bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cardiopulmonary bypass with low-priming volume on clinical outcomes in children undergoing congenital heart disease surgery
Authors: Wang Lei , Chen Qiang , Qiu Yong Qiang , Ye Jian Xi , Du Jian Zhi , Lv Xiao Chai , Hou Yan Ting , Chen Liang Wan 
Published: May 2020

AbstractBackgroundCardiopulmonary bypass (CPB) with high-priming volume can significantly activate the inflammatory response and increse the usage of packed red blood cells (PRBCs). As risks and complications related to transfusions are increasing, many cardiac centers are focusing on reducing the priming volume of CPB. In our center, efforts have also been made to reduce the priming volume, and the effects of CPB with low-priming volume on clinical outcomes in children undergoing congenital heart disease (CHD) surgery were investigated in this study to provide referential experiences for pediatric CPB.MethodsThe clinical case data of 158 children undergoing CHD surgery with CPB were collected. The children were divided into the low-priming-volume group (group A,n = 79) and the traditional group (group B,n = 79) according to the priming volume. The amount of PRBCs transfused, the postoperative hematological test results and the clinical outcomes of the two groups were compared by the independent samplet-test or the chi-square test.ResultsThe amount of PRBCs transfused during CPB and during the whole operation were significantly lower in group A than in group B (p < 0.01), but the hemoglobin (Hb) concentration was higher in group A on the first day after surgery (p < 0.01) and before hospital discharge. However, the latter showed no statistical significant difference. The lowest postoperative platelet count was higher in group A than in group B (p < 0.05). There was no statistical difference in the postoperative inflammatory markers and the main clinical outcomes between the two groups.ConclusionsThe usage of PRBCs in CPB with low-priming volume decreased significantly, but the postoperative Hb concentration and platelet count could still be maintained at a high level, improving the use efficiency of PRBCs. CPB with low-priming volume did not affect the postoperative recovery of patients, so it is worthy of continuous promotion and optimization.
Reproductive options for families at risk of Osteogenesis Imperfecta: a review
Authors: Zhytnik Lidiia , Simm Kadri , Salumets Andres , Peters Maire , Märtson Aare , Maasalu Katre 
Published: May 2020

Abstract
Background
Osteogenesis Imperfecta (OI) is a rare genetic disorder involving bone fragility. OI patients typically suffer from numerous fractures, skeletal deformities, shortness of stature and hearing loss. The disorder is characterised by genetic and clinical heterogeneity. Pathogenic variants in more than 20 different genes can lead to OI, and phenotypes can range from mild to lethal forms. As a genetic disorder which undoubtedly affects quality of life, OI significantly alters the reproductive confidence of families at risk. The current review describes a selection of the latest reproductive approaches which may be suitable for prospective parents faced with a risk of OI. The aim of the review is to alleviate suffering in relation to family planning around OI, by enabling prospective parents to make informed and independent decisions.

Main body
The current review provides a comprehensive overview of possible reproductive options for people with OI and for unaffected carriers of OI pathogenic genetic variants. The review considers reproductive options across all phases of family planning, including pre-pregnancy, fertilisation, pregnancy, and post-pregnancy. Special attention is given to the more modern techniques of assisted reproduction, such as preconception carrier screening, preimplantation genetic testing for monogenic diseases and non-invasive prenatal testing. The review outlines the methodologies of the different reproductive approaches available to OI families and highlights their advantages and disadvantages. These are presented as a decision tree, which takes into account the autosomal dominant and autosomal recessive nature of the OI variants, and the OI-related risks of people without OI.
The complex process of decision-making around OI reproductive options is also discussed from an ethical perspective.

Conclusion
The rapid development of molecular techniques has led to the availability of a wide variety of reproductive options for prospective parents faced with a risk of OI. However, such options may raise ethical concerns in terms of methodologies, choice management and good clinical practice in reproductive care, which are yet to be fully addressed.
Modeling the natural history of ductal carcinoma in situ based on population data
Authors: Chootipongchaivat Sarocha , van Ravesteyn Nicolien T. , Li Xiaoxue , Huang Hui , Weedon-Fekjær Harald , Ryser Marc D. , Weaver Donald L. , Burnside Elizabeth S. , Heckman-Stoddard Brandy M. , de Koning Harry J. , Lee Sandra J. 
Published: May 2020

Abstract
Background
The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision.

Methods
Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS.

Results
Without biopsy and surgical excision, the majority of DCIS (64–100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36–100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1–65.8%. IBC overdiagnosis ranged 1.3–2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years.

Conclusions
Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.
COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area
Authors:   Institut Curie Breast Cancer and COVID Group, Vuagnat Perrine , Frelaut Maxime , Ramtohul Toulsie , Basse Clémence , Diakite Sarah , Noret Aurélien , Bellesoeur Audrey , Servois Vincent , Hequet Delphine , Laas Enora , Kirova Youlia , Cabel Luc , Pierga Jean-Yves , Bozec Laurence , Paoletti Xavier , Cottu Paul , Bidard François-Clément 
Published: May 2020

Abstract
Background
Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France).

Methods
An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities.

Results
Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death.

Conclusions
This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.
APOE ε4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer’s disease
Authors: Konijnenberg Elles , Tijms Betty M. , Gobom Johan , Dobricic Valerija , Bos Isabelle , Vos Stephanie , Tsolaki Magda , Verhey Frans , Popp Julius , Martinez-Lage Pablo , Vandenberghe Rik , Lleó Alberto , Frölich Lutz , Lovestone Simon , Streffer Johannes , Bertram Lars , Blennow Kaj , Teunissen Charlotte E. , Veerhuis Robert , Smit August B. , Scheltens Philip , Zetterberg Henrik , Visser Pieter Jelle 
Published: May 2020

Abstract
Background
Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer’s disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprotein E (APOE) ε4 genotype plays a major role. We aimed to identify the molecular pathways associated with amyloid β aggregation using cerebrospinal fluid (CSF) proteomics and to study the potential modifying effects of APOE ε4 genotype.

Methods
We tested 243 proteins and protein fragments in CSF comparing 193 subjects with AD across the cognitive spectrum (65% APOE ε4 carriers, average age 75 ± 7 years) against 60 controls with normal CSF amyloid β, normal cognition, and no APOE ε4 allele (average age 75 ± 6 years).

Results
One hundred twenty-nine proteins (53%) were associated with aggregated amyloid β. APOE ε4 carriers with AD showed altered concentrations of proteins involved in the complement pathway and glycolysis when cognition was normal and lower concentrations of proteins involved in synapse structure and function when cognitive impairment was moderately severe. APOE ε4 non-carriers with AD showed lower expression of proteins involved in synapse structure and function when cognition was normal and lower concentrations of proteins that were associated with complement and other inflammatory processes when cognitive impairment was mild. Repeating analyses for 114 proteins that were available in an independent EMIF-AD MBD dataset (n = 275) showed that 80% of the proteins showed group differences in a similar direction, but overall, 28% effects reached statistical significance (ranging between 6 and 87% depending on the disease stage and genotype), suggesting variable reproducibility.

Conclusions
These results imply that AD pathophysiology depends on APOE genotype and that treatment for AD may need to be tailored according to APOE genotype and severity of the cognitive impairment.
Towards definitive management of allergic rhinitis: best use of new and established therapies
Authors: Hossenbaccus Lubnaa , Linton Sophia , Garvey Sarah , Ellis Anne K. 
Published: May 2020

Abstract
Background
Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa impacting up to 25% of Canadians. The standard of care for AR includes a treatment plan that takes into account patient preferences, the severity of the disease, and most essentially involves a shared decision-making process between patient and provider.

Body
Since their introduction in the 1940s, antihistamines (AHs) have been the most utilized class of medications for the treatment of AR. First-generation AHs are associated with adverse central nervous system (CNS) and anticholinergic side effects. On the market in the 1980s, newer generation AHs have improved safety and efficacy. Compared to antihistamines, intranasal corticosteroids (INCS) have significantly greater efficacy but longer onset of action. Intranasal AH and INCS combinations offer a single medication option that offers broader disease coverage and faster symptom control. However, cost and twice-per-day dosing remain a major limitation. Allergen immunotherapy (AIT) is the only disease-modifying option and can be provided through subcutaneous (SCIT) or sublingual (SLIT) routes. While SCIT has been the definitive management option for many years, SLIT tablets (SLIT-T) have also been proven to be safe and efficacious.

Conclusion
There is a range of available treatment options for AR that reflect the varying disease length and severity. For mild to moderate AR, newer generation AHs should be the first-line treatment, while INCS are mainstay treatments for moderate to severe AR. In patients who do not respond to INCS, a combination of intranasal AH/INCS (AZE/FP) should be considered, assuming that cost is not a limiting factor. While SCIT remains the option with the most available allergens that can be targeted, it has the potential for severe systemic adverse effects and requires weekly visits for administration during the first 4 to 6 months. SLIT-T is a newer approach that provides the ease of being self-administered and presents a reduced risk for systemic reactions. In any case, standard care for AR includes a treatment plan that takes into account disease severity and patient preferences.
Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment
Authors: Utami Kagistia Hana , Yusof Nur Amirah Binte Mohammad , Kwa Jing Eugene , Peteri Ulla-Kaisa , Castrén Maija L. , Pouladi Mahmoud A. 
Published: May 2020

AbstractFXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number of neuronal mRNAs. Absence of FMRP has been shown to lead to elevated protein synthesis and is thought to be a major cause of the synaptic plasticity and behavioural deficits in FXS. The increase in protein synthesis results in part from abnormal activation of key protein translation pathways downstream of ERK1/2 and mTOR signalling. Pharmacological and genetic interventions that attenuate hyperactivation of these pathways can normalize levels of protein synthesis and improve phenotypic outcomes in animal models of FXS. Several efforts are currently underway to trial this strategy in patients with FXS. To date, elevated global protein synthesis as a result of FMRP loss has not been validated in the context of human neurons. Here, using an isogenic human stem cell-based model, we show that de novo protein synthesis is elevated in FMRP-deficient neural cells. We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment. Finally, we examined the effect of normalizing protein synthesis on phenotypic abnormalities in FMRP-deficient neural cells. We find that treatment with metformin attenuates the increase in proliferation of FMRP-deficient neural progenitor cells but not the neuronal deficits in neurite outgrowth. The elevated level of protein synthesis and the normalization of neural progenitor proliferation by metformin treatment were validated in additional control and FXS patient-derived hiPSC lines. Overall, our results validate that loss of FMRP results in elevated de novo protein synthesis in human neurons and suggest that approaches targeting this abnormality are likely to be of partial therapeutic benefit in FXS.
Magnetic resonance imaging of the female pelvis after Cesarean section: a pictorial review
Authors: Bekiesinska-Figatowska Monika 
Published: May 2020

AbstractThe rate of Cesarean sections (C-sections) in Poland increased from 21.7% in 2001 to 43.85% in 2017 even though the Polish Society of Gynecologists and Obstetricians highlights the negative consequences of C-section for both mother and child and recommends to make every possible effort to reduce its percentage, following the World Health Organization recommendations. There is a long list of possible complications related to the uterine scar after C-section, including uterine scar dehiscence, uterine rupture, abdominal and pelvic adhesions, uterine synechiae, ectopic pregnancy, anomalous location of the placenta, placental invasion, and—rarely—vesicouterine or uterocutaneous fistulas. Ultrasound (US) remains the first-line modality; however, its strong operator- and equipment dependence and other limitations require further investigations in some cases. Magnetic resonance imaging (MRI) is the second-line tool which is supposed to confirm, correct, or complete the sonographic diagnosis thanks to its higher tissue resolution and bigger field of view. This article will discuss the spectrum of C-section complications in the MR image-rich form and will provide a systematic discussion of the possible pathology that can occur, showing comprehensive anatomical insight into the pelvis after C-section thanks to MRI that facilitates clinical decisions.
Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury
Authors: Seyedrazizadeh Seyedeh-Zahra , Poosti Sara , Nazari Abdoreza , Alikhani Mehdi , Shekari Faezeh , Pakdel Farzad , Shahpasand Koorosh , Satarian Leila , Baharvand Hossein 
Published: May 2020

Abstract
Background
Retinal and/or optic nerve injury is one of the leading causes of blindness due to retinal ganglion cell (RGC) degeneration. There have been extensive efforts to suppress this neurodegeneration. Various somatic tissue-derived mesenchymal stem cells (MSCs) demonstrated significant neuroprotective and axogenic effects on RGCs. An alternative source of MSCs could be human embryonic stem cells (ES-MSCs), which proliferate faster, express lower levels of inflammatory cytokines, and are capable of immune modulation. It has been demonstrated that MSCs secrete factors or extracellular vesicles that may heal the injury. However, possible therapeutic effects and underlying mechanism of human ES-MSC extracellular vesicles (EVs) on optic nerve injury have not been assessed.

Methods
EVs were isolated from human ES-MSCs. Then, ES-MSC EV was applied to an optic nerve crush (ONC) mouse model. Immunohistofluorescence, retro- and anterograde tracing of RGCs, Western blot, tauopathy in RGCs, and function assessments were performed during 2-month post-treatment to evaluate ONC improvement and underlying mechanism of human ES-MSC EV in in vivo.

Results
We found that the ES-MSC EV significantly improved Brn3a+ RGCs survival and retro- and anterograde tracing of RGCs, while preventing retinal nerve fiber layer (RNFL) degenerative thinning compared to the vehicle group. The EVs also significantly promoted GAP43+ axon counts in the optic nerve and improved cognitive visual behavior. Furthermore, cis p-tau, a central mediator of neurodegeneration in the injured RGCs, is detectable after the ONC at the early stages demonstrated tauopathy in RGCs. Notably, after EV treatment cis p-tau was downregulated.

Conclusions
Our findings propose that human ES-MSC EVs, as an off-the-shelf and cell-free product, may have profound clinical implications in treating injured RGCs and degenerative ocular disease. Moreover, the possible mechanisms of human ES-MSC EV are related to the rescue of tauopathy process of RGC degeneration.
RETRACTED ARTICLE: Polydatin improves osteogenic differentiation of human bone mesenchymal stem cells by stimulating TAZ expression via BMP2-Wnt/β-catenin signaling pathway
Authors: Shen Ying-Shan , Chen Xiao-Jun , Wuri Sha-Na , Yang Fan , Pang Feng-Xiang , Xu Liang-Liang , He Wei , Wei Qiu-Shi 
Published: May 2020

AbstractObjectivesPolydatin (PD), extracted fromPolygonum cuspidatum, has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis.Materials and methodshBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA.ResultsIn vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAsRUNX2,Osteopontin,DLX5,β-catenin,TAZ, andOsteocalcin(OCN). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model.ConclusionTaken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.