Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell

Abstract Mesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by the unpredictable therapeutic efficacy of MSC infusions reported in multiple clinical trials. A seminal recent study showed that infused MSCs are actively induced to undergo apoptosis by recipient cytotoxic T cells, a mechanism that triggers in vivo recipient-induced immunomodulation by such apoptotic MSCs, and the need for such recipient cytotoxic cell activity could be replaced by the administration of ex vivo-generated apoptotic MSCs. Moreover, the use of MSC-derived extracellular vesicles (MSC-EVs) is being actively explored as a cell-free therapeutic alternative over the parental MSCs. We hypothesized that the introduction of a “suicide gene” switch into MSCs may offer on-demand in vivo apoptosis of transplanted MSCs. Here, we prompted to investigate the utility of the iCasp9/AP1903 suicide gene system in inducing apoptosis of MSCs. iCasp9/AP1903-induced apoptotic MSCs (MSCiCasp9+) were tested in vitro and in in vivo models of acute colitis. Our data show a very similar and robust immunosuppressive and anti-inflammatory properties of both “parental” alive MSCGFP+ cells and apoptotic MSCiCasp9+ cells in vitro and in vivo regardless of whether apoptosis was induced in vivo or in vitro before administering MSCiCasp9+ lysates. This development of an efficient iCasp9 switch may potentiate the safety of MSC-based therapies in the case of an adverse event and, will also circumvent current logistic technical limitations and biological uncertainties associated to MSC-EVs.
Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer

Abstract Background Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC. Materials and Methods Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis. Results Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c. 2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor. Conclusion Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.
Creating a Dynamic Framework for Human Resource Management within Organizational Change

Although complex systems are part of organizational studies for several decades, they have witnessed significant changes in recent years. This research builds on existent work on complex systems by focusing on the shift toward power-law distributions. By using theories of complex systems, organizational change is shifting towards a stable environment. Evidentially, HRM is highly nested in those complex systems. Due to advancements in theoretical understanding of complexity and influenced by this, HRM is changing fundamentally towards a dynamic approach. It becomes evident that HRM is no longer a constant within the organization, but a necessary process within the translucent system. In consequence, a new notion of a dynamic HRM emerges which could be characterized “function follows process. ” Based on that, understanding HRM as complex systems HRM needs to observe the dynamic core of its processes as well as the out-comes of a changed governing distribution and derive from this its alternating functionality. HRM needs to sustain all necessary processes for the survival of its organization. In this paper I am describing this fluid HRM system and by using the complex systems framework, developing a dynamic and flexible approach to achieve an adaptable HRM within organizational change.
A New Cascaded Multilevel Inverter Topology with Voltage Sources Arranged in Matrix Structure

The paper unleashes a new idea to arrive at reduced switch count topological structures configured in the form of a matrix for a cascaded Multi level inverter (CMLI). The theory encircles to minimize the number of switches involved in the conduction path and there from acclaim reduced input current distortion, lower switching losses and electromagnetic interference. The focus extends to standardize the number of power devices required for reaching different levels of output voltage from the same architecture. It includes appropriate pulse width modulation (PWM) strategy to generate firing pulses and ensure the desired operation of the power modules. The investigative study carries with it MATLAB based simulation and experimental results obtained using suitable prototypes to illustrate the viability of the proposed concept. The promising nature of the performance projects a new dimension in the use of single phase MLIs for renewable energy related applications.
The Impact of Health Policy on Patients’ Awareness of the Risks Associated with Obesity: An International Multicenter Study in Poland and Germany

Background Recent studies indicate that the treatment of obesity is unsuccessful. The cause of this situation is that patients are not sufficiently educated about therapeutic methods and the health consequences of not treating obesity. Moreover, obesity prevention strategies differ significantly between EU countries. Objective The primary aim of this study was to examine and compare the level of obesity-related knowledge and illness perception among obese patients from Poland and Germany. Methods A prospective cross-sectional international multicentre study was conducted. The study included 564 subjects above 18 years old (210 German patients and 354 Polish patients) with obesity. A validated custom-made questionnaire was used to evaluate obesity-related knowledge. Patient illness perception was evaluated using Polish and German language versions of the standardized Brief Illness Perception Questionnaire (B-IPQ). Results Obese patients from Germany had significantly higher level of obesity-related knowledge than patients from Poland (22.01 ± 4.68 vs 19.17 ± 6.59, p<0.0001). Obesity-related knowledge was associated with the patient’s education, patient participation in therapeutic educational programs, patient’s perception of the illness, age and the number of healthcare professionals involved in the patient’s treatment process. Conclusion The level of obesity-related knowledge among both Polish and German patients is unsatisfactory. This study suggests that health education is required to facilitate informed choices and support the use of cognitive approaches educating patients on the health consequences of obesity.
Improved resilience following digital cognitive behavioral therapy for insomnia protects against insomnia and depression one year later

Abstract Background While the negative consequences of insomnia are well-documented, a strengths-based understanding of how sleep can increase health promotion is still emerging and much-needed. Correlational evidence has connected sleep and insomnia to resilience; however, this relationship has not yet been experimentally tested. This study examined resilience as a mediator of treatment outcomes in a randomized clinical trial with insomnia patients. Methods Participants were randomized to either digital cognitive behavioral therapy for insomnia (dCBT-I; n = 358) or sleep education control (n = 300), and assessed at pre-treatment, post-treatment, and 1-year follow-up. A structural equation modeling framework was utilized to test resilience as a mediator of insomnia and depression. Risk for insomnia and depression was also tested in the model, operationalized as a latent factor with sleep reactivity, stress, and rumination as indicators (aligned with the 3-P model). Sensitivity analyses tested the impact of change in resilience on the insomnia relapse and incident depression at 1-year follow-up. Results dCBT-I resulted in greater improvements in resilience compared to the sleep education control. Furthermore, improved resilience following dCBT-I lowered latent risk, which was further associated with reduced insomnia and depression at 1-year follow-up. Sensitivity analyses indicated that each point improvement in resilience following treatment reduced the odds of insomnia relapse and incident depression 1 year later by 76% and 65%, respectively. Conclusions Improved resilience is likely a contributing mechanism to treatment gains following insomnia therapy, which may then reduce longer-term risk for insomnia relapse and depression.
Association Between Childhood Body Size and Premenstrual Disorders in Young Adulthood

Key Points Question Are childhood body size and changes throughout adolescence associated with the risk of premenstrual disorders (PMDs) in young adulthood? Findings In a prospective cohort study of 6524 female participants in the US, higher childhood body mass index (BMI) was significantly associated with increased risk of PMDs and greater levels of premenstrual symptoms in young adulthood. Compared with individuals with normal BMI throughout adolescence, those with high BMI throughout adolescence reported significantly greater premenstrual symptoms in adulthood. Meaning These findings suggest that maintaining a normal body mass in childhood may be considered for lowering the burden of PMDs in adulthood.
Association between dosing and combination use of medications and outcomes in heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry

To assess the association between combination, dose and use of current guideline‐recommended target doses (TD) of renin–angiotensin system inhibitors (RASi), angiotensin receptor–neprilysin inhibitors (ARNi) and β‐blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction.
Selection on dispersal drives evolution of metabolic capacities for energy production in female wing‐polymorphic sand field crickets, Gryllus firmus

Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting for variation in dispersal and maximal metabolic rates. We used female wing‐polymorphic sand field crickets, Gryllus firmus, selected either for long wings (LW, flight‐capable) or short wings (SW, flightless) to test the hypothesis that selection on dispersal capability drives the evolution of metabolic capacities. While resting metabolic rates were similar, long‐winged crickets reached higher maximal metabolic rates than short‐winged crickets, resulting in improved running performance. We further provided insight into the mechanisms responsible for covariation between life history and metabolism by comparing mitochondrial content of tissues involved in powering locomotion and assessing the function of mitochondria isolated from long‐ and short‐winged crickets. Our results demonstrated that larger metabolic capacities in long‐winged crickets were underpinned by increases in mitochondrial content of dorsoventral flight muscle and enhanced bioenergetic capacities of mitochondria within the fat body, a tissue responsible for fuel storage and mobilization. Thus, selection on flight capability correlates with increases in maximal, but not resting metabolic rates, through modifications of tissues powering locomotion at the cellular and organelle levels. This allows organisms to meet high energetic demands of activity for life history. Dispersal capability should therefore explicitly be considered as a potential factor driving the evolution of metabolic capacities.
Efficacy of Brief Intervention for Alcohol Consumption during Pregnancy in Argentinean Women: A Randomized Controlled Trial

Abstract Introduction Although Brief Intervention (BI) has proven to reduce alcohol consumption during pregnancy in high income countries, there is no evidence from the Southern Cone of America. Thus, we conducted a study to assess BI efficacy among Argentinean pregnant women. Method and Materials We collected data on pregnant women receiving prenatal care at the public health system in Mar del Plata, Argentina. Women with less than 26 weeks of gestation (n = 486) were randomized to brief advice (BA) or BI. Three months later they were re-assessed; women with more than 26 weeks of gestation constituted a screening only control group (SC) (n = 154). Self-reported quantity and frequency of alcohol consumption, frequency of binge drinking, and related problems after three months were used as outcomes. We performed generalized estimating equations and clinical significance analyses. Also, we obtained newborn health indicators from the city’s health system database to use as objective outcomes. Women who did not participate in any of the three former conditions were randomly selected to constitute a non-screening control group (NSC) (n = 150). We compared objective outcomes among BI, BA, and NSC groups using the Wilcoxon rank test. Results In comparison with SC, BI and BA reduced alcohol consumption, without differences between the latter two. Newborns of women who received BI and BA had better health indicators compared with the NSC group. Conclusions performing either a BI or BA reduces alcohol consumption among Argentinean pregnant women and might lead to healthier newborns.
Regulation of Hepatic Gluconeogenesis by Nuclear Receptor Coactivator 6

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.
Unsupervised Category-Specific Partial Point Set Registration via Joint Shape Completion and Registration

We propose a self-supervised method for partial point set registration. Although recently proposed learning-based methods demonstrate impressive registration performance on full shape observations, these methods often suffer from performance degradation when dealing with partial shapes. To bridge the performance gap between partial and full point set registration, we propose to incorporate a shape completion network to benefit the registration process. To achieve this, we introduce a learnable latent code for each pair of shapes, which can be regarded as the geometric encoding of the target shape. By doing so, our model does not require an explicit feature embedding network to learn the feature encodings. More importantly, both our shape completion and point set registration networks take the shared latent codes as input, which are optimized simultaneously with the parameters of two decoder networks in the training process. Therefore, the point set registration process can benefit from the joint optimization process of latent codes, which are enforced to represent the information of full shapes instead of partial ones. In the inference stage, we fix the network parameters and optimize the latent codes to obtain the optimal shape completion and registration results. Our proposed method is purely unsupervised and does not require ground truth supervision. Experiments on the ModelNet40 dataset demonstrate the effectiveness of our model for partial point set registration.
Dynamization–Posterior Lumbar Interbody Fusion for Hemodialysis-Related Spondyloarthropathy: Evaluation of the Radiographic Outcomes and Reoperation Rate within 2 Years Postoperatively

Study Design Clinical case series. Purpose This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysis-related spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years. Overview of Literature HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes. Methods We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant. Results We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization–PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; p<0.01). The mean local lordosis was maintained throughout the postoperative course at 1- and 2-year follow-up (12.9°–12.8°, p=0.89 and 12.9°–11.8°, p=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease). Conclusions Dynamization–PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.
Hypothesis: Trans‐splicing Generates Evolutionary Novelty in the Photosynthetic Amoeba Paulinella

Plastid primary endosymbiosis has occurred twice, once in the Archaeplastida ancestor and once in the Paulinella (Rhizaria) lineage. Both events precipitated massive evolutionary changes, including the recruitment and activation of genes that are horizontally acquired (HGT) and the redeployment of existing genes and pathways in novel contexts. Here we address the latter aspect in Paulinella micropora KR01 (hereafter, KR01) that has independently evolved spliced leader (SL) trans‐splicing (SLTS) of nuclear–derived transcripts. We investigated the role of this process in gene regulation, novel gene origination, and endosymbiont integration. Our analysis shows that 20% of KR01 genes give rise to transcripts with at least one (but in some cases, multiple) sites of SL addition. This process, which often occurs at canonical cis‐splicing acceptor sites (internal introns), results in shorter transcripts that may produce 5′‐truncated proteins with novel functions. SL–truncated transcripts fall into four categories that may show: (i) altered protein localization, (ii) altered protein function, structure, or regulation, (iii) loss of valid alternative start codons, preventing translation, or (iv) multiple SL addition sites at the 5′‐terminus. The SL RNA genes required for SLTS are putatively absent in the heterotrophic sister lineage of photosynthetic Paulinella species. Moreover, a high proportion of transcripts derived from genes of endosymbiotic gene transfer (EGT) and HGT origin contain SL sequences. We hypothesize that truncation of transcripts by SL addition may facilitate the generation and expression of novel gene variants and that SLTS may have enhanced the activation and fixation of foreign genes in the host genome of the photosynthetic lineages, playing a key role in primary endosymbiont integration.
Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.