All patients underwent surgical treatment for infection control, and all patients, except one, received antimycobacterial therapy based on drug sensitivity assays. The median duration of the antimicrobial chemotherapy was 5 months (range: 3–20 months). At the final follow-up, 24 patients presented with absence of recurrence and one patient succumbed owing to heart failure after debridement. Our findings highlight the importance of vigilance and improvements in the diagnostic methods for musculoskeletal NTM infection. Aggressive surgical treatment and antimycobacterial drug treatment can help achieve satisfactory results.
Transcriptomic and Metabolomic Profiling Reveals That KguR Broadly Impacts the Physiology of Uropathogenic Escherichia coli Under in vivo Relevant Conditions
Authors: Yang Dawei , Jiang Fengwei , Huang Xinxin , Li Ganwu , Cai Wentong
Published: December 2021

Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). In contrast to the intestinal E. coli strains that reside in nutrient-rich gut environment, UPEC encounter distinct niches, for instance human urine, which is an oxygen- and nutrient-limited environment. Alpha-ketoglutarate (KG) is an abundant metabolite in renal proximal tubule cells; and previously we showed that two-component signaling system (TCS) KguS/KguR contributes to UPEC colonization of murine urinary tract by promoting the utilization of KG as a carbon source under anaerobic conditions. However, knowledge about the KguR regulon and its impact on UPEC fitness is lacking. In this work, we analyzed transcriptomic and metabolomic changes caused by kguR deletion under anaerobiosis when KG is present. Our results indicated that 620 genes were differentially expressed in the ΔkguR mutant, as compared to the wild type; of these genes, 513 genes were downregulated and 107 genes were upregulated. Genes with substantial changes in expression involve KG utilization, acid resistance, iron uptake, amino acid metabolism, capsule biosynthesis, sulfur metabolism, among others. In line with the transcriptomics data, several amino acids (glutamate, lysine, etc.) and uridine 5′-diphosphogalactose (involved in capsule biosynthesis) were significantly less abundant in the ΔkguR mutant. We then confirmed that the ΔkguR mutant, indeed, was more sensitive to acid stress than the wild type, presumably due to downregulation of genes belonging to the glutamate-dependent acid resistance system. Furthermore, using gene expression and electrophoretic mobility shift assays (EMSAs), we demonstrate that KguR autoregulates its own expression by binding to the kguSR promoter region. Lastly, we performed a genome-wide search of KguR binding sites, and this search yielded an output of at least 22 potential binding sites. Taken together, our data establish that in the presence of KG, KguR broadly impacts the physiology of UPEC under anaerobiosis. These findings greatly further our understanding of KguS/KguR system as well as UPEC pathobiology.
Reassortment Network of Influenza A Virus
Authors: Gong Xingfei , Hu Mingda , Chen Wei , Yang Haoyi , Wang Boqian , Yue Junjie , Jin Yuan , Liang Long , Ren Hongguang
Published: December 2021

Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments. Genetic exchange through reassortment of the segmented genomes often endows IAVs with new genetic characteristics, which may affect transmissibility and pathogenicity of the viruses. However, a comprehensive understanding of the reassortment history of IAVs remains lacking. To this end, we assembled 40,296 whole-genome sequences of IAVs for analysis. Using a new clustering method based on Mean Pairwise Distances in the phylogenetic trees, we classified each segment of IAVs into clades. Correspondingly, reassortment events among IAVs were detected by checking the segment clade compositions of related genomes under specific environment factors and time period. We systematically identified 1,927 possible reassortment events of IAVs and constructed their reassortment network. Interestingly, minimum spanning tree of the reassortment network reproved that swine act as an intermediate host in the reassortment history of IAVs between avian species and humans. Moreover, reassortment patterns among related subtypes constructed in this study are consistent with previous studies. Taken together, our genome-wide reassortment analysis of all the IAVs offers an overview of the leaping evolution of the virus and a comprehensive network representing the relationships of IAVs.
Effect of Mutations in GvpJ and GvpM on Gas Vesicle Formation of Halobacterium salinarum
Authors: Jost Alisa , Knitsch Regine , Völkner Kerstin , Pfeifer Felicitas
Published: December 2021

The two haloarchaeal proteins, GvpM and GvpJ, are homologous to GvpA, the major gas vesicle structural protein. All three are hydrophobic and essential for gas vesicle formation. The effect of mutations in GvpJ and GvpM was studied in Haloferax volcanii transformants by complementing the respective mutated gene with the remaining gvp genes and inspecting the cells for the presence of gas vesicles (Vac+). In case of GvpJ, 56 of 66 substitutions analyzed yielded Vac– ΔJ + Jmut transformants, indicating that GvpJ is very sensitive to alterations, whereas ten of the 38 GvpM variants resulted in Vac– ΔM + Mmut transformants. The variants were also tested by split-GFP for their ability to interact with their partner protein GvpL. Some of the alterations leading to a Vac– phenotype affected the J/L or M/L interaction. Also, the interactions J/A and J/M were studied using fragments to exclude an unspecific aggregation of these hydrophobic proteins. Both fragments of GvpJ interacted with the M1–25 and M60–84 fragments of GvpM, and fragment J1–56 of GvpJ interacted with the N-terminal fragment A1–22 of GvpA. A comparison of the results on the three homologous proteins indicates that despite their relatedness, GvpA, GvpJ, and GvpM have unique features and cannot substitute each other.
Linking Ethanol-Addictive Behaviors With Brain Catecholamines: Release Pattern Matters
Authors: Grinevich Vladimir P. , Krupitsky Evgeny M. , Gainetdinov Raul R. , Budygin Evgeny A.
Published: December 2021

Using a variety of animal models that simulate key features of the alcohol use disorder (AUD), remarkable progress has been made in identifying neurochemical targets that may contribute to the development of alcohol addiction. In this search, the dopamine (DA) and norepinephrine (NE) systems have been long thought to play a leading role in comparison with other brain systems. However, just recent development and application of optogenetic approaches into the alcohol research field provided opportunity to identify neuronal circuits and specific patterns of neurotransmission that govern the key components of ethanol-addictive behaviors. This critical review summarizes earlier findings, which initially disclosed catecholamine substrates of ethanol actions in the brain and shows how the latest methodologies help us to reveal the significance of DA and NE release changes. Specifically, we focused on recent optogenetic investigations aimed to reveal cause-effect relationships between ethanol-drinking (seeking and taking) behaviors and catecholamine dynamics in distinct brain pathways. These studies gain the knowledge that is needed for the better understanding addiction mechanisms and, therefore, for development of more effective AUD treatments. Based on the reviewed findings, new messages for researches were indicated, which may have broad applications beyond the field of alcohol addiction.
Gender Differences in 3-Month Outcomes of Erenumab Treatment—Study on Efficacy and Safety of Treatment With Erenumab in Men
Authors: Ornello Raffaele , Baraldi Carlo , Guerzoni Simona , Lambru Giorgio , Fuccaro Matteo , Raffaelli Bianca , Gendolla Astrid , Barbanti Piero , Aurilia Cinzia , Cevoli Sabina , Favoni Valentina , Vernieri Fabrizio , Altamura Claudia , Russo Antonio , Silvestro Marcello , Dalla Valle Elisabetta , Mancioli Andrea , Ranieri Angelo , Alfieri Gennaro , Latysheva Nina , Filatova Elena , Talbot Jamie , Cheng Shuli , Holle Dagny , Scheffler Armin , Nežádal Tomáš , Čtrnáctá Dana , Šípková Jitka , Matoušová Zuzana , Sette Lucia , Casalena Alfonsina , Maddestra Maurizio , Viola Stefano , Affaitati Giannapia , Giamberardino Maria Adele , Pistoia Francesca , Reuter Uwe , Sacco Simona
Published: December 2021

Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor.

Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9–12 of treatment compared with baseline: 0–29%, 30–49%, 50–75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9–12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes.

Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9–12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50–74% response, 35 (13.7%) had a 30–49% response, and 86 (33.6%) had a 0–29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes.

Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.
“ET Plus”: Instability of the Diagnosis During Prospective Longitudinal Follow-up of Essential Tremor Cases
Authors: Iglesias-Hernandez Daniella , Delgado Nikki , McGurn Margaret , Huey Edward D. , Cosentino Stephanie , Louis Elan D.
Published: December 2021

Background: A recent consensus statement introduced the term “ET plus”. Although investigators have quantified the prevalence of ET plus in cross-sectional studies, patients with ET plus have not been tracked longitudinally; hence, there is no understanding of its stability over time.

Methods: We present prospective, longitudinal phenotypic data on an ET cohort that was followed regularly at 18-month intervals (T1, T2, T3, T4) for up to 64 months. We assigned an ET or ET plus diagnosis to each case at each time interval.

Results: There were 201 participants at baseline. The proportion with ET plus increased from 58.7% at baseline to 72.1% at T4 (p = 0.046). Of 172 (85.6%) who received a diagnosis of ET plus at one or more time intervals, the diagnosis was unstable (e.g., with reversion) in 62 (36.0%). We also assessed the stability of the clinical features of ET plus. Rest tremor was the most unstable clinical feature of ET plus; it was present in 59 participants, among whom it reverted from present to absent in 23 (39.0%). By contrast, for “memory impairment” (i.e., either mild cognitive impairment or dementia), the proportion who reverted from present to absent was only 21.3%.

Conclusion: These data support our two a priori hypotheses: (1) the prevalence of ET plus would increase progressively, as it likely represents a more advanced stage of ET, and (2) the ET plus diagnosis would not be stable over time, as cases would fluctuate with respect to their phenotypic features and their assigned diagnoses.
40-Hz Blue Light Changes Hippocampal Activation and Functional Connectivity Underlying Recognition Memory
Authors: Lin Zhenglong , Hou Gangqiang , Yao Youli , Zhou Zhifeng , Zhu Feiqi , Liu Linjing , Zeng Lingwu , Yang Yatao , Ma Junxian
Published: December 2021

Research on light modulation has typically examined the wavelength, intensity, and exposure time of light, and measured rhythm, sleep, and cognitive ability to evaluate the regulatory effects of light variables on physiological and cognitive functions. Although the frequency of light is one of the main dimensions of light, few studies have attempted to manipulate it to test the effect on brain activation and performance. Recently, 40-Hz light stimulation has been proven to significantly alleviate deficits in gamma oscillation of the hippocampus caused by Alzheimer’s disease. Although this oscillation is one of the key functional characteristics of performing memory tasks in healthy people, there is no evidence that 40-Hz blue light exposure can effectively regulate brain activities related to complex cognitive tasks. In the current study, we examined the difference in the effects of 40-Hz light or 0-Hz light exposure on brain activation and functional connectivity during a recognition memory task. Through joint augmentation of visual area activation, 40-Hz light enhanced brain areas mostly in the limbic system that are related to memory, such as the hippocampus and thalamus. Conversely, 0-Hz light enhanced brain areas mostly in the prefrontal cortex. Additionally, functional connection analysis, with the hippocampus as the seed point, showed that 40-Hz light enhanced connection with the superior parietal lobe and reduced the connection with the default network. These results indicate that light at a frequency of 40 Hz can change the activity and functional connection of memory-related core brain areas. They also indicate that in the use of light to regulate cognitive functions, its frequency characteristics merit attention.
CRISPR-Cas-Led Revolution in Diagnosis and Management of Emerging Plant Viruses: New Avenues Toward Food and Nutritional Security
Authors: Sharma Susheel Kumar , Gupta Om Prakash , Pathaw Neeta , Sharma Devender , Maibam Albert , Sharma Parul , Sanasam Jyotsana , Karkute Suhas Gorakh , Kumar Sandeep , Bhattacharjee Bijoya
Published: December 2021

Plant viruses pose a serious threat to agricultural production systems worldwide. The world's population is expected to reach the 10-billion mark by 2057. Under the scenario of declining cultivable land and challenges posed by rapidly emerging and re-emerging plant pathogens, conventional strategies could not accomplish the target of keeping pace with increasing global food demand. Gene-editing techniques have recently come up as promising options to enable precise changes in genomes with greater efficiency to achieve the target of higher crop productivity. Of genome engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) proteins have gained much popularity, owing to their simplicity, reproducibility, and applicability in a wide range of species. Also, the application of different Cas proteins, such as Cas12a, Cas13a, and Cas9 nucleases, has enabled the development of more robust strategies for the engineering of antiviral mechanisms in many plant species. Recent studies have revealed the use of various CRISPR-Cas systems to either directly target a viral gene or modify a host genome to develop viral resistance in plants. This review provides a comprehensive record of the use of the CRISPR-Cas system in the development of antiviral resistance in plants and discusses its applications in the overall enhancement of productivity and nutritional landscape of cultivated plant species. Furthermore, the utility of this technique for the detection of various plant viruses could enable affordable and precise in-field or on-site detection. The futuristic potential of CRISPR-Cas technologies and possible challenges with their use and application are highlighted. Finally, the future of CRISPR-Cas in sustainable management of viral diseases, and its practical utility and regulatory guidelines in different parts of the globe are discussed systematically.
Prognostic Value of Microvascular Invasion in Eight Existing Staging Systems for Hepatocellular Carcinoma: A Bi-Centeric Retrospective Cohort Study
Authors: Xiang Yan-Jun , Wang Kang , Zheng Yi-Tao , Yu Hong-Ming , Cheng Yu-Qiang , Wang Wei-Jun , Shan Yun-Feng , Cheng Shu-Qun
Published: December 2021

Background

Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). However, whether the existing staging systems of hepatocellular carcinoma can distinguish the prognosis of patients with MVI and the prognostic value of MVI in different subtypes of hepatocellular carcinoma remains to be clarified.

Methods

A dual-center retrospective data set of 1,198 HCC patients who underwent R0 LR was included in the study between 2014 and 2016. Baseline characteristics and staging information were collected. Homogeneity and modified Akaike information criterion (AICc) were compared between each system. And the prognostic significance of MVI for overall survival (OS) was studied in each subgroup.

Results

In the entire cohort, there were no significant survival differences between Cancer of the Liver Italian Program (CLIP) score 2 and 3 (p = 0.441), and between Taipei Integrated Scoring System (TIS) score 3 and 4 (p = 0.135). In the MVI cohort, there were no significant survival differences between Barcelona Clinic Liver Cancer stages B and C (p=0.161), CLIP scores 2 and 3 (p = 0.083), TIS scores 0 and 1 (p = 0.227), TIS scores 2 and 3 (p =0.794), Tokyo scores 3 and 4 (p=0.353), and American Joint Committee on Cancer Tumor-Node-Metastasis 7th stage I and II (p=0.151). Among the eight commonly used HCC staging systems, the Hong Kong Liver Cancer (HKLC) staging system showed the highest homogeneity and the lowest AICc value in both the entire cohort and MVI cohort. In each subgroup of the staging systems, MVI generally exhibited poor survival outcomes.

Conclusions

The HKLC staging system was the most accurate model for discriminating the prognosis of MVI patients, among the eight staging systems. Meanwhile, our findings suggest that MVI may be needed to be incorporated into the current HCC staging systems as one of the grading criteria.
MicroRNA-20a Suppresses Tumor Proliferation and Metastasis in Hepatocellular Carcinoma by Directly Targeting EZH1
Authors: Zhang Qianqian , Deng Xiaohong , Tang Xiuxin , You Ying , Mei Meihua , Liu Danping , Gui Lian , Cai Yan , Xin Xiaoping , He Xiaoshun , Huang Junqi
Published: December 2021

Purpose

Hepatocellular carcinoma (HCC), a worldwide leading cause of morbidity and mortality, is the most frequent primary liver tumor. Most HCC patients are diagnosed with advanced liver cancer, resulting in a very low 5-year survival rate. Thus, there is an urgent need for the development of targeted therapies. In this study, we aimed to investigate the effect and mechanism of the miR-20a/EZH1 axis on the proliferation and metastasis of HCC and the inhibitory effect of the EZH1/EZH2 inhibitor UNC1999 on HCC.

Materials and Methods

The expression of miR-20a in human HCC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). The expressions of proteins were analyzed with immunohistochemistry and Western blotting. Luciferase assay was used to verify whether miR-20a targets EZH1 or EZH2. The effect of miR-20a on HCC progression was studied in vivo and in vitro. The tumor inhibitory effect of UNC1999 was confirmed in vivo. CCK8 assay, wound healing assay, cell migration and invasion assay were used to evaluate the synergistic effect of UNC1999 with sorafenib. RNA sequencing (RNA-seq) was performed to screen the differentially expressed genes in the Huh7 and SMMC7721 cell lines after UNC1999, sorafenib, and combination treatments.

Results

In this study, miR-20a showed a lower expression in both HCC tissues and cell lines. MiR-20a inhibited the proliferation and migration of SMMC7721 and Huh7 cells. The results of the luciferase assay and Western blot analysis revealed that miR-20a directly targeted EZH1, a histone methyltransferase. We demonstrated that miR-20a negatively regulated the expression of EZH1 and inhibited the proliferation and metastasis of HCC by reducing H3K27 methylation. We found UNC1999 inhibited tumor cells proliferation and enhanced the inhibitory effect of sorafenib.

Conclusion

We demonstrated that miR-20a suppresses the tumor proliferation and metastasis in HCC by directly targeting EZH1. UNC1999 can inhibit tumor proliferation in vivo and increase the sensitivity of hepatoma cell lines to sorafenib.
Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study
Authors: Shi Xue , Liu Xiaoqian , Li Xiaomei , Li Yahan , Lu Dongyue , Sun Xue , Li Ying , Hu Shunfeng , Zhang Yuanfeng , Zhou Xiangxiang , Wang Xin , Chen Haiping , Fang Xiaosheng
Published: December 2021

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.
The Metabolism Symbiosis Between Pancreatic Cancer and Tumor Microenvironment
Authors: Li Ying , Zhang Ju , Xu Jie , Liu Shanglong
Published: December 2021

Complex interactions occur between tumor cells and the tumor microenvironment. Studies have focused on the mechanism of metabolic symbiosis between tumors and the tumor microenvironment. During tumor development, the metabolic pattern undergoes significant changes, and the optimal metabolic mode of the tumor is selected on the basis of its individual environment. Tumor cells can adapt to a specific microenvironment through metabolic adjustment to achieve compatibility. In this study, the effects of tumor glucose metabolism, lipid metabolism, and amino acid metabolism on the tumor microenvironment and related mechanisms were reviewed. Selective targeting of tumor cell metabolic reprogramming is an attractive direction for tumor therapy. Understanding the mechanism of tumor metabolic adaptation and determining the metabolism symbiosis mechanism between tumor cells and the surrounding microenvironment may provide a new approach for treatment, which is of great significance for accelerating the development of targeted tumor metabolic drugs and administering individualized tumor metabolic therapy.
Case Report: Postoperative Recurrence of Adrenal Epithelioid Angiosarcoma Achieved Complete Response by Combination Chemotherapy With Liposomal Doxorubicin and Paclitaxel
Authors: Wei Hangping , Mao Jie , Wu Yandan , Zhou Qinfei
Published: December 2021

Background

Primary adrenal epithelioid angiosarcoma is an extremely rare cancer with a poor prognosis. Because of the rarity of this disease, treatment options have not been well-studied.

Case presentation

A 51-year-old man was admitted to Zhejiang Cancer Hospital, diagnosed with a recurrence of adrenal epithelioid angiosarcoma. He had undergone a surgical resection seven months earlier. Combination chemotherapy with liposomal doxorubicin and paclitaxel was administered. After two cycles of chemotherapy, his pain was relieved. Computed tomography (CT) suggested that the soft tissue tumour lesions in the surgical area had disappeared, mediastinal and mediastinal-hilar lymph nodes were significantly reduced or had disappeared, and the patient had achieved a partial response (PR). CT after six cycles of chemotherapy indicated that the patient had achieved a complete response (CR).

Conclusion

Combination chemotherapy with liposomal doxorubicin and paclitaxel may be a preferred therapy for recurrent or advanced adrenal epithelioid angiosarcoma.
Congenital Cytomegalovirus and Human Immunodeficiency Virus: Effects on Hearing, Speech and Language Development, and Clinical Outcomes in Children
Authors: Walsh Hannah , Zuwala Jillian , Hunter Jessica , Oh Yonghee
Published: December 2021

Prenatal infections can have adverse effects on an infant's hearing, speech, and language development. Congenital cytomegalovirus (CMV) and human immunodeficiency virus (HIV) are two such infections that may lead to these complications, especially when left untreated. CMV is commonly associated with sensorineural hearing loss in children, and it can also be associated with anatomical abnormalities in the central nervous system responsible for speech, language, and intellectual acquisition. In terms of speech, language, and hearing, HIV is most associated with conductive and/or sensorineural hearing loss and expressive language deficits. Children born with these infections may benefit from cochlear implantation for severe to profound sensorineural hearing losses and/or speech therapy for speech/language deficits. CMV and HIV simultaneously present in infants has not been thoroughly studied, but one may hypothesize these speech, language, and hearing deficits to be present with potentially higher severity. Early identification of the infection in combination with early intervention strategies yields better results for these children than no identification or intervention. The purpose of this review was to investigate how congenital CMV and/or HIV may affect hearing, speech, and language development in children, and the importance of early identification for these populations.
Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids
Authors: Tilaoui Mounir , Ait Mouse Hassan , Zyad Abdelmajid
Published: December 2021

Cancer is a complex multifactorial disease that results from alterations in many physiological and biochemical functions. Over the last few decades, it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, resulting in tumor relapse. Thus, there is a continuous need to discover new and effective anticancer drugs. Natural products from plants have served as a primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. The present review describes plant-based alkaloids, which have been reported as active or potentially active in cancer treatment within the past 4 years (2017–2020), both in preclinical research and/or in clinical trials. In addition, recent insights into the possible molecular mechanism of action of alkaloid prodrugs naturally present in plants are also highlighted.
Gastric Ulcer Healing Property of Bryophyllum pinnatum Leaf Extract in Chronic Model In Vivo and Gastroprotective Activity of Its Major Flavonoid
Authors: De Araújo Edilane Rodrigues Dantas , Guerra Gerlane Coelho Bernardo , Andrade Anderson Wilbur Lopes , Fernandes Júlia Morais , Da Silva Valéria Costa , De Aragão Tavares Emanuella , De Araújo Aurigena Antunes , de Araújo Júnior Raimundo Fernandes , Zucolotto Silvana Maria
Published: December 2021

Gastric ulcer is a common disease that develops complications such as hemorrhages and perforations when not properly treated. Extended use of drugs in the treatment of this pathology can provoke many adverse effects. Therefore, finding medicinal plants with gastroprotective and mucosal healing properties has gained increasing interest. Bryophyllum pinnatum (Crassulaceae), popularly known in Brazil as “saião” or “coirama,” has been used to treat inflammatory disorders. It is rich in flavonoids, and quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside-Bp1 is its major compound. In this study, we aimed to investigate ulcer healing properties of B. pinnatum against an acetic acid–induced chronic ulcer model and the gastroprotective activity of Bp1 against gastric lesions induced by ethanol and indomethacin. Ultrafast liquid chromatography was used to quantify the main compounds (mg/g of the extract)—quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (33.12 ± 0.056), kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (3.98 ± 0.049), and quercetin 3-O-α-L-rhamnopyranoside (4.26 ± 0.022) and showed good linearity, specificity, selectivity, precision, robustness, and accuracy. In vivo studies showed that treatment with the extract at 250 and 500 mg/kg stimulated the healing process in the gastric mucosa with significant ulceration index reduction, followed by improvement in the antioxidant defense system [increased glutathione (GSH) levels, decreased superoxide dismutase upregulation, and malondialdehyde (MDA) levels]. Moreover, the extract decreased interleukin-1β and tumor necrosis factor-a levels and myeloperoxidase (MPO) activity, increased interleukin 10 levels, showed a cytoprotective effect in histological analyzes and also downregulated the expression of cyclooxygenase-2 and NF-κB (p65). The pretreatment with Bp1 at a dose of 5 mg/kg reduced gastric lesions in the ethanol and indomethacin models, increased GSH, and decreased MDA levels. In addition, the pretreatment decreased MPO activity, interleukin-1β and tumor necrosis factor-α levels, while also showing a cytoprotective effect in histological analyzes. Our study suggests that treatment with B. pinnatum extract showed a higher inhibition percentage than pretreatment with the Bp1. This might in turn suggest that Bp1 has gastroprotective activity, but other compounds can act synergistically, potentiating its effect. We conclude that B. pinnatum leaf extract could be a new source of raw material rich in phenolic compounds to be applied in food or medicine.
Age-Related Decrease in Abdominal Pain and Associated Structural- and Functional Mechanisms: An Exploratory Study in Healthy Individuals and Irritable Bowel Syndrome Patients
Authors: Beckers Abraham B. , Wilms Ellen , Mujagic Zlatan , Kajtár Béla , Csekő Kata , Weerts Zsa Zsa R. M. , Vork Lisa , Troost Freddy J. , Kruimel Joanna W. , Conchillo José M. , Helyes Zsuzsanna , Masclee Ad A. M. , Keszthelyi Daniel , Jonkers Daisy M. A. E.
Published: December 2021

Introduction: The world population is ageing, resulting in increased prevalence of age-related comorbidities and healthcare costs. Limited data are available on intestinal health in elderly populations. Structural and functional changes, including altered visceroperception, may lead to altered bowel habits and abdominal symptoms in healthy individuals and irritable bowel syndrome (IBS) patients. Our aim was to explore age-related changes in gastrointestinal symptoms and underlying mechanisms.

Methods: In total, 780 subjects (IBS patients n = 463, healthy subjects n = 317) from two separate studies were included. Subjects were divided into different age groups ranging from young adult to elderly. Demographics and gastrointestinal symptom scores were collected from all participants using validated questionnaires. A subset of 233 IBS patients and 103 controls underwent a rectal barostat procedure to assess visceral hypersensitivity. Sigmoid biopsies were obtained from 10 healthy young adults and 10 healthy elderly. Expression of the visceral pain-associated receptors transient receptor potential (TRP) Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) genes were investigated by quantitative RT-PCR and immunofluorescence.

Results: Both elderly IBS and healthy individuals showed significantly lower scores for abdominal pain (p < 0.001) and indigestion (p < 0.05) as compared to respective young adults. Visceral hypersensitivity was less common in elderly than young IBS patients (p < 0.001). Relative TRPA1 gene transcription, as well as TRPA1 and TRPV1 immunoreactivity were significantly lower in healthy elderly versus healthy young adults (p < 0.05).

Conclusions: Our findings show an age-related decrease in abdominal pain perception. This may in part be related to decreased TRPA1 and/or TRPV1 receptor expression. Further studies are needed to reveal precise underlying mechanisms and the associations with intestinal health.
Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3
Authors: Dan William , Park Ga Hyun , Vemaraju Shruti , Wu Amy D. , Perez Kristina , Rao Meenakshi , Berkowitz Dan E. , Lang Richard A. , Yim Peter D.
Published: December 2021

Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.
Pharmacotherapy of Primary Impulsive Aggression in Violent Criminal Offenders
Authors: Felthous Alan R. , McCoy Bridget , Nassif Jose Bou , Duggirala Rajat , Kim Ellen , Carabellese Fulvio , Stanford Matthew S.
Published: December 2021

Primary impulsive aggression (PIA) can be implicated as a common factor that results in an arrest, disciplinary, and restraint measures during confinement, and criminal recidivism after release. Evidence suggests that anti-impulsive aggression agents (AIAAs) can diminish or prevent impulsive aggression even when occurring with personality pathology such as borderline or antisocial personality disorder (ASPD), common conditions in offender populations. A previous review identified agents that have been subjected to controlled drug trials of sufficient quality, and subsequently, a decisional algorithm was developed for selecting an AIAA for individuals with IA. This selection process began with the five agents that showed efficacy in two or more quality studies from the earlier review. Today, 8 years after the quality review study, the present authors undertook this follow-up literature review. The aims of the present review were to survey the literature to identify and assess: (1) drug trials of comparable quality published since the 2013 review, including trials of the previously identified AIAAs as well as trials of agents not included in the earlier review; (2) severity of aggressive outbursts; (3) the materiality of risks or side-effects that are associated with individual AIAAs as well as antipsychotic agents commonly used to control clinical aggression; (4) efficacy of these agents in special populations (e.g., females); and (5) cost and convenience of each agent. Improved pharmacotherapy of PIA by addressing risks, side effects and practicality as well as the efficacy of AIAAs, should promote the rehabilitation and reintegration of some pathologically aggressive offenders back into the community.
Relationships Between Work-to-Family Conflict and the Food Domain for Dual-Earner Parents With Adolescent Children
Authors: Schnettler Berta , Miranda-Zapata Edgardo , Orellana Ligia , Poblete Héctor , Lobos Germán , Adasme-Berríos Cristian , Lapo María , Beroiza Katherine
Published: December 2021

The impact of work-to-family conflict (WtoFC) can extend beyond family and work, and to other domains that contribute to well-being, such as the food domain. This study examined associations between WtoFC, perception of atmosphere of family meals (AFM), and satisfaction with food-related life (SWFoL) in dual-earner parents with adolescent children, and tested the mediating role of AFM between WtoFC and SWFoL. Questionnaires were administered to 473 different-sex dual-earner parents and one of their adolescent children (mean age 12.5 years, 51.4% male) in Temuco, Chile. Parents responded to a measure of work-to-family conflict; the three family members answered the Project-EAT Atmosphere of family meals scale, and the Satisfaction with Food-related Life Scale. Analyses were conducted using the Actor-Partner Interdependence Model and structural equation modeling. Results showed a negative association from WtoFC to SWFoL in both parents, while a more positive perception of atmosphere of family meals was linked to higher SWFoL in the three family members. Moreover, WtoFC was negatively linked to SWFoL in parents, while only mothers' WtoFC had a negative association with their adolescent children's SWFoL. Policymakers and organizations can contribute to workers' and their families' food-related well-being by fostering policies and measures to reduce WtoFC.
Learning Beliefs, Time on Platform, and Academic Performance During the COVID-19 in University STEM Students
Authors: Lobos Karla , Sáez-Delgado Fabiola , Cobo-Rendón Rubia , Mella Norambuena Javier , Maldonado Trapp Alejandra , Cisternas San Martín Nataly , Bruna Jofré Carola
Published: December 2021

Due to the closure of universities worldwide because of the COVID-19 pandemic, teaching methods were suddenly transformed to an emergency remote teaching (ERT) modality. Due to the practical nature of STEM courses, students cannot participate in activities in which manipulating objects is necessary for accomplishing learning objectives. In this study, we analyze the relation among STEM students learning beliefs at the beginning of ERT (T1) with their Learning Management systems (LMS) time-on-task and their final academic performance (T2) during the first semester of ERT. We used a prospective longitudinal design. 2063 students (32.3% females) from a university in Chile participated, where the academic year starts in March and finishes in December 2020. We assessed their learning and performance beliefs through an online questionnaire answered at the beginning of the academic period (T1). Then, using learning analytics, time invested in the CANVAS LMS and the academic performance achieved by students at the end of the semester (T2) were assessed. The results show that students mainly stated negative beliefs about learning opportunities during ERT (n = 1,396; 67.7%). In addition, 48.5% (n = 1,000) of students stated beliefs of “medium” academic performance for the first semester (T1). Students with lower learning beliefs at T1 spent less time in the LMS during the semester and had a lower academic performance at T2 than students who had higher learning beliefs at T1. The implications of these findings on the role of instructors and institutions of higher education are discussed.
Factors Associated With a High Motivation to Undergo Fertility Preservation in Female Cancer Patients
Authors: Di Mattei Valentina Elisabetta , Perego Gaia , Taranto Paola , Rancoita Paola M. V. , Maglione Mariangela , Notarianni Lisa , Mangili Giorgia , Bergamini Alice , Cioffi Raffaella , Papaleo Enrico , Candiani Massimo
Published: December 2021

Objective: Fertility loss due to cancer treatment can be a devastating experience for women and the couple. Undergoing fertility preservation can be a complex decision from both a medical and emotional point of view. The aim of the present study was to evaluate which socio-demographic and psychological factors predict a high motivation to undergo fertility preservation.

Methods: Fifty-eight female cancer patients who accessed an Oncofertility Unit completed: a questionnaire to collect socio-demographic characteristics and the level of motivation, the Beck-Depression Inventory-II, the State-Trait Anxiety Inventory-Y, and the Fertility Problem Inventory.

Results: Almost half of the sample (44.8%) declared a high motivation. At multiple logistic regression analysis only the “Need for parenthood” subscale of the FPI predicted a high motivation. We alternatively evaluated as possible predictor the construct “Representations about the importance of parenthood” (i.e., the sum of the “Need for Parenthood” and “Rejection of childfree lifestyle” subscales) in place of the two separate subscales. At multiple logistic regression analysis, only this variable predicted a high motivation to undergo fertility preservation.

Conclusion: The most important predictor of a high motivation to undergo fertility preservation is the individual desire for parenthood. This implies that, regardless of socio-demographic characteristics, any woman of childbearing age should receive an appropriate counseling about fertility preservation.