bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult neurogenesis mediates forgetting of multiple types of memory in the rat
Authors: Scott Gavin A. , Terstege Dylan J. , Roebuck Andrew J. , Gorzo Kelsea A. , Vu Alex P. , Howland John G. , Epp Jonathan R. 
Published: June 2021

AbstractThe formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampus-dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.
Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression
Authors: Kemper Marius , Schiecke Alina , Maar Hanna , Nikulin Sergey , Poloznikov Andrey , Galatenko Vladimir , Tachezy Michael , Gebauer Florian , Lange Tobias , Riecken Kristoffer , Tonevitsky Alexander , Aigner Achim , Izbicki Jakob , Schumacher Udo , Wicklein Daniel 
Published: June 2021

Abstract
Background
Mesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis.

Methods
Knockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated.

Results
The knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients.

Conclusion
Combined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
p38β - MAPK11 and its role in female cancers
Authors: Katopodis Periklis , Kerslake Rachel , Zikopoulos Athanasios , Beri Nefeli , Anikin Vladimir 
Published: June 2021

AbstractBackgroundThe p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using anin-silicoapproach.MethodsA detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.ResultsData using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen.ConclusionThis data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.
Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study
Authors: Mercurio Giovanna , D’Arrigo Sonia , Moroni Rossana , Grieco Domenico Luca , Menga Luca Salvatore , Romano Anna , Annetta Maria Giuseppina , Bocci Maria Grazia , Eleuteri Davide , Bello Giuseppe , Montini Luca , Pennisi Mariano Alberto , Conti Giorgio , Antonelli Massimo 
Published: June 2021

Abstract
Background
A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients.

Methods
Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed.

Results
Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72–0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001).

Conclusion
DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF.
Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.
Recommendations for designing and analysing multi-arm non-inferiority trials: a review of methodology and current practice
Authors: Emmerson Jake , Todd Susan , Brown Julia M. 
Published: June 2021

Abstract
Background and purpose
Multi-arm non-inferiority (MANI) trials, here defined as non-inferiority trials with multiple experimental treatment arms, can be useful in situations where several viable treatments exist for a disease area or for testing different dose schedules. To maintain the statistical integrity of such trials, issues regarding both design and analysis must be considered, from both the multi-arm and the non-inferiority perspectives. Little guidance currently exists on exactly how these aspects should be addressed and it is the aim of this paper to provide recommendations to aid the design of future MANI trials.

Methods
A comprehensive literature review covering four databases was conducted to identify publications associated with MANI trials. Literature was split into methodological and trial publications in order to investigate the required design and analysis considerations for MANI trials and whether they were being addressed in practice.

Results
A number of issues were identified that if not properly addressed, could lead to issues with the FWER, power or bias. These ranged from the structuring of trial hypotheses at the design stage to the consideration of potential heterogeneous treatment variances at the analysis stage. One key issue of interest was adjustment for multiple testing at the analysis stage. There was little consensus concerning whether more powerful p value adjustment methods were preferred to approximate adjusted CIs when presenting and interpreting the results of MANI trials.
We found 65 examples of previous MANI trials, of which 31 adjusted for multiple testing out of the 39 that were adjudged to require it. Trials generally preferred to utilise simple, well-known methods for study design and analysis and while some awareness was shown concerning FWER inflation and choice of power, many trials seemed not to consider the issues and did not provide sufficient definition of their chosen design and analysis approaches.

Conclusions
While MANI trials to date have shown some awareness of the issues raised within this paper, very few have satisfied the criteria of the outlined recommendations. Going forward, trials should consider the recommendations in this paper and ensure they clearly define and reason their choices of trial design and analysis techniques.
Ephedra alata fruit extracts: phytochemical screening, anti-proliferative activity and inhibition of DPPH, α-amylase, α-glucosidase, and lipase enzymes
Authors: Jaradat Nidal , Dacca Hanaa , Hawash Mohammed , Abualhasan Murad N. 
Published: June 2021

Abstract
Background
Discovering and screening for potential anti-obesity, anti-diabetic, anticancer, and antioxidant treatments from natural products still in recent times the main goal for many pharmaceutical scientists. The present investigation aimed to evaluate the chemical constituents of Ephedra alata fruits various extracts and to assess their antioxidant, antiobesity, antidiabetic, and cytotoxic effects.

Result
In this work, high content of flavonoids and phenols were observed in the methanol fraction of E. alata fruits, which reached 98.95 mg of RUE/g and 33.22 mg of GAE/g, respectively. The methanol fraction has significant inhibitory activity against DPPH, α-amylase, α-glucosidase, and lipase with an IC50 value of 1.07, 9.43, 46.16, and 66.48 µg/mL. respectively. Also has anticancer activity against HeLa cancer cell line. While the acetone fraction has potent antioxidant activity with IC50 5 µg/mL.

Conclusion
The DPPH and digestive enzymes assays results showed that the methanolic fraction of E. alata fruits has potent antioxidant, anti-diabetic, and anti-obesity activities, which can be an excellent candidate for biological and chemical analysis and can be further subjected for isolation of the therapeutically active compounds with anticancer potency.
Integrated NIRS and QTL assays reveal minor mannose and galactose as contrast lignocellulose factors for biomass enzymatic saccharification in rice
Authors: Hu Zhen , Wang Youmei , Liu Jingyuan , Li Yuqi , Wang Yanting , Huang Jiangfeng , Ai Yuanhang , Chen Peng , He Yuqing , Aftab Muhammad Nauman , Wang Lingqiang , Peng Liangcai 
Published: June 2021

Abstract
Background
Identifying lignocellulose recalcitrant factors and exploring their genetic properties are essential for enhanced biomass enzymatic saccharification in bioenergy crops. Despite genetic modification of major wall polymers has been implemented for reduced recalcitrance in engineered crops, it could most cause a penalty of plant growth and biomass yield. Alternatively, it is increasingly considered to improve minor wall components, but an applicable approach is required for efficient assay of large population of biomass samples. Hence, this study collected total of 100 rice straw samples and characterized all minor wall monosaccharides and biomass enzymatic saccharification by integrating NIRS modeling and QTL profiling.

Results
By performing classic chemical analyses and establishing optimal NIRS equations, this study examined four minor wall monosaccharides and major wall polymers (acid-soluble lignin/ASL, acid-insoluble lignin/AIL, three lignin monomers, crystalline cellulose), which led to largely varied hexoses yields achieved from enzymatic hydrolyses after two alkali pretreatments were conducted with large population of rice straws. Correlation analyses indicated that mannose and galactose can play a contrast role for biomass enzymatic saccharification at P < 0.0 l level (n = 100). Meanwhile, we found that the QTLs controlling mannose, galactose, lignin-related traits, and biomass saccharification were co-located. By combining NIRS assay with QTLs maps, this study further interpreted that the mannose-rich hemicellulose may assist AIL disassociation for enhanced biomass enzymatic saccharification, whereas the galactose-rich polysaccharides should be effectively extracted with ASL from the alkali pretreatment for condensed AIL association with cellulose microfibrils.

Conclusions
By integrating NIRS assay with QTL profiling for large population of rice straw samples, this study has identified that the mannose content of wall polysaccharides could positively affect biomass enzymatic saccharification, while the galactose had a significantly negative impact. It has also sorted out that two minor monosaccharides could distinctively associate with lignin deposition for wall network construction. Hence, this study demonstrates an applicable approach for fast assessments of minor lignocellulose recalcitrant factors and biomass enzymatic saccharification in rice, providing a potential strategy for bioenergy crop breeding and biomass processing.
Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus
Authors: Spadar Anton , Phelan Jody E. , Benavente Ernest Diez , Campos Monica , Gomez Lara Ferrero , Mohareb Fady , Clark Taane G. , Campino Susana 
Published: June 2021

AbstractMosquitoes of the genus Aedes are the main vectors of many viruses, e.g. dengue and Zika, which affect millions of people each year and for which there are limited treatment options. Understanding how Aedes mosquitoes tolerate high viral loads may lead to better disease control strategies. Elucidating endogenous viral elements (EVEs) within vector genomes may give exploitable biological insights. Previous studies have reported the presence of a large number of EVEs in Aedes genomes. Here we investigated if flavivirus EVEs are conserved across populations and different Aedes species by using ~ 500 whole genome sequence libraries from Aedes aegypti and Aedes albopictus, sourced from colonies and field mosquitoes across continents. We found that nearly all flavivirus EVEs in the Ae. aegypti reference genome originate from four separate putative viral integration events, and that they are highly conserved across geographically diverse samples. By contrast, flavivirus EVEs in the Ae. albopictus reference genome originate from up to nine distinct integration events and show low levels of conservation, even within samples from narrow geographical ranges. Our analysis suggests that flaviviruses integrated as long sequences and were subsequently fragmented and shuffled by transposable elements. Given that EVEs of Ae. aegypti and Ae. albopictus belong to different phylogenetic clades and have very differing levels of conservation, they may have different evolutionary origins and potentially different functional roles.
Graphical Abstract
Trends in taxonomy of Triatomini (Hemiptera, Reduviidae, Triatominae): reproductive compatibility reinforces the synonymization of Meccus Stål, 1859 with Triatoma Laporte, 1832
Authors: Cesaretto Natália Regina , de Oliveira Jader , Ravazi Amanda , Madeira Fernanda Fernandez , dos Reis Yago Visinho , de Oliveira Ana Beatriz Bortolozo , Vicente Roberto Dezan , Cristal Daniel Cesaretto , Galvão Cleber , de Azeredo-Oliveira Maria Tercília Vilela , da Rosa João Aristeu , Alevi Kaio Cesar Chaboli 
Published: June 2021

Abstract
Background
Meccus' taxonomy has been quite complex since the first species of this genus was described by Burmeister in 1835 as Conorhinus phyllosoma. In 1859 the species was transferred to the genus Meccus and in 1930 to Triatoma. However, in the twentieth century, the Meccus genus was revalidated (alteration corroborated by molecular studies) and, in the twenty-first century, through a comprehensive study including more sophisticated phylogenetic reconstruction methods, Meccus was again synonymous with Triatoma. Events of natural hybridization with production of fertile offspring have already been reported among sympatric species of the T. phyllosoma subcomplex, and experimental crosses demonstrated reproductive viability among practically all species of the T. phyllosoma subcomplex that were considered as belonging to the genus Meccus, as well as between these species and species of Triatoma. Based on the above, we carried out experimental crosses between T. longipennis (considered M. longipennis in some literature) and T. mopan (always considered as belonging to Triatoma) to evaluate the reproductive compatibility between species of the T. phyllosoma complex. In addition, we have grouped our results with information from the literature regarding crosses between species that were grouped in the genus Meccus with Triatoma, in order to discuss the importance of experimental crosses to confirm the generic reorganization of species.

Results
The crosses between T. mopan female and T. longipennis male resulted in viable offspring. The hatching of hybrids, even if only in one direction and/or at low frequency, demonstrates reproductive compatibility and homeology between the genomes of the parents.

Conclusion
Considering that intergeneric crosses usually do not result in viable offspring in Triatominae, the reproductive compatibility observed between the T. phyllosoma subcomplex species considered in the Meccus genus with species of the Triatoma genus shows that there is “intergeneric” genomic compatibility, which corroborates the generic reorganization of Meccus in Triatoma.

Graphical Abstract
Severe hemoperitoneum resulting from restart of letrozole after oocyte retrieval procedure: a case report
Authors: Huang Haipeng , Takai Yasushi , Samejima Kouki , Gomi Yosuke , Narita Tatsuya , Ichinose Shunichiro , Itaya Yukiko , Ono Yosihisa , Matsunaga Sigetaka , Saitoh Masahiro , Seki Hiroyuki 
Published: June 2021

Abstract
Background
In the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol.

Case presentation
We report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage.

Conclusions
The ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.