bluuebunny/crossref_metadata_2025_split huggingface dataset:
A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case–control study in California
Authors: Lyall Kristen , Ames Jennifer L. , Pearl Michelle , Traglia Michela , Weiss Lauren A. , Windham Gayle C. , Kharrazi Martin , Yoshida Cathleen K. , Yolken Robert , Volk Heather E. , Ashwood Paul , Van de Water Judy , Croen Lisa A. 
Published: March 2021

Abstract
Background
The Early Markers for Autism (EMA) study is a population-based case–control study designed to learn more about early biologic processes involved in ASD.

Methods
Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions.

Results
EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels.

Limitations
Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced.

Conclusions
Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.
Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report
Authors: Krsteska Blagica , Jovanovic Rubens , Eftimov Aleksandar , Ilievski Boro , Hadzi-Mancev Dragan , Osmani Bujar , Kostadinova-Kunovska Slavica 
Published: March 2021

Abstract
Background
Rectal signet ring cell carcinoma is a rare type of colorectal adenocarcinoma characterized by an aggressive biological behavior and poor prognosis. The co-occurrence of colorectal carcinoma and renal cell carcinoma (RCC) has found in many hundreds of patients, many of whom also have additional malignancies. Cancer to cancer metastasis is rare and an uncommon phenomenon in malignancy, especially at the time of initial diagnosis, suggesting a genetic susceptibility.

Case presentation
We present the case of a 66-year-old Macedonian man with synchronous rectal signet ring cell carcinoma and RCC with tumor to tumor metastasis feature. He underwent a left nephrectomy and anterior rectal resection after complaining of constipation for 3–4 months and the appearance of synchronous tumors on the imaging studies. Morphology and immunohistochemical analysis of specimens from the RCC revealed signet ring cells identical to the rectal signet ring cell carcinoma. The next-generation sequencing study revealed mutations in TP53 and ERBB2, and microsatellite stable signet ring cell carcinoma was determined by deoxyribonucleic acid (DNA) sequencing.

Conclusions
Cancer to cancer metastasis, although rare, needs to be considered in synchronous tumors. RCC, when diagnosed in multiple synchronous tumors, should be examined carefully. The paucity of reported cases indicates the need for advanced research in imaging methods for metastasis and new therapeutic approaches.
Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial
Authors: Krull Ashley A. , Setter Deborah O. , Gendron Tania F. , Hrstka Sybil C. L. , Polzin Michael J. , Hart Joseph , Dudakovic Amel , Madigan Nicolas N. , Dietz Allan B. , Windebank Anthony J. , van Wijnen Andre J. , Staff Nathan P. 
Published: March 2021

Abstract
Background
Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases.

Methods
In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS).

Results
Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs.

Conclusions
Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.
Online marketing practices of regenerative medicine clinics in US-Mexico border region: a web surveillance study
Authors: Chavez Javier , Shah Neal A. , Ruoss Severin , Cuomo Raphael E. , Ward Samuel R. , Mackey Tim K. 
Published: March 2021

Abstract
Introduction
The potential of regenerative medicine to improve human health has led to the rapid expansion of stem cell clinics throughout the world with varying levels of regulation and oversight. This has led to a market ripe for stem cell tourism, with Tijuana, Mexico, as a major destination. In this study, we characterize the online marketing, intervention details, pricing of services, and assess potential safety risks through web surveillance of regenerative medicine clinics marketing services in Tijuana.

Methods
We conducted structured online search queries from March to April 2019 using 296 search terms in English and Spanish on two search engines (Google and Bing) to identify websites engaged in direct-to-consumer advertising of regenerative medicine services. We performed content analysis to characterize three categories of interest: online presence, tokens of scientific legitimacy, and intervention details.

Results
Our structured online searches resulted in 110 unique websites located in Tijuana corresponding to 76 confirmed locations. These clinics’ online presence consisted of direct-to-consumer advertising mainly through a dedicated website (94.5%) or Facebook page (65.5%). The vast majority of these websites (99.1%) did not mention any affiliation to an academic institutions or other overt tokens of scientific legitimacy. Most clinics claimed autologous tissue was the source of treatments (67.3%) and generally did not specify route of administration. Additionally, of the Tijuana clinics identified, 13 claimed licensing, though only 1 matched with available licensing information.

Conclusions
Regenerative medicine clinics in Tijuana have a significant online presence using direct-to-consumer advertising to attract stem-cell tourism clientele in a bustling border region between Mexico and the USA. This study adds to existing literature evidencing the unregulated nature of online stem cell offerings and provides further evidence of the need for regulatory harmonization, particularly to address stem cell services being offered online across borders.
RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders
Authors: Markov Alexander , Thangavelu Lakshmi , Aravindhan Surendar , Zekiy Angelina Olegovna , Jarahian Mostafa , Chartrand Max Stanley , Pathak Yashwant , Marofi Faroogh , Shamlou Somayeh , Hassanzadeh Ali 
Published: March 2021

AbstractOver recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.
Prognostic superiority of International Prognostic Index over [18F]FDG PET/CT volumetric parameters in post-transplant lymphoproliferative disorder
Authors: Montes de Jesus F. , Dierickx D. , Vergote V. , Noordzij W. , Dierckx R. A. J. O. , Deroose C. M. , Glaudemans A. W. J. M. , Gheysens O. , Kwee T. C. 
Published: March 2021

Abstract
Background
Post-transplant lymphoproliferative disorders (PTLDs) are a spectrum of hematological malignancies occurring after solid organ and hematopoietic stem cell transplantation. [18F]FDG PET/CT is routinely performed at PTLD diagnosis, allowing for both staging of the disease and quantification of volumetric parameters, such as whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). In this retrospective study, we aimed to determine the prognostic value of MTV and TLG in PTLD patients, together with other variables of interest, such as the International Prognostic Index (IPI), organ transplant type, EBV tumor status, time after transplant, albumin levels and PTLD morphology.

Results
A total of 88 patients were included. The 1-, 3-, 5- year overall survival rates were 67%, 58% and 43% respectively. Multivariable analysis indicated that a high IPI (HR: 1.56, 95% CI: 1.13–2.16) and an EBV-negative tumor (HR: 2.71, 95% CI: 1.38–5.32) were associated with poor overall survival. Patients with a kidney transplant had a longer overall survival than any other organ recipients (HR: 0.38 95% CI: 0.16–0.89). IPI was found to be the best predicting parameter of overall survival in our cohort. Whole-body MTV, TLG, time after transplant, hypoalbuminemia and PTLD morphology were not associated with overall survival.

Conclusion
[18F]FDG PET/CT whole-body volumetric quantitative parameters were not predictive of overall survival in PTLD. In our cohort, high IPI and an EBV-negative tumor were found to predictors of worse overall survival while kidney transplant patients had a longer overall survival compared to other organ transplant recipients
Applications for CryoSat-2 satellite magnetic data in studies of Earth’s core field variations
Authors: Hammer Magnus D. , Finlay Christopher C. , Olsen Nils 
Published: March 2021

AbstractWe use 20 years of continuous magnetic field measurements from the Ørsted, CHAMP andSwarmsatellite missions, supplemented by calibrated platform magnetometer data from the CryoSat-2 satellite, to study time variations of the Earth’s core field at satellite altitude and at the core–mantle boundary (CMB). From the satellite data we derive composite time series of the core field secular variation (SV) with 4-month cadence, at 300 globally distributed Geomagnetic Virtual Observatories (GVO). A previous gap in the GVO series between 2010 and 2014 is successfully filled using CryoSat-2, and sub-decadal variations are identified during this period. Tests showed that similar sub-decadal SV patterns were obtained from the CryoSat-2 data regardless of whether IGRF-13 or CHAOS-6x9 was used in their calibration. Cryosat-2 radial field SV series at non-polar latitudes have a mean standard deviation level compared to smoothing spline fits of 3.5 nT/yr compared to 1.8 nT/yr for CHAMP and 0.9 nT/yr forSwarm. GVO radial SV series display regional fluctuations with 5–10 years duration and amplitudes reaching 20 nT/yr, most notably at low latitudes over Indonesia (2014), over South America and the South Atlantic (2007, 2011 and 2014), and over the central Pacific (2017). Applying the Subtractive Optimally Localized Averages (SOLA) method, we also map the radial SV at the CMB as a collection of locally averaged SV estimates. We demonstrate that using 2-year windows of CryoSat-2 data, it is possible to reliably estimate the SV and its time derivative, the secular acceleration (SA), at the CMB, with a spatial resolution, corresponding to spherical harmonic degree 10. Along the CMB geographic equator, we find strong SA features with amplitude$$\pm 2.5\mu \mathrm{T}/\mathrm{yr}^2$$±2.5μT/yr2under Indonesia from 2011–2014, under central America from 2015 to 2019, and sequences of SA with alternating sign under the Atlantic during 2004–2019. We find that platform magnetometer data from CryoSat-2 make a valuable contribution to the emerging picture of sub-decadal core field variations. Using 1-year windows of data from theSwarmsatellites, we show that it is possible to study SA changes at low latitudes on timescales down to 1 year, with spatial resolution corresponding to spherical harmonic degree 10. We find strong positive and negative SA features appearing side-by-side in the Pacific in 2017, and thereafter drift westward.
Source modeling and spectral analysis of the Crete tsunami of 2nd May 2020 along the Hellenic Subduction Zone, offshore Greece
Authors: Heidarzadeh Mohammad , Gusman Aditya Riadi 
Published: March 2021

AbstractTsunami hazard in the Eastern Mediterranean Basin (EMB) has attracted attention following three tsunamis in this basin since 2017 namely the July 2017 and October 2020 Turkey/Greece and the May 2020 offshore Crete Island (Greece) tsunamis. Unique behavior is seen from tsunamis in the EMB due to its comparatively small size and confined nature which causes several wave reflections and oscillations. Here, we studied the May 2020 event using sea level data and by applying spectral analysis, tsunami source inversion, and numerical modeling. The maximum tsunami zero-to-crest amplitudes were measured 15.2 cm and 6.5 cm at two near-field tide gauge stations installed in Ierapetra and Kasos ports (Greece), respectively. The dominant tsunami period band was 3.8–4.7 min. We developed a heterogeneous fault model having a maximum slip of 0.64 m and an average slip of 0.28 m. This model gives a seismic moment of 1.13 × 1019Nm; equivalent to Mw6.67. We observed three distinct wave trains on the wave record of the Ierapetra tide gauge: the first and the second wave trains carry waves with periods close to the source period of the tsunami, while the third train is made of a significantly-different period of 5–10 min.
Fast Fluorine-18 labeling and preclinical evaluation of novel Mucin1 and its Folate hybrid peptide conjugate for targeting breast carcinoma
Authors: Al Jammaz I. , Al-Otaibi B. , Al-Malki Y. , Abousekhrah A. , Okarvi S. M. 
Published: March 2021

AbstractBackgroundThere is a need to develop new and more potent radiofluorinated peptide and their hybrid conjugates for multiple-receptors targeting properties that overexpress on many cancers.MethodsWe have synthesized MUC1-[18F] SFB and MUC1-FA-[18F] SFB hybrid conjugates using a convenient and one-step nucleophilic displacement reaction. In vitro cell binding and in vivo evaluation in animals were performed to determine the potential of these radiolabeled compounds.ResultsRadiochemical yields for MUC1-[18F] SFB and MUC1-FA-[18F] SFB conjugates were greater than 70% in less than 30 min synthesis time. Radiochemical purities were greater than 97% without HPLC purification, which makes these approaches amenable to automation. In vitro studies on MCF7 breast cancer cells showed that the significant amounts of the radiofluorinated conjugates were associated with cell fractions and held good affinity and specificity for MCF7 cells. In vivo characterization in Balb/c mice revealed rapid blood clearance with excretion predominantly by urinary as well as hepatobiliary systems for MUC1-[18F] SFB and MUC1-FA-[18F] SFB, respectively.Biodistribution in SCID mice bearing MCF7 xenografts, demonstrated excellent tumor uptake (12% ID/g) and favorable kinetics for MUC1-FA-[18F] SFB over MUC1-[18F]SFB. The tumor uptake was blocked by the excess co-injection of cold peptides suggesting the receptor-mediated process.ConclusionInitial PET/CT imaging of SCID mice with MCF7 xenografts, confirmed these observations. These results demonstrate that MUC1-FA-[18F] SFB may be a useful PET imaging probe for breast cancer detection and monitoring tumor response to the treatment.
Comparative Antioxidant Analysis of Moringa oleifera Leaf Extracts from South Western States in Nigeria
Authors: Olaoye Ayonposi Bukola , Ologunde Charles Ayorinde , Molehin Olorunfemi Raphael , Nwankwo Ikechukwu 
Published: March 2021

Abstract
Background
Moringa oleifera is a medicinal plant that ethnobotanical studies have shown its inclusion in treatment of many ailments such as diarrhea, diabetes, epilepsy, wound healing and arthritis. It is a plant that was believed to originate from India but could now be found in both the tropics and the sub-topics. Earlier reports have not addressed the association between the location of plant collection and its antioxidant contents. In this study, Moringa oleifera leaves were collected from 21 locations within the south western states of Nigeria. Leaves from each of the locations were dried and evaluated for total phenols, tannin, saponin and flavonoid. DPPH scavenging activity, nitric oxide scavenging activity and inhibition of lipid peroxidation were also evaluated.

Results
All the parameters analysed showed significant within- and between-group differences. Some locations had greater DPPH scavenging ability than the standard (quercetin).

Conclusion
Environmental parameters like annual precipitation, minimum temperature and maximum temperature, and soil type of the location of the plants showed influence on the level of antioxidant, while further analysis using metaboanalyst showed a notable effect of soil type on the antioxidant activity.
Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model
Authors: Niborski Leticia L. , Paces-Fessy Mélanie , Ricci Pierbruno , Bourgeois Adeline , Magalhães Pedro , Kuzma-Kuzniarska Maria , Lesaulnier Celine , Reczko Martin , Declercq Edwige , Zürbig Petra , Doucet Alain , Umbhauer Muriel , Cereghini Silvia 
Published: March 2021

ABSTRACT
Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b ablation leads to more severe phenotypes. We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor site. Unlike heterozygous mice previously characterized, mice heterozygous for the splicing mutation exhibited decreased HNF1B protein levels and bilateral renal cysts from embryonic day 15, originated from glomeruli, early proximal tubules (PTs) and intermediate nephron segments, concurrently with delayed PT differentiation, hydronephrosis and rare genital tract anomalies. Consistently, mRNA sequencing showed that most downregulated genes in embryonic kidneys were primarily expressed in early PTs and the loop of Henle and involved in ion/drug transport, organic acid and lipid metabolic processes, while the expression of previously identified targets upon Hnf1b ablation, including cystic disease genes, was weakly or not affected. Postnatal analyses revealed renal abnormalities, ranging from glomerular cysts to hydronephrosis and, rarely, multicystic dysplasia. Urinary proteomics uncovered a particular profile predictive of progressive decline in kidney function and fibrosis, and displayed common features with a recently reported urine proteome in an RCAD pediatric cohort. Altogether, our results show that reduced HNF1B levels lead to developmental disease phenotypes associated with the deregulation of a subset of HNF1B targets. They further suggest that this model represents a unique clinical/pathological viable model of the RCAD disease.