bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Global Prevalence of Interstitial Lung Disease
Authors: Kaul Bhavika , Cottin Vincent , Collard Harold R. , Valenzuela Claudia
Published: November 2021

There are limited epidemiologic studies describing the global burden and geographic heterogeneity of interstitial lung disease (ILD) subtypes. We found that among seventeen methodologically heterogenous studies that examined the incidence, prevalence and relative frequencies of ILDs, the incidence of ILD ranged from 1 to 31.5 per 100,000 person-years and prevalence ranged from 6.3 to 71 per 100,000 people. In North America and Europe, idiopathic pulmonary fibrosis and sarcoidosis were the most prevalent ILDs while the relative frequency of hypersensitivity pneumonitis was higher in Asia, particularly in India (10.7–47.3%) and Pakistan (12.6%). The relative frequency of connective tissue disease ILD demonstrated the greatest geographic variability, ranging from 7.5% of cases in Belgium to 33.3% of cases in Canada and 34.8% of cases in Saudi Arabia. These differences may represent true differences based on underlying characteristics of the source populations or methodological differences in disease classification and patient recruitment (registry vs. population-based cohorts). There are three areas where we feel addition work is needed to better understand the global burden of ILD. First, a standard ontology with diagnostic confidence thresholds for comparative epidemiology studies of ILD is needed. Second, more globally representative data should be published in English language journals as current literature has largely focused on Europe and North America with little data from South America, Africa and Asia. Third, the inclusion of community-based cohorts that leverage the strength of large databases can help better estimate population burden of disease. These large, community-based longitudinal cohorts would also allow for tracking of global trends and be a valuable resource for collective study. We believe the ILD research community should organize to define a shared ontology for disease classification and commit to conducting global claims and electronic health record based epidemiologic studies in a standardized fashion. Aggregating and sharing this type of data would provide a unique opportunity for international collaboration as our understanding of ILD continues to grow and evolve. Better understanding the geographic and temporal patterns of disease prevalence and identifying clusters of ILD subtypes will facilitate improved understanding of emerging risk factors and help identify targets for future intervention.
Mining of Cyanobacterial Genomes Indicates Natural Product Biosynthetic Gene Clusters Located in Conjugative Plasmids
Authors: Popin Rafael Vicentini , Alvarenga Danillo Oliveira , Castelo-Branco Raquel , Fewer David Peter , Sivonen Kaarina
Published: November 2021

Microbial natural products are compounds with unique chemical structures and diverse biological activities. Cyanobacteria commonly possess a wide range of biosynthetic gene clusters (BGCs) to produce natural products. Although natural product BGCs have been found in almost all cyanobacterial genomes, little attention has been given in cyanobacterial research to the partitioning of these biosynthetic pathways in chromosomes and plasmids. Cyanobacterial plasmids are believed to disperse several natural product BGCs, such as toxins, by plasmids through horizontal gene transfer. Therefore, plasmids may confer the ability to produce toxins and may play a role in the evolution of diverse natural product BGCs from cyanobacteria. Here, we performed an analysis of the distribution of natural product BGCs in 185 genomes and mapped the presence of genes involved in the conjugation in plasmids. The 185 analyzed genomes revealed 1817 natural products BGCs. Individual genomes contained 1–42 biosynthetic pathways (mean 8), 95% of which were present in chromosomes and the remaining 5% in plasmids. Of the 424 analyzed cyanobacterial plasmids, 12% contained homologs of genes involved in conjugation and natural product biosynthetic pathways. Among the biosynthetic pathways in plasmids, manual curation identified those to produce aeruginosin, anabaenopeptin, ambiguine, cryptophycin, hassallidin, geosmin, and microcystin. These compounds are known toxins, protease inhibitors, odorous compounds, antimicrobials, and antitumorals. The present study provides in silico evidence using genome mining that plasmids may be involved in the distribution of natural product BGCs in cyanobacteria. Consequently, cyanobacterial plasmids have importance in the context of biotechnology, water management, and public health risk assessment. Future research should explore in vivo conjugation and the end products of natural product BGCs in plasmids via chemical analyses.
Tradition as a Stepping Stone for a Microbial Defined Water Kefir Fermentation Process: Insights in Cell Growth, Bioflavoring, and Sensory Perception
Authors: Köhler Sarah , Schmacht Maximilian , Troubounis Aktino H. L. , Ludszuweit Marie , Rettberg Nils , Senz Martin
Published: November 2021

A process development from a traditional grain-based fermentation to a defined water kefir fermentation using a co-culture of one lactic acid bacterium and one yeast was elaborated as a prerequisite for an industrially scalable, controllable, and reproducible process. Further, to meet a healthy lifestyle, a low ethanol-containing product was aimed for. Five microbial strains—Hanseniaspora valbyensis, Dekkera bruxellensis, Saccharomyces cerevisiae, Liquorilactobacillus nagelii, and Leuconostoc mesenteroides—were used in pairs in order to examine their influence on the fermentation progress and the properties of the resulting water kefir products against grains as a control. Thereby, the combination of H. valbyensis and L. mesenteroides provided the best-rated water kefir beverage in terms of taste and low ethanol concentrations at the same time. As a further contribution to harmonization and reduction of complexity, the usage of dried figs in the medium was replaced by fig syrup, which could have been proven as an adequate substitute. However, nutritional limitations were faced afterward, and thus, an appropriate supplementation strategy for yeast extract was established. Finally, comparative trials in 5-L scale applying grains as well as a defined microbial consortium showed both water kefir beverages characterized by a pH of 3.14, and lactic acid and aromatic sensory properties. The product resulting from co-culturing outperformed the grain-based one, as the ethanol level was considerably lower in favor of an increased amount of lactic acid. The possibility of achieving a water kefir product by using only two species shows high potential for further detailed research of microbial interactions and thus functionality of water kefir.
Microbial Ecology of French Dry Fermented Sausages and Mycotoxin Risk Evaluation During Storage
Authors: Coton Monika , Deniel Franck , Mounier Jérôme , Joubrel Rozenn , Robieu Emeline , Pawtowski Audrey , Jeuge Sabine , Taminiau Bernard , Daube Georges , Coton Emmanuel , Frémaux Bastien
Published: November 2021

Dry fermented sausages are produced worldwide by well-controlled fermentation processes involving complex microbiota including many bacterial and fungal species with key technological roles. However, to date, fungal diversity on sausage casings during storage has not been fully described. In this context, we studied the microbial communities from dry fermented sausages naturally colonized or voluntarily surface inoculated with molds during storage using both culture-dependent and metabarcoding methods. Staphylococci and lactic acid bacteria largely dominated in samples, although some halotolerant genera (e.g., Halomonas, Tetragenococcus, and Celerinatantimonas spp.) were also frequently observed. Fungal populations varied from 7.2 to 9.8 log TFU/cm2 sausage casing during storage, suggesting relatively low count variability among products. Fungal diversity identified on voluntarily inoculated casings was lower (dominated by Penicillium nalgiovense and Debaryomyces hansenii) than naturally environment-inoculated fermented sausages (colonized by P. nalgiovense, Penicillium nordicum, and other Penicillium spp. and sporadically by Scopulariopsis sp., D. hansenii, and Candida zeylanoïdes). P. nalgiovense and D. hansenii were systematically identified, highlighting their key technological role. The mycotoxin risk was then evaluated, and in situ mycotoxin production of selected mold isolates was determined during pilot-scale sausage productions. Among the identified fungal species, P. nalgiovense was confirmed not to produce mycotoxins. However, some P. nordicum, Penicillium chrysogenum, Penicillium bialowienzense, Penicillium brevicompactum, and Penicillium citreonigrum isolates produced one or more mycotoxins in vitro. P. nordicum also produced ochratoxin A during pilot-scale sausage productions using “worst-case” conditions in the absence of biotic competition. These data provide new knowledge on fermented sausage microbiota and the potential mycotoxin risk during storage.
Biological Characterization of Hepatitis B virus Genotypes: Their Role in Viral Replication and Antigen Expression
Authors: Elizalde María Mercedes , Tadey Luciana , Mammana Lilia , Quarleri Jorge Fabián , Campos Rodolfo Héctor , Flichman Diego Martín
Published: November 2021

Hepatitis B virus (HBV) inter-host evolution has resulted in genomic diversification reflected in the existence of nine genotypes (A-I) and numerous subgenotypes. There is growing evidence that genotypes influence HBV natural history, clinical outcomes, and treatment response. However, the biological characteristics underlying these differences have not yet been established. By transfecting HuH-7 cells with unit-length constructs of genotypes A2, B2, C1, D1, and F1b, we identified major differences in HBV replicative capacity and antigen expression across genotypes. Genotypes B2 and F1b showed a 2-fold increase in cccDNA levels compared to the other genotypes (p<0.005). Genotype A2 expressed the lowest pgRNA levels, with a 70-fold decrease in relation to the other genotypes (p<0.0001), while genotype B2 showed the lowest Precore RNA levels, with a 100-fold reduction compared to genotype A2 (p<0.0001). The highest intracellular HBV DNA levels were observed for genotype B2 and the lowest for genotypes A2 and C1 (p<0.0001). Regarding antigen expression, genotype F1b secreted the highest HBsAg levels and genotype D1 the lowest (p<0.0001), while genotypes A2 and B2 showed the highest intracellular HBsAg levels (p<0.0001). Interestingly, genotype C1 secreted the highest HBeAg levels, while genotype A2 showed the highest intracellular levels (p<0.0001). Finally, the analysis of the intra/extracellular antigen ratios revealed that most genotypes retained intracellularly 5–20% of the antigens, except the genotype A2 that retained 50% of the total expressed antigens. In conclusion, this study provides new insights into the biological characteristics of HBV genotypes, being the first study to comparatively analyze European (A and D) and Asian (B and C) genotypes with the Latin American (F) genotype. The differences in HBV replication and antigen expression might contribute to understand the differential role of genotypes in pathogenesis.
Gender Difference in Associations Between Telomere Length and Risk Factors in Patients With Stroke
Authors: Wang Yuqing , Jiao Fengjuan , Zheng Huancheng , Kong Qingsheng , Li Ran , Zhang Xiaojie , Yan Li , Hao Yanlei , Wu Yili
Published: November 2021

Multiple risk factors of stroke are associated with telomere length shortening. Although leukocyte telomere length (LTL) is shorter in patients with stroke, the heterogeneity is high. Risk factors may be differentially associated with LTL in male and female patients contributing to the heterogeneity. However, the gender difference in associations between LTL and risk factors in stroke patients has not been investigated. In this study, we investigated the gender difference in associations between LTL and risk factors in 312 stroke patients. Real-time quantitative PCR was used to determine relative LTL, and multiple linear regression analysis was applied for association analyses. We found that LTL was negatively associated with triglyceride (TG) in all patients [β(95% CI) = −0.69 (−1.26, −0.11), P < 0.05] after adjusting confounders. Importantly, LTL was negatively associated with lack of exercise [β(95% CI) = −1.80 (−3.12, −0.49), P < 0.05] and LDL levels [β(95% CI) = −3.22 (−6.05, −0.390), P < 0.05] in male patients, while LTL was negatively associated with dyssomnia [β(95%CI) = −2.00 (−3.96, −0.07), P < 0.05] and diabetes [β(95%CI) = −2.13 (−4.10, −0.27), P < 0.01] in female patients. Our study showed that LTL is differently associated with risk factors in male and female patients with stroke, indicating that gender difference should be considered when LTL is potentially applied as an index of risk and prognosis for stroke. Our study also provides an insight into that gender differences should be considered when developing intervention strategies for stroke prevention and treatment.
The Immunoglobulin Superfamily Member Basigin Is Required for Complex Dendrite Formation in Drosophila
Authors: Shrestha Brikha R. , Burgos Anita , Grueber Wesley B.
Published: November 2021

Coordination of dendrite growth with changes in the surrounding substrate occurs widely in the nervous system and is vital for establishing and maintaining neural circuits. However, the molecular basis of this important developmental process remains poorly understood. To identify potential mediators of neuron-substrate interactions important for dendrite morphogenesis, we undertook an expression pattern-based screen in Drosophila larvae, which revealed many proteins with expression in dendritic arborization (da) sensory neurons and in neurons and their epidermal substrate. We found that reporters for Basigin, a cell surface molecule of the immunoglobulin (Ig) superfamily previously implicated in cell-cell and cell-substrate interactions, are expressed in da sensory neurons and epidermis. Loss of Basigin in da neurons led to defects in morphogenesis of the complex dendrites of class IV da neurons. Classes of sensory neurons with simpler branching patterns were unaffected by loss of Basigin. Structure-function analyses showed that a juxtamembrane KRR motif is critical for this function. Furthermore, knock down of Basigin in the epidermis led to defects in dendrite elaboration of class IV neurons, suggesting a non-autonomous role. Together, our findings support a role for Basigin in complex dendrite morphogenesis and interactions between dendrites and the adjacent epidermis.
Simultaneous Quantification of 11 Phenolic Compounds and Consistency Evaluation in Four Dendrobium Species Used as Ingredients of the Traditional Chinese Medicine Shihu
Authors: Zhu An-Ling , Hao Jing-Wen , Liu Lei , Wang Qi , Chen Nai-Dong , Wang Guang-Lin , Liu Xiao-Quan , Li Qiang , Xu Hui-Min , Yang Wei-Han
Published: November 2021

The interchangeable use of different herbs to prepare the same formulation is a common practice in Traditional Chinese Medicine (TCM). However, this practice would require the component herbs to share similar compositions, at least in terms of the bioactive agents, to ensure they can replace each other in drug preparation. In this study, we developed an effective and comprehensive high-performance liquid chromatography-diode array detector (HPLC-DAD) method for simultaneous analysis of 11 phenolic compounds in the methanol extracts of Dendrobium huoshanense, Dendrobium nobile (D. nobile), Dendrobium chrysotoxum (D. chrysotoxum), and Dendrobium fimbriatum (D. fimbriatum), which have been identified as interchangeable ingredients for the same TCM preparation “Shihu” in the Chinese pharmacopeia (ChP). The consistency of the four Dendrobium species was evaluated on the basis of the presence of the 11 investigated compounds and the HPLC fingerprints of the methanol extracts of the plants. When gradient elution was performed with a solvent system of acetonitrile and water on a Zorbax Eclipse XDB-C18 (150 mm × 4.6 mm, 5 μm) with monitoring at 220 nm, all 11 investigated compounds were isolated at the baseline. The established HPLC method showed excellent linearity (all analytical curves showed relative coefficients [R2] > 0.999), sensitivity, precision (relative standard deviation [RSD] < 2%), and accuracy (recovery, 90.65–99.17%). These findings confirmed that the method we constructed was reliable. Quantification analysis showed significant differences in the contents of the investigated polyphenols in the four Dendrobium species. Evaluations of consistency revealed that the similarities among the four species were 0.299–0.906 in assessments based on the 11 polyphenols and 0.685–0.968 in assessments based on HPLC fingerprints. Thus, the components of the four Dendrobium species may be significantly different, and more experiments are required to determine whether they can be used interchangeably in the same amounts for preparing the formulation according to ChP.
A Retrospective Study of Latissimus Dorsi Flap in Immediate Breast Reconstruction
Authors: Zheng Hongmei , Zhu Guodong , Guan Qing , Fan Wei , Li Xiang , Yu Mancheng , Xu Juan , Wu Xinhong
Published: November 2021

Background

There are many different methods used for immediate breast reconstruction, but the advantages and disadvantages between distinct methods are not reported and compared directly.

Methods

We collected the data of patients who underwent breast reconstruction from 2010 to 2015 and classified a total of 103 patients into three groups: i) skin- or nipple-sparing mastectomy with implant and partial latissimus dorsi flap (MIPLD); ii) skin- or nipple-sparing mastectomy with the whole latissimus dorsi flap (MWLD); and iii) breast-conserving surgery and partial latissimus dorsi flap (BCSPLD). The outcome, safety, and cosmetic outcome of the latissimus dorsi muscle flap with or without implant were reported and compared.

Results

The procedures were successful in all cases. None of the patients had severe complications. The 5-year distant metastasis-free survival is 94.2%. All the patients exhibited good arm and back function. Based on the evaluation of the BREAST-Q score, the cosmetic outcome of Satisfaction with Breasts was excellent or good in 97.8% of the cases.

Conclusions

MIPLD, MWLD, and BCSPLD stand for three distinct methods for immediate breast reconstruction with good outcome and aesthetic effect. They were safe, were easy to perform, and provided quick recovery and good quality of life. Therefore, these three breast reconstructive methods are worthy of widespread use in clinical practice and provide different ways to reconstruct the breast according to the patients’ conditions and preferences.
TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer
Authors: Zhang Dexiang , Lu Pinxiang , Zhu Kaihua , Wu Haixia , Dai Yuedi
Published: November 2021

KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer cells. However, whether TFCP2 plays an important role in pancreatic cancer cell senescence is not clear. In this study, we found upregulation of TFCP2 expression in pancreatic cancer was associated with KRAS mutation. Overexpression of TFCP2 inhibited cell senescence. Knockdown of TFCP2 promoted cell senescence. Mechanistically, the interaction between TFCP2 and SREBP2 (sterol regulatory element binding transcription factor 2) synergistically activated the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis, and statins could reverse the inhibitory effect of TFCP2 on senescence. In conclusion, our study reveals a new mechanism underlying the TFCP2 regulation of pancreatic cancer cell senescence, providing a new target for the treatment of pancreatic cancer.
Innovative Synoptic Reporting With Seven-Point Sampling Protocol to Improve Detection Rate of Microvascular Invasion in Hepatocellular Carcinoma
Authors: Liao Bing , Liu Lijuan , Wei Lihong , Wang Yuefeng , Chen Lili , Cao Qinghua , Zhou Qian , Xiao Han , Chen Shuling , Peng Sui , Li Shaoqiang , Kuang Ming
Published: November 2021

Pathological MVI diagnosis could help to determine the prognosis and need for adjuvant therapy in hepatocellular carcinoma (HCC). However, narrative reporting (NR) would miss relevant clinical information and non-standardized sampling would underestimate MVI detection. Our objective was to explore the impact of innovative synoptic reporting (SR) and seven-point sampling (SPRING) protocol on microvascular invasion (MVI) rate and patient outcomes. In retrospective cohort, we extracted MVI status from NR in three centers and re-reviewed specimen sections by SR recommended by the College of American Pathologists (CAP) in our center. In prospective cohort, our center implemented the SPRING protocol, and external centers remained traditional pathological examination. MVI rate was compared between our center and external centers in both cohorts. Recurrence-free survival (RFS) before and after implementation was calculated by Kaplan-Meier method and compared by the log-rank test. In retrospective study, we found there was no significant difference in MVI rate between our center and external centers [10.3% (115/1112) vs. 12.4% (35/282), P=0.316]. In our center, SR recommended by CAP improved the MVI detection rate from 10.3 to 38.6% (P<0.001). In prospective study, the MVI rate in our center under SPRING was significantly higher than external centers (53.2 vs. 17%, P<0.001). RFS of MVI (−) patients improved after SPRING in our center (P=0.010), but it remained unchanged in MVI (+) patients (P=0.200). We conclude that the SR recommended by CAP could help to improve MVI detection rate. Our SPRING protocol could help to further improve the MVI rate and optimize prognostic stratification for HCC patients.
Untargeted GC-MS-Based Metabolomics for Early Detection of Colorectal Cancer
Authors: Zhu Guoxue , Wang Yi , Wang Wang , Shang Fang , Pei Bin , Zhao Yang , Kong Desong , Fan Zhimin
Published: November 2021

Background

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers in the world with a 5-year survival rate of approximately 68%. Although researchers accumulated many scientific studies, its pathogenesis remains unclear yet. Detecting and removing these malignant polyps promptly is the most effective method in CRC prevention. Therefore, the analysis and disposal of malignant polyps is conducive to preventing CRC.

Methods

In the study, metabolic profiling as well as diagnostic biomarkers for CRC was investigated using untargeted GC-MS-based metabolomics methods to explore the intervention approaches. In order to better characterize the variations of tissue and serum metabolic profiles, orthogonal partial least-square discriminant analysis was carried out to further identify significant features. The key differences in tR–m/z pairs were screened by the S-plot and VIP value from OPLS-DA. Identified potential biomarkers were leading in the KEGG in finding interactions, which show the relationships among these signal pathways.

Results

Finally, 17 tissue and 13 serum candidate ions were selected based on their corresponding retention time, p-value, m/z, and VIP value. Simultaneously, the most influential pathways contributing to CRC were inositol phosphate metabolism, primary bile acid biosynthesis, phosphatidylinositol signaling system, and linoleic acid metabolism.

Conclusions

The preliminary results suggest that the GC-MS-based method coupled with the pattern recognition method and understanding these cancer-specific alterations could make it possible to detect CRC early and aid in the development of additional treatments for the disease, leading to improvements in CRC patients’ quality of life.
Perifosine, a Bioavailable Alkylphospholipid Akt Inhibitor, Exhibits Antitumor Activity in Murine Models of Cancer Brain Metastasis Through Favorable Tumor Exposure
Authors: Taniguchi Keisuke , Suzuki Tomo , Okamura Tomomi , Kurita Akinobu , Nohara Gou , Ishii Satoru , Kado Shoichi , Takagi Akimitsu , Tsugane Momomi , Shishido Yoshiyuki
Published: November 2021

Metastatic brain tumors are regarded as the most advanced stage of certain types of cancer; however, chemotherapy has played a limited role in the treatment of brain metastases. Here, we established murine models of brain metastasis using cell lines derived from human brain metastatic tumors, and aimed to explore the antitumor efficacy of perifosine, an orally active allosteric Akt inhibitor. We evaluated the effectiveness of perifosine by using it as a single agent in ectopic and orthotopic models created by injecting the DU 145 and NCI-H1915 cell lines into mice. Initially, the injected cells formed distant multifocal lesions in the brains of NCI-H1915 mice, making surgical resection impractical in clinical settings. We determined that perifosine could distribute into the brain and remain localized in that region for a long period. Perifosine significantly prolonged the survival of DU 145 and NCI-H1915 orthotopic brain tumor mice; additionally, complete tumor regression was observed in the NCI-H1915 model. Perifosine also elicited much stronger antitumor responses against subcutaneous NCI-H1915 growth; a similar trend of sensitivity to perifosine was also observed in the orthotopic models. Moreover, the degree of suppression of NCI-H1915 tumor growth was associated with long-term exposure to a high level of perifosine at the tumor site and the resultant blockage of the PI3K/Akt signaling pathway, a decrease in tumor cell proliferation, and increased apoptosis. The results presented here provide a promising approach for the future treatment of patients with metastatic brain cancers and emphasize the importance of enriching a patient population that has a higher probability of responding to perifosine.
The Feasibility of Haar Feature-Based Endoscopic Ultrasound Probe Tracking for Implanting Hydrogel Spacer in Radiation Therapy for Pancreatic Cancer
Authors: Feng Ziwei , Hooshangnejad Hamed , Shin Eun Ji , Narang Amol , Lediju Bell Muyinatu A. , Ding Kai
Published: November 2021

Purpose

We proposed a Haar feature-based method for tracking endoscopic ultrasound (EUS) probe in diagnostic computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans for guiding hydrogel injection without external tracking hardware. This study aimed to assess the feasibility of implementing our method with phantom and patient images.

Materials and Methods

Our methods included the pre-simulation section and Haar features extraction steps. Firstly, the simulated EUS set was generated based on anatomic information of interpolated CT/MRI images. Secondly, the efficient Haar features were extracted from simulated EUS images to create a Haar feature dictionary. The relative EUS probe position was estimated by searching the best matched Haar feature vector of the dictionary with Haar feature vector of target EUS images. The utilization of this method was validated using EUS phantom and patient CT/MRI images.

Results

In the phantom experiment, we showed that our Haar feature-based EUS probe tracking method can find the best matched simulated EUS image from a simulated EUS dictionary which includes 123 simulated images. The errors of all four target points between the real EUS image and the best matched EUS images were within 1 mm. In the patient CT/MRI scans, the best matched simulated EUS image was selected by our method accurately, thereby confirming the probe location. However, when applying our method in MRI images, our method is not always robust due to the low image resolution.

Conclusions

Our Haar feature-based method is capable to find the best matched simulated EUS image from the dictionary. We demonstrated the feasibility of our method for tracking EUS probe without external tracking hardware, thereby guiding the hydrogel injection between the head of the pancreas and duodenum.
Evaluation of Different Breast Cancer Screening Strategies for High-Risk Women in Beijing, China: A Real-World Population-Based Study
Authors: Zhang Xi , Yang Lei , Liu Shuo , Li Huichao , Li Qingyu , Cheng Yangyang , Wang Ning , Ji Jiafu
Published: November 2021

Background

Mammography-based breast cancer screening has been widely implemented in many developed countries. Evidence was needed on participation and diagnostic performance of population-based breast cancer screening using ultrasound in China.

Methods

We used data from the Cancer Screening Program in Urban China in Beijing from 2014 to 2019 and was followed up until July 2020 by matching with the Beijing Cancer Registry database. Eligible women between the ages of 45 and 69 years were recruited from six districts and assessed their risk of breast cancer through an established risk scoring system. Women evaluated to be at high risk of breast cancer were invited to undergo both ultrasound and mammography. Participation rates were calculated, and their associated factors were explored. In addition, the performance of five different breast cancer screening modalities was evaluated in this study.

Results

A total of 49,161 eligible women were recruited in this study. Among them, 15,550 women were assessed as high risk for breast cancer, and 7,500 women underwent ultrasound and/or mammography as recommended, with a participation rate of 48.2%. The sensitivity of mammography alone, ultrasound alone, combined of ultrasound and mammography, ultrasound for primary screening followed by mammography for triage, and mammography for preliminary screening followed by ultrasound for triage were19.2%, 38.5%, 50.0%, 46.2%, and 19.2%, and the specificity were 96.1%, 98.6%, 94.7%, 97.6%, 95.7%, respectively. The sensitivity of combined ultrasound and mammography, ultrasound for primary screening followed by mammography for triage, was significantly higher than mammography alone (p=0.008 and p=0.039). Additionally, ultrasound alone (48,323 RMB ($7,550)) and ultrasound for primary screening followed by mammography for triage (55,927 RMB ($8,739)) were the most cost-effective methods for breast cancer screening than other modalities.

Conclusions

Ultrasound alone and ultrasound for primary screening and mammography are superior to mammography for breast cancer screening in high-risk Chinese women.
Generation of KS-133 as a Novel Bicyclic Peptide with a Potent and Selective VIPR2 Antagonist Activity that Counteracts Cognitive Decline in a Mouse Model of Psychiatric Disorders
Authors: Sakamoto Kotaro , Chen Lu , Miyaoka Tatsunori , Yamada Mei , Masutani Teruaki , Ishimoto Kenji , Hino Nobumasa , Nakagawa Shinsaku , Asano Satoshi , Ago Yukio
Published: November 2021

Worldwide, more than 20 million people suffer from schizophrenia, but effective and definitive new therapeutic drugs/treatments have not been established. Vasoactive intestinal peptide receptor 2 (VIPR2) might be an attractive drug target for the treatment of schizophrenia because both preclinical and clinical studies have demonstrated a strong link between high expression/overactivation of VIPR2 and schizophrenia. Nevertheless, VIPR2-targeting drugs are not yet available. VIPR2 is a class-B G protein-coupled receptor that possesses high structural homology to its subtypes, vasoactive intestinal peptide receptor 1 (VIPR1) and pituitary adenylate cyclase-activating polypeptide type-1 receptor (PAC1). These biological and structural properties have made it difficult to discover small molecule drugs against VIPR2. In 2018, cyclic peptide VIpep-3, a VIPR2-selective antagonist, was reported. The aim of this study was to generate a VIpep-3 derivative for in vivo experiments. After amino acid substitution and structure optimization, we successfully generated KS-133 with 1) a VIPR2-selective and potent antagonistic activity, 2) at least 24 h of stability in plasma, and 3) in vivo pharmacological efficacies in a mouse model of psychiatric disorders through early postnatal activation of VIPR2. To the best of our knowledge, this is the first report of a VIPR2-selective antagonistic peptide that counteracts cognitive decline, a central feature of schizophrenia. KS-133 may contribute to studies and development of novel schizophrenia therapeutic drugs that target VIPR2.
Cardiometabolic Comorbidities in Patients With Psoriasis: Focusing on Risk, Biological Therapy, and Pathogenesis
Authors: Cai Jiangluyi , Cui Lian , Wang Yu , Li Ying , Zhang Xilin , Shi Yuling
Published: November 2021

Psoriasis is a chronic inflammatory disease characterized by erythematous scaly plaques, accompanied by systemic damage that leads to the development of multiple comorbidities. In particular, the association between psoriasis and cardiometabolic comorbidities, including cardiovascular diseases (CVDs), obesity, diabetes mellitus, and metabolic syndrome, has been verified in a considerable number of clinical trials. Moreover, the increased risk of cardiometabolic comorbidities positively correlates with psoriasis severity. Biologic therapy targeting inflammatory pathways or cytokines substantially improves the life quality of psoriasis patients and may affect cardiometabolic comorbidities by reducing their incidences. In this review, we focus on exploring the association between cardiometabolic comorbidities and psoriasis, and emphasize the benefits and precautions of biologic therapy in the management of psoriasis with cardiometabolic comorbidities. The pathogenic mechanisms of cardiometabolic comorbidities in psoriasis patients involve common genetic factors, lipid metabolism, insulin resistance, and shared inflammatory pathways such as tumor necrosis factor-α and interleukin-23/Th-17 pathways.
The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease
Authors: Nowak Anna , Kojder Klaudyna , Zielonka-Brzezicka Joanna , Wróbel Jacek , Bosiacki Mateusz , Fabiańska Marta , Wróbel Mariola , Sołek-Pastuszka Joanna , Klimowicz Adam
Published: November 2021

Alzheimer’s disease, a neurodegenerative disease, is one of the most common causes of dementia if elderly people worldwide. Alzheimer’s disease leads to the alienation of individuals and their exclusion from social and professional life. It is characterized mainly by the degradation of memory and disorientation, which occurs as a result of the loss of neuronal structure and function in different brain areas. In recent years, more and more attention has been paid to use in the treatment of natural bioactive compounds that will be effective in neurodegenerative diseases, including Alzheimer’s disease.G. bilobaL. and its most frequently used standardized extract (EGb 761), have been used for many years in supportive therapy and in the prevention of cognitive disorders. The paper presents an overview of reports on the pathogenesis of Alzheimer’s disease, as well as a summary of the properties ofG. bilobaextract and its effects on the possible pathogenesis of the disease. By exploring more about the pathogenesis of the disease and the benefits ofG. bilobaextract for patients with Alzheimer’s disease, it will be possible to create an individualized therapeutic protocol to optimize the treatment.
Intraspecific Variation Along an Elevational Gradient Alters Seed Scarification Responses in the Polymorphic Tree Species Acacia koa
Authors: Sugiyama Anna , Friday James B. , Giardina Christian P. , Jacobs Douglass F.
Published: November 2021

Physical dormancy in seeds can challenge restoration efforts where scarification conditions for optimal germination and seedling vigor are unknown. For species that occur along wide environmental gradients, optimal scarification conditions may also differ by seed source. We examined intraspecific variation in optimal scarification conditions for germination and seedling performance in koa (Acacia koa), which occurs across a wide range of environmental conditions. To evaluate scarification responses, we recorded imbibition percentage, germination percentage, germination time, seedling abnormalities, early mortality, seedling growth, and seedling survivorship. From these, we developed a scarification index (SI) that integrates these measures simultaneously. We hypothesized that seeds from lower elevation sources exposed to higher temperatures would have harder seed coats and would require more intense scarification treatments. To test this hypothesis, we repeatedly exposed seeds to hot water differing in temperature and time until seeds imbibed. Supporting the hypothesis, seeds from lower elevation sources generally required more intense scarification, although we found substantial variation among sources. Koa seeds germinated in about a week following imbibition. Boiling seeds (i.e., maintaining at 100°C) was effective for imbibing seeds but it also substantially reduced germination percentages. Repeated exposure to 90 to 100°C water did not reduce germination percentage but decreased seedling performance and increased early mortality. No seeds remained unimbibed after six attempts of boiling germinated whereas seeds remaining unimbibed after 15 attempts of exposure to 90 to 100°C water showed high germination percentages. Abnormalities in seedling development were rare but increased with treatment intensity. Exposure to 100°C water for 1 min overall generated the best SI values but the best treatment differed by elevation, and the treatment with the best SI was rarely predicted from the highest germination percentages. Seeds that imbibed without any treatment germinated at the same level as manually filed seeds but produced poor seedling quality. Variation in mother tree environments along an elevational gradient can lead to differences in seed coat characteristics, which may explain differing responses to treatments. Scarification treatments affected processes beyond imbibition and germination and using an index like SI may improve efficiency by identifying optimal scarification treatments while reducing seed waste.
Integrated Transcriptomic and Proteomic Analysis in the Roadmap of the Xylem Development Stage in Populus tomentosa
Authors: Zhang Chong , Zhang Jiaxue , Liu Yadi , Liu Xiatong , Guo Xiaorui , Li Hui , Liu Di , Lu Hai
Published: November 2021

Xylem development plays an important role in the wood formation of plants. In this study, we found that xylem development was a rapid thickening process characterized by initially rapid increases in the number of tracheary elements and fiber cells and the thickness of the secondary walls that later plateaued. Transcriptome analysis showed that the xylan and lignin biosynthetic pathways, which are involved in the early rapid thickening of the xylem, were mainly upregulated in the second month. The expression of a total of 124 transcription factors (TFs), including 28 NAC TFs and 31 MYB TFs, peaked in 2- and 3-month-old plants compared with 1-month-old plants. Based on previous studies and the key cis-acting elements secondary wall NAC-binding elements, secondary wall MYB-responsive elements, W-box and TGTG[T/G/C], 10 TFs related to xylem development, 50 TFs with unknown function, 98 cell wall biosynthetic genes, and 47 programmed cell death (PCD) genes were used to construct a four-layer transcriptional regulatory network (TRN) with poplar NAC domain TFs to characterize the transcriptional regulation of cell wall biosynthesis and PCD in Populus tomentosa. The proteome revealed that post-transcriptional modification may be widely involved in lignification development. Overall, our results revealed that xylem development is a rapid thickening process in P. tomentosa, and expression patterns varied temporally from cell division to cell death.
Working With Type 1 Diabetes: Investigating the Associations Between Diabetes-Related Distress, Burnout, and Job Satisfaction
Authors: Cook Alexandra (Sasha) , Zill Alexander
Published: November 2021

The present study investigates the association between diabetes-related distress (DD) and work outcomes (burnout and job satisfaction) among employed people with type 1 diabetes. Employed adults with type 1 diabetes (N = 297) completed an online survey. Measures assessed emotional, social, food- and treatment-related DD, burnout, and job satisfaction, as well as the type of insulin treatment. We conducted multiple regression analyses to test our hypotheses. Emotional DD was significantly and positively associated with burnout. Social DD was significantly and negatively associated with job satisfaction. The type of treatment (insulin pen versus insulin pump) had no significant effect on the outcomes. This study sets the stage for research on the interactions between working conditions, work outcomes and illness symptoms, and problems of people with type 1 diabetes, and, generally, employees with chronic illnesses. The findings have implications for individual health and illness management, burnout prevention, and occupational health measures.
The Contribution of Basic Psychological Need Satisfaction to Psychological Well-Being via Autonomous Motivation Among Older Adults: A Cross-Cultural Study in China and France
Authors: Tang Minmin , Wang Dahua , Guerrien Alain
Published: November 2021

According to self-determination theory (SDT), the satisfaction of the universal needs for autonomy, competence, and relatedness is important in order to enhance autonomous motivation, which in turn promotes psychological well-being (PWB), regardless of age or culture. In contrast, some cross-cultural perspectives challenge SDT's universalistic viewpoint, especially SDT's view that autonomy yields universal positive effects across Western and Eastern societies. To test these theoretical frameworks across cultures, with special focus on the field of aging, this study examined the contribution of satisfying basic psychological needs to elderly people's PWB from Eastern and Western cultures (China and France). Elderly retired people living at home (NChina = 510, Mage = 68.49 years; NFrance = 170, Mage = 71.19 years) were invited to complete surveys assessing these variables and providing demographic information. Consistent with the hypothesis of SDT, results from structural equation modeling (SEM) indicated that needs satisfaction facilitates autonomous motivation, which in turn promotes PWB in both elderly Chinese and French. Moreover, the finding from subsequent moderation analysis confirmed the moderating effect of culture in the relationship between competence satisfaction and PWB, with the contribution of competence satisfaction on PWB being stronger among elderly Chinese than elderly French (p < 0.05). Our findings suggest that, the broad applicability of SDT notwithstanding, attending to cultural differences in elderly care remains important.
Examining Delayed Recall in Cochlear Implant Users Using the Montreal Cognitive Assessment, California Verbal Learning Test, Third Edition, and Item Specific Deficit Approach: Preliminary Results
Authors: Brumer Nadav , Elkins Elizabeth , Parada Jennifer , Hillyer Jake , Parbery-Clark Alexandra
Published: November 2021

Purpose:Recent studies using the Montreal Cognitive Assessment (MoCA) suggest delayed recall is challenging for cochlear implant (CI) users. To better understand the underlying processes associated with delayed recall in CI users, we administered the MoCA and the California Verbal Learning Test, Third Edition (CVLT-3), which provides a more comprehensive assessment of delayed recall ability.

Methods:The MoCA and CVLT-3 were administered to 18 high-performing CI users. For the CVLT-3, both the traditional scoring and a newer scoring method, the Item-Specific Deficit Approach (ISDA), were employed.

Results:The original MoCA score and MoCA delayed recall subtest score did not relate to performance on any CVLT-3 measures regardless of scoring metric applied (i.e., traditional or ISDA). Encoding performance for both the CVLT-3 and ISDA were related. Consolidation, which is only distinctly defined by the ISDA, related to CVLT-3 cued delay recall performance but not free delay recall performance. Lastly, ISDA retrieval only related to CVLT-3 measures when modified.

Conclusion:Performance on the MoCA and CVLT-3 in a high performing CI patient population were not related. We demonstrate that the ISDA can be successfully applied to CI users for the quantification and characterization of delayed recall ability; however, future work addressing lower performing CI users, and comparing to normal hearing controls is needed to determine the extent of potential translational applications. Our work also indicates that a modified ISDA retrieval score may be beneficial for evaluating CI users although additional work addressing the clinical relevance of this is still needed.
Sustainable Export Innovation Behavior of Firms Under Fiscal Incentive
Authors: Feng Chen , Shi Beibei , Yan Hong , Yang Siying , Bai Caiquan
Published: November 2021

The fiscal imbalance between the central and local governments under fiscal centralization may motivate local governments to pass tax burdens on firms. The causal identification of the tax system reform and the sustainable export innovation behavior of firms are of great significance. This study uses the income tax sharing policy of China to examine the impact of fiscal centralization on the sustainable export innovation behavior of firms. We find that this tax reform has significantly inhibited the increase of the export value-added rate of firms, and has an increasing trend with the share ratio between the Central Government and the local government. Moreover, this effect mainly comes from the crowding-out effect of imported intermediate goods on domestic intermediate goods. The tests show that the above conclusions are consistent with the general logic of local governments. When they face greater downward fiscal pressure, they will further pass the tax burden on local firms and force the firms to promote their export performance to expand the tax base. This short-sighted behavior of replacing “quality improvement” with “quantity increase” is an important factor that affects the sustainable export innovation behavior of firms and the climb in the global value chain.