bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Throughput and Automated Acoustic Trapping of Extracellular Vesicles to Identify microRNAs With Diagnostic Potential for Prostate Cancer
Authors: Ku Anson , Fredsøe Jacob , Sørensen Karina D. , Borre Michael , Evander Mikael , Laurell Thomas , Lilja Hans , Ceder Yvonne
Published: March 2021

Molecular profiling of extracellular vesicles (EVs) offers novel opportunities for diagnostic applications, but the current major obstacle for clinical translation is the lack of efficient, robust, and reproducible isolation methods. To bridge that gap, we developed a microfluidic, non-contact, and low-input volume compatible acoustic trapping technology for EV isolation that enabled downstream small RNA sequencing. In the current study, we have further automated the acoustic microfluidics-based EV enrichment technique that enables us to serially process 32 clinical samples per run. We utilized the system to enrich EVs from urine collected as the first morning void from 207 men referred to 10-core prostate biopsy performed the same day. Using automated acoustic trapping, we successfully enriched EVs from 199/207 samples (96%). After RNA extraction, size selection, and library preparation, a total of 173/199 samples (87%) provided sufficient materials for next-generation sequencing that generated an average of 2 × 106 reads per sample mapping to the human reference genome. The predominant RNA species identified were fragments of long RNAs such as protein coding and retained introns, whereas small RNAs such as microRNAs (miRNA) accounted for less than 1% of the reads suggesting that partially degraded long RNAs out-competed miRNAs during sequencing. We found that the expression of six miRNAs was significantly different (Padj < 0.05) in EVs isolated from patients found to have high grade prostate cancer [ISUP 2005 Grade Group (GG) 4 or higher] compared to those with GG3 or lower, including those with no evidence of prostate cancer at biopsy. These included miR-23b-3p, miR-27a-3p, and miR-27b-3p showing higher expression in patients with GG4 or high grade prostate cancer, whereas miR-1-3p, miR-10a-5p, and miR-423-3p had lower expression in the GG4 PCa cases. Cross referencing our differentially expressed miRNAs to two large prostate cancer datasets revealed that the putative tumor suppressors miR-1, miR-23b, and miR-27a are consistently deregulated in prostate cancer. Taken together, this is the first time that our automated microfluidic EV enrichment technique has been found to be capable of enriching EVs on a large scale from 900 μl of urine for small RNA sequencing in a robust and disease discriminatory manner.
Case Report: A 3D-Printed Surgical Guide for Breast-Conserving Surgery After Neoadjuvant Chemotherapy
Authors: Wu Zhen-Yu , Kim Guk Bae , Lee Sangwook , Choi Seung Hyun , Kim Namkug , Ko BeomSeok
Published: March 2021

Background

A challenging problem for patients undergoing breast-conserving surgery after neoadjuvant chemotherapy (NACT) is the accuracy of preoperative tumor localization. After chemotherapy, the original tumor is likely to shrink or scatter dramatically or even show complete remission. For breast-conserving surgery, the development of a guidance device to accurately estimate the resection area is imperative.

Case Presentation

We produced a three-dimensional (3D)–printed breast surgical guide (BSG) based on prone and supine magnetic resonance imaging (MRI). This device was tested on a patient who underwent breast-conserving surgery after NACT. Both ultrasonography and MRI revealed that the tumor shrank substantially after NACT. Identifying the target tumor area using pre-NACT MRI was feasible, and the tumor was safely removed with clear resection margins.

Conclusion

The BSG has several advantages over conventional methods for tumor localization after NACT. In particular, the BSG provided precise quantitative MRI information about the tumor area.
Case Report: Cutaneous Squamous Cell Carcinoma Arising From the Ulcer of the Lesions of Dupuytren’s Disease on the Palm
Authors: Sun Qingmiao , Fu Bin , Li Sheng , Fang Hong , Qiao Jianjun
Published: March 2021

Dupuytren’s disease is a benign fibromatosis that mainly involves the fascia of the palm and digits. The relationship between Dupuytren’s disease and the evolution of cutaneous squamous cell carcinoma is still unclear. Here we report the case of a 52-year-old female with squamous cell carcinoma arising from the ulcer of the lesions of Dupuytren’s disease on the left palm. To our knowledge, this is the first reported case in the English literature of squamous cell carcinoma on the palm of someone with Dupuytren’s disease.
CDKN2A Deletion in Melanoma Excludes T Cell Infiltration by Repressing Chemokine Expression in a Cell Cycle-Dependent Manner
Authors: Zhu Zhen , Song Hao , Xu Juan
Published: March 2021

T-cell-mediated immune response is the prerequisite for T-cell-based immunotherapy. However, the limitation of T-cell infiltration in solid tumors restricted the therapeutic effect of T-cell-based immunotherapy. The present study screened the molecular and genetic features of The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort, revealing that T-cell infiltration negatively correlated with genome copy number alteration. The analysis of the TCGA-SKCM cohort indicated that the copy number of CDKN2A was significantly decreased in patients with low T-cell infiltration. The results were validated in the other two melanoma cohorts (DFCI, Science 2015, and TGEN, Genome Res 2017). Besides, the immunohistochemistry analysis of CDKN2A and CD8 expression in 5 melanoma in situ and 15 invasive melanoma patients also showed that CD8 expression was decreased in the patients with low CDKN2A expression and there was a positive correlation between CDKN2A and CD8 expression in these patients. Interestingly, the CDKN2A deletion group and the group with low expression of T-cell markers shared similar gene and pathway alteration as compared with the normal CDKN2A group and the group with high expression of T-cell markers, especially the chemokine pathway. Further mechanistic study indicated that CDKN2A enhanced T cell recruitment and chemokine expression possibly through modulating MAPK and NF-κB signaling pathways in a cell cycle–dependent manner. Finally, we also found that CDKN2A deletion negatively correlated with the expression of T-cell markers in many other cancer types. In conclusion, CDKN2A deletion could inhibit T cell infiltration by inhibiting chemokine expression in a cell cycle dependent manner.
The Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51
Authors: Liu Guochao , Lim David , Cai Zuchao , Ding Wenwen , Tian Zhujun , Dong Chao , Zhang Fengmei , Guo Gongshe , Wang Xiaowei , Zhou Pingkun , Feng Zhihui
Published: March 2021

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related to the increase of its ubiquitination regulated by E3 ligase RFWD3 for the radiosensitization, which was opposite to normal cells, indicating that RFWD3-dependent ubiquitination on Rad51 was involved in the VPA-mediated radio-bidirectional effect. Through DMBA-transformed breast cancer rat model, VPA at 200 mg/kg radiosensitized tumor tissue cells by increasing RFWD3 and inhibited Rad51, while radioprotected normal tissue cells by decreasing RFWD3 and enhanced Rad51. In addition, we found high-level Rad51 was associated with tumorigenesis and poor prognosis in breast cancer patients. Our findings uncovered RFWD3-dependent Rad51 ubiquitination was the novel mechanism of VPA-mediated radio-bidirectional effect, VPA is a potential adjuvant treatment for tumor RT.
Radiation and CAR T-cell Therapy in Lymphoma: Future Frontiers and Potential Opportunities for Synergy
Authors: Fang Penny Q. , Gunther Jillian R. , Wu Susan Y. , Dabaja Bouthaina S. , Nastoupil Loretta J. , Ahmed Sairah , Neelapu Sattva S. , Pinnix Chelsea C.
Published: March 2021

CAR T-cell therapy has revolutionized the treatment approach to patients with relapsed/refractory hematologic malignancies; however, there continues to be opportunity for improvement in treatment toxicity as well as response durability. Radiation therapy can play an important role in combined modality treatments for some patients undergoing CAR T-cell therapy in various clinical settings. In this review, we discuss the current evidence for RT in the setting of CAR T-cell therapy for patients with hematologic malignancies and propose potential opportunities for future investigation of RT and CAR T-cell treatment synergy. Future research frontiers include investigation of hypotheses including radiation priming of CAR T-cell mediated death, pre-CAR T-cell tumor debulking with radiation therapy, and selection of high risk patients for early radiation salvage after CAR T cell therapy.
SLC39A8/Zinc Suppresses the Progression of Clear Cell Renal Cell Carcinoma
Authors: Liu Lilong , Hou Yaxin , Hu Junyi , Zhou Lijie , Chen Ke , Yang Xiong , Song Zhengshuai
Published: March 2021

Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype, which has high risk of metastasis or recurrence, accounting for 75–83% of renal cell carcinoma (RCC). Zrt‐ and Irt‐like proteins (ZIP) family members (SLC39A1-14) function to pass zinc into the cytoplasm for many critical biological processes when cellular zinc is depleted. However, the functional analysis of individual ZIP family genes in ccRCC is not clarified. This study aimed to investigate whether ZIP family genes are related to the clinicopathological features and survival of ccRCC patients, and to identify the function of key gene of ZIP family in ccRCC in vitro. Through bioinformatics analysis of tumor databases, SLC39A8 was identified as a key gene of ZIP family in ccRCC, which could be used as an effective indicator for diagnosing ccRCC and judging its prognosis. With the progression of tumor, the expression of SLC39A8 decreased progressively. The prognosis of patients with low expression of SLC39A8 is significantly worse. Furthermore, we found that overexpression of SLC39A8 or treatment with low concentration of zinc chloride could effectively inhibit the proliferation, migration and invasion of ccRCC cells. Moreover, the inhibition effect of SLC39A8 overexpression could be enhanced by low concentration zinc supplement. Therefore, this study provides a novel understanding for the role of SLC39A8/zinc in the regulation of ccRCC progression. These findings provide a new direction and target for progressive ccRCC drug development and combination therapy strategies.
COVID-19 in Cancer Patients, Risk Factors for Disease and Adverse Outcome, a Population-Based Study From Norway
Authors: Johannesen Tom Børge , Smeland Sigbjørn , Aaserud Stein , Buanes Eirik Alnes , Skog Anna , Ursin Giske , Helland Åslaug
Published: March 2021

Background

Cancer has been suggested as a risk factor for severe outcome of SARS-CoV-2 infection. In this population-based study we aimed to identify factors associated with higher risk of COVID-19 and adverse outcome.

Methods

Data on all confirmed SARS-CoV-2 positive patients in the period January 1 to May 31, 2020 were extracted from the Norwegian Surveillance System for Communicable Diseases. Data on cancer and treatment was available from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Prescription Database. Deaths due to COVID-19 were extracted from the Cause of Death Registry. From the Norwegian Intensive Care and Pandemic Registry we retrieved data on admittance to hospital and intensive care. We determined rates of COVID-19 disease in cancer patients and the rest of the population. We also ran multivariate analyses adjusting for age and gender.

Results

A total of 8 410 patients were diagnosed with SARS-CoV-2 infection in Norway during the study period, of which 547 (6.5%) were cancer patients. Overall, we found similar age adjusted rates of COVID-19 in the population with cancer as in the population without cancer. Unadjusted analysis showed that patients having undergone major surgery within the past 3 months had an increased risk of COVID-19 while we did not find increased Odds Ratio (OR) related to other oncological treatment modalities. No patients treated with stem cell or bone marrow transplant were diagnosed with COVID-19. The fatality rate of COVID-19 among cancer patients was 0.10. This was similar to non-cancer patients, when adjusting for age and sex with OR (95% CI) for death= 0.99 (0.68–1.42). Patients with distant metastases had significantly increased OR of death due to COVID-19 disease of 9.31 (95% CI 2.60–33.34). For the combined outcome death and/or admittance to hospital due to COVID-19, we found significant two-fold increased risk estimates for patients diagnosed with cancer less than one 1 year ago (OR 2.08, 95% CI 1.14–3.80), for those treated with anti-cancer drugs during the past 3 months (OR 1.80, 95% CI 1.07–3.01) and for patients undergoing major surgery during the past 3 months (OR 2.19, 95% CI 1.40–3.44).
miR-181d/RBP2/NF-κB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis
Authors: Zhou Minran , Yin Xiaolin , Zheng Lixin , Fu Yue , Wang Yue , Cui Zelong , Gao Zhenxing , Wang Xiaoming , Huang Tao , Jia Jihui , Chen Chunyan
Published: March 2021

Background

Chronic myeloid leukemia (CML) is a malignant clonal proliferative disease. Once it progresses into the phase of blast crisis (CML-BP), the curative effect is poor, and the fatality rate is extremely high. Therefore, it is urgent to explore the molecular mechanisms of blast crisis and identify new therapeutic targets.

Methods

The expression levels of miR-181d, RBP2 and NF-κB p65 were assessed in 42 newly diagnosed CML-CP patients and 15 CML-BP patients. Quantitative real-time PCR, Western blots, and cell proliferation assay were used to characterize the changes induced by overexpression or inhibition of miR-181d, RBP2 or p65. Luciferase reporter assay and ChIP assay was conducted to establish functional association between miR-181d, RBP2 and p65. Inhibition of miR-181d expression and its consequences in tumor growth was demonstrated in vivo models.

Results

We found that miR-181d was overexpressed in CML-BP, which promoted leukemia cell proliferation. Histone demethylase RBP2 was identified as a direct target of miR-181d which downregulated RBP2 expression. Moreover, RBP2 inhibited transcriptional expression of NF-κB subunit, p65 by binding to its promoter and demethylating the tri/dimethylated H3K4 region in the p65 promoter locus. In turn, p65 directly bound to miR-181d promoter and upregulated its expression. Therefore, RBP2 inhibition resulting from miR-181d overexpression led to p65 upregulation which further forwarded miR-181d expression. This miR-181d/RBP2/p65 feedback regulation caused sustained NF-κB activation, which contributed to the development of CML-BP.

Conclusions

Taken together, the miR-181d/RBP2/p65 feedback regulation promoted CML-BP and miR-181d may serve as a potential therapeutic target of CML-BP.
FLVCR1 Predicts Poor Prognosis and Promotes Malignant Phenotype in Esophageal Squamous Cell Carcinoma via Upregulating CSE1L
Authors: Zhou Suna , Zhang Mingxin , Zhou Chao , Meng Yinnan , Yang Haihua , Ye Wenguang
Published: March 2021

Objective

Dysregulation of feline leukemia virus subgroup C receptor 1(FLVCR1) expression has been investigated in several tumors. However, the expression and role of FLVCR1 in esophageal squamous cell carcinoma (ESCC) remain largely unknown.

Methods

FLVCR1 expression in tissues was measured by immunohistochemical staining (IHC). Celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, wound healing assay, Transwell migration, and invasion assay were applied to assess the effects of FLVCR1 on ESCC tumorigenesis. Coimmunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS) were used to identify protein interactions with FLVCR1. An in vivo imaging system (IVIS) was used to investigate the functions of FLVCR1 on the growth and metastatic capability of ESCC cells in a xenograft model and a tail vein metastasis model.

Results

Elevated expression of FLVCR1 was detected in ESCC tissues and predicted poor survival. Upregulated FLVCR1 was positively correlated with lymph node metastasis (N stage) and late tumor-node-metastasis (TNM) stage. FLVCR1 knockdown inhibited cell proliferation and colony formation ability, induced cell apoptosis, and repressed cell migration and invasion of ESCC in vitro. Inhibition of FLVCR1 markedly repressed tumorigenicity and metastasis of ESCC cells in vivo. Mechanistically, chromosome segregation 1–like (CSE1L) was identified to interact with FLVCR1 using a Co-IP assay. Moreover, the inhibitory effect of FLVCR1 knockdown on proliferation and migration was counteracted by the exogenous expression of CSE1L.

Conclusion

FLVCR1 plays a pivotal role in ESCC cell survival, growth, and migration. These functions may be partially dependent upon the protein interaction between FLVCR1 and CSE1L. In addition, FLVCR1 can be applied as a clinical prognostic marker for patients with ESCC.
CircRNA circ_0092314 Induces Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Elevating the Expression of S100P by Sponging miR-671
Authors: Shen Qian , Zheng Gang , Zhou Yi , Tong Jin , Xu Sanpeng , Gao Hui , Zhang Xiaofan , Fu Qiang
Published: March 2021

Background

Circular RNAs (circRNAs) is a novel class of non-coding RNAs that regulate gene expression during cancer progression. Circ_0092314 is a newly discovered circRNA that was upregulated in pancreatic cancer (PAAD) tissues. However, the detailed functions and underlying mechanisms of circ_0092314 in PAAD cells remain unclear.

Methods

We first determined the expression of circ_0092314 in PAAD and normal tissues and further investigated the functional roles of circ_0092314 in regulating epithelial-mesenchymal transition (EMT) of PAAD cells. We also assessed the regulatory action of circ_0092314 on the microRNA-671 (miR-671) and its target S100P.

Results

Circ_0092314 was markedly upregulated in PAAD tissues and cells, and its overexpression was closely correlated with worse prognosis of PAAD patients. Functionally, circ_0092314 promotes proliferation, invasion and EMT in vitro and tumor growth in vivo. Mechanistically, we demonstrated that circ_0092314 directly binds to miR-671 and relieve its suppression of the downstream target S100P, which induces EMT and activates the AKT signaling pathway. The tumor-promoting effects caused by overexpression of circ_0092314 could be revered by re-expression of miR-671 in PAAD cells.

Conclusions

Overall, our study demonstrates that circ_0092314 exerts critical roles in promoting the EMT features of PAAD cells, and provides insight into how elevated expression of circ_0092314 might influence PAAD progression.
Alternol Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis
Authors: Ren Yu , Wang Xue , Huang Shuaishuai , Xu Yangkai , Weng Guobin , Yu Rui
Published: March 2021

Purpose: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a member of the TNF family, can selectively induce cancer cell death while sparing normal cells. However, the application of TRAIL-based antitumor therapies has been hindered due to drug resistance. Alternol is a new compound isolated from microbial fermentation that possesses antitumor activity in different tumors. In our research, we discovered that alternol can sensitize TRAIL-induced apoptosis in renal carcinoma cells (RCCs).

Materials and Methods: Cytotoxic activity was measured by MTT assay. Apoptosis was probed using the PI/annexin V method. Real-time PCR and western blot were used to test the levels of mRNA and protein, respectively. Luciferase assay was used to investigate whether CHOP regulated the expression of death receptor (DR) 5 through transcription. A xenogeneic tumor transplantation model was used to evaluate the anticancer effects of alternol/TRAIL in vivo.

Results: When the mechanisms were investigated, we discovered that alternol increased DR5 expression. DR5 knockdown by siRNA eliminated the enhanced effect of alternol on TRAIL-mediated apoptosis. Alternol reduced the expression of antiapoptotic proteins and increased the levels of proapoptotic proteins. Moreover, alternol increased the level of CHOP, which is necessary for the enhancing effect of alternol on TRAIL-induced apoptosis, given that downregulation of CHOP abrogated the synergistic effect. DR5 upregulation induced by alternol required the production of reactive oxygen species (ROS). Removing ROS inhibited the induction of DR5 and blocked the antiapoptotic proteins induced by alternol.

Conclusion: Taken together, our research suggested that alternol increased TRAIL-mediated apoptosis via inhibiting antiapoptotic proteins and upregulating DR5 levels via ROS generation and the CHOP pathway.
Psychedelic Communitas: Intersubjective Experience During Psychedelic Group Sessions Predicts Enduring Changes in Psychological Wellbeing and Social Connectedness
Authors: Kettner H. , Rosas F. E. , Timmermann C. , Kärtner L. , Carhart-Harris R. L. , Roseman L.
Published: March 2021

Background:Recent years have seen a resurgence of research on the potential of psychedelic substances to treat addictive and mood disorders. Historically and contemporarily, psychedelic studies have emphasized the importance of contextual elements ('set and setting') in modulating acute drug effects, and ultimately, influencing long-term outcomes. Nevertheless, current small-scale clinical and laboratory studies have tended to bypass a ubiquitous contextual feature of naturalistic psychedelic use: its social dimension. This study introduces and psychometrically validates an adaptedCommunitas Scale,assessing acute relational experiences of perceived togetherness and shared humanity, in order to investigate psychosocial mechanisms pertinent to psychedelic ceremonies and retreats.

Methods:In this observational, web-based survey study, participants (N= 886) were measured across five successive time-points: 2 weeks before, hours before, and the day after a psychedelic ceremony; as well as the day after, and 4 weeks after leaving the ceremony location. Demographics, psychological traits and state variables were assessed pre-ceremony, in addition to changes in psychological wellbeing and social connectedness from before to after the retreat, as primary outcomes. Using correlational and multiple regression (path) analyses, predictive relationships between psychosocial 'set and setting' variables, communitas, and long-term outcomes were explored.

Results:The adapted Communitas Scale demonstrated substantial internal consistency (Cronbach's alpha = 0.92) and construct validity in comparison with validated measures of intra-subjective (visual, mystical, challenging experiences questionnaires) and inter-subjective (perceived emotional synchrony, identity fusion) experiences. Furthermore, communitas during ceremony was significantly correlated with increases in psychological wellbeing (r= 0.22), social connectedness (r= 0.25), and other salient mental health outcomes. Path analyses revealed that the effect of ceremony-communitas on long-term outcomes was fully mediated by communitas experienced in reference to the retreat overall, and that the extent of personal sharing or ‘self-disclosure’ contributed to this process. A positive relationship between participants and facilitators, and the perceived impact of emotional support, facilitated the emergence of communitas.

Conclusion:Highlighting the importance of intersubjective experience, rapport, and emotional support for long-term outcomes of psychedelic use, this first quantitative examination of psychosocial factors in guided psychedelic settings is a significant step toward evidence-based benefit-maximization guidelines for collective psychedelic use.
The Role of Autophagy in Skeletal Muscle Diseases
Authors: Xia Qianghua , Huang Xubo , Huang Jieru , Zheng Yongfeng , March Michael E. , Li Jin , Wei Yongjie
Published: March 2021

Skeletal muscle is the most abundant type of tissue in human body, being involved in diverse activities and maintaining a finely tuned metabolic balance. Autophagy, characterized by the autophagosome–lysosome system with the involvement of evolutionarily conserved autophagy-related genes, is an important catabolic process and plays an essential role in energy generation and consumption, as well as substance turnover processes in skeletal muscles. Autophagy in skeletal muscles is finely tuned under the tight regulation of diverse signaling pathways, and the autophagy pathway has cross-talk with other pathways to form feedback loops under physiological conditions and metabolic stress. Altered autophagy activity characterized by either increased formation of autophagosomes or inhibition of lysosome-autophagosome fusion can lead to pathological cascades, and mutations in autophagy genes and deregulation of autophagy pathways have been identified as one of the major causes for a variety of skeleton muscle disorders. The advancement of multi-omics techniques enables further understanding of the molecular and biochemical mechanisms underlying the role of autophagy in skeletal muscle disorders, which may yield novel therapeutic targets for these disorders.
Calcium Imaging Analysis of Cellular Responses to Hypercapnia and Hypoxia in the NTS of Newborn Rat Brainstem Preparation
Authors: Onimaru Hiroshi , Yazawa Itaru , Takeda Kotaro , Fukushi Isato , Okada Yasumasa
Published: March 2021

It is supposed that the nucleus of the solitary tract (NTS) in the dorsal medulla includes gas sensor cells responsive to hypercapnia or hypoxia in the central nervous system. In the present study, we analyzed cellular responses to hypercapnia and hypoxia in the NTS region of newborn rat in vitro preparation. The brainstem and spinal cord were isolated from newborn rat (P0-P4) and were transversely cut at the level of the rostral area postrema. To detect cellular responses, calcium indicator Oregon Green was pressure-injected into the NTS just beneath the cut surface of either the caudal or rostral block of the medulla, and the preparation was superfused with artificial cerebrospinal fluid (25–26°C). We examined cellular responses initially to hypercapnic stimulation (to 8% CO2 from 2% CO2) and then to hypoxic stimulation (to 0% O2 from 95% O2 at 5% CO2). We tested these responses in standard solution and in two different synapse blockade solutions: (1) cocktail blockers solution including bicuculline, strychnine, NBQX and MK-801 or (2) TTX solution. At the end of the experiments, the superfusate potassium concentration was lowered to 0.2 from 3 mM to classify recorded cells into neurons and astrocytes. Excitation of cells was detected as changes of fluorescence intensity with a confocal calcium imaging system. In the synaptic blockade solutions (cocktail or TTX solution), 7.6 and 8% of the NTS cells responded to hypercapnic and hypoxic stimulation, respectively, and approximately 2% of them responded to both stimulations. Some of these cells responded to low K+, and they were classified into astrocytes comprising 43% hypercapnia-sensitive cells, 56% hypoxia-sensitive cells and 54% of both stimulation-sensitive cells. Of note, 49% of the putative astrocytes identified by low K+ stimulation were sensitive to hypercapnia, hypoxia or both. In the presence of a glia preferential blocker, 5 mM fluoroacetate (plus 0.5 μM TTX), the percentage of hypoxia-sensitive cells was significantly reduced compared to those of all other conditions. This is the first study to reveal that the NTS includes hypercapnia and hypoxia dual-sensitive cells. These results suggest that astrocytes in the NTS region could act as a central gas sensor.
Comparative Plastomes and Phylogenetic Analysis of Cleistogenes and Closely Related Genera (Poaceae)
Authors: Wang Rong , Liu Kuan , Zhang Xue-Jie , Chen Wen-Li , Qu Xiao-Jian , Fan Shou-Jin
Published: March 2021

Cleistogenes (Orininae, Cynodonteae, Chloridoideae, Poaceae) is an ecologically important genus. The phylogenetic placement of Cleistogenes and phylogenetic relationships among Cleistogenes taxa remain controversial for a long time. To resolve the intra- and inter-generic relationships of Cleistogenes, the plastomes of 12 Cleistogenes taxa (including 8 species and 4 varieties), one Orinus species, 15 Triodia species, two Tripogon species, and two Aeluropus species were included in the present study. All the taxa showed a similar pattern in plastome structure, gene order, gene content, and IR boundaries. The number of simple sequence repeats ranged from 145 (O. kokonorica) to 161 (T. plurinervata and T. schinzii). Moreover, 1,687 repeats were identified in these taxa, including 1,012 forward, 650 palindromic, 24 reverse, and one complement. Codon usage analysis revealed that these plastomes contained 16,633 (T. stipoides) to 16,678 (T. tomentosa) codons. Sequence divergence analysis among Cleistogenes and closely related genera identified five non-coding regions (trnS-UGA-psbZ, rpl32-trnL-UAG, trnQ-UUG-psbK, trnD-GUC-psbM, trnT-GGU-trnE-UUC). Phylogenetic analysis of complete plastomes indicated that Cleistogenes is sister to a clade composed of Orinus and Triodia, whereas it did not support the sister relationship between the recently proposed subtribe Orininae (Cleistogenes and Orinus) and Triodia. The subtribe Orininae was not supported by our complete plastome data. The split between Cleistogenes and Orinus-Triodia clade go back to 14.01 Ma. Besides, our findings suggested that C. squarrosa and C. songorica are the successive early diverging groups in the phylogenetic analysis. The other 10 taxa are divided into two groups: a monophyletic group composed of Cleistogenes sp. nov. and C. caespitosa var. ramosa is sister to other eight Cleistogenes taxa. Cleistogenes was estimated to have experienced rapid divergence within a short period, which could be a major obstacle in resolving phylogenetic relationships within Cleistogenes. Collectively, our results provided valuable insights into the phylogenetic study of grass species.
Effect of Foliar Application of Various Nitrogen Forms on Starch Accumulation and Grain Filling of Wheat (Triticum aestivum L.) Under Drought Stress
Authors: Lv Xiaokang , Ding Yunpeng , Long Mei , Liang Wenxin , Gu Xiaoyan , Liu Yang , Wen Xiaoxia
Published: March 2021

Foliar nitrogen (N) fertilizer application at later stages of wheat (Triticum aestivum L.) growth is an effective method of attenuating drought stress and improving grain filling. The influences or modes of action of foliar application of various nitrogen forms on wheat growth and grain filling need further research. The objective of this study was to examine the regulatory effects of various forms of foliar nitrogen [NO3–, NH4+, and CO(NH2)2] on wheat grain filling under drought stress and to elucidate their underlying mechanisms. The relative effects of each nitrogen source differed in promoting grain filling. Foliar NH4+-N application notably prolonged the grain filling period. In contrast, foliar application of CO(NH2)2 and NO3–-N accelerated the grain filling rate and regulated levels of abscisic acid (ABA), z-riboside (ZR), and ethylene (ETH) in wheat grains. Analysis of gene expression revealed that CO(NH2)2 and NO3–-N upregulated the genes involved in the sucrose–starch conversion pathway, promoting the remobilization of carbohydrates and starch synthesis in the grains. Besides, activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were increased, whereas the content of malondialdehyde (MDA) declined under foliar nitrogen application (especially NH4+-N). Under drought stress, enhancement of carbohydrate remobilization and sink strength became key factors in grain filling, and the relative differences in the effects of three N forms became more evident. In conclusion, NH4+-N application improved the antioxidant enzyme system and delayed photoassimilate transportation. On the other hand, foliar applications of NO3–-N and CO(NH2)2 enhanced sink capacity and alleviated drought stress injury in wheat.
Homeland Political Trust Among Emigrants: The Case of Finland-Swedes
Authors: Vento Isak
Published: March 2021

How does emigrating affect one's political trust for their native country's political and state institutions? This question is increasingly relevant as a result of growing migration in the wake of globalization and the willingness to widen electoral laws and channels for participation to also include emigrated citizens in homeland politics. Despite the research conducted on homeland politics and voting from abroad in political science, the question of homeland political trust among emigrants has not been given sufficient attention. This could be seen as surprising from the perspective of trust research, which has exhaustively analyzed political and social trust. This paper seeks to map the effect of migration on political trust by comparing the trust in Finnish political and state institutions of emigrated Swedish-speaking Finns, also known as Finland-Swedes, and Finland-Swedes living in Finland. The Finland-Swedes are a resourceful minority with a sizeable diaspora, which in relative terms is comparable to nations with a renowned diaspora. The paper analyzes the political trust of migrants and residents with two high quality random surveys and using two methods, linear regression and propensity score matching, with analysis of average treatment effects to counter potential endogeneity of political trust and migrating citizens. The analyses show emigrants have on average significantly higher homeland political trust. Comparing the linear regression analysis and the average treatment effects after matching we get similar results, although the linear regression analysis that controls for potentially endogenous factors seems to somewhat exaggerate the effect of migration.
No Evidence for a Decrease in Physical Activity Among Swiss Office Workers During COVID-19: A Longitudinal Study
Authors: Aegerter Andrea Martina , Deforth Manja , Sjøgaard Gisela , Johnston Venerina , Volken Thomas , Luomajoki Hannu , Dratva Julia , Dressel Holger , Distler Oliver , Melloh Markus , Elfering Achim ,   the NEXpro Collaboration Group
Published: March 2021

Purpose

The COVID-19 lockdown interrupted normal daily activities, which may have led to an increase in sedentary behavior (Castelnuovo et al., 2020). The aim of this study was to investigate the effect of the COVID-19 pandemic on the level of physical activity among Swiss office workers.

Methods

Office workers from two Swiss organizations, aged 18–65 years, were included. Baseline data from January 2020 before the COVID-19 pandemic became effective in Switzerland were compared with follow-up data during the lockdown phase in April 2020. Levels of physical activity were assessed using the International Physical Activity Questionnaire. Paired sample t-tests or Wilcoxon signed-rank test were performed for statistical analysis.

Results

Data from 76 participants were analyzed. Fifty-four participants were female (71.1%). The mean age was 42.7 years (range from 21.8 to 62.7) at baseline. About 75% of the participants met the recommendations on minimal physical activity, both before the COVID-19 pandemic and during the lockdown. Weak statistical evidence for a decline in total physical activity in metabolic equivalent of task minutes per week (MET min/week) was found (estimate = −292, 95% CI from – ∞ to 74, p-value = 0.09), with no evidence for a decrease in the three types of activity: walking (estimate = −189, 95% CI from – ∞ to 100, p-value = 0.28), moderate-intensity activity (estimate = −200, 95% CI from – ∞ to 30, p-value = 0.22) and vigorous-intensity activity (estimate = 80, 95% CI from – ∞ to 460, p-value = 0.74). Across the three categories “high,” “moderate,” and “low” physical activity, 17% of the participants became less active during the lockdown while 29% became more active.

Conclusion

The COVID-19 pandemic did not result in a reduction in total physical activity levels among a sample of Swiss office workers during the first weeks of lockdown. Improved work-life balance and working times may have contributed to this finding.

Clinical Trial Registration

www.ClinicalTrials.gov, NCT04169646. Registered 15 November 2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04169646.
Affective Profiles and Anxiety or Non-Anxiety-Related Reasons for School Refusal Behavior: Latent Profile Analysis in Spanish Adolescents
Authors: Gonzálvez Carolina , Díaz-Herrero Ángela , Vicent María , Sanmartín Ricardo , Fernández-Sogorb Aitana , Ruiz-Esteban Cecilia
Published: March 2021

Little has been studied on the relationship between affect and school problems related with attendance. This study aims to identify different affective profiles and to determine whether these profiles differ from each other based on the four functional conditions of school refusal behavior. Participants comprised 1,816 Spanish adolescents aged 15–18 years (M = 16.39; SD = 1.05). The Positive and Negative Affect Schedule for Children-Short Form and the School Refusal Assessment Scale-Revised for Children (SRAS-R-C) were administered. Latent profile analysis revealed five affective profiles: low affective profile, self-fulfilling profile, low positive affect profile, self-destructive profile, and high affective profile. The self-destructive profile revealed the highest average scores in the first three factors of the SRAS-R-C, whereas the high affective profile reached the highest average score in the fourth factor. On the contrary, the self-fulfilling profile obtained the lowest average scores in the first two factors of the SRAS-R-C, whereas the low affective profile revealed the lowest average scores in the last two factors. Findings suggest the relevance of developing more adaptative affective profiles, such as the self-fulfilling profile, which would contribute to diminishing school attendance problems.
Health Patterns Reveal Interdependent Needs of Dutch Homeless Service Users
Authors: Everdingen Coline van , Peerenboom Peter Bob , Velden Koos van der , Delespaul Philippe
Published: March 2021

Background: Homelessness is an increasing problem in Western European countries. Dutch local authorities initiated cross-sectional reviews to obtain accurate health and needs information on Homeless Service (HS) users.

Methods: The Homeless People Treatment and Recovery (HOP-TR) study uses a comprehensive assessment strategy to obtain health data. Using a naturalistic meta-snowball sampling in 2015–2017, 436 Dutch HS users were assessed. The lived experience of HS users was the primary data source and was enriched with professional assessments. The InterRAI Community Mental Health questionnaire and “Homelessness Supplement” provided information in different areas of life. The approach for mental health assessments was transdiagnostic. Raw interview data were recoded to assess health and needs. The positive health framework structured symptomatic, social, and personal health domains relevant to recovery.

Results: Most subjects were males, low educated, with a migration background. The majority were long-term or intermittently homeless. Concurrent health problems were present in two domains or more in most (95.0%) subjects. Almost all participants showed mental health problems (98.6%); for a significant share severe (72.5%). Frequent comorbid conditions were addiction (78%), chronic physical conditions (59.2%), and intellectual impairments (39.9%).

Conclusion: The HOP-TR study reveals significant concurrent health problems among Dutch HS users. The interdependent character of different needs requires an integrated 3-D public health approach to comprehensively serve symptomatic, social, and personal dimensions, required to facilitate recovery.
Impact of the COVID-19 Lockdown on Air Quality and Resulting Public Health Benefits in the Mexico City Metropolitan Area
Authors: Hernández-Paniagua Iván Y. , Valdez S. Ivvan , Almanza Victor , Rivera-Cárdenas Claudia , Grutter Michel , Stremme Wolfgang , García-Reynoso Agustín , Ruiz-Suárez Luis Gerardo
Published: March 2021

Meteorology and long-term trends in air pollutant concentrations may obscure the results from short-term policies implemented to improve air quality. This study presents changes in CO, NO2, O3, SO2, PM10, and PM2.5 based on their anomalies during the COVID-19 partial (Phase 2) and total (Phase 3) lockdowns in Mexico City (MCMA). To minimise the impact of the air pollutant long-term trends, pollutant anomalies were calculated using as baseline truncated Fourier series, fitted with data from 2016 to 2019, and then compared with those from the lockdown. Additionally, days with stagnant conditions and heavy rain were excluded to reduce the impact of extreme weather changes. Satellite observations for NO2 and CO were used to contrast the ground-based derived results. During the lockdown Phase 2, only NO2 exhibited significant decreases (p < 0.05) of between 10 and 23% due to reductions in motor vehicle emissions. By contrast, O3 increased (p < 0.05) between 16 and 40% at the same sites where NO2 decreased. During Phase 3, significant decreases (p < 0.05) were observed for NO2 (43%), PM10 (20%), and PM2.5 (32%) in response to the total lockdown. Although O3 concentrations were lower in Phase 3 than during Phase 2, those did not decrease (p < 0.05) from the baseline at any site despite the total lockdown. SO2 decreased only during Phase 3 in a near-road environment. Satellite observations confirmed that NO2 decreased and CO stabilised during the total lockdown. Air pollutant changes during the lockdown could be overestimated between 2 and 10-fold without accounting for the influences of meteorology and long-term trends in pollutant concentrations. Air quality improved significantly during the lockdown driven by reduced NO2 and PM2.5 emissions despite increases in O3, resulting in health benefits for the MCMA population. A health assessment conducted suggested that around 588 deaths related to air pollution exposure were averted during the lockdown. Our results show that to reduce O3 within the MCMA, policies must focus on reducing VOCs emissions from non-mobile sources. The measures implemented during the COVID-19 lockdowns provide valuable information to reduce air pollution through a range of abatement strategies for emissions other than from motor vehicles.
Human- versus Artificial Intelligence
Authors: Korteling J. E. (Hans). , van de Boer-Visschedijk G. C. , Blankendaal R. A. M. , Boonekamp R. C. , Eikelboom A. R.
Published: March 2021

AI is one of the most debated subjects of today and there seems little common understanding concerning the differences and similarities of human intelligence and artificial intelligence. Discussions on many relevant topics, such as trustworthiness, explainability, and ethics are characterized by implicit anthropocentric and anthropomorphistic conceptions and, for instance, the pursuit of human-like intelligence as the golden standard for Artificial Intelligence. In order to provide more agreement and to substantiate possible future research objectives, this paper presents three notions on the similarities and differences between human- and artificial intelligence: 1) the fundamental constraints of human (and artificial) intelligence, 2) human intelligence as one of many possible forms of general intelligence, and 3) the high potential impact of multiple (integrated) forms of narrow-hybrid AI applications. For the time being, AI systems will have fundamentally different cognitive qualities and abilities than biological systems. For this reason, a most prominent issue is how we can use (and “collaborate” with) these systems as effectively as possible? For what tasks and under what conditions, decisions are safe to leave to AI and when is human judgment required? How can we capitalize on the specific strengths of human- and artificial intelligence? How to deploy AI systems effectively to complement and compensate for the inherent constraints of human cognition (and vice versa)? Should we pursue the development of AI “partners” with human (-level) intelligence or should we focus more at supplementing human limitations? In order to answer these questions, humans working with AI systems in the workplace or in policy making have to develop an adequate mental model of the underlying ‘psychological’ mechanisms of AI. So, in order to obtain well-functioning human-AI systems, Intelligence Awareness in humans should be addressed more vigorously. For this purpose a first framework for educational content is proposed.
Can Behaviorally Informed Urban Living Labs Foster the Energy Transition in Cities?
Authors: Della Valle Nives , Gantioler Sonja , Tomasi Silvia
Published: March 2021

Identifying governance schemes that promote cooperation among urban stakeholders is a priority in a context where rapid urbanization poses multiple and complex challenges for ensuring the sustainability of cities. Smart cities offer promising governance approaches, especially in the framework of the concept of Urban Living Labs (ULLs), as an enabling environment for so-called user-centric co-creation processes. While embedding a potential to promote solutions that tackle the challenges of urbanization, especially in relation to the energy transition, it is not yet clear how ULLs can effectively involve all relevant actors nor the extent of their impact, especially regarding behaviors. The study first analyzes the interplay between the challenge of urban energy transition and local governance schemes. Then, it explores how findings from behavioral sciences can inform the design of ULLs to effectively promote active engagement in the urban energy transition. Finally, it reviews the theoretical findings in relation to the ULL that has been taking shape in the city of Trento, Italy.