bluuebunny/crossref_metadata_2025 huggingface dataset:
A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice
Authors: Varshney Shweta , Wei Hua-Xing , Batista Frank , Nauman Mohd , Sundaram Subha , Siminovitch Katherine , Tanwar Ankit , Stanley Pamela
Published: October 2019

Background

Mouse NOTCH1 carries a highly conserved O-fucose glycan at Thr466 in epidermal growth factor-like repeat 12 (EGF12) of the extracellular domain. O-Fucose at this site has been shown by X-ray crystallography to be recognized by both DLL4 and JAG1 Notch ligands. We previously showed that aNotch1Thr466Ala mutant exhibits very little ligand-induced NOTCH1 signaling in a reporter assay, whereas a Thr466Ser mutation enables the transfer of O-fucose and reverts the NOTCH1 signaling defect. We subsequently generated a mutant mouse with the Thr466Ala mutation termedNotch1[12f](Notch1tm2Pst). Surprisingly, homozygousNotch1[12f/12f] mutants on a mixed background were viable and fertile.

Results

We now report that after backcrossing to C57BL/6 J mice for 11–15 generations, few homozygousNotch1[12f/12f] embryos were born. Timed mating showed that embryonic lethality occurred by embryonic day (E) ~E11.5, somewhat delayed compared to mice lackingNotch1orPofut1(the O-fucosyltransferase that adds O-fucose to Notch receptors), which die at ~E9.5. The phenotype of C57BL/6 JNotch1[12f/12f] embryos was milder than mutants affected by loss of a canonical Notch pathway member, but disorganized vasculogenesis in the yolk sac, delayed somitogenesis and development were characteristic. In situ hybridization of Notch target genesUncx4.1andDll3or western blot analysis of NOTCH1 cleavage did not reveal significant differences at E9.5. However, qRT-PCR of head cDNA showed increased expression ofDll3,Uncx4.1andNotch1in E9.5Notch1[12f/12f] embryos. Sequencing of cDNA fromNotch1[12f/12f] embryo heads and Southern analysis showed that theNotch1[12f] locus was intact following backcrossing. We therefore looked for evidence of modifying gene(s) by crossing C57BL/6 JNotch1[12f/+] mice to 129S2/SvPasCrl mice. Intercrosses of the F1 progeny gave viable F2Notch1[12f/12f] mice.

Conclusion

We conclude that the 129S2/SvPasCrl genome contains a dominant modifying gene that rescues the functions of NOTCH1[12f] in signaling. Identification of the modifying gene has the potential to illuminate novel factor(s) that promote Notch signaling when an O-fucose glycan is absent from EGF12 of NOTCH1.
Measurement of leaf lamina moisture with a low-cost electrical humidity sensor: case study on a wheat water-mutant
Authors: Rascio Agata , Rinaldi Michele , De Santis Giuditta , Pecchioni Nicola , Palazzo Gabriele , Palazzo Nicola
Published: October 2019

Background

The presence and persistence of water on the leaf can affect crop performance and thus might be a relevant trait to select for or against in breeding programmes. Low-cost, rapid and relatively simple methods are of significant importance for screening of large populations of plants for moisture analysis of detached leaves. Leaf moisture can be detected using an electric circuit, where the resistance changes are proportional to the moisture of the measured surface. In this study, we present a protocol to analyse genotypic differences through the electrical properties of living or stored tissues, performed using a commercial device. Expanded and non-expanded leaves were compared to determine the effects of leaf maturity on these data. Two wheat genotypes that differ in tissue affinity for bound water were used to define the influence of water status.

Results

The device indirectly estimates leaf moisture content using two electrodes applied to the leaf lamina of fresh and stored samples. Single moisture readings using this moisture meter had mean execution time of ~ 1.0 min. Exponential associations provided good fits for relationships between the moisture meter reading (MMR) and the electrical resistance applied to the electrodes. MMR normalised for the water/ dry matter ratio (MMRnorm) was lower for mature leaves of the water-mutant than those of wild-type, for the fully hydrated fresh leaves. MMR of fully mature leaves when partially dehydrated and measured after 10 min at 27 °C and 40% relative humidity was greater for the water-mutant than the wild-type.

Conclusions

This case study provides a low-cost tool to compare electrical-resistance estimates of leaf moisture content, together with a promising and rapid phenotyping protocol for genotypic screening of wheat under standard environmental conditions. Measurement of changes in MMR with time, of fresh and partially dehydrated leaves, or of MMR normalised to tissue water content allowed for differentiation between the genotypes. Furthermore, the differences observed between genotypes that here relate particular to tissue affinity for bound water suggest that not only the free-water fraction, but also other water fractions, can affect these electrically estimated leaf moisture measures.
Melatonin alleviates heat-induced damage of tomato seedlings by balancing redox homeostasis and modulating polyamine and nitric oxide biosynthesis
Authors: Jahan Mohammad Shah , Shu Sheng , Wang Yu , Chen Zheng , He Mingming , Tao Meiqi , Sun Jin , Guo Shirong
Published: October 2019

Background

Melatonin is a pleiotropic signaling molecule that plays multifarious roles in plants stress tolerance. The polyamine (PAs) metabolic pathway has been suggested to eliminate the effects of environmental stresses. However, the underlying mechanism of how melatonin and PAs function together under heat stress largely remains unknown. In this study, we investigated the potential role of melatonin in regulating PAs and nitric oxide (NO) biosynthesis, and counterbalancing oxidative damage induced by heat stress in tomato seedlings.

Results

Heat stress enhanced the overproduction of reactive oxygen species (ROS) and damaged inherent defense system, thus reduced plant growth. However, pretreatment with 100 μM melatonin (7 days) followed by exposure to heat stress (24 h) effectively reduced the oxidative stress by controlling the overaccumulation of superoxide (O2•−) and hydrogen peroxide (H2O2), lowering the lipid peroxidation content (as inferred based on malondialdehyde content) and less membrane injury index (MII). This was associated with increased the enzymatic and non-enzymatic antioxidants activities by regulating their related gene expression and modulating the ascorbate–glutathione cycle. The presence of melatonin induced respiratory burst oxidase (RBOH), heat shock transcription factors A2 (HsfA2), heat shock protein 90 (HSP90), and delta 1-pyrroline-5-carboxylate synthetase (P5CS) gene expression, which helped detoxify excess ROS via the hydrogen peroxide-mediated signaling pathway. In addition, heat stress boosted the endogenous levels of putrescine, spermidine and spermine, and increased the PAs contents, indicating higher metabolic gene expression. Moreover, melatonin-pretreated seedlings had further increased PAs levels and upregulated transcript abundance, which coincided with suppression of catabolic-related genes expression. Under heat stress, exogenous melatonin increased endogenous NO content along with nitrate reductase- and NO synthase-related activities, and expression of their related genes were also elevated.

Conclusions

Melatonin pretreatment positively increased the heat tolerance of tomato seedlings by improving their antioxidant defense mechanism, inducing ascorbate–glutathione cycle, and reprogramming the PAs metabolic and NO biosynthesis pathways. These attributes facilitated the scavenging of excess ROS and increased stability of the cellular membrane, which mitigated heat-induced oxidative stress.
Intestinal schistosomiasis of Ijinga Island, north-western Tanzania: prevalence, intensity of infection, hepatosplenic morbidities and their associated factors
Authors: Mueller Andreas , Fuss Antje , Ziegler Uwe , Kaatano Godfrey M. , Mazigo Humphrey D.
Published: October 2019

Background

Intestinal schistosomiasis is highly endemic in Tanzania and mass drug administration (MDA) using praziquantel is the mainstay of the control program. However, the MDA program covers only school aged children and does not include neither adult individuals nor other public health measures. The Ijinga schistosomiasis project examines the impact of an intensified treatment protocol with praziquantel MDA in combination with additional public health interventions. It aims to investigate the feasibility of eliminating intestinal schistosomiasis in a highly endemic African setting using an integrated community-based approach. In preparation of this project, we report about baseline data on S.mansoni prevalence, intensity of infection, related hepatosplenic morbidities and their associated factors.

Methods

A cross sectional study was conducted among 930 individuals aged 1–95 years living at Ijinga Island, north-western Tanzania in September 2016. Single stool and urine samples were collected from each study participant and processed using Kato Katz (KK) technique and point-of-care Circulating Cathodic (POC-CCA) antigen test for detection of S.mansoni eggs and antigen respectively. Ultrasonographical examination for S.mansoni hepatosplenic morbidities was done to all participants. For statistical analyses Fisher’s exact test, chi-square test, student-t-test, ANOVA and linear regression were used where applicable.

Results

Overall based on KK technique and POC-CCA test, 68.9% (95%CI: 65.8–71.8) and 94.5% (95%CI: 92.8–95.8) were infected with S.mansoni. The overall geometrical mean eggs per gram (GMepg) of faeces was 85.7epg (95%CI: 77.5–94.8). A total of 27.1, 31.2 and 51.9% of the study participants had periportal fibrosis (PPF-grade C-F), splenomegaly and hepatomegaly. Risk factors for PPF were being male (aRR = 1.08, 95%CI: 1.02–1.16, P < 0.01), belong to the age group 16–25 years (aRR = 1.23, 95%CI: 105–1.44, P < 0.01), 26–35 years (aRR = 1.42, 95%CI: 1.21–1.67, P < 0.001), 36–45 years (aRR = 1.56, 95%CI:1.31–1.84, P < 0.001) and ≥ 46 years (aRR = 1.64, 95%CI:1.41–1.92, P < 0.001). The length of the left liver lobe was associated with being female (P < 0.03), belong to the age group 1–5 years (P < 0.013), 6–15 years (P < 0.04) and S.mansoni intensity of infection (P < 0.034). Male sex (aRR = 1.15, 95%CI:1.06–1.24, P < 0.001) and belonging to the age groups 16–25 years (aRR = 1.27, 95%CI:1.05–1.54, P < 0.02) or 26–35 years (aRR = 1.32, 95%CI:108–1.61, P < 0.01) were associated with splenomegaly.

Conclusion

Schistosoma mansoni infection and its related morbidities (hepatomegaly, splenomegaly, periportal fibrosis) are common in the study area. Age, sex and intensity of infection were associated with periportal fibrosis. The prevalence of S.mansoni was above 50% in each age group and based on the observed prevalence, we recommend MDA to the entire community.
Association between the Charlson Comorbidity Index and the risk of 30-day unplanned readmission in patients receiving maintenance dialysis
Authors:   on behalf of China Kidney Disease Network Working Group, Lin Yu , Yang Chao , Chu Hong , Wu Jingyi , Lin Ke , Shi Ying , Wang Haibo , Kong Guilan , Zhang Luxia
Published: October 2019

Background

Patients receiving maintenance hemodialysis (HD) and peritoneal dialysis (PD) are frequently hospitalized. Reducing unplanned 30-day hospital readmissions is a key priority for improving the quality of health care. The purpose of this study was to assess the association between the Charlson Comorbidity Index (CCI), which has been used to evaluate multi-comorbidities status, and 30-day readmission in patients on HD and PD therapy.

Methods

The Hospital Quality Monitoring System (HQMS), a national administrative database for hospitalized patients in China was used to extract dialysis patients admitted from January 2013 to December 2015. The outcome was the unplanned readmission following the hospital discharge within 30 days. For patients with multiple hospitalizations, a single hospitalization was randomly selected as the index hospitalization. A cause-specific Cox proportional hazard model was utilized to assess the association of CCI with readmission within 30 days.

Results

Of the 124,721 patients included in the study, 19,893 patients (16.0%) were identified as experiencing unplanned readmissions within 30 days. Compared with patients without comorbidity (CCI = 2, scored for dialysis), the risk of 30-day readmission increased with elevated CCI score. The hazards ratio (HR) for those with CCI 3–4, 5–6 and > 6 was 1.01 (95% confidence interval [CI] 0.98–1.05), 1.09 (95% CI 1.05–1.14), and 1.14 (95% CI 1.09–1.20), respectively.

Conclusions

Our study indicated that CCI was independently associated with the risk of 30-day readmission for patients receiving dialysis including HD and PD, and could be used for risk-stratification.
PREPARE: protocol for a stepped wedge trial to evaluate whether a risk stratification model can reduce preterm deliveries among women with suspected or confirmed preterm pre-eclampsia
Authors:   PREPARE Research Group, Dias Marcos Augusto Bastos , De Oliveira Leandro , Jeyabalan Arundhanthi , Payne Beth , Redman Christopher W. , Magee Laura , Poston Lucilla , Chappell Lucy , Seed Paul , von Dadelszen Peter , Roberts James Michael
Published: October 2019

Background

Preeclampsia (PE) is a major cause of short and long-term morbidity for affected infants, including consequences of fetal growth restriction and iatrogenic prematurity. In Brazil, this is a special problem as PE accounts for 18% of preterm births (PTB). In the PREPARE (Prematurity REduction by Pre-eclampsia cARE) study, we will test a novel system of integrated care based on risk stratification and knowledge transfer, to safely reduce PTB.

Methods

This is a stepped wedge cluster randomised trial that will include women with suspected or confirmed PE between 20 + 0 and 36 + 6 gestational weeks. All pregnant women presenting with these findings at seven tertiary centres in geographically dispersed sites, throughout Brazil, will be considered eligible and evaluated in terms of risk stratification at admission. At randomly allocated time points, sites will transition to risk stratification performed according to sFlt-1/PlGF (Roche Diagnostics) measurement and fullPIERS score with both results will be revealed to care providers. The healthcare providers of women stratified as low risk for adverse outcomes (sFlt-1/PlGF ≤38 AND fullPIERS< 10% risk) will receive the recommendation to defer delivery. sFlt-1/PlGF will be repeated once and fullPIERS score twice a week. Rates of prematurity due to preeclampsia before and after the intervention will be compared. Additionally, providers will receive an active program of knowledge transfer about WHO recommendations for preeclampsia, including recommendations regarding antenatal corticosteroids for foetal benefits, antihypertensive therapy and magnesium sulphate for seizure prophylaxis. This study will have 90% power to detect a reduction in PTB associated with PE from a population estimate of 1.5 to 1.0%, representing a 33% risk reduction, and 80% power to detect a reduction from 2.0 to 1.5% (25% risk reduction). The necessary number of patients recruited to achieve these results is 750. Adverse events, serious adverse events, both anticipated and unanticipated will be recorded.

Discussion

The PREPARE intervention expects to reduce PTB and improve care of women with PE without significant adverse side effects. If successful, this novel pathway of care is designed for rapid translation to healthcare throughout Brazil and may be transferrable to other low and middle income countries.

Trial registration

ClinicalTrials.gov: NCT03073317.
Volunteers in a biography project with palliative care patients – a feasibility study
Authors: Hesse Michaela , Forstmeier Simon , Cuhls Henning , Radbruch Lukas
Published: October 2019

Background

Increasing the quality of life with short interventions for vulnerable patients is one of the objectives of palliative care. Biographical approaches are used in a range of different interventions which may require considerable resources of staff time and energy. This study evaluated the feasibility of training hospice volunteers in biographical interviews of patients confronted with a life-limiting disease. For the purpose of this study, we evaluated resources such as time needed for training, coordination and supervision, outcome such as completion of the intervention in appropriate time and risks such as causing distress in patients or volunteers as major determinants of feasibility.

Methods

Nine volunteers from a hospice service attended an advanced training with an introduction to palliative care, biography work, interview techniques, transcribing and writing. Volunteers interviewed a patient and developed a written narrative from the interview. Volunteers completed a questionnaire before training and were interviewed at the end of the project. The interviews were audiotaped, transcribed, and evaluated using descriptive and qualitative content analysis.

Results

Patients provided positive feedback from the intervention. Volunteers felt that their involvement was personally rewarding and were moved by the courage and confidence of the patients. There were no systematic problems or negative experiences reported neither by volunteers nor by patients.

Conclusions

We found the use of volunteers for biography work with patients in palliative care feasible and effective in this study. Volunteers needed supervision and ongoing support in providing this intervention.
Integrated virtual and cadaveric dissection laboratories enhance first year medical students’ anatomy experience: a pilot study
Authors: Darras Kathryn E. , Spouge Rebecca , Hatala Rose , Nicolaou Savvas , Hu Jeff , Worthington Anne , Krebs Claudia , Forster Bruce B.
Published: October 2019

Background

Radiology integration into medical anatomy courses is well established, but there is a paucity of literature on integrating virtual dissection into cadaveric dissection laboratories. Virtual dissection is the digital dissection of medical images on touchscreen anatomy visualization tables. The purpose of this pilot study was to investigate the feasibility of integrating virtual dissection into a first-year medical cadaver-based anatomy course and to assess students’ overall attitude towards this new technology.

Methods

All students in first-year medicine at a single medical school participated in this study (n = 292). Six virtual dissection laboratories, which focused on normal anatomy, were developed and integrated into a cadaver-based anatomy course. The virtual dissection table (VDT) was also integrated into the final anatomy spot exam. Following the course, students completed a short evidence-informed survey which was developed using a theoretical framework for curriculum evaluation. Numerical data were tabulated, and qualitative content analysis was performed on students’ unstructured comments.

Results

The survey response rate was 69.2% (n = 202/292). Most (78.7%) students reported that virtual dissection enhanced their understanding of the cadaveric anatomy and the clinical applications of anatomy. Most (73.8%) students also felt that the VDT was an effective use of the laboratory time. Thirteen narrative comments were collected, most of which (61.5%) identified strengths of the curriculum.

Conclusions

In this pilot study, students perceived that their learning was enhanced when virtual dissection was combined with a cadaver-based anatomy laboratory. This study demonstrates that there is potential for virtual dissection to augment cadaveric dissection in medical education.
Quality of antenatal care and associated factors in a rural county in Kenya: an assessment of service provision and experience dimensions
Authors: Afulani Patience A. , Buback Laura , Essandoh Francisca , Kinyua Joyceline , Kirumbi Leah , Cohen Craig R.
Published: October 2019

Background

This study aimed to assess the quality of antenatal care (ANC) women received in Migori county, Kenya—including both service provision and experience dimensions—and to examine factors associated with each dimension.

Methods

We used survey data collected in 2016 in Migori county from 1031 women aged 15–49 who attended ANC at least once in their most recent pregnancy. ANC quality service provision was measured by nine questions on receipt of recommended ANC services, and experience of care by 18 questions on information, communication, dignity, and facility environment. We summed the responses to the individual items to generate ANC service provision and experience of care scores. We used both linear and logistic regression to examine predictors.

Results

The average service provision score was 10.9 (SD = 2.4) out of a total of 16. Most women received some recommended services once, but not at the frequency recommended by the Kenyan Ministry of Health. About 90% had their blood pressure measured, and 78% had a urine test, but only 58 and 14% reported blood pressure monitoring and urine test, respectively, at every visit. Only 16% received an ultrasound at any time during ANC. The average experience score is 27.3 (SD = 8.2) out of a total score of 42, with key gaps demonstrated in communication. About half of women were not educated on pregnancy complications. Also, about one-third did not often understand the purposes of tests and medicines received and did not feel able to ask questions to the health care provider. In multivariate analysis, women who were literate, employed, and who received all their ANC in a health center had higher experiences scores than women who were illiterate (coefficient = 1.52, CI:0.26,2.79), unemployed (coefficient = 2.73, CI:1.46,4.00), and received some ANC from a hospital (coefficient = 1.99, CI: 0.84, 3.14) respectively. The wealthiest women had two times higher odds of receiving an ultrasound than the poorest women (OR = 2.00, CI:1.20,3.33).

Conclusion

Quality of ANC is suboptimal in both service provision and experience domains, with disparities by demographic and socioeconomic factors and facility type. More efforts are needed to improve quality of ANC and to eliminate the disparities.
A prospective risk assessment of the implementation of a schistosomiasis preventive mass drug administration for children aged five years and below in the uMkhanyakude district of KwaZulu-Natal
Authors: Ncube Mhlengi Vella , Chimbari Moses John
Published: October 2019

Background

Schistosomiasis is endemic in the uMkhanyakude district of KwaZulu-Natal, South Africa. The South Africa Department of Health (DoH) has decided to implement a schistosomiasis preventive mass drug administration program in all affected parts of the country. Quality management is part of the strategic objectives of the treatment program. We conducted a risk assessment and developed guidelines for the quality management of a schistosomiasis preventive treatment program for children aged 5 years and below in the uMkhanyakude District of KwaZulu-Natal.

Methods

We conducted a scenario planning exercise by interviewing 10 child health experts from the uMkhanyakude Health District to establish potential risks associated with a planned schistosomiasis preventive control treatment program for children aged 5 years old and below. The risks were analyzed using a modified Failure Mode and Effect Analysis (FMEA). An FMEA table was produced to guide the quality management of the planned schistosomiasis preventive control treatment program for children aged 5 years and below in the uMkhanyakude Health District.

Results

We identified potential risks, failure modes and possible failure corrective/preventive measures in the following activities that would be part of the mass treatment of children aged 5 years and below infected with schistosomiasis in the uMkhanyakude District. These included enrolment of children into the treatment program; general health checks; weight and height measurements; administration of drugs; reporting of side effects and monitoring and evaluation.

Conclusion

We were able to use FMEA guide quality management and identify potential risks associated with the planned schistosomiasis preventive treatment program for children aged 5 years old and below in the uMkhanyakude District of KwaZulu-Natal. The FMEA for this program will be useful to the quality management of schistosomiasis preventive treatment programs for this age group in other similar settings.
miR-190-5p in human diseases
Authors: Yu Yue , Cao Xu-Chen
Published: October 2019

miRNAs, a major class of small noncoding RNAs approximately 18–25 nucleotides in length, function by repressing the expression of target genes through binding to complementary sequences in the 3′-UTRs of target genes. Emerging evidence has highlighted their important roles in numerous diseases, including human cancers. Recently, miR-190 has been shown to be dysregulated in various types of human cancers that participates in cancer-related biological processes, including proliferation, apoptosis, metastasis, drug resistance, by regulating associated target genes, and to predict cancer diagnosis and prognosis. In this review, we summarized the roles of miR-190-5p in human diseases, especially in human cancers. Then we classified its target genes in tumorigenesis and progression, which might provide evidence for cancer diagnosis and prognosis, promising tools for cancer treatment, or leads for further investigation.
BLV: lessons on vaccine development
Authors: Abdala Alejandro , Alvarez Irene , Brossel Hélène , Calvinho Luis , Carignano Hugo , Franco Lautaro , Gazon Hélène , Gillissen Christelle , Hamaidia Malik , Hoyos Clotilde , Jacques Jean-Rock , Joris Thomas , Laval Florent , Petersen Marcos , Porquet Florent , Porta Natalia , Ruiz Vanesa , Safari Roghaiyeh , Suárez Archilla Guillermo , Trono Karina , Willems Luc
Published: October 2019

Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.
Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells
Authors: Siegrist Katelyn J. , Reynolds Steven H. , Porter Dale W. , Mercer Robert R. , Bauer Alison K. , Lowry David , Cena Lorenzo , Stueckle Todd A. , Kashon Michael L. , Wiley John , Salisbury Jeffrey L. , Mastovich John , Bunker Kristin , Sparrow Mark , Lupoi Jason S. , Stefaniak Aleksandr B. , Keane Michael J. , Tsuruoka Shuji , Terrones Mauricio , McCawley Michael , Sargent Linda M.
Published: October 2019

Background

The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC).

Results

Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024–2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND.

Conclusions

Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.
Anti-tumor effects of the ethanolic extract of Trichosanthes kirilowii seeds in colorectal cancer
Authors: Park Su Mi , Jeon Sang Kyu , Kim Ok Hyeon , Ahn Jung Yun , Kim Chang-Hyun , Park Sun-Dong , Lee Ju-Hee
Published: October 2019

Background

Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism.

Methods

The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model.

Results

TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice.

Conclusion

Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer.
CyclinD1 inhibits dicer and crucial miRNA expression by chromatin modification to promote the progression of intrahepatic cholangiocarcinoma
Authors: Qi Yongqiang , Wang Da , Huang Wenhua , Wang Bing , Huang Di , Xiong Fei , Chen Xiaoping , Chen Yongjun
Published: October 2019

Background

CyclinD1 is crucial for cell cycling and can regulate the expression of Dicer, a crucial regulator of microRNA maturation. However, little is known on how CyclinD1 regulates Dicer and miRNA expression, and the progression of intrahepatic cholangiocarcinoma (ICC).

Methods

The expression of CyclinD1 and Dicer in non-tumor cholangiocytes, ICC cells and tissues as well as their association with clinicopathological characteristics and survival were examined. The potential mechanisms by which CyclinD1 regulates Dicer and relative miRNA expression were determined by immunoprecipitation, ChIP sequence, BSP and luciferase reporter assays following induction of CyclinD1 over-expression or silencing and Dicer silencing. The impact of CyclinD1 and/or Dicer silencing on the growth of ICC was tested in vivo.

Results

Up-regulated CyclinD1 was associated with down-regulated Dicer expression in ICC tissues and poorer overall survival in patients with ICC. CyclinD1 interacted with the nuclear H3K9me3 and SUV39H1 and bound to the Dicer promoter to increase its CpG island methylation in ICC cells. Functionally, CyclinD1 silencing inhibited the malignancy of ICC cells, which were mitigated partially by Dicer silencing in ICC cells. Dicer silencing down-regulated miR-1914-5p and miR-541-5p expression, which targeted and promoted CyclinD1 and CDK6 expression in ICC cells.

Conclusions

Our findings uncover that CyclinD1 inhibits Dicer expression by chromatin modification to reduce miR-1914-5p/miR-541-5p expression, which positively-feedback enhances CyclinD1 and CDK6 expression and progression of ICC.
Cost analysis and efficacy of recruitment strategies used in a large pragmatic community-based clinical trial targeting low-income seniors: a comparative descriptive analysis
Authors: Kakumanu Sravya , Manns Braden J. , Tran Sophia , Saunders-Smith Terry , Hemmelgarn Brenda R. , Tonelli Marcello , Tsuyuki Ross , Ivers Noah , Southern Danielle , Bakal Jeff , Campbell David J. T.
Published: October 2019

Objective

One of the most challenging parts of running clinical trials is recruiting enough participants. Our objective was to determine which recruitment strategies were effective in reaching specific subgroups.

Study design and setting

We assessed the efficacy and costs of the recruitment strategies used in the Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) in Alberta, Canada.

Results

Twenty percent of the study budget ($354,330 CAD) was spent on recruiting 4013 participants, giving an average cost per enrolled of $88 CAD. Pharmacies recruited the most participants (n = 1217), at a cost of $128/enrolled. ”Paid media” had the highest cost ($806/enrolled), whereas ”word of mouth” and ”unpaid media” had the lowest (~$3/enrolled). Participants enrolled from ”seniors outreach” had the lowest baseline quality of life and income, while participants from ”word of mouth” had the lowest educational attainment.

Conclusion

The ”health care providers” strategies were especially successful — at a moderate cost per enrolled. The "media" strategies were less effective, short lasting, and more costly. No strategy was singularly effective in recruiting our targeted groups, emphasizing the importance of utilizing a variety of strategies to reach recruitment goals.

Trial registration

ClinicalTrials.gov, NCT02579655. Registered on 19 October 2015.
Optimization of pulmonary emphysema quantification on CT scans of COPD patients using hybrid iterative and post processing techniques: correlation with pulmonary function tests
Authors: de Boer E. , Nijholt I. M. , Jansen S. , Edens M. A. , Walen S. , van den Berg J. W. K. , Boomsma M. F.
Published: October 2019

Objectives

The aim of this study was to assess the effect of hybrid iterative reconstruction and post processing on emphysema quantification in low-dose CT scans of COPD patients using pulmonary function tests (PFT) as a reference.

Methods

CT scans of 23 COPD patients diagnosed with GOLD I or higher were reconstructed with iDose4 level 1 to 7 in IntelliSpace Portal (ISP) 6 and 7. ISP7 was used with and without specific denoising filter for COPD. The extent of emphysema was measured as percentage of lung voxels with attenuation < − 950 Hounsfield units (%LAA-950). The correlation between %LAA-950 and PFT, age, BMI, pack years, and the Clinical COPD Questionnaire (CCQ) and Medical Research Council dyspnea scale (MRC) was determined.

Results

Denoising significantly reduced %LAA-950 as was demonstrated by lower %LAA-950 in ISP7 with denoising filter and a significant reduction in %LAA-950 with higher iDose4 levels. All PFT except forced vital capacity (FVC) were significantly inversely correlated with %LAA-950. There was a trend toward a stronger correlation at higher iDose4 levels. %LAA-950 was also significantly correlated with BMI, GOLD class, and CCQ scores.

Conclusions

Our study showed that hybrid iterative reconstruction and use of post processing denoising can optimize the use of emphysema quantification in CT scans as a complimentary diagnostic tool to stage COPD in addition to PFT.
Suppressing immunotherapy by organ-specific tumor microenvironments: what is in the brain?
Authors: Zhang Chenyu , Yu Dihua
Published: October 2019

Recent breakthroughs in cancer immunotherapy have led to curative efficacy and significantly prolonged survival in a subset of patients of multiple cancer types; and immunotherapy has become the newest pillar of cancer treatment in addition to surgery, chemotherapy, radiotherapy and precision targeted therapies. In the metastatic disease setting, responses to immunotherapy are heterogeneous depending on the metastatic organ sites. The tissue-specific immuno-biology in the tumor microenvironments (TMEs) contributes to the differential therapeutic responses. Herein, we review the impact of tissue-specific tumor microenvironment on the efficacy of immunotherapy, with a focus on historically under-represented central nervous system (CNS) metastasis, which was excluded from most clinical trials. Retrospective examination of patient specimens and prospective clinical studies with immune checkpoint blockade (ICB) have established that brain can harbor an “active” immune microenvironment for effective immunotherapy. Regulation by the innate immune microglial cells and remodeling of the blood–brain barrier (BBB) may contribute to immunotherapeutic responses mediated by T lymphocytes. How to convert an “inactive” (cold) brain microenvironment into an “active” (hot) brain TME should be the focus of future efforts. Thus, procurement and complete examination of clinical specimens from brain metastases as well as development of appropriate preclinical brain metastasis models susceptible to external manipulation of the TME are critical steps towards that goal. A deeper understanding of the immuno-biology in distinct organ microenvironments will help to expand the benefits of immunotherapy to more needed patients.
Some Tauberian conditions on logarithmic density
Authors: Kılıçman Adem , Borgohain Stuti , Küçükaslan Mehmet
Published: October 2019

This article is based on the study on the λ-statistical convergence with respect to the logarithmic density and de la Vallee Poussin mean and generalizes some results of logarithmic λ-statistical convergence and logarithmic $(V,\lambda )$
(
V
,
λ
)
-summability theorems. Hardy’s and Landau’s Tauberian theorems to the statistical convergence, which was introduced by Fast long back in 1951, have been extended by J.A. Fridy and M.K. Khan (Proc. Am. Math. Soc. 128:2347–2355, 2000) in recent years. In this article we try to generalize some Tauberian conditions on logarithmic statistical convergence and logarithmic $(V,\lambda )$
(
V
,
λ
)
-statistical convergence, and we find some new results on it.
Existence and multiplicity results for some generalized Hammerstein equations with a parameter
Authors: López-Somoza Lucía , Minhós Feliz
Published: October 2019

This paper considers the existence and multiplicity of fixed points for the integral operator
$$ {\mathcal{T}}u(t)=\lambda \int _{0}^{T}k(t,s) f\bigl(s,u(s),u^{\prime }(s), \dots ,u^{(m)}(s)\bigr) \,\mathrm{d}s,\quad t\in {[} 0,T]\equiv I, $$
T
u
(
t
)
=
λ

∫
0
T

k
(
t
,
s
)
f

(
s
,
u
(
s
)
,

u
′

(
s
)
,
…
,

u

(
m
)

(
s
)
)

d
s
,

t
∈
[
0
,
T
]
≡
I
,
where $\lambda >0$
λ
>
0
is a positive parameter, $k:I\times I\rightarrow \mathbb{R}$
k
:
I
×
I
→
R
is a kernel function such that $k\in W^{m,1} ( I \times I ) $
k
∈

W

m
,
1

(
I
×
I
)
, m is a positive integer with $m\geq 1$
m
≥
1
, and $f:I\times \mathbb{R} ^{m+1}\rightarrow [ 0,+\infty [ $
f
:
I
×

R

m
+
1

→
[
0
,
+
∞
[
is an $\mathrm{L}^{1}$

L
1

-Carathéodory function.

The existence of solutions for these Hammerstein equations is obtained by fixed point index theory on new type of cones. Therefore some assumptions must hold only for, at least, one of the derivatives of the kernel or, even, for the kernel on a subset of the domain. Assuming some asymptotic conditions on the nonlinearity f, we get sufficient conditions for multiplicity of solutions.

Two examples will illustrate the potentialities of the main results, namely the fact that the kernel function and/or some derivatives may only be positive on some subintervals, which can degenerate to a point. Moreover, an application of our method to general Lidstone problems improves the existent results in the literature in this field.
Spectral information to get beyond color in the analysis of water-soluble varnish degradation
Authors: Martínez Domingo M. , Valero E. , Huertas R. , Durbán M. , Espejo T. , Blanc R.
Published: October 2019

Spectral images were captured of paper samples varnished with two water-soluble materials: gum arabic and egg white. The samples were submitted to degradation processes that partially or totally eliminated the varnish from the substrate (water immersion and ageing). The spectral information was used to obtain average color data and to characterize the spatial and color inhomogeneity across pixels, showing that the pixel spectral data are critical for an accurate characterization of the degradation process of the varnishes. Since the varnishes typically become yellower with ageing, this study introduces two novel and simple-to-compute yellowness indices based on the spectral information, which are validated against a standard colorimetric index (ASTM-E313 2015). The potential uses of spectral information are demonstrated with several pieces of a real antique map sample by comparing the spectral information measured before and after cleaning the sample. To sum up, the main contributions of this study are the characterization of the spatial homogeneity through pixel-based spectral and color information and the proposal of spectral-based yellowing indices for two critical applications (ageing process follow-up and effect of cleaning), as demonstrated with synthetic and historical samples of varnished paper respectively.
Innovative Professional Development and Community Building Activity Program Improves STEM URM Graduate Student Experiences
Authors: Moreira Rosana G. , Butler-Purry Karen , Carter-Sowell Adrienne , Walton Shannon , Juranek Isah V. , Challoo Linda , Regisford Gloria , Coffin Richard , Spaulding Angela
Published: October 2019

Background

Strong consensus exists on the need to expand participation of URM doctoral students in STEM fields, to increase their retention, reduce their average time to degree, and provide these students with the preparation necessary to compete for faculty positions. This paper provides a model for implementing effective strategies to support the success of URM STEM graduate students across a system with various types of institutions. An innovative professional development, participation incentive, and community building program for underrepresented minority (URM) Graduate students in STEM (science, technology, engineering, and mathematics) fields was instrumental in preparing them to secure academic positions, navigating graduate school successfully, and form a support network that helped them excel at the next level. The program provided sustained support and several activities in a collaborative environment for 84 Ph.D. and 84 Master’s students, in over 43 graduate programs. Data were collected using evaluation questionnaires containing open-ended responses and responses to specific items sent to the students after each activity, and a survey seeking their feedback on the program.

Results

In only 4 years, the program helped 13 students to secure faculty or post-doctoral positions, and improved the opinion of the professoriate career as thirteen students transitioned to the Ph.D. program and are now more interested in applying for faculty positions. The program was successful in developing and sustaining large-scale, distributed, yet interconnected STEM communities among the diverse Alliance system institutions and increased participation (from 58 in 2013 to 98 in 2017), reduced barriers, and promoted the success of URM doctoral students preparing for careers in the professoriate.

Conclusions

We have developed activities that connected students and faculty across institutions, providing multiple paths to the professoriate that align with students’ diverse academic career aspirations. This article illustrates that professional development, incentives, and community building interventions are essential in generating URM STEM education transformation.
Seasonal prevalence and histopathology of Beauveria bassiana infecting larvae of the leopard moth, Zeuzera pyrina L. (Lepidoptera: Cossidae)
Authors: Ibrahim Reda , Alahmadi Saeed , Binnaser Yaser S. , Shawer Dalia
Published: October 2019

The natural epizootic potential of the fungus, Beauveria bassiana, against larvae of the leopard moth, Zeuzera pyrina L. (Lepidoptera: Cossidae) was investigated under natural conditions in two different locations for two seasons (2015–2016 and 2016–2017) in Rasheed, Behiara Governorate, Egypt. In an orchard, located in the old cultivated land, Beauveria infected 1.9–5.6% of larvae of Z. pyrina in autumn (September to November), increased to 3.4–7.2% in winter (December to February). The infection did not exceed 3.1% in spring (March to May), and no infection was recorded in summer (June to August). While in an olive farm, located in a newly reclaimed land, in both seasons of survey, no infections were recorded from May to September, while in winter, the epizootics ranged from 1.4–3.1%, from 0.4 to 1.3% in spring, and from 0.3 to 2.1% in autumn. Histopathological analysis revealed that Beauveria most commonly penetrated larvae directly through the intersegmental integument and the first symptoms were observed 3 to 4 days later. Hyphae radiated inward from the point of ingress and the fungus developed sparsely within the body cavity prior to the death of the larva. Hyphal bodies were concentrated around the point of ingress, but some were found at distance from this site. Only in the vicinity of penetration, the hypodermis showed signs of histolysis. The saprophytic phase developed rapidly and the fungus invaded all internal organs. The conidiophores seemed to rupture the cuticle by mechanical pressure and emerged all over the host cadaver, with sporulation occurring 48 h later. Pathological changes in the hemolymph appeared to be the primary cause of larval mortality.