bluuebunny/crossref_metadata_2025 huggingface dataset:
A Lymph Node Targeted Adjuvant and Engineered Subunit Vaccine Promotes Potent Immunity to Epstein-Barr Virus in HLA-expressing Mice
Authors: Dasari Vijayendra , McNeil Lisa , Beckett Kirrilee , Solomon Matthew , Ambalathingal George , Steinbuck Martin , Jakubowski Aniela , Seenappa Lochana , Palmer Erica , Zhang Jeff , Haqq Chris , DeMuth Peter , Khanna Rajiv
Published: July 2022

Recent emergence of a causal like between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a novel vaccine formulation based on a lymph node targeting Amphiphile (AMP) vaccine adjuvant, AMP-CpG, admixed with EBV gp350 glycoprotein and a novel EBV-polyepitope protein (EBVpoly) that includes 20 CD8+ T-cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses were induced in mice with titers > 100,000 in AMP-CpG vaccinated mice. Immunization including AMP-CpG also induced high frequencies of polyfunctional gp350-specific CD4+ T-cells and EBVpoly-specific CD8+ T-cells that were 2-fold greater than soluble CpG and were maintained for > 7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases. Teaser: A lymph node targeted AMP-CpG subunit EBV vaccine induces potent and durable immunity in HLA expressing mice.
Robinson annulation methodsynthesis of (3-Benzoyl-4-hydroxy-4,6-diphenyl- 2-styryl-cyclohexyl)-phenyl-methanone:Antioxidant and Antibacterial studies
Authors: Suriyakala Tevaraj , Senthilkumar Velmurugan , Mohanraj Arumugam , Ravindran Gurusamy
Published: July 2022

The Robinson annulation represents a tandem process including the Michael addition and intramolecular Aldol condensation, affording (3-Benzoyl-4-hydroxy-4,6-diphenyl-2-styryl-cyclohexyl)-phenyl-methanone skeleton with symmetrical 1,5-Diketones and 1,5-Diphenyl-penta-2,4-dien-1-one being substrates.The reaction proceeds in NaOEt as a catalyst, with no by-product formation, and involves simple operation requiring, no column chromatography. Thus, this protocol fulfils all of the criteria that define green chemistry. All the new compounds have been characterized by 1HNMR and 13CNMR spectral analysis. The synthesised compounds were tested to antioxidant and antibacterialproperties.
Regulation of synaptic connectivity in schizophrenia by mutual neuron-microglia interaction
Authors: Breitmeyer Ricarda , Vogel Sabrina , Heider Johanna , Wüst Richard , Keller Anna-Lena , Binner Anna , Fitzgerald Julia , Fallgatter Andreas , Volkmer Hansjurgen
Published: July 2022

The examination of post-mortem brain tissue suggests synaptic loss as a central pathological hallmark of schizophrenia. Synaptic loss has been shown to be related to increased inflammation in the central nervous system. Aberrant activation of microglia, the immune cells of the human brain, may account for neuronal damage in schizophrenia. Induced pluripotent stem cells represent a promising tool for studying neuropsychiatric disease mechanisms. A recent challenge has been the development of protocols to derive microglia as well as neurons from schizophrenia patient-derived stem cells to better understand the mechanistic contribution of neuroinflammation to the disease. To address this, we present a co-culture model of neurons and microglia, both of human origin to show increased susceptibility of neurons to microglia-like cells derived from schizophrenia patients. Analysis of IBA-1 expression, NFκB signaling, transcription of inflammasome-related genes, and caspase-1 activation shows that enhanced, intrinsic inflammasome activation in patient-derived microglia exacerbates neuronal deficits such as synaptic loss in schizophrenia. Anti-inflammatory pretreatment of microglia with minocycline specifically rescued aberrant synapse loss in schizophrenia and reduced microglial activation. These findings open up possibilities for further research in larger cohorts, focused clinical work and longitudinal studies that could facilitate earlier therapeutic intervention.
Piperine as potential therapy of post-weaning porcine diarrheas: an in vitro study using a porcine duodenal enteroid model
Authors: Satitsri Saravut , Akrimajirachoote Nattaphong , Nunta Kanokkan , Ruennarong Nitwarat , Amnucksoradej Orawan , Muanprasat Chatchai
Published: July 2022

Post-weaning diarrhea in piglets is a major problem resulting in significant loss in pig production. This study aimed to investigate effects of piperine, an alkaloid abundantly found in black peppers, on biological activities related to pathogenesis of post-weaning diarrheas using a porcine duodenal enteroid model, a newly established intestinal stem cell-derived in vitro model recapitulating physiology of porcine small intestinal epithelia. Porcine duodenal enteroid models were treated with disease-relevant pathological inducers with or without piperine (8 µg/mL and/or 20 µg/mL) before measurements of oxidative stress, mRNA expression of proinflammatory cytokines, nuclear factor-kappa B (NF-κB) nuclear translocation, barrier leakage, and fluid secretion. We found that piperine (20 µg/mL) inhibited H2O2-induced oxidative stress, TNF-α-induced mRNA expression of proinflammatory cytokines without affecting NF-κB nuclear translocation, and prevented TNF-α-induced barrier leakage in porcine duodenal enteroid monolayers. Importantly, piperine inhibited fluid secretion induced by both forskolin and heat-stable toxins (STa) in a three-dimensional model of porcine duodenal enteroids. Collectively, piperine possesses both anti-inflammatory and anti-secretory effects in porcine enteroid models. Further research and development of piperine may provide novel interventions for treatment of post-weaning porcine diarrheas.
Leading on co-production programmes in five UK collaborative research partnerships (2008-2018): responses to four tensions from system leaders using auto-ethnography
Authors: Graaf Peter van der , Kislov Roman , Smith Helen , Langley Joe , Hamer Natalie , Cheetham Mandy , Wolstenholme Daniel , Cooke Jo , Mawson Sue
Published: July 2022

BackgroundDespite a growing enthusiasm for co-production in health care services and research, research on co-production practices is lacking. An abundance of conceptual frameworks, guidelines and principles are available but little empirical research is conducted on ‘how to do’ co-production of research to improve health care services. This paper brings together leadership insights from collaborative research partnerships in the UK on co-production practices with the aim to inform practical guidance for new partnerships facilitating the co-production of applied health research in the future. MethodsUsing an auto-ethnographic approach, experiential evidence was elicited through collective sense making from recorded conversations between the research team and leaders of five UK collaborative research partnerships (CLAHRCS). This approach applies a cultural analysis and interpretation of the leads’ behaviours, thoughts and experiences of co-production between 2008 and 2018 in relation to the academics, health practitioners, policy makers, and third sector organisations involved in co-produced research projects within the collaborative research partnerships. ResultsThe findings highlight a variation of practices across CLAHRCs with the context in which co-production occurs largely determining the nature of the process and outcomes. We identified four tensions in doing co-production: 1) idealistic, tokenistic vs realistic narratives, 2) power differences and (lack of) reciprocity, 3) excluding vs including language and communication, 4) Individual motivation vs structural issues.ConclusionsThe tensions were productive in helping collaborative research partnerships tailor co-production practices to their local needs and existing opportunities. As a result, practices varied within and between partnerships, which should not be reduced to one gold standard for co-production but should be celebrated. The links between the tensions informed solutions in each context, with strategic leadership identified as an important starting point; however, this role needs to be developed into more distributed forms of leadership over time to facilitate co-production practices between partners. Facilitating structures for co-production enabled power sharing through capacity and capability building, which resulted in more inclusive language and communication, and more realistic practices of co-production in research. We provide recommendations for creating more meaningful narratives around co-production and facilitating power sharing between partners.
Evaluation of municipal landfills based on leachate transport and aquifer vulnerability by DRASTIC index
Authors: Moghaddam Hamid Kardan , Moghaddam Hossein Kardan , Mirzavand Mohammad , Yalali Amir hooman
Published: July 2022

One of the problems with the current environment due to population growth and development is the issue of Waste, landfill, and leachate production. Waste as a high-volume output source, multiple potential users for landfill sites, and leachate are problems. The study investigates the proper location of the municipal landfill using multi-criteria ANP and entropy. Accordingly, four main criteria were defined for analyzing two methods for an appropriate place in the GIS environment. These four main criteria were taken into account with 15 modeling sub-criteria. Finally, the entropy method identified five suitable locations using the ANP method, and four appropriate sites were determined. The distribution of the selected sites by the entropy and ANP methods showed that the ANP method is more distant than the entropy method, and the two sites, A4 and A5 positions are more distant than the other aquatic sites. To evaluate the identified sites, the vulnerability of groundwater resources downstream of identified sites and the rate of leachate movement from these sites were considered. Based on the results of the DRASTIC Vulnerability Index and MODPATH, a particle-tracking Model, it was found that the northeast part of the city has a longer affected area due to the higher slope and higher permeability than the selected locations in the northwest. Accordingly, the area affected by the A3 site is also the only place where leachate effects enter the aquifer within three years due to its proximity.
Identification of Laportea bulbifera using the Complete Chloroplast Genome as a Super-Barcode
Authors: wang Wenting , Wang Xingwen , Shi Yuhua , yin Qinggang , Gao Ranran , Wang Mengyue , Xiang Li , Wu Lan
Published: July 2022

Laportea bulbifera, a Miao medicine grown in karst areas, has exerts a unique curative effect on skin itching in the elderly, with an annual sales of > 100 million Yuan. Owing to the shortage of resources and large morphological variations in L. bulbifera, it is difficult to identify the species correctly using only traditional methods, which seriously affects the safety of drug usage for patients. This study obtained the complete high-quality L. bulbifera chloroplast (cp) genome, using second- and third-generation high-throughput sequencing. The cp genome was 149,911 bp in length, with a typical quadripartite structure. A total of 127 genes were annotated, including 83 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. There was an inverted small single copy (SSC) structure in the L. bulbifera cp genome, one large-scale rearrangement of ~ 39 kb excised in the SSC and IR regions. The complete cp genome sequence used as a super-barcode and the highly variable regions (ycf1, matK, and ndhD), especially matK, can be used as specific barcodes to accurately distinguish L. bulbifera from counterfeits and closely related species. This study is important for the identification of L. bulbifera and lays a theoretical foundation for elucidating the phylogenetic relationship of the species.
Characterizing bacterial pathogen causing sugar beet dry rot of root at harvest and its suppression by endophytic bacteria
Authors: Safara Somayeh , Harighi Behrouz , Amini Jahanshir , Bahramnejad Bahman
Published: July 2022

Several bacteria play essential roles in causing post-harvest sugar beet root rot. In 2018 and 2019, a survey in field and storage revealed the presence of sugar beet dry rot of root. Seventeen bacteria were isolated from the harvested roots from various geographic locations in West Azerbaijan, Iran. Pathogenicity test in sugar beet root slices revealed that isolate Buk12 showed dry rot similar to those observed in the storage after seven days. Based on the petiole test, Buk12 produced slight discoloration in leaf petiole that extended into the leaf. Molecular identification showed that strain Buk12 had a high similarity to Pseudomonas thivervalensis based on partial nucleotide sequencing of the 16S rRNA gene. Endophytic bacteria produce secondary metabolites (SMs) and volatile organic compounds (VOCs) that have a significant role in the control of phytopathogens. In this study, the antagonistic activity of endophytic bacteria Streptomyces sp. B86, Bacillus sp. S411, Pseudomonas sp. B451, Bacillus sp. Andi542, Streptomyces sp. Sh800, and Staphylococcus sp. Bt870 were screened and their VOCs effects on the virulence traits of Pseudomonas thivervalensis Buk12 were evaluated. All endophytic bacteria tested showed antagonistic activity against the bacterial pathogen in vitro. The results of enzymatic activity, HCN production, and siderophore production were varied amongst strains. The VOCs emitted from endophytic bacteria significantly reduced dry root symptoms and the growth of P. thivervalensis Buk12 at different levels. Our results revealed that VOCs produced by all endophytic bacteria significantly reduced swarming motility, chemotaxis behavior, and attachment of P. thivervalensis Buk12 cells to sugar beet roots. The VOCs produced by endophytic bacteria except for Streptomyces sp. B86 significantly reduced twitching motility by P. thivervalensis Buk12. The influence of VOCs on biofilm formation by bacterial pathogen was varied amongst endophytic bacteria. The gas chromatography-mass spectrometry (GC-MS) analysis revealed that strains B86, S411, B451, Andi542, Sh800, and Bt870 produced 13, 13, 15, 23, 16, and 24 VOCs, respectively with high quality. Our findings provide new information regarding the potential of VOCs with antibacterial activity and as a biocontrol tool against postharvest bacterial root rot. To the best of our knowledge, this is the first report about bacteria as sugar beet dry rot agent from Iran and the isolation of endophytic bacteria from sea beet plants with biocontrol activity.
Continuing cyclin-dependent kinase 4/6 inhibition in metastatic breast cancer patients previously treated with another cyclin-dependant kinase 4/6 inhibitor: a protocol for systematic review and meta-analysis
Authors: Aguilar Alicia de Luna , Fuentes Javier David Benitez , Arcilla Jorge Bartolome , Shah Richa , Avagyan Manushak , Frick Clara , Lorenzo Alfonso Lopez de Sa , Rojas Carmen Toledano , Anton Fernando Moreno , Saenz Jose Angel Garcia
Published: July 2022

Background
Breast cancer is the most frequent cancer in women worldwide. Most breast cancer cases are estrogen receptor positive and epidermal growth factor receptor 2 negative (ER+/HER2-). A small proportion of these cases are metastatic, with Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors being the mainstay of treatment in this scenario. Evidence supports the existence of differences between the three approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in preclinical and clinical settings. However, literature regarding the use of a CDK4/6i in metastatic breast cancer patients (MBC) previously treated with another CDK4/6i is scarce.
Methods
A search will be performed on the PubMed, Embase, and Web of Science databases following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. In addition, a manual search of the San Antonio Breast Cancer Conference, American Society of Clinical Oncology annual conference, European Society of Medical Oncology annual conference, and European Society of Medical Oncology Breast annual conference will be performed.
Discussion
To our knowledge, no previous systematic review has evaluated the available evidence regarding the efficacy and safety of treatment with CDK4/6i in MBC previously treated with another CDK4/6i. This systematic review and meta-analysis will synthesise the existing data on the effectiveness and safety of using a CDK4/6i after prior exposure to another in MBC. It will also identify the gap in the literature for potential future research. This study's results will interest multiple audiences, including patients, their families, caregivers, and healthcare professionals. Results will be published in a peer-reviewed journal.
Systematic review registration:
PROSPERO CRD42022330355
Can global or national disability weights represent provincial level?
Authors: He Qin , Zhou Maigeng , Yin Peng , Jiang Bo , Qi Jinlei , Liu Yunning , Liu Jiangmei , You Jinling , Zhou Yuchang , Long Zheng , Xing Xiuya , Cheng Qianyao , Chen Yeji , Wang Huadong , Liu Zhirong
Published: July 2022

Background A universal set of disability weights(DWs) mainly based on the survey of North America, Australia and Europe, the participants in Asia was limited. The debate hasn’t yet settled whether a universal DW is desirable or useful. Taking the DWs of Anhui province in Central China as an introduction, through the same-cultural and cross-cultural comparisons, this paper attempts to answer the representative questions of DWs.Methods A web-based survey was conducted to estimate the DWs for 206 health states of Anhui province in 2020. Paired comparison (PC) data were analyzed and anchored by probit regression and fitting loess model. We compared the DWs in Anhui with other provinces in China and those in Global burden of disease (GBD) and Japan. Results Compared with Anhui province, the proportion of health states which showed 2 times or more differences ranged from 1.94% (Henan) to 11.17% (Sichuan) in China and domestic provinces. It was 19.88% in Japan and 21.51% in GBD 2103 respectively. In Asian countries or regions, most of the health states with top 15 DWs belonged to the category of mental, behavioral, and substance use disorders. But in GBD, most were infectious diseases and cancer. The differences of DWs in neighboring provinces were smaller than other geographically distant provinces or countries.Conclusion Global or national DWs may not represent provincial level, especially in the absence of the gold standards. And there is an urgent need for relevant gold standards.
Mothers' Decisions to Exclusively Breastfeed in Indonesia: The Implication of Socio-Economic and Mental Illness Factors
Authors: Relaksana Riki , Akbar Adhadian , Sihaloho Estro Dariatno , Ferdian Dani , Siregar Adiatma YM
Published: July 2022

Background:
In Indonesia, nearly half of all children aged < 6 months were not exclusively breastfed in 2017. This study aimed to estimate the cost of providing exclusive breastfeeding compared to partial exclusive breastfeeding and use of formula milk. This study also assessed the maternal socio-economic and mental health factors to providing exclusive breastfeeding.
Methods:
Data were collected in 2018 via a cross-sectional survey of 456 mothers in Bandung City and Purwakarta District who had children aged < 6 months. We used micro-costing to calculate the cost of productivity, equipment, supplies, and training for mothers when providing exclusive breastfeeding, partial exclusive breastfeeding, and formula milk. Logistic regression was used to determine the impact of several independent variables, including the mother's level of depression, on exclusive breastfeeding.
Results:
To breastfeed exclusively, a family needs to spend $ 116,95, which is less expensive than partial breastfeeding ($ 487,18) and providing only formula milk ($ 531,97). We also found that age, time spent on breastfeeding, and marital status positively influence the decision to breastfeed. On the other hand, working status, the number of children, and the total cost of the child’s nutrients negatively impact the decision. Finally, severe maternal depression symptoms were significantly negatively associated with the decision to exclusively breastfeed.
Conclusion:
The total cost of providing only formula milk is 3-times higher than the cost of exclusively breastfeeding, even after including the cost of providing breastfeeding time. The total cost and presence of severe depression symptoms are related to the mother’s decision to not exclusively breastfeed. This study found that exclusive breastfeeding is economically preferable to other methods and supports policies to reduce the time cost of exclusive breastfeeding and address the importance of the mother's mental health to ensure successful breastfeeding.
Diagnostic accuracy and significance of clinical analysis of liver stiffness measurement by Fibro touch in metabolic-related fatty liver disease
Authors: Qin Qian , Yan Hang , Chen Jingfeng , Wu Zhuoqing , Yang Yang , Su Yan , Huang Meng , Li Tiantian , Sun Yanfang , Wang Shoujun , Ding Suying
Published: July 2022

Background and Aim: We aimed to explore risk factors and construct a model of MAFLD with fibrosis fibrosis and compare the performance of the panels of APRI, FIB-4 and BARD.Methods: We retrieved clinical information and enrolled 3671 patients. Subjects were assigned to four groups: MAFLD, MAFLD with fibrosis, and MAFLD with advanced fibrosis. Multivariate regression analysis and randomforest model were to construct the model of MAFLD with fibrosis, the receiver operating characteristics (ROC) were used to compare the diagnostic efficacy of predictive model, APRI, BARD, FIB-4. Results: ①The proportion of fibrosis in MAFLD was higher than that of non-MAFLD group; Compared with the control group, advanced fibrosis (≥F3) has no statistical significance. ②Four variables were selected to build the model of MAFLD. The diagnostic accuracy (AUROC=0.730) was superior to that of APRI and random forest model. ③Multivariate logistic analysis showed that increased BMI and AST was risk factors for advanced fibrosis and elevated PLT was a protective factor for advanced fibrosis; The diagnostic power of the model (AUROC=0.714) was superior to that of the FIB-4 and BARD.Conclusion: The model of fibrosis stage with MAFLD is superior to other non-invasive markers of fibrosis of MAFLD, which can assist clinicians in screening and warning for potential risks of MAFLD with fibrosis.
Differences in soil microbial communities with successional stage depend on vegetation coverage and soil substrates in alpine desert shrublands
Authors: Dong Ruizhen , Wang Xiaoli , Wang Yanlong , Ma Yushou , Yang Shihai , Zhang Litian , Zhang Min , Qin Jinping , Quzha Renzeng
Published: July 2022

Background and aims In semiarid ecosystems, changes in plant communities are promoted under shrub canopies during restoration, but the link between shrub community restoration dynamics and changes in soil microbe communities is still unclear.Methods We characterized the community structure and plant interactions of soil microbes by combining different methodological approaches (including high-throughput sequencing of the 16S rRNA gene and ITS gene, analysis of phospholipid fatty acids (PLFAs) and chloroform fumigation) and the key driving factors along a successional gradient of Sophora moorcroftiana shrub community in the middle reaches of the Yarlung Zangbo River.Results Soil microbial biomass carbon (MBC) and nitrogen (MBN), total PLFAs, and alpha diversity increased significantly as the successional stage advanced, and MBC and MBN were positively correlated with the carbon and nitrogen contents in the soil. Mantel test showed that successional stage-induced changes in soil microbial beta diversity were mainly associated with shrub coverage and soil physicochemical properties. The relative abundances of bacterial PLFAs, particularly those of gram-negative bacteria, such as Bacteroidetes, Alphaproteobacteria and Betaproteobacteria, significantly decreased with succession; the opposite was true for Acidobacteria, Planctomycetes, Gemmatimonadetes Deltaproteobacteria and Gammaproteobacteria. However, the proportion of fungi did not significantly differ among the four successional stages; the dominant phyla were Ascomycota and Basidiomycota.Conclusion We suggest that shrubs directly shape soil microbial communities or indirectly affect such communities by altering soil substrates. Our findings advance the current understanding of sand-stabilizing plant–soil interactions during natural restoration and the reversal of desertification in stressful desert ecosystems.
Prostatic artery embolization compared to trans-urethral resection of the prostate and prostatic urethral lift: A real-world population-based study
Authors: Chughtai Bilal , Raizenne Brendan , Zheng Xinyan , Oumedjbeur Kussil , Mao Jialin , Zorn Kevin , Elterman Dean , Bhojani Naeem , McClure Timothy , Te Alexis , Kaplan Steven , Sedrakyan Art
Published: July 2022

Background There are growing interests for minimally invasive surgical techniques (MISTs) for the treatment of benign prostatic hyperplasia (BPH) associated lower urinary tract symptoms (LUTS). Prostatic artery embolization (PAE) uses selective angioembolization of prostatic arteries, thereby reducing size to improve LUTS/BPH. However, real-world data comparing surgical outcomes between MISTs and tissue resective techniques is lacking. We assessed the differences in surgical outcomes between PAE, transurethral resection of the prostate (TURP), and prostatic urethral lift (PUL) in a real world-population for LUTS/BPH. Methods We present an observational population-based study of 12,902 men with BPH in New York State who received PAE, TURP, and PUL in outpatient and ambulatory surgery settings from 2014 to 2018. For short-term outcomes, we report 30-day and 90-day risks of readmission to inpatient and emergency room (ER) with/without complications and compared them across groups using Chi-square tests and mixed effect logistic regressions. For long-term outcomes, we report surgical retreatment and stricture rates using Kaplan Meier failure curves and compared them using Log rank tests and Cox regression models. Results Of 12 902 men, 335 had PAE, 11 205 had TURP, and 1 362 had PUL. PAE patients had the highest 30-day (19.9%) and 90-day (35.6%) risks of readmission to inpatient or ER (p<0.01). Non-specific abdominal pain was the main diagnosis associated with 30-day and 90-day readmissions to inpatient or ER after PAE (14.3% and 26.8%, respectively). After 2 years of follow-up, PAE patients had the highest retreatment rate of 28.5% (95%CI: 23.7%-34.2%) compared to TURP (3.4% (95%CI: 3.1%-3.8%)) and PUL (8.5% (95%CI: 5.6%-12.9%)) (p<0.001). Conclusion In a real-world population, PAE was associated with the most frequent 30-day and 90-day readmission to inpatient or ER and the highest retreatment rate among all surgical techniques even when controlled for individual patient comorbidities and surgical volume.
PDO-ENSO Effects on Southern Brazilian Precipitation
Authors: Moraes Osvaldo L. L , Marengo Jose A.
Published: July 2022

The role of the Pacific decadal oscillation (PDO) was investigated in terms of the anomalous precipitation in southern Brazil related to the El Niño-Southern Oscillation (ENSO) using a long-term data set from 1961 to 2016 from 106-gauge stations. In addition, a direct comparison analysis was performed between El Niño plus positive PDO events and La Niña plus adverse PDO events to discover any modulating effects of PDO on precipitation. Our findings suggest that significant monthly favorable anomalous precipitation occurred in the entire region only during intense or extreme El Niño events, with no modulation effect from the PDO regardless of its intensity. However, monthly negative precipitation anomalies varied from small to medium at higher latitudes during robust La Niña periods, with some connection to adverse PDO events.
The ER Calcium Channel Csg2 Integrates Sphingolipid Metabolism with Autophagy
Authors: Liu Shiyan , Chen Mutian , Wang Yichang , Lei Yuqing , Zhang Yabin , Huang Ting , Li Huihui , Qi Shiqian , Geng Jia , Lu Kefeng
Published: July 2022

Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we found that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy.
Challenges of Implementing Family Physician Program in Urban Communities: A qualitative study
Authors: Hajibadali Parisa , Nadrian Haidar , Hashemiparast Mina
Published: July 2022

Background Family physician program plays a crucial role in promoting community‐based primary healthcare quality. This study aimed to explore the challenges and obstacles of implementing family physician program in an Iranian urban community context.Methods A qualitative study with conventional content analysis approach was conducted. Data were collected through semi-structured individual interviews until data saturation, and were concurrently analyzed. MAXQDA 10 was used to manage the data. The study was conducted between February and July 2019 in urban health centers of Bonab, Iran. Participants were nineteen healthcare recipients and healthcare providers from urban health centers in Bonab, Iran.Results Three main categories including ‘socio-cultural and economic challenges’, ‘interpersonal communication difficulties’ and ‘inefficient management’ emerged as the challenges of implementing urban family physician program in the community.Conclusions The implementation of family physician program is a long process that is influenced by various factors and elimination of barriers requires developing infrastructures and culture growth and improving the professional settings and interpersonal relationship.
A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen <10 ng/mL
Authors: Miyoshi Yasuhide , Kawahara Takashi , Uemura Hiroji
Published: July 2022

Background
There is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy.
Methods
A systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) just before biopsy. Patient’s age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses.
Results
The median patient’s age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively.
Conclusion
The study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.
Rural Households’ Perceptions of Rosehip and the Role It Plays in Rural Livelihoods in Lesotho
Authors: Makhorole Thato , Fraser Gavin , Phakathi Sandile
Published: July 2022

Despite the amount of research on the perceived negative impacts of invasive alien species, they remain integral to the rural communities due to their numerous livelihoods uses. More research is required, focusing on the impacts of invasive alien species on the livelihoods of rural communities. This paper investigates the community perceptions of rosehip (Rosa rubiginosa) in Lesotho and its contribution to rural communities. A sample of 160 participants was chosen using simple random sampling. Descriptive, Principal component analysis and the probit model were used to analyse the results. The study found that rosehip's livelihood benefits, and its abundance highly influence the social, economic and environmental perception of rural communities. However, the income from rosehip was found to be the lowest income component. Despite the income from rosehip being low, it acts as a safety net in the face of shocks such as limited job opportunities and food shortages to the poorer households who have few income sources.
Relationship between lymphocyte to C-reactive protein ratio and severity of coronary artery disease
Authors: Chen Ke , Liu Yehong , Xu Baida , Ye Ting , Chen Liang , Wu Gangyong , Zong Gangjun
Published: July 2022

Background: Coronary atherosclerosis is a systemic chronic inflammatory disease. Some laboratory parameters, such as the neutrophils-to-lymphocytes ratio (NLR), platelet-to-lymphocyte ratio (PLR) and the systemic immune inflammation index (SII), were used to assess the degree of inflammation and the severity of coronary artery disease (CAD). The lymphocyte-to-C-reactive protein ratio (LCR) is a new systemic immune inflammation index, and its relationship with the development and severity of CAD is not clear.Methods A total of 1107 patients underwent coronary angiography, including 479 in the control group and 628 in the CAD group. The routine and biochemical indexes in the venous blood of patients in each group before coronary angiography were assessed. LCR, SII, NLR and PLR were calculated, and statistical analysis was performed. Propensity score matching (PSM) and a logistic regression model was used to analyze the relationship between LCR and CAD.Results After PSM, 384 pairs of patients with or without CAD were successfully matched. After median binary classification of all indicators, univariate and multivariate logistic regression analysis showed that platelet was an independent related risk factor and LCR was an independent related protective factor. By the same method, in the coronary heart disease severity group, a total of 212 pairs were successfully matched, and it was finally determined that NLR and PLR were independent related risk factors, and LCR was an independent related protective factor.Conclusions LCR is an independent correlative protective factor affecting the occurrence and severity of CAD.
Celluar Immunotherapy: A promising therapeutic strategy for Patients with post-mastectomy early Breast Cancer
Authors: Liu Zhantao , Xu Jiantao , Zhou Jun , Song Yanqiu
Published: July 2022

Background: Early breast cancer(eBC) , in part, is a curable disease.Recurrence and metastasis are the main causes of such patients mortality. Although post-operative adjuvant therapy for breast cancer has made great strides, challenges remain and new therapeutic approaches are needed. Cellular immunotherapy(CIT) provides a promising new therapeutic to the management of eBC.This study aims to assess the efficacy and safty of sequential CIT after chemoradiotherapy in patients with post-mastectomy eBC as well as exploring the potential beneficiaries of CIT.Methods: From January 2010 to December 2014, 723 patients with post-mastectomy eBC were included in this retrospective study: 118 caces underwent CIT in addition to initial therapy; a further 605 cases received initial therapy only,such as chemoradiotherapy,endocrine therapy and targeted therapy, etc.Results: A comparison of the 5-year survival curves shows that the 5-year disease free survival(DFS) of patients in the CIT group was signifificantly higher than in the control group(86.44% vs 78.51%, P=0.045).The multivariate analysis identified CIT as a noteworthy independent risk factor for DFS(P=0.027, HR=0.552(0.325-0.935 )). Subgroup analysis revealed that adjuvant CIT markedly increased the DFS rate of patients with axillary lymph node metastasis and tumor–node–metastasis(TNM)stage III. None of the patients enrolled in the CIT group discontinued CIT due to adverse reactions.Conclusions: Our study suggests that CIT was a species of safe and effective mode of treatment improving the DFS for patients with post-mastectomy eBC, especially those with lymph node metastasis and advanced TNM stage, and the toxicity was tolerable and consisted primarily of reversible hyperthermia.
Classification, risk factors, and outcomes of patients with progressive hemorrhagic injury after traumatic brain injury
Authors: Wang Ren , Yang Dian-Xu , Ding Jun , Guo Yan , Ding Wan-Hai , Tian Heng-Li , Yuan Fang
Published: July 2022

Background
According to the pathoanatomic classification system, progressive hemorrhagic injury (PHI) can be categorized into progressive intraparenchymal contusion or hematoma (pIPCH), epidural hematoma (pEDH), subdural hematoma (pSDH), and traumatic subarachnoid hemorrhage (ptSAH). The clinical features of each type differ greatly. The objective of this study was to determine the predictors, clinical management, and outcomes of PHI according to this classification.
Methods
Multivariate logistic regression analysis was used to identify independent risk factors for PHI and each subgroup. Patients with IPCH or EDH were selected for subgroup propensity score matching (PSM) to exclude confounding factors before evaluating the association of hematoma progression with the outcomes by classification.
Results
In the present cohort of 419 patients, 123 (29.4%) demonstrated PHI by serial CT scan. Of them, progressive ICPH (58.5%) was the most common type, followed by pEDH (28.5%), pSDH (9.8%), and ptSAH (3.2%). Old age (≥ 60 years), lower motor Glasgow Coma Scale score, larger primary lesion volume, and higher level of D-dimer are independent risk factors related to PHI. These factors are also independent predictors for pIPCH, but not for pEDH. The time to first CT scan and presence of skull linear fracture are robust risk factors for pEDH. After PSM, the 6-month mortality and unfavorable survival rates were significantly higher in the pIPCH group than the in the non-pIPCH group (24.2% vs. 1.8% and 12.1% vs. 7.3%, respectively, p < 0.001), but not significantly different between the pEDH group and the non-pEDH group.
Conclusions
Understanding the specific patterns of PHI according to its classification can help increase the accuracy of prediction and suggest targeted prevention or treatment strategies to improve patients’ neurological outcomes.
Evaluation of biofouling characteristics on reverse osmosis membranes of disinfection-residual-bacteria (DRB) after seven kinds of disinfection
Authors: Wu Yin-Hu , Wang Haobin , Wang Wen-Long , Luo Li-Wei , Chen Gen-Qiang , Chen Zhuo , Xue Song , Xu Ao , Xu Yu-Qing , Ikuno Nozomu , Ishii Kazuki , Hu Hongying
Published: July 2022

Biofouling is a critical defect of the reverse osmosis (RO) system. It has been reported that disinfection processes tend to select certain undesirable disinfection-residual bacteria (DRB), leading to severe long-term biofouling potential. To provide constructive guidance on biofouling prevention in RO systems, this study evaluated the biofouling characteristics of RO membranes of DRB after the application of five mature disinfection methods (NaClO, NH2Cl, ClO2, UV, and O3) and two novel disinfection methods (K2FeO4 and flow-through electrode system (FES)). After a 32-day biofilm cultivation on the RO membranes, the DRB biofilm of K2FeO4 and O3 caused a slight normalised flux drop (22.4 ± 2.4% and 23.9 ± 1.7%, respectively) of RO membrane compared with the control group (non-disinfected, ~ 27% normalised flux drop). Moreover, the biofouling degree of the NH2Cl-DRB biofilm was similar to that of the control group. The remaining disinfection types aggravated membrane biofouling. The biofouling behaviour of DRB showed no relationship with bacterial concentration or activity. The thickness and density of the biofilms as well as the organics/bacterial number ratio in the DRB biofilm, helped explain the difference in the fouling degree between each group. Moreover, microbial community analysis showed that the relative abundance of typical highly secretory and biofouling-related genera, such as Pseudomonas, Sphingomonas, Acinetobacter, Methylobacterium, Sphingobium, and Ralstonia, were the main reasons for the difference in biofouling degree. All types of disinfection effectively prevented pathogen reproduction in the DRB biofilm. However, the relative abundance of (opportunistic) pathogens increased significantly after NaClO and ClO2 disinfection.
Improving recommendation diversity and serendipity with an Ontology-based algorithm for cold start environments
Authors: Kuznetsov Stanislav , Kordík Pavel
Published: July 2022

Every real-life system has several development phases. In the beginning, it has no interactions; wecall this the cold-start problem. After a while, where user interactions occur in the system, the sys-tem gets to a state where one part of the catalogue has some interaction that could be enough touse CF algorithms. However, there’s still a larger amount of items with a small amount of inter-action, so-called cold-item. We call this state a transition state. If most of the item in the systemhas interactions, we call this a regular state. The system needs a slightly different behaviour fromthe recommendation system at each stage. At the cold-start stage, we need exploration of thecatalogue and the involvement of the maximum number of cold-items to use CF as soon as pos-sible. In the transition phase, we need diversification because there are still many items with asmall amount of interaction. In the regular phase, we want to offer new relevant items to usersto surprise them and keep them from getting into the information bubble and thus have a betterexperience using the system. Our approach uses Ontology, which can provide semantic item simi-larity if the text attributes contain the exact words but even if the text attributes look different.This paper presents a Universal Ontological-Based Algorithm (OBACS) that uses diversificationmethods such as serendipity and diversity to improve user experience in all system developmentphases. We verify our approach experimentally on the Movie Database and describe the results.
Network of hotspot interactions cluster tau amyloid folds
Authors: Mullapudi Vishruth , Vacquer-Alicea Jaime , Bommareddy Vaibhav , Vega Anthony , Ryder Bryan , White Charles , Diamond Marc , Joachimiak Lukasz
Published: July 2022

Cryogenic electron microscopy has revealed unprecedented molecular insight into the conformation of β-sheet-rich protein amyloids linked to neurodegenerative diseases. It remains unknown how a protein can adopt a diversity of folds and form multiple distinct fibrillar structures. Here we develop an in silico alanine scan method to estimate the relative energetic contribution of each amino acid in an amyloid assembly. We apply our method to twenty-seven ex vivo and in vitro fibril structural polymorphs of the microtubule-associated protein tau. We uncover networks of energetically important interactions involving amyloid-forming motifs that stabilize the different fibril folds. We test our predictions in cellular and in vitro aggregation assays. Using a machine learning approach, we classify the structures based on residue energetics to identify distinguishing and unifying features. Our energetic profiling suggests that minimal sequence elements that control the stability of tau fibrils, allowing future design of protein sequences that fold into unique structures.
Mapping internal temperatures during high-rate battery applications
Authors: Shearing Paul , Heenan Thomas , Mombrini Isabella , Llewellyn Alice , Checchia Stefano , Tan Chun , johnson michael , Jnawali Anmol , Garbarino Gaston , Jervis Rhodri , Brett Dan , Michel Marco Di
Published: July 2022

Electric vehicles (EV) demand high charge/discharge rates creating potentially dangerous temperature rises. Lithium-ion cells are sealed during their manufacture, making internal temperatures challenging to probe1. Tracking current collector expansion using X-ray diffraction (XRD) permits non-destructive internal temperature measurements2; however, cylindrical cells are known to experience complex internal strain3,4. Here, we characterise the state-of-charge (SoC), mechanical strain, and temperature within Lithium-ion 18650 cells operated at high rates (>3C) via two advanced synchrotron XRD methods: firstly, as entire cross-sectional temperature maps during open-circuit cooling and secondly, single-point temperatures during charge/discharge cycling. We observed that a 20-minute discharge on an energy-optimised cell (3.5 Ah) resulted in internal temperatures >70 °C, whereas, a faster 12-minute discharge on a power-optimised cell (1.5 Ah) resulted in substantially lower temperatures (< 50 °C). However, when comparing the two cells under the same electrical current, the peak temperatures were similar, e.g., a 6A discharge resulted in 40°C peak temperatures for both cell types. We observe that the operando temperature rise is due to heat accumulation, strongly influenced by the charging protocol e.g., constant-current (CC) and/or constant-voltage (CV). Design mitigations for temperature-related battery issues should now be explored using this novel methodology to provide opportunities for improved thermal management during high-rate EV applications.