bluuebunny/crossref_metadata_2025 huggingface dataset:
The transformative dance of the crisis to resignify social educational work: auto-ethnographical reflections on a cooperative enquiry in Northern Italy during the COVID-19 pandemic
Authors: Cuppari Antonella
Published: April 2022

This contribution proposes an autoethnographic reflection on a cooperative enquiry involving social workers, volunteers and family members of people with intellectual disabilities in Northern Italy. The author, a social worker and doctoral student, recognises the complexity of her own positioning and reflects on the educational work that takes place in the social sphere, on the risks connected to a technocratic logic and on critical, and transformative possibilities offered by the crisis. The author proposes a systemic reflexivity that challenges the dominant discourses, connects the micro, meso and macro levels and promotes different ways of knowing. The dynamism of the body, linked to the author's experience in the field of contemporary dance, becomes a symbolic way to decolonise the posture of social workers and open it up to the transformative potential of a sensitive, conscious and incorporated social educational work.
Reflexões sobre a noção de angústia em Sartre: contribuições para a psicologia clínica
Authors: Carvalho Mikaelli Neves , Gabriel Nilson Lucas Dias
Published: April 2022

O presente artigo objetiva compreender a noção de angústia na obra de Jean-Paul Sartre (1905- 1980) e como suas colocações sobre o conceito podem contribuir para a psicologia clínica no Brasil. Tendo em vista esse processo, foram utilizados como marcos teóricos duas de suas obras: O Existencialismo é um Humanismo (1946) e O Ser e o Nada (1943), esta última, contém um capítulo destinado pelo autor apenas a “psicanálise existencial’’. Foi analisado como o conceito de angústia na obra do existencialista tem sido apropriada pelos pesquisadores do campo da psicologia, visto que a maior parte da confecção de trabalhos voltadas para o autor acontece no campo da filosofia, foram levantados dados a fim de explorar a possibilidade de correlacionar o conceito com outras temáticas dentro do campo da psicologia. Este artigo discorrerá brevemente sobre o existencialismo, o existencialismo sartreano, expondo as contribuições de Sartre para clínica em psicologia utilizando-se do livro Sartre e a Psicologia Clínica (2011) da autora Daniela Schneider, pesquisadora e autora sobre o tema.
RNA-Seq Based Toxicity Analysis of Mesoporous Polydopamine Nanoparticles in Mice Following Different Exposure Routes
Authors: Huang Zihua , Xie Luoyijun , Zhang Jifan , Li Qiyan , Liu Yulin , Fu Xuemei , Yuan Miaomiao , Li Qingjiao
Published: April 2022

Mesoporous polydopamine nanoparticles (MPDA NPs) are promising nanomaterials that have the prospect of clinical application for multi-strategy antitumor therapy, while the biosecurity of MPDA NPs remains indistinct. Here, transcriptome sequencing (RNA-Seq) was performed to systematically reveal the toxicity of MPDA NPs to five categories of organs after three different exposure routes, including intravenous injection, intramuscular injection, and intragastric administration. Our results uncovered that MPDA NPs could be deposited in various organs in small amounts after intravenous administration, not for the other two exposure routes. The number of differentially expressed genes (DEGs) identified in the heart, liver, spleen, lung, and kidney from the intragastric administration group was from 22 to 519. Similarly, the corresponding number was from 23 to 64 for the intramuscular injection group and was from 11 to 153 for the intravenous injection group. Functional enrichment analyses showed 6, 39, and 4 GO terms enriched for DEGs in intragastric administration, intramuscular injection, and intravenous injection groups, respectively. One enriched pathway was revealed in intragastric administration group, while no enriched pathway was found in other groups. Our results indicated that MPDA NPs produced only slight changes at the transcriptome level in mice, which provided new insights for further clinical application of MPDA NPs.
Dissection of the microRNA Network Regulating Hedgehog Signaling in Drosophila
Authors: He Tao , Fan Yu , Wang Yao , Liu Min , Zhu Alan Jian
Published: April 2022

The evolutionarily conserved Hedgehog (Hh) signaling plays a critical role in embryogenesis and adult tissue homeostasis. Aberrant Hh signaling often leads to various forms of developmental anomalies and cancer. Since altered microRNA (miRNA) expression is associated with developmental defects and tumorigenesis, it is not surprising that several miRNAs have been found to regulate Hh signaling. However, these miRNAs are mainly identified through small-scale in vivo screening or in vitro assays. As miRNAs preferentially reduce target gene expression via the 3′ untranslated region, we analyzed the effect of reduced expression of core components of the Hh signaling cascade on downstream signaling activity, and generated a transgenic Drosophila toolbox of in vivo miRNA sensors for core components of Hh signaling, including hh, patched (ptc), smoothened (smo), costal 2 (cos2), fused (fu), Suppressor of fused (Su(fu)), and cubitus interruptus (ci). With these tools in hand, we performed a genome-wide in vivo miRNA overexpression screen in the developing Drosophila wing imaginal disc. Of the twelve miRNAs identified, seven were not previously reported in the in vivo Hh regulatory network. Moreover, these miRNAs may act as general regulators of Hh signaling, as their overexpression disrupts Hh signaling-mediated cyst stem cell maintenance during spermatogenesis. To identify direct targets of these newly discovered miRNAs, we used the miRNA sensor toolbox to show that miR-10 and miR-958 directly target fu and smo, respectively, while the other five miRNAs act through yet-to-be-identified targets other than the seven core components of Hh signaling described above. Importantly, through loss-of-function analysis, we found that endogenous miR-10 and miR-958 target fu and smo, respectively, whereas deletion of the other five miRNAs leads to altered expression of Hh signaling components, suggesting that these seven newly discovered miRNAs regulate Hh signaling in vivo. Given the powerful effects of these miRNAs on Hh signaling, we believe that identifying their bona fide targets of the other five miRNAs will help reveal important new players in the Hh regulatory network.
An Optimized Tissue Dissociation Protocol for Single-Cell RNA Sequencing Analysis of Fresh and Cultured Human Skin Biopsies
Authors: Burja Blaž , Paul Dominique , Tastanova Aizhan , Edalat Sam G. , Gerber Reto , Houtman Miranda , Elhai Muriel , Bürki Kristina , Staeger Ramon , Restivo Gaetana , Lang Ramon , Sodin-Semrl Snezna , Lakota Katja , Tomšič Matija , Levesque Mitchell P. , Distler Oliver , Rotar Žiga , Robinson Mark D. , Frank-Bertoncelj Mojca
Published: April 2022

We present an optimized dissociation protocol for preparing high-quality skin cell suspensions for in-depth single-cell RNA-sequencing (scRNA-seq) analysis of fresh and cultured human skin. Our protocol enabled the isolation of a consistently high number of highly viable skin cells from small freshly dissociated punch skin biopsies, which we use for scRNA-seq studies. We recapitulated not only the main cell populations of existing single-cell skin atlases, but also identified rare cell populations, such as mast cells. Furthermore, we effectively isolated highly viable single cells from ex vivo cultured skin biopsy fragments and generated a global single-cell map of the explanted human skin. The quality metrics of the generated scRNA-seq datasets were comparable between freshly dissociated and cultured skin. Overall, by enabling efficient cell isolation and comprehensive cell mapping, our skin dissociation-scRNA-seq workflow can greatly facilitate scRNA-seq discoveries across diverse human skin pathologies and ex vivo skin explant experimentations.
Identification of Single Amino Acid Changes in the Rift Valley Fever Virus Polymerase Core Domain Contributing to Virus Attenuation In Vivo
Authors: Borrego Belén , Moreno Sandra , López-Valiñas Álvaro , de la Losa Nuria , Weber Friedemann , Núñez José Ignacio , Brun Alejandro
Published: April 2022

Rift Valley fever (RVF) is an arboviral zoonotic disease affecting many African countries with the potential to spread to other geographical areas. RVF affects sheep, goats, cattle and camels, causing a high rate of abortions and death of newborn lambs. Also, humans can be infected, developing a usually self-limiting disease that can turn into a more severe illness in a low percentage of cases. Although different veterinary vaccines are available in endemic areas in Africa, to date no human vaccine has been licensed. In previous works, we described the selection and characterization of a favipiravir-mutagenized RVFV variant, termed 40Fp8, with potential as a RVF vaccine candidate due to the strong attenuation shown in immunocompromised animal models. Compared to the parental South African 56/74 viral strain, 40Fp8 displayed 7 amino acid substitutions in the L-protein, three of them located in the central region corresponding to the catalytic core of the RNA-dependent RNA polymerase (RdRp). In this work, by means of a reverse genetics system, we have analyzed the effect on virulence of these amino acid changes, alone or combined, both in vitro and in vivo. We found that the simultaneous introduction of two changes (G924S and A1303T) in the heterologous ZH548-RVFV Egyptian strain conferred attenuated phenotypes to the rescued viruses as shown in infected mice without affecting virus immunogenicity. Our results suggest that both changes induce resistance to favipiravir likely associated to some fitness cost that could be the basis for the observed attenuation in vivo. Conversely, the third change, I1050V, appears to be a compensatory mutation increasing viral fitness. Altogether, these results provide relevant information for the safety improvement of novel live attenuated RVFV vaccines.
Early vs. Delayed Initiation of Treatment With P2Y12 Inhibitors in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Vicent Lourdes , Diaz-Arocutipa Carlos , Tarantini Giuseppe , Mojoli Marco , Hernandez Adrian V. , Bueno Héctor
Published: April 2022

Aims

Whether early or delayed dual antiplatelet therapy initiation is better in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is unclear. We assessed the evidence for comparing the efficacy and safety of early vs. delayed P2Y12 inhibitor initiation in NSTE-ACS.

Methods

The randomized controlled trials with available comparisons between early and delayed initiation of P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with NSTE-ACS until January 2021 were reviewed. The primary outcomes were trial-defined major adverse cardiovascular events (MACEs) and bleeding. Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, urgent coronary revascularization, and stroke. Frequentist random-effects network meta-analyses were conducted, ranking best treatments per outcome with p-scores.

Results

A total of nine trials with intervention arms including early and delayed initiation of clopidogrel (n = 5), prasugrel (n = 8), or ticagrelor (n = 6) involving 40,096 patients were included. Early prasugrel (hazard ratio [HR], 0.59; 95% confidence interval [95%CI], 0.40–0.87), delayed prasugrel (HR, 0.60; 95%CI 0.43–0.84), and early ticagrelor (HR, 0.84; 95%CI, 0.74–0.96) significantly reduced MACE compared with early clopidogrel, but increased bleeding risk. Delayed prasugrel ranked as the best treatment to reduce MACE (p-score=0.80), early prasugrel to reduce all-cause mortality, cardiovascular mortality, stent thrombosis, and stroke, and delayed clopidogrel to reduce bleeding (p-score = 0.84). The risk of bias was low for all trials.

Conclusion

In patients with NSTE-ACS, delayed prasugrel initiation was the most effective strategy to reduce MACE. Although early prasugrel was the best option to reduce most secondary cardiovascular outcomes, it was associated with the highest bleeding risk. The opposite was found for delayed clopidogrel.
Study on Optimization of Stope Structural Parameters and Filling Scheme of Wawu Phosphate Mine in Yichang City, China
Authors: Peng Gao , Gaoyi Dong , Jingsong Chen , Zhou Chunmei , Manqing Lin , Weizhong Zhang , Yang Sun
Published: April 2022

Reasonable stope structural parameters are very important to ensure the safety and efficiency of mining. In this paper, based on the elastic-plastic constitutive model of Mohr-Coulomb strength criterion, the reasonable span and critical span are calculated by using simply supported beam theory and mine room width calculation formula. PLAXIS2D finite element analysis software was used to conduct numerical simulation research on 7 m × 9 m, 5 m × 12 m stope structure parameter schemes and 7 m × 9m, 5 m × 12 m waste rock filling schemes. The optimal structure parameters of the stope were determined based on the calculation and analysis of displacement variation rule, surrounding rock stress distribution and plastic zone. The analysis and simulation results show that Case 1 one-time mining 7 m × 9 m and Case 3 one-time mining 5 m × 12 m, the plastic zone is connected, the simulation calculation is not convergent, and the stope is unstable. Case 2 waste rock filling 7 m × 9 m and Case 4 waste rock filling 5 m × 12 m, the distribution and change of stress, displacement and plastic zone in the goaf under the two cases are compared, and finally the waste rock filling 7 m × 9 m is obtained can improve the economy and safety of mining in the mining area, and verify the feasibility of implementing stope structural parameters and waste rock filling mining system is verified.
The Accuracy and Validity of the Simplified Pairs Method of Comparative Judgement in Highly Structured Papers
Authors: Leech Tony , Gill Tim , Hughes Sarah , Benton Tom
Published: April 2022

Comparative judgement (CJ) is often said to be more suitable for judging exam questions inviting extended responses, as it is easier for judges to make holistic judgements on a small number of large, extended tasks than a large number of smaller tasks. On the other hand, there is evidence it may also be appropriate for judging responses to papers made up of many smaller structured tasks. We report on two CJ exercises on mathematics and science exam papers, which are constructed mainly of highly structured items. This is to explore whether judgements processed by the simplified pairs version of CJ can approximate the empirical difference in difficulty of pairs of papers. This can then be used to maintain standards between exam papers. This use of CJ, not its other use as an alternative to marking, is the focus of this paper. Within the exercises discussed, panels of experienced judges looked at pairs of scripts, from different sessions of the same test, and their judgements were processed via the simplified pairs CJ method. This produces a single figure for the estimated difference in difficulty between versions. We compared this figure to the difference obtained from traditional equating, used as a benchmark. In the mathematics study the difference derived from judgement via simplified pairs closely approximated the empirical equating difference. However, in science, the CJ outcome did not closely align with the empirical difference in difficulty. Reasons for the discrepancy may include the differences in the content of the exams or the specific judges. However, clearly, comparative judgement need not lead to an accurate impression of the relative difficulty of different exams. We discuss self-reported judge views on how they judged, including what questions they focused on, and the implications of these for the validity of CJ. Processes used when judging papers made up of highly structured tasks were varied, but judges were generally consistent enough. Some potential challenges to the validity of comparative judgement are present with judges sometimes using re-marking strategies, and sometimes focusing attention on subsets of the paper, and we explore these. A greater understanding of what judges are doing when they judge comparatively brings to the fore questions of judgement validity that remain implicit in marking and non-comparative judgement contexts.
Progestin-Primed Ovarian Stimulation Protocol for Patients With Endometrioma
Authors: Yang Ai-Min , Feng Teng-Fei , Han Yan , Zhao Zhi-Ming , Wang Wei , Wang Yi-Zhuo , Zuo Xiao-Qi , Xu Xiuhua , Shi Bao-Jun , Li Lipeng , Hao Gui-Min , Cui Na
Published: April 2022

Objective

To evaluate the pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocol for patients with endometrioma underwent in vitro fertilization/intra-cytoplasmic sperm injection embryo transfer (IVF/ICSI-ET).

Design

Observational retrospective cohort study.

Setting

University affiliated reproductive center.

Study Participants

605 infertile patients with endometrioma underwent IVF/ICSI-ET from January 2016 to March 2021 were included in this study.

Methods

Multivariable logistic regression analyses were conducted to determine the independent effect of controlled ovarian stimulation (COS) protocols on reproductive outcomes of first embryo transfer (ET) cycles. The live birth was primary outcome, the implantation rate, biochemical pregnancy, clinical pregnancy and ongoing pregnancy were secondary outcomes.

Results

Compared to PPOS protocol, the probability of implantation showed no significant difference with ultra-long gonadotrophin-releasing hormone agonist (GnRHa) protocol and gonadotrophin-releasing hormone antagonist (GnRHant) protocol (OR 1.7, 95% CI 0.9-3.1, OR 1.2, 95% CI 0.7-2.1, respectively). The PPOS protocol was correlated with a significantly lower biochemical pregnancy and clinical pregnancy than ultra-long GnRHa protocol in the multivariable logistic regression analysis (OR 2.3, 95% CI 1.1-4.9, OR 2.4, 95% CI 1.1-5.3, respectively). However, there was no significant difference in terms of biochemical pregnancy, clinical pregnancy and ongoing pregnancy between PPOS and GnRHant protocol (OR 1.4, 95% CI 0.7-2.7, OR 1.3, 95% CI 0.7-2.4, OR 1.1, 95% CI 0.6-2.3, respectively). In addition, compared to PPOS protocol, ultra-long GnRHa protocol and GnRHant protocol demonstrated no statistical difference in ongoing pregnancy (OR 2.0, 95% CI 0.9-4.5, OR 2.1, 95% CI 0.6-2.3, respectively). Notably, the ultra-long GnRHa protocol was associated with a significant higher probability of live birth than PPOS protocol both in crude analysis and multivariable logistic regression analysis (OR 2.6, 95% CI 1.3-5.1, OR 2.5, 95% CI 1.1-5.7, respectively). Nevertheless, no statistical difference was found in live birth between PPOS and GnRHant protocol either in crude analysis and multivariable logistic regression analysis (OR1.2, 95% CI 0.6-2.3, OR 1.2, 95% CI 0.6-2.5, respectively).

Conclusions

Based on the reproductive outcomes of the first ET cycles in patients with endometrioma, PPOS protocol may associated with inferior reproductive outcomes in terms of biochemical pregnancy, clinical pregnancy and live birth than ultra-long GnRHa protocol. However, there was no significant difference in implantation rate, clinical pregnancy, ongoing pregnancy and live birth between PPOS and GnRHant protocol.
Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting
Authors: Ramírez-Rincón Alex , Builes-Montaño Carlos E. , Hincapié-García Jaime A. , Blanco Victor M. , Botero-Arango José F.
Published: April 2022

Background

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting.

Methods

An observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events.

Results

67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline.

Conclusions

This real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.
The Role of Fibroblast Growth Factor 19 Subfamily in Different Populations Suffering From Osteoporosis
Authors: Yu Xiawen , Xia Yue , Jia Jue , Yuan Guoyue
Published: April 2022

Fibroblast growth factor (FGF) 19 subfamily, also known as endocrine fibroblast growth factors (FGFs), is a newly discovered metabolic regulator, including FGF19, FGF21 and FGF23. They play significant roles in maintaining systemic homeostasis, regulating the balance of bile acid and glucolipid metabolism in humans. Osteoporosis is a chronic disease, especially in the current status of aging population, osteoporosis is the most prominent chronic bone disease, leading to multiple complications and a significant economic burden that requires long-term or even lifelong management. Members of the FGF family have been shown to be associated with bone mineral density (BMD), fracture repair and cartilage regeneration. Studies of the FGF19 subfamily in different populations with osteoporosis have been increasing in recent years. This review summarizes the role of the FGF19 subfamily in bone metabolism, and provides new options for the treatment of bone diseases such as osteoporosis.
Germline Mutations Related to Primary Hyperparathyroidism Identified by Next-Generation Sequencing
Authors: Park Hye-Sun , Lee Yeon Hee , Hong Namki , Won Dongju , Rhee Yumie
Published: April 2022

Primary hyperparathyroidism (PHPT) is characterized by overproduction of parathyroid hormone and subsequent hypercalcemia. Approximately 10% of PHPT cases are hereditary, and several genes, such as MEN1, RET, CASR, and CDC73, are responsible for the familial forms of PHPT. However, other genetic mutations involved in the etiology of PHPT are largely unknown. In this study, we identified genetic variants that might be responsible for PHPT, including familial PHPT, benign sporadic PHPT, and sporadic parathyroid cancer, using next-generation sequencing (NGS). A total of 107 patients with PHPT who underwent NGS from 2017 to 2021 at Severance Hospital were enrolled. We reviewed the pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Of the 107 patients (mean age: 47.6 ± 16.1 years, women 73.8%), 12 patients were diagnosed with familial PHPT, 13 with parathyroid cancer, and 82 with benign sporadic PHPT. Using NGS, we identified three pathogenic variants in two genes (CDC73 and MEN1), 10 likely pathogenic variants in six genes (CASR, CDC73, LRP5, MEN1, SDHA, and VHL), and 39 non-synonymous VUS variants that could be related to parathyroid disease. Interestingly, we identified one GCM2 variant (c.1162A>G [p.Lys388Glu]) and five APC variants that were previously reported in familial isolated hyperparathyroidism, benign sporadic PHPT, and parathyroid cancer. We also analyzed the characteristics of subjects with positive genetic test results (pathogenic or likely pathogenic variants), and 76.9% of them had at least one of the following features: 1) age < 40 years, 2) family history of PHPT, 3) multiglandular PHPT, or 4) recurrent PHPT. In this study, we analyzed the NGS data of patients with PHPT and observed variants that could possibly be related to PHPT pathogenesis. NGS screening for selected patients with PHPT might help in the diagnosis and management of the disease.
Current Guideline Risk Stratification and Cardiovascular Outcomes in Chinese Patients Suffered From Atherosclerotic Cardiovascular Disease
Authors: Li Sha , Liu Hui-Hui , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Xu Rui-Xia , Dong Qian , Qian Jie , Dou Ke-Fei , Li Jian-Jun
Published: April 2022

Background and Aims

Heterogeneity exists among patients with atherosclerotic cardiovascular disease (ASCVD) with regard to the risk of recurrent events. Current guidelines have definitely refined the disease and we aimed to examine the practicability in Chinese population.

Methods

A cohort of 9944 patients with ASCVD was recruited. Recurrent events occurred during an average of 38.5 months’ follow-up were collected. The respective and combinative roles of major ASCVD (mASCVD) events and high-risk conditions, being defined by 2018 AHA/ACC guideline, in coronary severity and outcome were studied.

Results

The number of high-risk conditions was increased with increasing number of mASCVD events (1.95 ± 1.08 vs. 2.16 ± 1.10 vs. 2.42 ± 1.22). Trends toward the higher to the highest frequency of multi-vessel coronary lesions were found in patients with 1- (71.1%) or ≥2 mASCVD events (82.8%) when compared to those without (67.9%) and in patients with 2- (70.5%) or ≥3 high-risk conditions (77.4%) when compared to those with 0-1 high-risk condition (61.9%). The survival rate was decreased by 6.2% between none- and ≥2 mASCVD events or by 3.5% between 0-1 and ≥3 high-risk conditions. Interestingly, diabetes was independently associated with outcome in patients with 1- [1.54(1.06-2.24)] and ≥2 mASCVD events [1.71(1.03-2.84)]. The positive predictive values were increased among groups with number of mASCVD event increasing (1.10 vs. 1.54 vs. 1.71).

Conclusion

Propitious refinement of ASCVD might be reasonable to improve the survival. Concomitant diabetes was differently associated with the incremental risk among different ASCVD categories, suggesting the need of an appropriate estimate rather than a ‘blanket’ approach in risk stratification.
Glucagon Test Is a Useful Predictor of Withdrawal From Insulin Therapy in Subjects With Type 2 Diabetes Mellitus
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Tatsumi Fuminori , Sugisaki Toshitomo , Kubo Masato , Nakao Erina , Dan Kazunori , Wamata Ryo , Iwamoto Hideyuki , Takahashi Kaio , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Shimoda Masashi , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: April 2022

There are many tests for evaluating endogenous insulin secretory capacity. However, there are only a limited number of studies that have examined in detail in clinical practice which method most accurately reflects the ability to secrete endogenous insulin especially in hyperglycemic state. The purpose of this study was to find the endogenous insulin secretory capacity and a possible predictor of insulin withdrawal in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia. In the endogenous insulin secretory test during hospitalization, CPR, CPR index, and ΔCPR after glucagon loading were all significantly higher in the insulin withdrawal group. On the other hand, there were no difference in fasting CPR index, HOMA-β, SUIT, and 24-hour urinary CPR excretion between the two groups. In the glucagon test of the insulin withdrawal group, the cutoff value of ΔCPR was 1.0 ng/mL, the withdrawal rate of ΔCPR of 1.0 ng/mL or more was 69.2%, and the withdrawal rate of less than 1.0 ng/mL was 25.0%. In conclusion, it is likely that glucagon test is the most powerful tool for predicting the possibility of insulin withdrawal as well as for evaluating endogenous insulin secretory capacity in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia.
Value of Immunohistochemical Expression of Apelin, Succinate Dehydrogenase B, Chromogranin B, Human Epidermal Growth Factor Receptor-2, Contactin 4, and Succinyl-CoA Synthetase Subunit Beta in Differentiating Metastatic From Non-Metastatic Pheochromocytoma and Paraganglioma
Authors: Wang Yong , Chen Danlei , Pang Yingxian , Xu Xiaowen , Guan Xiao , Liu Longfei
Published: April 2022

Objective

We aimed to retrospectively collect pathologically identified pheochromocytoma and paraganglioma (PPGL) tumor tissues from our center and investigate the expression of apelin and succinyl-CoA synthetase subunit beta (SUCLG2), human epidermal growth factor receptor-2 (HER2 or ERBB-2), contactin 4 (CNTN4), chromogranin B (CHGB), and succinate dehydrogenase B (SDHB) in metastatic and non-metastatic PPGLs, for exploring their roles in the diagnosis of metastatic PPGLs.

Methods

A total of 369 patients with pathologically and surgically confirmed PPGLs at Xiangya Hospital, Central South University, between June 2010 and June 2020 were retrospectively included. Sixty patients—12 patients with metastatic PPGLs and 48 patients with non-metastatic PPGLs—were selected through propensity score matching (1:4) to reduce the effect of PPGL type, sex, and age. We observed and quantified the expression of apelin, SDHB, CHGB, ERBB-2, CNTN4, and SUCLG2 in paraffin-embedded samples using immunohistochemical staining.

Results

No significant differences were observed between the metastatic group and non-metastatic group with respect to the expression of CNTN4 and SUCLG2. The expression of apelin, SDHB, CHGB, and ERBB-2 was significantly different between the two groups. The expression of apelin, SDHB, and CHGB was significantly lower in the metastatic group than that in the non-metastatic group (P < 0.001). ERBB-2 expression was significantly higher in the metastatic group than in the non-metastatic group (P = 0.042). Kaplan–Meier analysis revealed that patients with negative expression of apelin, SDHB, and CHGB showed significantly lower metastasis-free survival than those with positive expression. Multivariate Cox analysis revealed that SDHB and CHGB levels were independently associated with metastasis-free survival.

Conclusion

The expression levels of apelin, CHGB, SDHB, and ERBB-2 may be predictive biomarkers for the diagnosis of metastatic PPGLs. Patients with negative expression of apelin, CHGB, and SDHB should be subjected to frequent postoperative follow-up procedures
The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination
Authors: Ritch Sabrina J. , Telleria Carlos M.
Published: April 2022

Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.
Mechanism of Inflammatory Associated Impairment of Sperm Function, Spermatogenesis and Steroidogenesis
Authors: Hasan Hiba , Bhushan Sudhanshu , Fijak Monika , Meinhardt Andreas
Published: April 2022

Infection and inflammation are relevant entities of male reproductive disorders that can lead to sub-/infertility. Associated damage of the testis of affected men and in rodent models include leukocytic infiltration, edema formation, fibrosis, germ cell loss and reduced androgen levels. Negative effects on spermatogenesis are thought to be elicited by oxidative stress sustained mostly by increased levels of ROS and pro-inflammatory cytokines. Under normal conditions these cytokines have physiological functions. However, increased levels as seen in inflammation and infection, but also in obesity and cancer are harmful for germ cells and impair steroidogenesis. As a summary, there is mounting evidence that the activation of inflammatory pathways is a rather common feature in various forms of male testicular disorders that extends beyond established infectious/inflammatory cues. This mini review will focus on relevant entities and the mechanisms of how a dysbalance of local testicular factors contributes to disturbances of spermatogenesis and steroidogenesis.
Investigating the Role of Education, Foreign Investment, and Economic Development for Sustainable Environment in BRI Countries: Application of Method of Movements Quantile Regression
Authors: Yan Yong , Zhou Jianhua , Zhou Shiqi , Rao Daokai , Zhou Jie , Fareed Zeeshan
Published: April 2022

Environmental pollution comes from several sectors of activities. It is almost conceivable that the education sector subsidies to the disruption of the environmental quality. The study employs panel cointegration techniques and method of moments quantile regression (MMQR) to inspect the influence of income, education (scholarly enrollment and expenditure), and foreign direct investment on carbon dioxide (CO2) emissions for a panel of 46 Belt and Road initiative (BRI) countries spanning the period 1996–2016. The estimation shows that the hypothesis of environmental Kuznets is established for both the models. Using fully modified ordinary least squares (OLS), fixed effects OLS and dynamic OLS, long-run elasticities show that real income increases the emissions. At the same time, foreign direct investment and education contribute toward decreasing the emissions in the long run. Using the approach of MMQR, the estimated coefficients confirm that only economic growth positively affects pollution. However, education and foreign direct investment negatively influence CO2 emissions with different quantile levels. As policy recommendations, governments of the BRI region should improve the educational services by installing new technologies, equipment, and supplies, which leads to mitigation of the emission levels.
Study on Socio-Economic Factors of Haze Pollution in the Context of Sustainable Development: Based on Asymmetric Interaction Effects Perspective
Authors: Jia Wenxing , Pei Yanfeng
Published: April 2022

Haze pollution has been a global problem plaguing people for nearly two centuries, especially in developing countries, where haze pollution is getting worse and has become the culprit that restricts global sustainable development. As the largest developing country in the world, China’s regional characteristics of haze pollution are increasingly prominent, and the coverage is expanding, which means that there is a strong spatial interaction of haze pollution. The real world is composed of asymmetric spatial relationships, and asymmetric spatial interactions are more consistent with the reality of haze pollution. To this end, this paper identifies the asymmetric spatial interaction effects of haze pollution by using the time series econometric analysis framework and then constructs asymmetric spatial weights. In this paper, the spatial panel Durbin model and spatial effect decomposition technique are used for the empirical investigation to provide new empirical evidence to reveal the socio-economic influences of haze pollution. The study finds that haze pollution in China has a significant asymmetric spatial interaction and the degree of influence varies among cities. During the sample period, there is a significant inverted U-shaped relationship between economic development and haze pollution. However, the vast majority of cities have not passed the top inflection point of the inverted U-curve and are still in the stage where haze pollution is gradually intensifying with economic growth. High population density, high energy consumption, and unreasonable energy consumption structure aggravate haze pollution, while fixed-asset investment and science and technology expenditure help to reduce haze pollution. However, only the spatial spillover effect of the energy consumption structure is significant. Therefore, the improvement and implementation of more effective socio-economic prevention and control policies in the case of asymmetric interaction is the key to effectively dealing with heavy pollution weather, fighting the defense of the blue sky, and achieving sustainable development.
Benefits of Parasitism in Polluted Environments: A Review and Perspectives
Authors: Goutte Aurelie , Molbert Noëlie
Published: April 2022

The frequency and strength of biotic interactions are thought to be shaped by environmental conditions. In this study, we reviewed and discussed the potential effects of toxic chemicals in driving shifts along the parasite-mutualist continuum. Some parasites have the astonishing capacity to accumulate trace metals and organic pollutants from various taxa within freshwater, marine, and terrestrial ecosystems. Recent studies have provided evidence of clear benefits for the host: when exposed to contaminants, infected organisms exhibited reduced contamination levels, less severe oxidative stress, and histological alterations, as well as higher body condition and survival rate compared with their uninfected conspecifics. Such effects might arise when the costs of parasitism are lower than their benefits in specific environmental conditions. Assessing the potential outcomes for parasites exploiting contaminated hosts is a crucial but neglected issue, since ecotoxicological effects on parasites may alter interspecific relationships. We identified possible avenues for future research using innovative tools and long-term experimental manipulations of both parasitism and pollution to better understand how toxic chemicals can modulate the strength and direction of host-parasite interactions.
Coping With Dynamism: Phylogenetics and Phylogeographic Analyses Reveal Cryptic Diversity in Heleobia Snails of Atacama Saltpan, Chile
Authors: Valladares Moisés A. , Fabres Alejandra A. , Collado Gonzalo A. , Sáez Paola A. , Méndez Marco A.
Published: April 2022

The species that inhabit systems highly affected by anthropic activities usually exhibit this external influence in their gene pool. In this study, we investigated the genetic patterns of populations of Heleobia atacamensis, a freshwater microgastropod endemic to the Atacama Saltpan, a system historically exposed to environmental changes, and currently subjected to conditions associated with metallic and non-metallic mining and other anthropic activities. Molecular analyses based on nuclear and mitochondrial sequences indicate that the saltpan populations are highly fragmented and that the genetic structure is mainly explained by historical geographic isolation, with little influence of contemporary factors. The microsatellite results suggest a moderate genetic diversity and sharp differentiation mediated by isolation by distance. Additionally, despite the high environmental heterogeneity detected and the marked historical dynamism of the region, our data reveal no signs of demographic instability. The patterns of contemporary gene flow suggest a change in the current genetic structure, based on the geographic proximity and specific environmental conditions for each population. Our results, highlight the role of fragmentation as a modulator of genetic diversity, but also suggest that the historical persistence of isolated populations in naturally dynamic environments could explain the apparent demographic stability detected.
Evaluating Basin-Scale Forest Adaptation Scenarios: Wildfire, Streamflow, Biomass, and Economic Recovery Synergies and Trade-Offs
Authors: Povak Nicholas A. , Furniss Tucker J. , Hessburg Paul F. , Salter R. Brion , Wigmosta Mark , Duan Zhuoran , LeFevre Miles
Published: April 2022

Active forest management is applied in many parts of the western United States to reduce wildfire severity, mitigate vulnerability to drought and bark beetle mortality, and more recently, to increase snow retention and late-season streamflow. A rapidly warming climate accelerates the need for these restorative treatments, but the treatment priority among forest patches varies considerably. We simulated four treatment scenarios across the 3,450 km2 Wenatchee River basin in eastern Washington, United States. We used a decision support tool (DST) to assess trade-offs and synergies within and among treatments on wildfire risk and smoke emissions, water yield and snow retention, biomass production, and economic return. Treatment scenarios emphasized prescribed burning (BurnOnly), biomass production (MaxBiomass), gap-based thinning to optimize water yield (IdealWater), and a principle-based restoration scenario (RA1). Fire hazard, smoke emissions, and biomass production metrics were evaluated across scenarios using the Forest Vegetation Simulator, and water yields were modeled using the Distributed Hydrology Soil Vegetation Model. Simulations were summarized to both patch- (101–102 ha) and subwatershed- (103–104 ha) scales, and treatment effects were evaluated against an untreated baseline landscape. We used logic models to rank effect sizes by scenario across metrics along a continuum between −1 (no or weak effect) to +1 (large effect). All treatments produced benefits across one or more ecosystem services and led to synergistic benefits to water yield and wildfire hazard reduction. Tradeoffs among resource benefits were clear in wilderness where reliance on prescribed burning without mechanical treatment increased costs and eliminated the potential for biomass recovery. The BurnOnly scenario improved fire risk metrics and streamflow, but effect sizes were lower compared to other treatments. IdealWater showed the strongest benefits overall, demonstrating the ability to capture multiple resource benefits through spatially explicit thinning. Our study provides a framework for integrating strategic and tactical models that evaluate tradeoffs and synergies gained through varied management approaches. We demonstrate the utility of decision support modeling to enhance management synergies across large landscapes.
Transcriptome-Wide Analysis of RNA N6-Methyladenosine Modification in Adriamycin-Resistant Acute Myeloid Leukemia Cells
Authors: Fang Shu , Peng Bo , Wen Yanan , Yang Jingjing , Wang Hao , Wang Ziwei , Qian Kun , Wei Yan , Jiao Yifan , Gao Chunji , Dou Liping
Published: April 2022

Acute myeloid leukemia (AML) is one of the most aggressive hematopoietic malignancies. Patients still suffer from refractory/relapsed disease after anthracycline-based therapy, which leads to a poor prognosis. N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotes, the imbalance of which is reported to be associated with various pathological processes, including drug resistance. However, the relationship between m6A modification and drug resistance has not been well defined in AML. In this study, we analyzed the sequencing data of HL60 and its Adriamycin-resistant cell line HL60/ADR. We found a total of 40,550 m6A-methylated peaks, representing 15,640 genes in HL60, and 38,834 m6A-methylated peaks, representing 15,285 genes in HL60/ADR. KEGG pathway analysis showed that pathways were enriched in the FoxO signaling pathway, p53 signaling pathway, and Notch signaling pathway. MeRIP-seq results showed that the fold enrichment of the global m6A level in HL60/ADR was higher than that in HL60, and dot blot assay results indicated that the global m6A level was elevated in HL60/ADR cells compared with that in HL60 cells. Further analysis revealed that the expression level of METTL3 was elevated in HL60/ADR cells compared with that in HL60 cells. After a combined treatment of STM2457 (an inhibitor of METTL3) and Adriamycin, the proliferation of HL60/ADR was inhibited. Thus, we hypothesized that the abnormality of m6A modification played an important role in Adriamycin-resistant AML.
Evidence of a Causal Link Between the Well-Being Spectrum and the Risk of Myocardial Infarction: A Mendelian Randomization Study
Authors: Rukh Gull , Ahmad Shafqat , Lind Lars , Schiöth Helgi Birgir
Published: April 2022

Epidemiological studies have provided extensive evidence regarding the role of psychological risk factors in the pathogenesis of cardiovascular disease (CVD), but whether these associations are causal in nature is still unknown. We aimed to investigate whether the association between the wellbeing spectrum (WBS; derived from four psychological traits including life satisfaction, positive affect, neuroticism, and depressive symptoms) and CVD risk is causal. By employing a two-sample Mendelian randomization (MR) approach, the effect of the WBS on four CVD outcomes, including atrial fibrillation, heart failure, myocardial infarction, and ischemic stroke, was investigated. The genetically predicted WBS was associated with 38% lower risk for heart failure (odds ratio (OR): 0.62; 95% confidence interval [CI]: 0.50–0.78; P: 2.2 × 10−5) and 40% reduced risk of myocardial infarction (OR: 0.60; 95% CI: 0.47–0.78; P: 1.1 × 10−4). Of the WBS constituent traits, only depressive symptoms showed a positive causal association with heart failure and myocardial infarction. Neither WBS nor WBS constituent traits were associated with atrial fibrillation and ischemic stroke. In multivariable MR analyses, when genetic instruments for traditional CVD risk factors were also taken into consideration, the WBS was causally associated with a reduced risk for heart failure (OR: 0.72; 95% CI: 0.58–0.88; P: 0.001) and myocardial infarction (OR: 0.67; 95% CI: 0.52–0.86; P: 0.002). This study provides evidence that a higher WBS is causally associated with a decreased risk of developing CVD and, more specifically, myocardial infarction; moreover, the association is mainly driven by depressive symptoms. These results support current guidelines that suggest improving psychological wellbeing may help in reducing the burden of cardiovascular disease.