bluuebunny/crossref_metadata_2025 huggingface dataset:
"This Screening Cannot Be Done For Virgins Because They Have Not Had any Sexual Intercourse " Knowledge on Cervical Cancer Screening and Vaccination Among Females at Oyibi Community.
Authors: Osei Evans , Appiah Stella , Gaogli Judith , Oti-Boadi Ezekiel
Published: January 2021

BackgroundAwareness about cervical cancer screening and vaccination in the developed countries are high as compared to the developing countries. Sixty to eighty percent (60 - 80%) of the women who develop cervical cancer in sub-Saharan Africa live in the rural areas with inadequate awareness on cervical cancer screening. However, cervical cancer knowledge remained a significant direct predictor of screening behaviors. The study therefore aim to explore the Knowledge on Cervical Cancer Screening and Vaccination among females at Oyibi Community. A qualitative exploratory design was employed to purposively recruit 35 participants who were made up of 7 members in a group forming 5 Focus Group discussions in all. Data was retrieved using a semi-structured interview guide. ResultsThe study revealed two main themes with 7 subthemes. The two main themes were Cervical cancer screening and vaccination knowledge and Cervical cancer vaccination effectiveness and cost. The subthemes were; knowledge on cervical cancer screening types, knowledge about cervical cancer screening and vaccination centers, knowledge about how cancer screening is performed, knowledge about cervical cancer vaccination, cervical cancer screening and vaccination sources of information, knowledge about the effectiveness of cervical cancer vaccination and awareness about cervical cancer screening cost and vaccination cost. ConclusionThe study revealed low knowledge on screening and vaccination of cervical cancer, and effectiveness of cervical cancer vaccination but high awareness about the centers. There is therefore the need for heightened sensitization regarding cervical cancer screening and vaccination in rural communities to help reduce misconceptions and increase patronage rate.
Cost Effectiveness Analysis of a Polygenic Risk Tailored Breast Cancer Screening Programme in Singapore
Authors: Wong Jerry Zeng Yang , Chai Jia Hui , Yeoh Yen Shing , Riza Nur Khaliesah Mohamed , Liu Jenny , Teo Yik-Ying , Wee Hwee Lin , Hartman Mikael
Published: January 2021

BackgroundThis study aimed to evaluate the cost effectiveness of a breast cancer screening programme that incorporates genetic testing using breast cancer associated single nucleotide polymorphisms (SNPs) in Singapore, against the current biennial mammogram only screening programme.MethodsA Markov model was used to compare the costs and health outcomes of the current screening programme, against a polygenic risk tailored screening programme that advises long term screening depending polygenic risk. The model took the perspective of the healthcare system, with a time horizon of 40 years, following women from the age of 35 to 74. Epidemiological and cost data was taken from Asian studies. An annual discount rate of 3% was used. The model outcome was the incremental cost-effectiveness ratio (ICER), calculated from the difference in costs per quality adjusted life year (QALY). Scenarios with varying risk thresholds for each polygenic risk group were examined. One-way and probabilistic sensitivity analyses were performed to assess parameter uncertainty.ResultsThe ICER for a polygenic risk tailored breast cancer screening programme, compared to the current biennial mammogram only screening programme, was -3,713.80, with incremental costs <0 and incremental effects >0. Scenario analysis of different polygenic risk cutoffs showed that the ICERs remain negative, with all ICERs falling within the south east quadrant of the cost effectiveness plane, indicating that tailored screening dominates mammogram only screening with lower costs and higher QALYs. This suggests that a polygenic risk tailored breast cancer screening programme is cost effective, being cheaper than the current mammogram only programme while bringing no additional harm to women.ConclusionResults from this cost effectiveness analysis show that polygenic risk tailored screening is cost effective with an ICER of –3,713.80 SGD/QALY. Tailored screening remains cost effective even when varying percentile cutoffs for each risk group. While the results look promising for incorporating polygenic risk into the current breast cancer screening programme, further studies should be conducted due to various limitations.
An Activity Recognition Framework for Monitoring Non-Steady-State Locomotion of Individuals with Parkinson’s Disease
Authors: Kazemimoghadam Mahdieh , Fey Nicholas
Published: January 2021

Background: Fundamental knowledge in activity recognition of individuals with motor disorders such as Parkinson’s disease (PD) has been primarily limited to detection of steady-state/static tasks (e.g., sitting, standing, walking), and identification of non-steady-state locomotion on uneven terrains (stairs, ramps) has not received much attention. Furthermore, previous research has mainly relied on data from a large number of locations which could adversely affect user convenience and system performance. Methods: Here, individuals with mild stages of PD and healthy subjects performed non-steady-state circuit trials comprising stairs, ramp, and changes of direction. An offline analysis using a linear discriminant analysis (LDA) classifier and a Long-Short Term Memory (LSTM) neural network was performed for task recognition. The performance of accelerographic and gyroscopic information from varied lower/upper-body segments were tested across a set of user-independent and user-dependent training paradigms. Results: Comparing the F1 score of a given segment across classifiers showed improved performance using LSTM compared to LDA. Using LSTM, even a subset of information (e.g., feet data) in subject-independent paradigms appeared to provide F1 score > 0.8. However, employing LDA was shown to be at the expense of being limited to using a subject-dependent paradigm and/or biomechanical data from multiple body locations. Conclusion: The findings could inform a number of applications in the field of healthcare monitoring and developing advanced lower-limb assistive devices by providing insights into classification schemes capable of handling non-steady-state and unstructured locomotion in individuals with mild Parkinson’s disease.
Rigorous Method of Weights Calculation in Adjustment of Measurement Data with Different Qualities
Authors: Xiaoming Ye , Shijun Ding
Published: January 2021

In the traditional measurement theory, precision is defined as the dispersion of measured value, and is used as the basis of weights calculation in the adjustment of measurement data with different qualities, which leads to the trouble that trueness is completely ignored in the weight allocation. In this paper, following the concepts of pure probability theory, the measured value (observed value) is regarded as a constant, the error as a random variable, and the variance is interpreted as the dispersion of all possible values of the error. Thus, a rigorous formula for weights calculation and variance propagation is derived, which solves the theoretical problem of determining the weight values in the adjustment of multi-channel observation data with different qualities.
A Novel External Fixator to Facilitate Accurate and Efficient Fracture Treatment
Authors: Shen Mingkui , Wang Lulu , Ai Zizheng , Li Jingna , Liang Huaping , Dong Xieping
Published: January 2021

Background: The rapid popularization and application of bone external fixation technology has led to external fixators emerging as remarkable methods to treat various complex fractures. Because of their instability, assembly complexity and poor controllability, however, new external fixators are challenging to design in terms of facilitating accurate and efficient fracture treatment.Methods: We designed a novel external fixator that could feasibly treat clinical complex fractures. A prospective study was conducted on patients with various complex fractures from September 2017 to September 2019. During this period, we treated 24 patients with a universal joint external fixator and then evaluated its therapeutic effects. In this study, adult cadaver femur fracture fixations were modelled by using universal joint (UJ) and AO external fixators, and the mechanical stability was assessed by applying a biomechanical testing device.Results: The designed device not only fits the repair site but could also be conveniently installed and implanted. All patients achieved good fixation and fracture healing with the universal joint fracture external fixators. In in vitro biomechanical testing, constructs were loaded under axial compression, lateral compression and torsion. Overall axial stiffness showed no significant differences between the two groups. The lateral stiffness was 1.554 ± 0.017 mm for the UJ group and 1.342 ± 0.020 mm for the AO group (p<0.001) under a 600 N load, while the torsional stiffness was 15.727 ± 0.141° for the UJ group and 14.472 ± 0.292° for the AO group under a 40 Nm load.Conclusion: In this small and preliminary study, the universal joint external fixator, which achieved a stable mechanical structure, was capable of intensive and efficient treatment for comprehensive fractures. If these findings can be confirmed in a larger study, this external fixator may be widely used in certain situations where traditional external fixators are not a convenient option.
Postoperative Bisphosphonate Do Not Significantly Alter The Fusion Rate After Lumbar Spinal Fusion: A Meta-Analysis
Authors: Mei Jun , Song Xiaoxu , Guan Xiaoming , Wu Dou , Wang Junjie , Liu Qiang
Published: January 2021

BACKGROUND: To evaluate the effect of postoperative BP treatment on improving the fusion rate after lumbar spinal fusion surgery by performing a meta-analysis of randomized controlled trials (RCTs) and other comparative cohort studies.METHODS: A comprehensive search of PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for RCTs and other comparative cohort studies on the effect of BP treatment on improving the fusion rate after lumbar spinal fusion surgery. The primary outcome measures were the number of patients with bone formation grades A, B, and C at 12 months of follow-up, fusion rates at 12 and 24 months of follow-up, vertebral compression fracture (VCF) at 12 and 24 months of follow-up, pedicle screw loosening at 24 months follow-up, cage subsidence, the Oswestry Disability Index (ODI) and the visual analogue score (VAS) at 12 months of follow-up. The final search was performed in July 2020.RESULTS: Seven studies with 401 patients were included. Compared with the placebo, BP treatment did not significantly alter the number of patients with bone formation grades A, B and C, or the VAS at the 12-month follow-up or the fusion rates at the 12- and 24-month follow-ups. In addition, compared with the placebo, BPs significantly reduced the risks of VCF at the 12- and 24-month follow-ups, pedicle screw loosening at the 24-month follow-up, and cage subsidence and the ODI at the 12-month follow-up.CONCLUSIONS: Postoperative BPs do not clearly improve bone formation and the fusion rate, but they reduce VCF, cage subsidence and loosening of pedicle screws after lumbar fusion surgery compared with the control treatment.
Comparison of SDSG and CARDS Classifications for L5/S1 Lumbar Degenerative Spondylolisthesis: an Independent Inter- and Intra-observer Agreement Study
Authors: Sun Zhengwang , Xu Chongqing , Yin Mengchen , Yan Wangjun
Published: January 2021

Background: Lumbar degenerative spondylolisthesis (DS) has been a common disease that make increasing patients suffer from different degrees of low back pain and radicular symptoms. SDSG and CARDS systems are commonly used to classify the disease, and help to make a more detailed treatment plan. The objective of this study is to evaluate the reliability and reproducibility of SDSG and CARDS classifications, and to explore their clinical application value.Methods/Design: All 117 patients with L5/S1 lumbar DS were enrolled. 5 spine surgeons who have certain clinical experience were selected. They determined the classification according to S SDSG and CARDS systems, we used kappa (K) value to check the coefficient consistency for multi-factor and assess the inter- and intra-observer agreement. After 12 weeks, we repeated the analysis.Results: The inter-observer reliability and intra-observer reproducibility of SDSG system were substantial with K values of 0.704 and 0.861, while those of CARDS system were substantial with values of 0.620 and 0.878.Conclusion: SDSG system has better inter-observer reliability in comparison with CARDS system, and though CARDS system is more intuitive and simpler, it is more likely to produce deviations when using it. Since both SDSG and CARDS systems show substantial agreement and have great significance in surgical strategy of L5/S1 lumbar DS, they can be widely used in clinical practice.
Particularities of the Evolution of SARS-CoV-2 Infection in Children
Authors: MARIA TOTAN , Grigore Camelia , ANTONESCU ELISABETA , Gligor Felicia , Duica Lavinia , Silisteanu Sinziana , Maniu Ionela , Cristea Stefan , Grigore Nicolae
Published: January 2021

IntroductionSARS-CoV-2 virus infection was first reported in China in late 2019 and has spread rapidly around the world. There is little information about the peculiarities of COVID-19 infection in children because the number of infected children was small, around 2% of all diseases.MethodsIn this retrospective study, we recruited 143 children infected with SARS-CoV-2 between March and October 2020, in Sibiu, Romania. RT-PCR tests, serum SARS-CoV-2 IgG/ IgM antibodies, lung radiography, biochemical and hematological tests were performed during the hospitalization.ResultsOf the 143 children selected in the study, 47.0% were male and 53% were female. At admission, all children tested positive for SARS-CoV-2, collecting nasopharyngeal exudate.Clinical manifestations included: cough in 75.52% of cases, fever in 55.94% of cases, nasal obstruction in 50.34% of cases, rhinorrhea in 38.46% of cases, muscle pain in 26.57% of cases, fatigue in 17.48% of cases, diarrhea and headache in 14.68% of cases. In 21 children (14,68%), the number of leukocytes was increased. In 38 cases (26,57%), the lung radiograph showed changes similar to bronchopneumonia, and the other cases did not have pulmonary changes. The persistence of the virus in the body of infected children is above the average reported in studies performed in adults, the virus being identified in the respiratory tract between 16 and 34 days. IgG class antibodies in patients' serum appeared between the 4th day of hospitalization and up to a maximum of 25 days, with a mean of 16.5 days.ConclusionThe persistence of the virus in the body of infected children is above the average reported in studies performed in adults, the virus being identified in the respiratory tract between 16 and 34 days. IgG class antibodies in patients' serum appeared within a mean of 16.5 days. All children were treated with symptomatic support without complications.
The Long-term Outcomes of Hepatic Resection Between Single Tumor and Multiple Tumors of HCC Meeting UCSF Criteria
Authors: Zheng Jinli , Xie Wei , Huang Yang , Pu Xingyu , Jiang Li
Published: January 2021

Object: Searching the hepatectomy of hepatocellular carcinoma (HCC) within UCSF is limited. The study aims to compare the long-term surgical outcomes between single and multiple tumors to find an effective and safe treatment for the patients within UCSF criteria.Methods: We have enrolled 1006 patients meeting UCSF criteria, including 744 patients with single tumor and 262 patients with multiple tumors undergoing hepatic resection (HR). We divided the patients into two groups: single tumor group and multiple tumor group. By comparing the long-term outcomes between these two groups and analyzing the risk factors by the log-rank test and cox proportional hazards model in two groups.Results: The 1-, 3-, and 5-year OS rates in the single tumor group were significantly higher than the multiple tumors group (96.2%, 65.3% and 40.1% versus 93.1%, 47.6% and 22.5%, respectively, p<0.001). The 1-, 3- and 5-year RFS rates were 91.4%, 46.2%, and 24.6% in the single group and 90.8%, 31.1% and 13.0%, respectively (p<0.001). And the anatomic resection and MVI were the independent risk factors for single tumor, but it didn’t work for multiple tumors. The independent risk factors of multiple tumors are the diameter more than 2cm of the maximum tumor and the tumors located in different segments.Conclusion: The surgical resection will obtain a better outcomes for the HCC with single tumor meeting UCSF criteria than the multiple tumors. And the anatomic resection should be applied for the patients with single tumor, if possible.
Recurrent Colorectal Liver Metastasis Patients Would Benefit to Repeat Hepatic Resection
Authors: Liu Wei , Liu Jia-Ming , Wang Kun , Wang Hong-Wei , Xing Bao-Cai
Published: January 2021

Background
Local treatment remains the best option for recurrent colorectal liver metastasis. The current study aims to investigate predictive factors of survival outcomes and select candidates of local treatment for CRLM at first recurrence.
Methods
Data were collected retrospectively on CRLM patients who underwent hepatic resection and developed first recurrence between 2000 and 2019 at our institution. A nomogram to predict overall survival was established based on a multivariable Cox model of clinicopathologic factors. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index and calibration curve.
Results
Among 867 patients who underwent curative hepatic resection, 549 patients developed recurrence. Three hundred patients were evaluated to be resectable and liver-limited disease. Among of them, repeat liver resection and percutaneous radiofrequency ablation were performed in 88 and 85 patients, respectively. The other 127 patients only received systemic chemotherapy. Multivariable analysis identified node-positive primary, tumor size > 3 cm, early recurrence, RAS gene mutation and no local treatment were independent risk factors for survival outcome. Integrating these five variables, the nomogram showed good concordance statistics of 0.707. Compared with patients who only received systemic chemotherapy, radical local treatment did not improve survival outcome significantly (median OS: 21 vs. 15 months, p = 0.126) in high risk group (total score above 13).
Conclusion
Radical local treatment is crucial to prolong the survival of recurrent CRLM patients. The proposed model facilitates personalized assessment of prognosis for patients who developed first recurrence in liver.
Development of a Web Tool to Calculate the Cumulative Dose of Glucocorticoids
Authors: Montero-Pastor Nuria , Sánchez-Costa Jesús , Guerra-Rodríguez Mercedes , Moriano Clara , Loricera Javier , Díaz-González Federico
Published: January 2021

Glucocorticoids are associated with many serious side effects, most of which are related to dosing and time of use. Correct assessment of cumulative dose, especially in patients undergoing long-term treatment, is essential to determine the risk of undesirable glucocorticoid-related events. Unfortunately, there is no standard method currently available for determining exposure to glucocorticoids in daily clinical practice. The aim of this work was to create an easy-to-use free-access web application to help clinicians and researchers calculate, in a systematic way, the cumulative dose of corticosteroids in their patients. The total cumulative dose is calculated as the sum of all periods of treatment with different doses of oral or intravenous corticosteroids, and is expressed as the equivalent dose of prednisone in mg. The doses of glucocorticoids during the periods without information are estimated by first determining the average doses between the previous and subsequent periods for which such information is available, and then multiplying that average dose by the number of days of the period. If the day on which glucocorticoids were discontinued is unknown, it is assumed to be the day before the start of the next known treatment period. For unknown start dates, the day after the end of the known prior period is used. In conclusion, this tool simplifies and, through the systematic application of assumptions when information is incomplete, standardizes the glucocorticoids cumulative dose calculation, minimizing bias in the assessment of glucocorticoid-related side effects in the context of daily clinical practice.
The iDEM trial (intervention for Dengue Epidemiology in Malaysia) to measure the effectiveness of integrated vector management with targeted outdoor residual spraying and autodissemination devices on the incidence of dengue in urban Malaysia: Study protocol for a cluster randomized controlled trial
Authors: SAADATIAN-ELAHI Mitra , Alexander Neal , Möhlmann Tim , Langlois-Jacques Carole , Suer Remco , Ahmad Nazni Wasi , Mudin Rose Nani , Ariffin Farah Diana , Baur Frederic , Schmitt Frederic , Richardson Jason H , Rabilloud Muriel , Hamid Nurulhusna Ab
Published: January 2021

Background: In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 hours of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs. The principal objective of this cluster randomized controlled trial is to quantify the effectiveness of a preventive integrated vector management (IVM) strategy on the incidence of dengue as compared to routine vector control efforts. Methods: The trial is conducted in randomly allocated low and medium cost clusters located in the Federal Territory of Kuala Lumpur and Putrajaya. The IVM approach combines: targeted outdoor residual spraying with K-Othrine Polyzone, deployment of mosquito traps as auto-dissemination devices, and community engagement activities. The trial includes 280 clusters randomly allocated in a 1:1 ratio. The clusters receive either the preventive IVM in addition to the routine vector control activities, or the routine vector control activities only. Epidemiological data from monthly confirmed dengue cases during the study period will be obtained from the Vector Borne Disease Sector, Malaysian Ministry of Health e-Dengue surveillance system. Entomological surveillance data will be collected in 12 clusters randomly selected from each arm. To measure the effectiveness of the IVM approach on dengue incidence, a negative binomial regression model will be used to compare the incidence between control and intervention clusters. To quantify the effect of the interventions on the main entomological outcome, ovitrap index, a modified ordinary least squares regression model using a robust standard error estimator will be used. Discussion: Considering the ongoing expansion of dengue burden in Malaysia, setting up proactive control strategies is critical. Despite some limitations of the trial such as the use of passive surveillance to identify cases the results will be informative for a better understanding of effectiveness of proactive IVM approach in the control of dengue. Evidence from this trial may help justify investment in preventive IVM approaches as preferred to reactive case management strategies. Trial registration: ISRCTN, ISRCTN81915073, retrospectively registered on 17 April 2020 (https://doi.org/10.1186/ISRCTN81915073)
The Challenges of Recruitment to a Randomised Trial Registry – What Information Matters to the Patient?
Authors: Murphy Ellen , Shea Niamh O , O'Keeffe Aoife , Long Eva , Eustace Joseph , Shiely Frances
Published: January 2021

Background Randomised controlled trials (RCTs) are the gold standard for demonstrating efficacy of new therapies. Despite this, nephrology trials, especially of patients with end stage renal disease (ESRD) are much fewer in number than other specialties. Recruitment difficulties are cited as a particular challenge. Using registries to conduct RCTs is a reasonably new practice but is appealing as it combines the benefits of observational studies and clinical trials. There is limited literature on patient motivators, barriers, and consent to these registries. The purpose of our study is to establish this. MethodsWe conducted a cross-sectional questionnaire-based study. A questionnaire consisting of closed and open-ended questions was collected at a dialysis centre in Southwest Ireland representing a catchment patient population of approximately 430,000. Quantitative data were coded and analysed in SPSS (v16). Descriptive statistics were produced, and open-ended questions were analysed by thematic analysis. Results 87 patients completed the questionnaire. Motivators for participation included personal and altruistic benefits. Barriers/concerns include time requirements, risks (incl. data safety) and side effects along with impacts on current treatment. Though a total of 29.8% of patients ‘strongly agree/agree’ to having concerns regarding their data storage in a registry, 79.3% of patients were ‘very likely/likely’ to consent to participate in the registry. It was important to patients to have their GP (general practitioner) involved in the decision to participate, despite little day-to-day contact with their GP for renal dialysis management. ConclusionImproving patients understanding of clinical trials, emphasising personal and altruistic benefits, and addressing patient’s concerns regarding time and risks of involvement, may improve their likelihood to participate in a registry for RCTs and more broadly speaking, RCTs.
The COVID-19 Pandemic and New Clinical Trial Activations
Authors: Unger Joseph , Xiao Hong
Published: January 2021

Background The Covid-19 pandemic has caused severe disruptions in care for many patients. A key question is whether the landscape of clinical research has also changed. Methods In a retrospective cohort study, we examined the association of the COVID-19 outbreak with new clinical trial activations. Trial data for all interventional and observational oncology, cardiovascular, and mental health studies from January, 2015 through September, 2020 were obtained from clinicaltrials.gov. An interrupted time-series analysis with Poisson regression was used. Results We examined 62,252 trial activations. During the initial COVID-19 outbreak (February, 2020 through May, 2020), model-estimated monthly trial activations for U.S.-based studies were only 57% of the expected estimate had the pandemic not occurred (relative risk = 0.57, 95% CI, 0.52 to 0.61, p<.001). For non-U.S.-based studies, the impact of the pandemic was less dramatic (relative risk = 0.77, 95% CI, 0.73 to 0.82, p<.001), resulting in an overall 27% reduction in the relative risk of new trial activations for U.S.-based trials compared to non-U.S.-based trials (relative risk ratio = 0.73, 95% CI, 0.67 to 0.81, p<.001). Although a rebound occurred in the initial reopening phase (June, 2020 through September, 2020), the rebound was weaker for U.S.-based studies compared to non-U.S. based studies (relative risk ratio = 0.87, 95% CI, 0.80 to 0.95, p<.001). ConclusionsThese findings are consistent with the disproportionate burden of COVID-19 diagnoses and deaths during the initial phase of the pandemic in the U.S. Reduced activation of cancer clinical trials will likely slow the pace of clinical research and new drug discovery, with long-term negative consequences for cancer patients. An important question is whether the renewed outbreak period of winter 2020/2021 will have a similarly negative impact on the initiation of new clinical research studies for non-COVID-19 diseases.
Computational Modelling of Dual-Phase Lag Bioheat Process in Cooling of Cutaneous Tissue Exposed to High Heating for Burn Injury Prediction
Authors: Oguntala George , Hu Yim Fun , Sobamowo Gbeminiyi
Published: January 2021

Heat transfer in biological systems is critical in analytic and therapeutic burn applications. Timely burn evaluation and appropriate clinical management are critical to ameliorate the treatment outcome of burn patients. To apply appropriate burn treatment, it is necessary to understand the thermal parameters of the skin. The paper aims to model the non-Fourier bioheat process in the human skin using a multi-domain trivariate spectral collocation method to determine skin burn injury with non-ideal properties of tissue, blood perfusion and metabolism. The skin tissue internal water evaporation during direct heating is considered. Parametric studies on the effects of skin tissue properties, initial temperature, blood perfusion rate and heat transfer parameters for the thermal response and exposure time of triple-layer cutaneous tissues are carried out. The study shows that the initial tissue temperature, the thermal conductivity of the epidermis and dermis, relaxation and thermalisation time and convective heat transfer coefficient are critical parameters necessary for skin burn injury baseline examination. The thermal conductivity and blood perfusion rate also exhibit negligible effects on the burn injury threshold of the cutaneous tissue. The present study is aimed to assist burn evaluation for reliable experimentation, design and optimisation of thermal therapy delivery.
Human Bone Marrow-Derived, Pooled, Allogeneic Mesenchymal Stromal Cells Manufactured From Multiple Donors at Different Times Show Comparable Biological Functions in Vitro, and in Vivo to Repair Limb Ischemia
Authors: Thej Charan , Balasubramanian Sudha , Rengasamy Mathiyazhagan , Walvekar Ankita , Swamynathan Priyanka , Raj Swathi Sundar , Shahani Pradnya , Siddikuzzaman  , Kolkundkar Udaykumar , Seetharam Raviraja N , Gupta Pawan Kumar , Majumdar Anish Sen
Published: January 2021

Background: We have previously demonstrated that a pooled population of BM-derived, allogeneic mesenchymal stromal cells (BMMSC), Stempeucel®-1, produced under good manufacturing practices (GMP) conditions, showed clinical efficacy and safety in patients suffering from critical limb ischemia (CLI) due to Buerger's disease. While Stempeucel®-1 is currently used for CLI and other clinical indications, we wanted to ensure that the product's continuity is addressed by developing and characterizing a second-generation of pooled product (Stempeucel®-1A), manufactured identically from a second BM aspirates of the same three donors after a two-year interval.Methods: The two versions of Stempeucel® were manufactured and subjected to gene and protein expression analysis. The nature of various growth factors/cytokines secreted, and immunomodulatory activity of these two cell populations were compared directly by various in vitro assays. The preclinical efficacy of these two cell types was compared in an experimental model of hind limb ischemia (HLI) in BALB/c nude mice. The reversal of ischemia, blood flow and muscle regeneration were determined by functional scoring, Laser Doppler Imaging and immunohistochemical analyses. Results: Qualitative and quantitative analyses of genes and proteins involved in promoting angiogenic activity and immune regulatory functions revealed high levels of correlation between Stempeucel®-1 and Stempeucel®-1A cell populations. Moreover, i.m administration of these two cell products in the ischemic limbs of BALB/c nude mice showed significant repair (>70%) of toe and foot necrosis, leading to improved ambulatory function and limb salvage. Furthermore, a biodistribution kinetics study showed that Stempeucel®-1 was mostly localized in the ischemic muscles of mice for a significantly longer time compared to normal muscles, thus playing an essential role in modulating and reversing HLI damage. Conclusions: This study shows that with a reproducible manufacturing procedure, it is possible to generate large numbers of pooled mesenchymal stromal cells from human bone marrow samples to establish product equivalence. We conclude from these results that, for the first time, two pooled, allogeneic BMMSC products can be repeatedly manufactured at different time intervals using a two-tier cell banking process with robust and comparable angiogenic properties to treat ischemic diseases.
Effects of Low Intensity Pulsed Ultrasound on Expression of Bax and Bcl-2 in Premature Ovarian Failure Mice Induced by 4-Vinylcyclohexene Diepoxide
Authors: Xu Haopeng , Xia Yi , Qin Juan , Xu Jie , Li Chongyan , Wang Yan
Published: January 2021

BackgroundPremature ovarian failure (POF) is a common disease in the field of gynecological. This study was performed to determine the effects of low intensity pulsed ultrasound (LIPUS) on granulosa cells (GCs) apoptosis and protein expression of Bax and Bcl-2 in 4-vinylcyclohexene diepoxide (VCD)-induced POF mice. The aim of this research is to investigate the mechanisms of LIPUS on ovarian function and reserve capacity.MethodsThe current POF mice model was administrated with VCD (160 mg/kg) by intraperitoneal injection for 15 consecutive days. The mice were divided into POF group, LIPUS group and control group. In the LIPUS group, the right ovary of mice was treated by LIPUS (acoustic intensity was 200 mW/cm2, frequency was 0.3 MHz, and duty cycle was 20%) for 20 minutes, 15 consecutive days from day 16. The mice of the POF group and control group were treated without ultrasonic output. The basic observation, Hematoxylin and eosin staining (H&E staining), TUNEL assay and immunohistochemistry were applied to detect the results.ResultsThe results showed that VCD can induce estrus cycle disorder, follicular atresia and GCs apoptosis in mice to establish POF model successfully. LIPUS significantly promoted follicular development, inhibited excessive follicular atresia and GCs apoptosis. The mechanism may be achieved by increasing the protein expression of Bcl-2 and decreasing the expression of Bax in ovaries.ConclusionsThese findings have the potential to provide novel methodological foundation for the future research, which help treat POF patients in the clinic.
Oocyte Survival and Development During Follicle Formation and Folliculogenesis in Mice Lacking Aromatase
Authors: Toothaker Jessica M. , Roosa Kristen , Voss Alexandra , Getman Suzanne M. , Pepling Melissa
Published: January 2021

BackgroundAssembly of oocytes into primordial follicles is essential for establishing the ovarian reserve required for female fertility. In mice, this process begins during embryonic development. Primordial germ cells form cysts by incomplete mitosis until 13.5 days post coitum (dpc). These cysts break down just before birth. Some oocytes undergo apoptosis while surviving oocytes are enclosed by granulosa cells to form primordial follicles. Cyst breakdown and primordial follicle formation were previously shown to be inhibited by estradiol and estrogenic compounds in vitro, suggesting that estrogen is important for regulation of this process. MethodsTo determine the role of fetal estrogen in cyst breakdown and follicle formation these processes were quantified in aromatase deficient (ArKO) mice between 17.5 dpc and postnatal day (PND) 9. Ovaries of ArKO mice were also examined at 2-week intervals to determine if folliculogenesis is affected by lack of estrogen and the age at which the typical ArKO ovarian phenotype first appears. ResultsOocyte number, follicle assembly and follicle development in ArKO mice did not differ from controls between 17.5 dpc and PND9 except for a difference in the proportion of follicles at the primordial and primary stage at PND7. At 2 weeks, ArKO heterozygous and homozygous ovaries still had oocytes in cyst while all oocytes were enclosed in follicles in wildtype ovaries. From 2 to 8 weeks oocyte numbers were similar in all genotypes though there was a trend toward fewer total oocytes in ArKO homozygous females as compared to controls at 8 weeks and a significant reduction at 10 weeks. Abnormal structures such as hemorrhagic follicles and hemosiderin deposits were also observed starting at 6 weeks. ConclusionsThese results suggest that a lack of fetal estrogen does not affect the rate of cyst breakdown or primordial follicle formation perinatally, and maternal estrogen or other signals are the chief regulators. Furthermore, the typical ArKO ovarian phenotype occurs earlier than previously reported.
Effect of Antithyroid Antibodies in the First Trimester on Pregnancy Outcomes
Authors: Xie Jilai , Huang Changchang , Zhao Qiaohang , Zhou Ping , Jiang Lihong , Yu Danqing , Shen Yayu , Feng Chun , Jin Min
Published: January 2021

Background: Some women at reproductive age have positive antithyroid antibodies (ATAs). ATA includes thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Women with ATAs, no matter with or without thyroid dysfunction, they have a higher risk of adverse reproductive outcomes, such as infertility, miscarriage and preterm birth.Methods: This study aimed to evaluate the impact of ATAs on maturation of women reproductive system and pregnancy outcomes. And it’s a prospective study, performed in three independent centers from January 2019 to June 2020. Women were tested for TSH, free T3, free T4, total T3, total T4, TPOAb and/or TgAb. They were divided into four groups: TPOAb+TgAb+, TPOAb+TgAb-, TPOAb-TgAb+ and TPOAb-TgAb-. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. The continuous variables that were nonnormally distributed were compared using the Kruskal-Wallis test. The χ2 test or Fisher exact test was used to compare categorical variables.Results: A total of 3457 women undergoing TPOAb and/or TgAb testing were enrolled in this study. 13.77% and 16.85% women were positive for TPOAb and TgAb, respectively. TgAb positivity had a strong correlation with TPOAb (F=1160.568, P＜0.001). ATAs had no effect on age of menarche and menstrual cycle. Some obstetric complications occurred in both positive subjects, but TPOAb, TgAb and TSH alone or in combination cannot predict the presence of complications during pregnancy. Administration of L-T4 to pregnant women with TSH 2.5-4.94mIU/ml may reduce the risk of PROM in ATA- women. Of the women with one or two ATAs, there were no significant differences between LT4 therapy group and untreated group in other pregnancy outcomes.Conclusion: TPOAb or TgAb is probably not the main reason for poor pregnancy outcomes.
Adverse Neonatal Outcomes and Its Associated Factors Among Mothers with Short and Recommended Interpregnancy Interval, in Awi Zone Public Hospitals, 2020.
Authors: Fetene Jemberu Chane , Mulat Amlaku , Wudineh kihinetu Gelaye , Wubet Tigist
Published: January 2021

Background: Short interpregnancy interval is among modifiable risk factors for maternal and neonatal adverse outcomes for planned pregnancies. It is potentially associated with adverse neonatal outcomes which are known to have considerable public health significance. In Ethiopia neonatal mortality was found to be high according to recent mini Ethiopian Demographic Health Survey Report. More importantly information about adverse neonatal outcomes in relation to interpregnancy interval is poorly described yet in Ethiopia. Methods: Institution based comparative cross-sectional study was conducted in Awi zone public hospitals. A total of 482 mothers (241 with short and 241 with recommended IPI) were selected. The data was collected by using systematic random sampling technique through pretested structured questionnaire and entered in to Epi data version 3.1 then exported to Statistical Package of Social Science version 23.0 for analysis. Chi-square and independent t-test were used to compare means. Bivariable and multivariable logistic regression analyses was employed to estimate the crude and adjusted odds ratio with a confidence interval of 95% and P value of less than 0.05 considered statistically significant.Result: Among a total of selected mothers with short and recommended Interpregnancy interval (IPI) response rate was 237 (98.3%) and 238 (98.7%) respectively. Proportion of adverse neonatal outcomes were higher among short IPI groups (37.1%). Factors like, rural residence [AOR=6.9, 95%CI (3.32, 14.59)], and Cesarean section delivery [AOR=3.4, 95%CI (1.18, 10.09)] were significantly associated with adverse neonatal outcomes in short IPI groups. Factors like rural residence [AOR=6.1, 95%CI (2.11, 17.7)], unintended pregnancy [AOR=5.3, 95%CI (1.11, 25.00)], rupture of membrane [AOR=6.89, 95%CI (2.54, 18.65)] and induction of labor [AOR=13.4, 95%CI (3.17, 21.77)] were significantly associated in recommended IPI groups.Conclusion: Urban residency and vaginal mode of delivery were significantly associated with less risk of adverse neonatal outcomes in both IPI groups. Whereas, intended pregnancy status, spontaneous labor initiation and absence of ROM before labor were protective for adverse neonatal outcomes in recommended IPI mothers. Provision of proper health service coverage at rural area and minimizing C/S rate to reduce adverse neonatal outcome is recommended.
Hyperthyroidism as a Potential Risk Factor for Placental Abruption: A Case Control Study
Authors: Kotani Tomomi , Imai Kenji , Ushida Takafumi , Moriyama Yoshinori , Kobayashi Tomoko , Osuka Satoko , Tsuda Hiroyuki , Sumigama Seiji , Yamamoto Eiko , Hirakawa Akihiro , Iwase Akira , Kikkawa Fumitaka , Kajiyama Hiroaki
Published: January 2021

BackgroundOvert hyperthyroidism and hypothyroidism are associated with pregnancy complications; however, most women with these conditions are diagnosed before conception and are under treatment during pregnancy, especially in the developed countries. The purpose of this study was to investigate pregnancy complications among these women.MethodsA retrospective case-control study was conducted, and data on 3824 pregnant women who gave birth at Nagoya University Hospital located in Japan from 2005 to 2014 was collected. The pregnancy outcomes were divided and compared among three groups: the control group (n = 3709), the hyperthyroidism group (n = 52) and the hypothyroidism group (n = 63). Risk factors for placental abruption were also evaluated in singleton pregnancies (n = 3588) by multivariable logistic regression analysis. Moreover, in hyperthyroidism, thyroid function was also compared between successful and failed placentation group, and the latter group included placental abruption and preeclampsia. ResultsThe incidence of placental abruption was significantly higher in hyperthyroidism than in control and hypothyroidism groups (p < 0.01). Hyperthyroidism was independently associated with an increased risk of placental abruption (adjusted odds ratio = 12.52, 95% confidence interval = 2.91–53.88). Thyroid stimulating hormone (TSH) was significantly lower in failed placentation group than in successful placentation group (p < 0.05). ConclusionAccording to the results of our study, pregnancy outcomes in women with treated hypothyroidism were comparable with those in women without thyroid disease. Conversely, women with treated hyperthyroidism showed an independent risk of placental abruption, which might be related with lower TSH level at early gestation. However, further research is required to validate our findings.
The Prediction of Maternal Serum Alpha Fetoprotein Level and Fetal Nuchal Translucency, Forcases Involving Preterm Prelabor Rupture of Membranes
Authors: Chen Yiming , Chen Yijie , Chen Lei , Ning Wenwen , Wang Xiaoying , Zhang Zhifen
Published: January 2021

Objective: To investigate whether the values of maternal serum alpha-fetoprotein (AFP) and fetal nuchal translucency (NT) during the first and second trimesters can predict preterm prelabor rupture of membranes (PPROM). Methods: This retrospective case-control study analyzed the first and second trimester screening indicators and maternal outcomes of gravidas who were divided into the Non-PPROM group (594) and the PPROM group (591). Binary logistic regression analysis was used to calculate the OR and 95% CI. ROC and AUC were used for screening performance of AFP and NT. Results: The values of NT and AFP in the PPROM group were higher than the control group and the difference was statistically significant (all P<0.05). There was no significant difference with respect to PAPP-A, free-β hCG, and the calculated risk of trisomy 18 (all P>0.05). Binary logistic regression showed that NT and AFP MoM were risk factors for PPROM, with ORs of 1.719 and 3.549, respectively. The AUC according to the ROC for NT, AFP MoM and maternal weight in the first trimester +NT+AFP were 0.552, 0.618 and 0.630. Conclusions: NT and AFP during the first and second trimesters were identified as risk factors for PPROM and valuable markers to predict PPROM in late pregnancy. Multi-index joint prediction was more effective.
Epidemiological Trends of Maternal Hypertensive Disorders of Pregnancy at the Global, Regional, and National Levels: A Population-Based Study
Authors: Wang Wei , Xie Xin , Yuan Ting , Wang Yanyan , Zhao Fei , Zhou Zhangjian , Zhang Hao
Published: January 2021

Background. To report the cause-specific prevalence and trends of hypertensive disorders of pregnancy at global, regional and national levels from 1990 to 2019 by age and sociodemographic index.Methods. For hypertensive disorders of pregnancy, point prevalence, annual incidence, and years lived with disability numbers and age standardized rates per 100,000 population were compared across regional and national levels by age and sociodemographic index using data from the global Burden of Disease 2019 Study. Estimates are reported with uncertainty intervals.Results. The incidence of hypertensive disorders of pregnancy increased from 16.30 million to 18.08 million globally, with a total increase of 10.92% from 1990 to 2019. The age-standardized incidence rate decreased, with an estimated annual percentage change of -0.68 (95% CI -0.49 to -0.86). The number of deaths due to hypertensive disorders of pregnancy was approximately 27.83 thousand in 2019. This was a 30.05% decreased from 1990. Based on the incidence and prevalence, the number of deaths and years lived with disability were highest in the group aged 25-29 years, followed by the groups aged 30-34 and 20-24 years, while the estimated incidence rate was lowest in the group aged 25-29 years and higher in the youngest and oldest groups. Positive associations between incidence and sociodemographic index and human development index were found for all countries and regions in 2019. Age-standardized incidence rates were higher in countries/regions with lower sociodemographic indices and human development indices.Conclusion. Our study provides a comprehensive overview of the global burden of hypertensive disorders of pregnancy. The death and incidence burdens are decreasing in most countries and all regions except low-sociodemographic and -human development index areas. This is mainly because attention to prenatal examinations and health education has increased. Further investigations should focus on forecasting the global disease burden of specific hypertensive disorders of pregnancy and modifiable risk factors.