bluuebunny/crossref_metadata_2025_split huggingface dataset:
Death-stricken survivor mother: the lived experience of near miss mothers
Authors: Abdollahpour Sedigheh , Heydari Abbas , Ebrahimipour Hosein , Faridhoseini Farhad , Khadivzadeh Talat 
Published: January 2022

Abstract
Background
A Near Miss Mother (NMM) who survives life-threatening conditions, experiences intense physical, emotional, and psychological consequences following the maternal near-miss (MNM) events. The aim of this study was therefore to explore indepth understanding meaning of NMM everyday lived experiences on the social and cultural background of Iran.

Methods
This qualitative study utilized a hermeneutic phenomenology procedure. The study was conducted in hospitals affiliated with the Educational, Research and Treatment Centerwhich usually handle the NMMs. The sampling was purposeful with a maximum variation of eleven NMMs. Datawere collected using unstructured face-to-face interviews, and thetranscribed data were analyzed using Diekelmann, Allen, and Tanner’s seven-stage thematic analysis approach.

Results
"Death-stricken survivor mother" was the central emerged theme, and three extracted sub-themes included: "Distorted psyche on a journey to death", "physical destruction due to an ominous event ", and the "vicissitudinous life after reviving ". These sub-themes, in turn, involved 12 sub-themes that emerged from 38 common meanings and 1200 codes.

Conclusions
Findings demonstrate that the living conditions of NMMs are mixed in all aspects of the MNM event. They need a supportive program that includes additional follow-up visits, psychological support from the time of hospitalization until long-time after discharge, alleviation of social, sexual, and financial worries to return them to the normal life, as well as psychosocial rehabilitation to increase their life quality. Furthermore, post-discharge care in NMMs should be done actively and directly at their homes.
Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer’s disease related Aβ amyloidosis
Authors: Clark Alexander T. , Abrahamson Eric E. , Harper Matthew M. , Ikonomovic Milos D. 
Published: January 2022

Abstract
Background
Altered cerebrovascular function and accumulation of amyloid-β (Aβ) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer’s disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Aβ on cellular components of the NVU and capillary network are not well understood.

Methods
We exposed young adult (age range: 76–106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Aβ amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Aβ load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRβ-immunoreactive pericytes, and capillary densities in both genotypes.

Results
The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes.

Conclusion
In conditions of high brain concentrations of human Aβ, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.
Magnetic resonance findings may aid in diagnosis of protracted febrile myalgia syndrome: a retrospective, multicenter study
Authors: Aviran Neta , Amarilyo Gil , Lakovsky Yaniv , Tal Rotem , Garkaby Jenny , Haviv Rubi , Uziel Yosef , Spielman Shiri , Natour Hamada Mohammad , Herman Yonatan , Scheuerman Oded , Butbul Aviel Yonatan , Levinsky Yoel , Harel Liora 
Published: January 2022

Abstract
Background
Protracted febrile myalgia syndrome (PFMS) is a rare complication of Familial Mediterranean fever (FMF). The diagnosis is based on clinical symptoms and is often challenging, especially when PFMS is the initial manifestation of FMF. The aim of this report was to describe the magnetic resonance imaging (MRI) findings in pediatric patients with PFMS.

Results
There were three girls and two boys ranging in age from 6 months to 16 years, all of Mediterranean ancestry. Three had high-grade fever, and all had elevated inflammatory markers. MRI of the extremities yielded findings suggestive of myositis, which together with the clinical picture, normal CPK levels, and supporting family history of FMF, suggested the diagnosis of PFMS. Out of most common MEFV mutations tested, one patient was homozygous for M694V mutation, three were heterozygous for M694V mutation, and one was compound heterozygous for the M694V and V726A mutations.

Conclusions
MRI may serve as an auxiliary diagnostic tool in PFMS.
Descriptive review of internet-based cognitive behavior therapy on anxiety-related problems in children under the circumstances of COVID-19
Authors: Shirotsuki Kentaro , Sugaya Nagisa , Nakao Mutsuhiro 
Published: January 2022

Abstract
Background
COVID-19 continues to have a global impact and has yet to converge. Behavioral restrictions in daily life are widespread, forcing changes to the behavioral patterns of people. Significant changes have also occurred in children’s lives, raising concerns about mental health. The same is true for anxiety symptoms.

Research
In this paper, we described the COVID-19 pandemic effects on mental health, summarized Internet-based cognitive behavioral therapy (ICBT) as an applicability of cognitive behavioral therapy (CBT) for COVID-19, and summarized ICBT’s current state as a response for anxiety. An overview of previous intervention studies, including randomized controlled trials (RCTs) on ICBT, showed that many studies were highly effective against anxiety symptoms. Furthermore, regarding the follow-up of ICBT’s intervention effect, long-term effect maintenance was also clarified. It was likewise pointed out that ICBT may be used in the future since it is beneficial for children’s anxiety symptoms in telemedicine.

Conclusions
Based on these results from previous studies, we discuss ICBT’s applicability during the COVID-19 pandemic. Additionally, future measures and prospects for children’s mental health during the pandemic are discussed in this study.
Whose responsibility? Part 1 of 2: A scale to assess how stakeholders apportion responsibilities for addressing the needs of persons with mental health problems
Authors: Iyer Srividya N. , Pope Megan , Taksal Aarati , Mohan Greeshma , Rangaswamy Thara , Loohuis Heleen , Shah Jai , Joober Ridha , Schmitz Norbert , Margolese Howard C. , Padmavati Ramachandran , Malla Ashok 
Published: January 2022

Abstract
Background
Individuals with mental health problems have multiple, often inadequately met needs. Responsibility for meeting these needs frequently falls to patients, their families/caregivers, and governments. Little is known about stakeholders' views of who should be responsible for these needs and there are no measures to assess this construct. This study’s objectives were to present the newly designed Whose Responsibility Scale (WRS), which assesses how stakeholders apportion responsibility to persons with mental health problems, their families, and the government for addressing various needs of persons with mental health problems, and to report its psychometric properties.

Methods
The 22-item WRS asks respondents to assign relative responsibility to the government versus persons with mental health problems, government versus families, and families versus persons with mental health problems for seven support needs. The items were modelled on a World Values Survey item comparing the government’s and people’s responsibility for ensuring that everyone is provided for. We administered English, Tamil, and French versions to 57 patients, 60 family members, and 27 clinicians at two early psychosis programs in Chennai, India, and Montreal, Canada, evaluating test–retest reliability, internal consistency, and ease of use. Internal consistency estimates were also calculated for confirmatory purposes with the larger samples from the main comparative study.

Results
Test–retest reliability (intra-class correlation coefficients) generally ranged from excellent to fair across stakeholders (patients, families, and clinicians), settings (Montreal and Chennai), and languages (English, French, and Tamil). In the standardization and larger confirmatory samples, internal consistency estimates (Cronbach’s alphas) ranged from acceptable to excellent. The WRS scored average on ease of comprehension and completion. Scores were spread across the 1–10 range, suggesting that the scale captured variations in views on how responsibility for meeting needs should be distributed. On select items, scores at one end of the scale were never endorsed, but these reflected expected views about specific needs (e.g., Chennai patients never endorsed patients as being substantially more responsible for housing needs than families).

Conclusions
The WRS is a promising measure for use across geo-cultural contexts to inform mental health policies, and to foster dialogue and accountability among stakeholders about roles and responsibilities. It can help researchers study stakeholders’ views about responsibilities, and how these shape and are shaped by sociocultural contexts and mental healthcare systems.
Knockout of circRNAs by base editing back-splice sites of circularized exons
Authors: Gao Xiang , Ma Xu-Kai , Li Xiang , Li Guo-Wei , Liu Chu-Xiao , Zhang Jun , Wang Ying , Wei Jia , Chen Jia , Chen Ling-Ling , Yang Li 
Published: January 2022

AbstractMany circular RNAs (circRNAs) are produced from back-splicing of exons of precursor mRNAs and are generally co-expressed with cognate linear RNAs. Methods for circRNA-specific knockout are lacking, largely due to sequence overlaps between forms. Here, we use base editors (BEs) for circRNA depletion. By targeting splice sites involved in both back-splicing and canonical splicing, BEs can repress circular and linear RNAs. Targeting sites predominantly for circRNA biogenesis, BEs could efficiently repress the production of circular but not linear RNAs. As hundreds of exons are predominantly back-spliced to produce circRNAs, this provides an efficient method to deplete circRNAs for functional study.
Evolution of the repression mechanisms in circadian clocks
Authors: Tyler Jonathan , Lu Yining , Dunlap Jay , Forger Daniel B. 
Published: January 2022

Abstract
Background
Circadian (daily) timekeeping is essential to the survival of many organisms. An integral part of all circadian timekeeping systems is negative feedback between an activator and repressor. However, the role of this feedback varies widely between lower and higher organisms.

Results
Here, we study repression mechanisms in the cyanobacterial and eukaryotic clocks through mathematical modeling and systems analysis. We find a common mathematical model that describes the mechanism by which organisms generate rhythms; however, transcription’s role in this has diverged. In cyanobacteria, protein sequestration and phosphorylation generate and regulate rhythms while transcription regulation keeps proteins in proper stoichiometric balance. Based on recent experimental work, we propose a repressor phospholock mechanism that models the negative feedback through transcription in clocks of higher organisms. Interestingly, this model, when coupled with activator phosphorylation, allows for oscillations over a wide range of protein stoichiometries, thereby reconciling the negative feedback mechanism in Neurospora with that in mammals and cyanobacteria.

Conclusions
Taken together, these results paint a picture of how circadian timekeeping may have evolved.
Phiclust: a clusterability measure for single-cell transcriptomics reveals phenotypic subpopulations
Authors: Mircea Maria , Hochane Mazène , Fan Xueying , Chuva de Sousa Lopes Susana M. , Garlaschelli Diego , Semrau Stefan 
Published: January 2022

AbstractThe ability to discover new cell phenotypes by unsupervised clustering of single-cell transcriptomes has revolutionized biology. Currently, there is no principled way to decide whether a cluster of cells contains meaningful subpopulations that should be further resolved. Here, we present phiclust (ϕclust), a clusterability measure derived from random matrix theory that can be used to identify cell clusters with non-random substructure, testably leading to the discovery of previously overlooked phenotypes.
Ivermectin as an endectocide may boost control of malaria vectors in India and contribute to elimination
Authors: Ahmad Sundus Shafat , Rahi Manju , Saroha Poonam , Sharma Amit 
Published: January 2022

AbstractMalaria constitutes one of the largest public health burdens faced by humanity. Malaria control has to be an efficient balance between diagnosis, treatment and vector control strategies. The World Health Organization currently recommends indoor residual spraying and impregnated bed nets as two malaria vector control methods that have shown robust and persistent results against endophilic and anthropophilic mosquito species. The Indian government launched the National Framework for Malaria Elimination in 2016 with the aim to achieve the elimination of malaria in a phased and strategic manner and to sustain a nation-wide malaria-free status by 2030. India is currently in a crucial phase of malaria elimination and novel vector control strategies maybe helpful in dealing with various challenges, such as vector behavioural adaptations and increasing insecticide resistance among the Anopheles populations of India. Ivermectin can be one such new tool as it is the first endectocide to be approved in both animals and humans. Trials of ivermectin have been conducted in endemic areas of Africa with promising results. In this review, we assess available data on ivermectin as an endectocide and propose that this endectocide should be explored as a vector control tool for malaria in India.
Graphical Abstract
A dataset for dental anxiety and psychological distress in 1550 patients visiting dental clinics
Authors: Zinke Alexander , Bohl Christin , Berth Hendrik 
Published: January 2022

Abstract
Objectives
Information was collected to identify anxiety in dental patients visiting a dental clinic using the Dental Anxiety Scale, their level of psychological distress using the Brief Symptom Inventory-18 and identifying a correlation between these groups as well as the gender and age.

Data description
This data contains a set of 1550 patients’ answers to questionnaires taken before dental treatment in a dental clinic. It is divided into male and female patients as well as according to their age. The level of Dental Anxiety can be interpreted by answers chosen in the Dental Anxiety Scale (DAS) and the level of psychological distress by answers chosen in the Brief Symptom Inventory-18 (BSI-18). This dataset should help to encourage more research in the field of dental anxiety and we hope to see more comparisons with our data in the future or in different regions of the world.
CRISPR/Cas9 genome editing system confirms centriolin’s role in cytokinesis
Authors: Seronick Eric , Son Jae , Michael Cameron , Fogg Hannah , Gromley Zeynep , Gromley Adam 
Published: January 2022

Abstract
Objective
In addition to its function as the microtubule organizing center of the cell, the centrosome has functions in many other cellular processes including primary cilia formation, DNA damage checkpoints, and cell cycle progression. But the role of individual components of the centrosome in these processes remains unclear. Previous studies used siRNA (small interfering RNA) to “knock down” protein levels of the centrosome component centriolin, resulting in failed cytokinesis. Since this approach was transient, only targeting centriolin at the mRNA level, we sought to confirm these findings by permanently disrupting the gene encoding centriolin using the CRISPR/Cas9 system of genome editing.

Results
This study provides evidence that the CRISPR/Cas9 system is capable of effectively reducing centriolin protein levels in the cell. Furthermore, this disruption leads to a failure of cytokinesis that is reminiscent of the phenotype previously reported for the siRNA-mediated disruption of centriolin. Furthermore, no additional defects in cell division were observed, consistent with results seen with previous siRNA studies. We conclude that the CRISPR/Cas9 system is an effective means of permanently removing the cellular pools of centriolin and that the disruption of centriolin at both the mRNA level and genomic level lead to similar cell division defects.
Using parallel pre-trained types of DCNN model to predict breast cancer with color normalization
Authors: Al Noumah William , Jafar Assef , Al Joumaa Kadan 
Published: January 2022

Abstract
Objective
Breast cancer is the most common among women, and it causes many deaths every year. Early diagnosis increases the chance of cure through treatment. The traditional manual diagnosis requires effort and time from pathological experts, as it needs a joint experience of a number of pathologists. Diagnostic mistakes can lead to catastrophic results and endanger the lives of patients. The presence of an expert system that is able to specify whether the examined tissue is healthy or not, thus improves the quality of diagnosis and saves the time of experts. In this paper, a model capable of classifying breast cancer anatomy by making use of a pre-trained DCNN has been proposed. To build this model, first of all the image should be color stained by using Vahadane algorithm, then the model which combines three pre-trained DCNN (Xception, NASNet and Inceptoin_Resnet_V2) should be built in parallel, then the three branches should be aggregated to take advantage of each other. The suggested model was tested under different values of threshold ratios and also compared with other models.

Results
The proposed model on the BreaKHis dataset achieved 98% accuracy, which is better than the accuracy of other models used in this field.
Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer’s disease
Authors: Fang Jiansong , Zhang Pengyue , Wang Quan , Chiang Chien-Wei , Zhou Yadi , Hou Yuan , Xu Jielin , Chen Rui , Zhang Bin , Lewis Stephen J. , Leverenz James B. , Pieper Andrew A. , Li Bingshan , Li Lang , Cummings Jeffrey , Cheng Feixiong 
Published: January 2022

Abstract
Background
Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer’s disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful.

Methods
To address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein–protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics. When applied to AD, this approach integrates GWAS findings, multi-omics data from brain samples of AD patients and AD transgenic animal models, drug-target networks, and the human protein–protein interactome, along with large-scale patient database validation and in vitro mechanistic observations in human microglia cells.

Results
Through this approach, we identified 103 ARGs validated by various levels of pathobiological evidence in AD. Via network-based prediction and population-based validation, we then showed that three drugs (pioglitazone, febuxostat, and atenolol) are significantly associated with decreased risk of AD compared with matched control populations. Pioglitazone usage is significantly associated with decreased risk of AD (hazard ratio (HR) = 0.916, 95% confidence interval [CI] 0.861–0.974, P = 0.005) in a retrospective case-control validation. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR) agonist used to treat type 2 diabetes, and propensity score matching cohort studies confirmed its association with reduced risk of AD in comparison to glipizide (HR = 0.921, 95% CI 0.862–0.984, P = 0.0159), an insulin secretagogue that is also used to treat type 2 diabetes. In vitro experiments showed that pioglitazone downregulated glycogen synthase kinase 3 beta (GSK3β) and cyclin-dependent kinase (CDK5) in human microglia cells, supporting a possible mechanism-of-action for its beneficial effect in AD.

Conclusions
In summary, we present an integrated, network-based artificial intelligence methodology to rapidly translate GWAS findings and multi-omics data to genotype-informed therapeutic discovery in AD.
Puromycin-based purification of cells with high expression of the cytochrome P450 CYP3A4 gene from a patient with drug-induced liver injury (DILI)
Authors: Miyata Shoko , Saku Noriaki , Akiyama Saeko , Javaregowda Palaksha Kanive , Ite Kenta , Takashima Nagisa , Toyoda Masashi , Yura Kei , Kimura Tohru , Nishina Hiroshi , Nakazawa Atsuko , Kasahara Mureo , Nonaka Hidenori , Kiyono Tohru , Umezawa Akihiro 
Published: January 2022

Abstract
Background
Many drugs have the potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in hepatocytes. Hepatocytes can be accurately evaluated for drug-mediated CYP3A4 induction; this is the gold standard for in vitro hepatic toxicology testing. However, the variation from lot to lot is an issue that needs to be addressed. Only a limited number of immortalized hepatocyte cell lines have been reported. In this study, immortalized cells expressing CYP3A4 were generated from a patient with drug-induced liver injury (DILI).

Methods
To generate DILI-derived cells with high expression of CYP3A4, a three-step approach was employed: (1) Differentiation of DILI-induced pluripotent stem cells (DILI-iPSCs); (2) Immortalization of the differentiated cells; (3) Selection of the cells by puromycin. It was hypothesized that cells with high cytochrome P450 gene expression would be able to survive exposure to cytotoxic antibiotics because of their increased drug-metabolizing activity. Puromycin, a cytotoxic antibiotic, was used in this study because of its rapid cytocidal effect at low concentrations.

Results
The hepatocyte-like cells differentiated from DILI-iPSCs were purified by exposure to puromycin. The puromycin-selected cells (HepaSM or SI cells) constitutively expressed the CYP3A4 gene at extremely high levels and exhibited hepatocytic features over time. However, unlike primary hepatocytes, the established cells did not produce bile or accumulate glycogen.

Conclusions
iPSC-derived hepatocyte-like cells with intrinsic drug-metabolizing enzymes can be purified from non-hepatocytes and undifferentiated iPSCs using the cytocidal antibiotic puromycin. The puromycin-selected hepatocyte-like cells exhibited characteristics of hepatocytes after immortalization and may serve as another useful source for in vitro hepatotoxicity testing of low molecular weight drugs.