Miracle-dz/UniFAR-FTUs huggingface dataset:
Plagiocephaly after Neonatal Developmental Dysplasia of the Hip at School Age

Developmental dysplasia of the hip (DDH) may require early abduction treatment with infants sleeping on their back for the first few months of life. As sleeping on back is known to cause deformational plagiocephaly, we assessed school age children treated for dislocation or subluxation of the hip-joint in infancy. Plagiocephaly was analyzed by using cephalic index (CI) and oblique cranial length ratio (OCLR) as anthropometric measurements from 2D digital vertex view photographs. Six of the 58 (10.3%) DDH children and only one of the 62 (1.6%) control children had plagiocephaly (p = 0.041). Furthermore, cross bite was found in 14 (24.1%) of the DDH children and in 7 (10.3%) of the control children. Developmental dysplasia of the hip in infancy was associated with cranial asymmetries and malocclusions at school age. Preventive measures should be implemented.
American Urogynecologic Society Systematic Review: The Impact of Weight Loss Intervention on Lower Urinary Tract Symptoms and Urinary Incontinence in Overweight and Obese Women.

OBJECTIVE Obesity can contribute to urinary symptoms such as urgency, frequency, and incontinence. In addition to classic treatments, weight loss interventions offer a unique clinical opportunity to improve these symptoms. STUDY DESIGN The American Urogynecologic Society Systematic Review Group conducted a review of articles on the impact of surgical and behavioral weight loss (BWL) interventions on urinary symptoms in overweight and obese women. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS The review group identified 43 publications from 39 studies, including 10 reports that used data from 5 randomized trials. Overall, there is high-certainty evidence that BWL, such as diet and exercise, decreases the prevalence of stress urinary incontinence 15% to 18% and overall urinary incontinence (UI) by 12% to 17% at 1 to 2.9 years. The certainty of evidence on the long-term impact of these interventions was lower. The certainty of the evidence was moderate to low regarding the benefit of BWL on urgency UI and overactive bladder symptoms. No randomized trials evaluated the impact of surgical weight loss on urinary symptoms, and the certainty of evidence of other study types was very low. CONCLUSIONS There is high-certainty evidence that BWL results in modest improvements in stress and overall UI in overweight and obese women at 1 to 2.9 years after the intervention. Robust studies with low risk of bias are needed to assess whether these benefits are maintained over the long term and are associated with adverse events and to assess the impact of surgical weight loss interventions on urinary outcomes in overweight and obese women.
Patient and Clinician Perspectives on Quality-of-Care Topics for Users of Custom Ankle-Foot Orthoses

Supplemental digital content is available in the text. Objective As in all healthcare areas, there is a need to improve quality relevant to orthotic practice, but we lack information as to what aspects of healthcare quality are meaningful to measure. Thus, the objective was to identify issues that are important to the quality-of-care for people who use custom ankle-foot orthoses as identified by ankle-foot orthosis users, orthotists, and physical therapists. Design We conducted focus groups with custom ankle-foot orthosis users, orthotists, and physical therapists. A stenographer took verbatim notes and provided transcripts. Research staff members assessed the transcripts using thematic analysis. Results Participants included 5 ankle-foot orthosis users (1 focus group), 17 orthotists (2 focus groups), and 7 physical therapists (1 focus group). They discussed domains of quality-of-care relevant for people with ankle-foot orthoses. We identified 28 thematic codes addressing 10 broad themes of quality-of-care. Six of the broad themes (organizational characteristics, patient-clinician communication, care coordination, device fit and comfort, body function, activity, and participation) mapped to the National Quality Forum’s person- and family-centered care concepts. Environment of care, clinician competencies, and device characteristics and usage were important to orthotic practice but do not map to any National Quality Forum concept. Participants did not mention the National Quality Forum concept of shared decision-making. Conclusions The quality themes provide information as to what aspects of healthcare quality are meaningful to measure with respect to orthotic care, thus providing guidance on how to measure and improve ankle-foot orthosis service delivery.
Investigation of Piezoelectricity and Resistivity of Surface Modified Barium Titanate Nanocomposites

Polymer-ceramic nanocomposite piezoelectric and dielectric films are of interest because of their possible application to advanced embedded energy storage devices for printed wired electrical boards. The incompatibility of the two constituent materials; hydrophilic ceramic filler, and hydrophobic epoxy limit the filler concentration, and thus, their piezoelectric properties. This work aims to understand the role of surfactant concentration in establishing meaningful interfacial layers between the epoxy and ceramic filler particles by observing particle surface morphology, piezoelectric strain coefficients, and resistivity spectra. A comprehensive study of nanocomposites, comprising non-treated and surface treated barium titanate (BTO), embedded within an epoxy matrix, was performed. The surface treatments were performed with two types of coupling agents: Ethanol and 3-glycidyloxypropyltrimethoxysilan. The observations of particle agglomeration, piezoelectric strain coefficients, and resistivity were compared, where the most ideal properties were found for concentrations of 0.02 and 0.025. This work demonstrates that the interfacial core-shell processing layer concentration influences the macroscopic properties of nanocomposites, and the opportunities for tuning interfacial layers for desirable characteristics of specific applications.
Management of Liver Oligometastatic Esophageal Cancer: Overview and Critical Analysis of the Different Loco-Regional Treatments

Esophageal cancer (EC) is an aggressive disease that is associated with a poor prognosis. Since metastastic EC is usually considered suitable only for palliative therapy with an estimated 5-year overall survival (OS) less than 5%, the optimal management of patients with liver oligometastatic EC (LOEC) is still undefined. The aim of this review is to provide an overview of the different treatment options for LOEC. A literature search was conducted using PubMed, Embase, and Cochrane to identify articles evaluating different treatment strategies for LOEC. Among 828 records that were identified, 20 articles met the inclusion criteria. These studies included patients who have undergone any type of surgical procedure and/or loco-regional therapy. Liver resection resulted in the best survival for patients with low tumor burden (3 lesions): 5-year OS 30–50% versus 8–12% after only chemotherapy (CHT). The 5-year OS of loco-regional therapies was 23% with a local recurrence risk ranging 0–8% for small lesions (2 to 3 cm). An aggressive multidisciplinary approach for LOEC patients may improve survival. Surgery seems to be the treatment of choice for resectable LOEC. If unfeasible, loco-regional therapies may be considered. In order to better select these patients and offer a chance of cure, prospective trials and a definition of treatment protocols are needed.
Exploration of the Misfolding Mechanism of Transthyretin Monomer: Insights from Hybrid-Resolution Simulations and Markov State Model Analysis

Misfolding and aggregation of transthyretin (TTR) is widely known to be responsible for a progressive systemic disorder called amyloid transthyretin (ATTR) amyloidosis. Studies suggest that TTR aggregation is initiated by a rate-limiting dissociation of the homo-tetramer into its monomers, which can rapidly misfold and self-assemble into amyloid fibril. Thus, exploring conformational change involved in TTR monomer misfolding is of vital importance for understanding the pathogenesis of ATTR amyloidosis. In this work, microsecond timescale hybrid-resolution molecular dynamics (MD) simulations combined with Markov state model (MSM) analysis were performed to investigate the misfolding mechanism of the TTR monomer. The results indicate that a macrostate with partially unfolded conformations may serve as the misfolded state of the TTR monomer. This misfolded state was extremely stable with a very large equilibrium probability of about 85.28%. With secondary structure analysis, we found the DAGH sheet in this state to be significantly destroyed. The CBEF sheet was relatively stable and sheet structure was maintained. However, the F-strand in this sheet was likely to move away from E-strand and reform a new β-sheet with the H-strand. This observation is consistent with experimental finding that F and H strands in the outer edge drive the misfolding of TTR. Finally, transition pathways from a near native state to this misfolded macrostate showed that the conformational transition can occur either through a native-like β-sheet intermediates or through partially unfolded intermediates, while the later appears to be the main pathway. As a whole, we identified a potential misfolded state of the TTR monomer and elucidated the misfolding pathway for its conformational transition. This work can provide a valuable theoretical basis for understanding of TTR aggregation and the pathogenesis of ATTR amyloidosis at the atomic level.
How Can Systematic Reviews Teach Us More about the Implementation of the 3Rs and Animal Welfare?

Simple Summary The three Rs stand for Replacement, Reduction, and Refinement of animal studies and were published for the first time in 1959 by Russell and Burch. Replacement refers to avoiding the use of (non-human) animals in research. Reduction implies using fewer animals, for example, by better statistical methods and better literature studies, and Refinement means reducing the discomfort and improving the welfare of animals used in experiments. The three Rs have gained more interest and popularity since the 1970s, and have now become the crucial central element in the revised legislation in Europe, the EU Directive 2010/63EU, controlling the proper use of animals in experiments in the European member states. Animals are used in order to improve the health and welfare of other non-human animals, in veterinary medicine, and of humans, for toxicological purposes and in clinical medicine. Using animals in experiments has always been subject to ethical and societal debate. At Syrcle, we have introduced the methodology of systematic reviews for preclinical animal studies since 2012. This methodology comes from the clinical field and is a key element in evidence-based medicine, as systematic reviews summarise the scientific evidence as objectively as possible. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question. Introducing this methodology for the preclinical animal studies seems very logical, as animal studies in clinical medicine are performed for protecting humans from ineffective or unsafe treatments. Systematic reviews thus lead to summarising evidence from preclinical studies before entering clinical trials. In addition to protecting humans, systematic reviews can also be used to implement the three Rs. Examples of how systematic reviews contribute to implementing the three Rs are provided in the following article, thus demonstrating the value for protecting animals as well. Abstract This paper describes the introduction of the systematic review methodology in animal-based research and the added value of this methodology in relation to the 3Rs and beyond. The 3Rs refer to Replacement, Reduction, and Refinement of animal studies. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question. Examples are given on how SRs lead to the implementation of the 3Rs and better science. Additionally, a broader context is given regarding societal, political, and scientific developments. Various examples of systematic reviews are given to illustrate the current situation regarding reporting, quality, and translatability of animal-based research. Furthermore, initiatives that have emerged to move further towards more responsible and sustainable research is of benefit for both animals and humans.
P-MAPA and Interleukin-12 Reduce Cell Migration/Invasion and Attenuate the Toll-Like Receptor-Mediated Inflammatory Response in Ovarian Cancer SKOV-3 Cells: A Preliminary Study

Immunotherapies have emerged as promising complementary treatments for ovarian cancer (OC), but its effective and direct role on OC cells is unclear. This study examined the combinatory effects of the protein aggregate magnesium–ammonium phospholinoleate–palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) on cell migration/invasion, apoptosis, toll-like receptor (TLR)-mediated inflammation, and cytokine/chemokine profile in human OC cell line SKOV-3. P-MAPA and IL-12 showed cancer cell toxicity under low doses after 48 h. Although apoptosis/necrosis and the cell cycle were unchanged by the treatments, P-MAPA enhanced the sensitivity to paclitaxel (PTX) and P-MAPA associated with IL-12 significantly reduced the migratory potential and invasion capacity of SKOV-3 cells. P-MAPA therapy reduced TLR2 immunostaining and the myeloid differentiation factor 88 (MyD88), but not the TLR4 levels. Moreover, the combination of P-MAPA with IL-12 attenuated the levels of MyD88, interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB p65). The IL-12 levels were increased and P-MAPA stimulated the secretion of cytokines IL-3, IL-9, IL-10, and chemokines MDC/CCL22 and, regulated on activation, normal T cells expressed and secreted (RANTES)/CCL5. Conversely, combination therapy reduced the levels of IL-3, IL-9, IL-10, MDC/CCL22, and RANTES/CCL5. Collectively, P-MAPA and IL-12 reduce cell dynamics and effectively target the TLR-related downstream molecules, eliciting a protective effect against chemoresistance. P-MAPA also stimulates the secretion of anti-inflammatory molecules, possibly having an immune response in the OC microenvironment.
Multiple Sclerosis CD49d+CD154+ As Myelin-Specific Lymphocytes Induced During Remyelination

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) mediated by autoreactive lymphocytes. The role of autoreactive lymphocytes in the CNS demyelination is well described, whereas very little is known about their role in remyelination during MS remission. In this study, we identified a new subpopulation of myelin-specific CD49d+CD154+ lymphocytes presented in the peripheral blood of MS patients during remission, that proliferated in vitro in response to myelin peptides. These lymphocytes possessed the unique ability to migrate towards maturing oligodendrocyte precursor cells (OPCs) and synthetize proinflammatory chemokines/cytokines. The co-culture of maturing OPCs with myelin-specific CD49d+CD154+ lymphocytes was characterized by the increase in proinflammatory chemokine/cytokine secretion that was not only a result of their cumulative effect of what OPCs and CD49d+CD154+ lymphocytes produced alone. Moreover, maturing OPCs exposed to exogenous myelin peptides managed to induce CD40-CD154-dependent CD49d+CD154+ lymphocyte proliferation. We confirmed, in vivo, the presence of CD49d+CD154+ cells close to maturating OPCs and remyelinating plaque during disease remission in the MS mouse model (C57Bl/6 mice immunized with MOG35-55) by immunohistochemistry. Three weeks after an acute phase of experimental autoimmune encephalomyelitis, CD49d+/CD154+ cells were found to be co-localized with O4+ cells (oligodendrocyte progenitors) in the areas of remyelination identified by myelin basic protein (MBP) labelling. These data suggested that myelin-specific CD49d+CD154+ lymphocytes present in the brain can interfere with remyelination mediated by oligodendrocytes probably as a result of establishing proinflammatory environment.
Overexpression of PSAT1 Gene is a Favorable Prognostic Marker in Lower-Grade Gliomas and Predicts a Favorable Outcome in Patients with IDH1 Mutations and Chromosome 1p19q Codeletion

Patients with lower-grade gliomas (LGGs) have highly diverse clinical outcomes. Although histological features and molecular markers have been used to predict prognosis, the identification of new biomarkers for the accurate prediction of patient outcomes is still needed. The serine synthesis pathway (SSP) is important in cancer metabolism. There are three key regulators, including phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), and phosphoserine aminotransferase 1 (PSAT1), in SSP. However, their clinical importance in LGGs is still unknown. In this study, we used the bioinformatics tool in the Gene Expression Profiling Interactive Analysis (GEPIA) website to examine the prognostic significance of PHGDH, PSPH, and PSAT1 genes in LGGs. PSAT1 gene expression was then identified as a potential biomarker candidate for LGGs. Datasets from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were further used to explore the prognostic role of PSAT1 gene. Our results demonstrated that PSAT1 overexpression is a favorable prognostic marker of LGGs and significantly correlated with patient age ≤40, and a lower WHO histological grade, as well as mutations in IDH1, TP53 and ATRX, but not with chromosome 1p19q codeletions. More importantly, LGG patients with isocitrate dehydrogenase 1 (IDH1) mutations, chromosome 1p19q codeletions, and PSAT1 overexpression may have the best overall survival (five-year survival rate: 100%). Finally, we observed a coordinated biological reaction between IDH1 mutations and PSAT1 overexpression, and suggested overexpression of PSAT1 might enhance the function of mutant IDH1 to promote a favorable outcome in LGG patients. In conclusion, our study confirmed the importance of identifying the overexpression of PSAT1 as a favorable prognostic marker of LGGs, which may compensate for the limitation of IDH1 mutations and chromosome 1p19q codeletion in the prognostication of LGGs.
Prognostic and Predictive Value of PBRM1 in Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most frequent kidney solid tumor, the clear cell RCC (ccRCC) being the major histological subtype. The probability of recurrence and the clinical behavior of ccRCC will greatly depend on the different clinical and histopathological features, already incorporated to different scoring systems, and on the genomic landscape of the tumor. In this sense, ccRCC has for a long time been known to be associated to the biallelic inactivation of Von Hippel-Lindau (VHL) gene which causes aberrant hypoxia inducible factor (HIF) accumulation. Recently, next generation-sequencing technologies have provided the bases for an in-depth molecular characterization of ccRCC, identifying additional recurrently mutated genes, such as PBRM1 (≈40–50%), SETD2 (≈12%), or BAP1 (≈10%). PBRM1, the second most common mutated gene in ccRCC after VHL, is a component of the SWI/SNF chromatin remodeling complex. Different studies have investigated the biological consequences and the potential role of PBRM1 alterations in RCC prognosis and as a drug response modulator, although some results are contradictory. In the present article, we review the current evidence on PBRM1 as potential prognostic and predictive marker in both localized and metastatic RCC.
Effects of Backpacks on Ground Reaction Forces in Children of Different Ages When Walking, Running, and Jumping

Backpacks for transporting school loads are heavily utilized by children, and their mechanical advantages have been allowing children to transport heavy loads. These heavy loads may increase ground reaction forces (GRFs), which can have a negative effect on joints and bone health. The aim of this study was to investigate the effect of backpacks on the GRFs generated by children during walking, running, and jumping. Twenty-one children from the fifth (G-5, n = 9) and ninth (G-9, n = 12) grades walked, ran, and jumped over a force plate. When walking, the G-5 had GRF increments in the first (17.3%; p < 0.001) and second (15.4%; p < 0.001) peak magnitude, and in the total integral of the vertical force (20%; p < 0.001), compared to the control condition (i.e., no backpack), and the G-9 had increments of 10.4%, 9%, and 9% (p < 0.001), respectively. The G-9 did not prolong their total stance time (p > 0.05), unlike the G-5 (p = 0.001). When running, total stance time increased 15% (p < 0.001) and 8.5% (p < 0.001) proportionally to the relative load carried, in the G-5 and G-9, respectively. Peak GRF did not increase in any group when running or landing from a jump over an obstacle. It was found that GRF was affected by the backpack load when walking and running. However, when landing from a jump with the backpack, schoolchildren smoothed the landing by prolonging the reception time and thus avoiding GRF peak magnitudes.
The Composition of Surgical Wound Fluids from Breast Cancer Patients is Affected by Intraoperative Radiotherapy Treatment and Depends on the Molecular Subtype of Breast Cancer

Invasive oncological procedures affect the remaining tumor cells by increasing their survival, proliferation, and migration through the induction of wound healing response. The phenomena of local relapse after breast-conserving surgery (BCS) has resulted in a series of research and clinical trials with the aim of assessing whether localized intraoperative radiotherapy (IORT), may be beneficial in inhibiting local recurrences. Therefore, it is essential to assess the impact of intraoperative radiotherapy in modulating the immunological response and wound healing process. Thus, we decided to perform a quantitative analysis of the composition of surgical wound fluids (SWF) in two groups of breast cancer (BC) patients: those treated with BCS followed by IORT, and those who underwent BCS alone. We found that several cytokines, which are believed to have anti-tumor properties, were highly expressed in the luminal A breast cancer subtype in the IORT treatment group. Interestingly, we also found significant differences between IORT patients with tumors of different molecular subtypes. Based on these findings, we hypothesized that IORT treatment might be beneficial in changing the tumor bed microenvironment, making it less favorable for tumor recurrence due to decreased concentration of tumor-facilitating cytokines, especially in the luminal A subtype of BC.