bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinesin-5 Eg5 is essential for spindle assembly and chromosome alignment of mouse spermatocytes
Authors: She Zhen-Yu , Zhong Ning , Yu Kai-Wei , Xiao Yu , Wei Ya-Lan , Lin Yang , Li Yue-Ling , Lu Ming-Hui 
Published: March 2020

AbstractBackgroundMicrotubule organization is essential for bipolar spindle assembly and chromosome segregation, which contribute to genome stability. Kinesin-5 Eg5 is known to be a crucial regulator in centrosome separation and spindle assembly in mammalian somatic cells, however, the functions and mechanisms of Eg5 in male meiotic cell division remain largely unknown.ResultsIn this study, we have found that Eg5 proteins are expressed in mouse spermatogonia, spermatocytes and spermatids. After Eg5 inhibition by specific inhibitors Monastrol, STLC and Dimethylenastron, the meiotic spindles of dividing spermatocytes show spindle collapse and the defects in bipolar spindle formation. We demonstrate that Eg5 regulates spindle bipolarity and the maintenance of meiotic spindles in meiosis. Eg5 inhibition leads to monopolar spindles, spindle abnormalities and chromosome misalignment in cultured GC-2 spd cells. Furthermore, Eg5 inhibition results in the decrease of the spermatids and the abnormalities in mature sperms.ConclusionsOur results have revealed an important role of kinesin-5 Eg5 in male meiosis and the maintenance of male fertility. We demonstrate that Eg5 is crucial for bipolar spindle assembly and chromosome alignment in dividing spermatocytes. Our data provide insights into the functions of Eg5 in meiotic spindle assembly of dividing spermatocytes.
Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells
Authors: Tien Yun , Tsai Chiao-Ling , Hou Wei-Hsien , Chiang Yun , Hsu Feng-Ming , Tsai Yu-Chieh , Cheng Jason Chia-Hsien 
Published: March 2020

AbstractBackgroundSublethal radiation induces matrix metalloproteinase 9 (MMP-9)-mediated radioresistance in Lewis lung carcinoma (LLC) cells and their metastatic dissemination. We aim to determine if EGFR/HER2 activation associates with MMP-9-mediated radioresistance and invasiveness in irradiated LLC cells.MethodsLLC cells were treated with erlotinib or afatinib followed by sublethal radiation. After irradiation, we examined the phosphorylation of EGFR/HER2 and MMP-9 expression. Colony formation assay determined if the kinase inhibitors sensitize LLC cells to radiation. Matrigel-coated Boyden chamber assay assessed cellular invasiveness. Resulting tumors of wild-type LLC cells or HER2 knock-down mutant cells were irradiated to induce pulmonary metastases.ResultsAfatinib more effectively sensitized LLC cells to radiation and decreased invasiveness by inhibiting phosphorylation of EGFR, HER2, Akt, ERK, and p38, and down-regulating MMP-9 when compared to erlotinib. Afatinib abolished radiation-induced lung metastases in vivo. Furthermore, LLC HER2 knock-down cells treated with radiation had growth inhibition.ConclusionDual inhibition of radiation-activated EGFR and HER2 signaling by afatinib suppressed the proliferation and invasion of irradiated LLC cells. Increased radiosensitivity and decreased metastatic dissemination were observed by pharmacological or genetic HER2 inhibition in vivo. These findings indicate that HER2 plays a pivotal role in enhancing radioresistance and reducing metastatic potential of LLC cells.
A qualitative exploration of service users’ and staff members’ perspectives on the roles of inpatient settings in mental health recovery
Authors: De Ruysscher Clara , Vandevelde Stijn , Tomlinson Peter , Vanheule Stijn 
Published: March 2020

Abstract
Background
Today, international mental health care increasingly focuses on creating recovery-oriented systems of support. This study aims to unravel the daily practice of an inpatient psychiatric ward that engages with persons with complex mental health needs.

Methods
17 in-depth interviews were conducted with patients and staff of the ward. Data was analyzed by means of thematic analysis.

Results
Three important functions of the ward were identified in the participants’ experiences. First, it functions as an asylum, a safe environment where patients can ‘simply be’. Second, the ward is experienced as a particularizing space, as support is organized in an individualized way and patients are encouraged to reconnect with their own identity. Third, the ward functions as a transitional space towards a valuable community life, in which finding adequate housing is of central importance.

Conclusions
The results show that inpatient forms of support tally with personal and social dimensions of recovery and fulfill important roles in recovery-oriented systems of support.
Effect of an ICU diary on psychiatric disorders, quality of life, and sleep quality among adult cardiac surgical ICU survivors: a randomized controlled trial
Authors: Wang Shuo , Xin Hui-Ning , Chung Lim Vico Chiang , Liao Jin-Hua , Li Sai-Lan , Xie Na-Mei , Hu Rong-Fang 
Published: March 2020

Abstract
Background
Although studies on the effectiveness of the use of ICU diaries on psychiatric disorders and quality of life have been published, the results still seem to be controversial. The study aimed to determine the effects of using an ICU diary on psychiatric disorders, sleep quality, and quality of life (QoL) in adult ICU survivors in China.

Methods
One hundred and twenty-six patients who underwent a scheduled cardiac surgery and were expected to stay ≥ 24 h in ICU were randomized to two groups (63 in each group). The patients in the intervention group received the use of ICU diaries during the period of post-ICU follow-up, while the patients in the control group received usual care without ICU diaries. The primary outcome was significant PTSD symptoms (Chinese version of Impact of Event Scale-Revised, IES-R; total score ≥ 35 was defined as significant PTSD symptoms) and its severity in patients 3 months post-ICU. The secondary outcomes included memories of the ICU at 1 month, QoL (Medical Outcomes Study 36-item Short-Form, SF-36), sleep quality (Pittsburgh Sleep Quality Index Questionnaire, PSQI), anxiety, and depression symptoms (Hospital Anxiety and Depression Scale, HADS) at 3 months.

Results
Eighty-five and 83 patients completed the follow-up interviews at 1 month and 3 months post-ICU, respectively. Significant PTSD symptoms were reported by 6 of 41 (14.63%) in the intervention group vs 9 of 42 (21.43%) in the control group (risk difference, − 9% [95% CI, − 2% to 21%], P = 0.10). There was no significant differences between groups in IES-R score, symptoms of intrusion, symptoms of avoidance, numbers of memories of feeling and delusional memories, SF-36 score and anxiety score (P > 0.05), while significant differences were found in symptom of hyperarousal score, numbers of factual memories and PSQI score (P < 0.05). No adverse effect was reported.

Conclusions
Using an ICU diary is not useful for preventing PTSD symptoms and anxiety symptoms and preserving the quality of life of the patients at 3 months post-ICU, while it significantly improves the survivor’s factual memory of ICU and sleep quality, and prevents the hyperarousal symptom.

Trial registration
Chinese Clinical Trial Registry, ChiCTR-IOR-16009109, registered on 28 August 2016
Effect of postextubation high-flow nasal cannula therapy on lung recruitment and overdistension in high-risk patient
Authors: Zhang Rui , He Huaiwu , Yun Long , Zhou Xiang , Wang Xu , Chi Yi , Yuan Siyi , Zhao Zhanqi 
Published: March 2020

Abstract
Background
Postextubation high-flow nasal cannula (HFNC) is used as a support therapy in high-risk patients in ICU. This study aimed to determine the effects of HFNC therapy on lung recruitment and overdistension assessed by electrical impedance tomography (EIT).

Methods
Twenty-four patients who received HFNC within 24 h after extubation were prospectively enrolled in this study. EIT was used to monitor regional lung ventilation distributions at baseline (conventional oxygen therapy) and three flow rate levels of HFNC therapy (20, 40, and 60 L/min). Change of end-expiratory lung impedance (ΔEELI), regional recruitment (recruited-pixels) and overdistension (overdistended-pixels), and lung strain change were determined by EIT. EIT images were equally divided into four ventral-to-dorsal horizontal regions of interest (ROIs 1, 2, 3, and 4). “Overdistension-by HFNC” due to HFNC is defined as an increase of overdistened-pixels > 10 than baseline. Patients were divided into two groups: (1) high potential of recruitment (HPR), recruited-pixels > 10 pixels at 60 L/min than baseline, and (2) low potential of recruitment (LPR), recruited-pixels < 10 pixels at 60 L/min than baseline.

Results
When the flow rate gradually increased from baseline to 60 L/min, a significant and consistent increasing trend of global ΔEELI (%) (p < 0.0001), recruited-pixels (p < 0.001), and overdistended-pixels (p = 0.101) was observed. Moreover, the increase of ΔEELI was mainly distributed in ROI2 (p = 0.001) and ROI3 (p < 0.0001). The HPR group (13/24 patients) had significantly higher recruited-pixels than the LPR group (11/24 patients) at 20, 40, and 60 L/min. There were no significant differences in PaO2/FiO2, ΔEELI (%), and overdistention pixels between the two groups. The HPR group had 13 patients in which no one had “overdistension-by HFNC”, and the LPR group had 11 patients in which 4 patients had “overdistension-by HFNC” (0/13 vs. 4/11, p = 0.017).

Conclusions
Using EIT could identify diverse effects of HFNC on lung regional ventilation in postextubation situations. Further study is required to validate using “HFNC effect” based on lung recruitment and overdistension by EIT in clinical practice.

Trial registration
The study was retrospectively registered at www.clinicaltrials.gov (no. NCT04245241).
MiR-7 reduces the BCSC subset by inhibiting XIST to modulate the miR-92b/Slug/ESA axis and inhibit tumor growth
Authors: Li Miao , Pan Meng , You Chengzhong , Zhao Fengshu , Wu Di , Guo Mei , Xu Hui , Shi Fangfang , Zheng Danfeng , Dou Jun 
Published: March 2020

Abstract
Background
Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown.

Methods
We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays.

Results
MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7.

Conclusions
The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.
The genome evolution and domestication of tropical fruit mango
Authors: Wang Peng , Luo Yingfeng , Huang Jianfeng , Gao Shenghan , Zhu Guopeng , Dang Zhiguo , Gai Jiangtao , Yang Meng , Zhu Min , Zhang Huangkai , Ye Xiuxu , Gao Aiping , Tan Xinyu , Wang Sen , Wu Shuangyang , Cahoon Edgar B. , Bai Beibei , Zhao Zhichang , Li Qian , Wei Junya , Chen Huarui , Luo Ruixiong , Gong Deyong , Tang Kexuan , Zhang Bing , Ni Zhangguang , Huang Guodi , Hu Songnian , Chen Yeyuan 
Published: March 2020

AbstractBackgroundMango is one of the world’s most important tropical fruits. It belongs to the family Anacardiaceae, which includes several other economically important species, notably cashew, sumac and pistachio from other genera. Many species in this family produce family-specific urushiols and related phenols, which can induce contact dermatitis.ResultsWe generate a chromosome-scale genome assembly of mango, providing a reference genome for the Anacardiaceae family. Our results indicate the occurrence of a recent whole-genome duplication (WGD) event in mango. Duplicated genes preferentially retained include photosynthetic, photorespiration, and lipid metabolic genes that may have provided adaptive advantages to sharp historical decreases in atmospheric carbon dioxide and global temperatures. A notable example of an extended gene family is the chalcone synthase (CHS) family of genes, and particular genes in this family show universally higher expression in peels than in flesh, likely for the biosynthesis of urushiols and related phenols. Genome resequencing reveals two distinct groups of mango varieties, with commercial varieties clustered with India germplasms and demonstrating allelic admixture, and indigenous varieties from Southeast Asia in the second group. Landraces indigenous in China formed distinct clades, and some showed admixture in genomes.ConclusionsAnalysis of chromosome-scale mango genome sequences reveals photosynthesis and lipid metabolism are preferentially retained after a recent WGD event, and expansion of CHS genes is likely associated with urushiol biosynthesis in mango. Genome resequencing clarifies two groups of mango varieties, discovers allelic admixture in commercial varieties, and shows distinct genetic background of landraces.
Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex
Authors: Merker Matthias , Kohl Thomas A. , Barilar Ivan , Andres Sönke , Fowler Philip W. , Chryssanthou Erja , Ängeby Kristian , Jureen Pontus , Moradigaravand Danesh , Parkhill Julian , Peacock Sharon J. , Schön Thomas , Maurer Florian P. , Walker Timothy , Köser Claudio , Niemann Stefan 
Published: March 2020

Abstract
Background
A comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome sequencing data for genotypic drug susceptibility testing (DST).

Methods
We investigated mutations in 92 genes implicated in resistance to 21 anti-tuberculosis drugs using the genomes of 405 phylogenetically diverse MTBC strains. The role of phylogenetically informative mutations was assessed by routine phenotypic DST data for the first-line drugs isoniazid, rifampicin, ethambutol, and pyrazinamide from a separate collection of over 7000 clinical strains. Selected mutations/strains were further investigated by minimum inhibitory concentration (MIC) testing.

Results
Out of 547 phylogenetically informative mutations identified, 138 were classified as not correlating with resistance to first-line drugs. MIC testing did not reveal a discernible impact of a Rv1979c deletion shared by M. africanum lineage 5 strains on resistance to clofazimine. Finally, we found molecular evidence that some MTBC subgroups may be hyper-susceptible to bedaquiline and clofazimine by different loss-of-function mutations affecting a drug efflux pump subunit (MmpL5).

Conclusions
Our findings underline that the genetic diversity in MTBC has to be studied more systematically to inform the design of clinical trials and to define sound epidemiologic cut-off values (ECOFFs) for new and repurposed anti-tuberculosis drugs. In that regard, our comprehensive variant catalogue provides a solid basis for the interpretation of mutations in genotypic as well as in phenotypic DST assays.
Gallstones top to toe: what the radiologist needs to know
Authors: Murphy M. C. , Gibney B. , Gillespie C. , Hynes J. , Bolster F. 
Published: March 2020

AbstractGallstone-related disease can have significant associated morbidity and mortality worldwide. The incidence of gallstone-related disease in the Western world is on the increase. There are multiple different pathological manifestations of gallstone disease: the presentation, diagnosis and associated complications of which vary significantly depending on anatomical location. The role of imaging in gallstone-related disease is broad with radiology playing an essential role in the diagnosis, management and follow-up of gallstone-related pathologies. This paper distills the broad range of gallstone-related pathologies into an anatomical map, discussing the disease processes involved at each point along the biliary tree and reviewing the strengths and weaknesses of different imaging modalities for each distinct disease process.
Lung endothelial cells are sensitive to epsilon toxin from Clostridium perfringens
Authors: Dorca-Arévalo Jonatan , Dorca Eduard , Torrejón-Escribano Benjamín , Blanch Marta , Martín-Satué Mireia , Blasi Juan 
Published: March 2020

AbstractThe pore-forming protein epsilon toxin (Etx) from Clostridium perfringens produces acute perivascular edema affecting several organs, especially the brain and lungs. Despite the toxin evident effect on microvasculature and endothelial cells, the underlying molecular and cellular mechanisms remain obscure. Moreover, no Etx-sensitive endothelial cell model has been identified to date. Here, we characterize the mouse lung endothelial cell line 1G11 as an Etx-sensitive cell line and compare it with the well-characterized Etx-sensitive Madin-Darby canine kidney epithelial cell line. Several experimental approaches, including morphological and cytotoxic assays, clearly demonstrate that the 1G11 cell line is highly sensitive to Etx and show the specific binding, oligomerization, and pore-forming activity of the toxin in these cells. Recently, the myelin and lymphocyte (MAL) protein has been postulated as a putative receptor for Etx. Here, we show the presence of Mal mRNA in the 1G11 cell line and the presence of the MAL protein in the endothelium of some mouse lung vessels, supporting the hypothesis that this protein is a key element in the Etx intoxication pathway. The existence of an Etx-sensitive cell line of endothelial origin would help shed light on the cellular and molecular mechanisms underlying Etx-induced edema and its consequences.
Anti-inflammatory effects of Lactobacillus johnsonii L531 in a pig model of Salmonella Infantis infection involves modulation of CCR6+ T cell responses and ER stress
Authors: Yang Gui-Yan , Xia Bing , Su Jin-Hui , He Ting , Liu Xiao , Guo Liang , Zhang Shuai , Zhu Yao-Hong , Wang Jiu-Feng 
Published: March 2020

AbstractProbiotic pretreatment is an effective non-antibiotic strategy for preventing or controlling Salmonella infections. We found that Lactobacillus johnsonii L531, isolated from the colon of a clinically healthy weaned piglet, effectively prevented infection with Salmonella enterica serovar Infantis in a pig model. Newly weaned piglets were intragastrically administered Lactobacillus johnsonii L531 at 1.0 × 1010 CFU/day for 1 week before S. Infantis challenge. Pretreatment with L. johnsonii L531 lessened the severity of diarrhea and ileal inflammation in S. Infantis–infected piglets. Lactobacilli were more abundant in the ileum than jejunum after L. johnsonii L531 pretreatment. Treatment with L. johnsonii L531 reduced the abundance of total bacteria in the ileal mucosa and the production of lipocalin 2 in the jejunum of piglets challenged with Salmonella. Both intestinal morphology and transmission electron microscopy results indicated that L. johnsonii L531 alleviated intestinal tissue damage following S. Infantis challenge, especially in the villus and endoplasmic reticulum (ER). ER stress induced by S. Infantis was attenuated by L. johnsonii L531 treatment. The number of CD4− CCR6+ T cells decreased following S. Infantis challenge, but the percentage of CCR6− IFNγ+ T cells in peripheral blood increased. In intestinal mesenteric lymph nodes, S. Infantis increased the proportion of CCR6+ IFNγ+ T cells, whereas L. johnsonii L531 induced an increase in the proportion of CD4+ CCR6+ T cells in response to S. Infantis infection. Our data thus suggest that L. johnsonii L531 contributes to the maintenance of intestinal homeostasis by modulating T-cell responses and ER stress.
Intranasally administered protein coated chitosan nanoparticles encapsulating influenza H9N2 HA2 and M2e mRNA molecules elicit protective immunity against avian influenza viruses in chickens
Authors: Hajam Irshad Ahmed , Senevirathne Amal , Hewawaduge Chamit , Kim Jehyoung , Lee John Hwa 
Published: March 2020

AbstractChitosan nanoparticles (CNPs) represent an efficient vaccination tool to deliver immunogenic antigens to the antigen-presenting cells (APCs), which subsequently stimulate protective immune responses against infectious diseases. Herein, we prepared CNPs encapsulating mRNA molecules followed by surface coating with conserved H9N2 HA2 and M2e influenza proteins. We demonstrated that CNPs efficiently delivered mRNA molecules into APCs and had effectively penetrated the mucosal barrier to reach to the immune initiation sites. To investigate the potential of CNPs delivering influenza antigens to stimulate protective immunity, we intranasally vaccinated chickens with empty CNPs, CNPs delivering HA2 and M2e in both mRNA and protein formats (CNPs + RNA + Pr) or CNPs delivering antigens in protein format only (CNPs + Pr). Our results demonstrated that chickens vaccinated with CNPs + RNA + Pr elicited significantly (p < 0.05) higher systemic IgG, mucosal IgA antibody responses and cellular immune responses compared to the CNPs + Pr vaccinated group. Consequently, upon challenge with either H7N9 or H9N2 avian influenza viruses (AIVs), efficient protection, in the context of viral load and lung pathology, was observed in chickens vaccinated with CNPs + RNA + Pr than CNPs + Pr vaccinated group. In conclusion, we show that HA2 and M2e antigens elicited a broad spectrum of protection against AIVs and incorporation of mRNAs in vaccine formulation is an effective strategy to induce superior immune responses.