bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policies on return and reintegration of displaced healthcare workers towards rebuilding conflict-affected health systems: a review for The Lancet-AUB Commission on Syria
Authors: Rayes Diana , Meiqari Lana , Yamout Rouham , Abbara Aula , Nuwayhid Iman , Jabbour Samer , Abouzeid Marian 
Published: May 2021

Abstract
Background
War and armed conflicts severely disrupt all health system components, including the healthcare workforce. Although data is limited on the scale of health care worker (HCW) displacement in conflict zones, it is widely acknowledged that conflict conditions result in the displacement of a significant portion of qualified HCWs from their country of origin. While voluntary HCW return is integral to health system rebuilding in conflict-affected and post-conflict settings, there has been little exploration of the nature of national or international policies which encourage HCW return and reintegration to their home countries in the post-conflict period.

Methods
We conducted a systematic review to identify policies and policy recommendations intended to facilitate the return of displaced HCWs to their home countries and acknowledge their contribution to rebuilding the post-conflict health system. We searched three bibliographic databases and a range of organisational and national health agency websites to identify peer-reviewed articles and grey literature published in English or Arabic between 1 January 1990 to 24 January 2021, and extracted relevant information. We classified policies and policy recommendations using an adapted version of the UNHCR 4Rs Framework.

Results
We identified nine peer-review articles and four grey literature reports that fit our inclusion criteria, all of which were published in English. These covered issues of repatriation (n = 3), reintegration (n = 2), health system rehabilitation and reconstruction (n = 2); six documents covered several of these themes. Information was available for nine conflict contexts: Afghanistan, Iraq, Kosovo, Lebanon, Namibia, Northern Uganda, South Sudan, Timor Leste, and Zimbabwe. Findings demonstrate that health system rebuilding and rehabilitation serve as precursors and reinforcers of the successful return, repatriation, and reintegration of displaced HCWs.

Conclusions
Despite the significant numbers of HCWs displaced by conflict, this study identified few specific policies and limited information explicitly focused on the repatriation and reintegration of such workers to their home country in the post-conflict period. Additional research is needed to understand the particular barriers faced by conflict-displaced HCWs in returning to their home country. Conflict-affected and post-conflict states should develop policies and initiatives that address factors within and beyond the health sector to encourage displaced HCW return and provide sustainable reintegration solutions for those who return to post-conflict health systems.
Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
Authors: Magota Hirotoshi , Sasaki Masanori , Kataoka-Sasaki Yuko , Oka Shinichi , Ukai Ryo , Kiyose Ryo , Onodera Rie , Kocsis Jeffery D. , Honmou Osamu 
Published: May 2021

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.
ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling
Authors: Wu Qi , Zhou Xiaoqing , Li Peng , Ding Mao , You Shengjie , Xu Zhaoyu , Ye Junjie , Chen Xuedong , Tan Mingyue , Wang Jun , Wang Wei , Qiu Jianxin 
Published: May 2021

Abstract
Background
Regulator of cullins 1 (ROC1) is an important catalytic subunit of cullin–RING E3 ligase. Nuclear factor-kappa B (NF-κB) signaling is closely related to tumor invasion and metastasis. Earlier, we reported that ROC1 was associated with a poor prognosis in patients with bladder cancer (BCa). However, it is unclear whether ROC1 is involved in the NF-κB signaling associated with malignant BCa progression.

Methods
The expression of ROC1 and p65 in bladder cancer and paracancerous tissues were detected by immunohistochemistry (IHC). Pearson correlation was used to assess correlation between ROC1 and p65 protein expressions. The wound-healing and transwell assays were used to monitor cell invasion and migration. The effect of ROC1 on the expression of key proteins in the NF-κB signaling was determined by immunofluorescence and western blot (WB). Cycloheximide (CHX), MG132 and immunoprecipitation assays were used to evaluate the effect of ROC1 on the ubiquitination of phosphorylated inhibitor of kappa B alpha (p-IκBα). A lung metastasis mouse model was generated to detect the role of ROC1 in tumor metastasis.

Results
We found that ROC1 was up-regulated in BCa tissues and cell lines, and high ROC1 levels were positively correlated with higher tumour grade, lymph node metastasis, distant metastasis and poor prognosis. Linear-regression analysis showed significant a Pearson correlation between ROC1 and nuclear p65 expression in BCa tissue microarray (TMA) samples. Functional studies demonstrated that ROC1 promoted BCa cell invasion and migration. In vitro and in vivo experiments showed that ROC1 activated NF-κB signaling by enhancing the ubiquitination of p-IκBα, which caused p65 nuclear translocation and promoted the transcription of some metastasis-related target genes, such as urokinase-type plasminogen activator receptor (uPAR), intracellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and matrix metalloproteinase 9 (MMP9), resulting in promoting BCa metastasis.

Conclusion
ROC1 plays an important role in the progression of BCa and serves as a potential diagnostic and therapeutic target for patients with BCa.
Promoter G-quadruplex folding precedes transcription and is controlled by chromatin
Authors: Shen Jiazhen , Varshney Dhaval , Simeone Angela , Zhang Xiaoyun , Adhikari Santosh , Tannahill David , Balasubramanian Shankar 
Published: May 2021

AbstractBackgroundFour-stranded G-quadruplexes (G4s) are DNA secondary structures in the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of promoter G4s, transcription and chromatin state.ResultsTranscriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed by G4 ChIP-seq, does not depend on transcriptional activity. We then show that chromatin compaction can lead to loss of promoter G4s and is accompanied by a corresponding loss of RNA polymerase II (Pol II), thus establishing a link between G4 formation and chromatin accessibility. Furthermore, pre-treatment of cells with a G4-stabilising ligand mitigates the loss of Pol II at promoters induced by chromatin compaction.ConclusionsOverall, our findings show that G4 folding is coupled to the establishment of accessible chromatin and does not require active transcription.
scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing
Authors: Wilson Gavin W. , Derouet Mathieu , Darling Gail E. , Yeung Jonathan C. 
Published: May 2021

AbstractIdentifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to “collapse” molecular duplicates and accurately identify variants and their co-expression. We demonstrate that scSNV is fast, with a reduced false-positive variant call rate, and enables the co-detection of genetic variants and A>G RNA edits across twenty-two samples.
Migration-associated malaria from Africa in southern Spain
Authors: Pousibet-Puerto Joaquín , Lozano-Serrano Ana Belén , Soriano-Pérez Manuel Jesús , Vázquez-Villegas José , Giménez-López María José , Cabeza-Barrera María Isabel , Cuenca-Gómez José Ángel , Palanca-Giménez Matilde , Luzón-García María Pilar , Castillo-Fernández Nerea , Cabezas-Fernández María Teresa , Salas-Coronas Joaquín 
Published: May 2021

Abstract
Background
The western area of the province of Almeria, sited in southern Spain, has one of the highest immigrant population rates in Spain, mainly dedicated to agricultural work. In recent years, there has been a significant increase in the number of cases of imported malaria associated with migrants from countries belonging to sub-Saharan Africa. The objective of our study is to describe the epidemiological, clinical and analytical characteristics of malaria patients treated in a specialized tropical unit, paying special attention to the differences between VFR and non-VFR migrants and also to the peculiarities of microscopic malaria cases compared to submicroscopic ones.

Methods
Retrospective observational study of migrants over 14 years of age with imported malaria treated from October 2004 to May 2019. Characteristics of VFR and non-VFR migrants were compared. Malaria cases were divided into microscopic malaria (MM) and submicroscopic malaria (SMM). SMM was defined as the presence of a positive malaria PCR test together with a negative direct microscopic examination and a negative rapid diagnostic test (RDT). Microscopic malaria was defined as the presence of a positive RDT and/or a positive smear examination.

Results
Three hundred thirty-six cases of malaria were diagnosed, 329 in sub-Saharan immigrants. Of these, 78.1% were VFR migrants, in whom MM predominated (85.2% of cases). In non-VFR migrants, SMM represented 72.2% of the cases. Overall, 239 (72.6%) patients presented MM and 90 (27.4%) SMM. Fever was the most frequent clinical manifestation (64.4%), mainly in the MM group (MM: 81.1% vs SMM: 20.0%; p < 0.01). The most frequent species was P. falciparum. Patients with SMM presented fewer cytopenias and a greater number of coinfections due to soil-transmitted helminths, filarial and intestinal protozoa compared to patients with MM.

Conclusions
Imported malaria in our area is closely related to sub-Saharan migration. VFR migrants are the main risk group, highlighting the need for actions aimed at improving disease prevention measures. On the other hand, almost a third of the cases are due to SMM. This fact could justify its systematic screening, at least for those travelers at greater risk.

Graphical Abstract
First report of Theileria annulata in Nigeria: Findings from cattle ticks in Zamfara and Sokoto States
Authors: Mamman Adamu Haruna , Lorusso Vincenzo , Adam Babagana Mohammed , Dogo Goni Abraham , Bown Kevin J. , Birtles Richard J. 
Published: May 2021

AbstractBackgroundTicks and tick-borne pathogens (TBPs) represent a significant economic burden to cattle farming in sub-Saharan Africa including Nigeria. However, in the northern part of this country, where the largest livestock population resides, little is known about the contemporary diversity of ticks and TBPs. This area is particularly vulnerable to climate change, undergoing marked transformation of habitat and associated flora and fauna that is also likely to include ticks. This study aimed to document the occurrence of tick species and Apicomplexan TBPs in cattle from north-western Nigeria.MethodsIn 2017, ticks were collected from cattle in Zamfara and Sokoto States and identified morphologically. Additionally, a subset of ticks was screened molecularly for the detection of apicomplexan DNA.ResultsA total of 494 adult ticks were collected from 80 cattle in Zamfara and 65 cattle in Sokoto State. Nine tick species were encountered, among which the presence of one,Hyalomma turanicum, had not previously been recorded in Nigeria.Hyalomma rufipeswas the most prevalent tick infesting cattle in Zamfara State (76%), whileHyalomma dromedariiwas the most prevalent in Sokoto State (44%), confirming the widespread transfer of this species from camels onto livestock and its adaptation to cattle in the region. Of 159 ticks screened, 2 out of 54 (3.7%) from Zamfara State and 29 out of 105 (27.6%) from Sokoto State harboured DNA ofTheileria annulata, the agent of tropical theileriosis.ConclusionsThis study confirms the presence of a broad diversity of tick species in cattle from north-western Nigeria, providing the first locality records for Zamfara State. The occurrence ofH. turanicumindicates a distribution of this tick beyond northern Africa. This study provides the first report forT. annulatain Nigerian ticks. Given its enormous burden on livestock farming in north Africa and across Asia, further investigations are needed to better understand its epidemiology, vector transmission and potential clinical significance in cattle from northern Nigeria and neighbouring Sahelian countries.Graphical abstract
Imported Hyalomma ticks in the Netherlands 2018–2020
Authors: Uiterwijk Mathilde , Ibáñez-Justicia Adolfo , van de Vossenberg Bart , Jacobs Frans , Overgaauw Paul , Nijsse Rolf , Dabekaussen Charlotte , Stroo Arjan , Sprong Hein 
Published: May 2021

Abstract
Background
Ticks of the genus Hyalomma, which are vectors for several tick-borne diseases, are occasionally found in areas outside their endemic range including northern parts of Europe. The objective of this study was to analyse adult Hyalomma ticks that were recently found in the Netherlands.

Methods
Hyalomma ticks were morphologically identified. Cluster analysis, based upon sequence data (cox1 barcoding) for molecular identification, and pathogen detection were performed. Additionally, a cross-sectional survey of horses was conducted to actively search for Hyalomma ticks in summer 2019. Analysis of temperature was done to assess the possibility of (i) introduced engorged nymphs moulting to adults and (ii) establishment of populations in the Netherlands.

Results
Seventeen adult Hyalomma ticks (one in 2018, eleven in 2019, five in 2020) were found by citizens and reported. Fifteen ticks were detected on horses and two on humans. Twelve were identified as H. marginatum, one as H. rufipes and four, of which only photographic images were available, as Hyalomma sp. No Crimean-Congo haemorrhagic fever virus or Babesia/Theileria parasites were detected. One adult tick tested positive for Rickettsia aeschlimannii. In the cross-sectional horse survey, no Hyalomma ticks were found. Analysis of temperatures showed that engorged nymphs arriving on migratory birds in spring were able to moult to adults in 2019 and 2020, and that cumulative daily temperatures in the Netherlands were lower than in areas with established H. marginatum populations.

Conclusions
Our results show that Hyalomma ticks are regularly introduced in the Netherlands as nymphs. Under the Dutch weather conditions, these nymphs are able to develop to the adult stage, which can be sighted by vigilant citizens. Only one human pathogen, Rickettsia aeschlimannii, was found in one of the ticks. The risk of introduction of tick-borne diseases via Hyalomma ticks on migratory birds is considered to be low. Establishment of permanent Hyalomma populations is considered unlikely under the current Dutch climatic conditions.

Graphical Abstract
Using next generation sequencing of alpine plants to improve fecal metabarcoding diet analysis for Dall’s sheep
Authors: Williams Kelly E. , Menning Damian M. , Wald Eric J. , Talbot Sandra L. , Rattenbury Kumi L. , Prugh Laura R. 
Published: May 2021

Abstract
Objectives
Dall’s sheep (Ovis dalli dalli) are important herbivores in the mountainous ecosystems of northwestern North America, and recent declines in some populations have sparked concern. Our aim was to improve capabilities for fecal metabarcoding diet analysis of Dall’s sheep and other herbivores by contributing new sequence data for arctic and alpine plants. This expanded reference library will provide critical reference sequence data that will facilitate metabarcoding diet analysis of Dall’s sheep and thus improve understanding of plant-animal interactions in a region undergoing rapid climate change.

Data description
We provide sequences for the chloroplast rbcL gene of 16 arctic-alpine vascular plant species that are known to comprise the diet of Dall’s sheep. These sequences contribute to a growing reference library that can be used in diet studies of arctic herbivores.
hERG-deficient human embryonic stem cell-derived cardiomyocytes for modelling QT prolongation
Authors: Chang Yun , Li Ya-nan , Bai Rui , Wu Fujian , Ma Shuhong , Saleem Amina , Zhang Siyao , Jiang Youxu , Dong Tao , Guo Tianwei , Hang Chengwen , Lu Wen-jing , Jiang Hongfeng , Lan Feng 
Published: May 2021

Abstract
Background
Long-QT syndrome type 2 (LQT2) is a common malignant hereditary arrhythmia. Due to the lack of suitable animal and human models, the pathogenesis of LQT2 caused by human ether-a-go-go-related gene (hERG) deficiency is still unclear. In this study, we generated an hERG-deficient human cardiomyocyte (CM) model that simulates ‘human homozygous hERG mutations’ to explore the underlying impact of hERG dysfunction and the genotype–phenotype relationship of hERG deficiency.

Methods
The KCNH2 was knocked out in the human embryonic stem cell (hESC) H9 line using the CRISPR/Cas9 system. Using a chemically defined differentiation protocol, we obtained and verified hERG-deficient CMs. Subsequently, high-throughput microelectrode array (MEA) assays and drug interventions were performed to characterise the electrophysiological signatures of hERG-deficient cell lines.

Results
Our results showed that KCNH2 knockout did not affect the pluripotency or differentiation efficiency of H9 cells. Using high-throughput MEA assays, we found that the electric field potential duration and action potential duration of hERG-deficient CMs were significantly longer than those of normal CMs. The hERG-deficient lines also exhibited irregular rhythm and some early afterdepolarisations. Moreover, we used the hERG-deficient human CM model to evaluate the potency of agents (nifedipine and magnesium chloride) that may ameliorate the phenotype.

Conclusions
We established an hERG-deficient human CM model that exhibited QT prolongation, irregular rhythm and sensitivity to other ion channel blockers. This model serves as an important tool that can aid in understanding the fundamental impact of hERG dysfunction, elucidate the genotype–phenotype relationship of hERG deficiency and facilitate drug development.
Response patterns in adventitial layer of Echinococcus granulosus sensu stricto cysts from naturally infected cattle and sheep
Authors: Hidalgo Christian , Stoore Caroll , Baquedano María Soledad , Pereira Ismael , Franco Carmen , Hernández Marcela , Paredes Rodolfo 
Published: May 2021

AbstractCystic echinococcosis is a zoonotic disease caused by the metacestode of Echinococcus granulosus sensu lato. The disease is characterized by the development of cystic structures inside viscera of the intermediate host, mainly liver and lungs. These cysts are formed by three layers: germinal, laminated, and adventitial layer, the latter being the local host immune response. Metacestodes that develop protoscoleces, the infective stage to the definitive host, are termed fertile, whereas cysts that do not produce protoscoleces are termed non-fertile. Sheep usually harbor fertile cysts while cattle usually harbor non-fertile cysts. Adventitial layers with fibrotic resolution are associated to fertile cysts, whereas a granulomatous reaction is associated with non-fertile cysts. The aim of this study was to analyze cellular distribution in the adventitial layer of fertile and non-fertile E. granulosus sensu stricto cysts found in liver and lungs of cattle and sheep. A total of 418 cysts were analyzed, 203 from cattle (8 fertile and 195 non-fertile) and 215 from sheep (64 fertile and 151 non-fertile). Fertile cysts from cattle showed mixed patterns of response, with fibrotic resolution and presence of granulomatous response in direct contact with the laminated layer, while sheep fertile cysts always displayed fibrotic resolution next to the laminated layer. Cattle non-fertile cysts display a granulomatous reaction in direct contact with the laminated layer, whereas sheep non-fertile cysts display a granulomatous reaction, but in direct contact with the fibrotic resolution. This shows that cattle and sheep cystic echinococcosis cysts have distinct local immune response patterns, which are associated to metacestode fertility.
Existence theorem for a unique solution to a coupled system of impulsive fractional differential equations in complex-valued fuzzy metric spaces
Authors: Humaira  , Hammad Hasanen A. , Sarwar Muhammad , De la Sen Manuel 
Published: May 2021

AbstractIn this manuscript, the existence theorem for a unique solution to a coupled system of impulsive fractional differential equations in complex-valued fuzzy metric spaces is studied and the fuzzy version of some fixed point results by using the definition and properties of a complex-valued fuzzy metric space is presented. Ultimately, some appropriate examples are constructed to illustrate our theoretical results.