bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and Genomic Analysis of ValSw3-3, a New
Siphoviridae
Bacteriophage Infecting Vibrio alginolyticus
Authors: Chen Ling , Liu Quan , Fan Jiqiang , Yan Tingwei , Zhang Haoran , Yang Jinfang , Deng Deng , Liu Chaolan , Wei Ting , Ma Yingfei
Published: February 2020

Phage therapy has been considered a potential alternative to antibiotic therapy in treating bacterial infections. For controlling the vibriosis-causing pathogen
Vibrio alginolyticus
, well-documented phage candidates are still lacking. Here, we characterize a novel lytic
Vibrio
phage, ValSw3-3, based on its morphology, host range and infectivity, growth characteristics, stability under various conditions, and genomic features. Our results show that ValSw3-3 could be a potent candidate for phage therapy to treat
V. alginolyticus
infections due to its stronger infectivity and better pH and thermal stability than those of previously reported
Vibrio
phages. Moreover, genome sequence alignments, phylogenetic analysis,
in silico
proteomic comparison, and core gene analysis all support that this novel phage, ValSw3-3, and five unclassified phages form a clade distant from those of other known genera ratified by the ICTV. Thus, we propose a new viral genus within the
Siphoviridae
family to accommodate this clade, with ValSw3-3 as a representative member.
T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species
Authors: Grifoni Alba , Voic Hannah , Dhanda Sandeep Kumar , Kidd Conner K. , Brien James D. , Buus Søren , Stryhn Anette , Durbin Anna P. , Whitehead Stephen , Diehl Sean A. , De Silva Aruna D. , Balmaseda Angel , Harris Eva , Weiskopf Daniela , Sette Alessandro
Published: February 2020

The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.
Defining Stage-Specific Activity of Potent New Inhibitors of Cryptosporidium parvum Growth
In Vitro
Authors: Funkhouser-Jones Lisa J. , Ravindran Soumya , Sibley L. David
Published: February 2020

Currently, nitazoxanide is the only FDA-approved treatment for cryptosporidiosis; unfortunately, it is ineffective in immunocompromised patients, has varied efficacy in immunocompetent individuals, and is not approved in infants under 1 year of age. Identifying new inhibitors for the treatment of cryptosporidiosis requires standardized and quantifiable
in vitro
assays for assessing potency, selectivity, timing of activity, and reversibility. Here, we provide new protocols for defining which stages of the life cycle are susceptible to four highly active compound classes that likely inhibit different targets in the parasite. We also utilize a newly developed long-term culture system to define assays for monitoring reversibility as a means of defining cidal activity as a function of concentration and time of treatment. These assays should provide valuable
in vitro
parameters to establish conditions for efficacious
in vivo
treatment.
Bacterial Transformation Buffers Environmental Fluctuations through the Reversible Integration of Mobile Genetic Elements
Authors: Carvalho Gabriel , Fouchet David , Danesh Gonché , Godeux Anne-Sophie , Laaberki Maria-Halima , Pontier Dominique , Charpentier Xavier , Venner Samuel
Published: February 2020

Natural transformation is the acquisition, controlled by bacteria, of extracellular DNA and is one of the most common mechanisms of horizontal gene transfer, promoting the spread of resistance genes. However, its evolutionary function remains elusive, and two main roles have been proposed: (i) the new gene acquisition and genetic mixing within bacterial populations and (ii) the removal of infectious parasitic mobile genetic elements (MGEs). While the first one promotes genetic diversification, the other one promotes the removal of foreign DNA and thus genome stability, making these two functions apparently antagonistic. Using a computational model, we show that intermediate transformation rates, commonly observed in bacteria, allow the acquisition then removal of MGEs. The transient acquisition of costly MGEs with resistance genes maximizes bacterial fitness in environments with stochastic stress exposure. Thus, transformation would ensure both a strong dynamic of the bacterial genome in the short term and its long-term stabilization.
Repurposed Drugs That Block the Gonococcus-Complement Receptor 3 Interaction Can Prevent and Cure Gonococcal Infection of Primary Human Cervical Epithelial Cells
Authors: Poole Jessica , Day Christopher J. , Haselhorst Thomas , Jen Freda E.-C. , Torres Victor J. , Edwards Jennifer L. , Jennings Michael P.
Published: February 2020

Novel therapies that avert the problem ofNeisseria gonorrhoeaewith acquired antibiotic resistance are urgently needed. Gonococcal infection of the human cervix is initiated by an interaction between a galactose modification made to its surface appendages, pili, and the I-domain region of (host) complement receptor 3 (CR3). By targeting this crucial gonococcal–I-domain interaction, it may be possible to prevent cervical infection in females. To this end, we identified the I-domain galactose-binding epitope of CR3 and characterized its galactose lectin activity. Moreover, we identified two drugs, carbamazepine and methyldopa, as effective host-targeted therapies for gonorrhea treatment. At doses below those currently used for their respective existing indications, both carbamazepine and methyldopa were more effective than ceftriaxone in curing cervical infectionex vivo. This host-targeted approach would not be subject toN. gonorrhoeaedrug resistance mechanisms. Thus, our data suggest a long-term solution to the growing problem of multidrug-resistantN. gonorrhoeaeinfections.
Robustness in an Ultrasensitive Motor
Authors: Liu Guangzhe , Tao Antai , Zhang Rongjing , Yuan Junhua
Published: February 2020

The bacterial flagellar motor is an ultrasensitive motor. Its output, the probability of the motor turning clockwise, depends sensitively on the occupancy of the protein FliM (a component on the switch complex of the motor) by the input CheY-P molecules. With a limited cellular pool of CheY-P molecules, cell-to-cell variation of the FliM level would lead to large unwanted variation of the motor output if not compensated. Here, we showed that the motor output is robust against the variation of FliM level and identified the adaptive remodeling of the motor switch complex as the mechanism for this robustness.
Correlations between the Composition of the Bovine Microbiota and Vitamin B
12
Abundance
Authors: Franco-Lopez Julian , Duplessis Melissa , Bui An , Reymond Coralie , Poisson William , Blais Lya , Chong Jasmine , Gervais Rachel , Rico Daniel E. , Cue Roger I. , Girard Christiane L. , Ronholm Jennifer
Published: February 2020

In this paper, we examined the microbiome of the bovine rumen, feces, and milk and attempted to understand how the bacterial communities at each site affected the production and movement of vitamin B
12
around the animal’s body. It was determined that the composition of the bovine rumen microbiome correlates well with vitamin B
12
concentration, indicating that the rumen microbiota may be a good target for manipulation to improve production of this important vitamin.
Intranasal Bacterial Therapeutics Reduce Colonization by the Respiratory Pathogen Mannheimia haemolytica in Dairy Calves
Authors: Amat Samat , Alexander Trevor W. , Holman Devin B. , Schwinghamer Timothy , Timsit Edouard
Published: February 2020

Bovine respiratory disease (BRD) is one of the significant challenges for the modern dairy industry in North America, accounting for 23 to 47% of the total mortality among pre- and postweaned dairy heifers. Mass medication with antibiotics is a common practice to control BRD in dairy cattle. However, the emergence of multidrug-resistant BRD pathogens highlights the importance of developing alternatives to antibiotics for BRD mitigation. Using a targeted approach, we recently identified 6Lactobacillusstrains originating from the bovine respiratory microbiota as candidates to be used as bacterial therapeutics (BTs) for the mitigation of the BRD pathogenMannheimia haemolytica. Here, we demonstrated that intranasal inoculation of the BT strains reduced nasal colonization byM. haemolyticain dairy calves experimentally challenged with this pathogen. This study, for the first time, shows the potential use of intranasal BTs as an alternative to mitigate BRD pathogens in cattle.
Long-Term Phytoremediation of Coastal Saline Soil Reveals Plant Species-Specific Patterns of Microbial Community Recruitment
Authors: Wang Xiaogai , Sun Ruibo , Tian Yinping , Guo Kai , Sun Hongyong , Liu Xiaojing , Chu Haiyan , Liu Binbin
Published: February 2020

Despite knowing that phytoremediation by salt-tolerant plants is an effective technology for ameliorating saline soils and that microorganisms contribute significantly to plant stress tolerance and soil fertility, we still lack a comprehensive understanding of how microbes respond to the growth of salt-tolerant plants and the subsequent decline in soil salinity. The results of this study revealed different response patterns among bacterial, archaeal, and fungal communities and indicated that the decline in archaeal abundance might be a sign of successful remediation of coastal saline soils. The recruitment of specific fungal communities by different plant species indicated the importance of fungi in plant species-specific remediation functions. We also identified the taxa that may play key roles during remediation, and these taxa could potentially be used as indicators of phytoremediation. Overall, these findings highlight the importance of microbes in the phytoremediation of saline soil and suggest that the mechanisms involved are plant species specific.
Sport Medicine Diagnostic Coding System (SMDCS) and the Orchard Sports Injury and Illness Classification System (OSIICS): revised 2020 consensus versions
Authors: Orchard John W , Meeuwisse Willem , Derman Wayne , Hägglund Martin , Soligard Torbjørn , Schwellnus Martin , Bahr Roald
Published: February 2020

Coding in sports medicine generally uses sports-specific coding systems rather than the International Classification of Diseases (ICD), because of superior applicability to the profile of injury and illness presentations in sport. New categories for coding were agreed on in the ‘International Olympic Committee (IOC) consensus statement: Methods for recording and reporting of epidemiological data on injury and illness in sports 2020.’ We explain the process for determining the new categories and update both the Sport Medicine Diagnostic Coding System (SMDCS) and the Orchard Sports Injury and Illness Classification System (OSIICS) with new versions that operationalise the new consensus categories. The author group included members from an expert group attending the IOC consensus conference. The primary authors of the SMDCS (WM) and OSIICS (JO) produced new versions that were then agreed on by the remaining authors using expert consensus methodology. The SMDCS and OSIICS systems have been adjusted and confirmed through a consensus process to align with the IOC consensus statement to facilitate translation between the two systems. Problematic areas for defining body part categories included the groin and ankle regions. For illness codes, in contrast to the ICD, we elected to have a taxonomy of ‘organ system/region’ (eg, cardiovascular and respiratory), followed by an ‘aetiology/pathology’ (eg, environmental, infectious disease and allergy). Companion data files have been produced that provide translations between the coding systems. The similar structure of coding underpinning the OSIICS and SMDCS systems aligns the new versions of these systems with the IOC consensus statement and also facilitates easier translation between the two systems. These coding systems are freely available to the sport and exercise research community.
Prediction of caregiver burden in amyotrophic lateral sclerosis: a machine learning approach using random forests applied to a cohort study
Authors: Antoniadi Anna Markella , Galvin Miriam , Heverin Mark , Hardiman Orla , Mooney Catherine
Published: February 2020

Objectives

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that is characterised by the rapid degeneration of upper and lower motor neurons and has a fatal trajectory 3–4 years from symptom onset. Due to the nature of the condition patients with ALS require the assistance of informal caregivers whose task is demanding and can lead to high feelings of burden. This study aims to predict caregiver burden and identify related features using machine learning techniques.

Design

This included demographic and socioeconomic information, quality of life, anxiety and depression questionnaires, for patients and carers, resource use of patients and clinical information. The method used for prediction was the Random forest algorithm.

Setting and participants

This study investigates a cohort of 90 patients and their primary caregiver at three different time-points. The patients were attending the National ALS/Motor Neuron Disease Multidisciplinary Clinic at Beaumont Hospital, Dublin.

Results

The caregiver’s quality of life and psychological distress were the most predictive features of burden (0.92 sensitivity and 0.78 specificity). The most predictive features for Clinical Decision Support model were associated with the weekly caregiving duties of the primary caregiver as well as their age and health and also the patient’s physical functioning and age of onset. However, this model had a lower sensitivity and specificity score (0.84 and 0.72, respectively). The ability of patients without gastrostomy to cut food and handle utensils was also highly predictive of burden in this study. Generally, our models are better in predicting the high-risk category, and we suggest that information related to the caregiver’s quality of life and psychological distress is required.

Conclusion

This work demonstrates a proof of concept of an informatics solution to identifying caregivers at risk of burden that could be incorporated into future care pathways.
Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children: a prospective cohort study
Authors: Thysen Sanne M , Benn Christine Stabell , Gomes Victor Francisco , Rudolf Frauke , Wejse Christian , Roth Adam , Kallestrup Per , Aaby Peter , Fisker Ane
Published: February 2020

Objectives

To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children.

Design

Prospective cohort study.

Setting

Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases.

Participants

Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up.

Methods

Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017.

Main outcome measure

HR for neonatal BCG compared with no neonatal BCG by TB-exposure status.

Results

Among the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG.

Conclusion

Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.
CORE-Kids: a protocol for the development of a core outcome set for childhood fractures
Authors: Marson Ben Arthur , Manning Joseph C , James Marilyn , Craxford Simon , Deshmukh Sandeep R , Ollivere Benjamin J
Published: February 2020

Introduction

Limb fractures in children are common yet there are few trials that compare treatments for these injuries. There is significant heterogeneity in the outcomes reported in the paediatric orthopaedic literature, which limits the ability to compare study results and draw firm conclusions. The aim of the CORE-Kids Study is to develop a core outcome set for use in research studies of childhood limb fractures. A core outcome set will provide a minimum set of outcomes to be measured in all trials to minimise the heterogeneity of outcomes reported and minimise reporting bias. A core outcome set ensures that outcomes are reported that are relevant to families as well as clinicians. The core outcome set will include additional upper and lower limb modules.

Methods

The development of the core outcome set will require four phases to evaluate:

What are the outcomes that are relevant to professionals?

What are the outcomes that are relevant to families?

What are the most important of these outcomes?

Which outcomes should be included in the core outcome set?

This will be completed through a systematic review of trials to identify the outcomes domains that are relevant to trialists. A series of semi-structured interviews will be completed with families to identify the outcome domains that are relevant to families. These outcome domains will be used in a three-round Delphi Study to analyse the importance of these outcome domains to a range of stakeholders including parents, clinicians and researchers. Following this, the core outcome set will be decided at a consensus meeting.

Ethics and dissemination

Ethical approval has been awarded HRA/REC IRAS number 262503. Date of approval 06/08/2019. Dissemination will be through scientific literature and international societies.

Trial registration

Core Outcome Measures in Effectiveness Trials Initiative, registration number: 1274. Date of registration 13/12/2018.

PROSPERO registration number

CRD42018106605.
Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription
Authors: Salerno Debora , Chiodo Letizia , Alfano Vincenzo , Floriot Oceane , Cottone Grazia , Paturel Alexia , Pallocca Matteo , Plissonnier Marie-Laure , Jeddari Safaa , Belloni Laura , Zeisel Mirjam , Levrero Massimo , Guerrieri Francesca
Published: February 2020

Objective

The HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin.

Design

We explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA.

Results

We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the catalytic active subunit of the polycomb repressor complex 2 (PRC2) complex. Computational modelling and biochemical evidence suggest that HBx and EZH2 share two preferential binding sites in DLEU2 intron 1. HBx and DLEU2 co-recruitment on the cccDNA displaces EZH2 from the viral chromatin to boost transcription and viral replication. DLEU2-HBx association with target host promoters relieves EZH2 repression and leads to the transcriptional activation of a subset of EZH2/PRC2 target genes in HBV-infected cells and HBV-related HCCs.

Conclusions

Our results highlight the ability of HBx to bind RNA to impact on the epigenetic control of both viral cccDNA and host genes and provide a new key to understand the role of DLEU2 and EZH2 overexpression in HBV-related HCCs and HBx contribution to hepatocytes transformation.
Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial
Authors: Hennigan Barry , Berry Colin , Collison Damien , Corcoran David , Eteiba Hany , Good Richard , McEntegart Margaret , Watkins Stuart , McClure John D , Mangion Kenneth , Ford Thomas Joseph , Petrie Mark C , Hood Stuart , Rocchiccioli Paul , Shaukat Aadil , Lindsay Mitchell , Oldroyd Keith G
Published: February 2020

Introduction

There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia inGZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control.

Methods

We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ).

Results

104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the targetGZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the targetGZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months.

Conclusions

Non-invasive evidence of major ischaemia is uncommon in patients withGZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months.

Trial registration number

NCT02425969.
Sixth Immunotherapy of Cancer conference (ITOC): advances and perspectives—a meeting report
Authors: Pinto Catarina , Bergmann Michael , Briukhovetska Daria , Nuessler Volkmar , Sznol Mario , von Bergwelt-Baildon Michael , Kobold Sebastian
Published: February 2020

Immunotherapy has moved to the forefront of cancer treatment, illustrated by the accelerating pace of novel therapy approvals. In this complex environment, scientists rely on cutting edge conferences to stay informed. The Immunotherapy of Cancer (ITOC) conference was established jointly with the Society of the Immunotherapy of Cancer to bring the European researchers together. In its sixth edition, the ITOC conference has recently been held in Vienna, Austria.
TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma
Authors: De Keersmaecker Brenda , Claerhout Sofie , Carrasco Javier , Bar Isabelle , Corthals Jurgen , Wilgenhof Sofie , Neyns Bart , Thielemans Kris
Published: February 2020

Background

We previously reported that dendritic cell-based mRNA vaccination plus ipilimumab (TriMixDC-MEL IPI) results in an encouraging rate of tumor responses in patients with pretreated advanced melanoma. Here, we report the TriMixDC-MEL IPI-induced T-cell responses detected in the peripheral blood.

Methods

Monocyte-derived dendritic cells electroporated with mRNA encoding CD70, CD40 ligand, and constitutively active TLR4 (TriMix) as well as the tumor-associated antigens tyrosinase, gp100, MAGE-A3, or MAGE-C2 were administered together with IPI for four cycles. For 18/39 patients, an additional vaccine was administered before the first IPI administration. We evaluated tumor-associated antigen specific T-cell responses in previously collected peripheral blood mononuclear cells, available from 15 patients.

Results

Vaccine-induced enzyme-linked immunospot assay responses detected after in vitro T-cell stimulation were shown in 12/15 patients. Immune responses detected in patients with a complete or partial response were significantly stronger and broader, and exhibited a higher degree of multifunctionality compared with responses in patients with stable or progressive disease. CD8+ T-cell responses from patients with an ongoing clinical response, either elicited by TriMixDC-MEL IPI or on subsequent pembrolizumab treatment, exhibited the highest degree of multifunctionality.

Conclusions

TriMixDC-MEL IPI treatment results in robust CD8+ T-cell responses in a meaningful portion of stage III or IV melanoma patients, and obviously in patients with a clinical response. The levels of polyfunctional and multiantigen T-cell responses measured in patients with a complete response, particularly in patients evidently cured after 5+ years of follow-up, may provide a benchmark for the level of immune stimulation needed to achieve a durable clinical remission.

Trial registration number

NCT01302496.
Prophylactic efficacy on periprosthetic bone loss in calcar region after total hip arthroplasty of antiosteoporotic drugs: a network meta-analysis of randomised controlled studies
Authors: Chen Xi , Shen Yu , Ye Chenyi , Mumingjiang Yishake , Lu Jinwei , Yu Yunxian
Published: February 2020

Objectives

The aim of this study was to evaluate the effect of antiosteoporotic drugs on preventing periprosthetic bone loss in calcar 6 and 12 months after total hip arthroplasty.

Methods

The network meta-analysis was conducted guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. A systematic literature search was conducted and 21 studies that enrolled a total of 955 patients with 9 antiosteoporotic drugs met the inclusion criteria. Network meta-analysis and conventional meta-analysis were carried out for calculating standard mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the bone mineral density (BMD) in calcar (Gruen zone 7) as well as bone turnover markers (BTMs) including bone-specific alkaline phosphatase (BSAP) and collagen type I cross-linked N telopeptide (NTX) at 6 and 12 months between different antiosteoporotic drugs.

Results

At 6 months after total hip arthroplasty, zoledronate (SUCRA=86.4%), risedronate (SUCRA=51.3%) and etidronate (SUCRA=44.5%) were effective in retaining BMD in calcar; zoledronate was significantly more effective than etidronate (SMD=0.65, 95% CI 0.03 to 1.27). Teriparatide (SUCRA=84.5%), denosumab (SUCRA=82.5%), zoledronate (SUCRA=69.2%), alendronate+alfacalcidol (SUCRA=66.2%) and etidronate (SUCRA=51.5%) were the top five drugs in retaining BMD in calcar at 12 months after total hip arthroplasty and the efficacy were comparable. After simultaneously excluding studies in which the prosthesis were cement and the drug dosages as well as treatment durations were inconsistent with those in treating osteoporosis, the above results were robust with the exception that alendronate showed significant efficacy compared with placebo (SMD=1.22, 95% CI 0.46 to 1.99) and was comparable with those effective drugs at 12 months. Long-term residual effect was corroborated only in etidronate, alendronate and zoledronate from previous studies. BTMs were significantly decreased as early as 6 months (SMD of BSAP −0.49, 95% CI −0.84 to −0.13; SMD of NTX −0.93, 95% CI −1.21 to −0.64) and sustained until 12 months (SMD of BSAP −0.27, 95% CI −0.50 to −0.03; SMD of NTX −0.84, 95% CI −1.11 to −0.56) during the prophylaxis.

Conclusions

Antiosteoporotic drugs showed prophylactic efficacy on periprosthetic bone loss after total hip arthroplasty in calcar, the effectiveness varied. Zoledronate was the best recommendation due to its optimal efficacy both within 6 and 12 months as well as its residual effect in the long term. BTMs could be used as indicators for monitoring through the treatment. More head-to-head clinical trials are needed to confirm those findings.
LncRNA H19 promotes inflammatory response induced by cerebral ischemia–reperfusion injury through regulating the miR-138-5p–p65 axis
Authors: Li Hui , Tang Chenglu , Wang Dan
Published: February 2020

Recent studies have shown that long non-coding RNA(LncRNA) H19 is up-regulated in the brain of rats suffering from cerebral ischemia–reperfusion (I/R) injury, inducing severe disability and mortality. Little was known about the molecular mechanisms underlying the involvement of H19 in cerebral I/R injury. In this study, a rat model of I/R was induced by transient middle cerebral artery occlusion (tMCAO). PC-12 cells exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) were used as an in vitro model. Our results show that H19 is up-regulated in both in vivo and in our in vitro model. Further study indicated that knockdown of H19 promotes cell proliferation, decreases the rate of cell apoptosis, and ameliorates inflammation after OGD/R simulation. Our in vivo study shows that H19 knockdown ameliorates inflammation and improves neurological function in our rat model of tMCAO. Remarkably, the results from our luciferase reporter assays suggest that H19 negatively regulates the expression of miR-138-5p, and p65 was identified as a target of miR-138-5p. To sum up, this study demonstrated that H19 promotes an inflammatory response and improves neurological function in a rat model of tMCAO by regulating the expression of miR-138-5p and p65. This study reveals the important role and underlying mechanism of H19 in the progress of cerebral I/R injury, which could serve as a potential target for further treatment.
Permanence and extinction of stochastic regime-switching mutualism model
Authors: Lv Guangying , Zhang Beibei
Published: March 2020

This paper is concerned with the permanence and extinction of a stochastic regime-switching mutualism model. We aim to find the difference between the stochastic mutualism model with regime-switching and without regime-switching. By studying ergodicity of regime-switching diffusion processes, we establish the sufficient conditions to estimate the permanence and extinction of a species in a random switching environment. Moreover, compared with the system without switching, the advantages of the stochastic regime-switching mutualism model are given.
Posterior Reversible Encephalopathy Syndrome in a Patient with Hemorrhagic Fever with Renal Syndrome
Authors: Muco Ermira , Hasa Amela , Rroji Arben , Kushi Arta , Puca Edmond , Kraja Dhimiter
Published: February 2020

We presently report the case of hantavirus infection in a 45-year-old male who was hospitalized to our clinic of infectious diseases, with fever, myalgia, vomiting, nausea, headache, and abdominal pain. The physical findings included hepatomegaly, splenomegaly, rash, and conjunctival injection. Eight days before the start of complaints, the patient has cut trees in the mountain. An acute renal failure was observed with an oliguria and an increase of serum creatinine and blood urea nitrogen. Urinalysis shows albuminuria and hematuria. Elevations of amylase, lipase, and liver enzymes levels, low serum albumin level, and thrombocytopenia were observed. A positive ELISA test for hantavirus IgM/IgG antibodies confirmed hemorrhagic fever with renal syndrome. On the third day of hospitalization, the patient had seizures. The unenhanced head computed tomography (CT) performed after seizures showed subcortical bilateral hypodensities within frontal, parietal, and occipital regions corresponding to areas of increased signal intensity in magnetic resonance imaging (MRI) associated with cerebral edema in posterior reversible encephalopathy syndrome (PRES). The treatment consisted of supportive therapy. The patient underwent another head MRI with contrast enhancement after 2 months, which resulted normal.
Experimental Study on the Saturated Compacted Loess Permeability under K0 Consolidation
Authors: Hao Yan-zhou , Wang Tie-hang , Jin Xin , Cheng Lei , Li Jiang-le
Published: February 2020

This paper investigates the permeability characteristics of compacted loess by focusing on the anisotropy parallel and perpendicular to the compaction. Three tests are conducted on compacted loess: triaxial permeability test under confining pressure consolidation, triaxial permeability test under K0 consolidation, and SEM test. Samples are maintained and tested at different dry densities under saturated conditions. The test results show that the saturated permeability coefficient of compacted loess is exponentially related to the initial dry density under both confining pressure consolidation and K0 consolidation. The fitting equation can estimate the saturated permeability coefficient of compacted loess at different depths. The horizontal saturated permeability coefficient of compacted loess is larger than that in the vertical direction, showing obvious anisotropy. The saturated permeability anisotropy ratio is linearly related to the initial dry density. Comparing and analysing the saturated permeability coefficient, the saturated permeability coefficient of compacted loess under the K0 consolidation condition is smaller than that under the confining pressure consolidation condition. Under the condition of K0 consolidation, the connectivity of vertical and horizontal pores of compacted loess is weakened, the tortuosity is strengthened, and the void ratio is decreased. K0 consolidation makes the flake‐, plate‐, and needle‐like particles in compacted loess rotate continuously parallel to the compaction surface, which enhances the orientation of particles and leads to the saturated permeability anisotropy increase. The research results provide the basis for water field analysis in loess filling engineering.
SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review
Authors: El Mouhayyar Christopher , Riachy Ruba , Khalil Abir Bou , Eid Asaad , Azar Sami
Published: February 2020

The prevalence of diabetes and its associated complications is increasing throughout the decades. Promising diabetes medications were introduced to the market including GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors aiming to target these complications. The literature lacks sufficient data regarding these new medications and their influence on nephropathy, retinopathy, and neuropathy. This review expands on the major results of effects of the 3 drug classes on microvascular complications. In our review, both SGLT2 inhibitors and GLP-1 agonists appear to have promising nephroprotective outcomes at this stage, with less promising outcomes seen with DPP-4 inhibitors. Moreover, the retinoprotective outcomes of both SGLT2 inhibitors and DPP-4 inhibitors were only tested on mice, while those of GLP-1 agonists were assessed in few trials. In addition, the results of both GLP-1 agonists and DPP-4 inhibitors showed discrepancies in these studies. On the contrary, conclusions regarding the effect of these medications on neuroprotective outcomes cannot be drawn at the time due to the lack of clinical trials targeting these complications. Hence, a clearer picture of the microvascular outcomes will manifest over time with the release of multiple upcoming clinical trials.
Treatment Patterns and Healthcare Resource Utilization among Patients with Advanced or Metastatic Soft Tissue Sarcoma in US Community Practices
Authors: Nadler Eric , Aguilar Kathleen , Wentworth Chuck , Boyd Marley , Amirian E. Susan , Barker Scott , French Pearl , Wilson Thomas , Hess Lisa M.
Published: March 2020

Introduction. This study was designed to describe demographic and clinical characteristics of patients diagnosed with advanced or metastatic soft tissue sarcoma (STS) and to examine treatment and healthcare resource utilization patterns of this patient population in a United States (US) community-based oncology practice setting over time. Methods and Materials. A retrospective observational study was conducted within the US Oncology Network (USON). Patients were eligible if they were diagnosed with advanced or metastatic STS and were treated at a USON site between 01 July 2015 and 31 August 2018. Demographic, clinical, and treatment characteristics were described for the overall study population. Comparisons between patients by time period (prior to and after October 2016) were evaluated using the T test for continuous variables and chi-squared test for categorical variables. Data were available for analysis through 31 August 2018. Results. Demographic and clinical characteristics of the eligible study cohort (N = 376) were similar between patients who initiated treatment before and after October 2016 (all p>0.05). Forty-three unique regimens were observed in the first-line setting, with the predominant regimen (gemcitabine + docetaxel) received by 33.2% (n = 125) patients. Prior to October 2016, 45.4% of patients received first-line gemcitabine + docetaxel, while 29.0% received this regimen after October 2016. Conclusions. While demographic and clinical characteristics were similar, treatment patterns changed in 2016. Future research should evaluate the impact of changing drug approvals and clinical trial results on future treatment patterns.
Steroid Cell Tumour in Pregnancy: Reflection on a Rare Case and Review of the Literature
Authors: Weishaupt J. , Herbst U.
Published: February 2020

There are only a few cases of steroid cell tumours that have been described in the literature. Here, we present an exceptionally rare case of a steroid cell tumour arising from the ovary in early pregnancy.
Freight Time and Cost Optimization in Complex Logistics Networks
Authors: Sert Egemen , Hedayatifar Leila , Rigg Rachel A. , Akhavan Amir , Buchel Olha , Saadi Dominic Elias , Kar Aabir Abubaker , Morales Alfredo J. , Bar-Yam Yaneer
Published: February 2020

The complexity of providing timely and cost-effective distribution of finished goods from industrial facilities to customers makes effective operational coordination difficult, yet effectiveness is crucial for maintaining customer service levels and sustaining a business. Logistics planning becomes increasingly complex with growing numbers of customers, varied geographical locations, the uncertainty of future orders, and sometimes extreme competitive pressure to reduce inventory costs. Linear optimization methods become cumbersome or intractable due to the large number of variables and nonlinear dependencies involved. Here, we develop a complex systems approach to optimizing logistics networks based upon dimensional reduction methods and apply our approach to a case study of a manufacturing company. In order to characterize the complexity in customer behavior, we define a “customer space” in which individual customer behavior is described by only the two most relevant dimensions: the distance to production facilities over current transportation routes and the customer’s demand frequency. These dimensions provide essential insight into the domain of effective strategies for customers. We then identify the optimal delivery strategy for each customer by constructing a detailed model of costs of transportation and temporary storage in a set of specified external warehouses. In addition, using customer logistics and thek-means algorithm, we propose additional warehouse locations. For the case study, our method forecasts 10.5% savings on yearly transportation costs and an additional 4.6% savings with three new warehouses.
Dying in the Intensive Care Unit (ICU): A Retrospective Descriptive Analysis of Deaths in the ICU in a Communal Tertiary Hospital in Germany
Authors: Ay Esma , Weigand Markus. A. , Röhrig Rainer , Gruss Marco
Published: March 2020

Background. Modern intensive care methods led to an increased survival of critically ill patients over the last decades. But an unreflected application of modern intensive care measures might lead to prolonged treatment for incurable diseases, and an inadaequate or too aggressive therapy can prolong the dying process of patients. In this study, we analysed end-of-life decisions regarding withholding and withdrawal of intensive care measures in a German intensive care unit (ICU) of a communal tertiary hospital. Methods. Patient datasets of all adult patients dying in an ICU or an intermediate care unit (IMC) in a tertiary communal hospital (Klinikum Hanau, Germany) between 01.01.2011 and 31.12.2012 were analysed for withholding and withdrawal of intensive care measures. Results. During the two-year period, 1317 adult patients died in Klinikum Hanau. Of these, 489 (37%) died either in an ICU/IMC unit. The majority of those deceased patients (n = 427, 87%) was 60 years or older. In 306 (62%) of 489 patients, at least one life-sustaining measure was withheld or withdrawn. In 297 (61%) of 489 patients dying in ICU/IMC, any type of therapy was withheld, and in 139 patients (28%), any type of therapy was withdrawn. Mostly, cardiopulmonary resuscitation (n = 222), invasive (n = 121) and noninvasive (n = 40) ventilation followed by renal replacement therapy (n = 71) and catecholamine therapy (n = 66) were withheld. More invasive measures as ventilation or renal replacement therapy were withdrawn in 18 and 22 patients only. After withholding/withdrawal of therapy, most patients died within two days. More than 20% of patients dying in ICU/IMC did not have an analgesic medication. Conclusions. About one-third of patients dying in the hospital died in ICU/IMC. At least one life-sustaining therapy was limited/withdrawn in more than 60% of those patients. Withholding of a therapy was more common than active therapy withdrawal. Ventilation and renal replacement therapy were withdrawn in less than 5% of patients, respectively.
Antiangiogenesis Efficacy of Ethanol Extract from Amomum tsaoko in Ovarian Cancer through Inducing ER Stress to Suppress p‐STAT3/NF‐kB/IL‐6 and VEGF Loop
Authors: Chen Cheng , You Fei , Wu FengHua , Luo YuShen , zheng GuoHua , Xu HanLin , Liu Yi
Published: February 2020

Natural plants are considered as a huge treasure for anticancer. Amomum tsaoko, a plant of Zingiberaceae, is used widely as a food and traditional medicine in East Asia. In previous studies, Amomum tsaoko has antitumor effect on liver cancer cells, but the mechanism is not clear. Here, we demonstrated that ethanol extract from Amomum tsaoko (At‐EE) could inhibit ovarian cancer and decrease angiogenesis in vivo. At‐EE did not influence vascular endothelial cells directly, but decreased IL‐6 and VEGF secreted by ovarian cancer cells to inhibit angiogenesis through inhibition of p‐STAT3 and NF‐kB activation. In addition, we demonstrated that p‐STAT3 and NF‐kB could adjust each other and IL‐6 and VEGF also mediate p‐STAT3 and NF‐kB too, which created a loop. In addition, At‐EE interrupted p‐STAT3/NF‐kB/IL‐6 and VEGF loop through induced ER stress. These results reveal that p‐STAT3/NF‐kB/IL‐6 and VEGF is a cascade amplification loop in ovarian cancer for angiogenesis, and induced ER stress can interrupt it. Taken together, this work explored the anticancer activities of Amomum tsaoko, which could be a potential therapeutic candidate in the treatment of ovarian cancer.
Improving Effectiveness of Safety Training at Construction Worksite Using 3D BIM Simulation
Authors: Ahn Sungjin , Kim Taehui , Park Young-Jun , Kim Ji-Myong
Published: February 2020

Construction worker safety and safety training continue to be the main issues in the construction industry. As a means of improving construction worker safety, this study focuses on safety training at an actual construction worksite. In order to promote safety awareness among workers, it is imperative to develop more effective safety training. This study examined safety training as a method of improving construction worker safety, focusing on the effectiveness of the instructional delivery method. Effectiveness pertains to level of understanding of instruction and can be enhanced through improving instructional delivery method. This study aims to examine two different types of safety training methods: (1) the conventional lecture method and (2) innovative method using the 3D Building Information Modeling (BIM) simulation, reflecting the hazard condition of the actual site. An experiment is conducted, in which the two types of training are implemented and assessed through testing trainees’ understanding. The workers trained via BIM simulation showed a higher level of understanding than the group of workers who were trained conventionally. Also, a survey was conducted targeting safety managers, in which the workers evaluated lifelike quality of the training, active learning and enjoyment that each of the training methods can promote. This research will provide implications that an innovative method using the virtual reality is more effective than the conventional lecture method.
Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide
Authors: Wang Yun-peng , Guo Yu , Wen Ping-shan , Zhao Zhen-zhen , Xie Jian , Yang Kai , Yang Qing , Wang Jia-feng , Deng Xiao-ming
Published: February 2020

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.