bluuebunny/crossref_metadata_2025 huggingface dataset:
Type II porous ionic liquid based on metal-organic cage that enables L-tryptophan identification
Authors: Zhang Zhuxiu , Yang Baolin , Zhang Bingjie , Cui Mifen , Tang Jihai , Qiao Xu
Published: November 2021

Porous liquids with chemical separation properties are quite well-studied in general, but there is only a handful of reports in the context of identification and separation of non-gaseous molecules. Herein, we report the first example of Type-II porous ionic liquid that exhibits exceptional selectivity towards L-tryptophan (L-Trp) over other aromatic amino acids and the first in which coordination cages promote this selectivity. A previously known class of anionic organic-inorganic hybrid doughnut-like cage (HD) has been readily dissolved in trihexyltetradecylphosphonium chloride (THTP_Cl). The resulting liquid, HD/THTP_Cl, is thereby composed of common components, facile to prepare, and exhibit room temperature fluidity. The permanent porosity are manifested by the high-pressure isotherm for CH4 and modeling studies. With evidence from time-dependent amino acid uptake, competitive extraction studies and molecular dynamic simulations, HD/THTP_Cl exhibit better selectivity towards L-Trp than existing solid state sorbents, and we attribute it to not only the intrinsic porosity of HD but also the host-guest interactions between HD and L-Trp. Specifically, each HD unit is binded with nearly 5 L-Trp molecules, which is higher than the L-Trp occupation in the structure unit of other benchmark metal-organic frameworks.
Valorisation of Fish Bones: Effects of Preservation by Formic Acid on AL-extractable calcium, Phosphorus, Magnesium, and Potassium
Authors: Løes Anne-Kristin , Ahlin Johan Petter , Ahuja Ishita , Krogstad Tore , Smevoll Ståle , Waag Hanne
Published: November 2021

Fishbones contain significant amounts of plant nutrients. Fish residues may be preserved by acidification to pH < 4, which may affect the extractability and plant availability of nutrients when applied as fertilisers. Grinded bone material from cod ( Gadus morhua ) heads was mixed with formic acid to investigate if acidification would increase the concentrations of ammonium acetate-lactate (AL)-extractable nutrients. Two degrees of fineness of fishbones (coarse 2-4 mm; fine < 0.71 mm) were compared at pH 3.0 and 4.0 plus a water control in a laboratory study over 55 days. Samples for extraction of AL-soluble P, Ca, Mg and K were taken on day 2, 15, 34 and 55. Whereas acidification clearly increased the concentrations of AL-extractable calcium (Ca-AL) and magnesium (Mg-AL), extractable phosphorus (P-AL) was only significantly increased in finely grinded bones at pH 3. After 34 days, 6% of the total content of P was extracted by AL in fine fishbones at pH 3. Without acidification about 1% of the P was extracted, possibly from phospholipids. This P-AL concentration was well above P-AL extracted from acidified coarse fishbones and from fine fishbones acidified to pH 4. With acidification, about 30% of total Ca and 10% of total Mg were extracted by AL, and the Ca-AL and Mg-AL concentrations were closely correlated. The reason for lower P-AL in coarse fishbones at pH 3 and 4, and fine fishbones at pH 4 than in water controls may be a precipitation of apatite from phospholipids and dissolved calcium.
Improving De Novo Molecular Design with Curriculum Learning
Authors: Guo Jeff , Fialková Vendy , Arango Juan Diego , Margreitter Christian , Janet Jon Paul , Papadopoulos Kostas , Engkvist Ola , Patronov Atanas
Published: November 2021

Reinforcement learning (RL) is a powerful paradigm that has gained popularity across multiple domains. However, applying RL may come at a cost of multiple interactions between the agent and the environment. This cost can be especially pronounced when the single feedback from the environment is slow or computationally expensive, causing extensive periods of nonproductivity. Curriculum learning (CL) provides a suitable alternative by arranging a sequence of tasks of increasing complexity with the aim of reducing the overall cost of learning. Here, we demonstrate the application of CL for drug discovery. We implement CL in the de novo design platform, REINVENT, and apply it on illustrative de novo molecular design problems of different complexity. The results show both accelerated learning and a positive impact on the quality of the output when compared to standard policy based RL. To our knowledge, this is the first application of CL for the purposes of de novo molecular design. The code is freely available at https://github.com/MolecularAI/Reinvent.
Synthesis and Evaluation of Cyclic Diamino Benzamide Based D3 Receptor Ligands
Authors: Blass Benjamin E. , Chen Peng-Jen , Taylor Michelle , Griffine Suzy A. , Gordon John C. , Luedtke Robert R.
Published: November 2021

Dopamine (1) is a key neurotransmitter whose impact on pharmacological processes is mediated by a family of dopamine receptors designated D1, D2, D3, D4, and D5. Various diseases and conditions such as schizophrenia, drug abuse, depression, restless leg syndrome, Parkinson’s disease (PD), and inflammatory diseases have been linked to aberrant D3 activity. Herein, we report a series of novel D3 ligands with improved solubility over our previous lead compound, MC25-41 (2).
Influence of Access To Finance On The Competitive Growth of SMEs in Lesotho.
Authors: Amadasun Donald Edes Osakpamwan , Mutezo Ashley T.
Published: November 2021

Background: Access to finance is identified as one of the biggest problems faced by Small and Medium-Sized Enterprises (SMEs) in most developing economies. Consequently, access to finance has been identified as a dominant constraint facing the SMEs sector in Lesotho. This paper established the factors of access to finance that influence the competitive growth of the SME sector in Lesotho. The factors addressed include financial information access, bank and business support services, the structure of banks and collateral requirements by the financial sector. Findings: The results from our analysis indicated that there is a relationship between independent variables of financial information access, Bank and business support service, the structure of banks and the collateral requirement by commercial banks and such influence SMEs capacity to attain competitive growth in Lesotho. In addition, the results indicated that Basotho entrepreneurs and managers see the predictors as critical factors of access to finance that constrained most enterprises access to needed credit from banks and such influence SMEs capacity to attain competitive growth in Lesotho. Conclusions: The study concludes that access to finance significantly affect the competitive growth of SMEs in Lesotho. Thus, this study suggests that several specific and harmonized financial policy actions are needed in the Lesotho financial market to identify enabling policy that ease enterprises access to adequate funding programs. These funding programs should target improved financial schemes that are coordinated, competitive and directed towards SMEs access to finance; harmonized credit policy which guarantees a win-win for SMEs loan applicants and the financial market operators.
Eosinophilic pneumonia induced by lettuce: A case report
Authors: Sekiya Reina , Nagano Tatsuya , Moriyama Tatsuya , Kawaguchi Aki , Fukui Takafumi , Mimura Chihiro , Kimura Yohei , Ohnishi Hisashi , Kotani Yoshikazu , Nishiura Yoshihiro
Published: November 2021

Background: Lettuce (Lactuca sativa) belongs to the Composite family and is a vegetable widely consumed globally. Although lettuce is extensively cultivated and consumed, lettuce-associated occupational allergy is rarely reported. Herein, we are reporting a case of eosinophilic pneumonia induced by lettuce for the first time.Case presentation: A 56-year-old female lettuce farmer was admitted to the hospital with a low-grade fever, worsening cough, and dyspnoea. A blood test revealed eosinophilia and a high serum IgE concentration. A chest X-ray taken on admission showed an infiltrative shadow in the upper lung field. Chest CT revealed patchy ground glass opacity on the upper lung field and thickening of the bronchial wall. The bronchoalveolar lavage fluid contained 8% eosinophils. The IgG-binding proteins that reacted with the patient’s sera were identified by immunoblot analysis. She was diagnosed as lettuce induced eosinophilic pneumonia and was treated with prednisolone, and her symptoms and radiological findings improved. Wearing a mask and reducing the amount of the crop improved her symptoms the following year.Conclusions: This is the first case report about lettuce-induced eosinophilic pneumonia which occurred in a lettuce farmer. The avoidance from antigen is quite useful in this patient.
Covid-19 and Crisis Management: The Necessity of Innovation in the Business Model of SMEs in Order to Recover and Develop Fast After the Corona Crisis
Authors: Mirzaye Sina
Published: November 2021

We know that SMEs are among the businesses most affected by the COVID-19 shutdown. The first theoretical and practical observations in SMEs show that innovation in business models can be a solution to successfully improve and cope with the COVID-19 crisis. In a way that arouses curiosity, some SMEs have already begun to successfully change and reconciling their business models. This paper provides a qualitative analysis of six local SMEs in Iran to explore how SMEs adapt their business models to crisis. We collected interview data from managers with one of their middle managers for each case, which we triangle for analysis with secondary data. According to the results, BMI could be used during and after a crisis to generate new income, maintain and exit pre-crisis conditions, and develop.
An Indirect Method for the Quantitative Identification of Unstable Rock
Authors: DU YAN , Xie Mowen
Published: November 2021

Under the influence of continuous external factors (rainfall, earthquake, construction, etc.), the slope rock mass in a stable state gradually transited to an unstable rock, and then the unstable rock collapsed. However, a safety factor can identify the occurrence of failure but cannot identify the transition of stable rock to unstable rock; thus, it cannot realise the quantitative identification of unstable rocks. In this study, safety factor of adhesion (SFA ) and a relatively objective analysis method are proposed to effectively identify unstable rocks. SFA can be calculated by natural vibration frequency and applied as a mechanical index to judge unstable rock. When SFA is less than 1, the rock is defined as an unstable rock. Compared with the traditional method, the new method has the merits of simple operation, low cost and higher efficiency, and provides a relatively complete quantitative evaluation index and judgment criteria for quantitative identification of unstable rocks for engineers who are engaged in early warning and prevention of rock collapse.
Mental Well-Being During Stages of COVID-19 Lockdown Among Pregnant Women And New Mothers
Authors: Overbeck Gritt , Rasmussen Ida Scheel , Siersma Volkert , Kragstrup Jakob , Ertmann Ruth Kirk , Wilson Philip
Published: November 2021

Background: Pregnancy and early motherhood are sensitive times where epidemic disease outbreaks can affect mental health negatively. Countries and health care systems handled the pandemic and lockdowns differently and knowledge about how the COVID-19 pandemic affected the mental well-being of pregnant women and new mothers is limited and points in different directions. Aim. to investigate symptoms of anxiety and depression in a population of pregnant women and new mothers in various stages of infection pressure and lock down during the first 15 months of the COVID-19 pandemic in Denmark. Methods: The study population was nested an inception cohort of women recruited in their first trimester of pregnancy. Data about mental health of the woman was obtained in relation to pregnancy and child development (first trimester, 8 weeks postpartum and 5 months postpartum), and data were analysed cross-sectionally according to calendar time (periods defined by infection rate and lock-down during the COVID-19 epidemic).Results: No differences in reported levels of depressive symptoms between the six examined time periods of the pandemic were observed. Specifically, symptoms remained unchanged after the first lock-down. No major changes in anxiety symptoms were observed in relation to increased infection pressure or lockdowns, but a small increase was observed during the second lockdown in women 8 weeks postpartum. Conclusion: No clear change in mood among pregnant women was seen between during the stages of Covid-19 pandemic in Denmark.
Therapeutic Nucleus-Access BNCT Drug Combined CD47-Targeting Gene Editing in Glioblastoma
Authors: Chen Jiejian , Dai Qi , Yang QiYao , Bao Xiaoyan , Zhou Yi , Zhong Haiqing , Wu Linjie , Wang Tiantian , Zhang Zhicheng , Lu Yiying , Zhang Zhentao , Lin Mengting , Han Min , Wei Qichun
Published: November 2021

Glioblastoma is the most common brain primary malignant tumor with the highest mortality. Boron neutron capture therapy (BNCT) can efficiently kill cancer cells on the cellular scale, with high accuracy, short course and low side-effects, which is regarded as the most promising therapy for malignant brain tumors like glioma. As the keypoint of BNCT, all boron delivery agents currently in clinical use are beset by insufficient tumor uptake, especially in the tumor nucleus, which limits the clinical application of BNCT. In this study, nuclear targeting of boron is achieved by DOX-CB, consisting of doxorubicin (DOX) andcarborane (CB) utilizing the nuclear translocation property of DOX. The nucleus of GL261 cells takes up almost three times the concentration of boron required for BNCT. To further kill glioma and inhibit recurrence, a new multifunctional nanoliposome delivery system DOX-CB@lipo-pDNA-iRGDis constructed. It combines DOX-CB with immunotherapy strategy of blocking macrophage immune checkpoint pathway CD47-SIRPα by CRISPR-Cas9 system, coupling BNCT with immunotherapy simultaneously. Compared with clinical drug Borocaptate Sodium (BSH), DOX-CB@lipo-pDNA-iRGD significantly enhances the survival rate of tumor-bearing mice, reduces tumor stemness, and improves the prognosis. The excellent curative effect of this nanoliposome delivery system provides an insight into the combined treatment of BNCT.
Silencing lncRNA CDKN2B-AS1 Alleviates Childhood Asthma Progression Through Inhibiting ZFP36 Promoter Methylation and Promoting NR4A1 Expression
Authors: Chen Zhixin , Fan Nuandong , Shen Guangsheng , Yang Jing
Published: November 2021

LncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) was found to be upregulated in plasma of patients with bronchial asthma. This study aimed to explore the roles and mechanisms of CDKN2B-AS1 in childhood asthma. We found that CDKN2B-AS1 was upregulated and zinc finger protein 36 (ZFP36) mRNA was downregulated in blood samples of children with asthma compared with healthy controls as measured by RT-qPCR. Human bronchial epithelial cell line BEAS-2B was treated with LPS to induce inflammation model. Small interfering RNA against CDKN2B-AS1 (si-CDKN2B-AS1) was transfected into LPS-treated BEAS-2B cells, and we observed that CDKN2B-AS1 silencing increased cell viability and inhibited apoptosis and inflammation cytokine levels in LPS-treated BEAS-2B cells. Methylation-specific PCR, ChIP and RIP assays indicated that CDKN2B-AS1 inhibited ZFP36 expression by recruiting DNMT1 to promote ZFP36 promoter methylation. Co-IP assay verified the interaction between ZFP36 and nuclear receptor subfamily 4 group A member 1 (NR4A1) proteins. Then rescue experiments revealed that ZFP36 knockdown reversed the effects of CDKN2B-AS1 silencing on BEAS-2B cell functions. ZFP36 overexpression facilitated apoptosis, inflammation and p-p65 expression in BEAS-2B cells, while NR4A1 knockdown reversed these effects. Additionally, CDKN2B-AS1 silencing alleviated airway hyperresponsiveness and inflammation in ovalbumin (OVA)-induced asthma mice. In conclusion, silencing lncRNA CDKN2B-AS1 enhances BEAS-2B cell viability, reduces apoptosis and inflammation in vitro and alleviated asthma symptoms in OVA-induced asthma mice in vivo through inhibiting ZFP36 promoter methylation and NR4A1-mediated NF-κB signaling pathway.
Need for Increased Investment in Human Resource for Health in India: Estimating the Required Investment for Increased Production of Health Professionals for Achieving Universal Health Coverage and Sustainable Development Goals by 2030.
Authors: Karan Anup , Negandhi Himanshu , Kabeer Mehnaz , Zapata Tomas , Mairembam Dilip , De Graeve Hilde , Buchan James , Zodpey Sanjay
Published: November 2021

BACKGROUND: COVID-19 has reinforced the importance of having sufficient, well-distributed and competent health workforce. In addition to improving health outcomes, increased investment has the potential to generate employment, increase labour productivity along with fostering economic growth. With COVID-19 highlighting the gaps in human resources for health in India, there is a need to better and empirically understand the level of required investment for increasing the production of health workforce in India for achieving the UHC/SDGs.METHODS: The study used data from a range of sources including National Health Workforce Account 2018, Periodic Labour Force Survey 2018-19, population projection of Census of India, and review of government documents and reports. The study estimated shortages in the health workforce and required investments to achieve recommended health worker: population ratio thresholds by the terminal year of the SDGs 2030.RESULTS: Our results suggest that to meet the threshold of 34.5 skilled health worker per 10,000 population, there will be a shortfall of 0.16 million doctors and 0.65 nurses/midwives in the total stock of human resources for health by the year 2030. The shortages at the same threshold will be much higher (0.57 million doctors and 1.98 million nurses/midwives) in active health workforce by 2030. The shortages are even higher when compared with a higher threshold of 44.5 health workers per 10,000 population. The estimated investment for the required increase in the production of health workforce ranges from INR 523 billion to 2,580 billion for doctors. For nurses/midwives, the required investment is INR 1,096 billion. Such investment during 2021-25 has the potential of an additional employment generation within the health sector to the tune of 5.4 million and contribute to national income to the extent of INR 3,429 billion annually.Conclusion: India needs to significantly increase the production of doctors and nurses(/midwives) through investing in opening up of new medical colleges. Nursing sector should be prioritized to encourage talents to join nursing profession and provide quality education. India needs to set-up a benchmark of skill-mix ratio and provide attractive employment opportunities in health sector to increase the demand and absorb the new supply of graduates.
The Quality of Palliative Sedation in End-Stage Disease: Audit From a Department of Oncology and Haematology
Authors: Alessia Saviola , Matilde Schipilliti Francesca , Chrystel Isca , Salati Massimiliano , Dini Daniele , Fiorani Claudia , Postiglione Raffaella , Cantile Flavia , Ferrara Leonardo , Carboni Chiara , Potenza Leonardo , Dominici Massimo , Luppi Mario , Longo Giuseppe
Published: November 2021

PurposePalliative sedation (PS) plays a critical role to give suffering relief from refractory symptoms at the end of life. Our audit aimed to assess and improve quality of PS at the Department of Oncology and Hematology of University Hospital of Modena, to verify the adherence to international guidelines, the cooperation among members of care team, focusing with attention on family’s perception of this delicate situation. MethodsFrom December 2016 to June 2019, data of patients undergoing PS in the Department were collected by an electronic folder tool, “Sedation Tool” (ST), that recorded clinical and PS informations, D-PaP, Rudkin Score and family’s perception. Results245 patients were enrolled. 82% had a Karnofsky Performance Status 10-20%. The most common cancer types were lung and gastro-intestinal carcinomas (27% and 21% respectively). Refractory symptoms observed were confusion and agitation (76%), dyspnea (39%), pain (15%), delirium (10%), psychological distress (5%). Midazolam was the drug of choice for PS. Most of patients had Rudkin score 5 after 24 hours and 33% had terminal event within a period of 24 hours from the beginning of PS. During PS most of Patient’s relatives reported peacefulness (65%), agitation/impatience in 6% of cases, concern for suffering (16%). ConclusionPS is used in case of worsening general conditions at the end-stage disease to relieve refractory symptoms with dignity. The ST can become a simple instrument to evaluate and improve PS quality, providing more attention on the impact of PS on relatives to then possibly develop new supportive procedures for patients and their families.
Emergence And Circulation of Dengue Virus Serotype 2 In Guangzhou Over A Period of 20 Years
Authors: Jiang Liyun , Liu Yuan , Su Wenzhe , Cao Yimin , Jing Qinlong , Wu Xinwei , Yang Zhicong
Published: November 2021

Objectives The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here we present the genotype data for dengue virus serotype 2 (DENV-2) to improve the understanding of dengue epidemic. Methods We sequenced the envelope gene of DENV-2 obtained from patient serum sample, and subsequently performed the maximum-likelihood phylogenetic analysis using PhyMLv3.1, the maximum clade credibility analysis using BEAST v.1.10.4 and selection pressure analysis using Datamonkey 2.0 . Results The DENV-2 prevalent in Guangzhou region related to the strains of Southeast Asian countries.Our results suggest that the Malaysia/Indian subcontinent genotype is prevalent in Guangzhou and no genotype shift has occurred during the last 20 years. Episodic positive selection was detected at one site. Conclusions Prevention and monitoring imported cases are important for local control. The shift between the lineages of the Malaysia/Indian subcontinent genotype, which originated at different time points, may be the underlying cause of rising DENV-2 cases in Guangzhou.The low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.
A High-Speed Current Source for Magnetorheological Application
Authors: Lei Xie , Wang Yuhao , Lu Chuan , Yang Zhipeng , Liao Changrong
Published: November 2021

Current source is an indispensable component of magnetorheological (MR) systems. Though MR fluid has a phase change as fast as in 1 ms, the response of MR damper (MRD) to generate the damping force may be two orders of magnitude longer. Therefore, the rapid response of current source is a key to realize the real-time semi-active control of MR devices. This study proposes a programmable high-speed, low-cost current source exclusively for MR devices based on the synergy between supercapacitor and Buck converter (i.e., SSBC current source). SSBC current source features a strategy consisting of a lifting phase of supercapacitor and a following maintaining phase of Buck converter. Specifically, the high power density of supercapacitor contributes to rapidly lifting/raising the initial current, and then, like a “relay race”, the expected output is maintained through a Buck converter. Theoretical modeling and experiments are performed systematically. The response times (@ 95% of expected outputs) measured are 0.44, 0.84 and 1.88 ms for the outputs of 3, 6 and 9 A, respectively; these values are highlighted as the fastest level in this field. Besides, the response can be up to 24.6 and 43.7 times faster than the cases using supercapacitor and Buck converter to directly drive the MRD, respectively. SSBC current source is employed to generate a sequence of currents/magnetic inductions, only four variables of which need to be controlled programmatically: the order of lifting and maintaining phases, switching time of lifting phase, PWM duty cycle of Buck converter and duration of maintaining phase. The response time stability is verified by 100 cycles of on/off tests, showing a fluctuation of only 1.1%, which indicates a very reliable high-speed response. This study provides an exclusive power supply with a novel strategy for MR devices, which is believed to be an important promotion for MR technologies.
Cholangiocyte-Derived Exosomal Long Noncoding RNA PICALM-AU1 Promotes Pulmonary Endothelial Cell EndMT in Hepatopulmonary Syndrome
Authors: Yang Congwen , Yang Yihui , Chen Yang , Huang Jian , Li Caiyi , Li Dan , Tang Xi , Ning Jiaoling , Gu Jianteng , Yi Bin , lu kaizhi
Published: November 2021

Background: Hepatopulmonary syndrome (HPS) is an important clinical problem with limited understanding of disease pathologies. Exosome mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. A new lncRNA PICALM-AU1 was found and upregulated in the liver of subjects with HPS. However, the expression and biological functions of the lncRNA PICALM-AU1 are still unknown. Methods: HPS rat model was constructed by common bile duct ligation (CBDL). RNA macroarray was used to analyze the expression differential lncRNAs in HPS rat liver. PICALM-AU1 expression in the serum exosome was measured in 56 HPS patients and in 73 patients with liver cirrhosis but not HPS. qPCR, Fluorescence in situ hybridization were used to analyze PICALM-AU1 expression and location. Virus derived PICALM-AU1 upregulation and down regulation were applied in rats and PMVECs cells. The effects of PICALM-AU1 on PMVECs was determined via CCK8 assay and transwell assay. PICALM-AU1 and miR144-3p relationship was analysis by Dual-luciferase reporter assay.Results: In this study, we found lncRNA PICALM-AU1 expressed in the cholangiocyte of liver, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression.Conclusions: Taken together, our findings present a road map of targeting the newly identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the pathologic angiogenesis of HPS by promoting EndMT and represents a potential therapeutic target for HPS.
Mechanism of Peony and Licorice and Aconite Decoction in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking
Authors: li Zhiqiang , Jun Luo
Published: November 2021

Objective: To predict the key molecular mechanism of Shaoyao Liquorice Aconite Decoction in the treatment of osteoarthritis by using network pharmacology and molecular docking technology, and to provide a new target for the treatment of osteoarthritis. Methods: by means of traditional Chinese medicine database TCMSP screening peony licorice monkshood soup main active component of radix paeoniae alba, radix glycyrrhizae, and the corresponding targets, lateral root of aconite and retrieve OMIM, GeneCards, TDD, PharmGKB and Drugbank database related target for treatment of osteoarthritis, and then forecast drug targets and disease targets for intersection get peony licorice monkshood soup targets for the treatment of osteoarthritis.Then, STRING database and Cytoscape software were used to construct the "drug active component - action target" network and protein interaction network of Shaoyaogaofuzi Decoction in the treatment of osteoarthritis, and David database was used for GO function enrichment analysis and KEGG pathway enrichment analysis of shaoyaogaofuzi Decoction in the treatment of osteoarthritis.Finally, PyMOL, Chem3D, AutoDock, OpenBabel and other software were used to verify the molecular docking of the key active ingredients and key targets of Shaoyao Liquorice Aconite Decoction. Results: 162 active components were screened out.A total of 954 disease targets were collected, and a total of 72 disease targets were obtained after weight removal.Protein interaction analysis suggested that TNF, AKT1, IL6, IL1B and TP53 were the core targets of protein interaction network.Through GO enrichment analysis, 393 biological processes were obtained, and it was found that biological processes were mainly enriched in cell differentiation, migration, apoptosis, and cell stress response to organisms.A total of 116 Pathways were obtained through KEGG pathway enrichment analysis, mainly involving Pathways in cancer, TNF Signaling Pathway, Tuberculosis, Chagas disease, Hepatitis B, etc. Finally, the molecular docking of key active molecules and key targets was realized for verification.Conclusions: this study of compound Chinese medicine pharmacology, through the network of peony licorice monkshood soup ingredients with osteoarthritis, targets, pathway analysis, you can see that drugs in the treatment of osteoarthritis is not a simple single targeted therapy, but by many components, multi-channel, mutual communications between the multiple targets, on the treatment of osteoarthritis in the future to provide more advice.
Impact On Mental Health and Wellbeing in Indigenous Communities Due To Land Loss Resulting From Industrial Resource Development: Protocol for a Systematic Review
Authors: Burns Nicole , Linton Janice , Pollock Nathaniel , Brubacher Laura Jane , Green Nadia , Keeling Arn , Latta Alex , Martin Jessica , Rand Jenny , Ninomiya Melody Morton
Published: November 2021

Background

Indigenous Peoples are impacted by industrial development projects that take place on, or near, their communities. Existing literature on impacts of industrial projects on Indigenous Peoples primarily focus on physical health outcomes and rarely focus on the mental health impacts. To understand the full range of long-term and anticipated health impacts of industrial resource development on Indigenous communities, mental health impacts must be examined. It is well-established that there is a connection between the environment and Indigenous wellbeing, across interrelated dimensions of mental, physical, emotional, and spiritual health. This systematic review will synthesize the evidence on the mental health impacts of land dispossession due to resource extractive projects on Indigenous communities. Looking at the mental health impacts of land dispossession from industrial resource development on Indigenous communities is relevant for a variety of reasons including planning, mitigation strategies, decision making, and negotiations.
Methods

This review includes an Indigenous Advisory Team and a team of Indigenous and settler scholars. The literature search will use the OVID interface to search Medline, Embase, PsycINFO, and Global Health databases. Non-indexed peer reviewed journals related to Indigenous health or research will be scanned. Books and book chapters will be identified in the Scopus and PsycINFO databases. The grey literature search will also include Google and be limited to reports published by government, academic, and non-profit organizations. Reference lists of key publications will be checked for additional relevant publications, including theses, dissertations, reports, and other articles not retrieved in the online searches. Additional sources may be recommended by team members. Included documents will focus on Indigenous Peoples in North America, South America, Australia, Aotearoa New Zealand, and Circumpolar regions, research that reports on mental health, and research that is based on land loss connected to dams, mines, agriculture, oil and gas. Literature that meets the inclusion criteria will be screened at the title/abstract and full text stages by two team members in Covidence. The included literature will be rated with a quality appraisal tool and information will be extracted by two team members; a consensus of information will be reached and be submitted for analysis.
Discussion

The evidence from this review is relevant for land use policy, health impact assessments, economic development, mental health service planning, and communities engaging in development projects.
Systematic review registration:

Registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration number CRD42021253720)
Lanthanide-Based Metal–Organic Frameworks Solidified by Gelatin-Methacryloyl Hydrogels For Improving the Accuracy of Localization and Excision of Small Pulmonary Nodules
Authors: Ji Haoran , Wang Xiaofeng , Wang Pei , Gong Yan , Wang Yun , Liu Chang , Ji Guangyu , Wang Xiansong , Wang Mingsong
Published: November 2021

The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization, such as hookwires, microcoils, and indocyanine green (ICG), have a number of limitations. For example, hookwires and microcoils may cause complications because of their invasive features, while ICG undergoes rapid diffusion after injection and has limited application in the localization of deep-seated lesions. In contrast, lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.
The effect of air bubble position on ART outcome in frozen-thawed blastocyst transfer
Authors: Yang Tingting , Chen Bo , Sun Xiaoyan , Li Qingyang , Li Qiumei , Chen Xuemei , Zhao Li , Pan Ruihua
Published: November 2021

Background

So far, only few literatures have studied the relationship between blastocyst transfer position and ART outcomes, and the conclusions are still controversial. Our study is to evaluate the effect of air bubble position on ART outcome and to find the optimal embryo transfer position in frozen-thawed blastocyst transfer.
Methods

This study included a retrospective cohort analysis of 399 frozen-thawed single blastocyst transfers ultrasound-guided performed between June 1, 2017 and November 30, 2020. All of the women scheduled for frozen-thawed single blastocyst transfers ultrasound-guided. The primary outcome is clinical pregnancy rate and the secondary outcome is live birth rate. Statistical analyses were conducted using One-way Anova, Kruscal Whallis H test, chi-square test and Smooth curve fitting.
Results

When BFD was less than 19 mm, there was no significant change in clinical pregnancy rate as BFD increased (OR = 0.95, 95% CI: 0.89 to 1.02, P = 0.1373); when BFD was more than 19 mm, the clinical pregnancy rate decreased by 16% for every 1 mm increase in BFD (OR = 0.84, 95% CI: 0.72 to 0.98, P = 0.0363). The effect of BFD on live birth rate were similar to that on clinical pregnancy rate, the inflection point was 19mm, when BFD was more than 19 mm, the live birth rate decreases by 58% for every 1 mm increase in BFD (OR = 0.42, 95% CI: 0.21 to 0.86, P = 0.0174)
Conclusions

The ideal pregnancy outcome can be achieved within 19mm from uterus fundus after single blastocyst transfer, The clinical pregnancy and live birth at a distance of more 19mm from the uterus fundus have a cliff-like downward trend.
Potentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections
Authors: Xiu Weijun , Wan Ling , Yang Kaili , Li Xiao , Yuwen Lihui , Dong Heng , Mou Yongbin , Yang Dongliang , Wang Lianhui
Published: November 2021

Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide novel therapeutic routes. Here, photodynamic therapy (PDT)-activated chemotherapy by potentiating the hypoxia of biofilm infection microenvironment is proposed to tackle methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections. In this study, PDT was used not only to eradicate MRSA biofilms in normoxic conditions, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of MRSA and activates metronidazole to kill bacteria. Moreover, PDT-activated chemotherapy could polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize PDT with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.
Long Covid after Breakthrough COVID-19: the post-acute sequelae of breakthrough COVID-19
Authors: Al-Aly Ziyad , Bowe Benjamin , Xie Yan
Published: November 2021

The post-acute sequelae of COVID-19 have been described1, but whether breakthrough COVID-19 (that is the disease that ensues following vaccine breakthrough SARS-CoV-2 infection) results in post-acute sequelae is not yet clear. Here we use the national healthcare databases of the US Department of Veterans Affairs to characterize 6-month risks of incident post-acute sequelae in people with breakthrough COVID-19 who survived for at least 30 days after diagnosis. We show that compared to people with no evidence of COVID-19, beyond the first 30 days of illness, people with breakthrough COVID-19 exhibit a higher risk of death and broad array of incident post-acute sequelae in the pulmonary system, as well as extrapulmonary sequelae that include cardiovascular disorders, coagulation disorders, gastrointestinal disorders, general disorders (e.g., fatigue), kidney disorders, mental health disorders, metabolic disorders, musculoskeletal disorders, and neurologic disorders. Our analyses by care setting of the acute phase of the disease show that people who were not hospitalized during the first 30 days after diagnosis with breakthrough COVID-19 exhibit a small but not insignificant increase in risk of death and post-acute sequelae; the risks are further increased in people who were hospitalized during the acute phase of the disease. Our comparative approach shows that people with breakthrough COVID-19 exhibit lower risks of death and post-acute sequelae than people with COVID-19 who were not previously vaccinated for it; and in analyses among individuals who were hospitalized during the acute phase of the disease, people with breakthrough COVID-19 exhibit higher risks of death and post-acute sequelae than people with seasonal influenza. Altogether, our findings show increased risks of death and post-acute sequalae in people with breakthrough COVID-19; the risks are evident among those who were not hospitalized during the acute phase of the disease. Our comparative approach provides context for understanding the risks in relation to COVID-19 without prior vaccination and seasonal influenza. The findings will inform the ongoing effort to optimize strategies for prevention of breakthrough SARS-CoV-2 infections and will guide development and optimization of post-acute care pathways for people with breakthrough COVID-19.
Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for Ovarian Endometriosis
Authors: Murakami Mayuko , Osuka Satoko , Muraoka Ayako , Hayashi Shotaro , Bayasula Bayasula , Kasahara Yukiyo , Sonehara Reina , Hariyama Yumi , Shinjo Kanako , Tanaka Hideaki , Miyake Natsuki , Yoshita Sayako , Nakanishi Natsuki , Nakamura Tomoko , Goto Maki , Hiroaki Kajiyama
Published: November 2021

Background

Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility in addition to dysmenorrhea. Hormonal treatments for endometriosis suppress ovulation; hence, they are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins that sense pathogen-/danger‐associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as the inhibitors of the NLRP3 inflammasome.
Methods

The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with/without endometriosis and OE and stromal cells derived from the endometrium of patients with endometriosis and OE (endometrial stromal cells [ESCs] and cyst-derived stromal cells [CSCs]). The effect of an NLRP3 inhibitor (MCC950) on ESC and CSC survival and IL-1β production was evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function.
Results

NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs and IL-1β concentrations in CSC supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In addition, IL-1β and Ki67 levels in the OE-associated epithelia and oxidative stress markers of granulosa cells were reduced in the MCC950-treated group.
Conclusions

These results indicate that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis.
Factors Associated With Long-Term Survival in Gemcitabine-Concurrent Proton Radiotherapy For Non-Metastatic Locally Advanced Pancreatic Cancer: a Single-Center Retrospective Study
Authors: Ogura Yuta , Terashima Kazuki , Nanno Yoshihide , Park SungChul , Suga Masaki , Takahashi Daiki , Matsuo Yoshiro , Sulaiman Nor Shazrina , Tokumaru Sunao , Okimoto Tomoaki , Toyama Hirochika , Fukumoto Takumi
Published: November 2021

Background: Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC.Methods: The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes.Results: The median survival time of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median survival times of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P < 0.001). LAPCs with anterior peripancreatic invasion had more peritoneal recurrence within 6 months than those without anterior peripancreatic invasion (P = 0.039).Conclusions: GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.
Forest malaria and prospects for antimalarial chemoprophylaxis among forest goers: findings from a qualitative study in Thailand
Authors: Jongdeepaisal Monnaphat , Khonputsa Panarasri , Prasert Orathai , Maneenet Suphitsara , Pongsoipetch Kulchada , Jatapai Anchalee , Rojanaprasert Chawarat , Sudathip Prayuth , Maude Richard James , Pell Christopher
Published: November 2021

Background Across the Greater Mekong Sub-region, malaria remains a dangerous infectious disease, particularly for people who visit forested areas where residual transmission continues. Because vector control measures offer incomplete protection to forest goers, chemoprophylaxis has been suggested as a potential supplementary measure for malaria prevention and control. To implement prophylaxis effectively, additional information is needed to understand forest goers’ activities and their willingness to use malaria prevention measures, including prophylaxis, and how it could be delivered in communities. Drawing on in-depth interviews with forest goers and stakeholders, this article examines the potential acceptability and implementation challenges of malaria prophylaxis for forest goers in northeast Thailand. Methods In-depth interviews were conducted with forest goers (n = 11) and stakeholders (n = 16) including healthcare workers, community leaders, and policymakers. Interviews were audio-recorded, transcribed and coded using NVivo, employing inductive and deductive approaches, for thematic analysis.Results Forest goers were well aware of their (elevated) malaria risk and reported seeking care for malaria from local health care providers. Forest goers and community members have a close relationship with the forest but are not a homogenous group: their place and time-at-risk varied according to their activities and length of stay in the forest. Among stakeholders, the choice and cost of antimalarial prophylactic regimen - its efficacy, length and complexity, number of tablets, potential side effects, and long-term impact on users - were key considerations for its feasibility. They also expressed concern about adherence to the preventive therapy and potential difficulty treating malaria patients with the same regimen. Prophylaxis was considered a low priority in areas with perceived accessible health system and approaching malaria elimination.Conclusions In the context of multi-drug resistance, there are several considerations for implementing malaria prophylaxis: the need to target forest goers who are at-risk with a clear period of exposure, to ensure continued use of vector control measures and adherence to prophylactic antimalarials, and to adopt an evidence-based approach to determine an appropriate regimen. Beyond addressing current intervention challenges and managing malaria incidence in low-transmission setting, it is crucial to keep malaria services available and accessible at the village level and provide support, especially in areas home to highly mobile populations.