bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral metagenomic analysis of chickens with runting-stunting syndrome in the Republic of Korea
Authors: Kim Hye-Ryoung , Kwon Yong-Kuk , Jang Il , Bae You-Chan
Published: April 2020

Background and aims

Runting-stunting syndrome (RSS) in chickens, also known as malabsorption syndrome, which is characterized by mild to severe enteritis and diagnosed through typical histopathologic examination as well as clinical signs, results in considerable economic losses. Despite the many studies carried out over decades to determine the etiologic agents of RSS involved in the disease, several outbreaks remained without the elucidation of, potentially multiple, etiologies involved.

Methods

We performed comparative analysis of viral metagenomes from four chicken flocks affected with RSS using next-generation sequencing. Primers for the detection of chicken enteric viruses were designed from the sequencing data obtained with metagenomics. Multiplex reverse transcription–polymerase chain reaction (PCR) and PCR were performed to detect a variety of etiological agents previously described in natural cases of RSS.

Results

The most abundant viral families identified in this study were Astroviridae, Picornaviridae, Parvoviridae, Caliciviridae, Reoviridae and Picobirnaviridae. Chicken astrovirus sequences were present in all four samples, suggesting an association between chicken astrovirus and RSS and chicken astrovirus as a candidate pathogen responsible for RSS. Picobirnavirus and the newly identified chapparvovirus were found in chickens in the Republic of Korea for the first time, and the genetic diversity of enteric viruses and viral communities was showed.

Conclusions

Chicken astrovirus was consistently detected in broilers affected with RSS and the result of this study may contribute to knowledge of enteric diseases and viruses in chickens.
“Get us partnerships!” - a qualitative study of Angolan and Mozambican health academics’ experiences with North/South partnerships
Authors: Craveiro Isabel , Carvalho António , Ferrinho Paulo
Published: April 2020

Background

Sustainable Development Goal (SDG) 17 focuses on North/South partnerships for sustainable development. Literature on research partnerships and capacity -building often neglects how these processes are carried out in practice, their social impacts and participants’ subjective experiences.

Recognizing the increasingly global dimensions of Higher Education Institutions, the University Development and Innovation – Africa project (UDI-A) was designed to train lecturers and administrative staff of Angolan and Mozambican Universities through collaborations with European institutions, aiming at strengthening African academic and social landscapes through knowledge translation and dissemination.

This paper examines potential outcomes of UDI-A on participants’ academic pathways, investigating the conflict between different imaginaries of capacity-building and partnerships, focusing on how Angolan and Mozambican health sciences researchers experience international collaborations.

Methods

Semi-structured interviews were conducted with seven health academics, as well as a focus group discussion involving all participants. These were recorded, fully transcribed, anonymized and coded to identify common themes. A consent form was signed by all participants.

Results and discussion

UDI-A was considered innovative, fostering the improvement of pedagogical skills and increasing social entrepreneurship activities.

Participants arrived with a specific institutional mandate and believed that the training received should be incorporated into institutional practices to “modernize” these specific Portuguese speaking African Universities and the health sector. The institutional mechanisms put in place to attain this goal, Centres for Academic Development and Innovation (“CADIs”), were considered potential research and development hubs and drivers of academic and societal transformation.

Nevertheless, participants shared a sense of asymmetry (infrastructural, financial, in terms of access to information) between them and European trainers. Although this asymmetry was the underlying basis of this capacity-building project, they argued that UDI-A did not fully acknowledge their local contexts, compromising the prospective development of partnerships in the health field.

Conclusions

More attention should be devoted to understanding how participants experience capacity building processes, integrating the diversity of their aspirations and perceptions into subsequent phases of the project, requiring the development of methodological innovations to increase the impact of these programs.
Knowledge and interactions of the local community with the herpetofauna in the forest reserve of Quininí (Tibacuy-Cundinamarca, Colombia)
Authors: Ríos-Orjuela Juan Camilo , Falcón-Espitia Nelson , Arias-Escobar Alejandra , Espejo-Uribe María José , Chamorro-Vargas Carol Tatiana
Published: April 2020

Background

The study of human-nature relationship has made possible to understand the life dynamics of the communities and the biodiversity with which they cohabit. Although there has been a rise of ethnobiological studies over the last decade, little is known about human interaction with herpetofauna in South America and Colombia. In this work, we analyzed the knowledge, perception, and interaction of a local community located in the forest reserve of Quininí (RFPCQ) in Cundinamarca (Colombia), concerning to the herpetofauna that inhabits the area.

Methods

We performed semi-structured surveys containing 30 questions categorized into three groups: academic knowledge (1), use and cultural beliefs (2), and interactions (3) related to the herpetofauna that occurs in the region. The obtained data in question groups 1 and 2 are presented as a qualitative summary. For the question group 3, we assigned the answers to a hostility value according to the possible reaction of each individual interviewed in a hypothetical encounter with the herpetofauna and built tendency charts in order to see the positive or negative reactions due to the birthplace (urban/rural) and gender (male/female).

Results

The community recognized the presence of amphibians and reptiles that cohabit their space, as well as their potential habitats. Besides, the role of herpetofauna was recognized in the magical/religious traditions for some inhabitants of the region, mainly associated with the fate and cure of chronic diseases. In general, the perception of amphibians and reptiles varied according to the origin and gender of the people, which tend to have a more positive perception of reptiles than compared to amphibians in most cases.

Conclusions

Although there was a general lack of knowledge on the part of the inhabitants of the RFPCQ about the biological and ecological aspects of herpetofauna, the population recognized the basic information about the habitats of these animals within the reserve area. There is a wide variety of uses of amphibians and reptiles in traditional medicine. Greater efforts should be made in the transmission and dissemination of knowledge about the ecological functions of herpetofauna.
The OLIF working corridor based on magnetic resonance imaging: a retrospective research
Authors: Wang Zhe , Liu Lei , Xu Xiang-he , Cao Ming-de , Lu Hai , Zhang Kui-bo
Published: April 2020

Objective

To provide an anatomical basis for the development of oblique lumbar interbody fusion (OLIF) in Chinese patients.

Methods

Between November 2018 and June 2019, 300 patients’ lumbar MRI data were reviewed. According to the Moro system and zone method described by us, the axial view was vertically divided into 6 zones (A, I II, III, IV, P) and was horizontally divided into 4 zones (R, a, b, c, L). The locations of left psoas muscle and the major artery at L2/3, L3/4, and L4/5 levels were evaluated by the grid system. The aortic bifurcation segments will also be evaluated at the level of the vertebral body or the disc.

Results

At the L2/3 level, left psoas muscle and the major artery in zone Ib were found in 28.0% of subjects, in zone IIb in 20.3%, and in zone Ic in 20.0%; at the L3/4 level, in zone Ab in 20.7% of subjects, in zone Ac in 26.0%, and in zone Ic in 11.0%; and at the L4/5 level, areas in zone Ab in 31.0% of subjects, in zone Ac in 26.0%, and in zone Ib in 11.7%. The aortic bifurcation segments were mainly at the L4 level. The zone of the left psoas muscle at all levels, the zone of the major artery at L4/5 level, and the zone of the aortic bifurcation segments had significant correlation with gender difference (P < 0.05).

Conclusion

The left-sided OLIF at L2–L5 disc levels can be a feasible type of surgery for lumbar interbody fusion in the majority of Chinese patients. Before the operation, in order to screen out the appropriate surgical approach, routine lumbar magnetic resonance imaging is recommended to analyze the patient’s local anatomical features.
Finite element analysis of dual small plate fixation and single plate fixation for treatment of midshaft clavicle fractures
Authors: Zhang Fangxue , Chen Fancheng , Qi Yuhan , Qian Zhi , Ni Shuo , Zhong Zeyuan , Zhang Xu , Li Dejian , Yu Baoqing
Published: April 2020

Background

Midshaft clavicle fractures are one of the most familiar fractures. And, dual small plate fixation has been reported as can minimize hardware-related complications. However, the biomechanical properties of the dual small plate fixation have not yet been thoroughly evaluated. Here, we report the results of a finite element analysis of the biomechanical properties of midshaft clavicle fractures treated with dual small plating and superior and anteroinferior single plate fixation.

Methods

A three-dimensional (3D) finite element model of the midshaft clavicle fractures was created, whose 4-mm transverse fracture gap, having an angle < 30 degree and devoid of overlapping triangles, was simulated between the fractured segments of the middle-shaft of the clavicle. The equivalent von Mises stress and displacement of the model was used as the output measures for analysis.

Results

No significant differences were found between dual plating, superior or anteroinferior single plating in cantilever bending, axial compression, and axial torsion. Dual plating with a smaller plate-screw construct is biomechanically eligible to compare with superior and anteroinferior single plate fixation using larger plate-screw constructs.

Conclusions

This study demonstrated that larger plate-screw constructs for the treatment of simple are placed clavicular fractures; however, weight-bearing and exorbitant shoulder activity should be avoided after the operation. Therefore, dual plating may provide a viable option for fixing midshaft clavicle fractures and, thus, may be preferred for patients who need early activity.
Preoperative low scores of Life Satisfaction Rating predicts poor outcomes after total knee arthroplasty: a prospective observational study
Authors: Liu Kaiyuan , Yang Dong , Zan Pengfei , Fan Aoyuan , Zheng Zhi , Jiang Wenwei , Li Guodong
Published: April 2020

Background

Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient’s current mental state is suitable enough to accept a TKA surgery.

Methods

Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated.

Results

Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA.

Conclusion

Our outcomes can help clinicians evaluate whether a patient’s current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery.
Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the “kidney governing bone” theory
Authors: Yao Baojin , Liu Jia , Zhang Mei , Leng Xiangyang , Zhao Daqing
Published: April 2020

Background

Guzhi Zengsheng Zhitongwan (GZZSZTW) is an effective Chinese medicinal formulation for the treatment of osteoarthritis (OA) designed according to the “kidney governing bone” theory, which has been widely used as a golden guide for treating bone and cartilage diseases in traditional Chinese medicine. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney.

Methods

Preparation and quality control were performed as previously described. Since GZZSZTW is orally administered in the form of pills prepared in boiled water, the Chinese materia medica (CMM) mixture of this formula was extracted with distilled water by a reflux method and was then filtered through a 0.45-μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. The effects of GZZSZTW on gene expression and regulation of both kidney and bone tissues were investigated using a state-of-the-art RNA-seq technology.

Results

We demonstrated that GZZSZTW could enhance kidney function and suppress bone formation and resorption by modulating the activities of osteoblast and osteoclast, and might subsequently contribute to the inhibition of osteophyte formation during the process of OA. These effects might be achieved by the synergistic interactions of various herbs and their active components in GZZSZTW, which increased the expression levels of functional genes participating in kidney function, regulation, and repair, and then decreased the expression levels of genes involved in bone formation and resorption. Thus, our findings were consistent with the “kidney governing bone” theory, which has been widely used as a guide in clinical practice for thousands of years.

Conclusions

This study has deepened the current knowledge about the molecular effects of GZZSZTW on bone and kidney regulation. Furthermore, this study might be able to provide possible strategies to further prevent and treat joint diseases by using traditional Chinese medicinal formulations following the “kidney governing bone” theory.
The efficacy of hydrogel foams in talc Pleurodesis
Authors: Baxter Joy , Lima Thamires A. , Huneke Richard , Kanach Colin Joseph , Johal Priya , Reimold Emily , Alvarez Nicolas J. , Laub Glenn W.
Published: April 2020

Background

Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Pleurodesis with talc slurry is a standard treatment option, but clinical failures occur, possible due to poor talc delivery. A novel drug-delivery system was developed that fills the entire thoracic cavity with a liquid foam containing talc. The foam is designed to gel and adhere to the tissue walls at body temperature, to improve talc deposition and efficacy.

Methods

Rheology, foam stability, and ex-vivo coating and bio-adhesion studies were performed on three concentrations of a novel hydrogel talc foam system that was developed to improve delivery of talc to the pleural surfaces. A New Zealand rabbit model of pleurodesis was used to evaluate effectiveness of the foams at inducing adhesion formation and compared to talc slurry. The rabbits were recovered after they had one of the test agents instilled into their pleura, and then sacrificed after 28 days. Pleurodesis was assessed by a blinded pathologist using a standardized pathological scoring system.

Results

All talc foam formulations produced foams that gelled at physiological temperatures and were relatively stable for at least two hours. As the concentration of the formulation increased the gelation temperature decreased and the foam adhesiveness increased. Rabbits that received talc foam had significantly greater adhesion formation than talc slurry (mean score of 2.21 vs. 1.18 (p < 0.05)). Rabbits that received the 20% foam developed the most adhesions.

Conclusions

This study demonstrates that our triblock copolymer hydrogel foam delivery system enhances adhesion formation in an experimental model. This novel approach can have important clinical impact, potentially improving efficacy of existing therapies and reducing the need for more invasive treatments.
The use of cIMT as a predictor of postoperative stroke in patients undergoing surgical repair of acute type a aortic dissection
Authors: Zhang Kai , Qian Si-Chong , Pan Xu-Dong , Dong Song-Bo , Zheng Jun , Liu Hong , Wang Yue-Li , Sun Li-Zhong
Published: April 2020

Background

Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires surgical intervention. Stroke remains an extremely serious adverse outcome that can occur in ATAAD patients undergoing aortic arch repair, leading to higher rates of patient mortality and decreased postoperative quality of life. In the present study, we sought to determine whether carotid intima–media thickness (cIMT) is a reliable predictor of postoperative stroke risk.

Materials and methods

This was a prospective study of 76 patients with ATAAD undergoing aortic arch repair. For all patients, cIMT was determined preoperatively through a Doppler-based method. Incidence of different forms of neurological dysfunction, including temporary neurological dysfunction (TND) and stroke, was monitored in these patients, and the relationship between cIMT and stroke incidence was assessed using a receiver-operating characteristic (ROC) curve. Prognostic variables associated with stroke risk were further identified through univariate and multivariate analyses.

Results

A total of 26/76 (34.2%) patients in the present study suffered from neurological dysfunction, of whom 16 (21.0%) suffered from TND and 10 (13.2%) suffered a stroke. The remaining 50 patients (65.8%) did not suffer from neurological dysfunction. The cIMT values in the stroke, TND, and neurological dysfunction-free patients in this study were 1.12 ± 0.19 (mm), 0.99 ± 0.13 (mm), and 0.87 ± 0.13 (mm), respectively. A total of 4 patients in this cohort died during the study, including 1 in the TND group and 3 in the stroke group. An ROC curve analysis indicated that cIMT could predict stroke with an area under the curve value of 0.844 (95% CI, 0.719–0.969; p < 0.001). A multivariate analysis revealed that cIMT > 0.9 mm was independently associated with stroke risk (p = 0.018).

Conclusion

We found that cIMT can be used to predict postoperative stroke risk in ATAAD patients undergoing aortic arch repair, with a cIMT > 0.9 mm coinciding with increased stroke risk in these patients.

Trial registration

ChiCTR1900022289. Date of registration 4 April 2019 retrospectively registered.
Increased visceral arterial tortuosity in Marfan syndrome
Authors: Ágg Bence , Szilveszter Bálint , Daradics Noémi , Benke Kálmán , Stengl Roland , Kolossváry Márton , Pólos Miklós , Radovits Tamás , Ferdinandy Péter , Merkely Béla , Maurovich-Horvat Pál , Szabolcs Zoltán
Published: April 2020

Background

Clinical evidence suggests that the currently recommended approach to estimate the risk of aortic dissection in Marfan syndrome (MFS) is not reliable enough. Therefore, we investigated the possible role of visceral arterial tortuosity in the risk stratification.

Methods and results

Splenic and renal arteries of 37 MFS patients and 74 age and gender matched control subjects were segmented using CT angiography imaging. To measure tortuosity, distance metric (DM), sum of angles metric (SOAM), inflection count metric (ICM), and the ratio of ICM and SOAM (ICM/SOAM) were calculated. DM of the splenic, right and left renal artery was significantly higher in MFS patients than in controls (2.44 [1.92-2.80] vs. 1.75 [1.57-2.18]p < 0.001; 1.16 [1.10-1.28] vs. 1.11 [1.07-1.15]p = 0.011; 1.40 [1.29-1.70] vs. 1.13 [1.09-1.23]p < 0.001, respectively). A similar tendency for ICM and an opposite tendency for SOAM were observed. ICM/SOAM was significantly higher in the MFS group compared to controls in case of all three arteries (73.35 [62.26-93.63] vs. 50.91 [43.19-65.62]p < 0.001; 26.52 [20.69-30.24] vs. 19.95 [16.47-22.95]p < 0.001; 22.81 [18.64-30.96] vs. 18.38 [15.29-21.46]p < 0.001, respectively). MFS patients who underwent aortic root replacement had increased right and left renal DM and ICM/SOAM compared to MFS patients without surgery.

Conclusion

To our knowledge this is the first demonstration of increased arterial tortuosity in MFS on visceral arteries. Visceral arterial tortuosity, dominated by curves of lower frequency but higher amplitude according to the observed opposite tendency between the DM and SOAM metrics, could be a possible new predictor of serious manifestations of MFS.
NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma
Authors: Chen Hui , Deng Yang , Gan Xiaoliang , Li Yonghao , Huang Wenyong , Lu Lin , Wei Lai , Su Lishi , Luo Jiawen , Zou Bin , Hong Yanhua , Cao Yihai , Liu Yizhi , Chi Wei
Published: April 2020

Background

Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death.

Methods

A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma.

Results

Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades.

Conclusions

These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.
Detection of human cytomegalovirus in patients with epithelial ovarian cancer and its impacts on survival
Authors: Yin Min , Chen Aiping , Zhao Fei , Ji Xuechao , Li Chuan , Wang Guangning
Published: April 2020

Background

The cause of epithelial ovarian cancer (EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial.

Objective

To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival.

Methods

Formalin-fixed paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were analyzed for expression of HCMV immediate early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry.

Results

HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive HCMV-IE protein expression was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surgery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months,P = 0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034).

Conclusions

This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.
An Auristatin nanoconjugate targeting CXCR4+ leukemic cells blocks acute myeloid leukemia dissemination
Authors: Pallarès Victor , Unzueta Ugutz , Falgàs Aïda , Sánchez-García Laura , Serna Naroa , Gallardo Alberto , Morris Gordon A. , Alba-Castellón Lorena , Álamo Patricia , Sierra Jorge , Villaverde Antonio , Vázquez Esther , Casanova Isolda , Mangues Ramon
Published: April 2020

Background

Current acute myeloid leukemia (AML) therapy fails to eliminate quiescent leukemic blasts in the bone marrow, leading to about 50% of patient relapse by increasing AML burden in the bone marrow, blood, and extramedullar sites. We developed a protein-based nanoparticle conjugated to the potent antimitotic agent Auristatin E that selectively targets AML blasts because of their CXCR4 receptor overexpression (CXCR4+) as compared to normal cells. The therapeutic rationale is based on the involvement of CXCR4 overexpression in leukemic blast homing and quiescence in the bone marrow, and the association of these leukemic stem cells with minimal residual disease, dissemination, chemotherapy resistance, and lower patient survival.

Methods

Monomethyl Auristatin E (MMAE) was conjugated with the CXCR4 targeted protein nanoparticle T22-GFP-H6 produced in E. coli. Nanoconjugate internalization and in vitro cell viability assays were performed in CXCR4+ AML cell lines to analyze the specific antineoplastic activity through the CXCR4 receptor. In addition, a disseminated AML animal model was used to evaluate the anticancer effect of T22-GFP-H6-Auristatin in immunosuppressed NSG mice (n = 10/group). U of Mann-Whitney test was used to consider if differences were significant between groups.

Results

T22-GFP-H6-Auristatin was capable to internalize and exert antineoplastic effects through the CXCR4 receptor in THP-1 and SKM-1 CXCR4+ AML cell lines. In addition, repeated administration of the T22-GFP-H6-Auristatin nanoconjugate (9 doses daily) achieves a potent antineoplastic activity by internalizing specifically in the leukemic cells (luminescent THP-1) to selectively eliminate them. This leads to reduced involvement of leukemic cells in the bone marrow, peripheral blood, liver, and spleen, while avoiding toxicity in normal tissues in a luminescent disseminated AML mouse model.

Conclusions

A novel nanoconjugate for targeted drug delivery of Auristatin reduces significantly the acute myeloid leukemic cell burden in the bone marrow and blood and blocks its dissemination to extramedullar organs in a CXCR4+ AML model. This selective drug delivery approach validates CXCR4+ AML cells as a target for clinical therapy, not only promising to improve the control of leukemic dissemination but also dramatically reducing the severe toxicity of classical AML therapy.
Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3
Authors: Chen Xijuan , Liu Junqi , Zhang Qinglan , Liu Baoxing , Cheng Yan , Zhang Yonglei , Sun Yanan , Ge Hong , Liu Yingqiang
Published: April 2020

Background

Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC).

Methods

CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation.

Results

FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice.

Conclusion

The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis.
Distinct gene expression profiles associated with clinical outcomes in patients with ovarian clear cell carcinoma and high-grade serous ovarian carcinoma
Authors: Zhou Huimei , Liu Qian , Shi Xiaohua , Liu Yue , Cao Dongyan , Yang Jiaxin
Published: April 2020

Background

Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Southeast Asia. OCCC has a more unfavourable clinical outcome due to a poor response to platinum-based chemotherapy compared with serous carcinoma. The identification of biomarkers related to the prognosis of OCCC is critically important for an improved understanding of the biology that drives OCCC progression and leads to poor outcomes. To detect differences in gene expression profiles between OCCC and high-grade serous ovarian carcinoma (HGSOC), twelve patients with OCCC and twelve patients with HGSOC were recruited in whom the pathological diagnosis was confirmed on surgically resected specimens.

Results

Compared with HGSOC, OCCC has 609 differentially expression genes, and 199 are significantly different (P < 0.05). These genes are involved in the cell cycle, apoptosis, DNA damage repair, the PI3K pathway and so on. There were 164 differentially expressed genes in the PI3K pathway. There were 35 overexpressed genes in OCCC, while there were 12 overexpressed genes in HGSOC. Among these differentially expressed genes, we found that the MET gene and the CCNE1 gene were overexpressed in OCCC and associated with a worse prognosis.

Conclusions

In conclusion, there are many differentially expressed genes in OCCC and HGSOC, which indicates that the two kinds of tumours differ greatly in tumourigenesis and provides a theoretical basis for targeted therapy in the future. Further studies need to be performed to clarify the association of the differentially expressed genes with the unfavourable prognosis in OCCC.
Prenatal and postnatal determinants in shaping offspring’s microbiome in the first 1000 days: study protocol and preliminary results at one month of life
Authors: Raspini Benedetta , Porri Debora , De Giuseppe Rachele , Chieppa Marcello , Liso Marina , Cerbo Rosa Maria , Civardi Elisa , Garofoli Francesca , Monti Maria Cristina , Vacca Mirco , De Angelis Maria , Cena Hellas
Published: April 2020

Background

Fetal programming during in utero life defines the set point of physiological and metabolic responses that lead into adulthood; events happening in “the first 1,000 days” (from conception to 2-years of age), play a role in the development of non-communicable diseases (NCDs). The infant gut microbiome is a highly dynamic organ, which is sensitive to maternal and environmental factors and is one of the elements driving intergenerational NCDs’ transmission.

The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the correlation between several factors, from conception to the first year of life, and infant gut microbiome composition. We described the study design of the A.MA.MI study and presented some preliminary results.

Methods

A.MA.MI is a longitudinal, prospective, observational study conducted on a group of mother-infant pairs (n = 60) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected at T0, T1, T2 and T3, respectively before discharge, 1,6 and 12 months after birth.

Maternal and infant anthropometric measurements were assessed at each time. Other variables evaluated were: pre-pregnancy/gestational weight status (T0), maternal dietary habits/physical activity (T1-T3); infant medical history, type of feeding, antibiotics/probiotics/supplements use, environment exposures (e.g cigarette smoking, pets, environmental temperature) (T1-T3). Infant stool samples were planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods.

Results

Birth mode (cesarean section vs. vaginal delivery) and maternal pre pregnancy BMI (BMI < 25 Kg/m2 vs. BMI ≥ 25 Kg/m2), significant differences were found at genera and species levels (T0). Concerning type of feeding (breastfed vs. formula-fed), gut microbiota composition differed significantly at genus and species level (T1).

Conclusion

These preliminary and explorative results confirmed that pre-pregnancy, mode of delivery and infant factors likely impact infant microbiota composition at different levels.

Trial registration

ClinicalTrials.gov identifier: NCT04122612.
Body temperature at nursery admission in a cohort of healthy newborn infants: results from an observational cross-sectional study
Authors:   Collaboration Group, Merazzi Daniele , Bresesti Ilia , Tagliabue Paolo , Valsecchi Maria Grazia , De Lorenzo Paola , Lista Gianluca
Published: April 2020

Background

Exposure to hypothermia is somehow unavoidable when a baby comes to life. This is the reason why any possible effort should be made by every caregiver involved during birth, from labour to transfer into the maternity ward, to reduce it. Hypothermia has widely shown to be related to several neonatal problems, and the risks are more relevant when the babies are born prematurely.

Method

An observational study was conducted in April 2016 to assess the current practises to avoid hypothermia at birth in 20 Italian neonatal units. Each unit introduced local improvements in clinical practice and the same observational study was repeated 1 year later.

Results

A total of 4722 babies were analysed. An overall increase in adherence to local and international recommendations emerged from our study. Significant differences between 2016 and 2017 were found in regard to neonatal temperature at nursery entry (36.3 °C vs 36.5 °C, respectively, p < 0.0001), delayed cord clamping practice > 60″ (48.1% vs 68.1%, respectively, p < 0.0001) and skin-to-skin practice > 60′ (56.3% vs 60.9, respectively, p = 0.03). Statistical correlations with the risk of hypothermia were found for delivery room (OR 0.88 (CI 95%0.83–0.94), p < 0.0001) and maternal temperature (OR 0.57 (CI 95% 0.48–0.67), p < 0.0001).

Conclusion

Periodical assessment of the delivery room practice has shown to be effective in improving adherence to the international recommendations. Relationship between neonatal hypothermia and several other variables including the delivery room and mother temperature underlines how neonatal thermoregulation starts immediately after birth. Hence, a multi-disciplinary approach is needed to provide the optimal environment for a safe birth.
Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review
Authors: Auriti Cinzia , Rotunno Roberta , Diociaiuti Andrea , Manzoni Silvia Magni , Uva Andrea , Bersani Iliana , Santisi Alessandra , Dotta Andrea , El Hachem May
Published: April 2020

Background

Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge.

Case presentation

We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate.

Conclusions

The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.
Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery
Authors: Wiersema Renske , Jukarainen Sakari , Vaara Suvi T. , Poukkanen Meri , Lakkisto Päivi , Wong Hector , Linder Adam , van der Horst Iwan C. C. , Pettilä Ville
Published: April 2020

Background

The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes.

Methods

We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5.

Results

In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality.

Conclusions

In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.
Can hypnosis and virtual reality reduce anxiety, pain and fatigue among patients who undergo cardiac surgery: a randomised controlled trial
Authors: Rousseaux Floriane , Faymonville Marie-Elisabeth , Nyssen Anne-Sophie , Dardenne Nadia , Ledoux Didier , Massion Paul B. , Vanhaudenhuyse Audrey
Published: April 2020

Background

Different non-pharmacological techniques, including hypnosis and virtual reality (VR) are currently used as complementary tools in the treatment of anxiety, acute and chronic pain. A new technique called virtual reality hypnosis (VRH), which encompasses a combination of both tools, is regularly used although its benefits and underlying mechanisms remain unknown to date. With the goal to improve our understanding of VRH combination effects, it is necessary to conduct randomised and controlled research trials in order to understand their clinical interest and potential benefits.

Methods

Patients (n = 100) undergoing cardiac surgery at the Liège University Hospital will be randomly assigned to one of four conditions (control, hypnosis, VR or VRH). Each patient will receive two sessions of one of the techniques: one the day before the surgery and one the day after. Physiological assessments will be made on the monitor and patients will rate their levels of anxiety, fatigue, pain, absorption and dissociation.

Discussion

This study will help to expand knowledge on the application of virtual reality, hypnosis and VRH in the specific context of cardiac and intensive care procedures, and the influence of these non-pharmacological techniques on patient’s anxiety, fatigue, pain and phenomenological experience.

Trial registration

ClinicalTrials.gov: NCT03820700. Date registered on 29 January 2019.

Study recruitment date: October 6, 2018. Study anticipated completion date: December 28, 2020.
Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II superiority clinical trial
Authors: Molina-Morant D. , Fernández M. L. , Bosch-Nicolau P. , Sulleiro E. , Bangher M. , Salvador F. , Sanchez-Montalva A. , Ribeiro A. L. P. , de Paula A. M. B. , Eloi S. , Correa-Oliveira R. , Villar J. C. , Sosa-Estani S. , Molina I.
Published: April 2020

Background

Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials.

Methods/design

MULTIBENZ is a phase II, randomized, superiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018.

Conclusion

This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood.

Trial registration

ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.
Evaluation of organic fractions of municipal solid waste as renewable feedstock for succinic acid production
Authors: Stylianou Eleni , Pateraki Chrysanthi , Ladakis Dimitrios , Cruz-Fernández María , Latorre-Sánchez Marcos , Coll Caterina , Koutinas Apostolis
Published: April 2020

Background

Despite its high market potential, bio-based succinic acid production experienced recently a declining trend because the initial investments did not meet the expectations for rapid market growth. Thus, reducing the succinic acid production cost is imperative to ensure industrial implementation.

Results

Succinic acid production has been evaluated using hydrolysates from the organic fraction of municipal solid waste (OFMSW) collected from MSW treatment plants. A tailor-made enzymatic cocktail was used for OFMSW hydrolysate production containing up to 107.3 g/L carbon sources and up to 638.7 mg/L free amino nitrogen. The bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens were evaluated for succinic acid production with the latter strain being less efficient due to high lactic acid production. Batch A. succinogenes cultures supplemented with 5 g/L yeast extract and 5 g/L MgCO3 reached 29.4 g/L succinic acid with productivity of 0.89 g/L/h and yield of 0.56 g/g. Continuous cultures at dilution rate of 0.06 h−1 reached 21.2 g/L succinic acid with yield of 0.47 g/g and productivity of 1.27 g/L/h. Downstream separation and purification of succinic acid was achieved by centrifugation, treatment with activated carbon, acidification with cation exchange resins, evaporation and drying, reaching more than 99% purity. Preliminary techno-economic evaluation has been employed to evaluate the profitability potential of bio-based succinic acid production.

Conclusions

The use of OFMSW hydrolysate in continuous cultures could lead to a minimum selling price of 2.5 $/kg at annual production capacity of 40,000 t succinic acid and OFMSW hydrolysate production cost of 25 $/t sugars.