bluuebunny/crossref_metadata_2025 huggingface dataset:
An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers
Authors: Razo-Azamar Melissa , Nambo-Venegas Rafael , Meraz-Cruz Noemí , Guevara-Cruz Martha , Ibarra-González Isabel , Vela-Amieva Marcela , Delgadillo-Velázquez Jaime , Santiago Xanic Caraza , Escobar Rafael Figueroa , Vadillo-Ortega Felipe , Palacios-González Berenice
Published: June 2023

Background

Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM.

Methods

A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM.

Results

Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873–0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015–0.25 μmol/L and of C5:1 with a range of 0.015–0.19 μmol/L.

Conclusion

Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.
SETD5 haploinsufficiency affects mitochondrial compartment in neural cells
Authors: Zaghi Mattia , Longo Fabiana , Massimino Luca , Rubio Alicia , Bido Simone , Mazzara Pietro Giuseppe , Bellini Edoardo , Banfi Federica , Podini Paola , Maltecca Francesca , Zippo Alessio , Broccoli Vania , Sessa Alessandro
Published: June 2023

Background

Neurodevelopmental disorders (NDDs) are heterogeneous conditions due to alterations of a variety of molecular mechanisms and cell dysfunctions.SETD5haploinsufficiency leads to NDDs due to chromatin defects. Epigenetic basis of NDDs has been reported in an increasing number of cases while mitochondrial dysfunctions are more common within NDD patients than in the general population.

Methods

We investigated in vitro neural stem cells as well as the brain of theSetd5haploinsufficiency mouse model interrogating its transcriptome, analyzing mitochondrial structure, biochemical composition, and dynamics, as well as mitochondrial functionality.

Results

Mitochondrial impairment is facilitated by transcriptional aberrations originated by the decrease of the SETD5 enzyme. Low levels of SETD5 resulted in fragmented mitochondria, reduced mitochondrial membrane potential, and ATP production both in neural precursors and neurons. Mitochondria were also mislocalized in mutant neurons, with reduced organelles within neurites and synapses.

Limitations

We found several defects in the mitochondrial compartment; however, we can only speculate about their position in the hierarchy of the pathological mechanisms at the basis of the disease.

Conclusions

Our study explores the interplay between chromatin regulation and mitochondria functions as a possible important aspect ofSETD5-associated NDD pathophysiology. Our data, if confirmed in patient context, suggest that the mitochondrial activity and dynamics may represent new therapeutic targets for disorders associated with the loss of SETD5.
Features of a FAIR vocabulary
Authors: Xu Fuqi , Juty Nick , Goble Carole , Jupp Simon , Parkinson Helen , Courtot Mélanie
Published: June 2023

Background

The Findable, Accessible, Interoperable and Reusable(FAIR) Principles explicitly require the use of FAIR vocabularies, but what precisely constitutes a FAIR vocabulary remains unclear. Being able to define FAIR vocabularies, identify features of FAIR vocabularies, and provide assessment approaches against the features can guide the development of vocabularies.

Results

We differentiate data, data resources and vocabularies used for FAIR, examine the application of the FAIR Principles to vocabularies, align their requirements with the Open Biomedical Ontologies principles, and propose FAIR Vocabulary Features. We also design assessment approaches for FAIR vocabularies by mapping the FVFs with existing FAIR assessment indicators. Finally, we demonstrate how they can be used for evaluating and improving vocabularies using exemplary biomedical vocabularies.

Conclusions

Our work proposes features of FAIR vocabularies and corresponding indicators for assessing the FAIR levels of different types of vocabularies, identifies use cases for vocabulary engineers, and guides the evolution of vocabularies.
Inter-rater and intra-rater agreement of [99mTc]-labelled NM-01, a single-domain programmed death-ligand 1 (PD-L1) antibody, using quantitative SPECT/CT in non-small cell lung cancer
Authors: Hughes Daniel Johnathan , Chand Gitasha , Johnson Jessica , Bailey Damion , Adamson Kathryn , Goh Vicky , Cook Gary J. R.
Published: May 2023

Background

Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression. Non-invasive radiopharmaceutical techniques, including technetium-99m [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT, have the potential to improve the predictive value of PD-L1 assessment. This study aims to determine the inter- and intra-rater agreement of the quantitative measurement of [99mTc]NM-01 SPECT/CT in NSCLC.

Methods

Participants (n = 14) with untreated advanced NSCLC underwent [99mTc]NM-01 SPECT/CT at baseline (n = 3) or at baseline plus 9-week follow-up (n = 11). [99mTc]NM-01 uptake (of primary lung, lymph node, thoracic and distant metastases, and healthy reference tissues) was measured using SUVmax and malignant lesion-to-blood pool ratios with Siemens xSPECT Broad Quantification software by three independent raters. Intraclass correlation coefficients (ICC) were calculated and Bland–Altman plot analysis performed to determine inter- and intra-rater agreement.

Results

There was excellent inter-rater agreement of manual freehand SUVmax scores of primary lung tumour (T; n = 25; ICC 1.00; 95% CI 0.99–1.00), individual lymph node metastases (LN; n = 56; ICC 0.97; 95% CI 0.95–0.98), thoracic metastases (ThMet; n = 9; ICC 0.94; 95% CI 0.83–0.99) and distant metastases (DisMet; n = 21; ICC 0.91; 95% CI 0.83–0.96). The inter-rater ICCs of tumour-to-blood pool (T:BP), LN:BP, ThMet:BP and DisMet:BP measures of [99mTc]NM-01 uptake also demonstrated good or excellent agreement. Manual freehand scoring of T, LN, ThMet, DisMet and their ratios using [99mTc]NM-01 SPECT/CT following a 28-day interval was consistent for all raters with good or excellent intra-rater agreement demonstrated (ICCs range 0.86–1.00).

Conclusion

Quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC, using SUVmax of malignant primary or metastatic lesions and their ratios with healthy reference tissues, demonstrated good or excellent inter- and intra-rater agreement in this study. Further validation with ongoing and future larger cohort studies is now warranted.

Clinical trial registration

ClinicalTrials.gov identifier no. NCT04436406 (registered 18th June 2020; available at https://clinicaltrials.gov/ct2/show/NCT04436406) and NCT04992715 (registered 5th August 2021; available at https://clinicaltrials.gov/ct2/show/NCT04992715).
Uniform stability of a strong time-delayed viscoelastic system with Balakrishnan–Taylor damping
Authors: Li Haiyan
Published: May 2023

This paper studies a Balakrishnan–Taylor viscoelastic wave equation with strong time-dependent delay. Under suitable assumptions on the coefficients of the delay term, we establish a generalized stability result, which improve some earlier results in the literature.
Examination of sulfate resistance of nano-alumina added ordinary Portland cement paste, focusing on the two different crystallinity of nano-aluminas
Authors: Yu Juan , Sim Sungwon , Song Haemin , Kim Dohoon , Jang Kyungcheol , Jeon Dongho , Cho Seung , Oh Jae Eun
Published: June 2023

This study examined the influence of the crystallinity of added nano-alumina on the sulfate resistance of ordinary Portland cement (OPC) paste. Two crystalline types of nano-aluminas (α-and γ-phase) were incorporated in cement pastes, which were exposed to sulfate solution. In the results, both paste samples having α- and γ-phase aluminas had accelerated compressive strength loss and increased length expansion compared to the sample without alumina addition. In particular, the rapidly decreased dynamic elastic modulus of the nano-alumina added samples postulates the greatly increased internal stress likely by the increased formation of volume expansive reaction products, such as ettringite, which was supported by the XRD and TG results. The greater ettringite formation in the nano-alumina added samples was likely due to reactive AH3 (=Al(OH)3) gel formation as the higher consumption degree of portlandite in the alumina added samples indirectly indicates the active AH3 gel formation, resulting in additional ettringite formation from the reaction of AH3 with Na2SO4 solution. A further degree of sulfate attack was observed in the γ-alumina added sample for the long-term Na2SO4 exposure (180 days) mainly due to the greater degree of gypsum formation inducing more internal expansive stress compared to the α-alumina added sample.
Better richer than environmentally friendly? Describing preferences toward and factors affecting precision agriculture adoption in Italy
Authors: Troiano Stefania , Carzedda Matteo , Marangon Francesco
Published: May 2023

Precision agriculture is expected to support and strengthen the sustainability of food production. In spite of the demonstrated benefits of the application of Information Technology to improve agricultural practices, such as yield increase and input reduction, in Italy its adoption still lags behind. In order to understand limits of and perspectives on the adoption of such technologies, we conducted an explorative study. A survey with a choice experiment was carried out in Italy among 471 farmers and people interested in agricultural machinery and technologies. The results highlight how specific factors, such as excessive costs and lack of incentive policies, may limit the spread of precision agriculture. Conversely, the provision of adequate technical support would likely favor its adoption. Furthermore, latent class modeling was used to identify three segments of potential buyers: sustainability seekers; precision agriculture best features supporters; low emissions fans. Potential policy and market implications of this explorative study are discussed in the conclusion.
Addition of cariogenic pathogens to complex oral microflora drives significant changes in biofilm compositions and functionalities
Authors: Liu Yuan , Daniel Scott G. , Kim Hye-Eun , Koo Hyun , Korostoff Jonathan , Teles Flavia , Bittinger Kyle , Hwang Geelsu
Published: June 2023

Background

Dental caries is a microbe and sugar-mediated biofilm-dependent oral disease. Of particular significance, a virulent type of dental caries, known as severe early childhood caries (S-ECC), is characterized by the synergistic polymicrobial interaction between the cariogenic bacterium, Streptococcus mutans, and an opportunistic fungal pathogen, Candida albicans. Although cross-sectional studies reveal their important roles in caries development, these exhibit limitations in determining the significance of these microbial interactions in the pathogenesis of the disease. Thus, it remains unclear the mechanism(s) through which the cross-kingdom interaction modulates the composition of the plaque microbiome. Here, we employed a novel ex vivo saliva-derived microcosm biofilm model to assess how exogenous pathogens could impact the structural and functional characteristics of the indigenous native oral microbiota.

Results

Through shotgun whole metagenome sequencing, we observed that saliva-derived biofilm has decreased richness and diversity but increased sugar-related metabolism relative to the planktonic phase. Addition of S. mutans and/or C. albicans to the native microbiome drove significant changes in its bacterial composition. In addition, the effect of the exogenous pathogens on microbiome diversity and taxonomic abundances varied depending on the sugar type. While the addition of S. mutans induced a broader effect on Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog abundances with glucose/fructose, S. mutans-C. albicans combination under sucrose conditions triggered unique and specific changes in microbiota composition/diversity as well as specific effects on KEGG pathways. Finally, we observed the presence of human epithelial cells within the biofilms via confocal microscopy imaging.

Conclusions

Our data revealed that the presence of S. mutans and C. albicans, alone or in combination, as well as the addition of different sugars, induced unique alterations in both the composition and functional attributes of the biofilms. In particular, the combination of S. mutans and C. albicans seemed to drive the development (and perhaps the severity) of a dysbiotic/cariogenic oral microbiome. Our work provides a unique and pragmatic biofilm model for investigating the functional microbiome in health and disease as well as developing strategies to modulate the microbiome.
Teaching computing for complex problems in civil engineering and geosciences using big data and machine learning: synergizing four different computing paradigms and four different management domains
Authors: Babović Zoran , Bajat Branislav , Barac Dusan , Bengin Vesna , Đokić Vladan , Đorđević Filip , Drašković Dražen , Filipović Nenad , French Stephan , Furht Borko , Ilić Marija , Irfanoglu Ayhan , Kartelj Aleksandar , Kilibarda Milan , Klimeck Gerhard , Korolija Nenad , Kotlar Miloš , Kovačević Miloš , Kuzmanović Vladan , Lehn Jean-Marie , Madić Dejan , Marinković Marko , Mateljević Miodrag , Mendelson Avi , Mesinger Fedor , Milovanović Gradimir , Milutinović Veljko , Mitić Nenad , Nešković Aleksandar , Nešković Nataša , Nikolić Boško , Novoselov Konstantin , Prakash Arun , Protić Jelica , Ratković Ivan , Rios Diego , Shechtman Dan , Stojadinović Zoran , Ustyuzhanin Andrey , Zak Stan
Published: May 2023

This article describes a teaching strategy that synergizes computing and management, aimed at the running of complex projects in industry and academia, in the areas of civil engineering, physics, geosciences, and a number of other related fields. The course derived from this strategy includes four parts: (a) Computing with a selected set of modern paradigms—the stress is on Control Flow and Data Flow computing paradigms, but paradigms conditionally referred to as Energy Flow and Diffusion Flow are also covered; (b) Project management that is holistic—the stress is on the wide plethora of issues spanning from the preparation of project proposals, all the way to incorporation activities to follow after the completion of a successful project; (c) Examples from past research and development experiences—the stress is on experiences of leading experts from academia and industry; (d) Student projects that stimulate creativity—the stress is on methods that educators could use to induce and accelerate the creativity of students in general. Finally, the article ends with selected pearls of wisdom that could be treated as suggestions for further elaboration.
Slight pelvic obliquity is normal in a healthy population: a cross‐sectional study
Authors: Moharrami Alireza , Mirghaderi Peyman , Hoseini Zare Nima , Moazen‐Jamshidi Mir Mansour , Ebrahimian Mazaher , Mortazavi Seyed Mohammad Javad
Published: May 2023

Purpose

Pelvic obliquity (PO) has not been extensively investigated, and there is no gold standard for measurement. The PO is essential for surgeons in planning hip arthroplasty, which includes the restoration of leg length discrepancy (LLD). We aimed to establish a normative range of PO angles by measuring healthy individuals without musculoskeletal disorders.

Methods

Our study included 134 consecutive cases (70 females) referred to our institution between April 2020 and September 2021 for non‐orthopedic problems. Patients were screened for normal gait and posture using the visual observation method (VOM) and the Modified Gait Abnormality Rating Scale (GARS‐M). In standing standard radiographs, the PO angle was measured as the angle between the horizontal plane and the inter‐teardrop line.

Results

Patients' mean age and Body Mass Index (BMI) were 39.7 ± 16.8 and 22.3 ± 3.1, respectively. PO angles did not follow a normal distribution, with a median (IQR) of 2.0° (0.9°—3.1°). According to the Wilcoxon one‐sample test, the median PO angle differed significantly from zero (P < 0.001). The PO angle did not differ significantly between males and females (2° vs. 2°, P = 0.46), nor did it correlate significantly with age (P = 0.24). Considering the 95% percentile of PO angles was 5.6°, this range (0°—5.6°) was regarded as a normative value.

Conclusion

Normative values for PO in the normal healthy population range from 0° to 5.6°, with a median value of 2.0°. The PO angle was independent of age and sex and differed significantly from 0°. Slight pelvic obliquity may be normal, and physicians should not always assume that it is caused by pain, scoliosis, or weakness of the abductors.

Level of evidence

III.
Hormone replacement therapy does not increase thrombosis risk following THA: a national database study
Authors: McCormick Brian P. , Sequeira Sean B. , Hasenauer Mark D. , Boucher Henry R.
Published: June 2023

Purpose

Hormone replacement therapy (HRT) causes a significant increase in the risk of venous thrombosis. The risk of medical and surgery‐related complications among women taking HRT following total hip arthroplasty (THA) is poorly understood, and there are currently no guidelines in place regarding venous thromboembolism prophylaxis in this patient population. The purpose of this study was to evaluate the frequency of early medical and surgery‐related complications following THA among women taking HRT.

Methods

Women aged > 40 years of age who underwent primary THA were identified from a retrospective database review. A control group of non‐HRT users was matched using propensity scoring to HRT users. Rates of 90‐day medical complications and 1‐year surgery‐related complications were compared between cohorts using odds ratios. Postoperative anticoagulation regimens were also compared.

Results

There were 3,936 patients in the HRT cohort who were matched to 39,360 patients not taking HRT. There were no significant differences in rates of DVT (OR 0.94, p = 0.6601) or PE (OR 0.80, p = 0.4102) between cohorts. Patients on HRT were more likely to sustain a dislocation (OR 1.35, p = 0.0269) or undergo revision surgery (OR 1.23, p = 0.0105). HRT patients were more likely to be prescribed warfarin (OR 1.21, p = 0.0001) or enoxaparin (OR 1.18, p = 0.0022) and less likely to be prescribed rivaroxaban (OR 0.62, p < 0.0001) compared to controls.

Conclusions

HRT was not found to be an independent risk factor for thromboembolism following THA. Further research is warranted to better delineate the ideal perioperative medical management of HRT users undergoing THA.
Surgical treatment of inferior pole fractures of the patella: a systematic review
Authors: Chang Chih‐Hsun , Shih Chien‐An , Kuan Fa‐Chuan , Hong Chih‐Kai , Su Wei‐Ren , Hsu Kai‐Lan
Published: June 2023

Purpose

This study aimed to comprehensively review the existing evidence concerning surgical treatment of inferior pole fractures of the patella and to report the outcomes and complications of different fixation techniques.

Method

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Searches of PubMed, Scopus, and Web of Science were conducted in March 2023. Studies were screened against predecided inclusion and exclusion criteria. The extracted data included fracture characteristics, surgical techniques, and radiographic and functional outcomes. The Methodological Index for Non‐Randomized Studies (MINORS) quality assessment tool was used to assess the eligible literature. The primary outcome was postoperative range of motion of different surgical methods, and the secondary outcomes were other clinical results and complications.

Results

A total of 42 studies satisfied all the inclusion criteria and were deemed suitable for review. Fourteen case–control studies and 28 case series were selected, for a total of 1382 patients with a mean age of 51.0 years (range = 11–90). The follow‐up period ranged from 6 to 300 months. The surgical techniques were categorized based on the device used as follows: (1) rigid fixation device; (2) tensile fixation device; (3) mixed device; and (4) extra‐patella device.

Conclusion

Regarding the outcomes following surgical treatment of inferior pole fractures of the patella, the postoperative range of motion (ROM) of each technique ranged from 120° to 135°, with the exception of that involving the patellotibial wire which had poorer outcomes. The lowest functional score was also found in those using the patellotibial wire. Complications after surgery are rare, but approximately half of the patients required additional surgery for implant removal, particularly those whose initial surgery involved rigid fixation devices. It's worth noting that bony fragment excision is no longer recommended, and the combined use of multiple surgical devices is now more common.
Nomogram for preoperative estimation risk of lateral cervical lymph node metastasis in papillary thyroid carcinoma: a multicenter study
Authors: Zhu Jialin , Chang Luchen , Li Dai , Yue Bing , Wei Xueqing , Li Deyi , Wei Xi
Published: June 2023

Background

Lateral lymph node metastasis (LLNM) is frequent in papillary thyroid carcinoma (PTC) and is associated with a poor prognosis. This study aimed to developed a clinical-ultrasound (Clin-US) nomogram to predict LLNM in patients with PTC.

Methods

In total, 2612 PTC patients from two hospitals (H1: 1732 patients in the training cohort and 578 patients in the internal testing cohort; H2: 302 patients in the external testing cohort) were retrospectively enrolled. The associations between LLNM and preoperative clinical and sonographic characteristics were evaluated by the univariable and multivariable logistic regression analysis. The Clin-US nomogram was built basing on multivariate logistic regression analysis. The predicting performance of Clin-US nomogram was evaluated by calibration, discrimination and clinical usefulness.

Results

The age, gender, maximum diameter of tumor (tumor size), tumor position, internal echo, microcalcification, vascularization, mulifocality, and ratio of abutment/perimeter (A/P) > 0.25 were independently associated with LLNM metastatic status. In the multivariate analysis, gender, tumor size, mulifocality, position, microcacification, and A/P > 0.25 were independent correlative factors. Comparing the Clin-US nomogram and US features, Clin-US nomogram had the highest AUC both in the training cohort and testing cohorts. The Clin‑US model revealed good discrimination between PTC with LLNM and without LLNM in the training cohort (AUC = 0.813), internal testing cohort (AUC = 0.815) and external testing cohort (AUC = 0.870).

Conclusion

Our findings suggest that the ClinUS nomogram we newly developed can effectively predict LLNM in PTC patients and could help clinicians choose appropriate surgical procedures.
What are the barriers preventing the screening and management of neonatal hypoglycaemia in low-resource settings, and how can they be overcome?
Authors: Irvine Lauren M , Harris Deborah L
Published: June 2023

Over 25 years ago, the World Health Organization (WHO) acknowledged the importance of effective prevention, detection and treatment of neonatal hypoglycaemia, and declared it to be a global priority. Neonatal hypoglycaemia is common, linked to poor neurosensory outcomes and, if untreated, can cause seizures and death. Neonatal mortality in low and lower-middle income countries constitutes an estimated 89% of overall neonatal deaths. Factors contributing to high mortality rates include malnutrition, infectious diseases, poor maternal wellbeing and resource constraints on both equipment and staff, leading to delayed diagnosis and treatment. The incidence of neonatal hypoglycaemia in low and lower-middle income countries remains unclear, as data are not collected.

Data from high-resource settings shows that half of all at-risk babies will develop hypoglycaemia, using accepted clinical thresholds for treatment. Most at-risk babies are screened and treated, with treatment aiming to increase blood glucose concentration and, therefore, available cerebral fuel. The introduction of buccal dextrose gel as a first-line treatment for neonatal hypoglycaemia has changed the care of millions of babies and families in high-resource settings. Dextrose gel has now also been shown to prevent neonatal hypoglycaemia.

In low and lower-middle income countries, there are considerable barriers to resources which prevent access to reliable blood glucose screening, diagnosis, and treatment, leading to inequitable health outcomes when compared with developed countries. Babies born in low-resource settings do not have access to basic health care and are more likely to suffer from unrecognised neonatal hypoglycaemia, which contributes to the burden of neurosensory delay and death.
High-glutathione mesenchymal stem cells isolated using the FreSHtracer probe enhance cartilage regeneration in a rabbit chondral defect model
Authors: Cho Gun Hee , Bae Hyun Cheol , Cho Won Young , Jeong Eui Man , Park Hee Jung , Yang Ha Ru , Wang Sun Young , Kim You Jung , Shin Dong Myung , Chung Hyung Min , Kim In Gyu , Han Hyuk-Soo
Published: May 2023

Background

Mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration. However, the function of MSC can vary according to cell culture conditions, donor age, and heterogeneity of the MSC population, resulting in unregulated MSC quality control. To overcome these limitations, we previously developed a fluorescent real-time thiol tracer (FreSHtracer) that monitors cellular levels of glutathione (GSH), which are known to be closely associated with stem cell function. In this study, we investigated whether using FreSHtracer could selectively separate high-functioning MSCs based on GSH levels and evaluated the chondrogenic potential of MSCs with high GSH levels to repair cartilage defects in vivo.

Methods

Flow cytometry was conducted on FreSHtracer-loaded MSCs to select cells according to their GSH levels. To determine the function of FreSHtracer-isolated MSCs, mRNA expression, migration, and CFU assays were conducted. The MSCs underwent chondrogenic differentiation, followed by analysis of chondrogenic-related gene expression. For in vivo assessment, MSCs with different cellular GSH levels or cell culture densities were injected in a rabbit chondral defect model, followed by histological analysis of cartilage-regenerated defect sites.

Results

FreSHtracer successfully isolated MSCs according to GSH levels. MSCs with high cellular GSH levels showed enhanced MSC function, including stem cell marker mRNA expression, migration, CFU, and oxidant resistance. Regardless of the stem cell tissue source, FreSHtracer selectively isolated MSCs with high GSH levels and high functionality. The in vitro chondrogenic potential was the highest in pellets generated by MSCs with high GSH levels, with increased ECM formation and chondrogenic marker expression. Furthermore, the MSCs’ function was dependent on cell culture conditions, with relatively higher cell culture densities resulting in higher GSH levels. In vivo, improved cartilage repair was achieved by articular injection of MSCs with high levels of cellular GSH and MSCs cultured under high-density conditions, as confirmed by Collagen type 2 IHC, Safranin-O staining and O’Driscoll scores showing that more hyaline cartilage was formed on the defects.

Conclusion

FreSHtracer selectively isolates highly functional MSCs that have enhanced in vitro chondrogenesis and in vivo hyaline cartilage regeneration, which can ultimately overcome the current limitations of MSC therapy.

Graphical Abstract
Effects of common fertilizers on the soil ecosystem
Authors: Frattini Natalia , Pulido Carrasquero Alcibeth , Pronsato Lucía , Milanesi Lorena , Vasconsuelo Andrea
Published: June 2023

Background

The importance of this study lies in showing how certain usual practices of farmers such as burying stubble to fertilize soils or the routine use of fertilizers, affect soil quality. This is due to the effect that these practices have on the soil ecosystem. This study aims to reveal the importance of including bioindicators in soil analysis, showing how these activities negatively affect the soil ecosystem, which is responsible for maintaining soil quality.

Results

By evasion response assays, was observed that Eiseniafoetida avoided standing in the presence of urea 46%, phosphorous and nitrogen-based fertilizers, or crop waste; since earthworms exposed to soil-stubble (one part of ground tomato stubble, for every 5 parts of control soil), soil-fert (500 g of control soil, for each 50 g chemical fertilizer), or soil-urea (5 g/100 ml deionized water, watered over 500 g of control soil), exhibited significant avoidance responses (88.75% ± 17.3, 97.5% ± 5, and 91.25% ± 13.6 respectively. Data are means ± standard deviations *p < 0.05, with respect to the control). In addition, when earthworms could not escape from these stimuli, important morphological and histological changes, suggesting cell damage by apoptosis, were observed as decreased mobility.

Conclusions

This work shows the importance of evaluating soil quality, with sensitive systems that allow the detection of negative effects in stages that can be reversed. That is, with parameters other than the physicochemical ones; reaching an integral assessment of the soils since it includes the entire ecosystem, thus obtaining information about the possible future state of these soils.
Deep learning method for super-resolution reconstruction of the spatio-temporal flow field
Authors: Bao Kairui , Zhang Xiaoya , Peng Wei , Yao Wen
Published: June 2023

The high-resolution (HR) spatio-temporal flow field plays a decisive role in describing the details of the flow field. In the acquisition of the HR flow field, traditional direct numerical simulation (DNS) and other methods face a seriously high computational burden. To address this deficiency, we propose a novel multi-scale temporal path UNet (MST-UNet) model to reconstruct temporal and spatial HR flow fields from low-resolution (LR) flow field data. Different from the previous super-resolution (SR) model, which only takes advantage of LR flow field data at instantaneous (SLR) or in a time-series (MTLR), MST-UNet introduces multi-scale information in both time and space. MST-UNet takes the LR data at the current frame and the predicted HR result at the previous moment as the model input to complete the spatial SR reconstruction. On this basis, a temporal model is introduced as the inbetweening model to obtain HR flow field data in space and time to complete spatio-temporal SR reconstruction. Finally, the proposed model is validated by the spatio-temporal SR task of the flow field around two-dimensional cylinders. Experimental results show that the outcome of the MST-UNet model in spatial SR tasks is much better than those of SLR and MTLR, which can greatly improve prediction accuracy. In addition, for the spatio-temporal SR task, the spatio-temporal HR flow field predicted by the MST-UNet model has higher accuracy either.
Origins and localization of Tai Lue food culture in Northern Thailand
Authors: Krajangchom Sansanee
Published: June 2023

This qualitative investigation explores the cuisine of the Tai Lue people, an ethnic minority group in Northern Thailand. Through documentary analysis, field study and participatory action research, four traditional Tai Lue dishes were transformed for presentation to visitors. Community members developed these products in cooperation with a trained chef. The final products were marketed through a university podcast project and at a cultural fair. The results of the investigation were disrupted by the Covid pandemic, but the initial impact of the project indicates a prospective place in the wider post-pandemic environment for the indigenous cuisine of the Tai Lue. The following paper discusses this potential through the lens of the foodscape, regional development and authenticity.
Association of anandamide and 2-arachidonoylglycerol concentrations with clinical features and body mass index in eating disorders and obesity
Authors: Baenas Isabel , Miranda-Olivos Romina , Granero Roser , Solé-Morata Neus , Sánchez Isabel , Pastor Antoni , del Pino-Gutiérrez Amparo , Codina Ester , Tinahones Francisco J. , Fernández-Formoso José A. , Vilarrasa Núria , Guerrero-Pérez Fernando , Lopez-Urdiales Rafael , Virgili Núria , Soriano-Mas Carles , Jiménez-Murcia Susana , de la Torre Rafael , Fernández-Aranda Fernando
Published: May 2023

Background

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a pivotal role in stimulating motivational behavior toward food and energy metabolism. Aberrant functioning of the endocannabinoid system has been observed in extreme weight conditions (EWCs), suggesting it may influence pathophysiology. Then, we aimed to analyze fasting AEA and 2-AG plasma concentrations among individuals with EWC (i.e., anorexia nervosa [AN] and obesity with and without eating disorders [EDs]) compared with healthy controls (HCs), and its association with clinical variables and body mass index (BMI).

Methods

The sample included 113 adult women. Fifty-seven belonged to the obesity group, 37 without EDs (OB-ED) and 20 with ED (OB+ED classified within the binge spectrum disorders), 27 individuals from the AN group, and 29 from the HC group. Peripheral blood samples, several clinical variables, and BMI were evaluated.

Results

Unlike 2-AG, AEA concentrations showed significant differences between groups (p < 0.001). Increased AEA was observed in the OB-ED and OB+ED compared with both HC and AN group, respectively. Likewise, AEA was differentially associated with emotional dysregulation, general psychopathology, food addiction, and BMI in all clinical groups.

Conclusions

These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches.
An Intragastric Delivery Device Employing FDM Technology: 3D-Printed Tablet Containing Green Developed Mosapride-Saccharin Co-crystals
Authors: Amin Omnya Mahmoud , EL Qady Hesham Nassereldin , Abd El-Fattah Marwa Adel
Published: June 2023

Mosapride citrate (MC) is a poorly soluble short half-life drug with more pronounced absorption in the stomach. The present study aimed to incorporate MC co-crystals with enhanced solubility into 3D-printed floating tablets. MC co-crystals were prepared via the green method using Saccharin sod. as a co-former at a (1:1) molar ratio. The prepared co-crystals were assessed for solubility, FTIR, thermal behavior, and SEM. Then, it was incorporated into zero % infill 3D-printed tablets of different configurations at two thickness levels by the FDM printing technique. Printed tablets were evaluated for dimensions, weight deviation, friability, and in vitro floating behavior. Drug release and kinetic of the MC release were also assessed. Solubility study of the co-crystals showed a significant (p value < 0.05) increased solubility over pure MC. FTIR and thermal behavior confirmed hydrogen bonding formation during co-crystallization. The obstructed particles had an erratic protrusion form, similar to a nodule, as illustrated by SEM. The printed tablets showed acceptable physicochemical properties. Tablets floated for about ≥ 12 h without floating lag time. In vitro drug release exhibited variable extended release profiles with different lag times depending on the configuration indicating that the tablet’s wall thickness and surface area were the factors manipulated to control drug release. Kinetic analysis of the release data displayed intermediate kinetics between zero-order and diffusional kinetics. The intragastric extended release profile for MC co-crystals of improved solubility could be successfully, economically, and quickly developed utilizing the 3D printing technique.

Graphical Abstract
Interacting, running and tumbling: The active Dyson Brownian motion
Authors: Touzo L. , Le Doussal P. , Schehr G.
Published: June 2023

We introduce and study a model in one dimension of N run-and-tumble particles (RTP) which repel each other logarithmically in the presence of an external quadratic potential. This is an “active” version of the well-known Dyson Brownian motion (DBM) where the particles are subjected to a telegraphic noise, with two possible states ± with velocity ±v
0. We study analytically and numerically two different versions of this model. In model I a particle only interacts with particles in the same state, while in model II all the particles interact with each other. In the large time limit, both models converge to a steady state where the stationary density has a finite support. For finite N, the stationary density exhibits singularities, which disappear when

. In that limit, for model I, using a Dean-Kawasaki approach, we show that the stationary density of + (respectively −) particles deviates from the DBM Wigner semi-circular shape, and vanishes with an exponent 3/2 at one of the edges. In model II, the Dean-Kawasaki approach fails but we obtain strong evidence that the density in the large N limit (still) retains a Wigner semi-circular shape.
New Horizons: Gonadotropin-Releasing Hormone and Cognition
Authors: Prévot Vincent , Tena-Sempere Manuel , Pitteloud Nelly
Published: June 2023

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic–pituitary–gonadal axis, which controls the onset of puberty and fertility. Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition. This review will summarize the development and establishment of the GnRH system, with particular attention to the importance of its first postnatal activation, a phenomenon known as minipuberty, for later reproductive and nonreproductive functions. In addition, we will discuss the beneficial effects of restoring physiological (ie, pulsatile) GnRH levels on olfactory and cognitive alterations in preclinical Down syndrome and Alzheimer disease models, as well as the potential risks associated with long-term continuous (ie, nonphysiological) GnRH administration in certain disorders. Finally, this review addresses the intriguing possibility that pulsatile GnRH therapy may hold therapeutic potential for the management of some neurodevelopmental cognitive disorders and pathological aging in elderly people.
A False Pituitary Tumor
Authors: Hurtado Andrade Maria D , Tama Elif , Atkinson John L D , Chang Alice Y
Published: June 2023

A false pituitary tumor describes pituitary enlargement due to intracranial hypotension. Reported previously primarily in the neurological literature, we present this case referred to endocrinology for evaluation of a pituitary mass. A 24-year-old male was referred to endocrinology for evaluation of pituitary enlargement without a hypo-enhancing lesion on magnetic resonance imaging (MRI). The main symptom reported was headache that was worse in the standing position and in the afternoon. He had no symptoms or signs of pituitary mass-effect, or hormone excess or deficiencies. Past medical history was relevant for a history of nerve schwannoma status post resection with subsequent spinal fusion. Biochemical evaluation of pituitary hormones was normal. Upon review of his pituitary MRI, other abnormalities seen were suggestive of intracranial hypotension. Based on his history and imaging findings, he was diagnosed with intracranial hypotension causing a “false pituitary tumor” rather than pituitary enlargement or abnormality. Further evaluation revealed multiple spinal leaks that were patched. His symptoms subsided within a few days of repair. Endocrinologists should be aware of the possible misdiagnosis of a pituitary mass due to intracranial hypotension.
Causes of Death in Patients With Brain Metastases
Authors: Schnurman Zane , Mashiach Elad , Link Katherine E. , Donahue Bernadine , Sulman Erik , Silverman Joshua , Golfinos John G. , Oermann Eric Karl , Kondziolka Douglas
Published: May 2023

BACKGROUND AND OBJECTIVES:

Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities.

METHODS:

Using NYUMets-Brain—the largest, longitudinal, real-world, open data set of patients with brain metastases—patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number.

RESULTS:

Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived (P < .001), but there was no difference in rates of volume change per intracranial tumor (P = .95).

CONCLUSION:

Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.
Maturing differentiated human pluripotent stem cells in vitro: methods and challenges
Authors: Ottaviani Daniele , ter Huurne Menno , Elliott David A. , Bellin Milena , Mummery Christine L.
Published: June 2023

Human pluripotent stem cells (hPSCs), derived from individuals or genetically modified with disease-related mutations and variants, have revolutionised studies of human disease. Researchers are beginning to exploit the extraordinary potential of stem cell technology to screen for new drugs to treat intractable diseases, ideally without side-effects. However, a major problem is that the differentiated cell types on which these models are based are immature; they resemble fetal and not adult cells. Here, we discuss the nature and hurdles of hPSC maturation, using cardiomyocytes as an example. We review methods used to induce cardiomyocyte maturation in culture and consider remaining challenges for their integration into research on human disease and drug development pipelines.
deCLUTTER2+ – a pipeline to analyze calcium traces in a stem cell model for ventral midbrain patterned astrocytes
Authors: Grochowska Martyna M. , Ferraro Federico , Mascaro Ana Carreras , Natale Domenico , Winkelaar Amber , Boumeester Valerie , Breedveld Guido J. , Bonifati Vincenzo , Mandemakers Wim
Published: June 2023

Astrocytes are the most populous cell type of the human central nervous system and are essential for physiological brain function. Increasing evidence suggests multiple roles for astrocytes in Parkinson's disease, nudging a shift in the research focus, which historically pivoted around ventral midbrain dopaminergic neurons (vmDANs). Studying human astrocytes and other cell types in vivo remains challenging. However, in vitro-reprogrammed human stem cell-based models provide a promising alternative. Here, we describe a novel protocol for astrocyte differentiation from human stem cell-derived vmDAN-generating progenitors. This protocol simulates the regionalization, gliogenic switch, radial migration and final differentiation that occur in the developing human brain. We characterized the morphological, molecular and functional features of these ventral midbrain patterned astrocytes with a broad palette of techniques and identified novel candidate midbrain-astrocyte specific markers. In addition, we developed a new pipeline for calcium imaging data analysis called deCLUTTER2+ (deconvolution of Ca2+ fluorescent patterns) that can be used to discover spontaneous or cue-dependent patterns of Ca2+ transients. Altogether, our protocol enables the characterization of the functional properties of human ventral midbrain patterned astrocytes under physiological conditions and in disease.
A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum
Authors: Kirolos Sara A. , Hatfield Chance E. , Rahman Ryan J. , Consalvo Kristen M. , Dittenhauser Nolan K. , Gomer Richard H.
Published: June 2023

During developmental and immune responses, cells move towards or away from some signals. Although much is known about chemoattraction, chemorepulsion (the movement of cells away from a stimulus) remains poorly understood. Proliferating Dictyostelium discoideum cells secrete a chemorepellent protein called AprA. Examining existing knockout strains, we previously identified proteins required for AprA-induced chemorepulsion, and a genetic screen suggested that the enzyme phosphatidylinositol phosphate kinase A (PIPkinA, also known as Pik6) might also be needed for chemorepulsion. Here, we show that cells lacking PIPkinA are not repelled by AprA, and that this phenotype is rescued by expression of PIPkinA. To bias cell movement, AprA inhibits Ras activation at the side of the cell closest to the source of AprA, and we find that PIPkinA is required for AprA to inhibit Ras activation. PIPkinA decreases levels of phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], and possibly because of these effects, potentiates phagocytosis and inhibits cell proliferation. Cells lacking PIPkinA show normal AprA binding, suggesting that PIPkinA regulates chemorepulsion at a step between the AprA receptor and AprA inhibition of Ras activation.