bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons from the field: COVID-19 outbreak investigations in Kpone-Katamanso, Greater Accra, Ghana: a Global South approach to disease control and contact tracing
Authors: Danquah Esther P B , Darko Shadrack , Frimpong Adom , Head Michael G , Osei Bright 
Published: July 2022

Abstract
In the Kpone-Katamanso Municipality (Greater Accra, Ghana), as part of the coronavirus disease 2019 (COVID-19) pandemic response, public health teams implemented and carried out enhanced contact tracing and surveillance from March 2020 to March 2021. There were 725 confirmed COVID-19 cases during this time period, most of which were detected as part of the enhanced surveillance. This is resource intensive, but beneficial in the early detection of cases, thus reducing further community transmission and, in effect, stopping larger outbreaks at the source. A proactive approach to case detection can be successful in reducing community transmission and supporting the pandemic response.
Persistence of Trypanosoma cruzi vector-borne transmission among school-age children in the Bolivian Chaco documented by 24-month longitudinal serosurveillance
Authors: Spinicci Michele , Macchioni Fabio , Gamboa Herlan , Poma Veronica , Villagrán Ana Liz , Strohmeyer Marianne , Roselli Mimmo , Vargas Roberto , Bartoloni Alessandro , Gabrielli Simona 
Published: July 2022

Abstract

Background
Chagas disease represents a major public health concern in several Latin American countries, including Bolivia.

Methods
We present a longitudinal serosurvey for Trypanosoma cruzi antibodies among a cohort of 120 school-age children from rural communities in the Bolivian Chaco at three time points between 2017 and 2019. Serum samples extracted from dry blood spots collected on filter paper were tested for T. cruzi antibodies by enzyme-linked immunosorbent assay and rapid diagnostic test.

Results
T. cruzi antibodies were detected in 7/120 (5.8%), 8/120 (6.7%) and 11/120 (9.2%) samples in 2017, 2018 and 2019, respectively. An average incidence of 1.76 per 100 person-years was observed.

Conclusions
Our findings support the persistence of vector-borne T. cruzi transmission in this area, highlighting the need for strengthening multidisciplinary efforts against Chagas disease.
Pathology of T-cell-mediated drug hypersensitivity reactions and impact of tolerance mechanisms on patient susceptibility
Authors: Line James , Thomson Paul , Naisbitt Dean J. 
Published: July 2022

Purpose of review
T-cell-mediated drug hypersensitivity is responsible for significant morbidity and mortality, and represents a substantial clinical concern. The purpose of this article is to focus on T-cell reactions and discuss recent advances in disease pathogenesis by exploring the impact of tolerance mechanisms in determining susceptibility in genetically predisposed patients.

Recent findings
Certain drugs preferentially activate pathogenic T cells that have defined pathways of effector function. Thus, a critical question is what extenuating factors influence the direction of immune activation. A large effort has been given towards identifying phenotypic (e.g., infection) or genotypic (e.g., human leukocyte antigen) associations which predispose individuals to drug hypersensitivity. However, many individuals expressing known risk factors safely tolerate drug administration. Thus, mechanistic insight is needed to determine what confers this tolerance. Herein, we discuss recent clinical/mechanistic findings which indicate that the direction in which the immune system is driven relies upon a complex interplay between co-stimulatory/co-regulatory pathways which themselves depend upon environmental inputs from the innate immune system.

Summary
It is becoming increasingly apparent that tolerance mechanisms impact on susceptibility to drug hypersensitivity. As the field moves forward it will be interesting to discover whether active tolerance is the primary response to drug exposure, with genetic factors such as HLA acting as a sliding scale, influencing the degree of regulation required to prevent clinical reactions in patients.
Effects of systemic targeted immunosuppressive therapy on ocular surface
Authors: Mukhtar Sabrina , Jhanji Vishal 
Published: July 2022

Purpose of review
The purpose of this review is to give an overview of the corneal manifestations of targeted systemic immunotherapies and provide guidelines for management when applicable.

Recent findings
The advent of newer systemic immunosuppressive therapy has resulted in the need for more awareness of potential ocular side effects. Side effects can range from vortex keratopathy as seen with the tyrosine kinase inhibitors, to epithelial microcysts as reported in the use of cytarabine and belantamab mafodotin, spontaneous corneal perforations have been reported with programmed death 1 inhibitors, while eyelid cicatrization has been reported epidermal growth factor inhibitors. Several immunomodulatory therapies result in conjunctivitis which tends to respond to topical lubrication and corticosteroid treatment. Most manifestations listed in the review are limited to the anterior segment; however, some may lead to retinal and optic nerve changes which can be permanently damaging.

Summary
Ocular surface and corneal changes secondary to systemic immunosuppression can affect main components of the ocular surface. Although most adverse effects are reversible, few changes can be permanent and therefore close ophthalmologic monitoring is necessary.
Enrichment of breast cancer stem cells following cytotoxic chemotherapy is mediated by hypoxia-inducible factors
Authors: Samanta Debangshu , Gilkes Daniele M. , Xiang Lisha , Chaturvedi Pallavi , Semenza Gregg L. 
Published: July 2022

AbstractBreast cancers (BCs) that do not express the estrogen or progesterone receptor or human epidermal growth factor receptor 2 are known as triple negative breast cancers (TNBCs). Women with TNBC receive non-targeted chemotherapy with a durable response rate of less than 20%. BC stem cells (BCSCs) are a small subpopulation of BC cells that are characterized by the capacity for infinite self-renewal; are the only BC cells capable of forming a secondary (recurrent or metastatic) BC; and must be eliminated in order to eradicate BC. Hypoxia-inducible factors (HIFs) activate hundreds of genes in TNBCs and HIF-1α expression in the diagnostic tumor biopsy is associated with patient mortality. In this paper, we report that treatment of TNBC cells with cytotoxic chemotherapy increased HIF-1α and HIF-2α protein levels and HIF target gene expression. Chemotherapy also increased the percentage of BCSCs through pathways involving interleukin-6 (IL-6), IL-8, and multidrug resistance 1. HIF inhibitors blocked increased BCSC specification in response to cytotoxic chemotherapy and combination therapy led to tumor eradication. Increased HIF target gene expression in BC biopsies was correlated with increased mortality, especially in those patients treated with chemotherapy alone. Our results suggest that HIF-dependent BCSC enrichment provides a molecular and cellular basis for the high incidence of relapse in women with TNBC.
Identification and characterization of genetic risk shared across 24 chronic pain conditions in the UK Biobank
Authors: Zorina-Lichtenwalter Katerina , Bango Carmen I. , Van Oudenhove Lukas , Čeko Marta , Lindquist Martin A. , Grotzinger Andrew D. , Keller Matthew C. , Friedman Naomi P. , Wager Tor D. 
Published: July 2022

AbstractChronic pain is attributable to both local and systemic pathology. To investigate the latter, we focused on genetic risk shared among 24 chronic pain conditions in the UK Biobank. We conducted genome-wide association studies (GWAS) on all conditions and estimated genetic correlations among them, using these to model a factor structure in Genomic SEM. This revealed a general factor explaining most of the shared genetic variance in all conditions and an additional musculoskeletal pain-selective factor. Network analyses revealed a large cluster of highly genetically inter-connected conditions, with arthropathic, back, and neck pain showing the highest centrality. Functional annotation (FUMA) showed organogenesis, metabolism, transcription, and DNA repair as associated pathways, with enrichment for associated genes exclusively in brain tissues. Cross-reference with previous GWAS showed genetic overlap with cognition, mood, and brain structure. In sum, our results identify common genetic risks and suggest neurobiological and psychosocial mechanisms of vulnerability to chronic pain.
Non-invasive quantification of contractile dynamics in cardiac cells, spheroids and organs-on-a-chip using high frequency ultrasound
Authors: Strohm Eric M. , Callaghan Neal , Latifi Neda , Rafatian Naimeh , Funakoshi Shunsuke , Fernandes Ian , Radisic Milica , Keller Gordon , Kolios Michael C. , Simmons Craig A. 
Published: July 2022

ABSTRACTCell-based models that mimic in vivo heart physiology are poised to make significant advances in cardiac disease modeling and drug discovery. In these systems, cardiomyocyte (CM) contractility is an important functional metric, but current measurement methods are inaccurate, low-throughput, or require complex set-ups. To address this need, we developed a standalone non-invasive, label-free ultrasound technique operating at 40-200 MHz to measure the beat rate, beat rhythm, and force of contraction of cardiac models, ranging from single adult CMs to 3D microtissue constructs in standard cell culture formats. The high temporal resolution of 1000 fps resolved the beat profile of single mouse CMs paced at up to 9 Hz, revealing limitations of lower speed optical based measurements to resolve beat kinetics or characterize aberrant beats. Coupling of ultrasound with traction force microscopy enabled the measurement of CM longitudinal modulus and facile estimation of adult mouse CM contractile forces of 2.34 ± 1.40 μN, comparable to more complex measurement techniques. Similarly, measurements of beat rate, rhythm, and drug responses of CM spheroid and microtissue models were demonstrated. In conclusion, ultrasound can be used for the rapid characterization of CM contractile function in a wide range of commonly-studied configurations ranging from single cells to 3D tissue constructs using standard well plates, with applications in cardiac drug discovery and cardiotoxicity evaluation.
A new transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma
Authors: Alchahin Adele M. , Mei Shenglin , Tsea Ioanna , Hirz Taghreed , Kfoury Youmna , Dahl Douglas , Wu Chin-Lee , Subtelny Alexander O. , Wu Shulin , Scadden David T. , Shin John H. , Saylor Philip J. , Sykes David B. , Kharchenko Peter V. , Baryawno Ninib 
Published: July 2022

ABSTRACTClear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer in adults. When ccRCC is localized to the kidney, surgical resection or ablation of the tumor is often curative. However, in the metastatic setting, ccRCC remains a highly lethal disease. Here we take advantage of fresh patient samples that include treatment-naive primary tumor tissue, matched adjacent normal kidney tissue, as well as tumor samples collected from patients with bone metastases. Single-cell transcriptomic analysis of tumor cells from the primary tumors revealed a distinct transcriptional signature that was predictive of metastatic potential and patient survival. Analysis of supporting stromal cells within the tumor environment demonstrated vascular remodeling within the endothelial cells and a proliferative signature within the fibroblasts that was associated with poor survival. An in silico cell-to-cell interaction analysis highlighted the CXCL9/CXCL10-CXCR3 axis and the CD70-CD27 axis as potential therapeutic targets. Our findings provide biological insights into the interplay between tumor cells and the ccRCC microenvironment.
Evaluation of EN2 gene as a potential biomarker for bladder cancer
Authors: Aldoghachi Ahmed Faris , Baharudin Aminuddin , Ahmad Umar , Choy Chan Soon , Aik Ong Ting , Yunus Rosna , Razack Azad , Yusoff Khatijah , Veerakumarasivam Abhi 
Published: July 2022

AbstractBackgroundAmong the most prevalent cancers in the urinary tract is bladder cancer, a caner with a high rate of recurrence and metastasis as compared to other malignancies. To date, there have been many genes reported as potential bladder cancer biomarkers among which is the EN2 gene, a member of the homeobox family containing transcriptional factors. Several studies suggested the overexpression of EN2 to be involved with the development of a number of tumors such as bladder cancer. However, the process of involvement of EN2 in the bladder tumorigenesis remains elusive.MethodsRT-qPCR was carried out to determine the gene expression of 17 cell lines. The short-term silencing of EN2 expression was then implemented in high-expressing cell lines using siRNAs. Using the scratch assay, the outcome of modulating the in vitro EN2 expression on the bladder cancer migration was determined. Correlation between the IC50 values with the EN2 expression was analyzed by correlating the viability of cells following the Newcastle Disease Virus infection with the fold change. Immunohistochemistry was then performed to determine the expression of the EN2 protein in the bladder cancer tissues.ResultsIn the current study, EN2 was differentially expressed in bladder cancer in vitro and upon modulating the expression of EN2, we found a reduction in the migratory effect of bladder cancer in vitro. In addition, following 24 hours post infection, a moderate correlation between EN2 gene expression and NDV-mediated oncolysis was observed. No expression of EN2 in bladder cancer tissues suggesting the need for further studies to investigate the expression of EN2 protein in bladder cancer.ConclusionEN2 may be a potential prognostic or diagnostic bladder cancer biomarker, however, further investigations are required to evaluate the EN2 gene as a potential bladder cancer biomarker.
Discovery of a non-canonical GRHL1 binding site using deep convolutional and recurrent neural networks
Authors: Proft Sebastian , Leiz Janna , Heinemann Udo , Seelow Dominik , Schmidt-Ott Kai M. , Rutkiewicz Maria 
Published: July 2022

ABSTRACTTranscription factors regulate gene expression by binding to transcription factor binding sites (TFBSs). Most models for predicting TFBSs are based on position weight matrices (PWMs), which require a specific motif to be present in the DNA sequence and do not consider interdependencies of nucleotides. Novel approaches such as Transcription Factor Flexible Models or recurrent neural networks consequently provide higher accuracies. However, it is unclear whether such approaches can uncover novel non-canonical, hitherto unexpected TFBSs relevant to human transcriptional regulation. In this study, we trained a convolutional recurrent neural network with HT-SELEX data for GRHL1 binding and applied it to a set of GRHL1 binding sites obtained from ChIP-Seq experiments from human cells. We identified 46 non-canonical GRHL1 binding sites, which were not found by a conventional PWM approach. Unexpectedly, some of the newly predicted binding sequences lacked the CNNG core motif, so far considered obligatory for GRHL1 binding. Using isothermal titration calorimetry, we experimentally confirmed binding between the GRHL1-DNA binding domain and predicted GRHL1 binding sites, including a non-canonical GRHL1 binding site. Mutagenesis of individual nucleotides revealed a correlation between predicted binding strength and experimentally validated binding affinity across representative sequences. This correlation was neither observed with a PWM-based nor another deep learning approach. Our results show that convolutional recurrent neural networks may uncover unanticipated binding sites and facilitate quantitative transcription factor binding predictions.
Graphene Biointerface for Cardiac Arrhythmia Diagnosis and Treatment
Authors: Lin Zexu , Kireev Dmitry , Liu Ning , Gupta Shubham , LaPaino Jessica , Obaid Sofian N. , Chen Zhiyuan , Akinwande Deji , Efimov Igor R. 
Published: July 2022

ABSTRACTHeart rhythm disorders, known as arrhythmias, cause significant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are primarily treated by implantable devices, such as pacemakers and defibrillators, or by ablation therapy guided by electroanatomical mapping. Pharmacological treatments are mostly ineffective. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, we report for the first time on graphene biointerface forin vivocardiac electrophysiology. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we demonstrate sensing and stimulation of the open mammalian heart bothin vitroandin vivo.Furthermore, we demonstrate graphene pacemaker treatment of a pharmacologically-induced arrhythmia, AV block. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm×cm2at 1kHz, charge storage capacity up to 63.7 mC/cm2, and charge injection capacity up to 704 μC/cm2. Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials and optogenetic stimulation while performing electrical measurements and stimulation. Our report presents evidence of the significant potential of graphene biointerfaces for the future clinical device- and catheter-based cardiac arrhythmias therapies.
Driving Osteocytogenesis from Mesenchymal Stem Cells in Osteon-like Biomimetic Nanofibrous Scaffolds
Authors: Soheilmoghaddam Farhad , Hezaveh Hadi , Rumble Madeleine , Cooper-White Justin J. 
Published: July 2022

AbstractThe repair of critical-sized bone defects, resulting from tumor resection, skeletal trauma or infection, remains a significant clinical problem. A potential solution is a tissue-engineered approach that utilises the combination of human mesenchymal stem cells (hMSCs) with synthetic biomaterial scaffolds, mimicking many of the biochemical and biophysical cues present within the native bone. Unfortunately, osteocyte cells, the orchestrators of bone maturation and homeostasis, are rarely produced within such MSC-seeded scaffolds, limiting the formation of true mature cortical bone from these synthetic implants. In this contribution, a bone morphogenic protein-6 (BMP6)-presenting osteon-like scaffolds based on electrospun poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds and poly(ethylene glycol) (PEG) based-hydrogels is reported. BMP6 peptide is shown to drive higher levels of SMAD signalling than the full-length protein counterpart. Osteon-mimetic scaffolds promoted the formation of osteocyte-like cells displaying multi-dendritic morphology and osteocyte-specific marker, E11/gp38 (E11), along with significant production of dentin matrix protein 1 (DMP1), confirming maturation of the ososteocyte-like cells. These results demonstrate that osteon-like scaffolds presenting chemo-topographical cues can drive the formation of mature osteocyte-like cells from hMSCs,withoutthe need for osteogenic factor media supplements, providing a novel ex vivo production platform for osteocyte-like cells from human MSCs in cortical bone mimics.
Q-SHINE: a versatile sensor for glutamine measurement via ligand-induced dimerization
Authors: Seo Moon-Hyeong , Lim Yun , Kim Ji Yul , Jung Youn Hee , Lee Jae Hoon , Baek Min Seok , Jung Je Hyeong , Kim Ho-Youn , Lee Wookbin , Park Keunwan 
Published: July 2022

AbstractStudies on glutamine (Gln) metabolism have illuminated the vital role of Gln in cellular functions and its potential as a biomarker for disease detection. Despite the increasing interest in Gln metabolism, in-depth evaluations are challenging owing to limitations of conventional Gln-measuring methods. Thus, we developed a ligand-induced dimerization-based sensor for Gln, termed Q-SHINE, by splitting a glutamine binding protein into two separate domains. Q-SHINE enables highly accurate and convenient measurement of Gln concentration in bio-fluid samples, and the detection range is optimal for physiological Gln levels. Genetically encoded Q-SHINE sensors could also visualize intracellular Gln levels and quantify cytoplasmic and mitochondrial Gln change in living cells, which enabled detection of various cell responses to extracellular Gln supplement.
A Chromosome-level Assembly of the Japanese Eel Genome, Insights into Gene Duplication and Chromosomal Reorganization
Authors: Wang Hongbo , Wan Hin Ting , Wu Bin , Jian Jianbo , Ng Alice HM , Chung Claire Yik-Lok , Chow Eugene Yui-Ching , Zhang Jizhou , Wong Anderson OL , Lai Keng Po , Chan Ting Fung , Zhang Eric Lu , Wong Chris Kong-Chu 
Published: July 2022

AbstractJapanese eels (Anguilla japonica) are commercially important species that have been harvested extensively for foods. Currently, this and related species (American and European eels) are difficult to breed on a commercial basis. Wild stock is used for aquaculture. Due to pollution, overfishing, and international trafficking, eel populations are declining. The International Union for Conservation of Nature lists Japanese eels as critically endangered and on its red list. Here we presented a high-quality genome assembly for Japanese eels and demonstrated that large chromosome reorganizations occurred in the events of third-round whole-genome duplications (3R-WRD). Following multiple chromosomal fusion and fission rearrangement, the Anguilla lineage has reduced the haploid chromosomal number of 19 from the ancestral proto-chromosomal number of 25. Phylogenetic analysis of expanded gene families showed the gene families of olfactory receptors and voltage-gated Ca2+-channel expanded significantly. The expansion of olfactory receptors (group δ and ζ genes) and voltage-gated Ca2+-channel gene families are important for olfaction and neurophysiological functions. Following 3R-WGD, additional tandem (TD) and proximal (PD) duplications occurred to acquire immune-related genes for adaptation. The Japanese eel assembly presented here can be used to study other Anguilla species that are related to evolution and conservation.
Strandings of loggerhead sea turtles south of the Po River delta: insights from a highly impacted area
Authors: Marisaldi Luca , Torresan Andrea , Ferrari Andrea 
Published: July 2022

AbstractThe northern Adriatic Sea is an important foraging ground for the loggerhead sea turtle Caretta caretta (Linnaeus, 1758) within the Mediterranean Sea. Here, spatial-temporal patterns of loggerhead sea turtles strandings along a short portion (∼18 km) of the coast south of the Po River delta (Italy) during a three-year period (2019-2021) were investigated. A total of 244 records (alive, n=7; dead, n=237) were analysed and the curved carapace lengths (CCL, notch to tip, cm) mainly reflected sub-adults (average CCL=55.2 cm; 95% CI= 53.3-57). The month of July was identified as the critical month with the highest number of strandings, mirroring migratory processes toward this area during warmer months. Interaction with the trawl fishery was hypothesized as the main cause of mortality and a small fraction of deaths (6%; n=16) could be linked to boat strikes and net entanglement. The number of stranded turtles•km-1 as well as the absolute number of strandings along the short portion of monitored coast confirmed this area as the most impacted in Italy and perhaps in the whole Mediterranean Sea. This study provides valuable information to improve conservation efforts for this species and highlight that, with all due caution, monitoring stranding events can offer useful insights into the geographic ranges, seasonal distribution, and life history of marine species of conservation interest such as the loggerhead sea turtle.