bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of PTSD and generalized anxiety symptoms during the first wave of COVID-19 outbreak: an exploratory study of a large sample of the Italian population
Authors: Brivio Eleonora , Oliveri Serena , Guiddi Paolo , Pravettoni Gabriella 
Published: June 2021

Abstract
Background
During the COVID-19 pandemic, between March and May 2020, in Italy, people were asked to shelter in place and most had to put their life on hold, while news of the spread of the virus constantly were broadcasted. The change in habits and the potential exposure to a dangerous virus can be categorized as a catastrophic event, which are usually traumatic and therefore have psychological consequences for the people involved.

Objective
Assuming the COVID-19 pandemic as a possible traumatic event, this study aims to explore the contingent behavioural and psychological impact of COVID-19 spread and related lockdown on the Italian general population, through measuring anxiety and post-traumatic stress symptoms .

Methods
An ad hoc-survey was set up for the this exploratory research, including the standardized Italian versions of the Impact of Event Scale Revised (IES-R) and the Generalized Anxiety Scale (GAD-7), and ad hoc items concerning behavioural reactions due to the pandemic spread and related mass quarantine. Participants were recruited across convenient web-based and mobile app channels using a snowball sampling technique. Data was collected from March 25th to May 1st, 2020.

Participants
One-thousand one hundred and ninety-five individuals (851 women and 342 men) completed 60% or more of the survey and were considered for analyses. Mean age was 40 years (s.d. = 14.948). Participants resided in 78 Italian provinces (out of 107 territorial divisions), with 25.7% residing in the Milan province and 9.2% from the Monza and Brianza provinces, closest to the epicentre of the Italian outbreak.

Results
During the worst months of the first wave of the Pandemic, the Italian population suffered high level of distress (GAD-7 m = 6.89, s.d. = 5.08; IER-R mean score = 27.86, s.d. 17.46), respectively indicating mild presence of anxiety symptoms, and high levels of PTSD symptoms. Gender seems to be a discriminating variable with women scoring significantly higher than man, both for anxiety symptoms (H (1) = 82.91, p < .001) and all dimensions of PTSD symptoms (intrusion H (1) = 71.23, p < .001, avoidance H (1) = 61.28, p < .001), and hyperarousal (H (1) = 67.348, p < .001). People from Generations Y and Z show to be at higher risk of developing PTSD (V = .746, F (3,1041) =1017.19, p = .001) and GAD symptoms (F (3,1041) = 5.113, p = .002) than older generations.

Conclusions
Gender and generation appeared to be the most consistent risk factor for higher levels of generalized anxiety and PTSD symptoms in the current pandemic. Other variables – such as information seeking behaviours, parental and marriage status, chronic conditions – yielded less consistent evidence. Results indicate the need of including psychological interventions as a standard tool during the emergency management of a catastrophic events such as a pandemic.
Prevalence and factors associated with major depression among female sex workers in post-conflict Gulu district: a cross-sectional study
Authors: Ouma Simple , Tumwesigye Nazarius Mbona , Ndejjo Rawlance , Abbo Catherine 
Published: June 2021

Abstract
Background
Female sex workers operating in conflict-affected settings could be at a much greater risk of major depression. However, the epidemiology of major depression in this population remains understudied. We aimed to determine the prevalence and the factors associated with major depression among FSWs in the post-conflict Gulu district in Northern Uganda.

Methods
We conducted a cross-sectional study among 300 randomly selected adult female sex workers in Gulu. We utilized a pre-tested semi-structured questionnaire, embedded with MINI 7.0.0, to gather information from each participant through face-to-face interviews. We collected data on socio-demographic characteristics, sex-work-related characteristics, alcohol and drug use, HIV status, and major depression. Then, data were entered into EPI INFO 7 and analyzed using logistic regression with the aid of STATA 14.0.

Results
The mean age (SD) of the study participants was 26.4 (± 6) years, 57.7% attained primary education, 51.7% never married, and 42.1% were living with HIV. The prevalence of major depression among FSWs in the district was 47.7%. In addition, the majority of the FSWs with major depression (91.0%) had either severe (50.4%) or moderate (40.6%) depressive symptoms. Independently, life stress (adjusted OR = 10.8, 95%CI: 5.67–20.57), living with HIV (adjusted OR = 2.25, 95%CI: 1.25–4.05), verbal abuse (adjusted OR = 2.27, 95%CI: 1.27–4.08), and older age (adjusted OR = 1.06, 95%CI: 1.01–1.12) all showed positive associations with major depression. Conversely, provision of sexual services from clients’ homes (adjusted OR = 0.50, 95%CI: 0.25–0.97), use of a non-barrier modern family planning method (adjusted OR = 0.44, 95%CI: 0.24–0.82), and daily intake of alcohol (adjusted OR = 0.50, 95%CI: 0.28–0.88) all showed negative associations with major depression.

Conclusions
There is a high prevalence of major depression among female sex workers in post-conflict Gulu. The high prevalence of major depression underscores the need for government and development partners to urgently and adequately address the mental health needs of female sex workers.
DPARD: rationale, design and initial results from the Dutch national diabetes registry
Authors: Bak Jessica C. G. , Mul Dick , Serné Erik H. , de Valk Harold W. , Sas Theo C. J. , Geelhoed-Duijvestijn Petronella H. , Kramer Mark H. H. , Nieuwdorp Max , Verheugt Carianne L. 
Published: June 2021

Abstract
Background
Treatment of diabetes mellitus has majorly improved over the past century, however, the disease burden is high and its prevalence still expanding. Further insight in the diabetes population is imperative to improve the quality of diabetes care by enhancement of knowledge-based diabetes management strategies. To this end, in 2017 a Dutch nationwide consortium of diabetologists, paediatric endocrinologists, and diabetes patients has founded a national outpatient diabetes care registry named Dutch Pediatric and Adult Registry of Diabetes (DPARD). We aim to describe the implementation of DPARD and to provide an overview of the characteristics of patients included during the first 2 years.

Methods
For the DPARD cohort with long-term follow-up of observational nature, hospital data are gathered directly from electronic health records and securely transferred and stored. DPARD provides weekly updated clinical information on the diabetes population care on a hospital-level benchmarked against the national average.

Results
Between November 2017 and January 2020, 20,857 patients were included from 8 (11%) Dutch hospitals with a level of care distribution representative of all diabetic outpatients in the Netherlands. Among patients with known diabetes type, 41% had type 1 diabetes, 51% type 2 diabetes, and 8% had diabetes due to other causes. Characteristics of the total patient population were similar to patients with unknown diabetes classification. HbA1c levels decreased over the years, while BMI levels showed an increase over time.

Conclusions
The national DPARD registry aims to facilitate investigation of prevalence and long-term outcomes of Dutch outpatients with diabetes mellitus and their treatment, thus allowing for quality improvement of diabetes care as well as allowing for comparison of diabetes care on an international level.
Mechanical force system of double key loop with finite element analysis
Authors: Liu Jiali , Zhang Duanqiang , Xu Linyu , Cai Senxin , Guo Jinquan , Chen Jiang , Su Jiehua 
Published: June 2021

Abstract
Background
The mechanics of double key loop (DKL) are not well defined, and this finite element study was designed to explore its force system.

Methods
A simplified 3-dimensional finite element model of single and double key loops with an archwire between the lateral incisor and second premolar was established in Ansys Workbench 17.0. Activation in Type-1 (retraction at the distal end), Type-2 (retraction at the distal key) and Type-3 (Type-2 plus ligation between keys) was simulated. The vertical force, load/deflection ratio and moment/force ratio of stainless-steel and titanium-molybdenum alloy (TMA) loops were calculated and compared.

Results
The double key loop generated approximately 40% of the force of a single key loop. Type-2 loading of DKL showed a higher L/D ratio than Type-1 loading with a similar M/F ratio. Type-3 loading of DKL showed the highest M/F ratio with a similar L/D ratio as single key loop. The M/F ratio in Type-3 loading increased with the decreasing of retraction force. The DKL of TMA produced approximately 40% of the force and moment compared with those of SS in all loading types. When activated at equal distances below 1 mm, the M/F ratios of SS and TMA DKL with equal preactivation angles were almost the same.

Conclusion
The M/F ratio on anterior teeth increases with the preactivation angle and deactivation of DKL. The M/F ratio at a certain distance of activation mainly depends on the preactivation angle instead of the wire material. TMA is recommended as a substitute for SS in DKL for a lower magnitude of force.
Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy
Authors: Huang Chiun-Wei , Chuang Chia-Pao , Chen Yan-Jun , Wang Hsu-Yuan , Lin Jia-Jia , Huang Chiung-Yin , Wei Kuo-Chen , Huang Feng-Ting 
Published: June 2021

AbstractBackgroundFerritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood–brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system.ResultsIn this study, a unique integrin α2β1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2β1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days.ConclusionsWe believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine.Graphic Abstract
Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials
Authors: Coles Theresa M. , Hernandez Adrian F. , Reeve Bryce B. , Cook Karon , Edwards Michael C. , Boutin Marc , Bush Elizabeth , Degboe Arnold , Roessig Lothar , Rudolph Amy , McNulty Pauline , Patel Nikunj , Kay-Mugford Trish , Vernon Margaret , Woloschak Michael , Buchele Gustavo , Spertus John A. , Roe Matthew T. , Bury Denise , Weinfurt Kevin 
Published: June 2021

Abstract
Objectives
There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge.

Methods
Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States.

Results
Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims.

Conclusions
A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.
Sonication fluid culture of antibiotic-loaded bone cement spacer has high accuracy to confirm eradication of infection before reimplantation of new prostheses
Authors: Zhang Qingyu , Ding Baocong , Wu Jinglin , Dong Jun , Liu Fanxiao 
Published: June 2021

Abstract
Background
Sonication fluid culture of antibiotic-loaded bone cement spacer has been used to predict reinfection of two-stage revision, but its value remains disputable. This study aims to evaluate the association between the culture result of the sonicated spacer and the status of patients with periprosthetic joint infection receiving two-stage revision.

Materials and methods
A comprehensive electronic literature search was performed through four databases including PubMed, Embase/Ovid, and EBSCO, and the Cochrane Library to retrieve studies in which sonication fluid culture of the antibiotic spacer was conducted before reimplantation. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the association between the culture result of sonicated spacer and prognosis of the two-stage revision.

Results
Eleven eligible studies comprising 603 artificial joints with PJI (134 suffering a clinical failure of two-stage revision) were included in the quantitative analysis. The pooled incidences of positive culture of sonicated spacer and intraoperative tissue were 0.14 (95% confidence interval [CI] 0.08–0.21) and 0.14 (95% CI 0.08–0.20), respectively. A positive culture of sonicated antibiotic-loaded bone cement spacer illustrated moderate sensitivity (0.31, 95% CI 0.13–0.58) but high specificity (0.94, 95% CI 0.86–0.98) for the diagnosis of therapeutic failure of two-stage revision; the pooled DOR was 7.67 (95% CI, 3.63–16.22). Meanwhile, the pooled sensitivity, specificity, and DOR of intraoperative tissue culture during the two-stage revision to predict therapeutic failure were 0.32 (95% CI, 0.20–0.47), 0.96 (95% CI, 0.92–0.98), and 10.62 (95% CI, 4.90–23.01), respectively.

Conclusions
Sonication fluid culture of antibiotic-loaded bone cement spacer revealed high accuracy for confirming eradication of infection before reimplantation of new prostheses and therefore could be used as a supplement for assessing therapeutic effect for PJI. However, both sonication fluid culture and intraoperative tissue culture from antibiotic-loaded bone cement spacer showed restricted yield for the prediction of a septic failure after the two-stage revision of PJI. Large-scale, prospective studies are still needed to testify current findings.
High-throughput surface marker screen on primary human breast tissues reveals further cellular heterogeneity
Authors: Virtanen Siru , Schulte Reiner , Stingl John , Caldas Carlos , Shehata Mona 
Published: June 2021

Abstract
Background
Normal human breast tissues are a heterogeneous mix of epithelial and stromal subtypes in different cell states. Delineating the spectrum of cellular heterogeneity will provide new insights into normal cellular properties within the breast tissue that might become dysregulated in the initial stages of cancer. Investigation of surface marker expression provides a valuable approach to resolve complex cell populations. However, the majority of cell surface maker expression of primary breast cells have not been investigated.

Methods
To determine the differences in expression of a range of uninvestigated cell surface markers between the normal breast cell subpopulations, primary human breast cells were analysed using high-throughput flow cytometry for the expression of 242 cell surface proteins in conjunction with EpCAM/CD49f staining.

Results
We identified 35 surface marker proteins expressed on normal breast epithelial and/or stromal subpopulations that were previously unreported. We also show multiple markers were equally expressed in all cell populations (e.g. CD9, CD59, CD164) while other surface markers were confirmed to be enriched in different cell lineages: CD24, CD227 and CD340 in the luminal compartment, CD10 and CD90 in the basal population, and CD34 and CD140b on stromal cells.

Conclusions
Our dataset of CD marker expression in the normal breast provides better definition for breast cellular heterogeneity.
Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis
Authors: Chen Zhi-Qiang , Zan Yanjun , Milesi Pascal , Zhou Linghua , Chen Jun , Li Lili , Cui BinBin , Niu Shihui , Westin Johan , Karlsson Bo , García-Gil Maria Rosario , Lascoux Martin , Wu Harry X. 
Published: June 2021

Abstract
Background
Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived tree species. Although an extensive amount of phenotypic data already exists in breeding programs, accounting for its high heterogeneity is a great challenge. We combine spatial and factor-analytics analyses to standardize the heterogeneous data from 120 field experiments of 483,424 progenies of Norway spruce to implement the largest reported GWAS for trees using 134 605 SNPs from exome sequencing of 5056 parental trees.

Results
We identify 55 novel quantitative trait loci (QTLs) that are associated with phenotypic variation. The largest number of QTLs is associated with the budburst stage, followed by diameter at breast height, wood quality, and frost damage. Two QTLs with the largest effect have a pleiotropic effect for budburst stage, frost damage, and diameter and are associated with MAP3K genes. Genotype data called from exome capture, recently developed SNP array and gene expression data indirectly support this discovery.

Conclusion
Several important QTLs associated with growth and frost damage have been verified in several southern and northern progeny plantations, indicating that these loci can be used in QTL-assisted genomic selection. Our study also demonstrates that existing heterogeneous phenotypic data from breeding programs, collected over several decades, is an important source for GWAS and that such integration into GWAS should be a major area of inquiry in the future.
Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes
Authors: Tan Liqiang , Cheng Weisheng , Liu Fang , Wang Dan Ohtan , Wu Linwei , Cao Nan , Wang Jinkai 
Published: June 2021

AbstractBackgroundCanonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms.ResultsHere, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m6A levels than their cognate protein-coding genes, associated with de novo m6A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m6A motifs during evolution. The m6A sites of pseudogenes are evolutionarily younger than neutral sites and their m6A levels are increasing, supporting the idea that m6A on the RNAs of pseudogenes is under positive selection. We then find that the m6A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m6A RNA modification of two processed pseudogenes,DSTNP2andNAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genesDSTNandNAP1L4. In addition, the m6A ofDSTNP2regulation of DSTN is partially dependent on the miRNA miR-362-5p.ConclusionsOur discovery reveals a novel evolutionary role of m6A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.