bluuebunny/crossref_metadata_2025_split huggingface dataset:
CROPSR: An Automated Platform for Complex Genome-Wide CRISPR gRNA Design and Validation
Authors: Paul Hans Müller , Istanto Dave D , Heldenbrand Jacob , Hudson Matthew 
Published: October 2021

Abstract
Background: CRISPR/Cas9 technology has become an important tool to generate targeted, highly specific genome mutations. The technology has great potential for crop improvement, as crop genomes are tailored to optimize specific traits over generations of breeding. Many crops have highly complex and polyploid genomes, particularly those used for bioenergy or bioproducts. The majority of tools currently available for designing and evaluating gRNAs for CRISPR experiments were developed based on mammalian genomes that do not share the characteristics or design criteria for crop genomes. Results: We have developed the first open source tool for genome-wide design and evaluation of gRNA sequences for CRISPR experiments, CROPSR. The genome-wide approach provides a significant decrease in the time required to design a CRISPR experiment, including validation through PCR, at the expense of an overhead compute time required once per genome, at the first run. To better cater to the needs of crop geneticists, restrictions imposed by other packages on design and evaluation of gRNA sequences were lifted. A new machine learning model was developed to provide scores while avoiding situations in which the currently available tools sometimes failed to provide guides for repetitive, A/T-rich genomic regions. We show that our gRNA scoring model provides a significant increase in prediction accuracy over existing tools, even in non-crop genomes. Conclusions: CROPSR provides the scientific community with new methods and a new workflow for performing CRISPR/Cas9 knockout experiments. CROPSR reduces the challenges of working in crops, and helps speed gRNA sequence design, evaluation and validation. We hope that the new software will accelerate discovery and reduce the number of failed experiments.
Evolution of acoustic communication in fungus-growing ant societies
Authors: Murakami Takahiro , Sakamoto Hironori , Higashi Seigo 
Published: October 2021

Abstract
Do ants ‘talk’? If so, how important is talking in ant societies? Chemical communication, through pheromones for example, was thought to be the main communication tool in ant societies; however, a major question is whether chemical substances alone can control highly differentiated social behaviours. In this study, we focused on the ‘talk’ of agricultural ants, key organisms in the Neotropical ecosystem, and conducted a detailed acoustic analysis. Our results indicate that in fungus-growing ants, acoustic communication is a much more frequent and critical factor than previously believed. The frequency of stridulatory sound-production recordings from the ants were found to be significantly correlated with social structure complexity. Structural analysis indicated that both the area and number of slits in the stridulatory acoustic organs were significantly correlated with body size. The ability of leaf-cutting ants to maintain fungus gardens was significantly lower in the sound-inhibited group than in the pheromone secretion-inhibited group. These results suggest that ants that have become ‘chattier’ may induce altruistic behaviours and create more complex societies. The findings of this study may be applicable not only to social evolution studies but also for effectively controlling ant behaviours.
Prognostic Value of Tumor-Infiltrating Lymphocytes in DCIS: A Meta-Analysis
Authors: Wu Shuang-Ling , Yu Xinmiao , Mao Xiaoyun , Jin Feng 
Published: October 2021

Abstract
BackgroundTumor infiltrating lymphocytes (TILs) have been demonstrated to be associated with the prognosis of breast ductal carcinoma in situ (DCIS). In this systematic review and meta-analysis, we investigated the role of TILs and TIL subsets in predicting the recurrence risk of DCIS.MethodPubMed, Medline, Web of Science, Embase and Cochrane were searched to identify publications investigating the prognostic role of TILs in DCIS. After study screening, data extraction and risk of bias assessment, a meta-analysis was performed to assess the association between TILs (total TILs, CD4+, CD8+, FOXP3+, PD-L1+ TILs) and the risk of DCIS recurrence.ResultsA pooled analysis indicated that dense stromal TILs in DCIS were associated with a higher recurrence risk (HR 2.11 (95% CI 1.35-3.28)). Subgroup analysis showed that touching TILs (HR 4.73 (95% CI 2.28-9.80)) was more favorable than the TIL ratio (HR 1.49 (95% CI 1.11-1.99)) in estimating DCIS recurrence risk. Moreover, the predictive value of TILs is suitable for patients who are diagnosed with DCIS and then undergo surgery (HR 2.77, (95% CI 1.26-6.07)) or surgery accompanied by radiotherapy (HR 2.26, (95% CI 1.29-3.95)), but not for patients who receive comprehensive adjuvant therapies (HR 1.16, (95% CI 1.35-3.28)). Among subsets of TILs, dense stromal PD-L1+ TILs were valuable in predicting higher recurrence risk of DCIS.ConclusionThis systematic review and meta-analysis confirmed the predictive value of TILs and stromal PD-L1+ TILs in DCIS and indicated an appropriate assessment method for TILs and an eligible population.
Prevalence, Risk Factors and Morbidity Profile of Schistosoma Infection Among Adults in the Taabo Health and Demographic Surveillance System, South-central Côte d’Ivoire
Authors: Bassa Fidèle K. , Eze Ikenna C. , Assaré Rufin K. , Essé Clémence , Koné Siaka , Acka Félix , Laubhouet-Koffi Véronique , Kouassi Dinard , Bonfoh Bassirou , Utzinger Jürg , N'Goran Eliezer K. 
Published: October 2021

Abstract
Background: Schistosomiasis remains an important public health issue among adults and infected individuals not treated serve as a reservoir of the parasite. Despite this fact, evidence on the epidemiology of schistosomiasis in adults in Côte d’Ivoire is scanty. This study aimed to determine the prevalence and risk factors of schistosomiasis among adults in the Taabo health and demographic surveillance system in the south-central part of Côte d’Ivoire.Methods: A cross-sectional survey was carried out in April and May 2017 in the frame of the “Côte d’Ivoire Dual Burden of Disease Study” (CoDuBu). A total of 901 randomly selected individuals, aged 18-90 years, provided blood, stool and urine samples for the diagnosis of malaria and helminth infections. With an emphasis on schistosomiasis, stool samples were subjected to the Kato-Katz technique for detection of Schistosoma mansoni eggs, while urine samples were examined for eggs of Schistosoma haematobium and circulating cathodic antigen of S. mansoni. Risk factors and morbidity profiles were assessed using health examination and questionnaires. Multinomial logistic regressions were employed to identify independent risk factors and morbidity patterns associated with S. mansoni mono- and co-infections.Results: The prevalence of S. mansoni and S. haematobium was 23.2% and 1.0%, respectively. Most S. mansoni were mono-infections (81.3%). Independent determinants of S. mansoni infection were young age, low socioeconomic status (mono- and co-infection) and poor hygiene practices (co-infection). S. mansoni infection was independently associated with higher pain and symptom scores (mono-infection), poor self-rated health and low healthcare use (co-infection).Conclusions: This study showed that adults represent a substantial reservoir of S. mansoni. To sustain schistosomiasis control and improve people’s wellbeing, it is important to expand preventive chemotherapy from school-aged children to adults, coupled with hygiene and health education.
Migraine Abortive Treatment in Children and Adolescents in Israel
Authors: Genizi Jacob , Lahoud Dana , Cohen Rony 
Published: October 2021

Abstract
Migraine headaches in children may cause attacks that require abortive treatment. This study evaluated the incidence and efficacy of medications used for relieving migraine headache attacks in the pediatric population in Israel. Children 6–18 years of age who were diagnosed in our pediatric neurology clinic as having migraine headaches were enrolled into the study. Children and their parents recorded the children response to abortive treatment during three consecutive migraine attacks. Fifty children, with 116 migraine attacks, were included in the study (30 females; mean age 12; range 6–18). Forty-seven (94%) reported on abortive treatment on the first migraine attack, 43 (86%) on a second migraine attack and 26 (52%) on a third migraine attack. During the first recorded migraine attack, 41 children (87.5%) reported taking only one type of medication for each headache episode, mainly ibuprofen or acetaminophen; less than a quarter used dipyrone. The improvement rate after two hours was 65.4%±27 for ibuprofen, 59.8±35.3 for acetaminophen and 50.9±27.4 for dipyrone. In conclusion, Children with migraine in Israel mainly use a single medication for each headache episode. Ibuprofen is the most commonly used abortive treatment; however, acetaminophen was associated with a better response.
Petrography, Palynology, and Organic Geochemistry of Neogene Paralic Coal, Mukah,Sarawak, Malaysia: Implications For Paleomires, and Peat-Forming Conditions
Authors: Abidin Nor Syazwani Zainal , Mustapha Khairul Azlan , Abdullah Wan Hasiah , Konjing Zainey 
Published: October 2021

Abstract
The eight coal seams of Neogene paralic coals from Mukah coalfield, Sarawak, Malaysia, were investigated using petrographical, palynological, and organic geochemical analyses to describe coal-forming vegetation, conditions during peat development and precursor mires, and their associations in a sequence-stratigraphic context. The petrographic data of the coals implies the existence of oxygen-deficient and water-saturated conditions in the precursor mires. The condition of low mire oxidation was followed by biomass loss from the mires. The Mukah coals are suggested to be deposited in freshwater peat swamps, and the rich preservation of angiosperm pollens indicates that the organic matter in dense and lowland forest vegetation was mostly terrigenous. The overwhelming presence of Casuarina and Calamus types, suggesting the paleomires were closely linked to Kerapah/Kerangas peat forest and marginally bordered by rattan and supported by the biomarker data. Rheotrophic–ombrotrophic mires were temporarily formed because of water table fluctuations, which strongly depend on ever-wet climate changes and syn-depositional tectonic during the Neogene, resulting in balanced to high peat accumulation and preservation. A maximum thickness of 35m of peat deposits that formed between 10,000 and 175,000 years ago is suggested. The coals are proposed to be influenced by transgressive to initial highstand cycles within the paralic setting.
Key Role of Mitochondrial Mutation Leu107Ser (COX1) in Deltamethrin Resistance in Salmon Lice (Lepeophtheirus Salmonis)
Authors: Tschesche Claudia , Bekaert Michaël , Bassett David I. , Boyd Sally , Bron James E. , Sturm Armin 
Published: October 2021

Abstract
Deltamethrin (DTM) is used to treat Atlantic salmon (Salmon salar) against salmon lice (Lepeophtheirus salmonis) infestations. However, development of DTM resistance has been reported from North Atlantic L. salmonis populations, in which resistance is associated with mitochondrial (mtDNA) mutations. This study investigated the relationship between DTM resistance and mtDNA single nucleotide polymorphisms (SNPs). A total of 188 L. salmonis collected from Scottish aquaculture sites were assessed using DTM bioassays and genotyped at 18 SNP loci. Genotyping further included archived parasites of known DTM susceptibility status. The results identified eleven mtDNA haplotypes, three of which were associated with DTM resistance. Phylogenetic analyses of haplotypes suggested multiple origins of DTM resistance. L. salmonis laboratory strains IoA-00 and IoA-10 showed similarly high levels (~100-fold) of DTM resistance in bioassays. Both strains differed strongly in mtDNA haplotype, but shared the missense mutation Leu107Ser in the mitochondrial gene cytochrome c oxidase subunit 1 (COX1), which was detected in all further DTM resistant L. salmonis isolates assessed. In crossing experiments with a DTM-susceptible strains, maternal inheritance of DTM resistance is apparent with both IoA-10 (this study) and IoA-02 (earlier reports). We conclude that Leu107Ser (COX1) is a main genetic determinant of DTM resistance in L. salmonis.
The Study of the Old Estates of the Northwestern Black Sea Region of Ukraine in the Aspect of Increasing the Recreational and Tourist Potential
Authors: STOROZHUK Svitlana , PRONCHENKO Andrii 
Published: October 2021

Abstract
The paper is devoted to the study of cultural and natural sights of the Northwestern Black Sea region of Ukraine, revealing their historical significance, unique architectural and urban planning solutions, and favorable location. The study identified and analyzed manors that have survived in the suburban areas of large cities. In world practice, examples have been identified of preserving the cultural and natural heritage of suburban areas through the development of their recreational and tourist potential. On the basis of the investigated cultural and natural attractions of the Northwestern Black Sea region, weekend tourist routes have been developed. The main focus of scientific work is on the study and conservation of natural resources and unique historical palaces and estates on the example of the palace of the Kurisov family. This makes it possible to use effectively recreational areas to create an ecologically clean, comfortable environment for recreation of the population and the development of domestic tourism, as a result of the current global pandemic of the coronavirus infection COVID-19, which caused the closure of the borders of many foreign countries.
Molecular Link between Circadian Rhythmicity and Mood Disorders
Authors: Faltraco Frank , Palm Denise , Coogan Andrew , Simon Frederick , Tucha Oliver , Thome Johannes 
Published: October 2021

Background:The internal clock is driven by circadian genes [e.g., Clock, Bmal1, Per1-3, Cry1-2], hormones [e.g., melatonin, cortisol], as well as zeitgeber [‘synchronisers’]. Chronic disturbances in the circadian rhythm in patients diagnosed with mood disorders have been recognised for more than 50 years.Objectives:The aim of this review is to summarise the current knowledge and literature regarding circadian rhythms in the context of mood disorders, focussing on the role of circadian genes, hormones, and neurotransmitters.Method:The review presents the current knowledge and literature regarding circadian rhythms in mood disorders using the Pubmed database. Articles with a focus on circadian rhythms and mood disorders [n=123], particularly from 1973 to 2020, were included.Results:The article suggests a molecular link between disruptions in the circadian rhythm and mood disorders. Circadian disturbances, caused by the dysregulation of circadian genes, hormones, and neurotransmitters, often result in a clinical picture resembling depression.Conclusion:Circadian rhythms are intrinsically linked to affective disorders, such as unipolar depression and bipolar disorder.
CRISPR Systems Suitable for Single AAV Vector Delivery
Authors: Stevanovic Marta , Piotter Elena , McClements Michelle E. , MacLaren Robert E. 
Published: October 2021

Abstract:
CRISPR (clustered regularly interspaced short palindromic repeats)/Cas gene editing is
a revolutionary technology that can enable the correction of genetic mutations in vivo, providing
great promise as a therapeutic intervention for inherited diseases. Adeno-associated viral (AAV)
vectors are a potential vehicle for delivering CRISPR/Cas. However, they are restricted by their
limited packaging capacity. Identifying smaller Cas orthologs that can be packaged, along with the
required guide RNA elements, into a single AAV would be an important optimization for CRISPR/-
Cas gene editing. Expanding the options of Cas proteins that can be delivered by a single AAV not
only increases translational application but also expands the genetic sites that can be targeted for
editing. This review considers the benefits and current scope of small Cas protein orthologs that are
suitable for gene editing approaches using single AAV vector delivery.
Pharmacophore Based Design of Probable FGFR-1 Inhibitors from the 3D
Crystal Structure of Infigratinib - A Drug Used in the Treatment of
Cholangiocarcinomas
Authors: Sarker Koushik , Ghosh Avijit , Saha Abhijit , Mishra Suvasish , Sen Subrata 
Published: October 2021

Background:
Pemigatinib (INCB054828) and Infigratinib (BGJ398) are the few selective
drugs that are approved by the FDA to treat cholangiocarcinoma, a rare form of bile duct cancer. Infigratinib
is a pan FGFR inhibitor and has been found promising in Phase-3, first-line PROOF clinical trial. So,
screening drug-like compounds having similar pharmacophoric features like infigratinib is the inspiration
of the present work.

Objective:
The objective was to identify drug-like compounds with similar pharmacophoric features as in
infigratinib. The compounds screened through the 3D query pharmacophore of infigratinib were also
predicted for ADMET properties so that the compounds may have good bioavailability.

Method:
A pharmacophore was generated from the crystal structure of infigratinib with several pharmacophoric
features such as hydrogen bond donor, hydrophobic, positive ionizable, and ring aromatic.
MayBridge database containing 65,263 compounds was used for virtual screening (VS) using LibDock.
The initial Hit compounds were subjected to ADMET predictions. Finally, two Hit compounds were selected
and docked with the FGFR-1 receptor to predict the interaction of the ligand atoms with the amino
acid residues of the receptor's active site.

Result:
The fit score for infigratinib, N-(4-fluorophenyl)-2-(5-((2-(4-methoxy-2,5-dimethylphenyl)-2-
oxoethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)acetamide (Hit-1) and 4-(4-((2-(5,6-dimethyl-1H-benzo[d]
imidazol-2-yl)ethyl)carbamoyl)pyridin-2-yl)-1-methylpiperazin-1-ium (Hit-4) is 4.58901, 4.36649, and
3.71732, respectively. The LibDock score of infigratinib, Hit-1, and Hit-4 is 122.474, 123.289, and
123.353, respectively. The binding affinity score (-PLP1) of infigratinib, Hit-1, and Hit-4 is -143.19, -
102.72, and -91.71.

Conclusion:
The present study concluded that the two compounds designated as Hit-1 and Hit-4 have
been identified as binders of FGFR-1, and Hit-4 occupies the whole pharmacophoric space of infigratinib,
and both the compounds LibDock scores are better than the infigratinib. The two compounds Hit-1 and
Hit-4 may be synthesized and studied for their enzyme inhibition assay on FGFR-1 and biologically evaluated
on different cell lines for Cholangiocarcinoma.
Inhibition of ERN1 Signaling is Important for the Suppression of Tumor Growth
Authors: Minchenko Oleksandr H. , Tsymbal Dariia O. , Khita Olena O. , Minchenko Dmytro O. 
Published: October 2021

Background:
Endoplasmic reticulum to nucleus signaling 1 (ERN1) is a major signaling
pathway of endoplasmic reticulum stress and is crucial for malignant tumor growth.

Objective:
The article aims to discuss the recent progress in the discovery of endoplasmic reticulum
stress targets and their involvement in tumor growth.

Methods:
Literature from the PubMed database related to the endoplasmic reticulum stress involvement
in the tumor growth and chemoresistance was searched and reviewed.

Results:
The endoplasmic reticulum stress plays an important part in malignant tumor growth and
is involved in invasion and metastasis. Inhibition of protein kinase and endoribonuclease activities
of the ERN1 signaling protein significantly reduces tumor growth through down-regulation of angiogenesis
and cell proliferation but activates the invasion. ERN1 knockdown affects the expression
of many genes associated with the regulation of apoptosis, cell proliferation, and survival as
well as reprograms the hypoxic regulation of most gene expressions. Simultaneously, inhibition of
ERN1 endoribonuclease only has a stronger suppressive effect on tumor growth and decreases the
invasiveness.

Conclusion:
Present review summarizes the recent advances in inhibiting ERN1 signaling that regulates
tumor growth. Further understanding of the regulatory mechanisms of genome reprogramming
upon inhibition of ERN1 signaling may help discover new possibilities for developing novel
effective therapeutics.
Microwave-Assisted Domino Cyclization Reactions
Authors: Wagh Yogesh B. , Dalal Dipak S. 
Published: October 2021

Background:
Microwave-assisted domino cyclization reactions have attracted great interest
for researchers to synthesize complex compounds in shorter times with increased yields.
The domino reactions were used in various synthetic approaches and many drug deliveries in medicinal
chemistry with microwave-assisted approaches.

Methods:
Microwave irradiation has been applied for various domino reactions. The research related
to microwave-assisted domino cyclization was reviewed and the important methodologies
were collected from 2011-2021.

Results:
Only those methodologies that involve microwave-assisted domino cyclization reactions
during synthesis in a related manner have been reviewed. Along with some recent syntheses that
are microwave-assisted regarding new heterocyclic moieties are summarized.

Conclusion:
Microwave-assisted domino cyclization reactions can be employed to quickly explore
and increase molecular diversity in synthetic chemistry. We hope that this review will be helpful
to find out complex molecule synthesis by microwave-assisted domino cyclization reactions.
This review aimed to explain the applications of microwaves for the domino reactions from 2011-
2021. In this respect, microwave-mediated methods help researchers to make helpful studies.
Effect of Electronic Device Addiction on Sleep Quality and Academic Performance Among Health Care Students: Cross-sectional Study
Authors: Qanash Sultan , Al-Husayni Faisal , Falata Haneen , Halawani Ohud , Jahra Enas , Murshed Boshra , Alhejaili Faris , Ghabashi Ala’a , Alhashmi Hashem 
Published: October 2021

Background
Sleep quality ensures better physical and psychological well-being. It is regulated through endogenous hemostatic, neurogenic, and circadian processes. Nonetheless, environmental and behavioral factors also play a role in sleep hygiene. Electronic device use is increasing rapidly and has been linked to many adverse effects, raising public health concerns.

Objective
This study aimed to investigate the impact of electronic device addiction on sleep quality and academic performance among health care students in Saudi Arabia.

Methods
A descriptive cross-sectional study was conducted from June to December 2019 at 3 universities in Jeddah. Of the 1000 students contacted, 608 students from 5 health sciences disciplines completed the questionnaires. The following outcome measures were used: Smartphone Addiction Scale for Adolescents–short version (SAS-SV), Pittsburgh Sleep Quality Index (PSQI), and grade point average (GPA).

Results
The median age of participants was 21 years, with 71.9% (437/608) being female. Almost all of the cohort used smartphones, and 75.0% (456/608) of them always use them at bedtime. Half of the students (53%) have poor sleep quality, while 32% are addicted to smartphone use. Using multivariable logistic regression, addiction to smartphones (SAS-SV score >31 males and >33 females) was significantly associated with poor sleep quality (PSQI >5) with an odds ratio of 1.8 (1.2-2.7). In addition, male gender and older students (age ≥21 years) were significantly associated with lower GPA (<4.5), with an odds ratio of 1.6 (1.1-2.3) and 2.3 (1.5-3.6), respectively; however, addiction to smartphones and poor sleep quality were not significantly associated with a lower GPA.

Conclusions
Electronic device addiction is associated with increased risk for poor sleep quality; however, electronic device addiction and poor sleep quality are not associated with increased risk for a lower GPA.