Miracle-dz/UniFAR-FTUs huggingface dataset:
Reliability of the DIERS Formetric 4D Spine Shape Parameters in Adults without Postural Deformities

The DIERS formetric 4D provides a safe method to monitor and track the progression of postural deformities over time. However, further evaluation of reliability is necessary. Reference values are also needed to indicate postural change. The current study examined the reliability of spine shape parameters produced by the formetric 4D in adults without postural abnormalities and established reference values to determine when real change occurs. Thirty participants were scanned during 1 week. Intraclass correlation coefficients (ICCs) were calculated for 40 spine shape parameters for scans with participants stationary between scans, scans with repositioning between scans, and between days. Within-day and between-day standard error of measurement (SEM), absolute relative SEM, and smallest detectable change (SDC) were reported. ICC for stationary scans was excellent for 29 parameters, good for 10 parameters, and fair for 1 parameter. With repositioning, ICC was excellent for 27 parameters, good for 12 parameters, and fair for 1 parameter. Between days, ICC was excellent for 26 parameters, good for 10 parameters, and fair for 4 parameters. Within-day SEM% was greater than 10% for 6 parameters. Within-day SDC ranged from 1.80 to 25.03 units for a single scan and from 0.97 to 17.93 units for 6 scans. Between-day SEM% was greater than 10% for 9 parameters. Between-day SDC ranged from 1.44 to 28.24 units for a single scan and from 1.05 to 22.2 units for 6 scans. Thirty-six of the 40 spine shape parameters from the DIERS formetric 4D reliably distinguished between participants over time. Reference values were established that can be used to track patient postural change over time. Future research should investigate the clinical relevance of these 40 spine shape parameters and determine when a clinically important change in posture occurs.
Locally sequential synaptic reactivation during hippocampal ripples

Adjacent CA1 dendritic spines are sequentially and repeatedly activated during hippocampal sharp-wave ripples. The sequential reactivation of memory-relevant neuronal ensembles during hippocampal sharp-wave (SW) ripple oscillations reflects cognitive processing. However, how a downstream neuron decodes this spatiotemporally organized activity remains unexplored. Using subcellular calcium imaging from CA1 pyramidal neurons in ex vivo hippocampal networks, we discovered that neighboring spines are activated serially along dendrites toward or away from cell bodies. Sequential spine activity was engaged repeatedly in different SWs in a complex manner. In a single SW event, multiple sequences appeared discretely in dendritic trees, but overall, sequences occurred preferentially in some dendritic branches. Thus, sequential replays of multineuronal spikes are distributed across several compartmentalized dendritic foci of a postsynaptic neuron, with their spatiotemporal features preserved.
Comparison of Arachis monticola with Diploid and Cultivated Tetraploid Genomes Reveals Asymmetric Subgenome Evolution and Improvement of Peanut

Like many important crops, peanut is a polyploid that underwent polyploidization, evolution, and domestication. The wild allotetraploid peanut species Arachis monticola (A. monticola) is an important and unique link from the wild diploid species to cultivated tetraploid species in the Arachis lineage. However, little is known about A. monticola and its role in the evolution and domestication of this important crop. A fully annotated sequence of ≈2.6 Gb A. monticola genome and comparative genomics of the Arachis species is reported. Genomic reconstruction of 17 wild diploids from AA, BB, EE, KK, and CC groups and 30 tetraploids demonstrates a monophyletic origin of A and B subgenomes in allotetraploid peanuts. The wild and cultivated tetraploids undergo asymmetric subgenome evolution, including homoeologous exchanges, homoeolog expression bias, and structural variation (SV), leading to subgenome functional divergence during peanut domestication. Significantly, SV‐associated homoeologs tend to show expression bias and correlation with pod size increase from diploids to wild and cultivated tetraploids. Moreover, genomic analysis of disease resistance genes shows the unique alleles present in the wild peanut can be introduced into breeding programs to improve some resistance traits in the cultivated peanuts. These genomic resources are valuable for studying polyploid genome evolution, domestication, and improvement of peanut production and resistance.
The newly developed genomic-SSR markers uncover the genetic characteristics and relationships of olive accessions

Background Olive (Olea europaea L.) is an important oil and fruit crop worldwide, owning a rich germplasm with a large number of cultivars. Simple sequence repeats (SSRs) are excellent markers and have been used for the identification of olive cultivars. However, the limited number of SSR markers and the occurrence of confusion on the names of cultivars, as well as the possible appearance of clonal variation make it difficult to identify cultivars and interpret relationships among olive cultivars. Method SSR markers were designed based on trinucleotide repeat sequences by screening the whole genome of olive, and the polymorphic SSR markers were developed that were applied to the identification of 53 olive accessions. The genetic characteristics and relationships of these olive accessions were evaluated based on the developed SSR markers. Results Twenty-one highly polymorphic genomic-SSR markers were developed, covering most chromosomes of olive. These SSR markers could well distinguish all 53 olive accessions, confirming their effectiveness. DNA fingerprints of the 53 olive accessions were constructed based on the 21 SSR markers. The dendrogram clearly divided the tested accessions into two main groups, which was also supported by the results of principal coordinate analysis. A total of 31 private alleles were detected in 15 olive accessions, which reflected the genetic diversity within 53 olive accessions to some extent. Six homonymy cases were also clarified by genetic analysis. These results suggest that the newly developed olive SSR markers are informative for the exploitation, preservation and breeding of olive.
The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer

Purpose A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear. Methods The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay. Results We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB. Conclusion Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.
An Adolescent Female with Bipolar Disorder Presenting with Lithium-Induced Hyperthyroidism

Lithium therapy has been associated with several endocrine disorders including thyroid dysfunction, diabetes insipidus, and hyperparathyroidism. While its suppressive effect on thyroid function is well known, it is very rare to observe lithium-induced hyperthyroidism especially in the pediatric population. Here, we describe a case of lithium-induced hyperthyroidism in an adolescent female with bipolar disorder. The patient is a 17-year-old female who was treated with lithium for bipolar disorder and presented with symptoms and laboratory findings consistent with hyperthyroidism. Since thyroid autoantibodies were negative, thyroid dysfunction was attributed to lithium toxicity. Indeed, her clinical and biochemical hyperthyroid state resolved after stopping lithium therapy. Lithium-associated hyperthyroidism can occur in the pediatric population. We propose close monitoring of thyroid hormone levels in children on lithium therapy.
Associations Between Diagnosis with Type 2 Diabetes and Changes in Physical Activity among Middle-Aged and Older Adults in the United States

Abstract Background and Objectives Physical activity (PA) is an effective strategy for diabetes self-management and is central to the diabetes regimen. Diagnostic events present an opportunity for health behavior change; however, many older adults with type 2 diabetes (T2D) do not engage in regular PA. The relationships between diagnosis events and subsequent changes in PA are not well understood. Drawing upon life-course theory, this is the first study to examine whether the diagnosis of T2D is followed by a change in PA, whether these changes are sustained, and the sociodemographic characteristics associated with these changes. Research Design and Methods We examined associations between T2D diagnosis and PA changes among 2,394 adults ages 51+ from the Health and Retirement Study (2004–2014). PA changes were measured using metabolic equivalents of task (METs) estimated values accounting for the vigor and frequency of self-reported PA. Using piecewise mixed models, we examined initial and sustained changes in METs over time and tested whether these changes were modified by race/ethnicity, educational level, gender, and age at diagnosis. Results Across participants, a significant postdiagnosis increase was observed in self-reported PA following the diagnostic event (β: 0.54, 95% CI: 0.10, 0.97). The steepness of decline in PA participation over time did not change significantly following T2D diagnosis. Age at diagnosis and race/ethnicity significantly moderated these relationships: participants diagnosed at older ages were less likely to improve PA following diagnosis and non-Hispanic whites experienced relatively steeper rates of decline following diagnosis with T2D. Discussion and Implications Modest diagnosis-related increases in PA were observed among participants overall. The usual rate of decline in PA appears unaffected by diagnosis overall. Age at diagnosis and race/ethnicity moderated these relationships. Key implications for future research and clinical practice are discussed.
Immune Responses Induced by pVAX/TgERK7 against Toxoplasma gondii Infection in BALB/c Mice

Background: Toxoplasma gondii can infect all the warm-blooded vertebrates and cause serious toxoplasmosis. Extracellular signal-regulated kinase 7 in T. gondii (TgERK7) mediated the proliferation of this parasite may be a potential vaccine candidate. Thus, immune responses induced by TgERK7 were investigated in this study using a DNA vaccine strategy. Methods: pVAX/TgERK7 plasmid was constructed and used to immunize BALB/c mice for three times with two-week intervals. The challenge and the investigation of humoral and cellular immune responses were performed at two weeks post the last immunization, and the survival times of the infected mice were daily recorded until all of them were dead. Results: The innate immune response with higher concentrations of IFN-γ, TNF-α, IL2 and IL12p70 in sera (P < 0.05), and the adaptive immune responses were evoked by the DNA immunizations, including specific antibody, lymphocyte proliferation, and the CD3e+CD4+ and CD3e+CD8a+ T cell-mediated response effects. Interestingly, no significant difference was detected in their survival times among all the experimental groups of mice that were challenged with GT1 tachyzoites or PRU cysts (P>0.05). Conclusion: The successive immunizations with pVAX/TgERK7 can provoke the innate and adaptive immune responses of BALB/c mice, whereas the DNA vaccine-induced immunological efficacy is not sufficient for complete protection the host against T. gondii infection.
Multiple Myeloma Mimicking a Small Vessel Vasculitis Presentation

Multiple myeloma can have different clinical manifestations, and not all patients present with classic CRAB component. We describe a 46-year-old woman admitted to our hospital with a complaint of a bluish-to-black discoloration of the second toe that was rapidly progressive and acute kidney injury. We documented a Kappa light chain monoclonal gammopathy, increased presence of plasmacytes in bone marrow aspiration, and multiple lytic bone lesions, which led to a diagnosis of multiple myeloma. Although multiple myeloma presenting with blue finger syndrome is uncommon, it must always be considered as a differential diagnosis with this clinical finding.
Marked structural rearrangement of mannose 6-phosphate/IGF2 receptor at different pH environments

Two cryo-EM structures of IGF2R at different pH values imply the mechanism for its ligand release in endocytic compartments. Many cell surface receptors internalize their ligands and deliver them to endosomes, where the acidic pH causes the ligand to dissociate. The liberated receptor returns to the cell surface in a process called receptor cycling. The structural basis for pH-dependent ligand dissociation is not well understood. In some receptors, the ligand binding domain is composed of multiple repeated sequences. The insulin-like growth factor 2 receptor (IGF2R) contains 15 β strand–rich repeat domains. The overall structure and the mechanism by which IGF2R binds IGF2 and releases it are unknown. We used cryo-EM to determine the structures of the IGF2R at pH 7.4 with IGF2 bound and at pH 4.5 in the ligand-dissociated state. The results reveal different arrangements of the receptor in different pH environments mediated by changes in the interactions between the repeated sequences. These results have implications for our understanding of ligand release from receptors in endocytic compartments.
The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy

Inducible T cell costimulator (ICOS, cluster of differentiation (CD278)) is an activating costimulatory immune checkpoint expressed on activated T cells. Its ligand, ICOSL is expressed on antigen-presenting cells and somatic cells, including tumour cells in the tumour microenvironment. ICOS and ICOSL expression is linked to the release of soluble factors (cytokines), induced by activation of the immune response. ICOS and ICOSL binding generates various activities among the diversity of T cell subpopulations, including T cell activation and effector functions and when sustained also suppressive activities mediated by regulatory T cells. This dual role in both antitumour and protumour activities makes targeting the ICOS/ICOSL pathway attractive for enhancement of antitumour immune responses. This review summarises the biological background and rationale for targeting ICOS/ICOSL in cancer together with an overview of the principal ongoing clinical trials that are testing it in combination with anti-cytotoxic T lymphocyte antigen-4 and anti-programmed cell death-1 or anti-programmed cell death ligand-1 based immune checkpoint blockade.
Evaluation of Novel Stereotactic Cannula for Stem Cell Transplantation against Central Nervous System Disease

Cell therapy for central nervous system (CNS) disorders is beginning to prove its safety and efficiency. Intraparenchymal transplantation can be an option for cell delivery; however, one concern regarding this method is that the transplantation cannula may cause additional brain injuries. These include vessel damage, which results in brain hemorrhage, and clogging of the cannula by brain debris and/or cell clusters, which requires replacement of the cannula or forced injection causing jet flow of the cell suspension. We compared cannulas for cell delivery used in clinical trials, the Pittsburg and Mizuho cannulas, to a newly designed one, MK01, to assess their usability. MK01 has a spherical-shaped tip with a fan-like open orifice on the side of the cannula, which prevents vessel damage, clogging of brain debris, and jet flow phenomenon. We compared the extent of rat cervical and abdominal arterial damage with the cannula, the amount of debris in the cannula, the force needed to cause jet flow, and cell viability. While the viability of cells passed through the cannulas was almost the same among cannulas (approximately 95%), the Pittsburg cannula caused cervical arterial injury and subsequent hemorrhage, as it required a significantly smaller force to penetrate the arterial wall. Moreover, the Pittsburg cannula, but not the Mizuho and MK01 cannulas, showed high frequency of brain debris in the needle tip (approximately 80%) after brain puncture. While jet flow of the injection liquid was observed even when using smaller forces in the Pittsburg and Mizuho cannulas, MK01 constantly showed low jet flow occurrence. Thus, MK01 seems to be safer than the previously reported cannulas, although further investigation is necessary to validate its safety for clinical use.
Introducing tumor necrosis factor as a prominent player in celiac disease and type 1 diabetes mellitus

Aim: This study aimed to screen the common genes between celiac disease (CD) and type 1 diabetes mellitus to find critical ones. Background: Celiac disease is a chronic autoimmune disorder which is correlated to type 1 diabetes mellitus (T1DM) in several molecular pathways. Understanding the clear common molecular mechanism of both diseases is of interest to scientists. Methods: The related genes to the CD and T1DM were obtained from disease query of STRING and included in two separated PPI networks by Cytoscape software version 3.7. 1. The networks were analyzed by network analyzer and the hub nodes were determined. The common hubs between the two networks were selected for further analysis and enriched via gene ontology using ClueGO plugin of Cytoscape software. Also, an action map was provided by Cluepedia application of Cytoscape software. Results: Two separated networks of 2000 and 430 genes were constructed related to T1DM and CD, respectively. A total of 84 and 28 hubs were determined for T1DM and CD, respectively. There were 11 common hubs between the two networks. The first top hubs of Type 1 Diabetes Mellitus and CD networks were insulin (INS) and tumor necrosis factor (TNF), respectively. Also, 77 biological terms and pathways (in five clusters) were related to the common hubs. Action map revealed a close relationship between hubs. Conclusion: The result of this study indicated that TNF is key mediator of immune reactions in celiac disease and type 1 diabetes mellitus.
HPV vaccination and sexual behaviour in healthcare seeking young women in Luxembourg

Introduction Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Despite recommendations for HPV vaccination of young women from health authorities, parental concerns were raised whether vaccination could induce unsafe sexual behaviour in young women. Therefore, the primary aim of this study was to investigate if HPV vaccination in healthcare seeking adult women in Luxembourg was associated with unsafe sexual behaviour. Methods Seven hundred twenty-nine women (mean age = 22.5; range 18–43 years) were recruited either at Luxembourg family planning centres or at private gynaecology practices. All participants completed a questionnaire on vaccination status and sexual behaviour. Poisson and logistic regressions were used to study the association between sexual behaviour and vaccination status (N = 538). Both models were restricted to women younger than 26 years, since the first cohort being vaccinated would be 25 years old at the time of sampling. Assortativity of sexual mixing by age was also assessed for further transmission modelling for women <30 years reporting age of last/current sexual partner (N = 649). Women older than 29 years were excluded from the assortativity analysis due to restricted sample size. Results In total, 386/538 (71.8%) of participants reported receiving HPV vaccine. Vaccination uptake significantly varied by nationality and was higher in Portuguese 112/142 (78.9%) and in Luxembourgish 224/313(71.6%) residents, and lower in residents of other nationalities 50/83 (60.2%) (p = 0.011). HPV vaccination was not associated with unsafe sexual behaviour such as shorter relationship duration with current or last sexual partner (odds ratio (OR) = 1.05, 95% CI [0.94–1.16]), younger age of sexual debut (OR = 1.00, 95% CI [0.88–1.14]), increased number of lifetime sexual partners (OR = 0.95, 95% CI [0.87–1.03), higher age difference with sexual partner (OR = 1.01, 95% CI [0.95–1.08]), condom use (OR = 0.97, 95% CI [0.60–1.56]), nor with other factors like smoking (OR = 0.73, 95% CI [0.47–1.15]) and nationality. HPV vaccination was only associated with younger age (OR = 0.84, 95% CI [0.75–0.94]). Relationship duration, age of sexual debut, age difference with sexual partner, smoking, age and non-Portuguese foreign nationality were predictors of number of lifetime sexual partners. Assortativity analysis revealed that young women chose sexual partners who were 2.3 years older on average. Conclusions Our study found no association between unsafe sexual behaviour and HPV vaccination.