bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of astroglial major histocompatibility complex class I in the medial prefrontal cortex impairs visual discrimination learning in mice
Authors: Wulaer Bolati , Hada Kazuhiro , Sobue Akira , Itoh Norimichi , Nabeshima Toshitaka , Nagai Taku , Yamada Kiyofumi 
Published: December 2020

Abstract
Background
Immune molecules, such as cytokines, complement, and major histocompatibility complex (MHC) proteins, in the central nervous system are often associated with neuropsychiatric disorders. Neuronal MHC class I (MHCI), such as H-2D, regulate neurite outgrowth, the establishment and function of cortical connections, and activity-dependent refinement in mice. We previously established mice expressing MHCI specifically in astrocytes of the media prefrontal cortex (mPFC) using the adeno-associated virus (AAV) vector under the control of the GfaABC1D promoter. Mice expressing the soluble form of H-2D (sH-2D) in the mPFC (sH-2D-expressing mice) showed abnormal behaviors, including social interaction deficits and cognitive dysfunctions. However, the pathophysiological significance of astroglial MHCI on higher brain functions, such as learning, memory, and behavioral flexibility, remains unclear. Therefore, cognitive function in mice expressing sH-2D in astrocytes of the mPFC was tested using the visual discrimination (VD) task.

Methods
sH-2D-expressing mice were subjected to the VD and reversal learning tasks, and morphological analysis.

Results
In the pretraining, sH-2D-expressing mice required significantly more trials to reach the learning criterion than control mice. The total number of sessions, trials, normal trials, and correction trials to reach the VD criterion were also significantly higher in sH-2D-expressing mice than in control mice. A morphological study showed that dendritic complexity and spine density were significantly reduced in the dorsal striatum of sH-2D-expressing mice.

Conclusion
Collectively, the present results suggest that the overexpression of astroglial MHCI in the mPFC results in impaired VD learning, which may be accompanied by decreased dendritic complexity in the dorsal striatum and mPFC.
Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object-based attention test in mice
Authors: Wulaer Bolati , Kunisawa Kazuo , Kubota Hisayoshi , Suento Willy Jaya , Saito Kuniaki , Mouri Akihiro , Nabeshima Toshitaka 
Published: December 2020

AbstractDisturbances of attention are a common behavioral feature associated with neuropsychiatric disorders with largely unknown underlying causes. We previously developed an object-based attention test (OBAT) as a simple and practical method for evaluating attention in mice. Since its establishment, the test has become a popular method for assessing attention and related underlying mechanisms in various mouse models. However, the underlying neuronal network involved in this test has yet to be studied. The purpose of this study was to identify the principal brain regions activated in the OBAT. Accordingly, C57BL/6J mice were subjected to the OBAT and thereafter prepared for immunohistochemical quantification of c-Fos, an immediate early gene that is frequently used as a marker of neuronal activity, in 13 different brain regions. The number of c-Fos-positive cells was significantly higher in the prefrontal cortex (PFC), dorsomedial striatum (DMS), and dentate gyrus (DG) in the test group as compared to the control group. The neuronal activation of these brain regions during the OBAT indicates that these brain regions are necessary for the regulation of attention in this test. This was supported by excitotoxic lesioning of these brain regions, leading to impaired attention without causing locomotor dysfunction. This study is one of the first attempts to analyze the brain regions that regulate attention in the OBAT. These findings provide an initial insight into the role of these brain regions and ideas for studying the underlying neural and molecular mechanisms.
MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer
Authors: Zhao Shuhua , Zhang Xiaohong , Shi Yuan , Cheng Lu , Song Tingting , Wu Bing , Li Jia , Yang Hong 
Published: December 2020

AbstractBackgroundIncreasing evidence has revealed the close link between mitochondrial dynamic dysfunction and cancer. MIEF2 (mitochondrial elongation factor 2) is mitochondrial outer membrane protein that functions in the regulation of mitochondrial fission. However, the expression, clinical significance and biological functions of MIEF2 are still largely unclear in human cancers, especially in ovarian cancer (OC).MethodsThe expression and clinical significance of MIEF2 were determined by qRT-PCR, western blot and immunohistochemistry analyses in tissues and cell lines of OC. The biological functions of MIEF2 in OC were determined by in vitro and in vivo cell growth and metastasis assays. Furthermore, the effect of MIEF2 on metabolic reprogramming of OC was determined by metabolomics and glucose metabolism analyses.ResultsMIEF2 expression was significantly increased in OC mainly due to the down-regulation of miR-424-5p, which predicts poor survival for patients with OC. Knockdown of MIEF2 significantly suppressed OC cell growth and metastasis both in vitro and in vivo by inhibiting G1-S cell transition, epithelial-to-mesenchymal transition (EMT) and inducing cell apoptosis, while forced expression of MIEF2 had the opposite effects. Mechanistically, mitochondrial fragmentation-suppressed cristae formation and thus glucose metabolism switch from oxidative phosphorylation to glycolysis was found to be involved in the promotion of growth and metastasis by MIEF2 in OC cells.ConclusionsMIEF2 plays a critical role in the progression of OC and may serve as a valuable prognostic biomarker and therapeutic target in the treatment of this malignancy.
Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses
Authors: Tseng Chien-Hua , Chen Tzu-Tao , Wu Mei-Yi , Chan Ming-Cheng , Shih Ming-Chieh , Tu Yu-Kang 
Published: December 2020

Abstract
Background
Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients’ conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients.

Methods
Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence.

Results
Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74–0.95) and L-HES (OR 0.81; 95% CI 0.69–0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65–0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35–0.87).

Conclusions
Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients.

Trial registration

PROSPERO website, registration number: CRD42018115641).
Convergent network effects along the axis of gene expression during prostate cancer progression
Authors: Charmpi Konstantina , Guo Tiannan , Zhong Qing , Wagner Ulrich , Sun Rui , Toussaint Nora C. , Fritz Christine E. , Yuan Chunhui , Chen Hao , Rupp Niels J. , Christiansen Ailsa , Rutishauser Dorothea , Rüschoff Jan H. , Fankhauser Christian , Saba Karim , Poyet Cedric , Hermanns Thomas , Oehl Kathrin , Moore Ariane L. , Beisel Christian , Calzone Laurence , Martignetti Loredana , Zhang Qiushi , Zhu Yi , Martínez María Rodríguez , Manica Matteo , Haffner Michael C. , Aebersold Ruedi , Wild Peter J. , Beyer Andreas 
Published: December 2020

Abstract
Background
Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues.

Results
Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers.

Conclusions
This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.
Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China
Authors: Chao Xiaopei , Li Lei , Wu Ming , Wu Huanwen , Ma Shuiqing , Tan Xianjie , Zhong Sen , Lang Jinghe 
Published: December 2020

Abstract
Background
There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China.

Methods
This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up.

Discussion
The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility.

Trial registration
ClinicalTrials.gov NCT03739944. Registered on November 14, 2018
Metabolic engineering of Aspergillus niger via ribonucleoprotein-based CRISPR–Cas9 system for succinic acid production from renewable biomass
Authors: Yang Lei , Henriksen Mikkel Møller , Hansen Rasmus Syrach , Lübeck Mette , Vang Jesper , Andersen Julie Egelund , Bille Signe , Lübeck Peter Stephensen 
Published: December 2020

Abstract
Background
Succinic acid has great potential to be a new bio-based building block for deriving a number of value-added chemicals in industry. Bio-based succinic acid production from renewable biomass can provide a feasible approach to partially alleviate the dependence of global manufacturing on petroleum refinery. To improve the economics of biological processes, we attempted to explore possible solutions with a fungal cell platform. In this study, Aspergillus niger, a well-known industrial production organism for bio-based organic acids, was exploited for its potential for succinic acid production.

Results
With a ribonucleoprotein (RNP)-based CRISPR–Cas9 system, consecutive genetic manipulations were realized in engineering of the citric acid-producing strain A. niger ATCC 1015. Two genes involved in production of two byproducts, gluconic acid and oxalic acid, were disrupted. In addition, an efficient C4-dicarboxylate transporter and a soluble NADH-dependent fumarate reductase were overexpressed. The resulting strain SAP-3 produced 17 g/L succinic acid while there was no succinic acid detected at a measurable level in the wild-type strain using a synthetic substrate. Furthermore, two cultivation parameters, temperature and pH, were investigated for their effects on succinic acid production. The highest amount of succinic acid was obtained at 35 °C after 3 days, and low culture pH had inhibitory effects on succinic acid production. Two types of renewable biomass were explored as substrates for succinic acid production. After 6 days, the SAP-3 strain was capable of producing 23 g/L and 9 g/L succinic acid from sugar beet molasses and wheat straw hydrolysate, respectively.

Conclusions
In this study, we have successfully applied the RNP-based CRISPR–Cas9 system in genetic engineering of A. niger and significantly improved the succinic acid production in the engineered strain. The studies on cultivation parameters revealed the impacts of pH and temperature on succinic acid production and the future challenges in strain development. The feasibility of using renewable biomass for succinic acid production by A. niger has been demonstrated with molasses and wheat straw hydrolysate.
Outbreak of autochthonous cases of malaria in coastal regions of Northeast Brazil: the diversity and spatial distribution of species of Anopheles
Authors: Gomes Elainne Christine de Souza , Cruz Derciliano Lopes da , Santos Maria Alice Varjal Melo , Souza Renata Maria Costa , Oliveira Cláudia Maria Fontes de , Ayres Constância Flávia Junqueira , Domingos Renata Martins , Pedro Maria das Graça da Silva , Paiva Marcelo Henrique Santos , Pimentel Lílian Maria Lapa Montenegro 
Published: December 2020

Abstract
Background
Brazil has the fourth highest prevalence of malaria of all countries in the Americas, with an estimated 42 million people at risk of contracting this disease. Although most cases occur in the Amazon region, cases of an autochthonous nature have also been registered in the extra-Amazonian region where Anopheles aquasalis and An. albitarsis are the mosquito species of greatest epidemiological interest. In 2019, the municipality of Conde (state of Paraíba) experienced an epidemic of autochthonous cases of malaria. Here we present preliminary results of an entomological and case epidemiology investigation, in an attempt to correlate the diversity and spatial distribution of species of Anopheles with the autochthonous cases of this outbreak of malaria.

Methods
Case data were collected using case report forms made available by the Conde Municipal Health Department. The entomological survey was carried out from July to November 2019. The various methods of capture included the use of battery-powered aspirators, mouth aspirators, Shannon traps, BG-Sentinel traps (with and without dry ice) and CDC light traps. Captured mosquitoes were separated, packaged and sent to the laboratory for sexing and molecular identification of the various species of anophelines. The data were tabulated and analyzed using Microsoft Excel. Spatial analysis of the data was performed using ArcGis 10 software.

Results
In 2019, 20 autochthonous cases and one imported case of malaria caused by Plasmodium vivax were diagnosed, with three cases of relapses. A total of 3713 mosquitoes were collected, of which 3390 were culicines and 323 were anophelines. Nine species of genus Anopheles were identified, with the most abundant being An. aquasalis (38.9%), followed by An. minor (18.2%) and An. albitarsis (9.0%). Spatial analysis of the data showed that the area could be considered to be at risk of malaria cases and that there was a high prevalence of Anopheles.

Conclusions
The results presented indicate that this extra-Amazonian region has an environment conducive to maintenance of the malaria transmission cycle owing to the wide diversity of Anopheles species. This environment in combination with the high influx of people from endemic areas to the study area provides a perfect setting for the occurrence and maintenance of malaria.

Graphical Abstract
Insecticide resistance status of Aedes aegypti in Bangladesh
Authors: Al-Amin Hasan Mohammad , Johora Fatema Tuj , Irish Seth R. , Hossainey Muhammad Riadul Haque , Vizcaino Lucrecia , Paul Kishor Kumar , Khan Wasif A. , Haque Rashidul , Alam Mohammad Shafiul , Lenhart Audrey 
Published: December 2020

Abstract
Background
Arboviral diseases, including dengue and chikungunya, are major public health concerns in Bangladesh where there have been unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is to control the vector Aedes aegypti using pyrethroid insecticides. Although chemical control has long been practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has been conducted to date. The aim of this study was to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms.

Methods
Eggs of Aedes mosquitoes were collected using ovitraps from five districts across Bangladesh and in eight neighborhoods of the capital city Dhaka, from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3- to 5-day-old F0–F2 non-blood-fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms, and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410.

Results
High levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 to 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2×) doses of permethrin (5.1–44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr (knockdown resistance) alleles varied across the Dhaka Aedes populations. Leu410 was not detected in any of the tested populations.

Conclusions
The detection of widespread pyrethroid resistance and multiple resistance mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.

Graphical Abstract
Combined effect of water activity and pH on the growth of food-related ascospore-forming molds
Authors: Racchi Irene , Scaramuzza Nicoletta , Hidalgo Alyssa , Berni Elettra 
Published: December 2020

Abstract
Purpose
The contamination of raw materials, packaging, or processing environments by fungal ascospores is a real concern for food industries, where variable rates of spoilage can be reached in pasteurized acidic products such as fruit juices, fruit jams, or soft drinks. The aim of this work was to assess the combined effect of aw and pH on the growth of six isolates from three genera of ascospore-forming molds that may occur in raw materials and in food industrial environments, in order to determine the environmental conditions that prevent the spoilage of pasteurized foods and beverages.

Methods
Growth tests were carried out on 60-day-old ascospores from Aspergillus hiratsukae (≡Neosartorya hiratsukae), Aspergillus thermomutatus (≡Neosartorya pseudofischeri), Chaetomium flavoviride, Chaetomium globosum, Talaromyces bacillisporus, and Talaromyces trachyspermus. The tests were performed up to 90 days at 25 °C, using sucrose solutions at different aw (0.85, 0.88, 0.92, 0.95) and pH (3.20, 3.50, 3.80, 4.20, 4.60) values. Growth was characterized by fitting an ordinary logistic regression model to the collected growth data.

Results
The explained percentage of the growth/no growth models ranged between 81.0 and 99.3%: aw exerted the largest influence on the growth of all tested species, while pH was significant only for Chaetomium isolates. The minimum conditions for germination and growth were aw 0.92 and pH 3.50 or 3.80, respectively, for C. flavoviride (46 days) and C. globosum (39 days), aw 0.92 and pH 3.20 for T. trachyspermus (13 days), aw 0.88 and pH 3.20 for T. bacillisporus (39 days), and aw 0.88 and pH 3.20 for the two aspergilli (33 and 27 days, respectively, for A. hiratsukae and A. thermomutatus).

Conclusions
Most of the spoiling mycetes tested were well-adapted to the formulations considered; therefore, foods strategies aiming to inhibit their growth should explore also the hurdle effect exerted by other factors (e.g., antioxidants, organic acids, oxygen levels).