bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly
Authors: Karcher Nicolai , Nigro Eleonora , Punčochář Michal , Blanco-Míguez Aitor , Ciciani Matteo , Manghi Paolo , Zolfo Moreno , Cumbo Fabio , Manara Serena , Golzato Davide , Cereseto Anna , Arumugam Manimozhiyan , Bui Thi Phuong Nam , Tytgat Hanne L. P. , Valles-Colomer Mireia , de Vos Willem M. , Segata Nicola 
Published: July 2021

Abstract
Background
Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.

Results
We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.

Conclusions
We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.
DeepProg: an ensemble of deep-learning and machine-learning models for prognosis prediction using multi-omics data
Authors: Poirion Olivier B. , Jing Zheng , Chaudhary Kumardeep , Huang Sijia , Garmire Lana X. 
Published: July 2021

AbstractMulti-omics data are good resources for prognosis and survival prediction; however, these are difficult to integrate computationally. We introduce DeepProg, a novel ensemble framework of deep-learning and machine-learning approaches that robustly predicts patient survival subtypes using multi-omics data. It identifies two optimal survival subtypes in most cancers and yields significantly better risk-stratification than other multi-omics integration methods. DeepProg is highly predictive, exemplified by two liver cancer (C-index 0.73–0.80) and five breast cancer datasets (C-index 0.68–0.73). Pan-cancer analysis associates common genomic signatures in poor survival subtypes with extracellular matrix modeling, immune deregulation, and mitosis processes. DeepProg is freely available at https://github.com/lanagarmire/DeepProg
Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma
Authors: Meiller Clément , Montagne François , Hirsch Theo Z. , Caruso Stefano , de Wolf Julien , Bayard Quentin , Assié Jean-Baptiste , Meunier Léa , Blum Yuna , Quetel Lisa , Gibault Laure , Pintilie Ecaterina , Badoual Cécile , Humez Sarah , Galateau-Sallé Françoise , Copin Marie-Christine , Letouzé Eric , Scherpereel Arnaud , Zucman-Rossi Jessica , Le Pimpec-Barthes Françoise , Jaurand Marie-Claude , Jean Didier 
Published: July 2021

Abstract
Background
Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples.

Methods
Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic, or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed.

Results
Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed the contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment, were observed and led to a switch from a hot to a cold immune profile in three patients.

Conclusions
This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic, and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support the need for multi-sampling for the implementation of molecular-based precision medicine.
Imaging of gallbladder metastasis
Authors: Cocco Giulio , Delli Pizzi Andrea , Basilico Raffaella , Fabiani Stefano , Taraschi Alessio Lino , Pascucci Luca , Boccatonda Andrea , Catalano Orlando , Schiavone Cosima 
Published: July 2021

AbstractGallbladder metastasis (GM) is a rare condition, often with a late diagnosis or detected upon autopsy. There is no extensive literature on the imaging diagnosis of GM. Here we present a comprehensive review of the literature with the aim of helping to interpret the clinical findings and imaging features of such patients. Few studies on GM are reported in literature. GM by melanoma accounts for about 55.6% of cases. The remaining cases origin from breast cancer (13.6%), hepatocellular carcinoma (13.6%), renal cell carcinoma (6.8%), lung cancer (4.5%), lymphoma (3.5%) and gastric cancer (2.4%). The most common clinical presentation of GM is abdominal pain from cholecystitis due to obstruction of the cystic duct. The main ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) findings that clinicians and radiologists should consider in their everyday medical activity were discussed. The diagnosis of GM was often achieved through a combination of more than one imaging modality. In more than 90% of cases, the diagnosis of GM is often late and combined with other organs involvement in the terminal stage of the malignancy. The knowledge of the clinical features and different imaging techniques through careful evaluation of the gallbladder can help to achieve early diagnosis and avoid misdiagnosis or false negative results.
Synthetic data for annotation and extraction of family history information from clinical text
Authors: Brekke Pål H. , Rama Taraka , Pilán Ildikó , Nytrø Øystein , Øvrelid Lilja 
Published: July 2021

Abstract
Background
The limited availability of clinical texts for Natural Language Processing purposes is hindering the progress of the field. This article investigates the use of synthetic data for the annotation and automated extraction of family history information from Norwegian clinical text. We make use of incrementally developed synthetic clinical text describing patients’ family history relating to cases of cardiac disease and present a general methodology which integrates the synthetically produced clinical statements and annotation guideline development. The resulting synthetic corpus contains 477 sentences and 6030 tokens. In this work we experimentally assess the validity and applicability of the annotated synthetic corpus using machine learning techniques and furthermore evaluate the system trained on synthetic text on a corpus of real clinical text, consisting of de-identified records for patients with genetic heart disease.

Results
For entity recognition, an SVM trained on synthetic data had class weighted precision, recall and F1-scores of 0.83, 0.81 and 0.82, respectively. For relation extraction precision, recall and F1-scores were 0.74, 0.75 and 0.74.

Conclusions
A system for extraction of family history information developed on synthetic data generalizes well to real, clinical notes with a small loss of accuracy. The methodology outlined in this paper may be useful in other situations where limited availability of clinical text hinders NLP tasks. Both the annotation guidelines and the annotated synthetic corpus are made freely available and as such constitutes the first publicly available resource of Norwegian clinical text.
Acceleration of performance recovery and competitiveness through non-banking financing in SMEs based on green economy: impact of Covid-19 pandemic
Authors: Sriyono  , Biduri Sarwendah , Proyogi Bayu 
Published: July 2021

AbstractMany previous studies have examined the effects of Covid-19 on small-medium enterprises but never discussed how to accelerate small-medium enterprise performance. This study aims to accelerate the recovery of small-medium enterprise performance affected by Covid-19. This research type is interpretive qualitative, data validity test using credibility and transferability test, data analysis technique using research data reduction, presenting data, and drawing conclusions. The conclusions obtained in this study are financing coming from non-banks when the Covid-19 pandemic conditions are very beneficial for small-medium enterprises, and small-medium enterprises are still able to compete globally.
In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria
Authors: Askari Parvin , Namaei Mohammad Hasan , Ghazvini Kiarash , Hosseini Mehran 
Published: July 2021

AbstractBackgroundMelittin is one of the most studied antimicrobial peptides, and severalin vitroexperiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap betweenin vitroandin vivostudies.MethodsIn the first step,in vitrotoxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR)Acinetobacter baumannii, methicillin-resistantStaphylococcus aureus(MRSA), and KPC-producingKlebsiella pneumonia(KPC-KP) pathogens were tested using bothin vitroandin vivomethods.ResultsMelittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50value of 4.98 mg/kg in BALB/c mice.In vitroantimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads.ConclusionsThese results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.
Loading and release of cancer chemotherapy drugs utilizing simultaneous temperature and pH-responsive nanohybrid
Authors: Dahri Mohammad , Akbarialiabad Hossein , Jahromi Ahmad Miri , Maleki Reza 
Published: July 2021

Abstract
Background
Recently, the development of nanocarriers and the improvement of their biochemical properties have became of great importance. Single-walled carbon nanotubes (SWCNT) have many applications in drug delivery systems (DDS) as a common carbon-based structure. In the current work, the penetration, co-loading, and co-release of Doxorubicin (DOX) and Paclitaxel (PAX), as two cancer chemotherapy agents, were investigated using a novel modified copolymer with functionalized SWCNT.

Results
This study proposes a dual-responsive smart carrier that is sensitive to pH and temperature. The carrier consists of functionalized SWNT and Dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) grafting on SWCNT. This suggested carrier was investigated by utilizing molecular simulations. Interaction energies between DOX, PAX, and carrier as well as the affinity of drugs to the nanocarrier were studied. The energy analysis of drug release and adsorption presented that DOX and PAX delivery using this carrier is selective and sensitive at healthy and cancerous conditions. The attraction of DMAA-TMC, as a biodegradable and biocompatible copolymer, with SWCNT showed that degradation mechanism in acidic environment deformed the copolymer. This leads to a smart release mechanism in an acidic cancerous tissue. Additionally, it improves hydrophilicity, optimum nano-particle size, and cell cytotoxicity concerns.

Conclusions
The simulation results manifested a significant contribution of DMAA-TMC in the adsorption and release of cancer chemotherapy drugs in normal and neoplastic tissues. The interaction of copolymer also improves the biocompatibility and biodegradability of the SWCNT. Smart drug delivery carrier can be a valuable nanohybrid for loading, transporting, and releasing of cancer chemotherapy drugs.

Graphical abstract
Short antimicrobial peptidomimetic SAMP-5 effective against multidrug-resistant gram-negative bacteria
Authors: Kim Eun Young , Han So Hee , Kim Jong Min , Kim Seon-Myung , Shin Song Yub 
Published: July 2021

AbstractSAMP-5 is a short histidine-derived antimicrobial peptidomimetic with pendant dialkylated tail. In this study, we evaluated the potential of SAMP-5 as an antimicrobial agent to combat multidrug-resistant gram-negative bacteria. SAMP-5 showed potent antimicrobial activity (minimum inhibitory concentration 16-64 μg/ml) comparable to melittin against multidrug-resistant Escherichia coli (MDREC) and multidrug-resistant (MDRPA). SAMP-5 displayed no cytotoxicity against three mammalian cells such as mouse macrophage RAW264.7, mouse embryonic fibroblast NIH-3T3, and human bone marrow SH-SY5Y cells at the concentration of 128 μg/ml. SAMP-5 showed resistance to proteolytic degradation with pepsin, trypsin, α-chymotrypsin, and proteinase K. Importantly, unlike ciprofloxacin, no antibiotic resistance against SAMP-5 arose for Pseudomonas aeruginosa during 7 days of serial passage at 0.5 × MIC. Moreover, SAMP-5 showed synergy or additive effects against MDRPA and MDREC, when it combined with chloramphenicol, ciprofloxacin, and oxacillin. Collectively, our results suggested that SAMP-5 is a promising alternative and adjuvant to treat infections caused by multidrug-resistant gram-negative bacteria.
Permeable characteristics of surface film deposited on LiMn2O4 positive electrode revealed by redox-active indicator
Authors: Kim Hyun-seung , Yang Jin Hyuk , Han Ji Woo , Thao Le Thi , Ryu Ji Heon , Oh Seung M. , Kim Ki Jae 
Published: July 2021

AbstractHerein, the ferrocene redox indicator-based surface film characteristics of spinel lithium manganese oxide (LMO) were evaluated. The pre-cycling of spinel LMO generated a film on the LMO surface. The surface film deposited on LMO surface suppresses further electrolyte decomposition, while the penetration of approximately 0.7 nm-sized redox indicator is not prevented. The facile self-discharge of LMO and regeneration current from the ferrocenium molecule was observed from the redox indicator in a specifically designed four-electrode cell. From this electrochemical behavior, a small-sized HF molecule attack on the LMO surface through a carbonate-based electrolyte-derived film is defined; hence, the prevention of small-sized molecules into the deposited surface film is crucial for the enhancement of LiMn2O4-based lithium-ion batteries.
Pathogenesis and management of gastrointestinal inflammation and fibrosis: from inflammatory bowel diseases to endoscopic surgery
Authors: Iwata Kentaro , Mikami Yohei , Kato Motohiko , Yahagi Naohisa , Kanai Takanori 
Published: July 2021

AbstractGastrointestinal fibrosis is a state of accumulated biological entropy caused by a dysregulated tissue repair response. Acute or chronic inflammation in the gastrointestinal tract, including inflammatory bowel disease, particularly Crohn’s disease, induces fibrosis and strictures, which often require surgical or endoscopic intervention. Recent technical advances in endoscopic surgical techniques raise the possibility of gastrointestinal stricture after an extended resection. Compared to recent progress in controlling inflammation, our understanding of the pathogenesis of gastrointestinal fibrosis is limited, which requires the development of prevention and treatment strategies. Here, we focus on gastrointestinal fibrosis in Crohn’s disease and post-endoscopic submucosal dissection (ESD) stricture, and we review the relevant literature.
The need for adaptable global guidance in health systems strengthening for musculoskeletal health: a qualitative study of international key informants
Authors: Briggs Andrew M. , Jordan Joanne E. , Kopansky-Giles Deborah , Sharma Saurab , March Lyn , Schneider Carmen Huckel , Mishrra Swatee , Young James J. , Slater Helen 
Published: July 2021

Abstract
Background
Musculoskeletal (MSK) conditions, MSK pain and MSK injury/trauma are the largest contributors to the global burden of disability, yet global guidance to arrest the rising disability burden is lacking. We aimed to explore contemporary context, challenges and opportunities at a global level and relevant to health systems strengthening for MSK health, as identified by international key informants (KIs) to inform a global MSK health strategic response.

Methods
An in-depth qualitative study was undertaken with international KIs, purposively sampled across high-income and low and middle-income countries (LMICs). KIs identified as representatives of peak global and international organisations (clinical/professional, advocacy, national government and the World Health Organization), thought leaders, and people with lived experience in advocacy roles. Verbatim transcripts of individual semi-structured interviews were analysed inductively using a grounded theory method. Data were organised into categories describing 1) contemporary context; 2) goals; 3) guiding principles; 4) accelerators for action; and 5) strategic priority areas (pillars), to build a data-driven logic model. Here, we report on categories 1–4 of the logic model.

Results
Thirty-one KIs from 20 countries (40% LMICs) affiliated with 25 organisations participated. Six themes described contemporary context (category 1): 1) MSK health is afforded relatively lower priority status compared with other health conditions and is poorly legitimised; 2) improving MSK health is more than just healthcare; 3) global guidance for country-level system strengthening is needed; 4) impact of COVID-19 on MSK health; 5) multiple inequities associated with MSK health; and 6) complexity in health service delivery for MSK health. Five guiding principles (category 3) focussed on adaptability; inclusiveness through co-design; prevention and reducing disability; a lifecourse approach; and equity and value-based care. Goals (category 2) and seven accelerators for action (category 4) were also derived.

Conclusion
KIs strongly supported the creation of an adaptable global strategy to catalyse and steward country-level health systems strengthening responses for MSK health. The data-driven logic model provides a blueprint for global agencies and countries to initiate appropriate whole-of-health system reforms to improve population-level prevention and management of MSK health. Contextual considerations about MSK health and accelerators for action should be considered in reform activities.
Hypothermic treatment reduces matrix metalloproteinase-9 expression and damage in the liver following asphyxial cardiac arrest in rats
Authors: Kim Donghwi , Kim Bora , Sim Hyejin , Lee Tae-Kyeong , Tae Hyun-Jin , Lee Jae-Chul , Park Joon Ha , Cho Jun Hwi , Won Moo-Ho , Park Yoonsoo , Ahn Ji Hyeon 
Published: July 2021

Abstract
Background
Hypothermic treatment is known to protect organs against cardiac arrest (CA) and improves survival rate. However, few studies have evaluated the effects of hypothermia on CA-induced liver damages. This study was designed to analyzed the possible protective effects of hypothermia on the liver after asphyxial CA (ACA). Rats were randomly subjected to 5 min of ACA followed by return of spontaneous circulation (ROSC). Body temperature was controlled at 37 ± 0.5 °C (normothermia group) or 33 ± 0.5 °C (hypothermia group) for 4 h after ROSC. Liver tissues were extracted and examined at 6 h, 12 h, 1 day, and 2 days after ROSC.

Results
The expression of infiltrated neutrophil marker CD11b and matrix metallopeptidase-9 (MMP9) was investigated via immunohistochemistry. Morphological damage was assessed via hematoxylin and eosin (H & E) staining. Hypothermic treatment improved the survival rate at 6 h, 12 h, 1 day, and 2 days after ACA. Based on immunohistochemical analysis, the expression of CD11b and MMP9 was significantly increased from 6 h after ACA in the normothermia group. However, the expressions of CD11b and MMP9 was significantly decreased in the hypothermia group compared with that of the normothermia group. In addition, in the results of H & E, sinusoidal dilatation and vacuolization were apparent after ACA; however, these ACA-induced structural changes were reduced by the 4 h-long hypothermia.

Conclusions
In conclusion, hypothermic treatment for 4 h inhibited the increases in CD11b and MMP9 expression and reduced the morphological damages in the liver following ACA in rats. This study suggests that hypothermic treatment after ACA reduces liver damages by regulating the expression of CD11b and MMP9.
How does manufacturing output affect export behaviors in emerging market economies? Evidence from a dynamic panel ARDL for ten biggest emerging market economies
Authors: Sankaran Arumugam , Krishna Arjun , Vadivel Arjunan 
Published: July 2021

AbstractRealizing the export-led economic growth potential, the study aims to check the dynamic influence of manufacturing output premised on learning effects model on the export behavior of emerging market economies. Among the mean group and pooled mean group models in the umbrella method of autoregressive-distributed lag econometric technique, the latter one was chosen as it has added advantages. Also, it is supported by the Hausman test. The findings articulate that manufacturing value-added is an important ingredient, which influences the export testifying the existence of dynamic learning effects in export growth. A dynamic model of acquiring sophistication among exporters pinpoints the learning effects technique of exports. The export competitiveness is actualized through a dynamic learning process. The policy suggestion in this regard is to pace up mechanization of the economies, foster measures to reduce supply rigidities and labor market inflexibilities, and assist small and medium-scale enterprises and other types of firms in finding fresh avenues of long-term investment from foreign and advocating domestic supplies.