bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnomedicinal Study of Medicinal Plants Used by Mizo Tribes in Champhai District of Mizoram, India.
Authors: Laldingliani TBC , Thangjam Nurpen Meitei , Zomuanawma R , Bawitlung Laldingngheti , Pal Anirban , Kumar Awadhesh
Published: October 2021

Background
Medicinal plants have been used countless times for curing diseases mainly in developing countries. They are easily available with little to no side effects when compared to modern medicine. This manuscript encompasses information on ethnomedicinal plants in Champhai district, located in the North East Region (NER) of India. The region lies within Indo-Burma biodiversity hotspot. This study will be the first quantitative report on the ethnomedicinal plants used by the local tribes of this region. Knowledge of medicinal plants is mostly acquired by word of mouth and the knowledge is dying among the local youths with the prevalence of modern medicine. Hence, there is urgency in deciphering and recording such information.
Methods
Information was gathered through interviews with 200 informants across 15 villages of the Champhai District. From the data obtained, we calculated the Used Report (UR), Frequency of Citation (FC) and Informant Consensus Factor (Fic) for all the plant species. Secondary data was obtained from scientific databases such as Pubmed, Sci Finder and Science Direct. The scientific name of the plants were matched and arranged in consultation with the working list of all plant species (http://www.theplantlist.org ).
Results
93 plant species from 53 families were recorded. The most common families are Euphorbiaceae and Asteraceae with six and five species representatives respectively. Leaves were the most frequently used part of a plant and were usually used in the form of decoction. The plant species with the highest used report (UR) were Curcuma longa L. (136 FC) and Flueggea virosa (126 FC). The main illness categories as per Frequency of citation were Muscle/Bone Problem (0.962 Fic), Gastro-intestinal Disease (0.956 Fic) and Skin Care (0.953 Fic).
Conclusion
The people of Mizoram living in the Champhai district have an immense knowledge of ethnomedicinal plants. There are no new adverse effects recorded. We observed that there is a scope of scientific validation of 10 plant species for their pharmacological activity and 13 species for the phytochemical characterization or isolation of the phytochemicals. This might pave the path for developing a scientifically validated botanical or lead to semisyntheic derivatives intended for modern medicine.
An approach to evaluate mountain forest protection and management as a means for flood mitigation
Authors: Rüegg Janine , Moos Christine , Gentile Alice , Luisier Gilles , Elsig Alexandre , Prasicek Günther , Otero Iago
Published: October 2021

We are of the opinion that old environmental policies that are based on scientific knowledge at the time they are established need to be revisited in terms of the current knowledge and the effectiveness of these policies in protecting or promoting a particular ecosystem service. Here we use the first Swiss Federal Forest Law (1876) as a case example, which was established to protect mountain forests as a natural means of protection against natural hazards, particularly floods. We briefly summarize the current relevant scientific knowledge on i) reasons for reforestation in mountains and how the law may have contributed, ii) forest effects on hydrological regimes and their protection service against floods, and iii) other watershed changes affecting both reforestation and the forest-runoff interaction. We then present insights from a case study on the Upper Rhone catchments, which lead us to develop a methodological approach based on interdisciplinary collaboration among natural and social sciences to gain the needed data to answer the question of whether a forest protection law can serve as a means of flood protection. Specifically, we found that a means of data interpolation is key to answering this question given data are at different scales and resolutions, and suggest modeling methods to fill gaps. Such methods and collaborations are key for basing environmental laws and policies in current scientific knowledge and effectively manage ecosystems and their services.
Preclinical and Exploratory Clinical Studies of Novel 68Ga-labeled ᴅ-Peptide Antagonist for PET Imaging of TIGIT Expression in Cancers
Authors: Wang Xiaobo , Zhou Ming , Chen Bei , Liu Huanhuan , Fang Jianyang , Xiang Shijun , Hu Shuo , Zhang Xianzhong
Published: October 2021

Purpose

While TIGIT has been propelled under the spotlight as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive and quantitative evaluation of TIGIT expression in cancers. In this study, a 68Ga-labeled ᴅ-peptide antagonist, 68Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and first-in-human pilot study.
Methods

The ᴅ-enantiomer peptide antagonists were modified and radiolabeled with 68Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated in vivo. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT ex vivo. The safety and potential of 68Ga-GP12 for PET/CT imaging of TIGIT expression were further evaluated in a first-in-human pilot study with advanced NSCLC.
Results

68Ga-labeled ᴅ-peptides were conveniently produced with high radiochemical yields,radiochemical purity and molar activities. In vitro binding assays demonstrated 68Ga-GP12 has favorable affinity and specificity for TIGIT with a KD of 37.28 nM. In vivo and ex vivo studies demonstrated the favorable pharmacokinetics of 68Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. The primary and metastatic lesions found in the first-in-human studies of 68Ga-GP12 PET/CT imaging were comparable to that in 18F-FDG PET/CT imaging. Moreover, the inhomogenous intra-and-inter-tumoral uptake of 68Ga-GP12 was presented, reflecting the heterogeneity of TIGIT expression levels.
Conclusion

68Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.
Strategic planning of transportation infrastructure networks with case studies
Authors: Shahraki Abdol Aziz
Published: October 2021

This paper discusses necessary qualitative and quantitative improvements in transport infrastructure networks and analyzes travel behavior and origin-destination situations. This paper studies idea about the re-planning of transportation infrastructures theoretically and implements a case study strategy that applies the gravity model and graph technique. Additionally, it has a mathematical model that assists in designing traffic flow in new streets, sidewalks, plazas, and spaces, while suggesting new urban land-use policies and transportation infrastructure-locating techniques. This work considers the planning of ground, railroad, maritime, and air transportation to build a comprehensive system in the urban master planning process. It prioritizes public transportation and suggests necessary geometrical adjustments to upgrade the situation of the infrastructure and prepare Chabahar city for its strategic and oceanic role. The outcome in geometric corrections in sight distance and transverse and longitudinal curves in streets, sidewalks, and squares will assist cities in the Silk Road project environmentally and make the region attractive to tourists and investors' eyes.
Efficacy of interventions to reduce nosocomial transmission of SARS-CoV-2 in English NHS Trusts in Wave 1: A computational modelling study
Authors: Evans Stephanie , White Peter J , Wilcox Mark , Robotham Julie V
Published: October 2021

Nosocomial transmission of SARS-CoV-2 has the potential to place a large burden on the healthcare system through, for example, increased patient length of stay, pressure on specialist care capacity and staff shortages. In England, a number of interventions were applied in hospitals over wave 1 of the COVID-19 pandemic to limit the spread of SARS-CoV-2 among both hospital inpatients and healthcare workers (HCWs). Using a computational modelling approach, we have estimated the combined effect of these, and other changes within the hospital setting, to determine how many nosocomial infections were averted. While highly uncertain, due primarily to important gaps in the evidence base, model results suggest that in a scenario with high occupancy, no testing, reduced infection prevention and control (IPC) measures, increased visitors, and longer patient stays, approximately 5.2% (3.9-7.2%) of all susceptible inpatients (n=140,603; 95% CI, 89,352-197,977 patients in total), and 51.1% (43.6, 55.3%) of patient-facing HCWs could have been nosocomially infected with SARS-CoV-2 over wave 1 compared with the 1.0% (0.7, 1.2%) of patients (33,922; 24,089- 41,015) and 20.3% (15.8-29.4%) of HCW observed to be nosocomially infected. The most effective interventions for prevention of nosocomial infections in patients were decreasing occupancy, increasing spacing between beds, and testing patients on admission, resulting in a reduction of 23,434 (14,544, 31,341), 10,979 (2,458, 16,979), and 9,505, (4588, 12,823) infections, respectively. Although every intervention had some impact, it was the collective impact of all interventions that demonstrated greatest effect, averting 140,603 (89,352, 197,977) infections in inpatients. In HCWs, the most effective intervention was universal mask use, with inclusion of universal masking as part of IPC measures averting 46.0% (42.9-54.5%) of infections in HCWs resulting in 17,980 (2,772-28,450) fewer infections per 100,000 patient-facing HCWs. Interventions introduced over wave 1 of the SARS-CoV-2 pandemic in England reduced HCW infection rates by 51.1% (43.6-55.3%).
A simple and intuitive methodology for estimating red blood cell surface antigen expression variation using optical cell-detachment technique
Authors: LIN CHIH-LANG , WANG SHYANG-GUANG , TIEN MENG-TSUNG , CHIANG CHUNG-HAN , LEE YI-CHIEH , BALDECK PATRICE L. , SHIN CHOW-SHING
Published: October 2021

The analysis of surface antigens on cells, especially red blood cells (RBCs), has attracted increasing attention due to the recognition of antigenic variation that can facilitate early diagnoses. This paper presents an alternative methodology to estimate the variation of surface antigen expressions using an optical cell-detachment technique to validate the binding of individual RBCs stuck on corresponding antibody-coated surfaces. The detachment tests were implemented by an optical tweezers with gradually decreasing laser powers associated with serial antibody dilutions. Then, the antigen expression variation was estimated based on the known antibody dilution folds. The B- and B3-types of RBCs were selected for the demonstration subjects. With the semi-quantitative analysis, the proposed methodology was successfully verified for evaluating the variation of the RBC surface antigen expressions. The analysis result shows good consistency with the literature’s findings.
Mobile App and Digital System for Patients After Myocardial Infarction (AfterAMI); Study Protocol for a Randomized Controlled Trial
Authors: Krzowski Bartosz , Peller Michał , Boszko Maria , Hoffman Paulina , Żurawska Natalia , Jaruga Karolina , Skoczylas Kamila , Osak Gabriela , Kołtowski Łukasz , Grabowski Marcin , Opolski Grzegorz , Balsam Paweł
Published: October 2021

Background: Treatment of acute myocardial infarction has been studied and improved over the past years. However, the initial months after myocardial infarction are crucial from the perspective of the patient's prognosis. It is extremely important to take care of all cardiovascular risk factors.Mobile application ‘afterAMI’ supported by a web system is a novel telemedical tool developed to support patients and physicians during cardiac rehabilitation. The application has an educational model with a focus on cardiovascular risk factors and lifestyle after myocardial infarction. Moreover, it offers a module that controls vital signs like blood pressure, heart rate, weight, and many others. Additionally, the application will send reminders for better drug adherence.Methods: A group of 100 patients with myocardial infarction on admission at the 1st Chair and Department and of Cardiology, Medical University of Warsaw, will be recruited into the study. The project aims to assess the impact of the application-supported model of care in comparison with standard rehabilitation. At the end of the study, cardiovascular risk factors will be analysed, along with issues like rehospitalizations, patients' knowledge of risk factors, returning to work, and quality of life. In this prospective, open-label, randomized, single-center study, all 100 patients will be observed for 6 months after discharge from the hospital. Endpoints will be assessed during control visits 1- and 6-months after inclusion into the study.Discussion: This project is an example of a telemedical solution application embracing everyday clinical practices, conforming with multiple international cardiac societies’ guidelines. Cardiac rehabilitation process enhancements are required to improve patients’ prognosis. The evidence regarding the use of the mobile application in the described group of patients is limited and usually covers a small number of participants. The described study aims to discuss whether telemedicine use in this context is beneficial for the patients.Trial registration: ClinicalTrials.gov, NCT04793425, registered 11 March 2021.
Successful Management of Three Consecutive Cervical Pregnancy in the Same Patient- a Case Report
Authors: Chopra Seema , Agarwal Neha , Aggarwal Neelam , Gaba Nayana
Published: October 2021

Ectopic cervical pregnancy is an infrequent complication of the early gestation. Despite tremendous development in the management of ectopic pregnancy, there still lies dilemma in the diagnosis and management of cervical ectopic pregnancy. Traditionally dilation and evacuation has been used in the successful management of these kind of ectopic gestation. In this case report we describe an uncommon case of recurrent ectopic pregnancy and subsequent management.
A Novel Mixed Method Using MM-SE with Change in Routhain Array for Model Order Reduction
Authors: Sharma Aswant Kumar , Sambariya Dhanesh Kumar
Published: October 2021

The system modelling leads towards the higher-order differential equations. These systems are difficult to analyse. Therefore, for ease and understanding, the conversion of higher to lower order is required. The model order reduction(MOR) is a systematic procedure to tackle these kinds of situations. This paper offers a mixed method for MOR using the modified moment matching (MM) and stability equation (SE). The modification is applied in the routhain array of MM. The approach has been verified by examining the error between the original, proposed and compared with reduced order available in the literature. The obtained result has been compared on the basis of step response characteristics and the response indices error.
Using mHealth to Promote Mothers’ Brushing of Preschool Children’s Teeth: A Study Protocol using the Multi-phase Optimization Strategy (MOST)
Authors: Ihab Merna , Din Wafaa Essam El , Ammar Nour , Yassin Randa , Tantawi Maha El
Published: October 2021

BackgroundEarly childhood caries is a highly prevalent disease affecting young children. Parental brushing of children’s teeth is recommended during preschool years. Interventions to promote parental brushing of children’s teeth are assessed as a package in randomized clinical trials and the efficacy of separate components is not known. Methods and AnalysisThe aim of this study is to develop an optimized behavior modification intervention to increase mothers’ brushing of their pre-school children’s teeth using the Multi-phase Optimization Strategy (MOST) guided by the Theory of Planned Behavior. Behavior change will be assessed by the percent reduction in children’s dental plaque index after 6 months and mothers’ reporting of toothbrushing frequency. Two phases of MOST will be carried out. First: the preparation phase comprises the development of a conceptual framework, identifying candidate components, conducting a feasibility pilot study to assess the acceptability and the design features of three intervention components (motivational interviewing (MI), and two mobile health (mHealth) components: oral health promotion messages, and storytelling videos delivered using WhatsApp messenger) in addition to setting an optimization objective. Second: the optimization phase constitutes a factorial trial assessing the three intervention components and developing the intervention by selecting the most effective components within the optimization constraint. Each component will be set at two levels: yes (the intervention is applied) and no (the intervention is not applied). A linear regression model will be used to assess the effect of the intervention components on the percent reduction in dental plaque index (primary outcome measure). The secondary outcome measure is the change in the frequency of mother’s brushing of the child’s teeth. The combination of components making up the new optimized intervention will be selected.DiscussionThis will be the first study to apply the MOST framework in the field of dentistry. The results of this study can guide to the development of an optimized behaviour modification interventions using mHealth and MI. Trial Registration This trial was registered on June 11th, 2021, in Clinical trials.gov. Registration number: NCT04923581.
Bioinformatics Approach to Identify Common Gene Signatures of Patients With Coronavirus 2019 and Lung Adenocarcinoma
Authors: Liang Xiao , Chen Yali , Fan Yuchao
Published: October 2021

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.
Prevalence of Sleep Disturbance and correlates in Chinese Older Adults with type 2 diabetes
Authors: Gong Yu-Xing , Hou Cai-Lan , Wang Shi-Bin , Wang Fei , Huang Zhuo-Hui , Yang Jing-Jing , Jia Fu-jun
Published: October 2021

Objective

To examine the prevalence of sleep disturbances, the socio-demographic and clinical correlates in Chinese older adults with type 2 diabetes (T2DM).
Methods

A cross-sectional survey of 195 patients with T2DM was conducted using standardized instruments.
Results

The prevalence of any type of sleep disturbances was 38.5%, the incidence of DIS, DMS, and EMA were 23.6%, 25.6% and 26.2%, respectively. No statistically significant difference was observed in socio-demographic data between participants with and without sleep disturbances except age. Sleep disturbances were associated with more severe depressive symptoms and lower quality of life (QOL). Only 32% of patients suffering sleep disturbance received treatment.
Conclusions

Sleep disturbance is common in Chinese older patients with T2DM, but the rate of treatment appears low. More aggressive measures should be implemented to improve the assessment and treatment of sleep disturbances in patients with T2DM.
Improved U-Net3+ with Stage Residual for Brain Tumor Segmentation
Authors: Qin Chuanbo , Wu Yujie , Liao Wenbin , Zeng Junying , Liang Shufen , Zhang Xiaozhi
Published: October 2021

Background
For the coding part of U-Net3+, the brain tumor feature extraction ability is insufficient, leading to insufficient feature fusion when sampling on the network and reducing the segmentation accuracy.
Methods
In this study, we propose an improved U-Net3+ segmentation network based on stage residual. In the encoder part, the encoder based on the stage residual structure is used to reduce the degradation problem caused by the increase in network depth and enhance the feature extraction ability of the encoder, which is convenient for full feature fusion when sampling on the network. Besides, we used a filter response normalization (FRN) layer instead of a batch normalization layer to eliminate batch size impact on the network. Based on the improved U-Net3+ two-dimensional (2D) model with stage residual, IResUnet3+ three-dimensional (3D) model is constructed. We explore appropriate methods to deal with 3D data, which achieve accurate segmentation of the 3D network.
Results
The experimental results showed that: the sensitivity of WT, TC, and ET increased by 1.34%, 4.6%, and 8.44%, respectively. And the Dice coefficients of ET and WT were further increased by 3.43% and 1.03%, respectively. To facilitate further research, source code can be found at: https://github.com/YuOnlyLookOne/IResUnet3Plus.
Conclusion
In the segmentation task of brain tumor brats2018 dataset, compared with the classical networks u-net, v-net, resunet and u-net3 +, the proposed network has smaller parameters and significantly improved accuracy.
Effects of The Peripherally Acting µ-Opioid Receptor Antagonist Methylnaltrexone On Acute Pancreatitis Severity: Study Protocol for a Multicentre Double-Blind Randomised Placebo-Controlled Interventional Trial, The PAMORA-AP Trial
Authors: Knoph Cecilie Siggaard , Cook Mathias Ellgaard , Fjelsted Camilla Ann , Novovic Srdan , Mortensen Michael Bau , Nielsen Liv Bjerre Juul , Berner-Hansen Mark , Frøkjær Jens Brøndum , Olesen Søren Schou , Drewes Asbjørn Mohr
Published: October 2021

Background: Moderate to severe acute pancreatitis (AP) is associated with a high rate of complications and increased mortality, yet no targeted pharmacologic treatment currently exists. As pain is a dominant symptom in AP, patients are exposed to excess levels of both endo- and exogenous opioids, which may have harmful effects on the course of AP. This trial investigates the effects of the peripherally acting µ-opioid receptor antagonist (PAMORA) methylnaltrexone on disease severity and clinical outcomes in patients with moderate to severe AP. Methods: PAMORA-AP is a multicentre, investigator-initiated, double-blind, randomised, placebo-controlled, interventional trial, which will be conducted at four referral centres for acute pancreatitis in Denmark. Ninety patients with early-onset AP (pain onset within 48 hours) as well as predicted moderate to severe disease (two or more systemic inflammatory response syndrome criteria upon admission) will be prospectively included. Subsequently, participants will be randomised (1:1) to intravenous treatment with either methylnaltrexone or matching placebo (Ringer’s lactate) during 5 days of admission. The primary endpoint will be the group difference in disease severity as defined and measured by the Pancreatitis Activity Scoring System (PASS) score 48 hours after randomisation. Secondary endpoints include daily PASS scores; disease severity according to the Atlanta classification; quantification of need for analgesics, nutritional support, intravenous fluid resuscitation and antibiotics; duration of hospital admissions, readmission rates and mortality. Pain intensity and gut function will be self-reported using validated questionnaires. Exploratory endpoints include circulating levels of pro-and anti-inflammatory markers, polyethylene glycol recovery from the urine, circulating levels of blood markers of intestinal permeability, the prevalence of pancreatic complications on computed tomography (CT) scans, and colon transit time assessed using a CT-based radiopaque marker method. Discussion: This trial aims to evaluate the PAMORA methylnaltrexone as a novel targeted pharmacotherapy in patients with moderate to severe AP with the potential benefit of improved patient outcomes.Trial registration: ClinicalTrials.gov, Identifier: NCT04743570. Registered 28 January 2021, https://clinicaltrials.gov/ct2/show/NCT04743570. EudraCT, Identifier: 2020-002313-18.
The influence of hla genotype on the development of metal hypersensitivity following joint replacement
Authors: Langton David , Bhalekar Rohan , Joyce Thomas , Wainwright Benjamin , Nargol Matthew , Shyam Nish , Lie Benedicte , Pabbruwe Moreica , Stewart Alan , Waller Susan , Natu Shonali , Ren Renee , Hornick Rachelle , Darlay Rebecca , Su Edwin , Nargol Antoni
Published: October 2021

Joint replacement surgery provides pain relief and restoration of mobility for millions of patients around the world each year.[1] However, the release of wear debris from implant surfaces can limit the lifespan of a prosthesis through the promotion of inflammatory responses.[2] Implants must therefore be constructed from materials with sufficient durability and biocompatibility. One such material is cobalt chrome alloy, which is used in the majority of joint replacements.[3] Unfortunately, it is recognised that some patients develop lymphocyte mediated delayed type hypersensitivity (DTH) responses to this material,[4] a response which may result in extensive bone and soft tissue destruction.[5] A genetic predisposition to DTH has been proposed[6], though specific genes have yet to be identified, or the effects quantified. Here we show that variation in HLA class II genotype influences an individual’s susceptibility to DTH. HLA-DQ haplotypes encoding peptide binding grooves with greater affinity for the N terminal peptide sequence of albumin (containing two recognised metal binding sites) confer a greater risk of DTH. We describe the development and validation of a machine learning algorithm to investigate the possibility that a patient’s genotype and basic clinical parameters may be used to predict DTH. Incorporating this novel finding, gradient boosted survival analysis machine learning models were trained and validated using results from 606 patients from three international units. These models were assessed using Uno’s c-index, time-dependent AUROCs, and integrated calibration index performance statistics. At present, there are no tests in widespread clinical use which use a patient’s genetic profile to guide implant selection or inform post-operative management. The algorithm described herein may address this issue.
Systemic Treatment in Advanced Phyllodes Tumor of the Breast: A Multi-Institutional European Retrospective Case-Series Analyses
Authors: Palassini Elena , Mir Olivier , Grignani Giovanni , Vincenzi Bruno , Gelderblom Hans , Sebio Ana , Valverde Claudia , Baldi Giacomo Giulio , Brunello Antonella , Cardellino Giovanni Gerardo , Marrari Andrea , Badalamenti Giuseppe , Martin-Broto Javier , Ferraresi Virginia , Libertini Michela , Turano Salvatore , Gataa Ithar , Collini Paola , Tos Angelo Paolo Dei , Gennaro Massimiliano , Bini Federica , Provenzano Salvatore , Vullo Salvatore Lo , Mariani Luigi , Cesne Axel Le , Casali Paolo Giovanni
Published: October 2021

Background: We aimed at investigating outcome of systemic treatments in advanced breast PT. Methods: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centres involved in the study, were retrospectively reviewed. Results: 56 female patients were identified. Median age was 52 (range 25-76) years. Patients re-ceived a median number of 2 systemic treatments (range 1-4). Best responses according to RECIST were: 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were: 5.7 (IQR, 2.5-9.1) months with AI; 3.2 (IQR, 2.2-5.0) months with anthracycline alone; 3.4 (IQR, 1.4-6.7) months with HD-IFX; 2.1 (IQR, 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR, 0.7-6.6) months with trabectedin; 3.4 (IQR, 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR, 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR, 7.6-39.6) months. Conclusion: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however with a median PFS of 5.7 months. Other systemic treatments were poorly active.
Genetic Variants of Progesterone Receptor in Etiology of Preterm Delivery
Authors: Kolanowska Dorota , Kurzawińska Grażyna , Szpera-Goździewicz Agata , Drews Krzysztof , Malewski Zbyszko , Kozłowska-Wytyk Martyna , Kamiński Adam , Sulikowski Tadeusz , Seremak-Mrozikiewicz Agnieszka
Published: October 2021

Background: Preterm delivery (PTD) accounts for around 11% of pregnancies worldwide. Unfortunately, no diagnostic indicator, specific mechanism or genetic predisposition has yet been identified. One of the hypotheses suggest local or functional progesterone decrease as a potential reason for preterm uterine contractions leading to preterm delivery. It is believed that any change in progesterone receptor DNA may be crucial for higher risk of preterm delivery due to abnormal response to prostaglandins, normally inhibited by properly built progesterone. The aim of this study was to determine whether there is an association between progesterone gene polymorphisms (PROGINS and +331G/A) and preterm birth. Methods and Results: A total of 230 women were enrolled, including 115 cases of preterm deliveries (between 22 and 36 weeks of gestation) and 115 healthy mothers of full-term infants. Genomic DNA was isolated from the blood sample. Polymerase chain reaction (PCR) amplification was carried out in a final volume of 25µl. Genotyping was assayed by PCR. Statistical analysis of the results was conducted with p<0.05 accepted as statistically significant. For both PROGINS (Alu ins/del) and +331G/A (rs10895068) polymorphisms were equally frequent in case and control group. The prevalence of PGR alleles in both groups was also comparable.Conclusion: The results of our study showed no association between progesterone gene polymorphisms (PROGINS and +331G/A) and risk of preterm delivery. Identifying mechanisms to prolong the length of gestation, particularly in women at risk for preterm delivery, will improve both maternal and fetal outcomes.
Ultraviolet Aging Mechanism of Asphalt Molecular Based on Microscopic Simulation
Authors: Xiao Min min , Fan Lín
Published: October 2021

In order to reveal the nature of the Ultraviolet aging(UV-aging) behavior of asphalt molecules, simulation by Materials Studio software. The effect of UV aging on the transformation, aggregation and motion state of asphalt microstructure is analyzed by the changes in energy, density of dispersive phase, glass transition temperature and viscosity of the asphalt molecular system. The results show that UV aging enhances the bonding degree of asphalt molecules by increasing the heavy components in the asphalt molecules and increasing the distribution width between the asphalt molecule components, which improves the high-temperature resistance of asphalt. At the meantime, the UV aging causes the asphalt molecular movement state to solidify at low temperature so that the rheological behavior is difficult to occur by reducing the lightweight component and free volume of the asphalt molecule and increasing the glass transition temperature, which reduces the low-temperature resistance of asphalt. In addition, among the factors affecting the viscosity of asphalt molecular, the degree of influence of the molecular structure and molecular weight is significantly greater than the molecular activity. The addition of short branched chain hydrocarbon molecules to the UV-aged asphalt molecules could effectively reduce the viscosity of the asphalt molecules and improve the flowability of the asphalt molecules. The results of the study contribute to the understanding of the characteristics of changes in the microstructural pattern and dynamic behavior of asphalt molecules during UV aging, and achieve interpretation and prediction of changes in asphalt properties at the microscopic level.
Socioeconomic Patterns for Global Mangrove Cover Changes with Multivariate Analyses
Authors: Lin Ruihan , Yu Shen , Hong Bing
Published: October 2021

Socioeconomic patterns beyond the land conversions of global mangrove cover changes were few discussed. This study integrated databases of global mangrove covers, i.e., a multi-database in 1980-2016 with a combination of FAO country-survey and the global mangrove watch, and a mangrove biome cover database in 2000-2012. Annual mangrove cover change (%) of each mangrove holding country or territory was incorporated with its socioeconomic indicators in the two periods to testify possible socioeconomic patterns beyond the mangrove deforestation. The socioeconomic indicators consisted of GDP per capita and urban population percentile, and aquacultural indicators (production per capita, sales value per capita, contribution to the national GDP, and product price). Results indicated that annual mangrove cover change was interactively driven by multi-factors of national economy measures, urbanization, and aquaculture, instead of aquacultural dominance or GDP per capita alone. The multi-factor driven patterns of annual mangrove changes differed geographically among the continents. Temporal change of aquacultural product price was significantly and positively correlated to annual mangrove cover change (increase), especially in Asia and Oceania for both the periods, suggesting positive feedbacks of mangrove conservation and restoration in the two continents although the price was used to a motivator of mangrove deforestation, such as currently in Africa. These findings preliminarily bridge the knowledge gap between land conversion losses and socioeconomics of global mangrove cover changes.
Identification and Evaluation of Factors Affecting Nectar Volume and Concentrations of Croton Macrostachyus Hochst.ex Delile
Authors: Jilo Kasim Roba , Sime Getachew
Published: October 2021

Background: Secretion of nectar is highly influenced by many factors and the objective of the study was also to evaluate factors affecting concentrations of nectar of Croton macrostachyus Hochst.ex Delile. Age of plants highly affect nectar concentration and volume. Honey quality and its medicinal values depends on plants species variety and their sucrose concentration quality and quantity which is governed by many biotic and abiotic factors as well micro climate of the area. Wholesale of nectar and concentration of tend to show more differences in time of day for species study undertaken.Results: As results publicized that nectar concentration and volume of youngest age was not more affected by temperature and relative humidity like that of medium and oldest ages. Temperature and age have significant effect on volume (p = 0.0001) and their interactions is also significant (p = 0.01145). Temperature has significant effects on nectar concentration (p = 0.000). Interaction of relative humidity, time, and layers has significant effects on nectar concentration (p = 0.0024012). The oldest plants had the highest concentration of 10.1 w/w mornings and afternoon 36.5 w/w at 4:00 PM for whereas medium plants had nectar concentration of 5.7 w/w morning and afternoon 16.7 w/w and the smaller or younger plants had nectar concentration of 2.7 w/w mornings and afternoon 9.1 w/w and this shows age significantly affect nectar concentration and volume.Conclusions:Concentration and volume were affected by many biotic and abiotic factors. I conclude imminent fever intensification could harm nectar production since for croton also no nectar could be collected at 30 C⁰ and no nectar recreation was observed after this peak temperature this indicates environmental change can increase the temperature which will have negative influences on honey production in the future unless we combat against climate change which will affect honey production and productivity for the country and we will lose honey and its medicinal values also.
Tracking chromatin state changes using µMap photo-proximity labeling
Authors: Muir Tom , Seath Ciaran , MacMillan David , Burton Antony
Published: October 2021

Interactions between biomolecules, particularly proteins, underlie all cellular processes, and ultimately control cell fate. Perturbation of native interactions through mutation, changes in expression levels, or external stimuli leads to altered cellular physiology and can result in either disease or therapeutic effects. Mapping these interactions and determining how they respond to stimulus is the genesis of many drug development efforts, leading to new therapeutic targets and improvements in human health. However, in the complex environment of the nucleus it is challenging to determine protein-protein interactions due to low abundance, transient or multi-valent binding, and a lack of technologies that are able to interrogate these interactions without disrupting the protein binding surface under study. Chromatin remodelers, modifying enzymes, interactors, and transcription factors can all be redirected by subtle changes to the microenvironment, causing global changes in protein expression levels and subsequent physiology. Here, we describe the Chroma-µMap method for the traceless incorporation of Ir-photosensitizers into the nuclear microenvironment using engineered split inteins. These Ir-catalysts can activate diazirine warheads to form reactive carbenes within a ~10 nm radius, cross-linking with proteins within the immediate microenvironment for analysis via quantitative chemoproteomics. We demonstrate this concept on nine different nuclear proteins with varied function and in each case, elucidating their microenvironments. Additionally, we show that this short-range proximity labeling method can reveal the critical changes in interactomes in the presence of cancer-associated mutations, as well as treatment with small-molecule inhibitors. Chroma-µMap improves our fundamental understand-ing of nuclear protein-protein interactions, as well as the effects that small molecule therapeutics have on the local chromatin environment, and in doing so is expected to have a significant impact on the field of epigenetic drug discovery in both academia and industry.
The Mirror Reversal Mechanism on Black Hole Collapse and Singularity Eruption in Cosmic Continuum
Authors: Wang Xijia
Published: October 2021

In the Big Bang Theory and the Black Hole Theory, the existing laws of physics all fail atthe singularity, and the singularity has become a blind spot in the existing scientific theories. In Cosmiccontinuum, the cosmic system collapse into a Schwarzschild black hole under the action of a stronggravitational field, and the Planck spheres at the center of the black hole continues to collapse into darkmass bodies, forming dark celestial body and singularity. The Schwarzschild radius is the upper limit ofa black hole, and the Planck sphere is the lower limit of a black hole. The singularity is the conversionpoint between the old and new cosmic systems. The singularity erupts the Planck spheres under theaction of a strong gravitational field, and the Planck spheres expands outward to form a new cosmicsystem. The Planck sphere is both the end of the old cosmic system and the starting point of the newcosmic system. The black hole collapse and the singularity eruption are mirror images of each other.The Planck sphere is the front of the mirror, and the singularity is the back of the mirror.
Shockable Rhythm at Hospital Arrival as the Predictor of Favourable Neurological Outcome in Patients with Out-of-Hospital Cardiac Arrest (OHCA) Receiving Extracorporeal Cardiopulmonary Resuscitation (ECPR)
Authors: Su Pei-I , Tsai Min-Shan , Chen Wei-Ting , Wang Chih-Hung , Chang Wei-Tien , Huei-Ming Matthew , Chen Wen-Jone , Huang Chien-Hua
Published: October 2021

Introduction: For patients with out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation under advanced life support, extracorporeal cardiopulmonary resuscitation (ECPR) is the only lifesaving option. This study aimed to analyse the predictors of favourable neurological outcomes (FO, cerebral performance category 1-2) at hospital discharge among patients with OHCA following ECPR.Methods: In this single-centre retrospective study, 126 patients with OHCA who received ECPR between January 2012 and December 2019 were enrolled. The primary outcome was the FO at hospital discharge. The predictors of FO were assessed using multiple logistic regression analysis. Patients with an initial shockable rhythm were further analysed according to the cardiac rhythm at the time of hospital arrival. Results: Among the patients who received ECPR, the FO at hospital discharge was 21%. Certain resuscitation variables were associated with FO including witnessed collapse (P=0.014), bystander CPR (P=0.05), shorter no-flow time (P=0.008), and a shockable rhythm at hospital arrival (P=0.009). Multiple logistic regression showed that a shockable rhythm at hospital arrival was the only independent predictor of FO at discharge (odds ratio, 3.012; 95% confidence interval, 1.06-8.53; P=0.038). Among patients with an initial shockable rhythm, the group with a shockable rhythm at hospital arrival had a FO of 30%, which was significantly higher than the 11% in the non-shockable rhythm group (P=0.043).Conclusions: In patients with OHCA who received ECPR, a shockable rhythm at the time of hospital arrival was associated with favourable neurological outcomes at discharge. The ECPR selection criteria could consider the rhythm at hospital arrival.
The Treatment Pattern and Economic Burden of Homozygous Familial Hypercholesterolemia in China: A Study based on a Patient-Survey
Authors: yang yan , Wang Lvya , Yang Ya , Wen Wenhui , Tang Mi , He Jiangjiang , Hu Shanlian
Published: October 2021

Objective: The study aimed to investigate the treatment pattern and economic burden of homozygous familial hypercholesterolemia (HoFH) in China, and to evaluate the incidence rate of catastrophic health expenditure (CHE) of HoFH patients and their families.Methods: Patients with HoFH diagnosed and treated in Beijing An’Zhen Hospital was included. A questionnaire was developed to investigate and capture the relevant variables of the participants.Results: A total of 120 HoFH patients were investigated, and the number of children (age under 18) was 1.2 times more than adults (age above 18). There were 113 patients with basic medical insurance (including 61 patients with new rural cooperative medical insurance), 4 patients with commercial insurance and 3 patients without any insurance. There were 35 patients with atherosclerotic cardiovascular disease (ASCVD), including 29 adults and 6 children. Only 6 pediatric patients achieved their low-density lipoprotein cholesterol (LDL-C) treatment targets, and all 54 adult patients did not achieve it. The most commonly used treatment method was diet control with lipid-lowering drugs (16.67%), followed by diet control and lipid-lowering drugs using separately (16.67%). The proportion of patients whose annual personal income reached GDP per capita in 2019 was only 2.5%. The total economic burden of disease was 5,529,100 CNY / year, including direct medical costs of 3,427,200 CNY / year, direct non-medical costs of 1,504,500 CNY / year and indirect costs of 611,300 CNY / year; the per capita economic burden of disease was 46,100 CNY / year, including direct medical costs of 28,600 CNY / year, direct non-medical costs of 12,500 CNY / year and indirect costs of 5,100 CNY / year. There were 32 families with CHE due to the disease, accounting for 26.67%.Conclusion: Patients with HoFH in China are generally at young age, and the economic burden of disease for the family is heavy. The existing treatment is not effective, and it is easy to cause premature death due to ASCVD.
Auricular Acupressure for Adverse Events Following Immunization Related To COVID-19 Vaccine Injection: Study Protocol for a Multicenter, Three-Arm, Blinded Randomized Controlled Trial
Authors: Fu Qinwei , Xie Hui , Zhou Li , Li Xinrong , Liu Yang , Liu Min , Wang Chaoyu , Wang Xiaocen , Wang Zhiqiao , Tang Jinfan , Xiao Huan , Xiao Zhiyong , Zhou Jing , Feng Chengzhi , Wang Li , Ao Zhimin , Chen Xi , Su Chang , Wu Xuanyu , Zhao Maolan , Hu Sihan , Lin Hanwen , Huang Jiali , Xu Guo , Zhang Qinxiu , Jiang Luyun
Published: October 2021

Background
Some pain, fatigue, and gastrointestinal adverse reactions were observed in potential association with injection of COVID-19 vaccines. However, there were no preventive intervention for it. We aim to investigate efficacy of auricular acupressure (AA) therapy in preventing and (or) relieving AEFI after injection of COVID-19 vaccine.
Methods/design:
The study design is a randomized controlled, multicentre, three-arm, single-blind trial. Participants meeting the inclusion criteria will be advertised and enrolled, and assigned randomly in the medical institutions for post-injection observation. No less than 360 participants will be randomized into one of three groups: auricular acupressure group, sham auricular acupressure group and wait-list group. Interventions will be performed immediately, and will happen 4 to 5 times per day for 5 days. The primary clinical outcomes will be quality and quantity evaluation among participants who reported any AEFI and who reported local pain at injection site. Secondary outcomes will concern headache, muscle and (or) joint pain, fatigue, nausea, vomiting, diarrhoea, and other potential events. All the outcomes will be assessed at baseline, 1, 3, 5, 7, and 14 days after the injection. Both intention-to-treat and per-protocol analyses will be performed, with significance level determined at the 5 % level.
Discussion
Results of this trial will help clarify the value of auricular acupressure therapy in preventing and (or) relieving overall and certain adverse events following immunization after injection of COVID-19 vaccine.
Trial registration:
This trial was registered in the China Clinical Trial Registry (ChiCTR) (ChiCTR2100043210) on 8th February, 2021.