bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and laboratory findings in COVID-19 adult hospitalized patients from Alborz province / Iran: comparison of rRT-PCR positive and negative
Authors: Karimi Farnaz , Vaezi Amir Abbas , Qorbani Mostafa , Moghadasi Fatemeh , Gelsfid Saeed Hassani , Maghoul Arman , Mahmoodi Neda , Eskandari Zahra , Gholami Hossein , Mokhames Zakiye , Saleh Mahshid
Published: March 2021

Background

The novel coronavirus disease 2019 (COVID-19) was emergency turned into global public health after the first patients were detected in Wuhan, China, in December 2019. The disease rapidly expanded and led to an epidemic throughout China, followed by the rising number of cases worldwide. Given the high prevalence of COVID-19, rapid and accurate diagnostic methods are immediately needed to identify, isolate and treat the patients as soon as possible, decreasing mortality rates and the risk of public contamination by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

Methods

This case-control study was conducted in two hospitals in Alborz Province in Iran. All recruited cases in this study were symptomatic adults hospitalized as COVID-19 patients with compatible Computed tomographic (CT) scan findings and available rRT-PCR results. The patients were recruited in this study. The patients were categorized into positive and negative rRT-PCR groups and evaluated for symptoms, initial vital signs, comorbidity, clinical and laboratory findings. Finally, the results were assessed by SPSS software.

Results

Between March 5 to April 5, 2020, 164 symptomatic COVID-19 patients were studied. In total, there were 111 rRT-PCR positive (67.6%) and 53 rRT-PCR negative patients (32.4%). In terms of statistics, the frequency of symptoms revealed no difference, except for cough (P.V:0.008), dizziness (PV: 0.048), and weakness (P.V:0.022). Among initial vital signs, PR (P.V:0.041) and O2 Saturation (PV: 0.014) were statistically different between the two groups. Evaluation of comorbidities revealed no difference except for hyperlipidemia (P.V:0.024). In the comparison of laboratory findings, only WBC count (PV: 0.001), lymphocyte count (PV: 0.001), and Hb (P.V:0.008) were statistically different between the two groups.

Conclusion

In case of the negative rRT-PCR result, it is necessary to take a logical approach, and we recommended that the physician decides according to clinical manifestations, laboratory findings, and positive CT results.
Serial interval and incubation period of COVID-19: a systematic review and meta-analysis
Authors: Alene Muluneh , Yismaw Leltework , Assemie Moges Agazhe , Ketema Daniel Bekele , Gietaneh Wodaje , Birhan Tilahun Yemanu
Published: March 2021

Background

Understanding the epidemiological parameters that determine the transmission dynamics of COVID-19 is essential for public health intervention. Globally, a number of studies were conducted to estimate the average serial interval and incubation period of COVID-19. Combining findings of existing studies that estimate the average serial interval and incubation period of COVID-19 significantly improves the quality of evidence. Hence, this study aimed to determine the overall average serial interval and incubation period of COVID-19.

Methods

We followed the PRISMA checklist to present this study. A comprehensive search strategy was carried out from international electronic databases (Google Scholar, PubMed, Science Direct, Web of Science, CINAHL, and Cochrane Library) by two experienced reviewers (MAA and DBK) authors between the 1st of June and the 31st of July 2020. All observational studies either reporting the serial interval or incubation period in persons diagnosed with COVID-19 were included in this study. Heterogeneity across studies was assessed using the I2 and Higgins test. The NOS adapted for cross-sectional studies was used to evaluate the quality of studies. A random effect Meta-analysis was employed to determine the pooled estimate with 95% (CI). Microsoft Excel was used for data extraction and R software was used for analysis.

Results

We combined a total of 23 studies to estimate the overall mean serial interval of COVID-19. The mean serial interval of COVID-19 ranged from 4. 2 to 7.5 days. Our meta-analysis showed that the weighted pooled mean serial interval of COVID-19 was 5.2 (95%CI: 4.9–5.5) days. Additionally, to pool the mean incubation period of COVID-19, we included 14 articles. The mean incubation period of COVID-19 also ranged from 4.8 to 9 days. Accordingly, the weighted pooled mean incubation period of COVID-19 was 6.5 (95%CI: 5.9–7.1) days.

Conclusions

This systematic review and meta-analysis showed that the weighted pooled mean serial interval and incubation period of COVID-19 were 5.2, and 6.5 days, respectively. In this study, the average serial interval of COVID-19 is shorter than the average incubation period, which suggests that substantial numbers of COVID-19 cases will be attributed to presymptomatic transmission.
Shifting of global aphasia to Wernicke’s aphasia in a patient with intact motor function: a case report
Authors: Chuang Ya-Chi , Liu Chuan-Ching , Yu I-Ching , Tsai Yu-Lin , Chang Shin-Tsu
Published: March 2021

Background

Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome characterized by the dissociation of motor and language functions. Here, we present a case of GAWH with the patient later regaining speech fluency.

Case presentation

A 73-year-old man was admitted to our emergency department immediately after an episode of syncope. On arrival, we noted his global aphasia but without any focal neurologic signs. Computed tomography (CT) perfusion scans showed a large hypodense region over his left perisylvian area. Under the impression of acute ischaemic stroke, he received recombinant tissue plasminogen activator (rtPA) injection and was treated as an inpatient. The patient was later discharged with GAWH status and received regular speech rehabilitation. After 14 months of rehabilitation, the patient gradually recovered his language expression ability. The degree of aphasia was evaluated with the Concise Chinese Aphasia Test (CCAT), and we obtained brain single photon emission computed tomography (SPECT) scans to assess cerebral blood flow.

Conclusion

A patient with severe impairments of Broca’s and Wernicke’s areas was able to talk fluently despite being unintelligible. SPECT revealed relative high level of radioactivity uptake in the right frontal lobe, suggesting the deficits in speech fluency could have been compensated by the right hemisphere. Although this is a single case demonstration, the results may strengthen the role of the right hemisphere in GAWH patients and suggests additional study that examines the possible benefits of stimulating activity at right homologous regions for recovering language function after global aphasia.
Retinal microvascular parameters are not significantly associated with mild cognitive impairment in the Northern Ireland Cohort for the Longitudinal Study of Ageing
Authors: O’Neill R. A. , Maxwell A. P. , Paterson E. N. , Kee F. , Young I. , Hogg R. E. , Cruise S. , Murphy S. , McGuinness B. , McKay G. J.
Published: March 2021

Background

The retinal and cerebral microvasculature share similar embryological origins and physiological characteristics. Improved imaging technologies provide opportunistic non-invasive assessment of retinal microvascular parameters (RMPs) against cognitive outcomes. We evaluated baseline measures for associations between RMPs and mild cognitive impairment (MCI) from participants of the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA).

Methods

RMPs (central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension and tortuosity) were measured from optic disc centred fundus images and analysed using semi-automated software. Associations between RMPs and MCI were assessed by multivariable logistic regression with adjustment for potential confounders including age, sex, alcohol consumption, smoking status, educational attainment, physical activity, cardiovascular disease (CVD), hypertension, mean arterial blood pressure, triglycerides, diabetes, body mass index, and high density lipoprotein levels. P < 0.05 was considered statistically significant.

Results

Data were available for 1431 participants, of which 156 (10.9%) were classified with MCI defined by a Montreal Cognitive Assessment (MoCA) score ≤ 26, with subjective cognitive decline, in the absence of depression or problems with activities of daily living. Participants had a mean age of 62.4 ± 8.5 yrs. and 52% were female. As expected, individuals with MCI had a lower MoCA score than those without (23.5 ± 2.6 versus 26.3 ± 2.7, respectively), were more likely to be female, have a lower level of educational attainment, be less physically active, more likely to have CVD, have higher levels of triglycerides and lower levels of high density lipoprotein. No significant associations between RMPs and MCI were detected in unadjusted, minimally adjusted or fully adjusted regression models or subsequent sensitivity analyses.

Conclusion

Previous studies have reported both increased retinal venular calibre and reduced fractal dimension in association with mild cognitive impairment. Our study failed to detect any associations between RMPs and those individuals at an early stage of cognitive loss in an older community-based cohort.
Microbiological findings in early and late implant loss: an observational clinical case-controlled study
Authors: Korsch Michael , Marten Silke-Mareike , Stoll Dominic , Prechtl Christopher , Dötsch Andreas
Published: March 2021

Background

Implants are a predictable and well-established treatment method in dentistry. Nevertheless, looking at possible failures of dental implants, early and late loss have to be distinguished. The intent of the study was to report microbiological findings on the surface of implants with severe peri-implantitis, which had to be explanted.

Methods

53 specimens of implants from 48 patients without severe general illnesses have been examined. The groups investigated were implants that had to be removed in the period of osseointegration (early loss, 13 patients with 14 implants) or after the healing period (late loss, 14 patients with 17 implants). The implant losses were compared with two control groups (implants with no bone loss directly after completed osseointegration, two to four months after implant placement (17 patients with 17 implants) and implants with no bone loss and prosthetic restoration for more than three years (5 patients with 5 implants)). Data about the bacteria located in the peri-implant sulcus was collected using amplification and high throughput sequencing of the 16S rRNA gene.

Results

The biofilm composition differed substantially between individuals. Both in early and late implant loss,Fusobacterium nucleatumandPorphyromonas gingivalis were found to be abundant. Late lost implants showed higher bacterial diversity and in addition higher abundances ofTreponema, Fretibacterium, Pseudoramibacter and Desulfobulbus, while microbial communities of early loss implants were very heterogeneous and showed no significantly more abundant bacterial taxa.

Conclusions

Specific peri-implant pathogens were found around implants that were lost after a primarily uneventful osseointegration.P. gingivalisandF. nucleatumfrequently colonized the implant in early and late losses and could therefore be characteristic for implant loss in general. In general, early lost implants showed also lower microbial diversity than late losses. However, the microbial results were not indicative of the causes of early and late losses.
Correction to: Increase in excitability of hippocampal neurons during novelty-induced hyperlocomotion in dopamine-deficient mice
Authors: Fujita Masayo , Ochiai Yukiko , Takeda Taishi-Clark , Hagino Yoko , Kobayashi Kazuto , Ikeda Kazutaka
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer
Authors: Zivarpour Parinaz , Nikkhah Elhameh , Maleki Dana Parisa , Asemi Zatollah , Hallajzadeh Jamal
Published: March 2021

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person’s quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.
SRSF3 and SRSF7 modulate 3′UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels
Authors: Schwich Oliver Daniel , Blümel Nicole , Keller Mario , Wegener Marius , Setty Samarth Thonta , Brunstein Melinda Elaine , Poser Ina , Mozos Igor Ruiz De Los , Suess Beatrix , Münch Christian , McNicoll François , Zarnack Kathi , Müller-McNicoll Michaela
Published: March 2021

Background

Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3′ untranslated regions (3′UTRs). We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, connect APA with mRNA export. The mechanism underlying APA regulation by SRSF3 and SRSF7 remained unknown.

Results

Here we combine iCLIP and 3′-end sequencing and find that SRSF3 and SRSF7 bind upstream of proximal PASs (pPASs), but they exert opposite effects on 3′UTR length. SRSF7 enhances pPAS usage in a concentration-dependent but splicing-independent manner by recruiting the cleavage factor FIP1, generating short 3′UTRs. Protein domains unique to SRSF7, which are absent from SRSF3, contribute to FIP1 recruitment. In contrast, SRSF3 promotes distal PAS (dPAS) usage and hence long 3′UTRs directly by counteracting SRSF7, but also indirectly by maintaining high levels of cleavage factor Im (CFIm) via alternative splicing. Upon SRSF3 depletion, CFIm levels decrease and 3′UTRs are shortened. The indirect SRSF3 targets are particularly sensitive to low CFIm levels, because here CFIm serves a dual function; it enhances dPAS and inhibits pPAS usage by binding immediately downstream and assembling unproductive cleavage complexes, which together promotes long 3′UTRs.

Conclusions

We demonstrate that SRSF3 and SRSF7 are direct modulators of pPAS usage and show how small differences in the domain architecture of SR proteins can confer opposite effects on pPAS regulation.
Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri‐mir‐375 to miR-375
Authors: Wang Haoyu , Yuan Jing , Dang Xiaoqian , Shi Zhibin , Ban Wenrui , Ma Dong
Published: March 2021

Background

Spinal cord injury (SCI) is a disabling disorder, resulting in neurological impairments. This study investigated the mechanism of methyltransferase-like 14 (Mettl14) on apoptosis of spinal cord neurons during SCI repair by mediating pri-microRNA (miR) dependent N6-methyladenosine (m6A) methylation.

Methods

The m6A content in total RNA and Mettl14 levels in spinal cord tissues of SCI rats were detected. Mettl14 expression was intervened in SCI rats to examine motor function, neuron apoptosis, and recovery of neurites. The cell model of SCI was established and intervened with Mettl14. miR-375, related to SCI and positively related to Mettl14, was screened out. The expression of miR-375 and pri-miR-375 after Mettl14 intervention was detected. The expression of pri-miR-375 combined with DiGeorge critical region 8 (DGCR8) and that modified by m6A was detected. Furthermore, the possible downstream gene and pathway of miR-375 were analysed. SCI cell model with Mettl14 intervention was combined with Ras-related dexamethasone-induced 1 (RASD1)/miR-375 intervention to observe the apoptosis.

Results

Mettl14 level and m6A content in spinal cord tissue were significantly increased. After Mettl14 knockdown, the injured motor function was restored and neuron apoptosis was reduced. In vitro, Mettl14 silencing reduced the apoptosis of SCI cells; miR-375 was reduced and pri-miR-375 was increased; miR-375 targeted RASD1. Silencing Mettl14 inactivated the mTOR pathway. The apoptosis in cells treated with silencing Mettl14 + RASD1/miR-375 was inhibited.

Conclusions

Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.
The use of extracorporeal CO2 removal in acute respiratory failure
Authors: Giraud Raphaël , Banfi Carlo , Assouline Benjamin , De Charrière Amandine , Cecconi Maurizio , Bendjelid Karim
Published: March 2021

Background

Chronic obstructive pulmonary disease (COPD) exacerbation and protective mechanical ventilation of acute respiratory distress syndrome (ARDS) patients induce hypercapnic respiratory acidosis.

Main text

Extracorporeal carbon dioxide removal (ECCO2R) aims to eliminate blood CO2to fight against the adverse effects of hypercapnia and related acidosis. Hypercapnia has deleterious extrapulmonary consequences, particularly for the brain. In addition, in the lung, hypercapnia leads to: lower pH, pulmonary vasoconstriction, increases in right ventricular afterload, acute cor pulmonale. Moreover, hypercapnic acidosis may further damage the lungs by increasing both nitric oxide production and inflammation and altering alveolar epithelial cells. During an exacerbation of COPD, relieving the native lungs of at least a portion of the CO2could potentially reduce the patient's respiratory work, Instead of mechanically increasing alveolar ventilation with MV in an already hyperinflated lung to increase CO2removal, the use of ECCO2R may allow a decrease in respiratory volume and respiratory rate, resulting in improvement of lung mechanic. Thus, the use of ECCO2R may prevent noninvasive ventilation failure and allow intubated patients to be weaned off mechanical ventilation. In ARDS patients, ECCO2R may be used to promote an ultraprotective ventilation in allowing to lower tidal volume, plateau (Pplat) and driving pressures, parameters that have identified as a major risk factors for mortality. However, although ECCO2R appears to be effective in improving gas exchange and possibly in reducing the rate of endotracheal intubation and allowing more protective ventilation, its use may have pulmonary and hemodynamic consequences and may be associated with complications.

Conclusion

In selected patients, ECCO2R may be a promising adjunctive therapeutic strategy for the management of patients with severe COPD exacerbation and for the establishment of protective or ultraprotective ventilation in patients with ARDS without prognosis-threatening hypoxemia.
Social marketing-based interventions to promote healthy nutrition behaviors: a systematic review protocol
Authors: Doustmohammadian Azam , Bazhan Marjan
Published: March 2021

Background

Diet-related non-communicable diseases (NCDs) are rapidly increasing worldwide and constitute one of the leading causes of mortality and morbidity. Improving population diets can play an important role in preventing and managing the diseases. Effective and efficient interventions are needed to promote healthy eating behaviors among people. The objective of this review will be to evaluate the effectiveness of social marketing-based interventions to promote healthy nutrition behaviors.

Method

The following electronic databases will be searched from January 1990 onwards: PubMed/MEDLINE, EMBASE, Web of Science, and CENTRAL. We will include randomized and non-randomized trials, quasi-experimental studies, observational studies (e.g., cohort, cross-sectional, and before and after studies) evaluating the social marketing-based intervention.

The primary outcomes will be nutritional behaviors. Secondary outcomes will include the quality of life, nutritional status, and weight status. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random-effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, sex, and socio-economic condition).

Discussion

This study will summarize the evidence regarding the interventions’ components, implementation methods, and effectiveness of interventions based on the social marketing framework to promote healthy nutrition behaviors. This review can provide policymakers with the information needed to make decisions and plan to promote healthy eating behaviors and understand the factors influencing the implementation of these programs.

Systematic review registration

CRD42020163972
Inequalities in out-of-pocket health expenditure among women of reproductive age: after-effects of national health insurance scheme initiation in Ghana
Authors: Ekholuenetale Michael , Barrow Amadou
Published: March 2021

Background

Improvement in maternal healthcare is a public health priority. Unfortunately, in spite of the efforts made over time regarding universal coverage, there remain issues with accessibility and use of healthcare services up to now. In this study, we examined inequalities in out-of-pocket health expenditure among women of reproductive age in Ghana. We analyzed secondary data collected in Ghana Demographic and Health Survey (GDHS) - 2014. A total of 9,002 women of reproductive age were included in this study. Lorenz curves and the concentration index were used to examine neighborhood socioeconomic disadvantage inequalities in out-of-pocket expenditure for maternal healthcare utilization

Results

About two thirds (66.0%) of women of reproductive age in Ghana were covered by health insurance. In sum, women of high neighborhood socioeconomic disadvantage status had the least out-of-pocket expenditure for total healthcare utilization, laboratory investigations, antenatal care visits, post-natal care visits, care for new born for up to 3 months, and other healthcare services. The converse was however true for family planning service utilization. Using Concentration Index, we quantified the degree of neighborhood socioeconomic disadvantage inequalities in healthcare service utilizations.

Conclusion

This study showed a gap in health insurance coverage among women of reproductive age. There were also inequalities in out-of-pocket expenditure for healthcare services utilization. It is expedient for stakeholders in the healthcare system to make policies targeted at bridging the neighborhood socioeconomic differences in maternal healthcare use and develop programs to improve women’s financial protection. Moreover, enlightenment on health insurance availability and coverage should focus on women at risk of out-of-pocket expenditure.
Implementing the DEcision-Aid for Lupus (IDEAL): study protocol of a multi-site implementation trial with observational, case study design
Authors: Singh Jasvinder A. , Hearld Larry R. , Hall Allyson G. , Beasley T. Mark
Published: March 2021

Objective

To provide the details of the study protocol for an observational, case study design, implementation trial.

Methods

Implementing the DEcision-Aid for Lupus (IDEAL) study will put into practice a shared decision-making (SDM) strategy, using an individualized, culturally appropriate computerized decision-aid (DA) for lupus patients in 15 geographically diverse clinics in the USA. The overarching frameworks that guide this implementation study are the Consolidated Framework for Implementation Research (CFIR) and Powell’s typology of implementation strategies. All 15 clinics will receive standardized capacity-building activities for lupus DA implementation in the clinic, including education, training, technical assistance, re-training, and incorporation of a clinic champion in the core team of each site. In addition, clinics will also choose among clinic-targeted activities to integrate the DA into existing work processes and/or patient-targeted activities to raise awareness and educate patients about the DA. These activities will be chosen to stimulate participant recruitment and retention activities that support the implementation of the DA at their clinic. In study aim 1, using surveys and semi-structured interviews with clinic personnel in 15 lupus clinics, we will assess stakeholder needs and identify clinic and contextual characteristics that inform the implementation strategy component selection and influence implementation effectiveness. Study aim 2 is to implement and assess the effectiveness of the IDEAL (standardized and tailored) strategy in 15 lupus clinics by examining the changes in our primary outcome of penetration, i.e., the proportion of all eligible patients in the clinic that receive the lupus DA, and secondary outcomes include DA appropriateness, acceptability, success, permanence, and feasibility. Study aim 3 is to identify ways to sustain and disseminate our lupus DA via semi-structured debriefing interviews with key clinic personnel and patients.

Discussion

The study will enroll at least 500 patient participants with lupus across all 15 sites and assess the effectiveness in implementing the DA in various clinic settings across the USA.

Trial registration

ClinicalTrials.gov, NCT03735238. Protocol version number: 15, date 6/8/2020
3D inversion of time-domain electromagnetic data using finite elements and a triple mesh formulation
Authors: Zhang Bo , Engebretsen Kim Wann , Fiandaca Gianluca , Cai Hongzhu , Auken Esben
Published: March 2021

Over several decades, much research has been done to develop 3D electromagnetic inversion algorithms. Due to the computational complexity and the memory requirements for 3D time-domain electromagnetic (TEM) inversion algorithms, many real-world surveys are inverted within one dimension. To speed up calculations and manage memory for 3D inversions of TEM data, we have developed an approach using three uncoupled meshes: an inversion mesh, a forward-model mesh, and a mesh for Jacobian calculations. The inversion mesh is a coarse regular and structured mesh, such that constraints are easily enforced between the model parameters. Forward responses are calculated on a dense unstructured mesh to obtain accurate electromagnetic fields, whereas the Jacobian is calculated on a coarse unstructured mesh. We found that using a coarse mesh for the Jacobian is sufficient for the inversion to converge and, equally important, that it provides a significant speed boost in the overall inversion process, compared to calculating it on the forward-modeling mesh. The unstructured meshes are made of tetrahedral elements, and the electromagnetic fields are calculated using the finite-element method. The inversion optimization uses a standard Gauss-Newton formulation. For further speed up and memory optimizing of the inversion, we use domain decomposition for calculating the responses for each transmitter separately and parallelize the problem over domains using OpenMP. Compared to a 1D solution, the accuracy for the Jacobian is 1%–5% for the dense mesh and 2%–7% for the coarse mesh, but the calculation time is approximately five times faster for the coarse mesh. We also examined the algorithm on a small ground-based TEM data set acquired in an area where a 3D earth distorts the electromagnetic fields to such a degree that a 1D inversion is not feasible.
Modeling extra-deep electromagnetic logs using a deep neural network
Authors: Alyaev Sergey , Shahriari Mostafa , Pardo David , Omella Ángel Javier , Larsen David Selvåg , Jahani Nazanin , Suter Erich
Published: March 2021

Modern geosteering is heavily dependent on real-time interpretation of deep electromagnetic (EM) measurements. We have developed a methodology to construct a deep neural network (DNN) model trained to reproduce a full set of extra-deep EM logs consisting of 22 measurements per logging position. The model is trained in a 1D layered environment consisting of up to seven layers with different resistivity values. A commercial simulator provided by a tool vendor is used to generate a training data set. The data set size is limited because the simulator provided by the vendor is optimized for sequential execution. Therefore, we design a training data set that embraces the geologic rules and geosteering specifics supported by the forward model. We use this data set to produce an EM simulator based on a DNN without access to the proprietary information about the EM tool configuration or the original simulator source code. Despite using a relatively small training set size, the resulting DNN forward model is quite accurate for the considered examples: a multilayer synthetic case and a section of a published historical operation from the Goliat field. The observed average evaluation time of 0.15 ms per logging position makes it also suitable for future use as part of evaluation-hungry statistical and/or Monte Carlo inversion algorithms within geosteering workflows.
An adaptable technique for comparative image assessment: Application to crosswell electromagnetic survey design for fluid monitoring
Authors: Commer Michael , Alumbaugh David L. , Wilt Michael , Cihan Abdullah , Um Evan S. , Petrusak Robin , Birkholzer Jens T.
Published: March 2021

Reservoir integrity stewardship accompanying carbon capture and sequestration considers fluid extraction and reinjection as a risk-mitigating method against overpressuring that could lead to caprock damage and ensuing [Formula: see text] leakage. Crosswell electromagnetics offers a technically viable monitoring method with the spatial volume coverage necessary for reservoir-encompassing pressure management. However, a certain logistic dilemma for deep gas sequestration into saline and thus electrically conductive aquifers is that crosswell magnetic-field measurements underperform in the imaging of more resistive plume bodies, further exacerbated when vertical arrays intersect, as opposed to surround, plumes. Comparative synthetic-data plume imaging of such scenarios rates the information content of magnetic-field versus electric-field 3D crosswell layouts for reservoir and infrastructure conditions of a representative pilot site in a coastal area in Florida. The image quality of the resulting plume replications can be ranked numerically through a newly proposed semblance qualifier, appraising the model goodness of fit to a given reference. In contrast to common least-squares measures for goodness of fit, the semblance formulation uses classifying logistic function types, thus enabling a better distinction of predefined anomaly features.
Localization of deep voids through geophysical signatures of secondary dewatering features
Authors: Glaser Dan R. , Burch Katrina , Brinkley Dennis L. , Reppert Philip
Published: March 2021

Discrete deep targets are a significant challenge for most surface-based geophysical techniques, even when considering high property contrasts. In general, surface-based geophysical methods lose lateral and vertical resolution with depth as a result of the limited acquisition geometry and increased signal attenuation. The former can be overcome through use of cross-borehole methods, but lateral localization is still needed for optimal borehole placement. As such, a relatively small, deep void located near the maximum depth of investigation (DOI) is very unlikely to be detected. Yet, secondary features associated with these voids can be exploited for enhanced detection performance. When voids are located below the groundwater table, a significant amount of dewatering and pumping is required to make them a functional passageway. This dewatering not only removes water from the void space but also the surrounding formation, resulting in a much larger, if more diffuse, secondary target: an induced groundwater table gradient. Many geophysical sensing methods are sensitive to subsurface moisture content. We have implemented a 2D joint-petrophysical mixing model (JPM), using inverted electrical resistivity tomography (ERT) and inverted seismic refraction models to sense changes in the groundwater table gradient. Our results are validated using the depth to bedrock, groundwater-surface water information, ground-penetrating radar, and time-domain reflectometry methods. Our initial proof of concept is applied to a shallow area with a significant soil moisture gradient, through different surface soil types and bedrock. The 2D JPM results are used to generate an estimate of air, moisture, and matrix percent fractions in the investigation area, providing a clear delineation of the groundwater surface and associated gradient. This refined hydraulic gradient estimate can then be used to laterally locate a void at or below the DOI of ERT and seismic refraction.
Incidence and Predictors of Hypertension in a Cohort of Australian Women With and Without Polycystic Ovary Syndrome
Authors: Joham Anju E , Kakoly Nadira S , Teede Helena J , Earnest Arul
Published: March 2021

Context

There are limited studies in large population-based settings examining the relationship between polycystic ovary syndrome (PCOS) and hypertension.

Objective

To evaluate incidence of hypertension among women with and without PCOS over a 15-year period.

Design

Secondary analysis of longitudinal data from the Australian Longitudinal Study on Women’s Health.

Setting

General community.

Participants

Women were randomly selected from the national health insurance database. 9508 women, aged 21-42 years, were followed up from 2000 to 2015.

Methods

We conducted survival analysis using Cox proportional hazards model to identify predictors of hypertension and person-time analysis to calculate incidence rates of hypertension.

Results

9508 women were followed for 145 159 person years (PY), and 1556 (16.37%) women developed hypertension during follow-up. The incidence of hypertension was significantly higher (P = 0.001) among women with PCOS (17/1000 PY) compared to women without (10/1000 PY). Women with known PCOS status totaled 8223, of which 681 women (8.3%) had self-reported physician-diagnosed PCOS. Incidence rate difference of hypertension (cases attributable to PCOS) was 4-fold higher (15.8/1000 PY vs 4.3/1000 PY) among obese women with PCOS compared to age-matched lean women with PCOS. PCOS was independently associated with 37% greater risk of hypertension (hazard ratio 1.37, 95% confidence interval 1.14-1.65), adjusting for body mass index (BMI), family history of hypertension, occupation, and comorbidity with type 2 diabetes.

Conclusions

Women with PCOS are more likely to develop hypertension from early adulthood, independent of BMI, which is further exacerbated by obesity. Including PCOS in hypertension risk stratification assessments may aid efforts in early identification of the disorder.
Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa
Authors: Singhal Vibha , Bose Amita , Slattery Meghan , Haines Melanie S , Goldstein Mark A , Gupta Nupur , Brigham Kathryn S , Ebrahimi Seda , Javaras Kristin N , Bouxsein Mary L , Eddy Kamryn T , Miller Karen K , Schoenfeld David , Klibanski Anne , Misra Madhusmita
Published: March 2021

Context

Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.

Objective

To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.

Design

Double-blind, randomized, placebo-controlled 12-month longitudinal study.

Participants

Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study.

Intervention

Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1−). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range.

Main Outcome Measures

Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates.

Results

Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1− compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1− (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1− experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups.

Conclusions

We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
Effect of Testosterone Treatment on Bone Microarchitecture and Bone Mineral Density in Men: A 2-Year RCT
Authors: Ng Tang Fui Mark , Hoermann Rudolf , Bracken Karen , Handelsman David J , Inder Warrick J , Stuckey Bronwyn G A , Yeap Bu B , Ghasem-Zadeh Ali , Robledo Kristy P , Jesudason David , Zajac Jeffrey D , Wittert Gary A , Grossmann Mathis
Published: March 2021

Context

Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown.

Objective

We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution–peripheral quantitative computed tomography (HR-pQCT).

Methods

Men ≥ 50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect.

Results

Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P < 0.001 or 3.1% (1.2, 5.0); radial cortical vBMD, 8.96 mg HA/cm3 (3.30, 14.62), P = 0.005 or 2.9% (1.0, 4.9); total tibial vBMD, 4.16 mg HA/cm3 (2.14, 6.19), P < 0.001 or 1.3% (0.6, 1.9); and total radial vBMD, 4.42 mg HA/cm3 (1.67, 7.16), P = 0.002 or 1.8% (0.4, 2.0). Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, −48.1 ng/L [−81.1, −15.1], P < 0.001 and P1NP, −6.8 μg/L[−10.9, −2.7], P < 0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm2 (0.03, 0.05), P < 0.001 and the total hip, 0.01 g/cm2 (0.01, 0.02), P < 0.001.

Conclusion

In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.
The Impact of Low-dose Gliclazide on the Incretin Effect and Indices of Beta-cell Function
Authors: Cordiner Ruth L M , Mari Andrea , Tura Andrea , Pearson Ewan R
Published: March 2021

Aims/Hypothesis

Studies in permanent neonatal diabetes suggest that sulphonylureas lower blood glucose without causing hypoglycemia, in part by augmenting the incretin effect. This mechanism has not previously been attributed to sulphonylureas in patients with type 2 diabetes (T2DM). We therefore aimed to evaluate the impact of low-dose gliclazide on beta-cell function and incretin action in patients with T2DM.

Methods

Paired oral glucose tolerance tests and isoglycemic infusions were performed to evaluate the difference in the classical incretin effect in the presence and absence of low-dose gliclazide in 16 subjects with T2DM (hemoglobin A1c < 64 mmol/mol, 8.0%) treated with diet or metformin monotherapy. Beta-cell function modeling was undertaken to describe the relationship between insulin secretion and glucose concentration.

Results

A single dose of 20 mg gliclazide reduced mean glucose during the oral glucose tolerance test from 12.01 ± 0.56 to 10.82 ± 0.5mmol/l [P = 0.0006; mean ± standard error of the mean (SEM)]. The classical incretin effect was augmented by 20 mg gliclazide, from 35.5% (lower quartile 27.3, upper quartile 61.2) to 54.99% (34.8, 72.8; P = 0.049). Gliclazide increased beta-cell glucose sensitivity by 46% [control 22.61 ± 3.94, gliclazide 33.11 ± 7.83 (P = 0.01)] as well as late-phase incretin potentiation [control 0.92 ± 0.05, gliclazide 1.285 ± 0.14 (P = 0.038)].

Conclusions/Interpretation

Low-dose gliclazide reduces plasma glucose in response to oral glucose load, with concomitant augmentation of the classical incretin effect. Beta-cell modeling shows that low plasma concentrations of gliclazide potentiate late-phase insulin secretion and increase glucose sensitivity by 50%. Further studies are merited to explore whether low-dose gliclazide, by enhancing incretin action, could effectively lower blood glucose without risk of hypoglycemia.
IL-38 Exerts Anti-Inflammatory and Antifibrotic Effects in Thyroid-Associated Ophthalmopathy
Authors: Shi Lu , Ye Huijing , Huang Jun , Li Yanbing , Wang Xing , Xu Zhihui , Chen Jingqiao , Xiao Wei , Chen Rongxin , Yang Huasheng
Published: March 2021

Context

Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves’ disease. IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases.

Objective

We aimed to evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO.

Methods

Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts were isolated from patients with TAO. Enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, immunofluorescence, quantitative real-time PCR and Western blot analysis were performed.

Results

Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared with the controls, and levels were negatively correlated with the clinical activity score. In vitro, potent anti-inflammatory and antifibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways.

Conclusion

IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy.
Association of Genetically Predicted Serum Estradiol With Risk of Thromboembolism in Men: A Mendelian Randomization Study
Authors: Nethander Maria , Quester Johan , Vandenput Liesbeth , Ohlsson Claes
Published: March 2021

Context

An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men, but a possible causal role of estradiol for risk of thromboembolism in men remains unknown.

Objective

This work aimed to determine whether endogenous estradiol has a causal role in thromboembolism in men.

Methods

A 2-sample mendelian randomization study using gene-based genetic instruments assessed the association between endogenous estradiol genetically predicted by 22 variants in the aromatase CYP19A1 gene region and the risk of thromboembolism (5815 cases) in 170 593 unrelated men of White ancestry in the UK Biobank. The main outcome measure included thromboembolism based on self-reports, hospital episodes, and death.

Results

Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of thromboembolism (odds ratio per SD increase in estradiol 0.74; 95% CI, 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39; 95% CI, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of ischemic stroke (0.68; 95% CI, 0.49-0.95) but not myocardial infarction (0.97; 95% CI, 0.84-1.13).

Conclusion

Genetically predicted estradiol was inversely associated with the risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by CYP19A1 activity, may contribute to the overall impact of sex steroids on thromboembolism in men.
Implications of an Improved Model of the TSH Receptor Transmembrane Domain (TSHR-TMD-TRIO)
Authors: Mezei Mihaly , Latif Rauf , Das Bhaskar , Davies Terry F
Published: March 2021

The thyroid-stimulating hormone receptor (TSHR) is a G-protein-coupled receptor group A family member with 7 transmembrane helices. We generated 3 new models of its entire transmembrane region using a 600 ns molecular simulation. The simulation started from our previously published model, which we have now revised by also modeling the intracellular loops and the C-terminal tail, adding internal waters and embedding it into a lipid bilayer with a water layer and with ions added to complete the system. We have named this model TSHR-TMD-TRIO since 3 representative dominant structures were then extracted from the simulation trajectory and compared with the original model. These structures each showed small but significant changes in the relative positions of the helices. The 3 models were also used as targets to dock a set of small molecules that are known active compounds including a new TSHR antagonist (BT362), which confirmed the appropriateness of the model with some small molecules showing significant preference for one or other of the structures.