bluuebunny/crossref_metadata_2025 huggingface dataset:
Vulnerability and agency across treatment-seeking journeys for acutely ill children: how family members navigate complex healthcare before, during and after hospitalisation in a rural Kenyan setting
Authors: Zakayo Scholastica M. , Njeru Rita W. , Sanga Gladys , Kimani Mary N. , Charo Anderson , Muraya Kui , Sarma Haribondhu , Uddin Md. Fakhar , Berkley James A. , Walson Judd L. , Kelley Maureen , Marsh Vicki , Molyneux Sassy
Published: August 2020

Background

Child mortality rates during hospitalisation for acute illness and after discharge are unacceptably high in many under-resourced settings. Childhood vulnerability to recurrent illness, and death, is linked to their families’ situations and ability to make choices and act (their agency). We examined vulnerability and agency across treatment-seeking journeys for acutely ill children and considered the implications for policy and practice.

Method

A qualitative sub-study was embedded within the prospective CHAIN Network cohort study, which is investigating mechanisms of inpatient and post-hospital discharge mortality among acutely ill young children across a spectrum of nutritional status. Primary data were collected from household members of 20 purposively selected cohort children over 18 months through formal interviews (total n = 74), complemented by informal discussions and observations. Data were analysed using narrative and thematic approaches.

Results

Treatment-seeking pathways were often long and complex, particularly for children diagnosed as severely malnourished. Family members’ stories reveal that children’s carers, usually mothers, navigate diverse challenges related to intersecting vulnerabilities at individual, household and facility levels. Specific challenges include the costs of treatment-seeking, confusing and conflicting messaging on appropriate care and nutrition, and poor continuity of care. Strong power inequities were observed between family members and health staff, with many mothers feeling blamed for their child’s condition. Caregivers’ agency, as demonstrated in decision-making and actions, often drew on the social support of others but was significantly constrained by their situation and broader structural drivers.

Conclusion

To support children’s care and recovery, health systems must be more responsive to the needs of families facing multiple and interacting vulnerabilities. Reducing incurred treatment costs, improving interpersonal quality of care, and strengthening continuity of care across facilities is essential. Promising interventions need to be co-designed with community representatives and health providers and carefully tested for unintended negative consequences and potential for sustainable scale-up.
ALKBH5 suppresses malignancy of hepatocellular carcinoma via m6A-guided epigenetic inhibition of LYPD1
Authors: Chen Yunhao , Zhao Yanchun , Chen Junru , Peng Chuanhui , Zhang Yanpeng , Tong Rongliang , Cheng Qiyang , Yang Beng , Feng Xiaode , Lu Yuejie , Xie Haiyang , Zhou Lin , Wu Jian , Zheng Shusen
Published: August 2020

Background

N6-methyladenosine (m6A) modification is an emerging layer of epigenetic regulation which is widely implicated in the tumorigenicity of hepatocellular carcinoma (HCC), offering a novel perspective for investigating molecular pathogenesis of this disease. The role of AlkB homolog 5 (ALKBH5), one of the m6A demethylases, has not been fully explored in HCC. Here we clarify the biological profile and potential mechanisms of ALKBH5 in HCC.

Methods

Expression of ALKBH5 and its correlation with clinicopathological characteristics of HCC were evaluated using tissue microarrays and online datasets. And biological effects of ALKBH5 in HCC were determined in vitro and in vivo. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq), and following m6A dot blot, MeRIP-qPCR, RIP-qPCR or dual luciferase reporter assays were employed to screen and validate the candidate targets of ALKBH5.

Results

We demonstrated that ALKBH5 was down-regulated in HCC, and decreased ALKBH5 expression was an independent prognostic factor of worse survival in HCC patients. Functionally, ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m6A demethylation led to a post-transcriptional inhibition of LY6/PLAUR Domain Containing 1 (LYPD1), which could be recognized and stabilized by the m6A effector IGF2BP1. In addition, we identified that LYPD1 induced oncogenic behaviors of tumors in contrast to ALKBH5. Dysregulation of ALKBH5/LYPD1 axis impelled the progression of HCC.

Conclusion

Our study reveals that ALKBH5, characterized as a tumor suppressor, attenuates the expression of LYPD1 via an m6A-dependent manner in HCC cells. Our findings enrich the landscape of m6A-modulated tumor malignancy, and provide new insights into potential biomarkers and therapeutic targets of HCC treatment.
Impact of HIV-1 Vpr manipulation of the DNA repair enzyme UNG2 on B lymphocyte class switch recombination
Authors: Eldin Patrick , Péron Sophie , Galashevskaya Anastasia , Denis-Lagache Nicolas , Cogné Michel , Slupphaug Geir , Briant Laurence
Published: August 2020

Background

HIV-1 Vpr encodes a 14 kDa protein that has been implicated in viral pathogenesis through modulation of several host cell functions. In addition to pro-apoptotic and cytostatic properties, Vpr can redirect cellular E3 ubiquitin ligases (such as DCAF1-Cul4A E3 ligase complex) to target many host proteins and interfere with their functions. Among them, Vpr binds the uracil DNA glycosylase UNG2, which controls genome uracilation, and induces its specific degradation leading to loss of uracil removal activity in infected cells. Considering the essential role of UNG2 in antibody diversification in B-cells, we evaluated the impact of Vpr on UNG2 fate in B lymphocytes and examined the functional consequences of UNG2 modulations on class switch recombination (CSR).

Methods

The impact of Vpr-induced UNG2 deregulation on CSR proficiency was evaluated by using virus-like particles able to deliver Vpr protein to target cells including the murine model CSR B cell line CH12F3 and mouse primary B-cells. Co-culture experiments were used to re-examine the ability of Vpr to be released by HIV-1 infected cells and to effectively accumulate in bystander B-cells. Vpr-mediated UNG2 modulations were monitored by following UNG2 protein abundance and uracil removal enzymatic activity.

Results

In this study we report the ability of Vpr to reduce immunoglobulin class switch recombination (CSR) in immortalized and primary mouse B-cells through the degradation of UNG2. We also emphasize that Vpr is released by producing cells and penetrates bystander B lymphocytes.

Conclusions

This work therefore opens up new perspectives to study alterations of the B-cell response by using Vpr as a specific CSR blocking tool. Moreover, our results raise the question of whether extracellular HIV-1 Vpr detected in some patients may manipulate the antibody diversification process that engineers an adapted response against pathogenic intruders and thereby contribute to the intrinsic B-cell humoral defect reported in infected patients.
Passive, yet not inactive: robotic exoskeleton walking increases cortical activation dependent on task
Authors: Peters Sue , Lim Shannon B. , Louie Dennis R. , Yang Chieh-ling , Eng Janice J.
Published: August 2020

Background

Experimental designs using surrogate gait-like movements, such as in functional magnetic resonance imaging (MRI), cannot fully capture the cortical activation associated with overground gait. Overground gait in a robotic exoskeleton may be an ideal tool to generate controlled sensorimotor stimulation of gait conditions like ‘active’ (i.e. user moves with the device) and ‘passive’ (i.e. user is moved by the device) gait. To truly understand these neural mechanisms, functional near-infrared spectroscopy (fNIRS) would yield greater ecological validity. Thus, the aim of this experiment was to use fNIRS to delineate brain activation differences between ‘Active’ and ‘Passive’ overground gait in a robotic exoskeleton.

Methods

Fourteen healthy adults performed 10 walking trials in a robotic exoskeleton for Passive and Active conditions, with fNIRS over bilateral frontal and parietal lobes, and electromyography (EMG) over bilateral thigh muscles. Digitization of optode locations and individual T1 MRI scans were used to demarcate the brain regions fNIRS recorded from.

Results

Increased oxyhemoglobin in the right frontal cortex was found for Passive compared with Active conditions. For deoxyhemoglobin, increased activation during Passive was found in the left frontal cortex and bilateral parietal cortices compared with Active; one channel in the left parietal cortex decreased during Active when compared with Passive. Normalized EMG mean amplitude was higher in the Active compared with Passive conditions for all four muscles (p ≤ 0.044), confirming participants produced the conditions asked of them.

Conclusions

The parietal cortex is active during passive robotic exoskeleton gait, a novel finding as research to date has not recorded posterior to the primary somatosensory cortex. Increased activation of the parietal cortex may be related to the planning of limb coordination while maintaining postural control. Future neurorehabilitation research could use fNIRS to examine whether exoskeletal gait training can increase gait-related brain activation with individuals unable to walk independently.
Feasibility and potential effects of using the electro-dress Mollii on spasticity and functioning in chronic stroke
Authors: Palmcrantz Susanne , Pennati Gaia Valentina , Bergling Hanna , Borg Jörgen
Published: August 2020

Background

Spasticity after lesions of central motor pathways may be disabling and there is a need for new, cost-effective treatment methods. One novel approach is offered by the electro-dress Mollii®, primarily designed to enhance reciprocal inhibition of spastic muscles by multifocal, transcutaneous antagonist stimulation.

Methods

The Mollii® suit was set individually for 20 participants living with spasticity and hemiplegia after stroke and used in the home setting for 6 weeks. Usability and perceived effects were monitored by weekly telephone interviews. Outcome was assessed by use of the NeuroFlexor™ method for quantification of the neural component (NC) of resistance to passive stretch (spasticity), and the modified Ashworth scale (MAS) for total resistance, Fugl-Meyer Assessment of motor recovery for sensorimotor function in upper (FM-UE) and lower extremities (FM-LE), activity performance with the Action Research Arm Test (ARAT), Berg balance scale, 10 m and 6 min walk tests, and perceived functioning with the Stroke Impact Scale.

Results

Compliance was high (mean 19.25 of 21 sessions). Perceived positive effects were reported by 60% and most commonly related to decreased muscle tone (n = 9), improved gait pattern function (n = 7) and voluntary movement in the upper extremity (n = 6). On a group level, the NC decreased significantly in the wrist flexors of the affected hand (p = 0.023) and significant improvements according to FM-UE (p = 0.000) and FM-LE (p = 0.003) were seen after the intervention. No significant difference was detected with MAS or assessed activity performance, except for the ARAT (p = 0.000). FM-UE score change correlated significantly and fairly with the perceived effect in the upper extremity (r0.498p = 0.025) and in the corresponding analysis for the FM-LE and perceived effect in the lower extremity (r = 0.469p = 0.037).

Conclusion

This study indicates that the Mollii® method is feasible when used in the home setting to decrease spasticity and improve sensorimotor function. The results may guide a larger controlled study combined with rehabilitation interventions to enhance effects on activity and participation domains.

Trial registration

NCT04076878. Registered 2 September 2019 - Retrospectively registered
Crystalline silica particles cause rapid NLRP3-dependent mitochondrial depolarization and DNA damage in airway epithelial cells
Authors: Wu Rongrong , Högberg Johan , Adner Mikael , Ramos-Ramírez Patricia , Stenius Ulla , Zheng Huiyuan
Published: August 2020

Background

Respirable crystalline silica causes lung carcinomas and many thousand future cancer cases are expected in e.g. Europe. Critical questions are how silica causes genotoxicity in the respiratory epithelium and if new cases can be avoided by lowered permissible exposure levels. In this study we investigate early DNA damaging effects of low doses of silica particles in respiratory epithelial cells in vitro and in vivo in an effort to understand low-dose carcinogenic effects of silica particles.

Results

We find DNA damage accumulation already after 5–10 min exposure to low doses (5 μg/cm2) of silica particles (Min-U-Sil 5) in vitro. DNA damage was documented as increased levels of γH2AX, pCHK2, by Comet assay, AIM2 induction, and by increased DNA repair (non-homologous end joining) signaling. The DNA damage response (DDR) was not related to increased ROS levels, but to a NLRP3-dependent mitochondrial depolarization. Particles in contact with the plasma membrane elicited a Ser198 phosphorylation of NLRP3, co-localization of NLRP3 to mitochondria and depolarization. FCCP, a mitochondrial uncoupler, as well as overexpressed NLRP3 mimicked the silica-induced depolarization and the DNA damage response. A single inhalation of 25 μg silica particles gave a similar rapid DDR in mouse lung. Biomarkers (CC10 and GPRC5A) indicated an involvement of respiratory epithelial cells.

Conclusions

Our findings demonstrate a novel mode of action (MOA) for silica-induced DNA damage and mutagenic double strand breaks in airway epithelial cells. This MOA seems independent of particle uptake and of an involvement of macrophages. Our study might help defining models for estimating exposure levels without DNA damaging effects.
SILEX: a fast and inexpensive high-quality DNA extraction method suitable for multiple sequencing platforms and recalcitrant plant species
Authors: Vilanova Santiago , Alonso David , Gramazio Pietro , Plazas Mariola , García-Fortea Edgar , Ferrante Paola , Schmidt Maximilian , Díez María José , Usadel Björn , Giuliano Giovanni , Prohens Jaime
Published: August 2020

Background

The use of sequencing and genotyping platforms has undergone dramatic improvements, enabling the generation of a wealth of genomic information. Despite this progress, the availability of high-quality genomic DNA (gDNA) in sufficient concentrations is often a main limitation, especially for third-generation sequencing platforms. A variety of DNA extraction methods and commercial kits are available. However, many of these are costly and frequently give either low yield or low-quality DNA, inappropriate for next generation sequencing (NGS) platforms. Here, we describe a fast and inexpensive DNA extraction method (SILEX) applicable to a wide range of plant species and tissues.

Results

SILEX is a high-throughput DNA extraction protocol, based on the standard CTAB method with a DNA silica matrix recovery, which allows obtaining NGS-quality high molecular weight genomic plant DNA free of inhibitory compounds. SILEX was compared with a standard CTAB extraction protocol and a common commercial extraction kit in a variety of species, including recalcitrant ones, from different families. In comparison with the other methods, SILEX yielded DNA in higher concentrations and of higher quality. Manual extraction of 48 samples can be done in 96 min by one person at a cost of 0.12 €/sample of reagents and consumables. Hundreds of tomato gDNA samples obtained with either SILEX or the commercial kit were successfully genotyped with Single Primer Enrichment Technology (SPET) with the Illumina HiSeq 2500 platform. Furthermore, DNA extracted fromSolanum elaeagnifoliumusing this protocol was assessed by Pulsed-field gel electrophoresis (PFGE), obtaining a suitable size ranges for most sequencing platforms that required high-molecular-weight DNA such as Nanopore or PacBio.

Conclusions

A high-throughput, fast and inexpensive DNA extraction protocol was developed and validated for a wide variety of plants and tissues. SILEX offers an easy, scalable, efficient and inexpensive way to extract DNA for various next-generation sequencing applications including SPET and Nanopore among others.
Preoperative anterior coverage of the medial acetabulum can predict postoperative anterior coverage and range of motion after periacetabular osteotomy: a cohort study
Authors: Hayashi Shinya , Hashimoto Shingo , Matsumoto Tomoyuki , Takayama Koji , Kamenaga Tomoyuki , Niikura Takahiro , Kuroda Ryosuke
Published: August 2020

Background

We hypothesized that preoperative pelvic morphology may affect postoperative anterior coverage and postoperative clinical range of motion (ROM) leading to postoperative pincer type femoroacetabular impingement (FAI). The aim of this study was to evaluate the relationships between preoperative bone morphology and postoperative ROMs to prevent postoperative FAI after periacetabular osteotomy.

Methods

Sixty-eight patients (71 hips) with hip dysplasia participated in this study and underwent curved PAO. The acetabular fragment was usually moved only by lateral rotation of the acetabulum, without intraoperative anterior or posterior rotation. The pre- and postoperative three-dimensional center-edge (CE) angles were measured and compared to the postoperative ROM.

Results

Preoperative medial anterior CE angle was significantly associated with postoperative anterior CE angle, and the correlation coefficient of medial anterior CE and postoperative anterior CE was higher than the coefficient of preoperative anterior CE and postoperative anterior CE (preoperative anterior CE, rr = 0.27,p= 0.020; preoperative medial anterior CE, rr = 0.54,p< 0.001). Femoral anteversion correlated with postoperative internal rotation angle at 90° flexion (r= 0.32,p= 0.021). In multiple linear regressions, postoperative internal rotation angle at 90° flexion angle was significantly affected by both medial CE angle through the medial one fourth of femoral head and femoral anteversion.

Conclusions

Preoperative medial anterior acetabular coverage was associated with postoperative anterior acetabular coverage. Further, the combination with preoperative medial anterior acetabular coverage and femoral anteversion can predict postoperative internal rotation at 90° flexion. Therefore, the direction of acetabular reorientation should be carefully considered when the patients have high preoperative medial anterior CE angle and small femoral anteversion.
Composition and function of rhizosphere microbiome of Panax notoginseng with discrepant yields
Authors: Li Mengzhi , Chen Zhongjian , Qian Jun , Wei Fugang , Zhang Guozhuang , Wang Yong , Wei Guangfei , Hu Zhigang , Dong Linlin , Chen Shilin
Published: August 2020

Background

Panax notoginseng is a highly valuable medicinal plant. Reduced P. notoginseng yield is a common and serious problem that arises in a continuous cropping system. Variation in the composition and function of soil microbial community is considered the primary cause of yield reduction.

Methods

This study used shotgun metagenomic sequencing approaches to describe the taxonomic and functional features of P. notoginseng rhizosphere microbiome and screen microbial taxa and functional traits related to yields.

Results

At the family and genus level, a total of 43 families and 45 genera (relative abundance > 0.1%) were obtained, and the correlation with the yield of P. notoginseng was further analyzed. Nitrosomonadaceae, Xanthomonadaceae, Mycobacterium and Arthrobacter that were enriched in soils with higher yields were positively correlated with P. notoginseng yields, thereby suggesting that they might increase yields. Negative correlation coefficients indicated that Xanthobacteraceae, Caulobacteraceae, Oxalobacteraceae, Chitinophagaceae, Sphingomonas, Hyphomicrobium, Variovorax and Phenylobacterium might be detrimental to P. notoginseng growth. A total of 85 functional traits were significantly (P < 0.05) correlated with P. notoginseng yields. Functional traits, likely steroid biosynthesis and MAPK signaling pathway were positively correlated with P. notoginseng yields. In contrast, functional traits, such as bacterial secretion system, ABC transporters, metabolism of xenobiotics by cytochrome P450 and drug metabolism–cytochrome P450, were negatively associated with yields.

Conclusions

This study describes an overview of the rhizosphere microbiome of P. notoginseng with discrepant yields and identifies the taxa and functional traits related to yields. Our results provide valuable information to guide the isolation and culture of potentially beneficial microorganisms and to utilize the power of the microbiome to increase plant yields in a continuous cropping system.
Using the GHQ-12 to screen for mental health problems among primary care patients: psychometrics and practical considerations
Authors: Anjara S. G. , Bonetto C. , Van Bortel T. , Brayne C.
Published: August 2020

Background

This study explores the factor structure of the Indonesian version of the GHQ-12 based on several theoretical perspectives and determines the threshold for optimum sensitivity and specificity. Through a focus group discussion, we evaluate the practicality of the GHQ-12 as a screening tool for mental health problems among adult primary care patients in Indonesia.

Methods

This is a prospective study exploring the construct validity, criterion validity and reliability of the GHQ-12, conducted with 676 primary care patients attending 28 primary care clinics randomised for participation in the study. Participants’ GHQ-12 scores were compared with their psychiatric diagnosis based on face-to-face clinical interviews with GPs using the CIS-R. Exploratory and Confirmatory Factor Analyses determined the construct validity of the GHQ-12 in this population. The appropriate threshold score of the GHQ-12 as a screening tool in primary care was determined using the receiver operating curve. Prior to data collection, a focus group discussion was held with research assistants who piloted the screening procedure, GPs, and a psychiatrist, to evaluate the practicality of embedding screening within the routine clinic procedures.

Results

Of all primary care patients attending the clinics during the recruitment period, 26.7% agreed to participate (676/2532 consecutive patients approached). Their median age was 46 (range 18–82 years); 67% were women. The median GHQ-12 score for our primary care sample was 2, with an interquartile range of 4. The internal consistency of the GHQ-12 was good (Cronbach’s α = 0.76). Four factor structures were fitted on the data. The GHQ-12 was found to best fit a one-dimensional model, when response bias is taken into consideration. Results from the ROC curve indicated that the GHQ-12 is ‘fairly accurate’ when discriminating primary care patients with indication of mental disorders from those without, with average AUC of 0.78. The optimal threshold of the GHQ-12 was either 1/2 or 2/3 point depending on the intended utility, with a Positive Predictive Value of 0.68 to 0.73 respectively. The screening procedure was successfully embedded into routine patient flow in the 28 clinics.

Conclusions

The Indonesian version of the GHQ-12 could be used to screen primary care patients at high risk of mental disorders although with significant false positives if reasonable sensitivity is to be achieved. While it involves additional administrative burden, screening may help identify future users of mental health services in primary care that the country is currently expanding.
The IL1β-IL1R signaling is involved in the stimulatory effects triggered by hypoxia in breast cancer cells and cancer-associated fibroblasts (CAFs)
Authors: Lappano Rosamaria , Talia Marianna , Cirillo Francesca , Rigiracciolo Damiano Cosimo , Scordamaglia Domenica , Guzzi Rita , Miglietta Anna Maria , De Francesco Ernestina Marianna , Belfiore Antonino , Sims Andrew H. , Maggiolini Marcello
Published: August 2020

Background

Hypoxia plays a relevant role in tumor-related inflammation toward the metastatic spread and cancer aggressiveness. The pro-inflammatory cytokine interleukin-1β (IL-β) and its cognate receptor IL1R1 contribute to the initiation and progression of breast cancer determining pro-tumorigenic inflammatory responses. The transcriptional target of the hypoxia inducible factor-1α (HIF-1α) namely the G protein estrogen receptor (GPER) mediates a feedforward loop coupling IL-1β induction by breast cancer-associated fibroblasts (CAFs) to IL1R1 expression by breast cancer cells toward the regulation of target genes and relevant biological responses.

Methods

In order to ascertain the correlation of IL-β with HIF-1α and further hypoxia-related genes in triple-negative breast cancer (TNBC) patients, a bioinformatics analysis was performed using the information provided by The Invasive Breast Cancer Cohort of The Cancer Genome Atlas (TCGA) project and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets. Gene expression correlation, statistical analysis and gene set enrichment analysis (GSEA) were carried out with R studio packages. Pathway enrichment analysis was evaluated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. TNBC cells and primary CAFs were used as model system. The molecular mechanisms implicated in the regulation of IL-1β by hypoxia toward a metastatic gene expression profile and invasive properties were assessed performing gene and protein expression studies, PCR arrays, gene silencing and immunofluorescence analysis, co-immunoprecipitation and ChiP assays, ELISA, cell spreading, invasion and spheroid formation.

Results

We first determined that IL-1β expression correlates with the levels of HIF-1α as well as with a hypoxia-related gene signature in TNBC patients. Next, we demonstrated that hypoxia triggers a functional liaison among HIF-1α, GPER and the IL-1β/IL1R1 signaling toward a metastatic gene signature and a feed-forward loop of IL-1β that leads to proliferative and invasive responses in TNBC cells. Furthermore, we found that the IL-1β released in the conditioned medium of TNBC cells exposed to hypoxic conditions promotes an invasive phenotype of CAFs.

Conclusions

Our data shed new light on the role of hypoxia in the activation of the IL-1β/IL1R1 signaling, which in turn triggers aggressive features in both TNBC cells and CAFs. Hence, our findings provide novel evidence regarding the mechanisms through which the hypoxic tumor microenvironment may contribute to breast cancer progression and suggest further targets useful in more comprehensive therapeutic strategies.
Is prehospital use of active external warming dangerous for patients with accidental hypothermia: a systematic review
Authors: Mydske Sigurd , Thomassen Øyvind
Published: August 2020

Background

Optimal prehospital management and treatment of patients with accidental hypothermia is a matter of frequent debate, with controversies usually revolving around the subject of rewarming. The rule of thumb in primary emergency care and first aid for patients with accidental hypothermia has traditionally been to be refrain from prehospital active rewarming and to focus on preventing further heat loss. The potential danger of active external rewarming in a prehospital setting has previously been generally accepted among the emergency medicine community based on a fear of potential complications, such as “afterdrop”, “rewarming syndrome”, and “circum-rescue collapse”. This has led to a reluctancy from health care providers to provide patients with active external rewarming outside the hospital. Different theories and hypotheses exist for these physiological phenomena, but the scientific evidence is limited. The research question is whether the prehospital use of active external rewarming is dangerous for patients with accidental hypothermia. This systematic review intends to describe the acute unfavourable adverse effects of active external rewarming on patients with accidental hypothermia.

Methods

A literature search of the Cochrane Library, MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL], and SveMed+ was carried out, and all articles were screened for eligibility. All article formats were included.

Results

Two thousand three hundred two articles were screened, and eight articles met our search criteria. Three articles were case reports or case series, one was a prospective study, two were retrospective studies, one article was a literature review, and one article was a war report from the Napoleonic Wars.

Conclusions

One of the main findings in this article was the poor scientific quality and the low number of articles meeting our inclusion criteria. When conducting this review, we found no scientific evidence of acceptable quality to prove that the use of active external rewarming is dangerous for patients with accidental hypothermia in a prehospital setting. We found several articles claiming that active external rewarming is dangerous, but most of them do not cite references or provide evidence.
Retrospective review of outcomes in patients with DNA-damage repair related pancreatic cancer
Authors: Macklin-Mantia Sarah K. , Hines Stephanie L. , Kasi Pashtoon M.
Published: August 2020

Background

Patients with DNA-damage response genes (DDR)-related pancreas cancer (BRCA1/2 or other DNA-damage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). However, data is scarce pertaining to outcomes in this subset of patients. Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes.

Methods

Pancreas cancer patients with a germline pathogenic variant in BRCA1/2 or other DDR gene were identified retrospectively through review of medical records (medical genetics/oncology) and genetic testing results at our institution. Data regarding clinical outcomes, therapy received, and survival was subsequently extracted.

Results

A total of 11 patients with pancreas cancer were identified to carry a pathogenic DDR-variant: BRCA1 (3), ATM (4), BRCA2 (2), PALB2 (1) and FANCC (1). Five of these individuals had prior history of other cancers. Clinically these tumors were localized (4), locally advanced (3), and metastatic (4) at diagnosis. Four out of 11 patients were still alive at time of data review. Survival in the 7 patients who had died was 13.7, 140.0, 20.5, 22.3, 23.5, 25.8, and 111.5 months. All patients with advanced disease had exposure to platinum chemotherapy.

Conclusions

Historical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors.
A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection
Authors: Cruces Pablo , Retamal Jaime , Hurtado Daniel E. , Erranz Benjamín , Iturrieta Pablo , González Carlos , Díaz Franco
Published: August 2020

Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.

In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.
The asynchronous establishment of chromatin 3D architecture between in vitro fertilized and uniparental preimplantation pig embryos
Authors: Li Feifei , Wang Danyang , Song Ruigao , Cao Chunwei , Zhang Zhihua , Wang Yu , Li Xiaoli , Huang Jiaojiao , Liu Qiang , Hou Naipeng , Xu Bingxiang , Li Xiao , Gao Xiaomeng , Jia Yan , Zhao Jianguo , Wang Yanfang
Published: August 2020

Background

Pigs are important animals for agricultural and biomedical research, and improvement is needed for use of the assisted reproductive technologies. Determining underlying mechanisms of epigenetic reprogramming in the early stage of preimplantation embryos derived from in vitro fertilization (IVF), parthenogenesis, and androgenesis will not only contribute to assisted reproductive technologies of pigs but also will shed light into early human development. However, the reprogramming of three-dimensional architecture of chromatin in this process in pigs is poorly understood.

Results

We generate three-dimensional chromatin profiles for pig somatic cells, IVF, parthenogenesis, and androgenesis preimplantation embryos. We find that the chromosomes in the pig preimplantation embryos are enriched for superdomains, which are more rare in mice. However, p(s) curves, compartments, and topologically associated domains (TADs) are largely conserved in somatic cells and are gradually established during preimplantation embryogenesis in both mammals. In the uniparental pig embryos, the establishment of chromatin architecture is highly asynchronized at all levels from IVF embryos, and a remarkably strong decompartmentalization is observed during zygotic genome activation (ZGA). Finally, chromosomes originating from oocytes always establish TADs faster than chromosomes originating from sperm, both before and during ZGA.

Conclusions

Our data highlight a potential unique 3D chromatin pattern of enriched superdomains in pig preimplantation embryos, an unusual decompartmentalization process during ZGA in the uniparental embryos, and an asynchronized TAD reprogramming between maternal and paternal genomes, implying a severe dysregulation of ZGA in the uniparental embryos in pigs.
ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium
Authors: Nakatsuka Nathan , Harney Éadaoin , Mallick Swapan , Mah Matthew , Patterson Nick , Reich David
Published: August 2020

We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors: for example, less than 1.5% standard error in cases with less than 10% contamination and 500,000 sequences covering SNPs. This method is optimized for application to aDNA, taking advantage of characteristic aDNA damage patterns to provide calibrated contamination estimates, and is available at https://github.com/nathan-nakatsuka/ContamLD.
Recruitment and retention of mothers of preschoolers and school-aged children in a social media-delivered healthy eating intervention: lessons learned from a randomized controlled trial
Authors: Dumas Audrée-Anne , Lemieux Simone , Lapointe Annie , Provencher Véronique , Robitaille Julie , Desroches Sophie
Published: August 2020

Background

Social media represent cost-effective platforms to advance the dissemination and uptake of health research to improve population health. However, there is limited evidence available to support researchers overcome methodological challenges related to recruitment and retention of participants in studies using social media for delivering behavior change interventions. This study aims to describe the recruitment and the retention strategies used in a randomized controlled trial (RCT) that evaluated a blog-delivered healthy eating intervention among mothers of preschoolers and school-aged children.

Methods

Eighty-four adult mothers of children aged between two and 12 years old living in Quebec City, Quebec, Canada, were recruited between October 2015 and February 2017 using traditional methods (e.g. institutional email lists, flyers, newspapers, and word of mouth) and Facebook advertisements. Retention rates were calculated at the end of the 6-month intervention and at a 12-month follow-up assessment. Sociodemographic characteristics, Internet use behaviors and retention rates of mothers recruited through traditional methods and Facebook were compared using Wilcoxon-Mann-Whitney tests and Fisher exact tests.

Results

Of the 196 mothers who responded to the recruitment call, 87 (44.4%) were eligible and 84 (42.9%) were randomized to the trial, representing a recruitment success of 76.4% (84/110) from the planned sample size target. Among those, a minority (3.6%) were recruited using Facebook. Those mothers presented similar sociodemographic characteristics to those recruited using traditional methods. Retention rates were 73.8% and 66.7% at 6 and 12 months, respectively, with similar rates between mothers recruited using Facebook and traditional methods. Various challenges associated with population retention were highlighted with lack of time being mothers’ main reason for withdrawing from the study.

Conclusions

The methodological challenges experienced during the conduct of the blog-delivered healthy eating intervention allowed to draw upon several lessons regarding the recruitment process and the retention of mothers of preschoolers and school-aged children to inform future social media-delivered research. Recommendations for future research include exploring mothers’ perceptions and preferences to tailor social media recruitment, ensure that interventions are delivered to them using social media platforms that are already integrated into their routine, and are providing remote outcome assessments to increase participant retention.

Trial registration

Clinical Trial Protocol NCT03156803. Registered on 17 May 2017, retrospectively registered.
A new synergistic relationship between xylan-active LPMO and xylobiohydrolase to tackle recalcitrant xylan
Authors: Zerva Anastasia , Pentari Christina , Grisel Sacha , Berrin Jean-Guy , Topakas Evangelos
Published: August 2020

Background

Hemicellulose accounts for a significant part of plant biomass, and still poses a barrier to the efficient saccharification of lignocellulose. The recalcitrant part of hemicellulose is a serious impediment to the action of cellulases, despite the use of xylanases in the cellulolytic cocktail mixtures. However, the complexity and variety of hemicelluloses in different plant materials require the use of highly specific enzymes for a complete breakdown. Over the last few years, new fungal enzymes with novel activities on hemicelluloses have emerged. In the present study, we explored the synergistic relationships of the xylan-active AA14 lytic polysaccharide monooxygenase (LPMO), PcAA14B, with the recently discovered glucuronoxylan-specific xylanase TtXyn30A, of the (sub)family GH30_7, displaying xylobiohydrolase activity, and with commercial cellobiohydrolases, on pretreated natural lignocellulosic substrates.

Results

PcAA14B and TtXyn30A showed a strong synergistic interaction on the degradation of the recalcitrant part of xylan. PcAA14B was able to increase the release of xylobiose from TtXyn30A, showing a degree of synergism (DS) of 3.8 on birchwood cellulosic fibers, and up to 5.7 on pretreated beechwood substrates. The increase in activity was dose- and time- dependent. A screening study on beechwood materials pretreated with different methods showed that the effect of the PcAA14B–TtXyn30A synergism was more prominent on substrates with low hemicellulose content, indicating that PcAA14B is mainly active on the recalcitrant part of xylan, which is in close proximity to the underlying cellulose fibers. Simultaneous addition of both enzymes resulted in higher DS than sequential addition. Moreover, PcAA14B was found to enhance cellobiose release from cellobiohydrolases during hydrolysis of pretreated lignocellulosic substrates, as well as microcrystalline cellulose.

Conclusions

The results of the present study revealed a new synergistic relationship not only among two recently discovered xylan-active enzymes, the LPMO PcAA14B, and the GH30_7 glucuronoxylan-active xylobiohydrolase TtXyn30A, but also among PcAA14B and cellobiohydrolases. We hypothesize that PcAA14B creates free ends in the xylan polymer, which can be used as targets for the action of TtXyn30A. The results are of special importance for the design of next-generation enzymatic cocktails, able to efficiently remove hemicelluloses, allowing complete saccharification of cellulose in plant biomass.
Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice
Authors: Jhan Kai-Yuan , Lai Guan-Jhih , Chang Pi-Kai , Tang Ren-Yu , Cheng Chien-Ju , Chen Kuang-Yao , Wang Lian-Chen
Published: August 2020

Background

Parasitic infections may cause significant effects on behavior, learning, and memory of the host. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damage has been observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in humans and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite.

Methods

Each mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively.

Results

The worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice from day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice from day 13 and day 12, respectively with corresponding changes in their dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice which occurred from day 14 post-infection.

Conclusions

Results of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice.
Climate and tree seed production predict the abundance of the European Lyme disease vector over a 15-year period
Authors: Bregnard Cindy , Rais Olivier , Voordouw Maarten Jeroen
Published: August 2020

Background

To predict the risk of tick-borne disease, it is critical to understand the ecological factors that determine the abundance of ticks. In Europe, the sheep tick (Ixodes ricinus) transmits a number of important diseases including Lyme borreliosis. The aim of this long-term study was to determine the abiotic and biotic factors driving the annual abundance of I. ricinus at a location in Switzerland where Lyme borreliosis is endemic.

Methods

Over a 15-year period (2004 to 2018), we monitored the abundance of I. ricinus ticks on a monthly basis at three different elevations on Chaumont Mountain in Neuchâtel, Switzerland. We collected climate variables in the field and from nearby weather stations. We obtained data on beech tree seed production from the literature, as the abundance of Ixodes nymphs can increase dramatically two years after a masting event. We used AIC-based model selection to determine which ecological variables drive annual variation in tick density.

Results

We found that elevation site, year, seed production by beech trees two years prior, and mean annual relative humidity together explained 73.2% of the variation in our annual estimates of nymph density. According to the parameter estimates of our models, (i) the annual density of nymphs almost doubled over the 15-year study period, (ii) changing the beech tree seed production index from very poor mast (1) to full mast (5) increased the abundance of nymphs by 86.2% two years later, and (iii) increasing the field-collected mean annual relative humidity from 50.0 to 75.0% decreased the abundance of nymphs by 46.4% in the same year. Climate variables collected in the field were better predictors of tick abundance than those from nearby weather stations indicating the importance of the microhabitat.

Conclusions

From a public health perspective, the increase in nymph abundance is likely to have increased the risk of tick-borne disease in this region of Switzerland. Public health officials in Europe should be aware that seed production by deciduous trees is a critical driver of the abundance of I. ricinus, and hence the risk of tick-borne disease.
Coronavirus in cat flea: findings and questions regarding COVID-19
Authors: Villar Margarita , Fernández de Mera Isabel G. , Artigas-Jerónimo Sara , Contreras Marinela , Gortázar Christian , de la Fuente José
Published: August 2020

The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Recent evidence raised the question about the possibility that cats may be a domestic host for SARS-CoV-2 with unknown implications in disease dissemination. Based on the fact that the domestic cat flea, Ctenocephalides felis, are abundant ectoparasites infesting humans, companion animals and wildlife and that coronavirus-like agents have been identified in the ectoparasite tick vector, Ixodes uriae of seabirds, herein we considered the presence of coronaviruses in general and SARS-CoV-2 in particular in C. felis. We identified coronavirus-derived and cell receptor angiotensin-converting enzyme RNA/proteins in C. felis. Although current evidence suggests that pets are probably dead-end-hosts with small risk of transmission to humans, our results suggested that cat flea may act as biological and/or mechanical vectors of SARS-CoV. Although preliminary, these results indicate a possibility of ectoparasites acting as reservoirs and vectors of SARS-CoV and related beta-coronavirus although with little disease risk due to systemic transmission route, low viremia, virus attenuation or other unknown factors. These results support the need to further study the role of animal SARS-CoV-2 hosts and their ectoparasite vectors in COVID-19 disease spread.