bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative red blood cell infusion and deep vein thrombosis in patients with femoral and pelvic fractures: a propensity score matching
Authors: Wu Linqin , Cheng Bo
Published: June 2021

Background

The relationship between perioperative red blood cell (RBC) infusion and deep vein thrombosis (DVT) has not been determined.

Objectives

To analyze the time-event relationship between perioperative RBC infusion and DVT in patients with femoral and pelvic fractures after adjusting for confounding factors and to provide reference for optimizing DVT risk factors.

Methods

The clinical data of 569 patients with femoral and pelvic fractures who received surgical treatment from May 2018 to December 2019 were retrospectively analyzed. Propensity score matching (PSM) was performed on 20 covariates of DVT. With the formation or progression of DVT after RBC infusion as the end point, the time-event relationship between perioperative RBC infusion and DVT in patients was analyzed by binary logistic regression.

Results

After 1:1 PSM of 569 patients included in this study, 126 patients were in the transfusion group and the non-transfusion group, respectively. Before PSM (P = 0.023, OR = 1.496 [95% CI, 1.058-2.115]), perioperative RBC infusion was associated with DVT formation for femoral and pelvic fractures. This conclusion was still obtained after PSM (P = 0.038, OR = 1.728, 95% CI = (1.031, 2.896)). The risk of DVT in patients with RBC infusion of 2-4U and > 4U is 1.833 and 2.667 times that of ≤ 2U, respectively. After excluding patients who received preoperative RBC infusion and had DVT formation or progression prior to RBC infusion, perioperative RBC infusion was still associated with the formation of DVT in femoral and pelvic fractures (P = 0.037, OR = 2.231 [95% CI, 1.049-4.745]).

Conclusion

Perioperative RBC infusion is one of the causes of DVT in patients with femoral and pelvic fractures, and the risk of DVT is positively correlated with the amount of RBC infusion.
The effect of N-acetyl cysteine injection on renal function after coronary artery bypass graft surgery: a randomized double blind clinical trial
Authors: Javaherforooshzadeh Fatemeh , Shaker Zahra , Rashidi Mahboobeh , Akhondzadeh Reza , Hayati Fatemeh
Published: June 2021

Background

This study aimed to compare the effects of N-acetyl cysteine on renal function after coronary artery bypass graft surgery.

Methods

In this randomized clinical trial conducted in Golestan Hospital, Ahvaz, Iran, 60 candidates for coronary artery bypass graft surgery were selected and divided into two N-acetyl cysteine and control groups (30 people each). Patients received 3 (2 intraoperative and 1 postoperative) doses of IV N-acetyl cysteine (100 mg/kg) (n = 30) or placebo (n = 30) over 24 h. Prescription times were as follows: after induction of anesthesia, in the Next 4 h, and in the 16 h after on. Primary outcomes were serum levels of BUN and Cr, at baseline,4 and 48 h after surgery. And also need renal replacement therapy (RRT). Secondary outcomes included the hemodynamic variables, Blood products transfusion.

Results

There were significant differences in BUN between groups at 4 h (P = 0.02) and 48 h after surgery (P = 0.001) There were significant differences in Cr level between groups at 4 h (P < 0.001) and 48 h after surgery (P = 0.001).

MAP at different times (at 4 h p = 0.002 and 48 h after surgery P < 0.001) were significantly different between the two groups. There was a significant difference between the two groups in terms of the unit of Packed cell transfusion (P = 0.002) and FFP transfusion (P < 0.001).

Conclusion

In the present study, we found that administration of N-acetyl cysteine can reduce the incidence of acute kidney injury in patients undergoing coronary artery bypass graft surgery and improved kidney functions.

Trial registry

IRCT20190506043492N3 Registered at 2020.06.07.
Posttraumatic stress disorder symptoms among trauma-exposed adolescents from low- and middle-income countries
Authors: Stupar Dusko , Stevanovic Dejan , Vostanis Panos , Atilola Olayinka , Moreira Paulo , Dodig-Curkovic Katarina , Franic Tomislav , Doric Ana , Davidovic Nikolina , Avicenna Mohamad , Multazam Isa Noor , Nussbaum Laura , Thabet Abdul Aziz , Ubalde Dino , Petrov Petar , Deljkovic Azra , Monteiro Antonio Luis , Ribas Adriana , Jovanovic Mirjana , Joana Oliveira , Knez Rajna
Published: June 2021

Background

Exposure to traumatic events in childhood is associated with the development and maintenance of various psychiatric disorders, but most frequently with posttraumatic stress disorder (PTSD). The aim of this study was to evaluate the types of traumatic events experienced and the presence and predictors of PTSD symptoms among adolescents from the general population from ten low- and middle-income countries (LMICs).

Methods

Data were simultaneously collected from 3370 trauma-exposed adolescents (mean age = 15.41 [SD = 1.65] years, range 12–18; 1465 (43.5%) males and 1905 (56.5%) females) in Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, the Palestinian Territories, the Philippines, Romania, and Serbia, with Portugal, a high-income country, as a reference point. The UCLA PTSD Reaction Index for the DSM-5 (PTSD-RI-5) was used for the assessment of traumatic events and PTSD symptoms.

Results

The most frequently reported traumatic events were death of a close person (69.7%), witnessing violence other than domestic (40.5%), being in a natural disaster (34.4%) and witnessing violent death or serious injury of a close person (33.9%). In total, 28.5% adolescents endorsed two to three DSM-5 PTSD criteria symptoms. The rates of adolescents with symptoms from all four DSM-5 criteria for PTSD were 6.2–8.1% in Indonesia, Serbia, Bulgaria, and Montenegro, and 9.2–10.5% in Philippines, Croatia and Brazil. From Portugal, 10.7% adolescents fall into this category, while 13.2% and 15.3% for the Palestinian Territories and Nigeria, respectively. A logistic regression model showed that younger age, experiencing war, being forced to have sex, and greater severity of symptoms (persistent avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity) were significant predictors of fulfilling full PTSD criteria.

Conclusions

Nearly every third adolescent living in LMICs might have some PTSD symptoms after experiencing a traumatic event, while nearly one in ten might have sufficient symptoms for full DSM-5 PTSD diagnosis. The findings can inform the generation of PTSD burden estimates, allocation of health resources, and designing and implementing psychosocial interventions for PTSD in LMICs.
Preclinical models as patients’ avatars for precision medicine in colorectal cancer: past and future challenges
Authors: Durinikova Erika , Buzo Kristi , Arena Sabrina
Published: June 2021

Colorectal cancer (CRC) is a complex and heterogeneous disease, characterized by dismal prognosis and low survival rate in the advanced (metastatic) stage. During the last decade, the establishment of novel preclinical models, leading to the generation of translational discovery and validation platforms, has opened up a new scenario for the clinical practice of CRC patients. To bridge the results developed at the bench with the medical decision process, the ideal model should be easily scalable, reliable to predict treatment responses, and flexibly adapted for various applications in the research. As such, the improved benefit of novel therapies being tested initially on valuable and reproducible preclinical models would lie in personalized treatment recommendations based on the biology and genomics of the patient’s tumor with the overall aim to avoid overtreatment and unnecessary toxicity. In this review, we summarize different in vitro and in vivo models, which proved efficacy in detection of novel CRC culprits and shed light into the biology and therapy of this complex disease. Even though cell lines and patient-derived xenografts remain the mainstay of colorectal cancer research, the field has been confidently shifting to the use of organoids as the most relevant preclinical model. Prioritization of organoids is supported by increasing body of evidence that these represent excellent tools worth further therapeutic explorations. In addition, novel preclinical models such as zebrafish avatars are emerging as useful tools for pharmacological interrogation. Finally, all available models represent complementary tools that can be utilized for precision medicine applications.
Patient-Reported OUtcome measures in key African languages to promote Diversity in research and clinical practice (PROUD)—protocol for a systematic review of measurement properties
Authors: Heine Martin , Mokkink Lidwine B. , van Zyl Chanel , Derman Wayne , Hanekom Susan
Published: June 2021

Introduction

Sub-Saharan Africa is a subcontinent with a proud cultural richness and diversity, yet inexplicably also a region with severe health care challenges and inequity. To challenge this health equity gap and reduce the burden of disease, the patient’s voice in monitoring and evaluation of health and health care interventions is paramount. The aim of this two-phased review is to map the availability of patient-reported outcome measures (PROMs) in a selection of non-English, African Languages, and systematically evaluate the measurement properties of the PROMs that were identified.

Methods

This systematic review will be conducted in two phases. In phase 1, we will scope the literature for patient-reported outcome measures (PROMs), either developed from scratch or through translation and validation in a sub-Saharan African country and a selection of non-English, African languages (n = 31; spoken in > 10 million people and/or a national language). The availability of PROMs will be mapped against the previously reported burden of disease in the respective countries included. Subsequently, in phase 2, we systematically evaluate the measurement properties of these PROMs using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology for systematic reviews on PROMs. To ensure rigour, secondary searches will be developed to specifically locate articles that report on the measurement properties of the PROMs identified during phase 1. The evidence will be graded using the modified GRADE approach.

Discussion

This review will provide a comprehensive overview and quality appraisal of PROMs developed in non-English, African languages. Consequently, this review when concluded may be an important first step in promoting access to these PROMs for use in clinical practice and research, as well as facilitate identification and prioritization of key knowledge gaps.
Computed tomography imaging of septic shock. Beyond the cause: the “CT hypoperfusion complex”. A pictorial essay
Authors: Di Serafino Marco , Viscardi Daniela , Iacobellis Francesca , Giugliano Luigi , Barbuto Luigi , Oliva Gaspare , Ronza Roberto , Borzelli Antonio , Raucci Antonio , Pezzullo Filomena , De Cristofaro Maria Giovanna , Romano Luigia
Published: June 2021

Septic shock is a medical emergency that represents one of the most important underlying causes for presentation to the Emergency Department. Sepsis is defined as organ dysfunction, life-threatening event caused by a deregulated inflammatory host response to infection, with a mortality risk ranging from 10 to 40%. Early sepsis identification is the cornerstone of management and diagnostic imaging can play a pivotal role in this clinical context. The choice of imaging modality depends on several factors, associated with the clinical condition and the presence or absence of localising signs and symptoms. The diagnostic accuracy of contrast-enhanced total-body CT has been well established during septic shock, allowing for a rapid, panoramic, and detailed study of multiple body areas, simultaneously. The aim of this article is to illustrate the controversial CT hypoperfusion complex in patients with septic shock, characterised by the following imaging features: decreased enhancement of the viscera; increased mucosal enhancement; luminal dilation of the small bowel; mural thickening and fluid-filled loops of the small bowel; the halo sign and flattening of the inferior vena cava; reduced aortic diameter; peripancreatic oedema; abnormal parenchymal perfusion; and other controversial findings that are variably associated with each other and reversible during the early stages. Increasing physicians’ awareness of the significance of these findings could prompt alternative approaches to the early assessment and management of septic shock. In this perspective, CT imaging represents a useful tool for a complete, rapid and detailed diagnosis of clinically suspected septic shock, which can be used to improve patient outcomes.
Challenge of prostate MRI segmentation on T2-weighted images: inter-observer variability and impact of prostate morphology
Authors: Montagne Sarah , Hamzaoui Dimitri , Allera Alexandre , Ezziane Malek , Luzurier Anna , Quint Raphaelle , Kalai Mehdi , Ayache Nicholas , Delingette Hervé , Renard-Penna Raphaële
Published: June 2021

Background

Accurate prostate zonal segmentation on magnetic resonance images (MRI) is a critical prerequisite for automated prostate cancer detection. We aimed to assess the variability of manual prostate zonal segmentation by radiologists on T2-weighted (T2W) images, and to study factors that may influence it.

Methods

Seven radiologists of varying levels of experience segmented the whole prostate gland (WG) and the transition zone (TZ) on 40 axial T2W prostate MRI images (3D T2W images for all patients, and both 3D and 2D images for a subgroup of 12 patients). Segmentation variabilities were evaluated based on: anatomical and morphological variation of the prostate (volume, retro-urethral lobe, intensity contrast between zones, presence of a PI-RADS ≥ 3 lesion), variation in image acquisition (3D vs 2D T2W images), and reader’s experience. Several metrics including Dice Score (DSC) and Hausdorff Distance were used to evaluate differences, with both a pairwise and a consensus (STAPLE reference) comparison.

Results

DSC was 0.92 (± 0.02) and 0.94 (± 0.03) for WG, 0.88 (± 0.05) and 0.91 (± 0.05) for TZ respectively with pairwise comparison and consensus reference. Variability was significantly (p < 0.05) lower for the mid-gland (DSC 0.95 (± 0.02)), higher for the apex (0.90 (± 0.06)) and the base (0.87 (± 0.06)), and higher for smaller prostates (p < 0.001) and when contrast between zones was low (p < 0.05). Impact of the other studied factors was non-significant.

Conclusions

Variability is higher in the extreme parts of the gland, is influenced by changes in prostate morphology (volume, zone intensity ratio), and is relatively unaffected by the radiologist’s level of expertise.
The preoperative localisation of small parathyroid adenomas improves when adding Tc-99m-Sestamibi SPECT to multiphase contrast-enhanced CT
Authors: Sandqvist Patricia , Farnebo Jacob , Nilsson Inga-Lena , Grybäck Per , Sundin Anders , Sanchez-Crespo Alejandro
Published: June 2021

Objectives

To investigate the incremental value of Sestamibi SPECT combined with a non-enhanced and contrast-enhanced CT, using SPECT/CT, for the preoperative localisation of small parathyroid adenomas (PTA).

Methods

Retrospectively, 147 patients surgically cured from primary hyperparathyroidism, as verified by biochemistry 6 months postoperatively, were included. All patients had preoperatively undergone a dual time 99mTechnetium-Sestamibi SPECT (S) with multiphase CT including native (N), arterial (A) and venous (V) phases. Independently, two radiologists blinded from both the surgical and the preoperative imaging reports, sequentially performed PTA localisation starting with either [A] or [V], thereafter [A + N] or [V + N] and finally with the complete [A + N + S] or [V + N + S]. PTA localisation was reported for each image-set. The readers results were combined and the diagnostic performance for each image set was determined. Sensitivity was also calculated for the different quartiles of PTA weight distribution.

Results

The median adenoma weight was 315 mg. No statistically significant differences in diagnostic performance between arterial and venous based image sets were found. The net effect of adding [N] was to increase specificity. Sestamibi SPECT significantly increased the overall diagnostic accuracy for arterial- and venous-based image sets, p = 0.0008 and p = 0.001, respectively. [A + N + S] was found to have the highest diagnostic performance with 86.5% sensitivity and 94.9% overall accuracy. [A + N + S] was particularly advantageous for locating PTA in the lower weight quartiles.

Conclusions

Native CT-phase and dual time point Sestamibi SPECT increase specificity and sensitivity, respectively. These, in combination with a single contrast-enhanced CT-phase is the most optimal examination protocol for preoperative localisation of PTA using SPECT/CT.
A procedure for in vitro evaluation of the immunosuppressive effect of mouse mesenchymal stem cells on activated T cell proliferation
Authors: Marinescu Catalina-Iolanda , Preda Mihai Bogdan , Burlacu Alexandrina
Published: June 2021

Background

Mesenchymal stem/stromal cells (MSC) represent adult cells with multipotent capacity. Besides their capacity to differentiate into multiple lineages in vitro and in vivo, increasing evidence points towards the immunomodulatory capacity of these cells, as an important feature for their therapeutic power. Although not included in the minimal criteria established by the International Society for Cellular Therapy as a defining MSC attribute, demonstration of the immunomodulatory capacity of MSC can be useful for the characterization of these cells before being considered MSC.

Methods

Here we present a simple and reliable protocol by which the immunosuppressive effect of mouse bone marrow-derived MSC can be evaluated in vitro. It is based on the measuring of the proliferation of activated T cells cultured in direct contact with irradiated MSC.

Results

Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation, which can be quantified as a percentage of maximum proliferation. Our data shows that batch-to-batch variability can be determined within one or multiple experiments, by extracting the area under curve of T cell proliferation plotted against the absolute number of MSC in co-culture.

Conclusions

The validation of the immunosupressive capacity of MSC could be added to the characterization of the cells before being used in various MSC-based approaches to treat immunological diseases. Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation. The immunosuppressive properties of MSC vary between batches, but not between different passages of the same batch.
WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis
Authors: Choi Yoon Jung , Heck Adam M. , Hayes Brian J. , Lih Daniel , Rayner Samuel G. , Hadland Brandon , Zheng Ying
Published: June 2021

The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45− hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.
Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy
Authors: Zeng Ruijie , Wang Jinghua , Zhuo Zewei , Luo Yujun , Sha Weihong , Chen Hao
Published: June 2021

Necrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.
MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis
Authors: Ni Haiwei , Qin Hai , Sun Cheng , Liu Yichen , Ruan Guojing , Guo Qianqian , Xi Tao , Xing Yingying , Zheng Lufeng
Published: June 2021

Background

Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness.

Methods

Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored.

Results

MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis.

Conclusion

MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.
Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane
Authors: McBride Jeffrey D. , Rodriguez-Menocal Luis , Guzman Wellington , Khan Aisha , Myer Ciara , Liu Xiaochen , Bhattacharya Sanjoy K. , Badiavas Evangelos V.
Published: June 2021

Background

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood. Variation in EV protein cargo is important to understand, as it may be useful in identifying potential therapeutic applications in clinical trials. We hypothesized that the donors would share both important similarities and differences in cargo relating to cell proliferation, angiogenesis, Wnt signaling, and basement membrane formation—processes shown to be critical for effective cutaneous wound healing.

Methods

We harvested BM-MSC EVs from four healthy human donors who underwent strict screening for whole bone marrow donation and further Good Manufacturing Practices-grade cell culture expansion for candidate usage in clinical trials. BM-MSC EV protein cargo was determined via mass spectrometry and Proteome Discoverer software. Corresponding proteomic networks were analyzed via the UniProt Consortium and STRING consortium databases.

Results

More than 3000 proteins were identified in each of the donors, sharing > 600 proteins among all donors. Despite inter-donor variation in protein identities, there were striking similarities in numbers of proteins per biological functional category. In terms of biologic function, the proteins were most associated with transport of ions and proteins, transcription, and the cell cycle, relating to cell proliferation. The donors shared essential cargo relating to angiogenesis, Wnt signaling, and basement membrane formation—essential processes in modulating cutaneous wound repair.

Conclusions

Healthy donors of BM-MSC EVs contain important similarities and differences among protein cargo that may play important roles in their pro-regenerative functions. Further studies are needed to correlate proteomic signatures to functional outcomes in cutaneous repair.
Tonsil-derived mesenchymal stem cells enhance allogeneic bone marrow engraftment via collagen IV degradation
Authors: Lee Hyun-Ji , Kim Yu-Hee , Choi Da-Won , Cho Kyung-Ah , Park Joo-Won , Shin Sang-Jin , Jo Inho , Woo So-Youn , Ryu Kyung-Ha
Published: June 2021

Background

Co-transplantation of bone marrow cells (BMCs) and mesenchymal stem cells (MSCs) is used as a strategy to improve the outcomes of bone marrow transplantation. Tonsil-derived MSCs (TMSCs) are a promising source of MSCs for co-transplantation. Previous studies have shown that TMSCs or conditioned media from TMSCs (TMSC-CM) enhance BMC engraftment. However, the factors in TMSCs that promote better engraftment have not yet been identified.

Methods

Mice were subjected to a myeloablative regimen of busulfan and cyclophosphamide, and the mRNA expression in the bone marrow was analyzed using an extracellular matrix (ECM) and adhesion molecule-targeted polymerase chain reaction (PCR) array. Nano-liquid chromatography with tandem mass spectrometry, real-time quantitative PCR, western blots, and enzyme-linked immunosorbent assays were used to compare the expression levels of metalloproteinase 3 (MMP3) in MSCs derived from various tissues, including the tonsils, bone marrow, adipose tissue, and umbilical cord. Recipient mice were conditioned with busulfan and cyclophosphamide, and BMCs, either as a sole population or with control or MMP3-knockdown TMSCs, were co-transplanted into these mice. The effects of TMSC-expressed MMP3 were investigated. Additionally, Enzchek collagenase and Transwell migration assays were used to confirm that the collagenase activity of TMSC-expressed MMP3 enhanced BMC migration.

Results

Mice subjected to the myeloablative regimen exhibited increased mRNA expression of collagen type IV alpha 1/2 (Col4a1 and Col4a2). Among the various extracellular matrix-modulating proteins secreted by TMSCs, MMP3 was expressed at higher levels in TMSCs than in other MSCs. Mice co-transplanted with BMCs and control TMSCs exhibited a higher survival rate, weight recovery, and bone marrow cellularity compared with mice co-transplanted with BMCs and MMP3-knockdown TMSCs. Control TMSC-CM possessed higher collagenase activity against collagen IV than MMP3-knockdown TMSC-CM. TMSC-CM also accelerated BMC migration by degrading collagen IV in vitro.

Conclusions

Collectively, these results indicate that TMSCs enhance BMC engraftment by the secretion of MMP3 for the modulation of the bone marrow extracellular matrix.
Upstream region of OprD mutations in imipenem-resistant and imipenem-sensitive Pseudomonas isolates
Authors: Kiani Masoumeh , Astani Akram , Eslami Gilda , Khaledi Mansoor , Afkhami Hamed , Rostami Soodabeh , Zarei Mohadeseh , Rezaei Khozani Nahid , Zandi Hengameh
Published: June 2021

The current study was aimed at investigating the prevalence of the mutations upstream of the oprD coding region and its promoters among imipenem-resistant and sensitive Pseudomonas aeruginosa isolated from educational hospitals in Yazd City, Iran. All isolates were identified by the conventional biochemical tests. Then, the antibiotic resistance of these isolates was determined using the disk diffusion method according to the CLSI guidelines. Also, the E.test was performed to determine the minimum inhibitory concentrations (MIC) of imipenem. The mutations of this gene were recognized by the amplification of this region and subsequently sequenced. Sequencing of the genomic region upstream of oprD these regions were done in the 29 clinical strains. Statistical analysis was done by the statistical software SPSS-18. Seventy (77.7%) of isolates had MIC ≥ 16 and were resistant to imipenem. Mutations of the upstream of the oprD gene and its promoters were seen in 25 (86.2%) isolates and 4 isolates had no mutation. One isolate had a base substitution A→Cat nt 25 in the coding region and this isolate had a point mutation leading to an amino acid change at positions 9 (I→L). Our study results indicated that none of the strains had mutation in Shine-Dalgarno and the point mutations were the most common mutations upstream of the oprD coding region among P. aeruginosa isolates. Mutations were observed in imipenem-resistant isolates and it seems this mechanism is effective in resistance of isolates to imipenem and this confirmed that the indiscriminate use of antibiotic should be controlled.
Resource sharing of mobile edge computing networks based on auction game and blockchain
Authors: Zhang Xiuxian , Zhu Xiaorong , Chikuvanyanga M.A.M , Chen Meijuan
Published: June 2021

The edge clouds in mobile edge computing networks are isolate which may belong to different companies or organizations, and hence the communication, computation, and storage resources are not efficiently utilized. To solve this problem, we propose the resource-sharing model of edge clouds which is based on blockchain technology and auction game. In this model, the blockchain platform is regarded as the bridge of the resource sharing, composed of edge clouds, clouds, third-party spectrum and computation management, identity authentication institutions, etc. It is used to record the users’ transaction information and broadcast the intelligent terminals’ resource requirements to all edge clouds in the blockchain platform through smart contracts. Then, an optimization problem of the joint allocation of communication and computation resources is formulated to maximize the utility of intelligent terminals. And an efficient improved sealed second-price auction game is proposed to allocate communication and computation resources and determine the optimal price of resources under the intelligent terminals’ QoS constraints. Simulation results show that the model can effectively improve the system resources utilization and the successful transaction rate.
HTPC: heterogeneous traffic-aware partition coding for random packet spraying in data center networks
Authors: Huang Jiawei , Wang Shiqi , Li Shuping , Zou Shaojun , Hu Jinbin , Wang Jianxin
Published: June 2021

Modern data center networks typically adopt multi-rooted tree topologies such leaf-spine and fat-tree to provide high bisection bandwidth. Load balancing is critical to achieve low latency and high throughput. Although the per-packet schemes such as Random Packet Spraying (RPS) can achieve high network utilization and near-optimal tail latency in symmetric topologies, they are prone to cause significant packet reordering and degrade the network performance. Moreover, some coding-based schemes are proposed to alleviate the problem of packet reordering and loss. Unfortunately, these schemes ignore the traffic characteristics of data center network and cannot achieve good network performance. In this paper, we propose a Heterogeneous Traffic-aware Partition Coding named HTPC to eliminate the impact of packet reordering and improve the performance of short and long flows. HTPC smoothly adjusts the number of redundant packets based on the multi-path congestion information and the traffic characteristics so that the tailing probability of short flows and the timeout probability of long flows can be reduced. Through a series of large-scale NS2 simulations, we demonstrate that HTPC reduces average flow completion time by up to 60% compared with the state-of-the-art mechanisms.
Understanding the effects of intramuscular injection and feed withdrawal on Salmonella Typhimurium shedding and gut microbiota in pullets
Authors: Joat Nitish Narendra , Khan Samiullah , Chousalkar Kapil
Published: June 2021

Background

Gut microbiota plays a key role in health, immunity, digestion, and production in layers. Factors such as environment, diet, diseases, stress, and flock management significantly affect gut microbiota; however, it is not known how potential stressors such as intramuscular injections or feed withdrawal alter the composition of gut microbiota that result in increased the shedding level of foodborne pathogens. In the current study, the effects of intramuscular corticosterone injection and feed withdrawal were evaluated to understand their role inSalmonellaTyphimurium shedding and changes in the composition of gut microbiota in layers.

Results

Salmonellashedding was observed for 8 weeks post-infection. There was a significant increase inSalmonellaTyphimurium count after intramuscular injection and feed withdrawal. TheSalmonellainfected and the negative control groups showed significant differences in the abundance of different genera in gut microbiota at week 1 and up to week 7 post infection. The infected group showed a significant reduction in alpha diversity of gut microbiota. Firmicutes reduced significantly (P < 0.05) after intramuscular injection, while the feed withdrawal groups did not cause any significant changes in Proteobacteria-Firmicutes ratio. Furthermore, intramuscular injection resulted in a significant change in alpha diversity of gut microbiota.

Conclusions

Exposure of chicks to relatively low dose ofSalmonellaTyphimurium can lead to persistent shedding in pullets. TheSalmonellaTyphimurium infection disrupted the gut microbiota composition immediately after infection. The potential stress of intramuscular injection and feed withdrawal significantly increased theSalmonellaTyphimurium count in faeces. The intramuscular injection also resulted in a significant alteration of the Proteobacteria-Firmicutes ratio, which could increase the risk of dysbiosis.
Where should police forces target their residential burglary reduction efforts? Using official victimisation data to predict burglary incidences at the neighbourhood level
Authors: Hunter James , Ward Bethany , Tseloni Andromachi , Pease Ken
Published: June 2021

Expected crime rates that enable police forces to contrast recorded and anticipated spatial patterns of crime victimisation offer a valuable tool in evaluating the under-reporting of crime and inform/guide crime reduction initiatives. Prior to this study, police forces had no access to expected burglary maps at the neighbourhood level covering all parts of England and Wales. Drawing on analysis of the Crime Survey for England and Wales and employing a population terrain modelling approach, this paper utilises household and area characteristics to predict the mean residential burglary incidences per 1000 population across all neighbourhoods in England and Wales. The analysis identifies distinct differences in recorded and expected neighbourhood burglary incidences at the Output Area level, providing a catalyst for stimulating further reflection by police officers and crime analysts.
Ultra-accurate microbial amplicon sequencing with synthetic long reads
Authors: Callahan Benjamin J. , Grinevich Dmitry , Thakur Siddhartha , Balamotis Michael A. , Yehezkel Tuval Ben
Published: June 2021

Background

Out of the many pathogenic bacterial species that are known, only a fraction are readily identifiable directly from a complex microbial community using standard next generation DNA sequencing. Long-read sequencing offers the potential to identify a wider range of species and to differentiate between strains within a species, but attaining sufficient accuracy in complex metagenomes remains a challenge.

Methods

Here, we describe and analytically validate LoopSeq, a commercially available synthetic long-read (SLR) sequencing technology that generates highly accurate long reads from standard short reads.

Results

LoopSeq reads are sufficiently long and accurate to identify microbial genes and species directly from complex samples. LoopSeq perfectly recovered the full diversity of 16S rRNA genes from known strains in a synthetic microbial community. Full-length LoopSeq reads had a per-base error rate of 0.005%, which exceeds the accuracy reported for other long-read sequencing technologies. 18S-ITS and genomic sequencing of fungal and bacterial isolates confirmed that LoopSeq sequencing maintains that accuracy for reads up to 6 kb in length. LoopSeq full-length 16S rRNA reads could accurately classify organisms down to the species level in rinsate from retail meat samples, and could differentiate strains within species identified by the CDC as potential foodborne pathogens.

Conclusions

The order-of-magnitude improvement in length and accuracy over standard Illumina amplicon sequencing achieved with LoopSeq enables accurate species-level and strain identification from complex- to low-biomass microbiome samples. The ability to generate accurate and long microbiome sequencing reads using standard short read sequencers will accelerate the building of quality microbial sequence databases and removes a significant hurdle on the path to precision microbial genomics.
Diurnal variation in the human skin microbiome affects accuracy of forensic microbiome matching
Authors: Wilkins David , Tong Xinzhao , Leung Marcus H. Y. , Mason Christopher E. , Lee Patrick K. H.
Published: June 2021

Background

The human skin microbiome has been recently investigated as a potential forensic tool, as people leave traces of their potentially unique microbiomes on objects and surfaces with which they interact. In this metagenomic study of four people in Hong Kong, their homes, and public surfaces in their neighbourhoods, we investigated the stability and identifiability of these microbiota traces on a timescale of hours to days.

Results

Using a Canberra distance-based method of comparing skin and surface microbiomes, we found that a person could be accurately matched to their household in 84% of tests and to their neighbourhood in 50% of tests, and that matching accuracy did not decay for household surfaces over the 10-day study period, although it did for public surfaces. The time of day at which a skin or surface sample was taken affected matching accuracy, and 160 species across all sites were found to have a significant variation in abundance between morning and evening samples. We hypothesised that daily routines drive a rhythm of daytime dispersal from the pooled public surface microbiome followed by normalisation of a person’s microbiome by contact with their household microbial reservoir, and Dynamic Bayesian Networks (DBNs) supported dispersal from public surfaces to skin as the major dispersal route among all sites studied.

Conclusions

These results suggest that in addition to considering the decay of microbiota traces with time, diurnal patterns in microbiome exposure that contribute to the human skin microbiome assemblage must also be considered in developing this as a potential forensic method.
Prevalence and spatial distribution patterns of human echinococcosis at the township level in Sichuan Province, China
Authors: He Wei , Wang Li-Ying , Yu Wen-Jie , Zhang Guang-Jia , Zhong Bo , Liao Sha , Wang Qi , Li Rui-Rui , Yang Liu , Yao Ren-Xin , Liu Yang , Danba Zeli , Qin Sheng-Chao , Wang Shi-An , Wang Yan-Xia , Huang Yan , Wang Qian
Published: June 2021

Background

Echinococcosis is a global zoonotic parasitic disease caused by Echinococcus larvae. This disease is highly endemic in Sichuan Province, China. This study investigates the prevalence and spatial distribution characteristics of human echinococcosis at the township level in Sichuan Province, geared towards providing a future reference for the development of precise prevention and control strategies.

Methods

Human prevalence of echinococcosis was evaluated using the B-ultrasonography diagnostic method in Sichuan Province between 2016 and 2019. All data were collected, collated, and analyzed. A spatial distribution map was drawn to intuitively analyze the spatial distribution features. Eventually, the spatial autocorrelation was specified and local indicators of spatial association (LISA) clustering map was drawn to investigate the spatial aggregation of echinococcosis at the township level in Sichuan Province.

Results

The prevalence of echinococcosis in humans of Sichuan Province was 0.462%, among which the occurrence of cystic echinococcosis (CE) was 0.221%, while that of alveolar echinococcosis (AE) was 0.244%. Based on the results of the spatial distribution map, a predominance of echinococcosis in humans decreased gradually from west to east and from north to south. The Global Moran’s I index was 0.77 (Z = 32.07, P < 0.05), indicating that the prevalence of echinococcosis in humans was spatially clustered, exhibiting a significant spatial positive correlation. Further, the findings of local spatial autocorrelation analysis revealed that the “high–high” concentration areas were primarily located in some townships in the northwest of Sichuan Province. However, the “low–low” concentration areas were predominantly located in some townships in the southeast of Sichuan Province.

Conclusions

Our findings demonstrated that the prevalence of echinococcosis in humans of Sichuan Province follows a downward trend, suggesting that the current prevention and control work has achieved substantial outcomes. Nevertheless, the prevalence in humans at the township level is widely distributed and differs significantly, with a clear clustering in space. Therefore, precise prevention and control strategies should be formulated for clusters, specifically strengthening the “high–high” clusters at the township level.

Graphic Abstract
Automatic identification of differences in behavioral co-occurrence between groups
Authors: Tian Yiming , Maekawa Takuya , Korpela Joseph , Amagata Daichi , Hara Takahiro , Matsumoto Sakiko , Yoda Ken
Published: June 2021

Background

Recent advances in sensing technologies have enabled us to attach small loggers to animals in their natural habitat. It allows measurement of the animals’ behavior, along with associated environmental and physiological data and to unravel the adaptive significance of the behavior. However, because animal-borne loggers can now record multi-dimensional (here defined as multimodal) time series information from a variety of sensors, it is becoming increasingly difficult to identify biologically important patterns hidden in the high-dimensional long-term data. In particular, it is important to identify co-occurrences of several behavioral modes recorded by different sensors in order to understand an internal hidden state of an animal because the observed behavioral modes are reflected by the hidden state. This study proposed a method for automatically detecting co-occurrence of behavioral modes that differs between two groups (e.g., males vs. females) from multimodal time-series sensor data. The proposed method first extracted behavioral modes from time-series data (e.g., resting and cruising modes in GPS trajectories or relaxed and stressed modes in heart rates) and then identified two different behavioral modes that were frequently co-occur (e.g., co-occurrence of the cruising mode and relaxed mode). Finally, behavioral modes that differ between the two groups in terms of the frequency of co-occurrence were identified.

Results

We demonstrated the effectiveness of our method using animal-locomotion data collected from male and female Streaked Shearwaters by showing co-occurrences of locomotion modes and diving behavior recorded by GPS and water-depth sensors. For example, we found that the behavioral mode of high-speed locomotion and that of multiple dives into the sea were highly correlated in male seabirds. In addition, compared to the naive method, the proposed method reduced the computation costs by about 99.9%.

Conclusion

Because our method can automatically mine meaningful behavioral modes from multimodal time-series data, it can be potentially applied to analyzing co-occurrences of locomotion modes and behavioral modes from various environmental and physiological data.
The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma
Authors: Viet Chi T. , Yu Gary , Asam Kesava , Thomas Carissa M. , Yoon Angela J. , Wongworawat Yan Chen , Haghighiabyaneh Mina , Kilkuts Courtney A. , McGue Caitlyn M. , Couey Marcus A. , Callahan Nicholas F. , Doan Coleen , Walker Paul C. , Nguyen Khanh , Kidd Stephanie C. , Lee Steve C. , Grandhi Anupama , Cheng Allen C. , Patel Ashish A. , Philipone Elizabeth , Ricks Olivia L. , Allen Clint T. , Aouizerat Bradley E.
Published: June 2021

Background

Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality.

Methods

We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score.

Results

5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915.

Conclusions

The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.