bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in access and utilisation of mental health services in the perinatal period for women from ethnic minorities—a population-based study
Authors: Jankovic Jelena , Parsons Jake , Jovanović Nikolina , Berrisford Giles , Copello Alex , Fazil Qulsom , Priebe Stefan
Published: September 2020

Background

Barriers to accessing mental health care during pregnancy and the first postnatal year (perinatal period) seem to be greater for ethnic minority women; however, there is no reliable large-scale data about their actual use of mental health services during this period. Our study aims to explore access rates to secondary mental health services, including involuntary admissions to psychiatric inpatient care and patterns of engagement for ethnic minority women aged 18+ who gave birth in 2017 in England, UK.

Methods

Two datasets from the National Commissioning Data Repository, the Acute Inpatient Dataset and Mental Health Services Dataset, were linked. Datasets covering the full perinatal period for each woman were included. Rates were standardised by age and deprivation.

Results

Out of 615,092 women who gave birth in England in 2017, 22,073 (3.5%) started a contact with mental health services during the perinatal period. In total, 713 (3.2%) were admitted to inpatient care, and 282 (39.5%) involuntarily. Ethnicity data was available for 98% of the sample. Black African, Asian and White Other women had significantly lower access to community mental health services and higher percentages of involuntary admissions than White British women. Black African, Asian and White Other women had a higher number of attended community contacts and fewer non-attendances/cancellations of appointments than White British women.

Conclusion

Access to mental health services during the perinatal period varies significantly between women from different ethnic groups. Access to community mental health services should be facilitated for Black African, Asian and White Other women during the perinatal period, which may reduce rates of involuntary hospital admissions for these groups. The pattern of engagement with community services for women from these ethnicities indicates that access appears to be a problem rather than utilisation.
MiR-596 activated by EP300 controls the tumorigenesis in epithelial ovarian cancer by declining BRD4 and KPNA4
Authors: Wang Deying , Cui Yulan , Xu Aili , Zhao Lin , Li Peiling
Published: September 2020

Background

Epithelial ovarian cancer (EOC), a subclass of ovarian cancer (OC), is usually diagnosed at advanced stages due to the lack of effective screening means. Mounting reports have disclosed the vitally important roles of microRNAs (miRNAs) in carcinogenesis. Here, we aimed to find out possible miRNAs participating in EOC development.

Methods

qRT-PCR ad western blot respectively examined the mRNA and protein levels of studied genes. CCK-8, colony formation, flow cytometry, TUNEL and spheroid formation assays were appropriately employed for examining cell proliferation, cell cycle, apoptosis and stemness. The interaction between molecules was affirmed by luciferase reporter, RNA pull down and ChIP assays.

Results

In consistent with the observation of a past study, miR-596 expression was relatively low in EOC cells. Up-regulating miR-596 suppressed EOC cell proliferation and stemness. EP300 transcriptionally activated miR-596 to serve as a tumor-repressor in EOC. Then BRD4 and KPNA4, whose knockdown led to restraining effects on cell growth and stemness, were both revealed to be targeted by miR-596 in EOC. Lastly, rescue assays affirmed the tumor-restraining role of miR-596-BRD4/KPNA4 axis in EOC.

Conclusion

EP300-activated miR-596 hampered cell growth and stemness via targeting BRD4 and KPNA4 in EOC, proofing miR-596 as a promising therapeutic target in treating EOC patients.
The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis
Authors: Shao Ying , Lu Bingjian
Published: September 2020

Background

Carcinomas are highly heterogeneous with regard to various cancer cells within a tumor microenvironment (TME), which is composed of stromal cells, blood vessels, immunocytes, and modified extracellular matrix.

Focus of the study

Circular RNAs (circRNAs) are non-coding RNAs that are expressed in cancer and stromal cells. They are closely associated with cancer metastasis as their expression in tumor cells directs the latter to migrate to different organs. circRNAs packaged in exosomes might be involved in this process. This is particularly important as the TME acts in tandem with cancer cells to enhance their proliferation and metastatic capability. In this review, we focus on recent studies on the crosstalk between circRNAs and the TME during cancer metastasis.

Conclusion

We particularly emphasize the roles of the interaction between circRNAs and the TME in anoikis resistance, vessel co-option, and local circRNA expression in directing homing of exosome.
Effectiveness of peer-learning assisted primary school students educating the rural community on insecticide-treated nets utilization in Jimma-zone Ethiopia
Authors: Kebede Yohannes , Abebe Lakew , Alemayehu Guda , Sudhakar Morankar , Birhanu Zewdie
Published: September 2020

Background

Making insecticide-treated nets (ITNs) utilization a social norm would support the global goal of malaria eradication and Ethiopian national aim of its elimination by 2030. Jimma zone is one of the endemic settings in Ethiopia. This study aimed to report effects of malaria education, delivered by students, on community behaviours; particularly ITNs.

Methods

In pre-posttest, cross-sectional household surveys conducted in rural villages of 5 districts in Jimma Zone, Ethiopia, 762 households were sampled. The intervention engaged students from primary schools in participatory peer education within small groups, followed by exposing parents with malaria messages aimed at influencing perceptions and practices. The data were analysed using SPSS version 20.0. Proportions/means differences were computed to compare changes in exposure, knowledge, perceptions, and practices using 95% CI at p < 0.05. Regression analyses were conducted to assess exposures to school-based education, content intensity, perception, and access related predictors of ITN utilization over the intervention periods.

Results

Over the intervention periods, the findings showed significant improvement in exposure to and content intensity of malaria messages delivered by students, effect size (ES) = 44.5% and 19.3%, p < 0.001, respectively. ITN utilization (ES = 25.8%), and the reported behaviour of giving ITN priority to children under 5 years old and pregnant women increased by ES = 16.3% and  24.8%, respectively. The exposure status or content intensity of malaria education, in turn, significantly improved comprehensive knowledge about malaria (β = +1.82), misconceptions about causes (β = − 11.46), awareness of caring for ITN (β = +24.79), identifying ITN as effective preventive methods (OR = 1.93), attitude towards ITN (β = +0.20), perceived efficacy of ITN (OR = 1.04), acceptance of ITN as a means to control the danger of malaria (β = +8.08%), and ITN utilization (OR = 1.85). Nonetheless, perceived threat (β = − 0.19) significantly negatively correlated with exposure to students’ messages. Socio-demography, access, exposures to messages, and parental perception that students were good reminders predicted ITN utilization over the intervention periods with some changing patterns.

Conclusions

Exposing the community to malaria education through students effectively supports behaviour change, particularly ITN usage, to be more positive towards desired malaria control practices. A school-based strategy is recommended to the national effort to combat malaria.
A family of partial-linear single-index models for analyzing complex environmental exposures with continuous, categorical, time-to-event, and longitudinal health outcomes
Authors: Wang Yuyan , Wu Yinxiang , Jacobson Melanie H. , Lee Myeonggyun , Jin Peng , Trasande Leonardo , Liu Mengling
Published: September 2020

Background

Statistical methods to study the joint effects of environmental factors are of great importance to understand the impact of correlated exposures that may act synergistically or antagonistically on health outcomes. This study proposes a family of statistical models under a unified partial-linear single-index (PLSI) modeling framework, to assess the joint effects of environmental factors for continuous, categorical, time-to-event, and longitudinal outcomes. All PLSI models consist of a linear combination of exposures into a single index for practical interpretability of relative direction and importance, and a nonparametric link function for modeling flexibility.

Methods

We presented PLSI linear regression and PLSI quantile regression for continuous outcome, PLSI generalized linear regression for categorical outcome, PLSI proportional hazards model for time-to-event outcome, and PLSI mixed-effects model for longitudinal outcome. These models were demonstrated using a dataset of 800 subjects from NHANES 2003–2004 survey including 8 environmental factors. Serum triglyceride concentration was analyzed as a continuous outcome and then dichotomized as a binary outcome. Simulations were conducted to demonstrate the PLSI proportional hazards model and PLSI mixed-effects model. The performance of PLSI models was compared with their counterpart parametric models.

Results

PLSI linear, quantile, and logistic regressions showed similar results that the 8 environmental factors had both positive and negative associations with triglycerides, with a-Tocopherol having the most positive and trans-b-carotene having the most negative association. For the time-to-event and longitudinal settings, simulations showed that PLSI models could correctly identify directions and relative importance for the 8 environmental factors. Compared with parametric models, PLSI models got similar results when the link function was close to linear, but clearly outperformed in simulations with nonlinear effects.

Conclusions

We presented a unified family of PLSI models to assess the joint effects of exposures on four commonly-used types of outcomes in environmental research, and demonstrated their modeling flexibility and effectiveness, especially for studying environmental factors with mixed directional effects and/or nonlinear effects. Our study has expanded the analytical toolbox for investigating the complex effects of environmental factors. A practical contribution also included a coherent algorithm for all proposed PLSI models with R codes available.
Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island
Authors: Crawford Kathryn A. , Hawley Nicola , Calafat Antonia M. , Jayatilaka Nayana K. , Froehlich Rosemary J. , Has Phinnara , Gallagher Lisa G. , Savitz David A. , Braun Joseph M. , Werner Erika F. , Romano Megan E.
Published: September 2020

Background

Organophosphate esters (OPEs)—used as flame retardants and plasticizers—are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors.

Methods

We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks’ gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex.

Results

We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = − 0.50 cm, 95%CI = − 0.86, − 0.14) and female weight (β = − 0.19 kg, 95%CI = − 0.36, − 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28).

Conclusions

Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.
Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook
Authors: Horvath Lena , Thienpont Bernard , Zhao Liyun , Wolf Dominik , Pircher Andreas
Published: September 2020

Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1highexpression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome.

We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.
Assessing mental well-being in a Sinhala speaking Sri Lankan population: validation of the WHO-5 well-being index
Authors: Perera B. P. R. , Jayasuriya R. , Caldera A. , Wickremasinghe A. R.
Published: September 2020

Purpose

The WHO-5 well-being index is a widely used, short rating scale that measures subjective well-being. We translated the WHO-5 index into Sinhala and tested its psychometric properties including measurement invariance among diverse groups in a community sample in Sri Lanka.

Methods

The sample of 267 persons aged between 16 and 75 years was recruited from a semi-urban area. 219 completed a paper-based questionnaire and 48 responded to an online survey. Construct validity was tested for factorial validity (Confirmatory Factor Analysis -CFA), convergent validity and known group validity. Composite reliability for congeneric measures and test-retest reliability were also tested. Multi-group CFA (MG-CFA) was used to test measurement invariance.

Results

The translated Sinhala version demonstrated good content and face validity. Internal consistency reliability of the five items had a Cronbach’s alpha of 0.85 and test-retest reliability over 2 weeks was satisfactory (Pearson r = 0.72, p < 0.001, ICC = 0.82). Confirmatory factor analysis supported factorial validity with a $$ {\chi}_5^2 $$

χ

5
2

=4.99 (p = 0.28), a RMSEA of 0.03 (90% C.I. =0.00–0.10), a SRMR of 0.02, a TLI of 0.99 and a CFI of 0.99; factor loadings were between 0.55 and 0.89. Measurement invariance was acceptable for configural, metric and scalar invariance for gender.

WHO-5 scores were significantly negatively correlated with the Patient Health Questionnaire (PHQ-9) (Pearson’s r = − 0.45, p < 0.001) scores and the Kessler Psychological Distress Scale (K10) scores (Pearson’s r = − 0.56, p < 0.001).

Conclusion

The Sinhala translation of WHO-5 well-being index has shown acceptable psychometric properties and can be used for assessing mental well-being in the community in Sri Lanka. Further testing of the measure with larger and diverse (including different ethnic/cultural) groups are indicated to test measurement invariance of the measure.
What should community organisations consider when deciding to partner with researchers? A critical reflection on the Zilla Budakattu Girijana Abhivrudhhi Sangha experience in Karnataka, India
Authors: Pratt Bridget , Seshadri Tanya , Srinivas Prashanth N.
Published: September 2020

Background

Community organisations and community members are increasingly being involved in health research projects worldwide as part of the engagement movement. Achieving deeper forms of community engagement like partnership demands that decision-making power be shared with community partners. However, how can community partners assess if meaningful engagement and shared decision-making will be possible when approached by prospective research partners? In this paper, we explore how community organisations decide to join health research projects when approached by health researchers.

Methods

Case study research was undertaken on a health systems research project in Karnataka, India called Participation for Local Action, which was carried out by local researchers in partnership with the Zilla Budakattu Girijana Abhivrudhhi Sangha, a community development organisation. In-depth interviews were conducted with the researchers, Sangha leaders and field investigators from their community.

Results

Thematic analysis identified two main themes – ‘context’ and ‘deciding to engage’. The Sangha’s experience offers lessons to other community organisations that can help them when deciding to engage with researchers in terms of what features to look for in research partners and in proposed research projects, what requests to make of prospective research partners, and what sorts of outcomes or partnership agreements to accept. These lessons may be especially applicable in contexts where relationships of trust already exist between partners and where they have the skills to lead data collection and analysis.

Conclusions

We hope that this guidance will help empower community organisations to select good research partners and promote more equitable partnerships between community partners and academic researchers.
Users with spinal cord injury experience of robotic Locomotor exoskeletons: a qualitative study of the benefits, limitations, and recommendations
Authors: Kinnett-Hopkins Dominique , Mummidisetty Chaithanya K. , Ehrlich-Jones Linda , Crown Deborah , Bond Rachel A. , Applebaum Marc H. , Jayaraman Arun , Furbish Catherine , Forrest Gail , Field-Fote Edelle , Heinemann Allen W.
Published: September 2020

Background

Persons with spinal cord injury (SCI) may experience both psychological and physiological benefits from robotic locomotor exoskeleton use, and knowledgeable users may have valuable perspectives to inform future development. The objective of this study is to gain insight into the experiences, perspectives, concerns, and suggestions on the use of robotic locomotor exoskeletons by civilians and veterans living with SCI.

Methods

Participants reported their demographic characteristics and the extent of robotic exoskeleton use in an online survey. Then, 28 experienced robotic locomotor exoskeleton users participated in focus groups held at three regional hospitals that specialize in rehabilitation for persons with SCI. We used a qualitative description approach analysis to analyze the data, and included thematic analysis.

Results

Participants expressed that robotic exoskeletons were useful in therapy settings but, in their current form, were not practical for activities of daily living due to device limitations. Participants detailed the psychological benefits of being eye-level with their non-disabled peers and family members, and some reported physiologic improvements in areas such as bowel and bladder function. Participants detailed barriers of increased fatigue, spasticity, and spasms and expressed dissatisfaction with the devices due to an inability to use them independently and safely. Participants provided suggestions to manufacturers for technology improvements.

Conclusions

The varied opinions and insights of robotic locomotor exoskeletons users with SCI add to our knowledge of device benefits and limitations.
The FCTC dilemma on heated tobacco products
Authors: Gruszczynski Lukasz , Melillo Margherita
Published: September 2020

Background

In October 2018, the Conference of the Parties of the Framework Convention on Tobacco Control (FCTC or Convention) adopted its first decision on novel and emerging tobacco products, including heated tobacco products (HTPs). The decision remains ambiguous, e.g. by making a distinction between tobacco sticks and HTP devices. Against this background, the article seeks to answer two interrelated questions: whether and to what extent HTPs are covered by the FCTC, and whether regime provided by the Convention is suitable for their regulation.

Results

HTPs need to be classified under the FCTC as tobacco products. The distinction made by the Conference of the Parties between sticks and devices leads however to unsatisfactory results as it creates loopholes in tobacco control standards existing at the international level. A better approach, as argued in this article, is to conceptualize the notion of ‘tobacco products’ in functional terms as a combination of both a device and stick.

While subjecting HTPs to all FCTC disciplines is, in light of our current scientific knowledge, a rational approach, such classification can be modified in the future once a sufficient amount of new evidence on their risk profile is collected. Any decision on the optimal regulatory model for HTPs will need to take into account not only health risks and potential benefits for individual users, but also the specific systemic concerns (e.g. HTPs as a gateway product). The state of scientific research is however not the only factor that will determine the fate of HTPs under the Convention. What is equally important is a conceptualization of the FCTC’s objectives. If a complete eradication of the tobacco epidemic is the ultimate goal, reduced levels of risk may not be enough to justify the different (i.e. more lenient) regulatory regime for HTPs.

Conclusions

The Conference of the Parties should clarify the definition of tobacco products in light of recent changes in the market. When designing the regulatory regime for HTPs under the FCTC in the future, one has to consider not only scientific evidence but also pay attention to the objective of the Convention (or more generally to the values that underlie the current tobacco control paradigm).
Fermentation of Danggui Buxue Tang, an ancient Chinese herbal mixture, together with Lactobacillus plantarum enhances the anti-diabetic functions of herbal product
Authors: Guo Rui , Guo Shuchen , Gao Xiong , Wang Huaiyou , Hu Weihui , Duan Ran , Dong Tina T. X. , Tsim Karl W. K.
Published: September 2020

Background

Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix at a ratio of 5: 1, is prescribed for menopausal women. Flavonoids and its flavonoid glycosides are considered as the major active ingredients within the herbal decoction; however, their amount is not controllable during the preparation. Besides, the aglycons within DBT are believed to have better gut absorption and pharmacological efficacy.

Methods

The herbal extract of DBT was fermented withLactobacillus plantarum. The amounts of flavonoid glucosides and its aglycones in the fermented product were analyzed by using UPLC-MS/MS. In addition, in vitro assays were employed to evaluate the efficacy of the fermented DBT in regulating the activities of α-glucosidase, α-amylase and lipase, as well as their antioxidant capacity (DPPH and T-AOC assays) and anti-glycation property (BSA-methylglyoxal, BSA-fructose, and arginine-methylglyoxal models).

Results

The fermentation of DBT withL. plantarumdrove a completed conversion of calycosin-7-O-β-D-glucoside and ononin to calycosin and formononetin, respectively. The chemical transformation could be probably mediated by β-glycosidase within the fermented product. Several in vitro assays corresponding to anti-diabetic functions were compared between parental DBT against its fermented product, which included the activities against α-glucosidase, α-amylase and lipase, as well as anti-oxidation and anti-glycation. The fermented DBT showed increased activities in inhibiting α-glycosidase, suppressing DPPH radical-scavenging and anti-glycation, as compared to the original herbal product.

Conclusion

These results suggested that DBT being fermented with the probioticL. plantarumcould pave a new direction for fermentation of herbal extract, as to strengthen its pharmacological properties in providing health benefits.
Toe flexor strength is associated with mobility in older adults with pronated and supinated feet but not with neutral feet
Authors: Kusagawa Yuki , Kurihara Toshiyuki , Imai Aiko , Maeo Sumiaki , Sugiyama Takashi , Kanehisa Hiroaki , Isaka Tadao
Published: September 2020

Background

Older adults are known to have more pronated foot posture and decreased toe flexor strength (TFS), as well as decreased mobility in daily life compared to young adults. Although foot posture is reported to be an influential factor for walking biomechanics in young adults, there is less information on this subject in older adults. Age‐related reduction in TFS is shown to be associated with impairments of functional performance, but it is poorly understood whether foot posture influences the relationships between TFS and functional performances. Therefore, the present study aimed to elucidate this concern by examining older women.

Methods

Seventy community‐dwelling older women (76.8 ± 4.4 years) voluntarily participated in this study. Foot posture was evaluated by the 6‐item foot posture index (FPI). Based on the FPI score, participants were allocated to pronated, neutral, or supinated group (n = 33, 26, and 11, respectively). TFS was assessed using a toe grip dynamometer in a seated position. Scores of 30‐s chair stand, timed up‐and‐go, 5‐m comfortable‐speed walking, and static balance tests were determined to evaluate functional performances. Pearson's correlation coefficients were computed to examine the relationships between TFS and functional performances in each group.

Results

TFS positively correlated with comfortable walking speed in the pronated (r = 0.37, p = 0.03) and supinated (r = 0.76, p < 0.001) groups, but not in the neutral group (r = 0.17, p = 0.42). For the two significant relationships, an analysis of covariance showed that there was no significant difference between the pronated and supinated groups in the slopes of the regression lines, suggesting a similar relative contribution of TFS to comfortable walking speed between the two groups. In addition, TFS tended to negatively correlate with timed up‐and‐go time in the pronated (r = − 0.32, p = 0.07) and supinated (r = − 0.56, p = 0.08) groups, and positively correlate with 30‐s chair stand score in the pronated group (r = 0.31, p = 0.08).

Conclusions

The present study indicates that TFS would be associated with mobility, walking performance in particular, in older women with pronated and supinated feet but not with neutral feet.
Impact of the COVID-19 epidemic at a high-volume facility in gynecological oncology in Tokyo, Japan: a single-center experience
Authors: Nogami Yuya , Kobayashi Yusuke , Tsuji Kosuke , Yokota Megumi , Nishio Hiroshi , Nakamura Masaru , Yamagami Wataru , Morisada Tohru , Tominaga Eiichiro , Banno Kouji , Aoki Daisuke
Published: September 2020

Background

The number of cases of novel coronavirus disease 2019 (COVID-19) in Japan have risen since the first case was reported on January 24, 2020, and 6225 infections have been reported as of June 30, 2020. On April 8, 2020, our hospital began screening patients via pre-admission reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and chest computed tomography (CT). Although no patients exhibited apparent pneumonia, treatment delay or changes in treatment plans were required for a few patients based on the results of screening tests. During an emerging infectious disease pandemic, the likelihood of being infected, as well as the disease itself, affects clinical decision making in several ways. We summarized and presented our experience.

Case presentation

After the introduction of pre-admission screening, RT-PCR and CT were performed in 200 and 76 patients, respectively, as of June 30, 2020. The treatment of five patients, including two patients with cervical cancer, two patients with ovarian tumors, and one patient with ovarian cancer, was affected by the results. Two asymptomatic RT-PCR-positive patients did not develop COVID-19, but their treatment was delayed until the confirmation of negative results. The other three patients were RT-PCR-negative, but abnormal CT findings suggested the possibility of COVID-19, which delayed treatment. The patients receiving first-line preoperative chemotherapy for ovarian cancer had clinically evident exacerbations because of the treatment delay.

Conclusion

During the epidemic phase of an emerging infectious disease, we found that COVID-19 has several other effects besides its incidence. The postponing treatment was the most common, therefore, treatment of ovarian tumors and ovarian cancer was considered to be the most likely to be affected among gynecological diseases. Protocols that allow for easy over-diagnosis can be disadvantageous, mainly because of treatment delays, and therefore, the protocols must be developed in light of the local infection situation.
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging
Authors: Jager Agnes , de Vries Elisabeth G. E. , der Houven van Oordt C. Willemien Menke-van , Neven Patrick , Venema Clasina M. , Glaudemans Andor W. J. M. , Wang Yamei , Bagley Rebecca G. , Conlan Maureen G. , Aftimos Philippe
Published: September 2020

Background

Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT).

Methods

Eligible patients were postmenopausal women with ER+, HER2− ABC; tumor progression after ≥ 6 months of 1–3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1.

Results

Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity.

Conclusion

Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity.

Trial registration

ClinicalTrials.gov, NCT02650817. Registered on 08 January 2016
Dual-energy CT in gout patients: Do all colour-coded lesions actually represent monosodium urate crystals?
Authors: Christiansen Sara Nysom , Müller Felix Christoph , Østergaard Mikkel , Slot Ole , Møller Jakob M. , Børgesen Henrik F. , Gosvig Kasper Kjærulf , Terslev Lene
Published: September 2020

Background

Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated.

The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients.

Methods

DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions.

Results

In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions).

The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions.

Conclusion

Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.
Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?
Authors: Fernández-Ortiz Ana M. , Ortiz Ana M. , Pérez Silvia , Toledano Esther , Abásolo Lydia , González-Gay Miguel A. , Castañeda Santos , González-Álvaro Isidoro
Published: September 2020

Background

An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease.

Methods

We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C.

Results

After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios.

Conclusions

High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.
Reduced mitochondrial D-loop methylation levels in sporadic amyotrophic lateral sclerosis
Authors: Stoccoro Andrea , Smith Adam R. , Mosca Lorena , Marocchi Alessandro , Gerardi Francesca , Lunetta Christian , Cereda Cristina , Gagliardi Stella , Lunnon Katie , Migliore Lucia , Coppedè Fabio
Published: September 2020

Background

Mitochondrial dysregulation and aberrant epigenetic mechanisms have been frequently reported in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and several researchers suggested that epigenetic dysregulation in mitochondrial DNA (mtDNA) could contribute to the neurodegenerative process. We recently screened families with mutations in the major ALS causative genes, namely C9orf72, SOD1, FUS, and TARDBP, observing reduced methylation levels of the mtDNA regulatory region (D-loop) only in peripheral lymphocytes of SOD1 carriers. However, until now no studies investigated the potential role of mtDNA methylation impairment in the sporadic form of ALS, which accounts for the majority of disease cases. The aim of the current study was to investigate the D-loop methylation levels and the mtDNA copy number in sporadic ALS patients and compare them to those observed in healthy controls and in familial ALS patients. Pyrosequencing analysis of D-loop methylation levels and quantitative analysis of mtDNA copy number were performed in peripheral white blood cells from 36 sporadic ALS patients, 51 age- and sex-matched controls, and 27 familial ALS patients with germinal mutations in SOD1 or C9orf72 that represent the major familial ALS forms.

Results

In the total sample, D-loop methylation levels were significantly lower in ALS patients compared to controls, and a significant inverse correlation between D-loop methylation levels and the mtDNA copy number was observed. Stratification of ALS patients into different subtypes revealed that both SOD1-mutant and sporadic ALS patients showed lower D-loop methylation levels compared to controls, while C9orf72-ALS patients showed similar D-loop methylation levels than controls. In healthy controls, but not in ALS patients, D-loop methylation levels decreased with increasing age at sampling and were higher in males compared to females.

Conclusions

Present data reveal altered D-loop methylation levels in sporadic ALS and confirm previous evidence of an inverse correlation between D-loop methylation levels and the mtDNA copy number, as well as differences among the major familial ALS subtypes. Overall, present results suggest that D-loop methylation and mitochondrial replication are strictly related to each other and could represent compensatory mechanisms to counteract mitochondrial impairment in sporadic and SOD1-related ALS forms.
Attractor-state itinerancy in neural circuits with synaptic depression
Authors: Chen Bolun , Miller Paul
Published: September 2020

Neural populations with strong excitatory recurrent connections can support bistable states in their mean firing rates. Multiple fixed points in a network of such bistable units can be used to model memory retrieval and pattern separation. The stability of fixed points may change on a slower timescale than that of the dynamics due to short-term synaptic depression, leading to transitions between quasi-stable point attractor states in a sequence that depends on the history of stimuli. To better understand these behaviors, we study a minimal model, which characterizes multiple fixed points and transitions between them in response to stimuli with diverse time- and amplitude-dependencies. The interplay between the fast dynamics of firing rate and synaptic responses and the slower timescale of synaptic depression makes the neural activity sensitive to the amplitude and duration of square-pulse stimuli in a nontrivial, history-dependent manner. Weak cross-couplings further deform the basins of attraction for different fixed points into intricate shapes. We find that while short-term synaptic depression can reduce the total number of stable fixed points in a network, it tends to strongly increase the number of fixed points visited upon repetitions of fixed stimuli. Our analysis provides a natural explanation for the system’s rich responses to stimuli of different durations and amplitudes while demonstrating the encoding capability of bistable neural populations for dynamical features of incoming stimuli.
Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome
Authors: Jain Ayushi , Nilatawong Phubed , Mamak Narinrat , Jensen Laran T. , Jensen Amornrat Naranuntarat
Published: September 2020

Background

Shwachman-Diamond syndrome (SDS) is a congenital disease that affects the bone marrow, skeletal system, and pancreas. The majority of patients with SDS have mutations in the SBDS gene, involved in ribosome biogenesis as well as other processes. A Saccharomyces cerevisiae model of SDS, lacking Sdo1p the yeast orthologue of SBDS, was utilized to better understand the molecular pathogenesis in the development of this disease.

Results

Deletion of SDO1 resulted in a three-fold over-accumulation of intracellular iron. Phenotypes associated with impaired iron-sulfur (ISC) assembly, up-regulation of the high affinity iron uptake pathway, and reduced activities of ISC containing enzymes aconitase and succinate dehydrogenase, were observed in sdo1∆ yeast. In cells lacking Sdo1p, elevated levels of reactive oxygen species (ROS) and protein oxidation were reduced with iron chelation, using a cell impermeable iron chelator. In addition, the low activity of manganese superoxide dismutase (Sod2p) seen in sdo1∆ cells was improved with iron chelation, consistent with the presence of reactive iron from the ISC assembly pathway. In yeast lacking Sdo1p, the mitochondrial voltage-dependent anion channel (VDAC) Por1p is over-expressed and its deletion limits iron accumulation and increases activity of aconitase and succinate dehydrogenase.

Conclusions

We propose that oxidative stress from POR1 over-expression, resulting in impaired activity of ISC containing proteins and disruptions in iron homeostasis, may play a role in disease pathogenesis in SDS patients.
Identification of multidimensional Boolean patterns in microbial communities
Authors: Golovko George , Kamil Khanipov , Albayrak Levent , Nia Anna M. , Duarte Renato Salomon Arroyo , Chumakov Sergei , Fofanov Yuriy
Published: September 2020

Background

Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.

Results

We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.

Conclusions

The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities.