bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy
Authors: Huang Junfeng , Xu Zhourui , jiang Yihang , Law Wing-cheung , Dong Biqin , Zeng Xierong , Ma Mingze , Xu Gaixia , Zou Jizhao , Yang Chengbin
Published: July 2021

Chemo-photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efficacy and application potential are largely subjected to the uncontrollability and biotoxicity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework-8 on gold nanoroad (Au@ZIF-8), was designed and fabricated for efficient drug loading and controlled release. Owing to the large surface area and guest-matching pore size of ZIF-8, doxorubicin (DOX) was successfully loaded into the Au@ZIF-8 with a high drug loading efficiency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF-8 layer was quickly degraded, which resulted in an on-demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efficient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour-bearing nude mice experiment due to the synergistic effect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF-8. This work robustly suggested that Au@ZIF-8 could be further explored as a drug delivery system for chemo-photothermal synergistic therapy.
CMTM7 as a novel molecule of ATG14L-Beclin1-VPS34 complex enhances autophagy by Rab5 to regulate tumorigenicity
Authors: Liu Baocai , Lu Yinliang , Zhang Tingting , Yu Xinyue , Wang Qian , Chi Yunbo , Jin Shunzi , Cheng Guanghui
Published: July 2021

Background

CMTM7 is a tumor suppressor that positively regulates EGFR degradation by promoting Rab5 activation, and plays a vital role in tumor progression. Rab5 forms complexes with Beclin1 and VPS34, and acts in the early stage of autophagy. However, the affects of CMTM7 on autophagy and its mechanism are still unclear.

Methods

The effect of CMTM7 on autophagy induction was confirmed by western blotting, confocal microscopy and transmission electron microscopy. Co-immunoprecipitation was used to analyse the interaction of CMTM7 with autophagy initiation complex and Rab5. The xenograft model in nude mice was used to elucidate the function of CMTM7 in tumorigenicity and autophagy in vivo.

Results

In this study, we first demonstrated that CMTM7 facilitated the initiation of autophagosome formation, which consequently promoted the subsequent multistage process of autophagic flux, i.e. from autophagosome assembly till autolysosome formation and degradation. Confocal and co-immunoprecipitation showed that CMTM7 interacted with Rab5, VPS34, Beclin1, and ATG14L, but not with ULK1, UVRAG and LC3B. CMTM7 also increased the activity of ATG14L-linked VPS34 complex and its association with Rab5. Both in vitro and in vivo experiments demonstrated that knockdown of CMTM7 enhanced tumor growth by impairing autophagy.

Conclusion

These findings highlighted the role of CMTM7 in the regulation of autophagy and tumorigenicity, revealing it as a novel molecule that is associated with the interaction of Rab5 and ATG14L-Beclin1-VPS34 complex.
Model for in-vivo estimation of stiffness of tibiofemoral joint using MR imaging and FEM analysis
Authors: Jogi Sandeep Panwar , Thaha Rafeek , Rajan Sriram , Mahajan Vidur , Venugopal Vasantha Kumar , Singh Anup , Mehndiratta Amit
Published: July 2021

Background

Appropriate structural and material properties are essential for finite-element-modeling (FEM). In knee FEM, structural information could extract through 3D-imaging, but the individual subject’s tissue material properties are inaccessible.

Purpose

The current study's purpose was to develop a methodology to estimate the subject-specific stiffness of the tibiofemoral joint using finite-element-analysis (FEA) and MRI data of knee joint with and without load.

Methods

In this study, six Magnetic Resonance Imaging (MRI) datasets were acquired from 3 healthy volunteers with axially loaded and unloaded knee joint. The strain was computed from the tibiofemoral bone gap difference (ΔmBGFT) using the knee MR images with and without load. The knee FEM study was conducted using a subject-specific knee joint 3D-model and various soft-tissue stiffness values (1 to 50 MPa) to develop subject-specific stiffnessversusstrain models.

Results

Less than 1.02% absolute convergence error was observed during the simulation. Subject-specific combined stiffness of weight-bearing tibiofemoral soft-tissue was estimated with mean values as 2.40 ± 0.17 MPa. Intra-subject variability has been observed during the repeat scan in 3 subjects as 0.27, 0.12, and 0.15 MPa, respectively. All subject-specific stiffness-strain relationship data was fitted well with power function (R2 = 0.997).

Conclusion

The current study proposed a generalized mathematical model and a methodology to estimate subject-specific stiffness of the tibiofemoral joint for FEM analysis. Such a method might enhance the efficacy of FEM in implant design optimization and biomechanics for subject-specific studies.

Trial registrationThe institutional ethics committee (IEC), Indian Institute of Technology, Delhi, India, approved the study on 20th September 2017, with reference number P-019; it was a pilot study, no clinical trail registration was recommended.
Microglial responses to CSF1 overexpression do not promote the expansion of other glial lineages
Authors: De Ishani , Maklakova Vilena , Litscher Suzanne , Boyd Michelle M. , Klemm Lucas C. , Wang Ziyue , Kendziorski Christina , Collier Lara S.
Published: July 2021

Background

Colony-stimulating factor 1 (CSF1) expression in the central nervous system (CNS) increases in response to a variety of stimuli, and CSF1 is overexpressed in many CNS diseases. In young adult mice, we previously showed that CSF1 overexpression in the CNS caused the proliferation of IBA1+ microglia without promoting the expression of M2 polarization markers.

Methods

Immunohistochemical and molecular analyses were performed to further examine the impact of CSF1 overexpression on glia in both young and aged mice.

Results

As CSF1 overexpressing mice age, IBA1+ cell numbers are constrained by a decline in proliferation rate. Compared to controls, there were no differences in expression of the M2 markers ARG1 and MRC1 (CD206) in CSF1 overexpressing mice of any age, indicating that even prolonged exposure to increased CSF1 does not impact M2 polarization status in vivo. Moreover, RNA-sequencing confirmed the lack of increased expression of markers of M2 polarization in microglia exposed to CSF1 overexpression but did reveal changes in expression of other immune-related genes. Although treatment with inhibitors of the CSF1 receptor, CSF1R, has been shown to impact other glia, no increased expression of oligodendrocyte lineage or astrocyte markers was observed in CSF1 overexpressing mice.

Conclusions

Our study indicates that microglia are the primary glial lineage impacted by CSF1 overexpression in the CNS and that microglia ultimately adapt to the presence of the CSF1 mitogenic signal.
Case report of peritoneal carcinomatosis of plasma cell origin in a patient with newly diagnosed HIV: A terminal event
Authors: Sahra Syeda , Jahangir Abdullah , Anwar Muhammad Yasir , Glaser Allison , Jahangir Ahmad
Published: July 2021

Background

B-cell tumors and plasma cell malignancies have been identified in persons living with the human immunodeficiency virus (PLHIV). The literature review has revealed numerous reports of solitary plasmacytomas with metastasis in PLHIV.

Case report

A young patient with no prior medical or surgical history presented with tumor lysis syndrome secondary to metastatic plasma cell Epstein-Baer virus (EBV) related malignancy with peritoneal carcinomatosis. The history and clinical picture promptly led to the diagnosis of HIV. The subsequent hospital course was dismal, and lifespan was cut short by multi-organ failure.

Conclusion

This case is being reported to highlight the suspicion of HIV in patients presenting acutely with aggressive plasma cell malignancies.
Molecular detection and identification of Culex flavivirus in mosquito species from Jeju, Republic of Korea
Authors: Chatterjee Shilpa , Kim Choon-Mee , Yun Na Ra , Kim Dong-Min , Song Hyeon Je , Chung Kyeoung A
Published: July 2021

Background

Mosquito-borne flaviviruses are prime pathogens and have been a major hazard to humans and animals. They comprise several arthropod-borne viruses, including dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus.Culexflavivirus (CxFV) is a member of the insect-specific flavivirus (ISF) group belonging to the genusFlavivirus, which is widely distributed in a variety of mosquito populations.

Methods

Viral nucleic acid was extracted from adult mosquito pools and subjected to reverse transcriptase nested polymerase chain reaction (PCR) using target-specific primers for detecting CxFV nonstructural protein 5 (NS5). The PCR-positive samples were then sequenced, and a phylogenetic tree was constructed, including reference sequences obtained from GenBank.

Results

21 pools, belonging toCulex pipiens pallens(Cx. p. pallens)were found to be positive for the CxFV RNA sequence, with a minimum infection rate of 14.5/1000 mosquitoes. The phylogenetic analysis of the NS5 protein sequences indicated that the detected sequences were closely related to strains identified in China, with 95–98% sequence similarities.

Conclusion

Our findings highlight the presence of CxFV inCx. p. pallensmosquito species in Jeju province, Republic of Korea. This is the first study reporting the prevalence of CxFV inCulex Pipiens (Cx. pipiens)host in the Jeju province, which can create possible interaction with other flaviviruses causing human and animal diseases. Although, mosquito-borne disease causing viruses were not identified properly, more detailed surveillance and investigation of both the host and viruses are essential to understand the prevalence, evolutionary relationship and genetic characteristic with other species.
Maternal and child factors associated with timely initiation of breastfeeding in sub-Saharan Africa
Authors: Appiah Francis , Ahinkorah Bright Opoku , Budu Eugene , Oduro Joseph Kojo , Sambah Francis , Baatiema Linus , Ameyaw Edward Kwabena , Seidu Abdul-Aziz
Published: July 2021

Background

The probability of not breastfeeding within the first hour after delivery (timely initiation of breastfeeding) is particularly pronounced in sub-Saharan Africa. In this study, we examined the maternal and child factors associated with timely initiation of breastfeeding in sub-Saharan Africa.

Methods

We pooled data from 29 sub-Saharan African countries’ Demographic and Health Surveys conducted from 2010 to 2018. A total of 60,038 childbearing women were included. Frequencies, percentages, and binary logistic regression analyses were carried out. Binary logistic regression was used to examine the maternal and child factors associated with timely initiation of breastfeeding and the results were presented as adjusted odds ratios (aOR) at 95% confidence interval (CI). 

Results

We found a prevalence of 55.81% of timely initiation of breastfeeding in the sub-region. The country with the highest prevalence of timely initiation of breastfeeding was Burundi (86.19%), whereas Guinea had the lowest prevalence (15.17%). The likelihood of timely initiation of breastfeeding was lower among married women, compared to never married women (aOR 0.91; 95% CI 0.85, 0.98); working women compared to non-working women (aOR 0.90; 95% CI 0.87, 0.93); women who watched television at least once a week, compared to those who never watched television (aOR 0.74; 95% CI 0.70, 0.78); women who delivered through caesarean section, compared to vaginal birth (aOR 0.30; 95% CI 0.27, 0.32); and those with multiple births, compared to those with single births (aOR 0.67; 95% CI 0.59, 0.76). Women who lived in Central Africa were less likely to initiate breastfeeding timely compared to those who lived in West Africa (aOR 0.80; 95% CI 0.75, 0.84).

Conclusions

The findings call for the need for a behavioural change communication programmes, targeted at timely initiation of breastfeeding, to reverse and close the timely initiation of breastfeeding gaps stratified by the maternal and child factors. Prioritising policies to enhance timely initiation of breastfeeding is needed, particularly among Cental African countries where timely initiation of breastfeeding remains a challenge. Sufficient supportive care, especially for mothers with multiple births and those who undergo caesarean section, is needed to resolve timely initiation of breastfeeding inequalities.
The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives
Authors: Wang Jiaqi , Lu Shanshan , Yang Fuming , Guo Yi , Chen Zelin , Yu Nannan , Yao Lin , Huang Jin , Fan Wen , Xu Zhifang , Gong Yinan
Published: July 2021

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.
Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort
Authors: Tan Dandan , Ge Lin , Fan Yanbin , Chang Xingzhi , Wang Shuang , Wei Cuijie , Ding Juan , Liu Aijie , Wang Shuo , Li Xueying , Gao Kai , Yang Haipo , Que Chengli , Huang Zhen , Li Chunde , Zhu Ying , Mao Bing , Jin Bo , Hua Ying , Zhang Xiaoli , Zhang Bingbing , Zhu Wenhua , Zhang Cheng , Wang Yanjuan , Yuan Yun , Jiang Yuwu , Rutkowski Anne , Bönnemann Carsten G. , Wu Xiru , Xiong Hui
Published: July 2021

Background

LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy.

Methods

Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed.

Results

One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029).

Conclusions

This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.
Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment
Authors: Poleur Margaux , Ulinici Ana , Daron Aurore , Schneider Olivier , Farra Fabian Dal , Demonceau Marie , Annoussamy Mélanie , Vissière David , Eggenspieler Damien , Servais Laurent
Published: July 2021

Background

Normative data are necessary for validation of new outcome measures. Recently, the 95th centile of stride speed was qualified by the European Medicines Agency as a valid secondary outcome for clinical trials in subjects with Duchenne muscular dystrophy. This study aims to obtain normative data on spontaneous stride velocity and length in a non-controlled environment and their evolution after 12 months.

Method

Ninety-one healthy volunteers (50 females, 41 males), with a mean age of 16 years and 2 months, were recruited and assessed at baseline and 12 months later. The 4-stair climb, 6-min walk test, 10-m walk test and rise from floor assessments were performed. Stride length, stride velocity, and the distance walked per hour were studied in an everyday setting for one month after each evaluation.

Results

Of the 91 subjects assessed, 82 provided more than 50 h of recordings at baseline; and 73 subjects provided the same at the end of the year. We observed significant positive correlations of the stride length with age and height of participants, and a significant increase of the median stride length in children after the period. In this group, the 95th centile stride velocity was not correlated with age and was stable after one year. All measures but the 10MWT were stable in adults after a one-year period.

Conclusion

This study provides with data on the influence of age, height, and gender on stride velocity and length as well as accounting for natural changes after one year in controls.
Post-infection cognitive impairments in a cohort of elderly patients with COVID-19
Authors: Liu Yu-Hui , Wang Ye-Ran , Wang Qing-Hua , Chen Yang , Chen Xian , Li Ying , Cen Yuan , Xu Cheng , Hu Tian , Liu Xu-Dong , Yang Ling-Li , Li Si-Jing , Liu Xue-Fei , Liu Chun-Mei , Zhu Jie , Li Wei , Zhang Li-Li , Liu Juan , Wang Yan-Jiang
Published: July 2021

Background

Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.

Methods

This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.

Results

Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline.

Conclusions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.
Diagnostic evaluation and ablation treatments assessment in hepatocellular carcinoma
Authors: Granata Vincenza , Grassi Roberta , Fusco Roberta , Belli Andrea , Cutolo Carmen , Pradella Silvia , Grazzini Giulia , La Porta Michelearcangelo , Brunese Maria Chiara , De Muzio Federica , Ottaiano Alessandro , Avallone Antonio , Izzo Francesco , Petrillo Antonella
Published: July 2021

This article provides an overview of diagnostic evaluation and ablation treatment assessment in Hepatocellular Carcinoma (HCC). Only studies, in the English language from January 2010 to January 202, evaluating the diagnostic tools and assessment of ablative therapies in HCC patients were included. We found 173 clinical studies that satisfied the inclusion criteria.

HCC may be noninvasively diagnosed by imaging findings. Multiphase contrast-enhanced imaging is necessary to assess HCC. Intravenous extracellular contrast agents are used for CT, while the agents used for MRI may be extracellular or hepatobiliary. Both gadoxetate disodium and gadobenate dimeglumine may be used in hepatobiliary phase imaging. For treatment-naive patients undergoing CT, unenhanced imaging is optional; however, it is required in the post treatment setting for CT and all MRI studies. Late arterial phase is strongly preferred over early arterial phase. The choice of modality (CT, US/CEUS or MRI) and MRI contrast agent (extracelllar or hepatobiliary) depends on patient, institutional, and regional factors. MRI allows to link morfological and functional data in the HCC evaluation. Also, Radiomics is an emerging field in the assessment of HCC patients.

Postablation imaging is necessary to assess the treatment results, to monitor evolution of the ablated tissue over time, and to evaluate for complications. Post- thermal treatments, imaging should be performed at regularly scheduled intervals to assess treatment response and to evaluate for new lesions and potential complications.
Prehospital characteristics of COVID-19 patients in Helsinki – experience of the first wave of the pandemic
Authors: Kuisma Markku , Harve-Rytsälä Heini , Pirneskoski Jussi , Boyd James , Lääperi Mitja , Salo Ari , Puolakka Tuukka
Published: July 2021

Background

There is a lack of knowledge how patients with COVID-19 disease differ from patients with similar signs or symptoms (but who will have a diagnosis other than COVID-19) in the prehospital setting. The aim of this study was to compare the characteristics of these two patient groups met by the emergency medical services.

Methods

All prehospital patients after the World Health Organisation (WHO) pandemic declaration 11.3.2020 until 30.6.2020 were recruited for the study. The patients were screened using modified WHO criteria for suspected COVID-19. Data from the electronic prehospital patient reporting system were linked with hospital laboratory results to check the laboratory confirmation for COVID-19. For comparison, we divided the patients into two groups: screening- and laboratory-positive patients with a hospital diagnosis of COVID-19 and screening-positive but laboratory-negative patients who eventually received a different diagnosis in hospital.

Results

A total of 4157 prehospital patients fulfilled the criteria for suspected COVID-19 infection during the study period. Five-hundred-thirty-six (12.9%) of the suspected cases received a laboratory confirmation for COVID-19. The proportion of positive cases in relation to suspected ones peaked during the first 2 weeks after the declaration of the pandemic. In the comparison of laboratory-positive and laboratory-negative cases, there were clinically insignificant differences between the groups in age, tympanic temperature, systolic blood pressure, heart rate, on-scene time, urgency category of the call and mode of transportation. Foreign-language-speakers were overrepresented amongst the positive cases over native language speakers (26,6% vs. 7,4%,p < 0,001). The number of cases in which no signs or symptoms of COVID-19 disease were reported, but patients turned out to have a positive test result was 125 (0,3% of the whole EMS patient population and 11,9% of all verified COVID-19 patients encountered by the EMS).

Conclusions

In a sample of suspected COVID-19 patients, the laboratory-positive and laboratory-negative patients were clinically indistinguishable from each other during the prehospital assessment. Foreign-language-speakers had a high likelihood of having Covid-19. The modified WHO criteria still form the basis of screening of suspected COVID-19 patients in the prehospital setting.
Treatment of the lung injury of drowning: a systematic review
Authors: Thom Ogilvie , Roberts Kym , Devine Susan , Leggat Peter A. , Franklin Richard C.
Published: July 2021

Background

Drowning is a cause of significant global mortality. The mechanism of injury involves inhalation of water, lung injury and hypoxia. This systematic review addressed the following question: In drowning patients with lung injury, what is the evidence from primary studies regarding treatment strategies and subsequent patient outcomes?

Methods

The search strategy utilised PRISMA guidelines. Databases searched were MEDLINE, EMBASE, CINAHL, Web of Science and SCOPUS. There were no restrictions on publication date or age of participants. Quality of evidence was evaluated using GRADE methodology.

Results

Forty-one papers were included. The quality of evidence was very low. Seventeen papers addressed the lung injury of drowning in their research question and 24 had less specific research questions, however included relevant outcome data. There were 21 studies regarding extra-corporeal life support, 14 papers covering the theme of ventilation strategies, 14 addressed antibiotic use, seven papers addressed steroid use and five studies investigating diuretic use. There were no clinical trials. One retrospective comparison of therapeutic strategies was found. There was insufficient evidence to make recommendations as to best practice when supplemental oxygen alone is insufficient. Mechanical ventilation is associated with barotrauma in drowning patients, but the evidence predates the practice of lung protective ventilation. There was insufficient evidence to make recommendations regarding adjuvant therapies.

Conclusions

Treating the lung injury of drowning has a limited evidentiary basis. There is an urgent need for comparative studies of therapeutic strategies in drowning.
Haploflow: strain-resolved de novo assembly of viral genomes
Authors: Fritz Adrian , Bremges Andreas , Deng Zhi-Luo , Lesker Till Robin , Götting Jasper , Ganzenmueller Tina , Sczyrba Alexander , Dilthey Alexander , Klawonn Frank , McHardy Alice Carolyn
Published: July 2021

With viral infections, multiple related viral strains are often present due to coinfection or within-host evolution. We describe Haploflow, a deBruijn graph-based assembler for de novo genome assembly of viral strains from mixed sequence samples using a novel flow algorithm. We assess Haploflow across multiple benchmark data sets of increasing complexity, showing that Haploflow is faster and more accurate than viral haplotype assemblers and generic metagenome assemblers not aiming to reconstruct strains. We show Haploflow reconstructs viral strain genomes from patient HCMV samples and SARS-CoV-2 wastewater samples identical to clinical isolates.
Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial
Authors: Jensterle Mojca , Ferjan Simona , Battelino Tadej , Kovač Jernej , Battelino Saba , Šuput Dušan , Vovk Andrej , Janež Andrej
Published: July 2021

Background

Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown.

Methods and analysis

This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake.

Discussion

This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists.

Ethics and disseminations

The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal.

Trial registration

ClinicalTrials.govNCT04263415. Retrospectively registered on 10 February 2020
A two-step actin polymerization mechanism drives dendrite branching
Authors: Shi Rebecca , Kramer Daniel A. , Chen Baoyu , Shen Kang
Published: July 2021

Background

Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood.

Methods

We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP.

Results

We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth.

Conclusions

We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor.
An incidental finding of testicular seminoma in the context of acute pulmonary embolism: a case report
Authors: Mayne Kaitlin J. , Lewis Emma , Vickers Lewis
Published: July 2021

Background

Clinical guidelines do not recommend further investigation for occult malignancy in the scenario of unprovoked venous thromboembolism in the absence of additional clinical features suggestive of malignancy. We present the case of a young gentleman with pulmonary embolism who was diagnosed with testicular seminoma despite lack of symptoms or signs suggestive of malignancy. This is a unique case describing a scenario not well documented in existing literature where contravention of clinical guidelines had a potentially advantageous outcome for the patient.

Case presentation

A 37-year-old white male presented with seemingly unprovoked acute pulmonary embolism with right heart strain. He did not have any predisposing factors for venous thromboembolism and did not have any symptoms or signs suggestive of malignancy. Clinical guidelines do not recommend further investigation to screen for malignancy in this scenario. Despite this, our young, otherwise healthy patient proceeded to computed tomography scanning, resulting in the diagnosis of localized testicular seminoma. Testicular ultrasound described normal-sized testes (despite a discrete lesion in the right testis), suggesting this was not detectable by the patient or clinician on routine examination. The patient was anticoagulated and had an inferior vena cava filter inserted to facilitate orchidectomy followed by adjuvant radiotherapy.

Conclusions

This case highlights the importance of considering malignancy in seemingly unprovoked venous thromboembolism and the availability of guidelines to direct further investigation. Our patient’s treatment was not in line with clinical guidelines and was considered a “lucky find.”
A dedicated paediatric [18F]FDG PET/CT dosage regimen
Authors: Cox Christina P. W. , van Assema Daniëlle M. E. , Verburg Frederik A. , Brabander Tessa , Konijnenberg Mark , Segbers Marcel
Published: July 2021

Background

The role of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in children is still expanding. Dedicated paediatric dosage regimens are needed to keep the radiation dose as low as reasonably achievable and reduce the risk of radiation-induced carcinogenesis. The aim of this study is to investigate the relation between patient-dependent parameters and [18F]FDG PET image quality in order to propose a dedicated paediatric dose regimen.

Methods

In this retrospective analysis, 102 children and 85 adults were included that underwent a diagnostic [18F]FDG PET/CT scan. The image quality of the PET scans was measured by the signal-to-noise ratio (SNR) in the liver. The SNR liver was normalized (SNRnorm) for administered activity and acquisition time to apply curve fitting with body weight, body length, body mass index, body weight/body length and body surface area. Curve fitting was performed with two power fits, a nonlinear two-parameter model α p−d and a linear single-parameter model α p−0.5. The fit parameters of the preferred model were combined with a user preferred SNR to obtain at least moderate or good image quality for the dosage regimen proposal.

Results

Body weight demonstrated the highest coefficient of determination for the nonlinear (R2 = 0.81) and linear (R2 = 0.80) models. The nonlinear model was preferred by the Akaike’s corrected information criterion. We decided to use a SNR of 6.5, based on the expert opinion of three nuclear medicine physicians. Comparison with the quadratic adult protocol confirmed the need for different dosage regimens for both patient groups. In this study, the amount of administered activity can be considerably reduced in comparison with the current paediatric guidelines.

Conclusion

Body weight has the strongest relation with [18F]FDG PET image quality in children. The proposed nonlinear dosage regimen based on body mass will provide a constant and clinical sufficient image quality with a significant reduction of the effective dose compared to the current guidelines. A dedicated paediatric dosage regimen is necessary, as a universal dosing regimen for paediatric and adult is not feasible.
Differing susceptibility of C57BL/6J and DBA/2J mice—parents of the murine BXD family, to severe acute respiratory syndrome coronavirus infection
Authors: Li Kui , Shen Yang , Miller Mark A. , Stabenow Jennifer , Williams Robert W. , Lu Lu
Published: July 2021

The ongoing coronavirus disease-2019 (COVID-19) pandemic, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that is closely related to SARS-CoV, poses a grave threat to global health and has devastated societies worldwide. One puzzling aspect of COVID-19 is the impressive variation in disease manifestations among infected individuals, from a majority who are asymptomatic or exhibit mild symptoms to a smaller, largely age-dependent fraction who develop life-threatening conditions. Some of these differences are likely the consequence of host genetic factors. Systems genetics using diverse and replicable cohorts of isogenic mice represents a powerful way to dissect those host genetic differences that modulate microbial infections. Here we report that the two founders of the large BXD family of mice—C57BL/6J and DBA/2J, differ substantially in their susceptibility to a mouse-adapted SARS-CoV, MA15. Following intranasal viral challenge, DBA/2J develops a more severe disease than C57BL/6J as evidenced by more pronounced and sustained weight loss. Disease was accompanied by high levels of pulmonary viral replication in both strains early after infection but substantially delayed viral clearance in DBA/2J. Our data reveal that the parents of the BXD family are segregated by clear phenotypic differences during MA15 infection and support the feasibility of using this family to systemically dissect the complex virus-host interactions that modulate disease progression and outcome of infection with SARS-CoV, and provisionally also with SARS-CoV-2.
Robust hand gesture recognition using multiple shape-oriented visual cues
Authors: Bakheet Samy , Al-Hamadi Ayoub
Published: July 2021

Robust vision-based hand pose estimation is highly sought but still remains a challenging task, due to its inherent difficulty partially caused by self-occlusion among hand fingers. In this paper, an innovative framework for real-time static hand gesture recognition is introduced, based on an optimized shape representation build from multiple shape cues. The framework incorporates a specific module for hand pose estimation based on depth map data, where the hand silhouette is first extracted from the extremely detailed and accurate depth map captured by a time-of-flight (ToF) depth sensor. A hybrid multi-modal descriptor that integrates multiple affine-invariant boundary-based and region-based features is created from the hand silhouette to obtain a reliable and representative description of individual gestures. Finally, an ensemble of one-vs.-all support vector machines (SVMs) is independently trained on each of these learned feature representations to perform gesture classification. When evaluated on a publicly available dataset incorporating a relatively large and diverse collection of egocentric hand gestures, the approach yields encouraging results that agree very favorably with those reported in the literature, while maintaining real-time operation.
Implicit nonlinear fractional differential equations of variable order
Authors: Benkerrouche Amar , Souid Mohammed Said , Sitthithakerngkiet Kanokwan , Hakem Ali
Published: July 2021

In this manuscript, we examine both the existence and the stability of solutions to the implicit boundary value problem of Caputo fractional differential equations of variable order. We construct an example to illustrate the validity of the observed results.
Postoperative atrial fibrillation in paraesophageal hernia repair: can it be prevented?
Authors: Mardini Jennifer , Bruceta Melanio , Parrella-O’Donnell William , Karamchandani Kunal
Published: July 2021

Acute ischemic thromboembolic stroke is one of the most feared complications of atrial fibrillation (AF), and the risk increases with higher CHA2DS2-VASc scores. Postoperative atrial fibrillation (POAF) is common after noncardiac surgery, particularly after thoracic surgery, and can result in significant morbidity and mortality. We report the case of an 85-year-old female with a history of untreated hypertension (HTN) and no prior history of AF, who presented 5 days after an elective repair of a paraesophageal hernia with recurrence of a large type III paraesophageal hiatal hernia, AF, and subsequent acute thromboembolic ischemic stroke. Patient’s AF resolved shortly after treatment with calcium channel blocker. The risk of stroke is high in patients who develop AF and a period of 48 h after onset of AF is usually considered safe as the risk of stroke is low in this time period. However, this may not be the case during the perioperative period and preventive measures such as preoperative calcium channel blocker could be considered. Our case highlights that acute ischemic thromboembolic stroke might develop earlier tha 48 h after onset of POAF in patients undergoing paraesophageal hernia repair. Initiation of a calcium channel blocker should be considered during preoperative evaluation for patients undergoing paraesophageal hernia repairs, especially in those with untreated HTN.
A LC–ESI–MS/MS analysis procedure coupled with solid phase extraction and MeOH extraction method for determination of pyrrolizidine alkaloids in Tussilago farfara and Lithospermi erythrorhzion
Authors: Ko Kyung Yuk , Jeong Se Hee , Choi Eun Young , Lee Kyungjin , Hong Yongmin , Kang Il hyun , Cho Sooyeul , Lee Chulhyun
Published: July 2021

Pyrrolizidine alkaloids (PAs) that are plant toxin naturally produced for protection against herbivores in some plant families. They are associated with the potential hepatotoxic and carcinogenic diseases serious hepatic disease in humans and animals. As the concern of human health risk posed by exposure to PAs has been gradually increased, precise and reliable analysis is required for monitoring PAs. The present study developed a new and simple pretreatment using 50% MeOH (methanol) for quantification analysis of the PAs contained with high content in the herbal medicines. Another pretreatment method using cation-ion exchange solid-phase extraction (MCX-SPE) was employed for determining most of the PAs that are not contained in the herbal medicines. That is, the proposed LC–MS/MS method coupled with MCX-SPE extraction and 50% MeOH extraction method was developed. And to evaluate the reliability of its application for Farfarae Flos and Lithospermi Radix, a validation study was conducted. In addition, monitory study was performed with ten samples in each herbal medicine. As a result, the proposed method had good linearity with r2 ≥ 0.997. Also, the recoveries indicated to be in the ranges of 70.4–118.0% for the Farfarae Flos, 70.2–119.7% for the Lithospermi Radix. In two herbal medicines, the intra-day precision was revealed to satisfy the reference criteria in most of the PAs. In monitoring results, most of the PAs were not contained in two herbal medicines, whereas a part of PAs revealed to have high concentration in Farfarae Flos and Lithospermi Radix. The proposed method is considered as a simple and reliable method to quantify 28 PAs present in two herbal medicines. Especially, the simple MeOH extraction method seems to be available for quantification analysis of certain PAs in herbal medicines with high content.
Bta-miR-34b controls milk fat biosynthesis via the Akt/mTOR signaling pathway by targeting RAI14 in bovine mammary epithelial cells
Authors: Wang Yujuan , Wang Xiaoyu , Wang Meng , Zhang Li , Zan Linsen , Yang Wucai
Published: July 2021

Background

The biosynthesis of milk fat affects both the technological properties and organoleptic quality of milk and dairy products. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that inhibit the expression of their mRNA targets and are involved in downstream signaling pathways that control several biological processes, including milk fat synthesis. miR-34b is a member of the miR-34 miRNA cluster, which is differentially expressed in the mammary gland tissue of dairy cows during lactation and dry periods. Previous studies have indicated miR-34b is a potential candidate gene that plays a decisive role in regulating milk fat synthesis; therefore, it is important to focus on miR-34b and investigate its regulatory effect on the biosynthesis of milk fat in bovine mammary epithelial cells (BMECs).

Results

In this study, elevated miR-34b levels reduced milk fat synthesis, upregulated 1,999 genes, and downregulated 2,009 genes in BMECs. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes suggested that miR-34b may play an inhibitory role in milk fat synthesis via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway by reducing phosphorylation levels. Notably, the mTOR activator MHY1485 rescued the inhibitory effect of miR-34b. Furthermore, we demonstrated that retinoic acid-induced protein 14 (RAI14) is a target of miR-34b via TargetScan and immunofluorescence assays. RAI14 mRNA and protein levels were significantly decreased by the miR-34b mimic and increased by the miR-34b inhibitor. Moreover, the reduction in RAI14 levels led to the inhibition of the Akt/mTOR signaling pathway.

Conclusions

Overall, our results identified a miR-34b-RAI14-Akt/mTOR regulatory network, while also providing a theoretical basis for the molecular breeding of dairy cows.