bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmaceutical nationalism as an instrument to ensure the access to medicines
Authors: Kashyntseva Oksana
Published: July 2021

Keywords: pharmaceutical nationalism, access to drugs, compulsory licensing, governmentuse, exclusion from intellectual property rights

The article concerns the emergence of the phenomena of«pharmaceutical nationalism» in the year of the COVID-19 pandemic. Pharmaceuticalnationalism is manifested in the qualitative and quantitative aspects. In the contextof a qualitative manifestation of pharmaceutical nationalism, we presume the politicalwill on establishing of a new state protectionist policy to local manufacturers ofmedicines, the establishing of preferences, exemptions of the patent monopoly basingon international legal instruments (TRIPS-flex). The quantitative aspect of pharmaceuticalnationalism is the primacy of satisfaction of the needs of the domestic marketof medicines in quantities that could ensure the biological security of individually foreach state, independently of the interests of others. The article also raises the issue ofthe need and means of forming pharmaceutical nationalism in Ukraine.The world community is calling for the demonopolization of research results on theprevention and treatment of COVID-19. WHO invites developers and companies towork together to ensure the disclosure of treatments and methods if they prove effective.International Federation of Library Associations and Institutions also presentedan open letter to WIPO urging WIPO to use all available flexible intellectual propertymechanisms to maximize global access to information (research data) on the treatmentof COVID-19. Canada, Israel and the EU are working to prevent the monopolizationof COVID-19 prevention and treatment.Ukraine should actively work to develop legislation in the field of compulsory licensing,as provided for in Art. 31 TRIPS Agreement. From a political point of view, itis the historical chance of Ukraine to become «he second India» or «the first Ukraine»in Europe in the production of generic medicines and biosimilars.
Protein-Based Nanohydrogels for Bioactive Delivery
Authors: Chander Subhash , Kulkarni Giriraj T. , Dhiman Neerupma , Kharkwal Harsha
Published: July 2021

Hydrogels possess a unique three-dimensional, cross-linked network of polymers capable of absorbing large amounts of water and biological fluids without dissolving. Nanohydrogels (NGs) or nanogels are composed of diverse types of polymers of synthetic or natural origin. Their combination is bound by a chemical covalent bond or is physically cross-linked with non-covalent bonds like electrostatic interactions, hydrophobic interactions, and hydrogen bonding. Its remarkable ability to absorb water or other fluids is mainly attributed to hydrophilic groups like hydroxyl, amide, and sulphate, etc. Natural biomolecules such as protein- or peptide-based nanohydrogels are an important category of hydrogels which possess high biocompatibility and metabolic degradability. The preparation of protein nanohydrogels and the subsequent encapsulation process generally involve use of environment friendly solvents and can be fabricated using different proteins, such as fibroins, albumin, collagen, elastin, gelatin, and lipoprotein, etc. involving emulsion, electrospray, and desolvation methods to name a few. Nanohydrogels are excellent biomaterials with broad applications in the areas of regenerative medicine, tissue engineering, and drug delivery due to certain advantages like biodegradability, biocompatibility, tunable mechanical strength, molecular binding abilities, and customizable responses to certain stimuli like ionic concentration, pH, and temperature. The present review aims to provide an insightful analysis of protein/peptide nanohydrogels including their preparation, biophysiochemical aspects, and applications in diverse disciplines like in drug delivery, immunotherapy, intracellular delivery, nutraceutical delivery, cell adhesion, and wound dressing. Naturally occurring structural proteins that are being explored in protein nanohydrogels, along with their unique properties, are also discussed briefly. Further, the review also covers the advantages, limitations, overview of clinical potential, toxicity aspects, stability issues, and future perspectives of protein nanohydrogels.
Alone With Goffman: Impression Management and the TV Series
Authors: Beames Simon , Andkjær Søren , Radmann Aage
Published: July 2021

Alone is an American reality television series on the History Channel. The show features 10 contestants who are vying to outlast each other while living off the land. Notably, there is no camera crew, and the contestants must film themselves everyday; the production team creates a weekly program that marks the journey of each individual. This study sought to understand the degree to which participants are able to shape their public identities through the video footage they shot and that was subsequently edited in Alone’s cutting room. The research team employed an explorative case study methodology, which allowed them to watch hours of publicly available official video clips from the History Channel’s Alone YouTube channel. The analysis was driven by theory (Goffman’s The Presentation of Self conceptual framework) and an inductive thematic analysis, which took place in a cyclical fashion through interpretation meetings at the end of each of the six series that were watched. The findings first showed that the contestants were performing to multiple audiences, such as their families, the public, the producers, and even God. Second, the boundary between the frontstage and the backstage was highly blurred. Third, the contestants were able to continue shaping and “repairing” their identities through their own social media outlets after the program. Finally, the theme of gendered approaches to living outdoors shone through in ways that were very complex, overlapping, and non-binary. There is an undeniably strong “impression management tension” between the selves that participants wanted to project and the narratives that were constructed by the Alone program’s producers.
Benefits Beyond Borders: Assessing Landowner Willingness-to-Accept Incentives for Conservation Outside Protected Areas
Authors: Mariyam Dincy , Puri Mahi , Harihar Abishek , Karanth Krithi K.
Published: July 2021

Unplanned land-use change surrounding protected areas (PAs) can lead to degradation and fragmentation of wildlife habitats, thereby placing tremendous pressure on PAs especially in tropical countries. Incentivizing the expansion of habitats beyond PAs will not only benefit wildlife but also has the potential to create livelihood opportunities for marginalized communities living adjacent to PAs. Our study explored landowners’ willingness to participate in an incentive-based, wildlife-friendly land-use program using a discrete choice modeling approach. We surveyed 699 landowners living in 287 villages within a five-kilometer buffer around Nagarahole and Bandipur National Parks in India. We found that landowners preferred wildlife-friendly land-use over their ongoing farming practices. Landowners preferred short-term programs, requiring enrolling smaller parcels of land for wildlife-friendly land-use, and offering higher payment amounts. Landowners with larger landholdings, a longer history of living next to the PA, and growing fewer commercial crops were more likely to prefer enrolling large parcels of land. Landowners who grew more commercial crops were likely to prefer long term programs. We also estimated the average monetary incentive to be INR 64,000 (US$ 914) per acre per year. Wildlife-friendly land use, in developing economies like India with shrinking wildlife habitats and expanding infrastructural developments, could supplement rural incomes and potentially expand habitat for wildlife, thereby being a promising conservation strategy.
Evolutionary History of DNA Methylation Related Genes in Bivalvia: New Insights From Mytilus galloprovincialis
Authors: Gerdol Marco , La Vecchia Claudia , Strazzullo Maria , De Luca Pasquale , Gorbi Stefania , Regoli Francesco , Pallavicini Alberto , D’Aniello Enrico
Published: July 2021

DNA methylation is an essential epigenetic mechanism influencing gene expression in all organisms. In metazoans, the pattern of DNA methylation changes during embryogenesis and adult life. Consequently, differentiated cells develop a stable and unique DNA methylation pattern that finely regulates mRNA transcription during development and determines tissue-specific gene expression. Currently, DNA methylation remains poorly investigated in mollusks and completely unexplored in Mytilus galloprovincialis. To shed light on this process in this ecologically and economically important bivalve, we screened its genome, detecting sequences homologous to DNA methyltransferases (DNMTs), methyl-CpG-binding domain (MBD) proteins and Ten-eleven translocation methylcytosine dioxygenase (TET) previously described in other organisms. We characterized the gene architecture and protein domains of the mussel sequences and studied their phylogenetic relationships with the ortholog sequences from other bivalve species. We then comparatively investigated their expression levels across different adult tissues in mussel and other bivalves, using previously published transcriptome datasets. This study provides the first insights on DNA methylation regulators in M. galloprovincialis, which may provide fundamental information to better understand the complex role played by this mechanism in regulating genome activity in bivalves.
Case Report: Triple Primary Malignant Tumors of the Esophagus, Stomach, and Colon in a Patient With Genetic Analysis
Authors: Zhan Xiaoli , He Lingzhe , Song Kai , Cao Shuliang , Meng Erhong , Wang Yuedong
Published: July 2021

The incidence of multiple primary malignant tumors (MPMTs) has increased greatly with the progress of tumor diagnosis and therapy technology. However, triple primary cancer is still very rare, and its genetic change is not clear yet. This case report described a 70-year-old Chinese male patient with triple primary cancers of the esophagus, stomach and right-sided colon. Pathological examination confirmed that each malignant tumor developed independently. Next-generation sequencing (NGS) using a 599-gene panel revealed five TP53 mutations in three tumor tissues. These variations might contribute to development of the triple primary malignant tumors in the patient. The patient underwent laparoscopic feeding jejunostomy and postoperative radiotherapy for synchronous esophageal and gastric carcinomas. Then, he underwent laparoscopic-assisted resection of right-sided colonic cancer and lysis of abdominal adhesions. By the time of submitting this manuscript, the patient had been well and no sign of recurrence or metastasis had been observed. To the best of our knowledge, this case is the first one to clarify the genetic abnormalities of triple primary cancers of esophagus, stomach and colon in a Chinese patient. It may contribute to understanding the molecular pathogenesis of multiple primary digestive malignancies and providing valuable treatment strategies for the similar patients in the future.
Epitranscriptomic Analysis of m6A Methylome After Peripheral Nerve Injury
Authors: Zhang Lei , Hao Dingyu , Ma Pengyi , Ma Boyuan , Qin Jia , Tian Guangyuan , Liu Zihao , Zhou Xianhu
Published: July 2021

N6-methyladenosine (m6A) is one of the most plentiful internal RNA modifications, especially in eukaryotic messenger RNA (mRNA), which plays pivotal roles in the regulation of mRNA life cycle and nerve development. However, the mRNA m6A methylation pattern in peripheral nervous injury (PNI) has not been investigated. In this study, sciatic nerve samples were collected from 7 days after sciatic nerve injury (SNI) and control rats. Quantitative real-time PCR demonstrated that m6A-related methyltransferase/demethylase genes were remarkably upregulated in SNI group compared with control group. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to reveal the m6A methylation landscape. The results showed that 4,014 m6A peaks were significantly altered, including 2,144 upregulated and 1,870 downregulated m6A peaks, which were corresponded to 1,858 genes. Moreover, 919 differentially expressed genes were identified by the conjoint analysis of MeRIP-seq and RNA-seq. GO and KEGG pathway analyses were performed to determine the biological functions and signaling pathways of the m6A-modified genes. Notably, these genes were mainly related to the immune system process, cell activation, and nervous system development in GO analysis. KEGG pathway analysis revealed that these genes were involved in the cell cycle, B cell receptor signaling pathway, axon guidance pathway, and calcium signaling pathway. Furthermore, the m6A methylation and protein expression levels of autophagy-related gene (Atg7) were increased, together with the activation of autophagy. These findings shed some light on the epigenetic regulation of gene expression, which may provide a new opinion to promote functional recovery after PNI.
Genome-Wide Scanning for Signatures of Selection Revealed the Putative Genomic Regions and Candidate Genes Controlling Milk Composition and Coat Color Traits in Sahiwal Cattle
Authors: Illa Satish Kumar , Mukherjee Sabyasachi , Nath Sapna , Mukherjee Anupama
Published: July 2021

Background

In the evolutionary time scale, selection shapes the genetic variation and alters the architecture of genome in the organisms. Selection leaves detectable signatures at the genomic coordinates that provide clues about the protein-coding regions. Sahiwal is a valuable indicine cattle adapted to tropical environments with desirable milk attributes. Insights into the genomic regions under putative selection may reveal the molecular mechanisms affecting the quantitative and other important traits. To understand this, the present investigation was undertaken to explore signatures of selection in the genome of Sahiwal cattle using a medium-density genotyping INDUS chip.

Result

De-correlated composite of multiple selection signals (DCMS), which combines five different univariate statistics, was computed in the dataset to detect the signatures of selection in the Sahiwal genome. Gene annotations, Quantitative Trait Loci (QTL) enrichment, and functional analyses were carried out for the identification of significant genomic regions. A total of 117 genes were identified, which affect a number of important economic traits. The QTL enrichment analysis highlighted 14 significant [False Discovery Rate (FDR)-corrected p-value ≤ 0.05] regions on chromosomes BTA 1, 3, 6, 11, 20, and 21. The top three enriched QTLs were found on BTA 6, 20, and 23, which are associated with exterior, health, milk production, and reproduction traits. The present study on selection signatures revealed some key genes related with coat color (PDGFRA, KIT, and KDR), facial pigmentation (LEF), milk fat percent (MAP3K1, HADH, CYP2U1, and SGMS2), sperm membrane integrity (OSTC), lactation persistency (MRPS30, NNT, CCL28, HMGCS1, NIM1K, ZNF131, and CCDC152), milk yield (GHR and ZNF469), reproduction (NKX2-1 and DENND1A), and bovine tuberculosis susceptibility (RNF144B and PAPSS1). Further analysis of candidate gene prioritization identified four hub genes, viz., KIT, KDR, MAP3K1, and LEF, which play a role in coat color, facial pigmentation, and milk fat percentage in cattle. Gene enrichment analysis revealed significant Gene ontology (GO) terms related to breed-specific coat color and milk fat percent.

Conclusion

The key candidate genes and putative genomic regions associated with economic traits were identified in Sahiwal using single nucleotide polymorphism data and the DCMS method. It revealed selection for milk production, coat color, and adaptability to tropical climate. The knowledge about signatures of selection and candidate genes affecting phenotypes have provided a background information that can be further utilized to understand the underlying mechanism involved in these traits in Sahiwal cattle.
Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Acute Kidney Injury: Short-Term Recovery Predicts Long-Term Outcome
Authors: Huang Xiaohan , Chen Liangliang , Lan Lan , Ren Pingping , Ni Anqi , Ma Yanhong , Wang Yaomin , Zhu Yilin , Xu Ying , Chen Jianghua , Han Fei
Published: July 2021

Background

Kidney involvement is common in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It tends to be aggressive, and in some patients, the kidney involvement may reach the criteria of acute kidney injury (AKI). Here, we aim to describe the clinical characteristics of these patients and find risk factors for poor outcomes.

Methods

Patients diagnosed with AAV in our hospital from February 2003 to February 2017 were included. Those who reached the KDIGO AKI criteria were reclassified according to the KDIGO AKI stage. The clinical features of these patients were analyzed. Also, according to the variation of serum creatinine 3 months after AKI episode, patients were further divided into two groups: patients whose serum creatinine (Scr) level at the third month decreased by 30% or more from the peak Scr level was classified into G1 and others were classified into G2. Long-term renal and survival outcomes of these patients were analyzed with a Cox model. The renal endpoint was reaching end-stage renal disease (ESRD), and the survival endpoint was death. Nomograms were built based on cox models.

Results

Of 141 AAV patients included, during the median follow-up period of 64.0 (IQR 34.8, 85.4) months, 36 (25.5%) patients reached renal endpoints, and 22 (15.6%) patients died. The median renal survival time was 35.9 (IQR 21.3, 72.6) months and the median survival time was 48.4 (IQR 26.8, 82.8) months. Multivariate analysis showed that poor recovery of Scr level at 90 days (P < 0.001, RR = 9.150, 95%CI 4.163–20.113), BVAS score (P = 0.014, RR = 1.110, 95% CI1.021–1.207), and AKI stage 3 (P = 0.012 RR = 3.116, 95%CI 1.278–7.598) were independent risk factors for renal endpoints; poor recovery of Scr level at 90 days (P = 0.010, RR = 3.264, 95%CI 1.326–8.035), BVAS score (P = 0.010, RR = 1.171, 95%CI 1.038–1.320) and age (P = 0.017, RR = 1.046, 95%CI 1.008–1.086) were independent risk factors for all-cause death. The c-index of nomograms is 0.830 for the renal outcome and 0.763 for the survival outcome.

Conclusion

KDIGO AKI stage 3 is the risk factor for ESRD in AAV patients with AKI. The BVAS score and level of kidney function recovery at 90 days are the independent risk factors for both ESRD and all-cause death and are of predictive value for the outcome.
Risk Factors for New Zealand Sea Lion (Phocarctos hookeri) Pup Mortality: Ivermectin Improves Survival for Conservation Management
Authors: Michael Sarah A. , Hayman David T. S. , Gray Rachael , Roe Wendi D.
Published: July 2021

Septicaemia due to hypervirulent (HV) Klebsiella pneumoniae is the leading cause of neonatal pup mortality in endangered New Zealand sea lions (Phocarctos hookeri) at Enderby Island, in the New Zealand sub-Antarctic. Accounting for approximately 60% of annual pup mortality at this site following an epizootic event in 2001–02, HV K. pneumoniae is also emerging worldwide as a significant community-acquired human pathogen. To facilitate efficient direct mitigation to reduce pup mortality, a case-control study and prospective cohort study were conducted to identify risk factors amenable to active management. Additionally, to investigate impacts of hookworm (Uncinaria spp.), a nested treatment trial with the anthelmintic ivermectin was undertaken concurrently. During two austral summer field seasons (2016–2018), 698 pups were captured for treatment trial recruitment and the collection of morphometric measurements, biological samples and risk factor data. Gastrointestinal carriage of the virulent phenotype of K. pneumoniae was a consistent risk factor, while ivermectin treatment and higher body condition index consistently reduced risk of HV K. pneumoniae mortality. Significantly fewer ivermectin-treated pups were found dead (24.1% control, 11.1% treatment), with a trend towards a higher proportion of HV K. pneumoniae deaths amongst the control group. This study provides evidence to support ivermectin treatment as a pup mortality mitigation strategy in New Zealand sea lions at Enderby Island. If applied to larger colonies where HV K. pneumoniae and hookworm impact pup survival, this intervention could have population-scale benefits for this endangered species. Further work is required to understand how ivermectin prevents HV K. pneumoniae septicaemia, but removal of hookworms before intestinal mucosal damage occurs could limit systemic spread of virulent bacteria from the gastrointestinal tract.
STAT3 but Not STAT5 Contributes to the Protective Effect of Electroacupuncture Against Myocardial Ischemia/Reperfusion Injury in Mice
Authors: Guo Hui-Hui , Jing Xin-Yue , Chen Hui , Xu Hou-Xi , Zhu Bing-Mei
Published: July 2021

Electroacupuncture (EA) can help reduce infarct size and injury resulting from myocardial ischemia/reperfusion (I/R); however, the underlying molecular mechanism remains unknown. We previously reported that STAT5 plays a critical role in the cardioprotective effect of remote ischemic preconditioning (RIPC). Here, we assessed the effects of electroacupuncture pretreatment (EAP) on myocardial I/R injury in the presence and/or absence of Stat5 in mice and investigated whether EAP exerts its cardioprotective effects in a STAT5-dependent manner. Adult Stat5fl/fl and Stat5-cKO mice were exposed to EAP at Neiguan (PC6) for 7 days before the induction of I/R injury by left anterior descending (LAD) coronary artery ligation. The myocardial infarct size (IS), area at risk, and apoptotic rate of cardiomyocytes were detected. RT-qPCR and western blotting were used to measure gene and protein expression, respectively, in homogenized heart tissues. RNA-seq was used to identify candidate genes and pathways. Our results showed that EAP decreased IS and the rate of cardiomyocyte apoptosis. We further found that STAT5 was activated by EAP in Stat5fl/fl mice but not in Stat5-cKO mice, whereas the opposite was observed for STAT3. Following EAP, the levels of the antiapoptotic proteins Bcl-xL, Bcl-2, and p-AKT were increased in the presence of Stat5, while that of interleukin 10 (IL-10) was increased in both Stat5fl/fl and Stat5-cKO. The gene expression profile in heart tissues was different between Stat5fl/fl and the Stat5-cKO mice with EAP. Importantly, the top 30 DEGs under EAP in the Stat5-cKO mice were enriched in the IL-6/STAT3 signaling pathway. Our results revealed for the first time that the protective effect of EAP following myocardial I/R injury was attributable to, but not dependent on, STAT5. Additionally, we found that EAP could activate STAT3 signaling in the absence of the Stat5 gene, and could also activate antiapoptotic, survival, and anti-inflammatory signaling pathways.
Comparison of Different Lymph Node Staging Schemes for Predicting Survival Outcomes in Node-Positive Endometrioid Endometrial Cancer Patients
Authors: Yang Xi-Lin , Huang Nan , Wang Ming-Ming , Lai Hua , Wu Da-Jun
Published: July 2021

Objective: To compare the prognostic predictive performance of six lymph node (LN) staging schemes: American Joint Committee on Cancer (AJCC) N stage, number of retrieved lymph nodes (NRLN), number of positive lymph nodes (NPLN), number of negative lymph nodes (NNLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) among node-positive endometrioid endometrial cancer (EEC) patients.

Methods: A total of 3,533 patients diagnosed with node-positive EEC between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. We applied X-tile software to identify the optimal cutoff value for different staging schemes. Univariate and multivariate Cox regression models were used to assess the relationships between different LN schemes and survival outcomes [disease-specific survival (DSS) and overall survival (OS)]. Moreover, Akaike information criterion (AIC) and Harrell concordance index (C-index) were used to evaluate the predictive performance of each scheme in both continuous and categorical patterns.

Results: N stage (N1/N2) was not an independent prognostic factor for node-positive EEC patients based on multivariate analysis (DSS: p = 0.235; OS: p = 0.145). Multivariate model incorporating LNR demonstrated the most superior goodness of fit regardless of continuous or categorical pattern. Regarding discrimination power of the models, LNR outperformed other models in categorical pattern (OS: C-index = 0.735; DSS: C-index = 0.737); however, LODDS obtained the highest C-index in continuous pattern (OS: 0.736; DSS: 0.739).

Conclusions: N stage (N1/N2) was unable to differentiate the prognosis for node-positive EEC patients in our study. However, LNR and LODDS schemes seemed to have a better predictive performance for these patients than other number-based LN schemes whether in DSS or OS, which revealed that LNR and LODDS should be more helpful in prognosis assessment for node-positive EEC patients than AJCC N stage.
The COM-Poisson Process for Stochastic Modeling of Osmotic Inactivation Dynamics of Listeria monocytogenes
Authors: Polese Pierluigi , Del Torre Manuela , Stecchini Mara Lucia
Published: July 2021

Controlling harmful microorganisms, such as Listeria monocytogenes, can require reliable inactivation steps, including those providing conditions (e.g., using high salt content) in which the pathogen could be progressively inactivated. Exposure to osmotic stress could result, however, in variation in the number of survivors, which needs to be carefully considered through appropriate dispersion measures for its impact on intervention practices. Variation in the experimental observations is due to uncertainty and biological variability in the microbial response. The Poisson distribution is suitable for modeling the variation of equi-dispersed count data when the naturally occurring randomness in bacterial numbers it is assumed. However, violation of equi-dispersion is quite often evident, leading to over-dispersion, i.e., non-randomness. This article proposes a statistical modeling approach for describing variation in osmotic inactivation of L. monocytogenes Scott A at different initial cell levels. The change of survivors over inactivation time was described as an exponential function in both the Poisson and in the Conway-Maxwell Poisson (COM-Poisson) processes, with the latter dealing with over-dispersion through a dispersion parameter. This parameter was modeled to describe the occurrence of non-randomness in the population distribution, even the one emerging with the osmotic treatment. The results revealed that the contribution of randomness to the total variance was dominant only on the lower-count survivors, while at higher counts the non-randomness contribution to the variance was shown to increase the total variance above the Poisson distribution. When the inactivation model was compared with random numbers generated in computer simulation, a good concordance between the experimental and the modeled data was obtained in the COM-Poisson process.
Hemispheric Difference of Regional Brain Function Exists in Patients With Acute Stroke in Different Cerebral Hemispheres: A Resting-State fMRI Study
Authors: Gao Jingchun , Yang Canhong , Li Qixiong , Chen Lanpin , Jiang Yijing , Liu Songyan , Zhang Jing , Liu Gang , Chen Junqi
Published: July 2021

Objective

To explore the different compensatory mechanisms of brain function between the patients with brain dysfunction after acute ischemic stroke (AIS) in the dominant hemisphere and the non-dominant hemisphere based on Resting-state Functional Magnetic Resonance Imaging (Rs-fMRI).

Methods

In this trial, 15 healthy subjects (HS) were used as blank controls. In total, 30 hemiplegic patients with middle cerebral artery acute infarction of different dominant hemispheres were divided into the dominant hemisphere group (DH) and the non-dominant hemisphere group (NDH), scanned by a 3.0 T MRI scanner, to obtain the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) and compare the differences.

Results

Compared with the HS, increased ALFF values in the brain areas, such as the bilateral midbrain, were observed in DH. Meanwhile decreased ReHo values in the brain areas, such as the right postcentral gyrus (BA3), were also observed. Enhanced ALFF values in the brain areas, such as the left BA6, and enhanced ReHo values in the brain areas, such as the left precuneus, were observed in the NDH. The ALFF and ReHo values of the right BA9 and precentral gyrus were both increased. Compared with DH, the NDH group showed lower ALFF values in the left supplementary motor area and lower ReHo values in the right BA10.

Conclusion

After acute infarction in the middle cerebral artery of the dominant hemisphere, a compensation mechanism is triggered in brain areas of the ipsilateral cortex regulating motor-related pathways, while some brain areas related to cognition, sensation, and motor in the contralateral cortex are suppressed, and the connection with the peripheral brain regions is weakened. After acute infarction in the middle cerebral artery of the non-dominant hemisphere, compensatory activation appears in motor control-related brain areas of the dominant hemisphere. After acute middle cerebral artery infarction in the dominant hemisphere, compared with the non-dominant hemisphere, functional specificity in the bilateral supplementary motor area weakens. After acute middle cerebral artery infarction in different hemispheres, there are hemispheric differences in the compensatory mechanism of brain function.
Chronic Isolation Stress Affects Central Neuroendocrine Signaling Leading to a Metabolically Active Microenvironment in a Mouse Model of Breast Cancer
Authors: Berry Alessandra , Collacchi Barbara , Capoccia Sara , D'Urso Maria Teresa , Cecchetti Serena , Raggi Carla , Sestili Paola , Aricò Eleonora , Pontecorvi Giada , Puglisi Rossella , Ortona Elena , Cirulli Francesca
Published: July 2021

Social isolation is a powerful stressor capable of affecting brain plasticity and function. In the case of breast cancer, previous data indicate that stressful experiences may contribute to a worse prognosis, activating neuroendocrine and metabolism pathways, although the mechanisms underlying these effects are still poorly understood. In this study, we tested the hypothesis that chronic isolation stress (IS) may boost hypothalamic–pituitary–adrenal (HPA) axis activity, leading to changes in the hypothalamic expression of genes modulating both mood and metabolism in an animal model of breast cancer. This centrally activated signaling cascade would, in turn, affect the mammary gland microenvironment specifically targeting fat metabolism, leading to accelerated tumor onset. MMTVNeuTg female mice (a model of breast cancer developing mammary hyperplasia at 5 months of age) were either group-housed (GH) or subjected to IS from weaning until 5 months of age. At this time, half of these subjects underwent acute restraint stress to assess corticosterone (CORT) levels, while the remaining subjects were characterized for their emotional profile in the forced swimming and saccharin preference tests. At the end of the procedures, all the mice were sacrificed to assess hypothalamic expression levels of Brain-derived neurotrophic factor (Bdnf), Neuropeptide Y (NpY), Agouti-Related Peptide (AgRP), and Serum/Glucocorticoid-Regulated Protein Kinase 1 (SgK1). Leptin and adiponectin expression levels, as well as the presence of brown adipose tissue (BAT), were assessed in mammary fat pads. The IS mice showed higher CORT levels following acute stress and decreased expression of NpY, AgRP, and SgK1, associated with greater behavioral despair in the forced swimming test. Furthermore, they were characterized by increased consumption of saccharin in a preference test, suggesting an enhanced hedonic profile. The IS mice also showed an earlier onset of breast lumps (assessed by palpation) accompanied by elevated levels of adipokines (leptin and adiponectin) and BAT in the mammary fat pads. Overall, these data point to IS as a pervasive stressor that is able to specifically target neuronal circuits, mastered by the hypothalamus, modulating mood, stress reactivity and energy homeostasis. The activation of such IS-driven machinery may hold main implications for the onset and maintenance of pro-tumorigenic environments.
Bioinformatic Analysis of the Proteome in Exosomes Derived From Plasma: Exosomes Involved in Cholesterol Metabolism Process of Patients With Spinal Cord Injury in the Acute Phase
Authors: Wu Chunshuai , Yu Jinjuan , Xu Guanhua , Gao Hong , Sun Yue , Huang Jiayi , Sun Li , Zhang Xu , Cui Zhiming
Published: July 2021

Spinal cord injury (SCI) is a common but severe disease caused by traffic accidents. Coronary atherosclerotic heart disease (CHD) caused by dyslipidemia is known as the leading cause of death in patients with SCI. However, the quantitative analysis showed that the cholesterol and lipoprotein concentrations in peripheral blood (PB) did not change significantly within 48 h after SCI. Due to the presence of the Blood spinal cord barrier (BSCB), there are only few studies concerning the plasma cholesterol metabolism in the acute phase of SCI. Exosomes have a smaller particle size, which enables them relatively less limitation of BSCB. This study uses exosomes derived from the plasma of 43 patients in the acute phase of SCI and 71 patients in the control group as samples. MS proteomics and bioinformatics analysis found 590 quantifiable proteins, in which 75 proteins were upregulated and 153 proteins were downregulated, and the top 10 differentially expressed proteins are those including downregulating proteins: HIST1H4A, HIST2H3A, HIST2H2BE, HCLS1, S100A9, HIST1H2BM, S100A8, CALM3, YWHAH, and SFN, and upregulating proteins: SERPIND1, C1QB, SPTLC3, IGHV4-28, C4A, IGHV4-38-2, IGHV4-30-2, SLC15A1, C4B, and ACTG2. Enrichment analysis showed that the largest part of proteins was related to cholesterol metabolism among the downregulated proteins. The main components of cholesterol [ApoB-48 and ApoB-100 increased, ApoA-I, ApoA-II, ApoA-IV, ApoC, ApoE, and Apo(a) decreased] were changed in exosomes derived from plasma of patients. ELISA analysis showed that some components were disordered in the acute phase of SCI. These results suggested that the exosomes might be involved in cholesterol metabolism regulation in the acute phase of SCI.
Improved Speech in Noise Perception in the Elderly After 6 Months of Musical Instruction
Authors: Worschech Florian , Marie Damien , Jünemann Kristin , Sinke Christopher , Krüger Tillmann H. C. , Großbach Michael , Scholz Daniel S. , Abdili Laura , Kliegel Matthias , James Clara E. , Altenmüller Eckart
Published: July 2021

Understanding speech in background noise poses a challenge in daily communication, which is a particular problem among the elderly. Although musical expertise has often been suggested to be a contributor to speech intelligibility, the associations are mostly correlative. In the present multisite study conducted in Germany and Switzerland, 156 healthy, normal-hearing elderly were randomly assigned to either piano playing or music listening/musical culture groups. The speech reception threshold was assessed using the International Matrix Test before and after a 6 month intervention. Bayesian multilevel modeling revealed an improvement of both groups over time under binaural conditions. Additionally, the speech reception threshold of the piano group decreased during stimuli presentation to the left ear. A right ear improvement only occurred in the German piano group. Furthermore, improvements were predominantly found in women. These findings are discussed in the light of current neuroscientific theories on hemispheric lateralization and biological sex differences. The study indicates a positive transfer from musical training to speech processing, probably supported by the enhancement of auditory processing and improvement of general cognitive functions.
The Enhancement of Intestinal Immunity in Offspring Piglets by Maternal Probiotic or Synbiotic Supplementation Is Associated With the Alteration of Gut Microbiota
Authors: Wang Kai , Hu Chengjun , Tang Wu , Azad Md. Abul Kalam , Zhu Qian , He Qinghua , Kong Xiangfeng
Published: July 2021

A total of 64 pregnant Bama mini-pigs were used to investigate the effects of maternal probiotic or synbiotic supplementation during gestation and lactation on immune response, intestinal morphology, and microbiota community of offspring piglets. The sows were assigned randomly to one of four groups, control group (basal diet), antibiotic group (basal diet supplemented with 50 g/t virginiamycin), probiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig), or synbiotic group (basal diet supplemented with 200 mL/d probiotic fermentation broth per pig + 500 g/t xylo-oligosaccharides) during pregnancy and lactation periods. After weaning, two piglets close to the average body weight (BW) per litter were selected and fed a basal diet. Eight piglets with similar BW were selected from each group for sample collection at 65 d-old. The results showed that plasma interleukin (IL)-2 and lipopolysaccharide concentrations were decreased (P < 0.05) in the probiotic group, while the immunoglobulin A (IgA) concentration in the probiotic and synbiotic groups was increased (P < 0.05), when compared with the control group. The jejunal IL-10, interferon-α, and secretory IgA (sIgA) concentrations were increased (P < 0.05) in the probiotic and synbiotic groups, as well as the ileal sIgA concentration in the probiotic group. The jejunal villus height (VH) and the ratio of VH to crypt depth were increased (P < 0.05) in the probiotic group, as well as the ileal VH in the synbiotic group. Furthermore, the piglets from the antibiotic group exhibited a lower microbiota diversity in the jejunum and ileum. The piglets from the synbiotic group had higher relative abundances of Actinobacteria, Bifidobacterium, Turicibacter, and Clostridium in the jejunum compared with the antibiotic group. Dietary probiotic treatment increased (P < 0.05) the relative abundance of Psychrobacter in the ileum compared with the antibiotic and control groups. Spearman's correlation analysis revealed that the relative abundances of Bifidobacterium, Clostridium, and Blautia in the jejunum and Psychrobacter in the ileum, were positively correlated with the alterations of immunoglobulin and cytokines. Collectively, these findings suggest that maternal interventions with probiotic or synbiotic are promising strategies for improving the immune response of offspring piglets by altering the gut microbiota.
Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
Authors: Gil-Gil Miguel J. , Bellet Meritxell , Bergamino Milana , Morales Serafín , Barnadas Agustí , Manso Luís , Saura Cristina , Fernández-Ortega Adela , Garcia-Martinez Elena , Martinez-Jañez Noelia , Melé Mireia , Villagrasa Patricia , Celiz Pamela , Perez Martin X. , Ciruelos Eva , Pernas Sonia
Published: July 2021

Background

The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).

Methods

In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.

Results

Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).

Conclusion

At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.

Trial Registration Number

ClinicalTrials.gov reference NCT00563953.
Development of a Nomogram Based on Preoperative Bi-Parametric MRI and Blood Indices for the Differentiation Between Cystic-Solid Pituitary Adenoma and Craniopharyngioma
Authors: Zhao Zhen , Xiao Dongdong , Nie Chuansheng , Zhang Hao , Jiang Xiaobing , Jecha Ali Rajab , Yan Pengfei , Zhao Hongyang
Published: July 2021

Background

Given the similarities in clinical manifestations of cystic-solid pituitary adenomas (CS-PAs) and craniopharyngiomas (CPs), this study aims to establish and validate a nomogram based on preoperative imaging features and blood indices to differentiate between CS-PAs and CPs.

Methods

A departmental database was searched to identify patients who had undergone tumor resection between January 2012 and December 2020, and those diagnosed with CS-PAs or CPs by histopathology were included. Preoperative magnetic resonance imaging (MRI) features as well as blood indices were retrieved and analyzed. Radiological features were extracted from the tumor on contrast-enhanced T1 (CE-T1) weighted and T2 weighted sequences. The two independent samples t-test and principal component analysis (PCA) were used for feature selection, data dimension reduction, and radiomics signature building. Next, the radiomics signature was put in five classification models for exploring the best classifier with superior identification performance. Multivariate logistic regression analysis was then used to establish a radiomic-clinical model containing radiomics and hematological features, and the model was presented as a nomogram. The performance of the radiomics-clinical model was assessed by calibration curve, clinical effectiveness as well as internal validation.

Results

A total of 272 patients were included in this study: 201 with CS-PAs and 71 with CPs. These patients were randomized into training set (n=182) and test set (n=90). The radiomics signature, which consisted of 18 features after dimensionality reduction, showed superior discrimination performance in 5 different classification models. The area under the curve (AUC) values of the training set and the test set obtained by the radiomics signature are 0.92 and 0.88 in the logistic regression model, 0.90 and 0.85 in the Ridge classifier, 0.88 and 0.82 in the stochastic gradient descent (SGD) classifier, 0.78 and 0.85 in the linear support vector classification (Linear SVC), 0.93 and 0.86 in the multilayers perceptron (MLP) classifier, respectively. The predictive factors of the nomogram included radiomic signature, age, WBC count, and FIB. The nomogram showed good discrimination performance (with an AUC of 0.93 in the training set and 0.90 in the test set) and good calibration. Moreover, decision curve analysis (DCA) demonstrated satisfactory clinical effectiveness of the proposed radiomic-clinical nomogram.

Conclusions

A personalized nomogram containing radiomics signature and blood indices was proposed in this study. This nomogram is simple yet effective in differentiating between CS-PAs and CPs and thus can be used in routine clinical practice.
Effect of a Topical Nonsteroidal Anti-Inflammatory Drug (0.1% Pranoprofen) on VEGF and COX-2 Expression in Primary Pterygium
Authors: Yao Bangtao , Wang Fei , Zhao Xiaogui , Wang Bei , Yue Xiaoli , Ding Yuhua , Liu Gang
Published: July 2021

Purpose:To evaluate the effect of a topical nonsteroidal anti-inflammatory drug (0.1% pranoprofen) on the expression of VEGF and Cox-2 in primary pterygium.

Methods:This was a prospective, randomized study. Between January 2019 and April 2020, 120 patients diagnosed with primary pterygium were enrolled and randomly divided into three groups before operation: 1) 40 patients in group 1 received topical pranoprofen 0.1% four times daily for 4 weeks, 2) 40 patients in group 2 received topical fluorometholone 0.1% four times daily for 4 weeks, and 3) patients in group 3 did not receive treatment. For each group, the age, sex, eye type, best-corrected visual acuity (BCVA), intraocular pressure (IOP), duration of onset, combined systemic diseases, and the results regarding vascular endothelial growth factor (VEGF) and cyclo-oxygen-ase-2 (COX-2) in postoperative pterygial tissues were evaluated in detail.

Results:There were no significant differences regarding age, sex, eye type, combined systemic diseases, duration of onset, IOP, and BCVA within the three groups (p> 0.05). The reduction of VEGF and CoX-2 expression of pterygial vascular endothelial cells in group 1 were statistically significant compared to group 2 and group 3 (p< 0.05). There were significant correlations between COX-2 and VEGF expression of pterygial tissues within the three groups (p< 0.05).

Conclusion:The present findings suggested that the topical pranoprofen 0.1% could reduce the expression of VEGF and COX-2 in primary pterygium. We confirmed that treatment with pranoprofen offers advantages in early intervention and has therapeutic potential in reducing the postoperative recurrence of primary pterygium patients.

Clinical Trial registration: The study was registered with the Chinese Clinical Trial Registry. (http://www.chictr.org.cn/index.aspx, Registration Number: ChiCTR2100047726).