bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttraumatic stress disorder symptoms among trauma-exposed adolescents from low- and middle-income countries
Authors: Stupar Dusko , Stevanovic Dejan , Vostanis Panos , Atilola Olayinka , Moreira Paulo , Dodig-Curkovic Katarina , Franic Tomislav , Doric Ana , Davidovic Nikolina , Avicenna Mohamad , Multazam Isa Noor , Nussbaum Laura , Thabet Abdul Aziz , Ubalde Dino , Petrov Petar , Deljkovic Azra , Monteiro Antonio Luis , Ribas Adriana , Jovanovic Mirjana , Joana Oliveira , Knez Rajna 
Published: June 2021

AbstractBackgroundExposure to traumatic events in childhood is associated with the development and maintenance of various psychiatric disorders, but most frequently with posttraumatic stress disorder (PTSD). The aim of this study was to evaluate the types of traumatic events experienced and the presence and predictors of PTSD symptoms among adolescents from the general population from ten low- and middle-income countries (LMICs).MethodsData were simultaneously collected from 3370 trauma-exposed adolescents (mean age = 15.41 [SD = 1.65] years, range 12–18; 1465 (43.5%) males and 1905 (56.5%) females) in Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, the Palestinian Territories, the Philippines, Romania, and Serbia, with Portugal, a high-income country, as a reference point. The UCLA PTSD Reaction Index for the DSM-5 (PTSD-RI-5) was used for the assessment of traumatic events and PTSD symptoms.ResultsThe most frequently reported traumatic events were death of a close person (69.7%), witnessing violence other than domestic (40.5%), being in a natural disaster (34.4%) and witnessing violent death or serious injury of a close person (33.9%). In total, 28.5% adolescents endorsed two to three DSM-5 PTSD criteria symptoms. The rates of adolescents with symptoms from all four DSM-5 criteria for PTSD were 6.2–8.1% in Indonesia, Serbia, Bulgaria, and Montenegro, and 9.2–10.5% in Philippines, Croatia and Brazil. From Portugal, 10.7% adolescents fall into this category, while 13.2% and 15.3% for the Palestinian Territories and Nigeria, respectively. A logistic regression model showed that younger age, experiencing war, being forced to have sex, and greater severity of symptoms (persistent avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity) were significant predictors of fulfilling full PTSD criteria.ConclusionsNearly every third adolescent living in LMICs might have some PTSD symptoms after experiencing a traumatic event, while nearly one in ten might have sufficient symptoms for full DSM-5 PTSD diagnosis. The findings can inform the generation of PTSD burden estimates, allocation of health resources, and designing and implementing psychosocial interventions for PTSD in LMICs.
Preclinical models as patients’ avatars for precision medicine in colorectal cancer: past and future challenges
Authors: Durinikova Erika , Buzo Kristi , Arena Sabrina 
Published: June 2021

AbstractColorectal cancer (CRC) is a complex and heterogeneous disease, characterized by dismal prognosis and low survival rate in the advanced (metastatic) stage. During the last decade, the establishment of novel preclinical models, leading to the generation of translational discovery and validation platforms, has opened up a new scenario for the clinical practice of CRC patients. To bridge the results developed at the bench with the medical decision process, the ideal model should be easily scalable, reliable to predict treatment responses, and flexibly adapted for various applications in the research. As such, the improved benefit of novel therapies being tested initially on valuable and reproducible preclinical models would lie in personalized treatment recommendations based on the biology and genomics of the patient’s tumor with the overall aim to avoid overtreatment and unnecessary toxicity. In this review, we summarize different in vitro and in vivo models, which proved efficacy in detection of novel CRC culprits and shed light into the biology and therapy of this complex disease. Even though cell lines and patient-derived xenografts remain the mainstay of colorectal cancer research, the field has been confidently shifting to the use of organoids as the most relevant preclinical model. Prioritization of organoids is supported by increasing body of evidence that these represent excellent tools worth further therapeutic explorations. In addition, novel preclinical models such as zebrafish avatars are emerging as useful tools for pharmacological interrogation. Finally, all available models represent complementary tools that can be utilized for precision medicine applications.
Patient-Reported OUtcome measures in key African languages to promote Diversity in research and clinical practice (PROUD)—protocol for a systematic review of measurement properties
Authors: Heine Martin , Mokkink Lidwine B. , van Zyl Chanel , Derman Wayne , Hanekom Susan 
Published: June 2021

Abstract
Introduction
Sub-Saharan Africa is a subcontinent with a proud cultural richness and diversity, yet inexplicably also a region with severe health care challenges and inequity. To challenge this health equity gap and reduce the burden of disease, the patient’s voice in monitoring and evaluation of health and health care interventions is paramount. The aim of this two-phased review is to map the availability of patient-reported outcome measures (PROMs) in a selection of non-English, African Languages, and systematically evaluate the measurement properties of the PROMs that were identified.

Methods
This systematic review will be conducted in two phases. In phase 1, we will scope the literature for patient-reported outcome measures (PROMs), either developed from scratch or through translation and validation in a sub-Saharan African country and a selection of non-English, African languages (n = 31; spoken in > 10 million people and/or a national language). The availability of PROMs will be mapped against the previously reported burden of disease in the respective countries included. Subsequently, in phase 2, we systematically evaluate the measurement properties of these PROMs using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology for systematic reviews on PROMs. To ensure rigour, secondary searches will be developed to specifically locate articles that report on the measurement properties of the PROMs identified during phase 1. The evidence will be graded using the modified GRADE approach.

Discussion
This review will provide a comprehensive overview and quality appraisal of PROMs developed in non-English, African languages. Consequently, this review when concluded may be an important first step in promoting access to these PROMs for use in clinical practice and research, as well as facilitate identification and prioritization of key knowledge gaps.
Computed tomography imaging of septic shock. Beyond the cause: the “CT hypoperfusion complex”. A pictorial essay
Authors: Di Serafino Marco , Viscardi Daniela , Iacobellis Francesca , Giugliano Luigi , Barbuto Luigi , Oliva Gaspare , Ronza Roberto , Borzelli Antonio , Raucci Antonio , Pezzullo Filomena , De Cristofaro Maria Giovanna , Romano Luigia 
Published: June 2021

AbstractSeptic shock is a medical emergency that represents one of the most important underlying causes for presentation to the Emergency Department. Sepsis is defined as organ dysfunction, life-threatening event caused by a deregulated inflammatory host response to infection, with a mortality risk ranging from 10 to 40%. Early sepsis identification is the cornerstone of management and diagnostic imaging can play a pivotal role in this clinical context. The choice of imaging modality depends on several factors, associated with the clinical condition and the presence or absence of localising signs and symptoms. The diagnostic accuracy of contrast-enhanced total-body CT has been well established during septic shock, allowing for a rapid, panoramic, and detailed study of multiple body areas, simultaneously. The aim of this article is to illustrate the controversial CT hypoperfusion complex in patients with septic shock, characterised by the following imaging features: decreased enhancement of the viscera; increased mucosal enhancement; luminal dilation of the small bowel; mural thickening and fluid-filled loops of the small bowel; the halo sign and flattening of the inferior vena cava; reduced aortic diameter; peripancreatic oedema; abnormal parenchymal perfusion; and other controversial findings that are variably associated with each other and reversible during the early stages. Increasing physicians’ awareness of the significance of these findings could prompt alternative approaches to the early assessment and management of septic shock. In this perspective, CT imaging represents a useful tool for a complete, rapid and detailed diagnosis of clinically suspected septic shock, which can be used to improve patient outcomes.
Challenge of prostate MRI segmentation on T2-weighted images: inter-observer variability and impact of prostate morphology
Authors: Montagne Sarah , Hamzaoui Dimitri , Allera Alexandre , Ezziane Malek , Luzurier Anna , Quint Raphaelle , Kalai Mehdi , Ayache Nicholas , Delingette Hervé , Renard-Penna Raphaële 
Published: June 2021

Abstract
Background
Accurate prostate zonal segmentation on magnetic resonance images (MRI) is a critical prerequisite for automated prostate cancer detection. We aimed to assess the variability of manual prostate zonal segmentation by radiologists on T2-weighted (T2W) images, and to study factors that may influence it.

Methods
Seven radiologists of varying levels of experience segmented the whole prostate gland (WG) and the transition zone (TZ) on 40 axial T2W prostate MRI images (3D T2W images for all patients, and both 3D and 2D images for a subgroup of 12 patients). Segmentation variabilities were evaluated based on: anatomical and morphological variation of the prostate (volume, retro-urethral lobe, intensity contrast between zones, presence of a PI-RADS ≥ 3 lesion), variation in image acquisition (3D vs 2D T2W images), and reader’s experience. Several metrics including Dice Score (DSC) and Hausdorff Distance were used to evaluate differences, with both a pairwise and a consensus (STAPLE reference) comparison.

Results
DSC was 0.92 (± 0.02) and 0.94 (± 0.03) for WG, 0.88 (± 0.05) and 0.91 (± 0.05) for TZ respectively with pairwise comparison and consensus reference. Variability was significantly (p < 0.05) lower for the mid-gland (DSC 0.95 (± 0.02)), higher for the apex (0.90 (± 0.06)) and the base (0.87 (± 0.06)), and higher for smaller prostates (p < 0.001) and when contrast between zones was low (p < 0.05). Impact of the other studied factors was non-significant.

Conclusions
Variability is higher in the extreme parts of the gland, is influenced by changes in prostate morphology (volume, zone intensity ratio), and is relatively unaffected by the radiologist’s level of expertise.
The preoperative localisation of small parathyroid adenomas improves when adding Tc-99m-Sestamibi SPECT to multiphase contrast-enhanced CT
Authors: Sandqvist Patricia , Farnebo Jacob , Nilsson Inga-Lena , Grybäck Per , Sundin Anders , Sanchez-Crespo Alejandro 
Published: June 2021

Abstract
Objectives
To investigate the incremental value of Sestamibi SPECT combined with a non-enhanced and contrast-enhanced CT, using SPECT/CT, for the preoperative localisation of small parathyroid adenomas (PTA).

Methods
Retrospectively, 147 patients surgically cured from primary hyperparathyroidism, as verified by biochemistry 6 months postoperatively, were included. All patients had preoperatively undergone a dual time 99mTechnetium-Sestamibi SPECT (S) with multiphase CT including native (N), arterial (A) and venous (V) phases. Independently, two radiologists blinded from both the surgical and the preoperative imaging reports, sequentially performed PTA localisation starting with either [A] or [V], thereafter [A + N] or [V + N] and finally with the complete [A + N + S] or [V + N + S]. PTA localisation was reported for each image-set. The readers results were combined and the diagnostic performance for each image set was determined. Sensitivity was also calculated for the different quartiles of PTA weight distribution.

Results
The median adenoma weight was 315 mg. No statistically significant differences in diagnostic performance between arterial and venous based image sets were found. The net effect of adding [N] was to increase specificity. Sestamibi SPECT significantly increased the overall diagnostic accuracy for arterial- and venous-based image sets, p = 0.0008 and p = 0.001, respectively. [A + N + S] was found to have the highest diagnostic performance with 86.5% sensitivity and 94.9% overall accuracy. [A + N + S] was particularly advantageous for locating PTA in the lower weight quartiles.

Conclusions
Native CT-phase and dual time point Sestamibi SPECT increase specificity and sensitivity, respectively. These, in combination with a single contrast-enhanced CT-phase is the most optimal examination protocol for preoperative localisation of PTA using SPECT/CT.
A procedure for in vitro evaluation of the immunosuppressive effect of mouse mesenchymal stem cells on activated T cell proliferation
Authors: Marinescu Catalina-Iolanda , Preda Mihai Bogdan , Burlacu Alexandrina 
Published: June 2021

Abstract
Background
Mesenchymal stem/stromal cells (MSC) represent adult cells with multipotent capacity. Besides their capacity to differentiate into multiple lineages in vitro and in vivo, increasing evidence points towards the immunomodulatory capacity of these cells, as an important feature for their therapeutic power. Although not included in the minimal criteria established by the International Society for Cellular Therapy as a defining MSC attribute, demonstration of the immunomodulatory capacity of MSC can be useful for the characterization of these cells before being considered MSC.

Methods
Here we present a simple and reliable protocol by which the immunosuppressive effect of mouse bone marrow-derived MSC can be evaluated in vitro. It is based on the measuring of the proliferation of activated T cells cultured in direct contact with irradiated MSC.

Results
Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation, which can be quantified as a percentage of maximum proliferation. Our data shows that batch-to-batch variability can be determined within one or multiple experiments, by extracting the area under curve of T cell proliferation plotted against the absolute number of MSC in co-culture.

Conclusions
The validation of the immunosupressive capacity of MSC could be added to the characterization of the cells before being used in various MSC-based approaches to treat immunological diseases. Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation. The immunosuppressive properties of MSC vary between batches, but not between different passages of the same batch.
WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis
Authors: Choi Yoon Jung , Heck Adam M. , Hayes Brian J. , Lih Daniel , Rayner Samuel G. , Hadland Brandon , Zheng Ying 
Published: June 2021

AbstractThe human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45− hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.
Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy
Authors: Zeng Ruijie , Wang Jinghua , Zhuo Zewei , Luo Yujun , Sha Weihong , Chen Hao 
Published: June 2021

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.
MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis
Authors: Ni Haiwei , Qin Hai , Sun Cheng , Liu Yichen , Ruan Guojing , Guo Qianqian , Xi Tao , Xing Yingying , Zheng Lufeng 
Published: June 2021

Abstract
Background
Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness.

Methods
Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored.

Results
MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis.

Conclusion
MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.
Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane
Authors: McBride Jeffrey D. , Rodriguez-Menocal Luis , Guzman Wellington , Khan Aisha , Myer Ciara , Liu Xiaochen , Bhattacharya Sanjoy K. , Badiavas Evangelos V. 
Published: June 2021

Abstract
Background
Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood. Variation in EV protein cargo is important to understand, as it may be useful in identifying potential therapeutic applications in clinical trials. We hypothesized that the donors would share both important similarities and differences in cargo relating to cell proliferation, angiogenesis, Wnt signaling, and basement membrane formation—processes shown to be critical for effective cutaneous wound healing.

Methods
We harvested BM-MSC EVs from four healthy human donors who underwent strict screening for whole bone marrow donation and further Good Manufacturing Practices-grade cell culture expansion for candidate usage in clinical trials. BM-MSC EV protein cargo was determined via mass spectrometry and Proteome Discoverer software. Corresponding proteomic networks were analyzed via the UniProt Consortium and STRING consortium databases.

Results
More than 3000 proteins were identified in each of the donors, sharing > 600 proteins among all donors. Despite inter-donor variation in protein identities, there were striking similarities in numbers of proteins per biological functional category. In terms of biologic function, the proteins were most associated with transport of ions and proteins, transcription, and the cell cycle, relating to cell proliferation. The donors shared essential cargo relating to angiogenesis, Wnt signaling, and basement membrane formation—essential processes in modulating cutaneous wound repair.

Conclusions
Healthy donors of BM-MSC EVs contain important similarities and differences among protein cargo that may play important roles in their pro-regenerative functions. Further studies are needed to correlate proteomic signatures to functional outcomes in cutaneous repair.