bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Role of NOGO Gene Block in Enhancing the Neuro-regenerative Effect of Mesenchymal Stem Cells.
Authors: Youssef Eman , Gabr Hala , Kishk Nirmeen A , Zickri Maha Baligh , Botros Shahira KA , Ashour Amal S.
Published: January 2021

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal disease. Mesenchymal stem cells (MSCs) have a therapeutic potential in neuronal diseases, factors as NOGO-A limit axonal regeneration. In this study, gene silencing was used to suppress Nogo-A expression in MSCs to enhance its neuro-regenerative role. Methods: mouse models of motor neuron degeneration were created, effect of non-modified and plasmid transfected MSCs were studied clinically and histologically. Group 1 received no treatment. Group 2 received IV injection of non modified MSCs and sacrificed after 8 days (subgroup 2a) and 15 days (subgroup 2b) following treatment, Group 3 received IV injection of transfected MSCs and were sacrificed after 8 days (subgroup 3a) and 15 days (subgroup 3b) following treatment. Results: A significant increase in weight and motor scores of subgroups 2a & 2b occurred in comparison to subgroups1a & 1b respectively (p values <0.001, <0.001, 0.001 & 0.026 respectively), GAP43 expression in group 2 mice was significantly higher compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in group 2 were significantly lower compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in subgroup 2b were significantly less in comparison to subgroup 2a (p values = 0.002 and 0.03) indicating an improvement with time. GAP43 in subgroup 2b was significantly higher compared to subgroup 2a (p value = 0.030).Weight and motor power in group 3 mice was significantly higher when compared to group 1 on days; 14 and 21 (p values <0.001, <0.001, <0.001 and 0.008) respectively. Deformed neurons and glial cells in group 3 mice were significantly lower when compared to group 1 mice (p values <0.001). GAP43 expression in group 3 mice was significantly higher when compared to group1 (p value <0.001). Deformed neurons in subgroup 3b was significantly less than subgroup 3a (p value <0.001). GAP43 expression in group 3 mice was significantly increased when compared to group 2 mice (p value <0.001).Conclusion: NOGO-A gene SiRNA is a potential enhancer of the neuro-regenerative action of MSCs.
A Recombinant Protein SARS-CoV-2 Candidate Vaccine Elicits High-titer Neutralizing Antibodies in Macaques.
Authors: Baisa Gary , Rancour David , Mansfield Keith , Burns Monika , Martin Lori , Cunha Daise , Fischer Jessica , Muecksch Frauke , Hatziioannou Theodora , Bieniasz Paul D. , Schomburg Fritz , Luke Kimberly
Published: January 2021

BackgroundVaccines that generate robust and long-lived protective immunity against SARS-CoV-2 infection are urgently required. MethodsWe assessed the potential of vaccine candidates based on the SARS-CoV-2 spike in cynomolgus macaques (M. fascicularis) by examining their ability to generate spike binding antibodies with neutralizing activity. Antigens were derived from two distinct regions of the spike S1 subunit, either the N-terminal domain or an extended C-terminal domain containing the receptor-binding domain and were fused to the human IgG1 Fc domain. Three groups of 2 animals each were immunized with either antigen, alone or in combination. The development of antibody responses was evaluated through 20 weeks post-immunization. ResultsA robust IgG response to the spike protein was detected as early as 2 weeks after immunization with either protein and maintained for over 20 weeks. Sera from animals immunized with antigens derived from the RBD were able to prevent binding of soluble spike proteins to the ACE2 receptor, shown by in vitro binding assays, while sera from animals immunized with the N-terminal domain alone lacked this activity. Crucially, sera from animals immunized with the extended receptor binding domain but not the N-terminal domain had potent neutralizing activity against SARS-CoV-2 pseudotyped virus, with titers in excess of 10,000, greatly exceeding that typically found in convalescent humans. Neutralizing activity persisted for more than 20 weeks. ConclusionsThese data support the utility of spike subunit-based antigens as a vaccine for use in humans.
Spatial Variability of Saturated Hydraulic Conductivity and its Links with other Soil Properties at the Commune Scale
Authors: Usowicz Boguslaw , Lipiec Jerzy
Published: January 2021

Saturated hydraulic conductivity (SHC) is a key property for evaluating soil water movement and quality. Most studies on spatial variability of SHC have been performed soil at a field or smaller scale. Therefore, the aim of this work was to assess (quantify) the spatial distribution of SHC at the commune scale and its relationship with other soil properties, including intrinsic sand, silt, and clay contents, relatively stable organic carbon, cation exchange capacity (CEC), dynamic water content (WC), total porosity (FI), and dry bulk density (BD) in the surface layer (0–20 cm). The spatial relationships were assessed using a semivariogram and a cross-semivariogram. The studied commune (140 km2) with predominantly permeable sandy soils with low fertility and productivity is located in the south-eastern part of Poland (Podlasie region). The mean sand and organic carbon contents are 74 andobablyctknąć, czy o to chodzid mniej znacznie mniejszed? ? 0.86 and their ranges (in %) are 45-95 and 0.002-3.75, respectively. The number of individual samples varied from 216–228 (for SHC, WC, BD, FI) to 691 for the other soil properties. The best fitting models were adjusted to the empirical semivariogram (exponential) and the cross-semivariogram (exponential, Gaussian, or linear) used to draw maps with kriging. The results showed that, among the soil properties studied, SHC was most variable (coefficient of variation 77.3%) and significantly (p <0.05) positively correlated with total porosity (r = 0.300) and negatively correlated with soil bulk density (r = –0.283). The mean SHC was 2.597 m day–1 and ranged from 0.01 up to 11.54 m day–1. The spatial autocorrelation (range) of SHC in the single (direct) semivariograms was 0.081° (8.1 km), while it favourably increased up to 0.149–0.81° (14.9–81 km) in the cross-semivariograms using the OC contents, textural fractions, and CEC as auxiliary variables. The generated spatial maps allowed outlining two sub-areas with predominantly high SHC above 3.0 m day–1 in the northern sandier (sand content >74%) and less silty (silt content <22%) part and, with lower SHC in the southern part of the commune. Generally, the spatial distribution of the SHC values in the commune area depended on the share of individual intrinsic textural fractions. On the other hand, the ranges of the spatial relationship between SHC and the intrinsic and relatively stable soil properties were much larger (from ~15 to 81 km) than between SHC and the dynamic soil properties (0.3-0.9 km). This knowledge is supportive for making decisions related to land management aimed at reduction of hydraulic conductivity and chemical leaching and improvement of soil water resources and crop productivity.
Corticosteroids Treatment for Patients With Coronavirus Disease-2019 (COVID-19) With Different Disease Severity: a Systematic Review and Meta-analysis Protocol
Authors: Lou Shaofei , Huang Kaizhuang , Jiang Jiao , Li Ningjun
Published: January 2021

Introduction: As the coronavirus disease 2019 (COVID-19) pandemic progresses, identifying effective antiviral agents to treat the COVID-19 is of most urgency. Efficacy and safety of corticosteroids in patients with COVID-19 still are debated. Because high-quality randomized clinical trials (RCTs) on the use of corticosteroids for patients with COVID-19 recently were published recently, we aim to conduct a systematic review and meta-analysis of RCTs on corticosteroids therapy in patients with different disease severity to ascertain the effect on survival. Methods: We will undertake a comprehensive literature search among PubMed, EMBASE, Cochrane Library, medRxiv, and bioRxiv from their inception onwards to identify relevant RCTs. Two reviewers will independently extract data and conduct risk of bias assessments. The primary outcome is all-cause mortality, mortality of mechanically ventilated patients and patients who did not receive oxygen therapy. Secondary outcomes include need for mechanical ventilation or oxygen therapy and incidence of adverse outcomes. Heterogeneity of the estimates across studies will be assessed. Outcomes will be analyzed to pooled risk ratio and pertinent 95% confidence interval. A subgroup analysis will be conducted by disease severity to explore the source of heterogeneity. The systematic review and meta-analysis will be presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Discussion: This systematic review will provide an overview of the current state of evidence concerning the effect of corticosteroids on survival of patients with COVID-19 depended on the disease severity. Also, this systematic review will show the limitations and strengths of the studies available in the literature, as well as recommendations for future avenues of research will be given. PROSPERO registration number: CRD42020227740.
Active Behavior of Triple-Negative Breast Cancer With Adipose Tissue Invasion: A Single Center and Retrospective Review
Authors: yamaguchi junzo , Moriuchi Hiroki , Ueda Takashi , Kawashita Yujo , Hazeyama Takanori , Tateishi Masaki , Aoki Shigehisa , Uchihashi Kazuyoshi , Nakamura Mikio
Published: January 2021

BackgroundInteractions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). MethodsA total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model.ResultsPatients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). ConclusionsAdipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.
Life-Long Coral Skeletal Acclimatization at CO2 Vents in Papua New Guinea Reveals Species- and Environment-Specific Effects
Authors: Prada Fiorella , Brizi Leonardo , Franzellitti Silvia , Mengoli Stefano , Fermani Simona , Polishchuk Iryna , Baraldi Nicola , Ricci Francesco , Palazzo Quinzia , Caroselli Erik , Pokroy Boaz , Giorgini Loris , Dubinsky Zvy , Fantazzini Paola , Falini Giuseppe , Goffredo Stefano , Fabricius Katharina
Published: January 2021

The responses of corals and other marine calcifying organisms to ocean acidification (OA) are variable and span from no effect to severe responses. Here we investigated the effect of long-term exposure to OA on skeletal parameters of four tropical zooxanthellate corals living at two CO2 vents in Papua New Guinea, namely in Dobu and Upa Upasina. The skeletal porosity of Galaxea fascicularis, Acropora millepora, and Pocillopora damicornis was higher (from 17% to 38%, depending on the species) at the seep site compared to the control only at Upa Upasina. Massive Porites showed no differences at any of the locations. Pocillopora damicornis also showed a ~ 7% decrease of micro-density and an increase of the volume fraction of the larger pores, a decrease of the intraskeletal organic matrix content with an increase of the intraskeletal water content, and no variation in the organic matrix related strain and crystallite size. The fact that the skeletal parameters varied only at one of the two seep sites suggests that other local environmental conditions interact with OA to modify the coral skeletal parameters. This might also contribute to explain the great deal of responses to OA reported for corals and other marine calcifying organisms.
Prevalence of Non-alcoholic Fatty Liver Disease and Its Associated Factors in Admixed Individuals With Type 1 Diabetes: a Cross-sectional Study in a Tertiary Care Center in Brazil
Authors: Barros Bianca Senger Vasconcelos , Monteiro Fernanda Cruz , Terra Carlos , Gomes Marilia Brito
Published: January 2021

Background: Data on non-alcoholic fatty liver disease (NAFLD) in admixed individuals with type 1 diabetes (T1D) is lacking. We investigated NAFLD in an admixed population with T1D from a tertiary care center in Brazil. Methods: Ninety-five participants with T1D, aged 39 ± 13 years, with disease duration of 21 ± 9 years, being 55 (57.9%) females, from a university hospital in Rio de Janeiro, were screened for NAFLD with hepatic ultrasound (US) and transient elastography (TE). Results: Prevalence of NAFLD was, respectively, 12.6% and 16.8% when US and TE were used. Fibrosis was present in 8% of participants. A total of 31.6% of participants had at least one of the hepatic exams altered, which was associated with higher anthropometric measurements, presence of metabolic syndrome and higher triglycerides levels, even within the normal range.Conclusion: In our study, prevalence of NAFLD in US approximates from the one found with TE. Screening should be reserved for participants with T1D and metabolic syndrome, as this was the main factor associated with NAFLD. Triglycerides levels were the only component of metabolic syndrome associated with NAFLD. Further studies are necessary to determine the best screening strategy for NAFLD in individuals with T1D from admixed populations.
Weight regain after Bariatric Surgery increases the request for Traditional Chinese Medicine Results from the cross-sectional BARBQTCM survey
Authors: Walker Benedict , Kessler Ulf , Kordasz Marcin , Rothe Steffi , Tsai Catherine , Zehetner Jörg , Panhofer Peter
Published: January 2021

Background: To investigate patient attitudes towards Traditional Chinese Medicine (TCM) after bariatric surgery with special emphasis on postoperative weight regain (WR).Methods: We retrospectively compared experiences with Complementary Additive Medicine (CAM) and the desire for additional TCM between patients with stable weight (SW) and WR by means of the disease-specific BARBQTCM survey during postoperative follow-up in a single bariatric center.Results: Out of 467 participating patients, 150 (32.1%) had WR after bariatric surgery. Median age was 49 years and 78.4% of the patients were female. 233 patients (49.9%) had already had experience with CAM and 125 (26.8%) with TCM. 381 patients (81.6%) were interested in using TCM at the time of the survey. Acceptance of TCM was lower in men (OR 0.35, P<0.01) and decreased with age (OR 0.95, P<0.001). Overall, the request for TCM was lower in the SW cohort compared to the WR group (77.3% versus 90.7%; OR 0.29, P<0.01). There was a positive correlation between preoperative experience with CAM and postoperative request for TCM (OR 5, P<0.001). The proportion of patients who were interested in outpatient TCM twice or more monthly was higher in patients with WR than in those with SW (94.0% versus 84.2%, P<0.01).Conclusions: The overall acceptance of CAM and TCM was high in our bariatric surgical patients. WR increased the rate of acceptance of TCM. We conclude that CAM and TCM should be offered during postoperative follow-up after bariatric surgery as part of an integrative medical approach.
Assessment and Documentation of Indigenous and Introduced Soil and Water Conservation Measures in Some Parts of Southern Ethiopia
Authors: Kassa Dawit Kanito , Bekele Tsegaye , Dawit Tesfaye , T/yohannes Seyfu
Published: January 2021

BackgroundIn Ethiopia, soil and water conservation activities were started after the famines of 1973 and 1985. Following this, different conservation measures were implemented by the government, non-government organizations, and the community to facilitate the optimum level of production from a given area of land while keeping soil loss below a critical value. This study was conducted at Wolaita, Hadiya, Kambata Tambaro, and Dawro Zones of Southern Ethiopia. It was designed to identify indigenous and introduced soil and water conservation practices, measure and describe identified practices, and document the identified practice for further reference. ResultsThe result revealed that three types of soil and water conservation practices namely biological, physical, and agronomical were implementing in the study areas. The result from the technical evaluation showed that soil bund and fanya juu has channel depth and embankment height lower than the recommended dimension. The result also indicated that less attention was given to indigenous soil and water conservation practices. Besides, the sustainability gap in constructed conservation practices was widely perceived. ConclusionsFarmers in the study area are well acquainted with soil erosion, its cause, and consequent reduction in land productivity. They confirm that implementing SWC measures are insurance to sustain and boost soil fertility and land productivity. In southern Ethiopia government and peoples were invested much more time, money, knowledge, and manpower to construct SWC measures. But, year by year structures get damage and yet seem not substantial to achieve the sector of sustainable agriculture. Besides, the study revealed that identified practices such as traditional cutoff drain, fanya juu, soil bund, stone-faced soil bund, fanya juu, brushwood, and gabion check-dams have technical, social, and institutional difficulties. The major gap observed with indigenous conservation practices is, it had been taken less attention by different stakeholders including GOs, NGOs, and research institutes. As a result, their respective dimension was not modified, effective measures were not up-scaled and circulated to other areas having similar agroecology and farming system. Thus, apparently, traditional conservation measures are aggravating soil erosion and their construction did not consider the downstream effect on dwelling community, water bodies, and aquatic lives.
Polyethylenimine-based Magnetic Nanocomplexes Enhanced Cisplatin Toxicity on Ovarian Cancer Cells in Presence of Static Magnetic Field
Authors: Ashoori Faranak , Hajipour-Verdom Behnam , Satari Mohammad , Abdolmaleki Parviz
Published: January 2021

BackgroundThe drug resistance of cancer cells is a major problem in the chemotherapy. Cisplatin (CIS) is one of the most effective chemotherapeutics used for ovarian cancer. Resistance to different chemo-drugs has developed over times. Here, we investigated the experimental approach to increase the CIS cytotoxicity and overcoming cell resistance through nanoparticle-based combination treatments. Polyethylenimine (PEI)-based magnetic iron oxide nanocomplexes were used to transfer the drugs in both genetically matched CIS-resistant (A2780CP) and -sensitive (A2780) ovarian cancer cells in presence of 20 mT static magnetic field. Magnetic nanoparticles (MNPs) were synthesized and bonded to PEI cationic polymer that leads to formation of binary complexes (PM). In the following, binding of CIS to PM binary complexes two including ternary complexes PM/C (PEI-MNP/CIS) and PMC (PEI-MNP-CIS) formed. ResultsOur results showed that the CIS cytotoxicity increased at different concentrations of CIS and PEI in all of binary and ternary treatments overtimes. Furthermore, CIS induced S and G2/M phase’s cell cycle arrest as well as reactive oxygen species (ROS) production in the both cell lines. Ternary complexes enhanced apoptosis more than binary complexes in the treated-cells. ConclusionsPEI-based magnetic noncomplex can be considered as a novel carrier for increasing the CIS cytotoxicity and probably overcoming drug resistance in ovarian cancer cells.
The Combined Anti-inflammatory Strategy of Beta-2 Adrenergic Agonist and Glucocorticoid on the Laying Hen Model of Ovarian Cancer: the Immune Traits and Ovarian Inflammatory Functions
Authors: Hatefi Ali , Shahneh Ahmad Zare , Pirsaraie Zarbakht Ansari , Alizadeh Ali Mohammad , Atashnak Mohammad Pouya , Masoudi Reza , Pio Frederic
Published: January 2021

Background: Ovarian cancer known as one of the most lethal gynecological malignancies mainly in older women, has been documented to link with chronic inﬂammation. Objective: This study was aimed to evaluate the combined strategy of glucocorticoid (GC) Fluticasone and beta-2 adrenergic agonist (BAA) Salmeterol on the ovarian inflammatory functions of the laying hen as a model of women ovarian cancer. Methods: White Leghorn hens aged 92 weeks were used for four weeks to be supplemented by individual of GC and BAA administration and their combination at three ratios GC:BAA 1:4 (GC+BAA1), 1:2 (GC+BAA2), and 1:1 (GC+BAA3), and beta blocker (BB) Propranolol. Ovulation rate and follicular growth were determined based on laying frequency and visual evaluation, respectively, the mRNA expressions of follicular beta-2 adrenergic receptor (β2ADR), cyclooxygenases (COX) 1 and 2, and cytokines were measured by real-time PCR. The plasma concentration of ovarian hormones cellular and humoral immune responses were measured via ELISA, neutrophil (heterophil) to lymphocyte ratio (NLR), and sheep red blood cell (SRBC) test, respectively. Results: As compared to control, combination groups of GC+BAA1 and 2 brought about a significant decrease in the mRNA expression of β2ADR, COX-2, and cytokines (P< 0.05). The ovulation rate was reduced in all combination ratios (P< 0.05). A signiﬁcant reduction was observed in the plasma estradiol content on GC+BAA groups (P< 0.05) and the content of progesterone and androgen were statistically similar in some of these groups. Although NLR was similar in GC+BAA2 and 3, these groups had more content in the whole immunoglobulin (Ig) and IgM (P< 0.05). The results indicated that body weight and food consummation were decreased in all of the combination groups (P< 0.05). Conclusion: The GC and BAA combination may result in a signiﬁcant reduction in some of the boosting factors on ovarian cancer, like ovulation intensity, pro-inflammatory mediators, and some of the ovarian steroid hormones that could define as the therapeutic approaches for the chronic inflammation-based carcinomas like ovarian cancer.
Minimally Invasive Pedicle Subtraction Osteotomy via Tubular Retractor for Adult Rigid Spinal Kyphoscoliosis: a Case Report and Review of the Literature
Authors: Xing ZeJun , Ma Zhuo , Ma Xun
Published: January 2021

Objective To describe a new technique, minimally invasive pedicle subtraction osteotomy (MIS PSO) via tubular retractor, for severe rigid adult spinal deformity.Methods We present a case with severe rigid thoracolumbar kyphoscoliosis and describe the surgical procedure , to which this patient responded favorably.Results No surgical complications were seen and estimated blood loss was 600ml. The operation process time was about 5 hours. She received 2 unit of packed red blood cells intraoperatively. VAS was 8.5 points at pre-operation and 2 .0 points at 2 years follow-up. The ODI score improved from 33 to 9. Fusion was confirmed by wedging of L2 vertebral body on CT reconstructive films. Routine x-rays showed that spinal imbalance was corrected and maintained at the final follow up. Maximal ambulation distance increased to 5000 feet at 2 years follow-up.Conclusion A MIS PSO is a feasible option for the treatment of certain subtypes of adult spinal deformity. It is technically feasible that although limited by learning curve of minimally invasive tubular technique and open PSO technique. Both operation skill of the surgeons and proper patient selection is the key to successfully treating adult patients with deformity using MIS PSO.
Exploring the Coping Strategies of Older Persons During COVID-19 Lockdown in Nigeria: A Qualitative Study
Authors: Adedeji Isaac , Lawal Saheed Akinmayowa , Aluko-Arowolo Sola
Published: January 2021

The authors have requested that this preprint be removed from Research Square.
Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome
Authors: Chen Lei , Yin Liang , Qi Zilong , Li Jinmin , Wang Xinning , Ma Kun , Liu Xiangyang
Published: January 2021

Background: Renal cancer is a common malignant tumor with an increasing incidence rate. Methods: In this study, based on the gene expression profiles, we analyzed the compositions of tumor-infiltrating immune cells (TIICs) in renal cancer and paracancerous samples using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal carcinoma and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. Results: After analyzed the difference of TIICs composition between renal cancer and paired paracancerous samples, we found that M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples compared with paracancerous samples. Survival analysis showed that high overall TIICs proportion , the low proportion of resting mast cells and the high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis, and they presented a distinct prognosis. Cluster 1 had superior survival outcomes, while cluster 2 had an inferior survival outcome. Conclusions: Our study indicated that overall TIICs proportion, certain TIICs subset proportion, including resting mast cells and activated memory CD4 T cells, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.
KLF5-mediated Eppk1 expression promotes cell proliferation in cervical cancer via the p38 signaling pathway
Authors: Ma Dong , Pan Zhe , Chang Quan , Zhang Jin-jin , Liu Xiao , Hua Na , Li Guo-Hua
Published: January 2021

Background: Epiplakin1 (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. However, the role of Eppk1 in cervical cancer (CC) remains unknown.Methods: To express Eppk1 and KLF5 and their correlation, we used RNA-sequence, RT-qPCR, TCGA database and immunofluorescence staining in vitro and in different pathological cervical tissues. In CC cell lines, we tested adenovirus-mediated over expression or knockdown of KLF5 and siRNA-mediated knockdown of Eppk1 and a suiting assessment of cell proliferation and cell signaling by western blot and CCK8 tests. We studied the mechanism by which KLF5 regulates Eppk1 expression by reporter gene test and chromatin immunoprecipitation test.Results: Eppk1 expression promoted in CC tissues and cell lines compared with increased KLF5 expression. The results of immunofluorescence staining further showed the increased co-expression of Eppk1 and KLF5 correlated substantially with tumorigenesis in cervical tissues. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanically, KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments reported that KLF5 promoted cell proliferation in Hela partly dependent on Eppk1 upregulation. Besides, KLF5-mediated activation of p38 signaling significantly decreased after Eppk1 knockdown compared with decline of proliferation, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation. Finally, Eppk1 expression is positively correlated with tumor size in clinicopathological features of CC. Conclusions: Eppk1 may be an effective therapeutic target for affecting p38 signaling pathway and cell proliferation in cervical cancer.
Men perspectives on attending antenatal care visits together with their pregnant partners in Misungwi district, rural Tanzania: a qualitative study
Authors: Boniphace Maendeleo , Matovelo Dismas , Laisser Rose , Swai Hadija , Yohana Victoria , Tinka Sylvia , Mwaikasu Lusako , Mercader Hannah , Brenner Jennifer L , Mitchell Jennifer
Published: January 2021

Background: Mens’attendance with their pregnant partners at facility-based antenatal care (ANC) visits is important for maternal and child health and gender equality yet remains uncommon in parts of rural Tanzania. This study examined men’s perspectives on attending ANC with their pregnant partners in Misungwi District, Tanzania.Methods: Twelve individual interviews and five focus group discussions were conducted using semi-structured questionnaires with fathers, expectant fathers, and in-depth interviews were done to health providers, volunteer community health workers, and village leaders. Interviews were recorded and transcribed in Swahili and later translated to English. The research team conducted thematic analysis to identify common themes among interviews. Results: We identified two broad themes on the barriers to male attendance at facility-based ANC visits: (1) Perceived exclusion during ANC visits among men (2) Traditional gender norms resulting to low attendance among men.Conclusion: Attendance at health facility for ANC visits by men with their pregnant partners in the study areas were challenged by structural and local cultural norms. At the facility men were uncomfortable to sit with women due to lack of specific waiting area for men and that they perceived to be neglected. Local cultural norms demanded women to have secrecy in pregnancy while men perceived not to have a role of being with their partners during ANC visits.
Combined Macromolecule biomaterials together with fluid shear stress promote the osteogenic differentiation capacity of equine adipose -derived mesenchymal stem cells
Authors: Elashry Mohamed I. , Baulig Nadine , Wagner Alena-Svenja , Klymiuk Michele C. , Kruppke Benjamin , Hanke Thomas , Wenisch Sabine , Arnhold Stefan
Published: January 2021

Background: Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose derived MSCs morphology, viability, adherence, migration and osteogenic differentiation.Methods: MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or mechanical fluid shear stress (FSS) culture conditions. The data were generated by histological means, live cell imaging, cell viability, adherence and migration assays, semi-quantification of alkaline phosphatase (ALP) activity and quantification of the osteogenic markers runt related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) expression.Results: The data revealed that combined mechanical FSS with MC but not B30 enhanced MSCs viability and promoted their migration. Combined osteogenic medium with MC, B30 and B30Str increased ALP activity compared to cultivation in basal medium. Osteogenic induction with MC, B30 and B30Str resulted in diffused matrix mineralization. The combined osteogenic induction with biomaterials under mechanical FSS increased Runx2 protein expression either in comparison to those cells cultivated in BM or those cells induced under static culture. Runx2 and ALP expression was upregulated following combined osteogenic differentiation together with B30 and B30Str regardless of static or FSS culture.Conclusions: Taken together, the data revealed that FSS in conjunction with biomaterials promoted osteogenic differentiation of MSCs. This combination may be considered as a marked improvement for clinical applications to cure bone defects.
A Standard Set of Outcome Measures for the Comprehensive Assessment of Osteogenesis Imperfecta.
Authors: Nijhuis Wouter , Franken Anton , Ayers Kara , Damas Chantal , Folkestad Lars , Forlino Antonella , Fraschini Paolo , Hill Claire , Janus Guus , Kruse Richard , Wekre Lena , Michiels Lieve , Montpetit Kathleen , Panzeri Leonardo , Porquet-Bordes Valerie , Rauch Frank , Sakkers Ralph , Salles Jean-Pierre , Semler Oliver , Sun Jony , To Michael , Tosi Laura , Yao Yangyang , Yeung Eric Hiu Kwong , Zhytnik Lidiia , Zillikens Carola , Verhoef Marjolein
Published: January 2021

Background: Osteogenesis Imperfecta (OI) is a genetic disorder also known as ‘brittle bone disease’. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes thus making the comparison of outcome measures available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future. Methods: The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search.After reviewing the outcomes extracted from the literature, trials and registries, the working group agreed on a final selection of domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups who prioritized the outcome domains by taking into account the items important to the OI community. All content was collected and analyzed and final domains were determined. A consensus of appropriate measuring instruments for each domain was reached with Delphi rounds. The entire approach was in line with the International Consortium for Health Outcomes Measurement ICHOM methodology13. Results: More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults. Conclusion: The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set.
Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: A population-based study
Authors: Sato Akira , Matsubayashi Keisuke , Morishima Toshitaka , Nakata Kayo , Kawakami Koji , Miyashiro Isao
Published: January 2021

Background: Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan.

Methods: Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test.

Results: Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer.

Conclusions: The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.
Feedback of patient survey on medication improves the management of polypharmacy: A pilot trial
Authors: Hirose Yuta , Shikino Kiyoshi , Ohira Yoshiyuki , Matsuoka Sumihide , Mikami Chihiro , Tsuchiya Hayami , Yokokawa Daiki , Ikegami Akiko , Tsukamoto Tomoko , Noda Kazutaka , Uehara Takanori , Ikusaka Masatomi
Published: January 2021

Background: Patient awareness surveys on polypharmacy have been reported previously, but no previous study has examined the effects of sending feedback to health professionals on reducing medication use. Our study aimed to conduct a patient survey to examine factors contributing to polypharmacy, feedback the results to health professionals, and analyze the resulting changes in the number of polypharmacy patients and prescribed medications. Methods: We conducted a questionnaire survey of patients in Study 1, while feedback of survey results health professionals, and before-after scrutiny of medical receipt data comprised polypharmacy in Study 2. In Study 1, we examined polypharmacy and its contributing factors by performing logistic regression analysis. In Study 2, we performe a t-test and a chi-square test. Results: In the questionnaire survey, significant differences were found in the following 3 items: age (odds ratio (OR)=3.14; 95% confidence interval (CI)=2.01-4.91), number of medical institutions (OR=2.34; 95%CI=1.50-3.64), and patients' difficulty with asking their doctors to deprescribe their medications (OR=2.21; 95%CI=1.25-3.90). After the feedback, the percentage of polypharmacy patients decreased from 21.5% to 20.1% and the mean number of prescribed medications per patient decreased from 8.2 to 7.7 (p<0.001, respectively). Conclusions: Providing feedback to health professionals on polypharmacy survey results may lead to a decrease in the number of polypharmacy patients. Factors contributing to polypharmacy included age (75 years or older), the number of medical institutions (2 or more institutions), and patients' difficulty with asking their physicians to deprescribe their medications. Feedback to health professionals reduced the percentage of polypharmacy patients and the number of prescribed medications.
Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) over Lenalidomide and Dexamethasone (Rd) in Relapsed and Refractory Multiple Myeloma Patients in Routine Clinical Practice
Authors: Minarik Jiri , Pika Tomas , Radocha Jakub , Jungova Alexandra , Straub Jan , Jelinek Tomas , Pour Ludek , Pavlicek Petr , Mistrik Martin , Brozova Lucie , Krhovska Petra , Machalkova Katerina , Jindra Pavel , Spicka Ivan , Plonkova Hana , Stork Martin , Bacovsky Jaroslav , Capkova Lenka , Sykora Michal , Kessler Petr , Stejskal Lukas , Heindorfer Adriana , Ullrychova Jana , Skacel Tomas , Maisnar Vladimir , Hajek Roman
Published: January 2021

Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods: A total of 344 patients treated with IRD (N=127) or RD (N=217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51 – 0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0 % in the IRD group vs 66.2 % in the RD group with a complete response rate (CR) of 11.1 % vs 8.8 %, and very good partial response (VGPR) 22.2 % vs 13.9 %, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.
Evaluation of 18F-FDG PET/CT Images Acquired with a Reduced Scan Time Duration in Lymphoma Patients using the Digital Biograph Vision
Authors: Weber Manuel , Jentzen Walter , Hofferber Regina , Herrmann Ken , Fendler Wolfgang Peter , Rischpler Christoph , Umutlu Lale , Conti Maurizio , Costa Pedro Fragoso , Sra Miriam , Kersting David
Published: January 2021

Background

The superior accuracy and sensitivity of 18 F-FDG-PET/CT in comparison to morphological imaging alone leads to an upstaging in up to 30% of lymphoma patients. Novel digital PET/CT scanners might enable to reduce administered tracer activity or scan time duration while maintaining diagnostic performance; this might allow for a higher patient throughput or a reduced radiation exposure, respectively. In particular, the radiation exposure reduction is of interest due to the often young age and high remission rate of lymphoma patients.

Methods

Twenty patients with (suspected) lymphoma (6 for initial staging, 12 after systemic treatment, 2 in suspicion of recurrence) sequentially underwent 18 F-FDG-PET/CT examinations on a digital PET/CT (Siemens Biograph Vision) with a total scan time duration of 15 minutes (reference acquisition protocol) and 5 minutes (reduced acquisition protocol) using continuous-bed-motion. Both data sets were reconstructed using either standalone time of flight (TOF) or in combination with point spread function (PSF), each with 2 and 4 iterations. Lesion detectability by blinded assessment (separately for supra- and infradiaphragmal nodal lesions and for extranodal lesions), lesion image quantification, and image noise were used as metrics to assess diagnostic performance. Additionally, Deauville Score was compared for all patients after systemic treatment.

Results

All defined regions were correctly classified in the images acquired with reduced emission time, and therefore, no changes in staging were observed. Lesion quantification was acceptable, that is, mean absolute percentage deviation of maximum and peak standardized uptake values were 6.8% and 6.4% (derived from 30 lesions). A threefold reduction of scan time duration led to an increase in image noise from 7.1% to 11.0% (images reconstructed with 4 iterations) and from 4.7% to 7.2% (images reconstructed with 2 iterations). No deviations in Deauville Score were observed.

Conclusion

These results suggest that scan time duration or administered tracer activity can be reduced threefold without compromising diagnostic performance. Especially a reduction of administered activity might allow for a lower radiation exposure and better health economics. Larger trials are warranted to confirm our results.
Does chemotherapy or radiotherapy affect the postoperative complication in patients who underwent immediate breast reconstruction with tissue expander?
Authors: Jung Sung Mi , Jeon Byung-Joon , Woo Jinsun , Ryu Jai Min , Lee Se Kyung , Chae Byung-Joo , Yu Jonghan , Kim Seok Won , Nam Seok Jin , Bang Sa Ik , Mun Goo-Hyun , Pyon Jai-Kyong , Lee Jeong Eon
Published: January 2021

Background: Immediate breast reconstruction with tissue expander in patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander.

Methods: We conducted a retrospective study of 1,081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1,022 patients (94.5%).

Results: In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications ( p < 0.001). Chemotherapy ( p = 0.775) or radiotherapy ( p = 0.825) were not risk factors for postoperative complications.

Conclusions: IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR.

Trial registration: Patients were selected and registered retrospectively, and medical records were evaluated.