bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering miRNAs involved in crosstalk between auxin and cold stress in Arabidopsis roots
Authors: Aslam Mohammad , Sugita Kenji , Qin Yuan , Rahman Abidur
Published: August 2020

Background: The phytohormone auxin and microRNA-mediated regulation of gene expressions are key regulators for plant growth and development at both optimal and under low-temperature stress conditions. However, the mechanistic link between microRNA and auxin in regulating plant cold stress response remains elusive. Results: To better understand the role of microRNA in the crosstalk between auxin and cold stress responses, we took advantage of the mutants of Arabidopsis thaliana with altered response to auxin transport and signal. Screening of the mutants for root growth recovery after cold stress at 4°C revealed that the auxin signaling mutant, solitary root 1 ( slr1; mutation in Aux/IAA14), shows a hypersensitive response to cold stress. Genome-wide expression analysis of miRNA in wild-type and slr1 mutant roots using next-generation sequencing revealed 180 known and 71 novel cold-responsive microRNAs. Cold stress also increased the abundance of 26 nt-31 nt small RNA population in slr1 compared with wild-type. Comparative analysis of microRNA expression shows significant differential expression of 13 known and 7 novel miRNAs in slr1 at 4°C compared with wild-type. Target gene expression analysis of the members from one potential candidate miRNAs, miR169 revealed the possible involvement of miR169- NF-YA module in the auxin-mediated cold stress response. Conclusions: Taken together, these results indicate that SLR/IAA14, a transcriptional repressor of auxin signaling, plays a crucial role in integrating miRNA in auxin and cold responses.
Effects of circadian clock and light on melatonin concentration in Hypericum perforatum L. (St. John’s Wort)
Authors: Ming-Hsiu Chung , Deng Tzu-Shing
Published: August 2020

Background

Melatonin acts as a signaling hormone and entraining agent in many organisms. We studied the spatiotemporal regulation and influence of light (photoperiods, intensities, and spectral qualities) on melatonin concentration in the medicinal herb Hypericum perforatum L. Furthermore, melatonin concentrations in the leaves of eight species of the Hypericum genus were compared and analyzed using high-performance liquid chromatography.

Results

Melatonin concentration was found to be the highest in its flowers and leaves. The leaves exhibited a rhythmic variation in melatonin concentration of approximately 24 h under both light–dark entrained (Zeitgeber time) and constant light [circadian time (CT)] conditions, with melatonin concentration peaking at approximately CT6 in the middle of the subjective day. Melatonin concentration was influenced significantly by not only photoperiods but also applied light’s wavelength and intensity. It was approximately six times higher under long-day conditions (18-h light:6-h dark) than under short-day photoperiods (10-h light:14-h dark) and was the highest (131 μg/g fresh weight [FW]) under treatment with blue light at an intensity of 45 µmol·m 2 /s of photons. The melatonin concentration of the two examined Hypericum spp. , namely H. kouytchense Lev. and H. coris L., were approximately twice that of H. perforatum L.

Conclusion

Our findings provide first insights on melatonin-related functions and mechanisms in the circadian system of H. perforatum and useful resources for further melatonin-oriented research and possible applications in agriculture and pharmaceutical industries.
Evaluation of 68Ga-PSMA PET/CT Images Acquired with a Reduced Scan Time Duration in Prostate Cancer Patients using the Digital Biograph Vision
Authors: Weber Manuel , Hofferber Regina , Herrmann Ken , Fendler Wolfgang Peter , Conti Maurizio , Wetter Axel , Kersting David , Rischpler Christoph , Jentzen Walter , Costa Pedro Fragoso
Published: August 2020

Aim: 68Ga-PSMA PET/CT allows for a superior detection of prostate cancer tissue, especially in the context of a low tumor burden. Digital PET/CT bears the potential of reducing scan time duration / administered tracer activity due to, for instance, its higher sensitivity and improved time coincidence resolution. It might thereby expand 68Ga-PSMA PET/CT that is currently limited by 68Ge/68Ga-generator yield. Our aim was to clinically evaluate the influence of a reduced scan time duration in combination with different image reconstruction algorithms on the diagnostic performance.Methods: Twenty prostate cancer patients (11 for biochemical recurrence, 5 for initial staging, 4 for metastatic disease) sequentially underwent 68Ga-PSMA PET/CT on a digital Siemens Biograph Vision. PET data were collected in continuous-bed-motion mode with a mean scan time duration of 16.7 min (reference acquisition protocol) and 4.6 min (reduced acquisition protocol). 4 iterative reconstruction algorithms were applied using a time-of-flight (TOF) approach alone or combined with point-spread-function (PSF) correction, each with 2 or 4 iterations. To evaluate the diagnostic performance, the following metrics were chosen: (a) per-region detectability, (b) the tumor maximum and peak standardized uptake values (SUVmax and SUVpeak) and (c) image noise using the liver’s activity distribution.Results: Overall, 98% of regions (91% of affected regions) were correctly classified in the reduced acquisition protocol independent of the image reconstruction algorithm. Two nodal lesions (each ≤4 mm) were not identified (leading to downstaging in 1/20 cases). Mean absolute percentage deviation of SUVmax (SUVpeak) was approximately 9% (6%) for each reconstruction algorithm. The mean image noise increased from 13% to 21% (4 iterations) and from 10% to 15% (2 iterations) for PSF+TOF and TOF images.Conclusions: High agreement at 3.5-fold reduction of scan time in terms of per-region detection (98 % of regions) and image quantification (mean deviation ≤ 10 %) was demonstrated; however, small lesions can be missed in about 10% of patients leading to downstaging (T1N0M0 instead of T1N1M0) in 5 % of patients. Our results suggest that a reduction of scan time duration or administered 68Ga-PSMA activities can be considered in metastatic patients, where missing small lesions would not impact patient management. Limitations include the small and heterogeneous sample size and the lack of follow-up.
Multidisciplinary Approach to Enhancing Provider Well-Being in a Metropolitan Medical Group in the United States
Authors: Shields Lisa Barbara , Jennings James T. , Honaker Joshua T.
Published: August 2020

Background: Physician burnout refers to depersonalization, emotional exhaustion, and a sense of lower personal accomplishment. Affecting approximately 50% of physicians in the United States, physician burnout negatively impacts both the physician and patient. Over a 3-year-period, this prospective study evaluated the multidisciplinary approach to decreasing provider burnout and improving provider well-being in our metropolitan community. Methods: A multidisciplinary Well-Being Task Force was established at our Institution in 2017 to assess the myriad factors that may play a role in provider burnout and offer solutions to mitigate the stressors that may lead to decreased provider well-being. Four multifaceted strategies were implemented: (1) provider engagement & growth; (2) workflow/office efficiencies; (3) relationship building; and (4) communication. Providers at our Institution took the Mayo Clinic’s well-being index survey on 3 occasions over 3 years. Their scores were compared to those of providers nationally at baseline and at 1 and 2 years after implementing organizational and individualized techniques to enhance provider well-being. Lower well-being index scores reflected better well-being. Results: The average overall well-being index scores of our Institution’s providers decreased from 1.76 at baseline to 1.32 2 years later compared to an increase in well-being index scores of physicians nationally (1.73 to 1.85). Both male and female providers’ average well-being index scores at our Institution decreased over the 3 years of this study, from 1.72 to 1.58 for males and 1.78 to 1.21 for females, while physicians’ scores nationally increased for both genders. The average well-being index scores were highest for providers at our Institution who graduated from medical school less than 5 years earlier (2.0) and who graduated 15-24 years earlier (2.3), whereas the average lowest scores were observed in providers who graduated ³ 25 years earlier (1.37). Obstetricians/gynecologists and internal medicine physicians had the highest average well-being index scores (2.48 and 2.4, respectively) compared to other medical specialties. The turnover rate of our Institution’s providers was 5.6% in 2017 and 3.9% in 2019, reflecting a 30% decrease. Conclusion: This study serves as a model to reduce provider burnout and enhance well-being through both organizational and individual interventions.
Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study
Authors: Liu Qiang , Hebert James R. , Shivappa Nitin , Guo Jianjun , Tao Ke , Zeng Chao , Lei Guanghua , Lin Jianhao , Zhang Yuqing
Published: August 2020

Background To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest. Methods In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DIITM) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident: (1) radiographic knee OA (ROA) (i.e., a KL grade ≥2), (2) symptomatic knee OA (SxOA) (i.e., a combination of a frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess potential mediation by BMI in the DII-OA relation. Results Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI): 1.15 to 2.62, Ptrend= 0.007). The corresponding OR for SxOA was 1.43 (95% CI: 1.16 to 1.76, Ptrend = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI: 1.04,1.13) for ROA and 1.13 (95% CI: 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of total effect, respectively. Conclusions A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting inflammatory potential of diet may be beneficial to reduce risk of knee OA.
Social determinants of male partner involvement in women's Prevention of Mother to Child Transmission care Program in Malawi
Authors: Triulzi Isotta , Keiser Olivia , Somerville Claire , Salimu Sangwani , Ciccacci Fausto , Palla Ilaria , Sagno Jean Baptiste , Gondwe Jane , Marazzi Cristina , Orlando Stefano , Palombi Leonardo , Turchetti Giuseppe
Published: August 2020

Background

Male partners are rarely present during PMTCT (Prevention-Mother-To-Child-Transmission) services in Sub-Saharan Africa (SSA). Men’s involvement is increasingly recognised as an important element of women’s access to care. This study aims to identify the socio-demographic characteristics, HIV-Knowledge, Attitude and Practice (KAP) among women accompanied and not accompanied by their male partners.

Methods
We included pregnant women enrolled in PMTCT programme between August 2018 and November 2019 in the Southern Region of Malawi. Eligible women were aged 18 years or older, living with a male partner, enrolled for the first time in one of the four selected facilities. We provided a KAP survey to women and their partners attending the facilities. Our primary objective was to assess and analyse the proportion of women who were accompanied by their partner at least once. We applied descriptive statistics and logistic regressions to study the association between being accompanied and explanatory variables.

Results
We enrolled 128 HIV-positive women: 82 (64.1%) were accompanied by their male partners and 46 (35.9%) were alone. Women’s unemployment and possession of a vehicle are negatively associated with male attendance (respectively adjusted OR 0.32 [95% CI, 0.13-0.83] and 0.23 [95% CI, 0.07-0.77]), whereas high women’s level of knowledge of HIV is positively associated with male attendance (adjusted OR 2.33 [95% CI, 1.01-5.40]). Level of attitude and practice toward HIV were not significantly associated to our study variable.

Conclusions
Our study shows a high male involvement in Malawi compared to other studies performed in SSA. This study highlights the factors affecting male attendance which are women’s level of knowledge on HIV, economic condition (employment and means of transport) and healthcare system inequality including geographical accessibility. Moreover, the study points out that gender power relationships and stringent gender norms play a crucial role thus they should be considered to enhance male involvement.
Establishment of assay method- and trimester-specific reference intervals for thyroid hormones during pregnancy in Chengdu, China
Authors: Huang Cheng , Wu Ying , Chen Linong , Yuan Zhiya , Yang Shuzhe , Liu Chenggui
Published: August 2020

Background: The reference intervals of thyroid hormone will change at different stages of pregnancy because of physiological alterations. On the other hand, the reference intervals of hyroid hormone will also change in different detection systems due to manufacturer’s methodology as well as different race. The objective in this study was to establish the assay method- and trimester-specific reference intervals for thyroid stimulating hormone, free thyroxine, and free triiodothyronine for pregnant women in the Chengdu.Methods: A prospective, population-based cohort study involved 23701 reference samples of pregnant women during the three trimesters and 8646 non-pregnant women with pre-pregnancy clinical and laboratory tests. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid stimulating hormone, free thyroxine, and free triiodothyronine at each trimester of pregnant women according to ATA Guidelines.Results: The reference interval of thyroid stimulating hormone in the 2.5th and 97.5th percentiles has a significant increasing trend from first trimester, to second trimester, and to third trimester, which was 0.08-3.79 mIU/L for first trimester, and 0.12-3.95 mIU/L for second trimester, and 0.38-4.18 mIU/L for third trimester, respectively (P < 0.001). However, the reference intervals of free thyroxine and free triiodothyronine in the 2.5th and 97.5th percentiles have significant decreasing trends from first trimester, to second trimester, and to third trimester, which were 11.87-18.83 pmol/L and 3.77-5.50 pmol/L for first trimester, and 11.22-18.19 pmol/L and 3.60-5.41 pmol/L for second trimester, and 10.19-17.42 pmol/L and 3.37-4.79 pmol/L for third trimester, respectively (both P < 0.001).Conclusion: It is necessary to establish assay method- and trimester-specific reference intervals for thyroid stimulating hormone, free thyroxine, and free triiodothyronine because the reference intervals of these thyroid hormones are significantly different at different stages of pregnancy.
Real-time PCR on skin biopsies for super-spreaders’ detection in bovine besnoitiosis.
Authors: Grisez Christelle , Bottari Leslie , Prévot Françoise , Alzieu Jean-Pierre , Liénard Emmanuel , Corbière Fabien , Rameil Marie , Desclaux Xavier , Lacz Christophe , Boulon Christian , Petermann Julie , Mével Jeanne Le , Vilardell Carine , Jacquiet Philippe
Published: August 2020

Background: Bovine besnoitiosis, an emerging disease in Europe that can be transmitted by vectors, is caused by the Apicomplexa Besnoitia besnoiti. Bovine besnoitiosis is difficult to control due to the complexity of its diagnosis in the acute stage of the disease, poor treatment success and chronically asymptomatic cattle acting as parasite reservoirs. When serological prevalence is low, detection and specific culling of seropositive cattle is feasible; however, economic considerations preclude this approach when serological prevalence is high. The aims of this study were to evaluate the accuracy of detection of super-spreaders in highly infected herds and to test their selective elimination as a new control strategy for bovine besnoitiosis. Methods: Previous real-time PCR analyses performed on skin tissues from 160 asymptomatic animals sampled at slaughterhouses showed that the tail base was the best location to evaluate the dermal parasite DNA load. All seropositive animals (N = 518) from eight dairy or beef cattle farms facing a high serological prevalence of besnoitiosis were sampled at the tail base and their skin sample analysed by real-time PCR. A recommendation of rapid and selective culling of super-spreaders was formulated and provided to the cattle breeders. Subsequent serological monitoring of naïve animals was used to evaluate the interest of this control strategy over time.Results: Among the 518 seropositive animals, a low proportion of individuals (14.5%) showed Ct values below 36, 17.8% had doubtful results (36 < Ct ≤ 40) and 67.8% had negative PCR results. These proportions were grossly similar on the eight farms, regardless of their production type (beef or dairy cattle), size, geographic location or history of besnoitiosis. Within two weeks of the biopsy, the rapid culling of super-spreaders was implemented on only three farms. The numbers of newly infected animals were lower on these farms compared to those where super-spreaders were maintained in the herd. Conclusions: Real-time PCR analyses performed on skin biopsies of seropositive cattle showed huge individual variabilities in parasite DNA load. The rapid culling of individuals considered as super-spreaders seems to be a new and encouraging strategy for bovine besnoitiosis control.
Baseline total metabolic tumor volume combined with international peripheral T-cell lymphoma project may improve prognostic stratification for patients with peripheral T-cell lymphoma (PTCL)
Authors: Jiang Chong , Teng Yue , Chen Jieyu , Wang Zhen , Zhou Zhengyang , Ding Chongyang , Xu Jingyan
Published: August 2020

Purpose: The aim of this study was to explore the prognostic value of total metabolic tumor volume (TMTV) at baseline 18F-FDG PET/CT in patients diagnosed with peripheral T-cell lymphoma (PTCL).Materials and methods: Eighty-four newly diagnosed PTCL patients who underwent baseline 18F-FDG PET/CT prior to treatment between March 2009 and January 2019 were enrolled in this retrospective study. The FDG-avid lesions in each patient were segmented using semiautomated software to calculate the maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) values using the boundaries of voxels presenting with the 41% SUVmax threshold method. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate patient prognosis. The log-rank test and Cox regression analyses were used to evaluate PFS and OS.Results: ROC curve analysis indicated an ideal TMTV cut-off value of 228.8 cm3. During the 4-131 month (29.2±28.5 months) follow-up period, high TMTV was significantly associated with worse PFS and OS. TMTV and the international peripheral T-cell lymphoma project score (IPTCLP) were independent predictors of PFS and OS with multivariate analysis. The combination of TMTV and the IPTCLP may provide significantly better risk substratification in PFS and OS of PTCL patients.Conclusions: Both TMTV and IPTCLP are independent predictors of PTCL patient survival outcomes. Moreover, the combination of TMTV and IPTCLP improved patient risk stratification and may contribute to personalized therapeutic regimens.
Thoughts on Higher Medical Education Under Major Public Health Emergencies: Thinking Ahead After COVID-19 Outbreak — A Descriptive study
Authors: Lin Wei , Chen Yan , Shi Songchang , Liang Jixing , Huang Huibin , Li Liantao , Cai Liangchun , Zong Liyao , Wang Nengying , Wen Junping , Chen Gang
Published: August 2020

Background

The spread of coronavirus disease 2019 (COVID-19) has posed great threat to the global population’s health and nearly every medical school throughout the world suspended classes as a precaution against the virus. The aim of this research is to explore a more advanced online teaching and learning pattern for medical school in the future especially during a Public Health Emergency of International Concern (PHEIC).
Methods

This is a descriptive study conducted in a medical school. We applied a new blended teaching model, that is, online TBL via 5G network (hereinafter referred as blended teaching model) before the outbreak and when universities responded to the COVID-19 outbreak by closing campuses, they shifted to home-based online learning which is not based on TBL via other prevalent forms of wireless internet connection(hereinafter referred as traditional online teaching model). Fifty fourth-year medical students receiving the “5 + 3” pattern courses regarding internal medicine were enrolled in the study. A five-point Likert scale questionnaire that contains 20 items was used to compare the effect of the two kinds of teaching patterns. It evaluated the indicators of core competencies of students including professionalism, attitude towards learning, knowledge and learning skills, teamwork skills, motivation in learning, adaptability and acceptance of the courses and network environment.
Results

According to the descriptive statistical analysis of the first part of the questionnaire (question 1–16), the average score of adaptability and acceptance of the courses is 2.60 less than 3, indicating that students are more adapted to traditional online teaching model; the average score of the rest of the questions is greater than 3, indicating that blended teaching model is superior to traditional online teaching model. The number of male students who are inclined to blended teaching model is 0.13 times as much as that of female students (95%CI:0.028 ~ 0.602, p = 0.009).
Conclusion

Blended teaching model makes up for some deficiencies of the traditional online teaching methods. For instance, it can monitor students’ learning efficiency and test their real-time learning effectiveness; 5G network meets the requirement of multiple user access in the online TBL. It is a more advanced online teaching and learning pattern for medical school and may be a more suitable method during PHEIC in the future. However, as the students can hardly quickly adapt to this new model, teachers should change their ideas to form a "student-centered" teaching concept, acquire more knowledge of online teaching, and get fully prepared for online TBL before class to ensure a better study experience.
Reconstruction of massive tibial bone and soft-tissue defects by trifocal bone transport combined with soft-tissue transport: experience from 31 cases
Authors: Xu Yong-Qing , Fan Xin-Yu , He Xiao-Qing , Wen Hong Jie
Published: August 2020

Background The study was designed to investigate the safety and efficacy of trifocal bone transport (TFT) and soft-tissue transport with the Ilizarov technique for large posttraumatic tibial bone and soft tissue defects. Methods We retrospectively reviewed 31 patients with massive posttraumatic tibial bone and soft tissue defects from May 2009 to May 2016. All of the eligible patients were managed by TFT and soft-tissue transport. The median age was 33.4 years (range, 2-58 years). The mean defect of bone was 11.87cm ± 2.78cm (range, 8.2-18.2cm) after radical resection performed by TFT. The soft tissue defects ranged from 7cm x 8cm to 24cm x 12cm. The observed results included bone union time, wound close time and true complications. The Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system was used to assess bone and functional results and postoperative complications were evaluated by Paley classification. Results The mean duration of follow-up after frame removal was 32 months (range, 12-96 months). All cases achieved complete union in both the elongation sites and the docking sites, and eradication of infection. The mean bone transport time was 94.04 ± 23.33 days (range, 63.7-147 days). The mean external fixation time was 22.74 ± 6.82 months (range, 14-37 months), and the mean external fixation index (EFI) was 1.91 ± 0.3 months/cm (range, 1.2–2.5 months/cm). The bone results were excellent in 6 patients, good in 14 patients, fair in 8 patients and poor in 3 patients. The functional results were excellent in 8 patients, good in 15 patients, fair in 5 patients and poor in 3 patients. Conclusion The TFT in concert with soft-tissue transport technique can be used successfully to manage large tibial bone and soft-tissue defects. Soft-tissue transport can offer a feasible method for the defects with good soft tissue coverage on the bone ends. However, imprecision in the series results precludes a definitive conclusion, and comparative study is needed to assess whether soft-tissue transport is more effective than flap transfer for such soft-tissue defect.
Assessing Functional Diversity-Productivity Relationships in Temperate Forests in Northern Mexico
Authors: Vargas-Larreta Benedicto , López-Martínez Jorge O. , Corral-Rivas Jose Javier , Hernández Francisco Javier
Published: August 2020

Background: Studies on the relationships between biodiversity and ecosystem productivity have suggested that species richness and functional diversity are the main drivers of ecosystem processes. There is no general pattern regarding the relationship found in various studies, and positive, unimodal, negative, and neutral relationships keep the issue controversial. In this study, taxonomic diversity vs functional diversity as drivers of above-ground biomass were compared, and the mechanisms that influence biomass production were investigated by testing the complementarity and the mass-ratio hypoteses.Methods: Using data from 414 permanent sampling plots, covering 23% of temperate forests in the Sierra Madre Occiental (Mexico), we estimated the above-ground biomass (AGB) for trees ≥7.5 cm d.b.h. in managed and unmanaged stands. We evaluated AGB-diversity relationships (species richness, Shannon-Wiener and Simpson indices), AGB-weighted mean community values ​​(CWM) of tree species functional traits (maximum height, leaf size, and wood density) and five measures of functional diversity (functional dispersion, functional richness, functional uniformity, functional diversity, and RaoQ index).Results: We reveal a consistent hump-shaped relationship between aboveground biomass and species richness in managen and unmanaged forest. CWM_Hmax was the most important predictor of AGB in both managed and unmanaged stands, which suggests that the mechanism that explains the above-ground biomass in these ecosystems is dominated by certain highly productive species in accordance of the mass-ratio hypothesis. There were no significant relationships between taxonomic diversity metrics (Shannon-Wiener and Simpson indices) or measures of functional diversity with AGB. The results support the mass-ratio hypothesis to explain the AGB variations.Conclusions: We concluded that diversity does not influence biomass production in the temperate mixed-species and uneven-aged forests of northern Mexico. These forests showed the classic hump-shaped productivity-species richness relationship, with biomass accumulation increasing at low to intermediate levels of species plant diversity and decreasing at high species richness. Functional diversity explains better forest productivity than classical diversity metrics.
Relationship Between Cartilage Oligomeric Matrix Protein Level and Helper T Cell 17/regulatory T Cell Balance in Patients With Rheumatoid Arthritis
Authors: HAN Rong
Published: August 2020

Objective To explore the correlation among the level of cartilage oligomeric matrix protein(COMP) as well as the balancing relationship of helper T cell 17(Th17) /regulatory T cells(Treg) of serum in patients with Rheumatoid Arthritis (RA). Methods 40 patients with RA in the Second Hospital of Shanxi Medical University from May 2019 to May 2020 were selected as RA group, while 40 healthy subjects were collected as a control group. After collecting their serum, the figure of Th17, as well as Treg cells, were encountered by flow cytometry(FC), and the proportion of Th17/Treg was counted. Cytometric was also used to detect serum interleukin(IL)-17, IL-10 and IL-6 concentration. Enzyme-linked immunosorbent (ELISA)was also applied to track down the concentrations of COMP as well as tumor necrosis factor-α(TNF-α). All indicators above were considered among groups, and the interrelationship between COMP and the expression of various cells as well as related cytokines was analyzed. Results The concentration of COMP, Th17 and Th17/Treg in RA group were higher than those in the control group, while Treg was lower than that in the control group, and the variation was statistically weighty(P<0.05). The levels of IL-17, IL-6 and TNF-α in RA group were higher than those in the control group, while the concentration of IL-2 was smaller than that of the control group, the differences were statistically weighty(P<0.01). Interrelationship analysis displayed that COMP was undeniably correlated with Th17, Th17/Treg, IL-17, IL-6 as well as TNF-α levels(r =0.687, 0.478, 0.759, 0.903, 0.813, all P<0.01). There was a negative correlation between the levels of COMP and Treg, IL-2(r =-0.356, -0.455, all P<0.01). Conclusion Compared with healthy people, COMP in peripheral blood of patients with RA is abnormally high, and there is obvious T cell immune abnormality, suggesting that COMP may participate in the development of RA by regulating Th17/Treg balance.
Effects of a two-year health-enhancing physical activity program on skeletal muscle protein profiles in people with rheumatoid arthritis
Authors: Ossipova Elena , Idborg Helena , Fridén Cecilia , Jakobsson Per-Johan , Kosek Eva , Malm Christer , Nordgren Birgitta , Opava Christina , Tegner Yelverton , Vanluyten Jone , Korotkova Marina , Lundberg Ingrid
Published: August 2020

Background

Rheumatoid arthritis (RA) induces loss of muscle mass and impairments, which discourage physical activity. Consequently, RA is associated with decreased levels of exercise. Positive effects of exercise on physical and mental health without increasing pain or disease activity have been demonstrated but the influence of moderate-intensity physical activity on the molecular effects in skeletal muscle in people with RA remains unclear. In this pilot study we investigated the impact of a two-year health-enhancing physical activity (HEPA) program on protein profiles in skeletal muscle biopsies from people with RA based on a unique set of interdisciplinary variables.
Methods

Six people with RA participated. Muscle biopsies were taken from m. vastus lateralis, and perceived disease impact, anthropometrics and physical capacity tests were assessed at baseline and year 1 and 2. Mass spectrometry-based quantitative proteomics and immunohistochemistry analysis were employed to examine molecular changes in the skeletal muscle in response to long-term HEPA.
Results

The study participants had moderate to low adherence to the HEPA program, the perceived disease impact and anthropometric parameters were not altered. Among the physical capacity tests, the Timed-stands test showed a significant improvement after one year. Mean pressure pain threshold was significantly reduced after 1- and 2-year HEPA participation. Proteome analysis of the muscle biopsies showed an up-regulation of proteins in the mitochondrial respiratory chain and predicted increased ATP production and improved muscle contractility in response to HEPA. Molecular pathways identified by proteome analysis revealed correlations to pain variables.
Conclusions

Our results indicate that long-term physical activity in people with RA may up-regulate proteins in the mitochondrial respiratory chain predicting increased ATP production and muscle contractility similar to what has been reported in healthy young men and might have a positive impact on muscle tissue by decreased muscle cell death.
Breast Cancer in Togolese Women: Immunohistochemistry Subtypes
Authors: ADANI-IFE Ablavi , AMEGBOR Koffi , DOH Kwamé , DARRE Tchin
Published: August 2020

Background
Molecular classification of breast cancer is an important factor for prognostic and clinical outcome. There are no data regarding molecular breast cancer subtypes among Togolese women. The objective of this study was to evaluate the expression of ER, PR, HER2 and molecular subtypes of breast cancer receptor in Togolese patients and to establish the correlation between clinical and histological data and molecular types.
Methods
Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR and HER2) were assessed in patients who have been diagnosed with invasive breast cancer from March 2016 to March 2020 in the department of oncology. The analysis of variance and the Chi-square Test were used to analyze the data.
Results
A total of 117 cases were collected. Mean age of patients was 52.05 ± 12.38 with an age range of 30 to 85 years. Half of patients were over 50 years old and majority (70.9%) was postmenopausal. More than half of patients (52.1%) presented with T3-T4tumors.The most common histologic subtype of breast cancer was invasive ductal carcinoma of no special type (95.7%). Tumors grade 2 were predominant (51.3%) followed by grade 3 (42.7%). Advanced carcinomas were found in 69 patients (59%). The percentage of ER+, PR + and HER2 positive tumors was 50.4%, 37.6% and 15.4% respectively. The predominant molecular subtype was Luminal A (42.7%) followed by Triple negative (41.9%), Luminal B subtype (9.4%) and HER2 enriched (6%). There was significant association between tumor size and breast cancer subtypes (p = 0.026) but no correlation was found with age, stage, menopausal status and histologic grade.
Conclusion
Breast carcinoma in our patients are high grade tumors and are diagnosed at advanced stage. Luminal A and triple negative are the two predominant breast cancer subtypes in Togolese women. Consequently, Receptor testing availability should be a priority in order to offer the best breast cancer treatment.
A Microdose Clinical Trial to Evaluate 64Cu-NOTA-Trastuzumab as a Positron Emission Tomography Imaging Agent in Patients with Breast Cancer
Authors: Lee Inki , Lim Ilhan , Byun Byung Hyun , Kim Byung Il , Choi Chang Woon , Woo Sang-Keun , Kim Kwang Il , Lee Kyo Chul , Kang Joo Hyun , Seong Min-Ki , Kim Hyun-Ah , Noh Woo Chul , Lim Sang Moo
Published: August 2020

Background: The purpose of this study was to evaluate the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labelled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.Methods: PET images at 1, 24, and 48 hours after injection of 296 MBq of 64Cu-NOTA-Trastuzumab were obtained on seven patients with breast cancer. The maximum standardized uptake value (SUVmax) was evaluated in the tumors, including the primary tumor and metastatic lesions. The mean SUVmax (SUVmean) was evaluated in the normal organs including the blood pool, liver, kidney, muscle, spleen, bladder, lung, and bone. In addition, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed by gathering the feedback of adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration.Results: The overall values of SUVmean in each normal organ decreased with time on 64Cu-NOTA-Trastuzumab PET images. The average values of SUVmean of the liver were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 hour, 24 hours, and 48 hours after injection. The average values of SUVmean of the blood were evaluated as 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 hour, 24 hours, and 48 hours after injection. The SUVmax of HER2-positive tumors showed relatively higher than that of HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 hours after injection, respectively). Tumor to background ratios were calculated higher in the HER2-positive tumors than those of HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq).Conclusions: 64Cu-NOTA-Trastuzumab showed specific uptake at the HER2-expressing tumors. It suggests that 64Cu-NOTA-Trastuzumab can be a feasible monitoring tool for HER2 tumor status in the patients with breast cancer with safe.Trial registration: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr
Systemic Inflammation Causes Microglial Dysfunction with a Mixed AD-Like Pathology.
Authors: Bathini Praveen , Dupanloup Isabel , Zennaro Elena , Terrabuio Eleonora , Fisher Amrei , Babaliani Edona , Doucey Marie-Agnes , Alberi Lavinia
Published: August 2020

Background Alzheimer's disease (AD) is the primary cause of cognitive deficit in elderly humans. Late-onset AD (LOAD) is sporadic, multifactorial, non-Mendelian accounting at present for 95% of the cases in contrast to the genetic form. Risk factors for sporadic AD include Gene: Environment interactions. There is increasing evidence that lifestyle and environmental stress such as infection and chronic inflammation are underlying culprits of neurodegenerative dementia. To date, very few mouse models reproduce the pathophysiological progression of sporadic AD, while the majority of studies have employed transgenic animals reproducing the familial form. Methods We have re-engineered the Polyinosinic:polycytidylic acid (PolyI:C) sterile infection model in wildtype C57Bl6 mice to obtain chronic low-grade systemic inflammation. We have conducted a cross-sectional analysis of aging PolyI:C and Saline control mice (3 months, 6 months, 9 months and 16 months), taking the hippocampus as a reference brain region, based on its vulnerability, and compared the brain aging phenotype to AD progression in humans with mild AD, severe AD and Controls (CTL). Results We found that PolyI:C mice display both peripheral and central inflammation with a peak at 6 months, associated with memory deficits. The hippocampus is characterized by a pronounced and progressive tauopathy. In PolyI:C brains, microglia undergo aging-dependent morphological rearrangements progressively adopting a phagocytic phenotype. Transcriptomic analysis reveals a profound change in gene expression over the course of aging, with a peak in differential expression at 9 months. We confirm that the proinflammatory marker Lcn2 is one of the genes with the strongest upregulation in PolyI:C mice upon aging. Validation in brains from patients with increasing severity of AD shows a general tendency of the genes to decline except for GFAP. Conclusions The PolyI:C model of sterile infection demonstrates that peripheral chronic inflammation is sufficient to cause neuropathological processes resembling a mixed-AD, with progressive tau hyperphosphorylation, changes in microglia morphology, and gene reprogramming reflecting the increased neuroinflammation and the loss of neuronal functionality seen to some extent in humans.
Communication Skills of Resident Physicians in Aseer Region, Saudi Arabia
Authors: Habbash Asma Saad , Siddiqui Aesha Farheen
Published: August 2020

Background: Effective communication improves patient-physician relationship and the overall quality of care. Objectives: The aim of this study was to evaluate communication skills of resident physicians at different health care facilities in Abha, Saudi Arabia.Methods: A cross-sectional, questionnaire-based study on a total of 210 resident doctors.Results: The communication skills scores were nearly normally distributed with a mean score of 113.30 ± 32.25.In comparing the skills by various socio-demographic factors, it was noted that gender and age played a significant role in specific communication skills. There was significant difference in mean scores of younger and older physicians in domains of interpretation and clarification (p < 0.001), asking (p < 0.001), feedback (p < 0.01), punishment and reward skills (p < 0.001). In asking skills, there was significant difference in mean scores of male and females (p < 0.001). Residents in the specialty of Internal Medicine had significantly higher scores than other specialties (CI 95% = 107.74–127.07; p < 0.001). Fifth-year residents had significantly higher scores than those of other levels (CI 95% =123.94-142.05; p < 0.001). Residents with more than one year of experience after the basic degree had significantly higher scores than residents with lesser experience (CI 95% = 123.76–137.68; p < 0.001). Residents who had taken training in communication skills had higher scores than those who had no prior training (CI 95% = 112.78-124.48; p = 0.07). Conclusion:The resident physicians are lacking in communication skills. Results of this study point towards a lingering need to focus on training of physicians in effective communication and efforts should be made to include it as a core competency in medical curriculum.
Integrated analysis identifies hypertension-GWAS-loci regulated, differentially expressed genes in aorta and blood of aortic dissection
Authors: Cao Yu , Xiong Da , Li Kunlin , Dai Guolin , Li Yongwu , Zhong Minghua , Zhang Jinping , Jiang Lihong , Zhao Wei , Li Hongrong
Published: August 2020

Background: Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta. Hypertension is the most common risk factor of aortic dissection. However, only a small proportion of subjects with hypertension will develop aortic dissection. Genetic basis and effect genes determining the development and progression of aortic dissection remained to be identified. In this study, we attempted to recognize the underlying effect genes from reliable large-scale genome-wide association studies (GWASs) of hypertension.Methods: As most GWAS locus functions through its biological role in gene expression regulation, we initially converted the GWAS signals to transcriptomic profiles in aorta using the Functional Summary-based Imputation (FUSION) algorithm. The FUSION derived genes were then checked whether they were differentially expressed in aorta of subjects with and without aortic dissection.Results: We found 23 genes that were regulated by hypertension GWAS loci and were altered in aorta of dissection patients. In particular, the DCAF16 gene could be detected in blood, providing a possibility of non-invasive early detection or prediction of hypertensive individuals at risk of aortic dissection.Conclusions: Our analyses identified effect genes in aorta and provided a possibility of non-invasive early detection of aortic dissection.Trial registration: Retrospectively registered.
A Comparison of therapeutic strategies consisting of different combinations of surgery and/or radiotherapy in Pulmonary MALT-MZL: A population-based Analysis of SEER Data, 1992-2013
Authors: Du Xinyi , Quan Lin , Miao Yi , Cao Lei , Huang Rong , Liu Hailing , Fan Lei , Xu Wei , Li Jianyong
Published: August 2020

Background

Pulmonary marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type (MALT) is recognized as the most common type of primary pulmonary lymphomas. However, due to its relatively-low proportion, the studies focused on this patient population were limited. We aimed to reveal the status of surgery and radiotherapy in survival of pulmonary MALT lymphoma patients.
Methods

A retrospective analysis was conducted on patients who were pathologically diagnosed as pulmonary MALT lymphoma between 1992 and 2013. Their treatment information was collected in Surveillance, Epidemiology, and End Results (SEER) database. According to the different treatments, they were divided into four groups: Both Surgery and Radiation(SR), Surgery(S), Radiation(R) and No Surgery Or Radiation(NSR). The further subgroup analyses were performed according to age of onset and clinical stages. Overall survival (OS) was calculated from diagnosis up to the date of death or the last follow-up of each patient. Survival curves constructed by the Kaplan-Meier method and log-rank test were utilized for comparison.
Results

There were 860 pulmonary MALT lymphoma patients were enrolled. The median OS was 55.0 months (0-256.0 months). The OS between patients who underwent surgery and/or radiotherapy(S/R/SR) or not(NSR)(473 VS 387) had shown a significant difference of each other(P < 0.0001), so did the comparison among the four subgroups(SR VS S VS R VS NSR, P < 0.0001). Although there wasn’t any statistical difference in the OS between SR and S groups (P = 0.1174), further analysis on the causes of death revealed that, additional radiation therapy may lead to good short-term efficacy, while elevated mortality associated with long-term pulmonary complications was noteworthy. In the subgroup analyses, patients in stage I-II and over 60 years old shared similar trends with total population involved in the study(P = 0.0001;P < 0.0001).
Conclusions

The present study confirmed the value of surgery and the possible effects of radiotherapy among patients with pulmonary MALT lymphoma by clinical data from a large number of samples. If the improved radiotherapy regimens are chosen or the pulmonary complications caused by radiotherapy are well-managed, chances will be high that extra benefits could be achieved by combining radiotherapy with the surgical-based therapy.
Decomposing the Effect of Women Educational Status on Fertility Across the Six Geo-political Zones in Nigeria: 2003-2018
Authors: Olowolafe Tubosun Alex
Published: August 2020

Background: High level of fertility has been consistently reported in Nigeria. Women education is often identified as one of the important factors that have contributed to reduction in fertility across countries. It is essential to identify the factors that explain the fertility variation in educational status and know the extent of association of these factors across the regions in Nigeria. Thus, this study aimed to examine the fertility differentials among uneducated and educated women in Nigeria.Methods: A cross-sectional population-based design which involved secondary data analyses of the weighted sample of 2003 (n1=7620), 2008 (n2=33385), 2013 (n3=38948) and 2018 (n4=41821) Nigeria Demographic and Health Survey data sets was used. Fertility was measured from information on the full births history of women aged 15-49 years. Oaxaca-Blinder decomposition was used to identify factors that explain fertility differentials among educated and not educate women (α=0.05).Result: Total fertility rate estimate was higher among uneducated women (6.7) than educated women (4.5) in 2018. The pattern was similar across the regions and survey periods. The mean children ever born among women aged 45-49 years was significantly higher among the uneducated than educated women in each of the survey year. Maternal age at first marriage, wealth index and age at first birth were contributory factors to the dissimilarities found in fertility between the educated and uneducated women. Risk difference (RD) of high fertility between uneducated-educated women was highest in South-East (RD=56.9; 95%CI=49.1-64.8) and least in North-East (RD=15.0; 95%CI=9.9-20.1).Conclusion: The fertility level in Nigeria was high but more prominent among the uneducated than educated. Improving the level of educational enrolment of women of reproductive age will facilitate reduction in the fertility rate in Nigeria.