bluuebunny/crossref_metadata_2025_split huggingface dataset:
The current landscape of coronavirus-host protein–protein interactions
Authors: Perrin-Cocon Laure , Diaz Olivier , Jacquemin Clémence , Barthel Valentine , Ogire Eva , Ramière Christophe , André Patrice , Lotteau Vincent , Vidalain Pierre-Olivier 
Published: August 2020

AbstractIn less than 20 years, three deadly coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2, have emerged in human population causing hundreds to hundreds of thousands of deaths. Other coronaviruses are causing epizootic representing a significant threat for both domestic and wild animals. Members of this viral family have the longest genome of all RNA viruses, and express up to 29 proteins establishing complex interactions with the host proteome. Deciphering these interactions is essential to identify cellular pathways hijacked by these viruses to replicate and escape innate immunity. Virus-host interactions also provide key information to select targets for antiviral drug development. Here, we have manually curated the literature to assemble a unique dataset of 1311 coronavirus-host protein–protein interactions. Functional enrichment and network-based analyses showed coronavirus connections to RNA processing and translation, DNA damage and pathogen sensing, interferon production, and metabolic pathways. In particular, this global analysis pinpointed overlooked interactions with translation modulators (GIGYF2-EIF4E2), components of the nuclear pore, proteins involved in mitochondria homeostasis (PHB, PHB2, STOML2), and methylation pathways (MAT2A/B). Finally, interactome data provided a rational for the antiviral activity of some drugs inhibiting coronaviruses replication. Altogether, this work describing the current landscape of coronavirus-host interactions provides valuable hints for understanding the pathophysiology of coronavirus infections and developing effective antiviral therapies.
Treadmill exercise has minimal impact on obesogenic diet-related gut microbiome changes but alters adipose and hypothalamic gene expression in rats
Authors: Leigh Sarah-Jane , Kaakoush Nadeem O. , Escorihuela Rosa M. , Westbrook R. Frederick , Morris Margaret J. 
Published: August 2020

AbstractBackgroundExercise has been extensively utilised as an effective therapy for overweight- and obesity-associated changes that are linked to health complications. Several preclinical rodent studies have shown that treadmill exercise alongside an unhealthy diet improves metabolic health and microbiome composition. Furthermore, chronic exercise has been shown to alter hypothalamic and adipose tissue gene expression in diet-induced obesity. However, limited work has investigated whether treadmill exercise commenced following exposure to an obesogenic diet is sufficient to alter microbiome composition and metabolic health.MethodsTo address this gap in the literature, we fed rats a high-fat/high-sugar western-style cafeteria diet and assessed the effects of 4 weeks of treadmill exercise on adiposity, diet-induced gut dysbiosis, as well as hypothalamic and retroperitoneal white adipose tissue gene expression. Forty-eight male Sprague-Dawley rats were allocated to either regular chow or cafeteria diet and after 3 weeks half the rats on each diet were exposed to moderate treadmill exercise for 4 weeks while the remainder were exposed to a stationary treadmill.ResultsMicrobial species diversity was uniquely reduced in exercising chow-fed rats, while microbiome composition was only changed by cafeteria diet. Despite limited effects of exercise on overall microbiome composition, exercise increased inferred microbial functions involved in metabolism, reduced fat mass, and altered adipose and hypothalamic gene expression. After controlling for diet and exercise, adiposeIl6expression and liver triglyceride concentrations were significantly associated with global microbiome composition.ConclusionsModerate treadmill exercise induced subtle microbiome composition changes in chow-fed rats but did not overcome the microbiome changes induced by prolonged exposure to cafeteria diet. Predicted metabolic function of the gut microbiome was increased by exercise. The effects of exercise on the microbiome may be modulated by obesity severity. Future work should investigate whether exercise in combination with microbiome-modifying interventions can synergistically reduce diet- and obesity-associated comorbidities.
RETRACTED ARTICLE: Treatment for lumbar spinal stenosis secondary to ligamentum flavum hypertrophy using percutaneous endoscopy through interlaminar approach: a retrospective study
Authors: Liu Yi , Qi Yingjie , Diaty Diarra Mohamed , Zheng Guanglei , Shen Xiaoqiang , Lin Shangben , Chen Jiaqi , Song Yongwei , Gu Xiaomin 
Published: August 2020

AbstractBackgroundThis paper is to describe percutaneous endoscopy in the treatment of lumbar spinal stenosis secondary to ligamentum flavum hypertrophy targeted and to investigate the efficacy and safety of percutaneous endoscopy in the treatment of this kind of lumbar spinal stenosis in elderly patients.MethodA retrospective analysis of 40 elderly patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy admitted between January 2016 and January 2018 was performed. According to different surgical methods, they were divided into two groups: the control group and the endoscopy group (interlaminar approach), 20 people per group. There were 9 males and 11 females in the control group; the age of patients was 65.65 ± 4.44 years, and the average disease duration was 4.55 ± 1.85 years. Besides, there were 10 males and 10 females in the endoscopy group; the age of patients was 67.30 ± 4.23 years, and the average disease duration was 4.95 ± 2.04 years. Collect and count surgical-related indicators, preoperative and postoperative radiologic findings, incision visual analog scale (VAS), lumbar and leg pain VAS, lumbar Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) scores of all patients.ResultA series of surgical indicators (including the operation time, the quantity of bleeding, and postoperative hospital stay) in the endoscopy group was significantly lower than that in the control group (p< 0.05). The incision VAS score in the endoscopy group was also significantly lower than that in the control group at each time after surgery (p< 0.05). Besides, compared with the control group, in the endoscopy group, the leg pain VAS score and lumbar ODI score after surgery were significantly decreased (p< 0.05). Compared with the control group, in the endoscopy group, the lumbar JOA score was significantly higher (p< 0.05).ConclusionPercutaneous endoscopic technique is a small trauma, quick recovery, safe, and effective minimally invasive surgery for patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy.
Synergistic apoptosis following endoplasmic reticulum stress aggravation in mucinous colon cancer
Authors: Dilly Ashok K. , Honick Brendon D. , Lee Yong J. , Bartlett David L. , Choudry Haroon A. 
Published: August 2020

Abstract
Background
Mucinous colon cancers (MCC) are characterized by abundant production of mucin 2 (MUC2) protein and are less sensitive to standard systemic chemotherapy. We postulated that severe/persistent endoplasmic reticulum stress (ERS) aggravation in MCC would overwhelm compensatory cytoprotective pathways and induce apoptosis.

Results
Basal levels of ERS markers were higher in MCC and dnTCF-LS174T cells than non-mucinous tumors and these levels were significantly increased by combinatorial treatment with ERS aggravators celecoxib + orlistat. Combination treatment inhibited cell viability and synergistically induced apoptosis. Treatment-induced cell death was ERS-dependent, apoptotic pathways were not activated following knockdown of ERS protein CHOP. Dual drug treatment significantly reduced mucinous tumor growth in vivo and induced ERS and apoptosis, consistent with in vitro experiments.

Conclusions
Novel therapies are needed since MCC are more resistant to standard systemic chemotherapy. This study suggests ERS aggravation is a viable therapeutic strategy to reduce tumor growth in MCC.
P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice
Authors: Ruan Zhi , Delpech Jean-Christophe , Venkatesan Kalavai Srinidhi , Van Enoo Alicia A. , Hu Jianqiao , Ikezu Seiko , Ikezu Tsuneya 
Published: August 2020

Abstract
Background
Neuronal accumulation of misfolded microtubule-associated protein tau is a hallmark of neuropathology in Alzheimer’s disease, frontotemporal dementia, and other tauopathies, and has been a therapeutic target. Microglia can spread tau pathology by secreting tau-containing exosomes, although the specific molecular target is yet to be identified for the therapeutic intervention. P2X purinoceptor 7 (P2RX7) is an ATP-gated cation channel, enriched in microglia and triggers exosome secretion. The purpose of the study is to examine the therapeutic effect of an orally applicable, CNS-penetrant P2RX7 specific inhibitor on the early disease stage of a tauopathy mouse model.

Methods
Three-months-old P301S tau mice were treated with P2RX7-specific inhibitor GSK1482160 or vehicle for 30 days, followed by behavioral, biochemical and immunohistochemical assessment. GSK1482160 was also tested for exosome secretion from primary cultured murine astrocytes, neurons and microglia in vitro.

Results
Oral administration of GSK1482160 significantly reduced accumulation of MC1+ and Alz50+ misfolded tau in hippocampal regions, which was accompanied with reduced accumulation of Tsg101, an exosome marker, in hippocampal neurons. Proximity ligation assay demonstrated complex formation of Alz50+ tau and Tsg101 in hippocampal neurons, which was reduced by GSK1482160. On the other hand, GSK1482160 had no effect on microglial ramification or CD68 expression, which was significantly enhanced in P301S mice, or pro/anti-inflammatory cytokine gene expression. Strikingly, GSK1482160-treated P301S mice show significantly improved working and contextual memory as determined by Y-maze and fear conditioning tests. GSK1482160 also significantly increased accumulation of Tsg101 and CD81 in microglia in vivo, suggesting its suppression of P2RX7-induced exosome secretion from microglia. This effect was confirmed in vitro, as ATP-induced secretion of tau-containing exosome was significantly suppressed by GSK1482160 treatment from primary murine microglia, but not from neurons or astrocytes.

Discussion
The oral administration of P2RX7 inhibition mitigates disease phenotypes in P301S mice, likely by suppressing release of microglial exosomes. P2RX7 could be a novel therapeutic target for the early stage tauopathy development.
Mental health response to the COVID-19 pandemic in Kenya: a review
Authors: Jaguga Florence , Kwobah Edith 
Published: August 2020

Abstract
Background
The COVID-19 pandemic has exerted considerable impact on public mental health globally. With the pandemic rapidly rising in sub-Saharan Africa including Kenya, there is need to provide evidence to guide the mental health response in the region.

Objectives
The objective of this review is (1) to describe the mental health response to the COVID-19 pandemic in Kenya, guided by the Mental Health Preparedness and Action Framework (2) to offer context specific recommendations for improvement of the mental health response in Kenya. Such information could be useful in decision-making in Kenya as well as in the greater sub-Saharan Africa region.

Methods
This narrative review is based on information obtained from official government documents released from 13th March 2020, the beginning of the pandemic in Kenya, up to 31st July 2020.

Discussion
The COVID-19 response in Kenya has no formal mental health response plan. There is an unmet need for psychological first aid in the community. While guidelines for the management of mental health conditions during the COVID-19 pandemic have been prepared, implementation remains a major challenge due to a poorly resourced mental health system. There is no mental health surveillance system in place limiting ability to design evidence-based interventions.

Conclusion
We propose four key strategies for strengthening the mental health response in order to mitigate the harmful impact of COVID-19 on public mental health in Kenya: (1) preparation of a formal mental health response plan specific to the COVID-19 pandemic with allocation of funding for the response (2) training of community health workers and community health volunteers on psychological first aid to enable access to support for those in need during the pandemic (3) scaling up of mobile health to increase access to care (4) conducting systematic and continuous text message surveys on the mental health impact of the COVID-19 pandemic in order to inform decision-making.
Discordance in 21-gene recurrence scores between paired breast cancer samples is inversely associated with patient age
Authors: Bernhardt Sarah M. , Dasari Pallave , Wrin Joseph , Raymond Wendy , Edwards Suzanne , Walsh David , Townsend Amanda R. , Price Timothy J. , Ingman Wendy V. 
Published: August 2020

Abstract
Background
The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age.

Methods
RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm.

Results
There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI − 0.14, − 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation- and HER2-associated genes.

Conclusion
The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.
Immune parameters associated with survival in metaplastic breast cancer
Authors: Chao Xue , Liu Lili , Sun Peng , Yang Xia , Li Mei , Luo Rongzhen , Huang Yuhua , He Jiehua , Yun Jingping 
Published: August 2020

Abstract
Background
Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.

Methods
A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.

Results
We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.

Conclusions
The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.
CRISPR and transposon in vivo screens for cancer drivers and therapeutic targets
Authors: Noorani Imran , Bradley Allan , de la Rosa Jorge 
Published: August 2020

AbstractHuman cancers harbor substantial genetic, epigenetic, and transcriptional changes, only some of which drive oncogenesis at certain times during cancer evolution. Identifying the cancer-driver alterations amongst the vast swathes of “passenger” changes still remains a major challenge. Transposon and CRISPR screens in vivo provide complementary methods for achieving this, and each platform has its own advantages. Here, we review recent major technological breakthroughs made with these two approaches and highlight future directions. We discuss how each genetic screening platform can provide unique insight into cancer evolution, including intra-tumoral heterogeneity, metastasis, and immune evasion, presenting transformative opportunities for targeted therapeutic intervention.
Substitution of perioperative albumin deficiency disorders (SuperAdd) in adults undergoing vascular, abdominal, trauma, or orthopedic surgery: protocol for a randomized controlled trial
Authors: Schaller Stefan J. , Fuest Kristina , Ulm Bernhard , Schmid Sebastian , Bubb Catherina , von Eisenhart-Rothe Rüdiger , Friess Helmut , Kirchhoff Chlodwig , Stadlbauer Thomas , Luppa Peter , Blobner Manfred , Jungwirth Bettina 
Published: August 2020

AbstractBackgroundHypalbuminemia is associated with numerous postoperative complications, so a perioperative albumin substitution is often considered. The objective of SuperAdd is to investigate whether substitution of human albumin, aiming to maintain a serum concentration > 30 g/l, can reduce postoperative complications in normovolemic surgical patients in comparison with standard care.Methods/designSuperAdd is a single-center, prospective, randomized, outcome-assessor blinded, patient blinded controlled trial. The primary outcome is the frequency of postoperative complications identified using the Postoperative Morbidity Survey graded ≥ 2 according to the Clavien-Dindo Score. Adult patients at risk to develop hypalbuminemia, i.e., ASA III or IV or high-risk surgery, are recruited after written informed consent was obtained. The albumin concentration is assessed before the induction of anesthesia and every 3 h until admission to the postanesthesia care unit. If albumin concentrations drop below 30 g/l, patients are randomly allocated to the control or the treatment group. The study intervention is a goal-directed human albumin substitution aimed at a concentration > 30 g/l during surgery and postanesthesia care unit stay. The patients in the control group are treated according to standard clinical care. Postoperative visits are to be performed on days 1, 3, 5, 8, and 15, as well as by telephone 6 months after surgery.DiscussionSuperAdd is the first clinical trial in a surgical population investigating the effect of a goal-directed albumin substitution aiming at a serum level > 30 g/l. The nonrestrictive selection of patients guarantees that the patients without albumin screening will most likely not develop hypalbuminemia, thus ensuring generalizability of the study results.Trial registrationEudraCT 2016-001313-24. Registered on 5 September 2016. Clinical Trials NCT03167645. Registered on 18 October 2016 and has the Universal Trial Number (UTN) U1111-1181-2625.
Investigating the molecular basis of multiple insecticide resistance in a major malaria vector Anopheles funestus (sensu stricto) from Akaka-Remo, Ogun State, Nigeria
Authors: Atoyebi Seun M. , Tchigossou Genevieve M. , Akoton Romaric , Riveron Jacob M. , Irving Helen , Weedall Gareth , Tossou Eric , Djegbe Innocent , Oyewole Isaac O. , Bakare Adekunle A. , Wondji Charles S. , Djouaka Rousseau 
Published: August 2020

AbstractBackgroundUnderstanding the mechanisms used byAnophelesmosquitoes to survive insecticide exposure is key to manage existing insecticide resistance and develop more suitable insecticide-based malaria vector control interventions as well as other alternative integrated tools. To this regard, the molecular basis of permethrin, DDT and dieldrin resistance inAnopheles funestus(sensu stricto) at Akaka-Remo was investigated.MethodsBioassays were conducted on 3–5-day-old adultAn. funestus(s.s.) mosquitoes for permethrin, DDT and dieldrin susceptibility test. The molecular mechanisms of mosquito resistance to these insecticides were investigated using microarray and reverse transcriptase PCR techniques. The voltage-gated sodium channel region of mosquitoes was also screened for the presence of knockdown resistance mutations (kdrwest and east) by sequencing method.ResultsAnopheles funestus(s.s.) population was resistant to permethrin (mortality rate of 68%), DDT (mortality rate of 10%) and dieldrin (mortality rate of 8%) insecticides. Microarray and RT-PCR analyses revealed the overexpression of glutathione S-transferase genes, cytochrome P450s, esterase, trypsin and cuticle proteins in resistant mosquitoes compared to control. TheGSTe2was the most upregulated detoxification gene in permethrin-resistant (FC = 44.89), DDT-resistant (FC = 57.39) and dieldrin-resistant (FC = 41.10) mosquitoes compared to control population (FC = 22.34). The cytochrome P450 gene,CYP6P9bwas also upregulated in both permethrin- and DDT-resistant mosquitoes. The digestive enzyme, trypsin (hydrolytic processes) and the cuticle proteins (inducing cuticle thickening leading to reduced insecticides penetration) also showed high involvement in insecticide resistance, through their overexpression in resistant mosquitoes compared to control. Thekdreast and west were absent in all mosquitoes analysed, suggesting their non-involvement in the observed mosquito resistance.ConclusionsThe upregulation of metabolic genes, especially theGSTe2and trypsin, as well as the cuticle proteins is driving insecticide resistance ofAn. funestus(s.s.) population. However, additional molecular analyses, including functional metabolic assays of these genes as well as screening for a possible higher cuticular hydrocarbon and lipid contents, and increased procuticle thickness in resistant mosquitoes are needed to further describe their distinct roles in mosquito resistance.