Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperexcitability of Cortical Oscillations in Patients with Somatoform Pain Disorder: A Resting-State EEG Study

Patients with somatoform pain disorder (SPD) suffer from somatic pain that cannot be fully explained by specific somatic pathology. While the pain experience requires the integration of sensory and contextual processes, the cortical oscillations have been suggested to play a crucial role in pain processing and integration. The present study is aimed at identifying the abnormalities of spontaneous cortical oscillations among patients with SPD, thus for a better understanding of the ongoing brain states in these patients. Spontaneous electroencephalography data during a resting state with eyes open were recorded from SPD patients and healthy controls, and their cortical oscillations as well as functional connectivity were compared using both electrode-level and source-level analysis. Compared with healthy controls, SPD patients exhibited greater resting-state alpha oscillations (8.5-12.5 Hz) at the parietal region, as reflected by both electrode-level spectral power density and exact low-resolution brain electromagnetic tomography (eLORETA) cortical current density. A significant correlation between parietal alpha oscillation and somatization severity was observed in SPD patients, after accounting for the influence of anxiety and depression. Functional connectivity analysis further revealed a greater frontoparietal connectivity of the resting-state alpha oscillations in SPD patients, which was indexed by the coherence between pairs of electrodes and the linear connectivity between pairs of eLORETA cortical sources. The enhanced resting-state alpha oscillation in SPD patients could be relevant with attenuated sensory information gating and excessive integration of pain-related information, while the enhanced frontoparietal connectivity could be reflecting their sustained attention to bodily sensations and hypervigilance to somatic sensations.
Nerve-sparing versus non-nerve-sparing radical hysterectomy: surgical and long-term oncological outcomes

Objectives There are controversies regarding the long-term oncological safety of preservation of pelvic innervation during radical hysterectomy (RH). This study aimed to analyze the feasibility and safety of nerve-sparing radical hysterectomy (NSRH) for cervical cancer compared with non-NSRH following 17 years of experience in a tertiary cancer referral center. Materials and Methods Between May 1999 and June 2016, all patients who underwent RH for cervical cancer were followed-up prospectively. Comparison analyses regarding surgical outcomes, complications, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were performed between patients treated with NSRH and non-NSRH. Results A total of 188 patients were included (113 non-NSRH and 75 NSRH). The median follow-up was 112 months. Estimated blood loss and hospital stay were all significantly lower in the NSRH group. Overall intraoperative complication rate (p = 0.02) and need for transfusion (p = 0.016) were lower in the NSRH group. There were no differences in the median operation time, OS, DFS, CSS, or recurrence rates between the NSRH and non-NSRH group. Conclusions Our study provides a wide perspective on the developments of nerve-sparing procedures for the management of women with early-stage cervical cancer. Our results suggest that NSRH is a feasible and safe procedure, with reduced morbidity outcomes.
Clinical Aspects of HyFoSy as Tubal Patency Test in Subfertility Workup

Background Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG) was the first step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and less painful alternative. Objectives and Rationale The aim of this narrative review is to provide an overview of the currently available HyFoSy literature and related clinical aspects. Search Methods A literature search was conducted using PubMed and Embase from the introduction of HyFoSy to March 2019. Unfortunately, a meta-analysis was not possible due to a too small number of studies, being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes Nine small studies concluded that the accuracy and effectiveness as a test for tubal patency of 2D- and 3D-HyFoSy are comparable or even better than HSG or HyCoSy. With or without using Doppler techniques, 3D-HyFoSy does not seem to offer benefits above real-time 2D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less painful procedure compared to HSG, without a need for the use of analgesics. There are suggestions about an increased pregnancy rate in the first three cycles after the procedure but in no studies pregnancy outcome after HyFoSy was compared with other or no intervention. Wider Implications HyFoSy is a promising and safe alternative for HSG with regard to accuracy and effectiveness. HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for analgesics. However more research is needed to make clear statements regarding a therapeutic effect of HyFoSy.
Mechano-thermo-chromic device with supersaturated salt hydrate crystal phase change

We demonstrated a reversible transparency-changing smart glass that can be operated by mechanical impacts and heat. Active control of transparency/color is the key to many functional optoelectric devices. Applying an electric field to an electrochromic or liquid crystal material is the typical approach for optical property control. In contrast to the conventional electrochromic method, we developed a new concept of smart glass using new driving mechanisms (based on mechanical stimulus and thermal energy) to control optical properties. This mechano-thermo-chromic smart glass device with an integrated transparent microheater uses a sodium acetate solution, which shows a unique marked optical property change under mechanical impact (mechanochromic) and heat (thermochromic). Such mechano-thermo-chromic devices may provide a useful approach in future smart window applications that could be operated by external environment conditions.
Effect of Harmine on Nicotine-Induced Kidney Dysfunction in Male Mice

Background: The nicotine content of cigarettes plays a key role in the pathogenesis of kidney disease. Harmine is a harmal-derived alkaloid with antioxidant properties. This study was designed to evaluate the effects of harmine against nicotine-induced damage to the kidneys of mice. Methods: In this study, 64 male mice were randomly assigned to eight groups: saline and nicotine-treated groups (2.5 mg/kg), harmine groups (5, 10, and 15 mg/kg), and nicotine (2.5 mg/kg) + harmine-treated groups (5, 10, and 15 mg/kg). Treatments were administered intraperitoneally daily for 28 days. The weights of the mice and their kidneys, kidney index, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Results: Nicotine administration significantly improved kidney malondialdehyde (MDA) level, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the saline group (P < 0.05). The harmine and harmine + nicotine treatments at all doses significantly reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels and increased the glomeruli number and tissue FRAP level compared to the nicotine group (P < 0.05). Conclusions: It seems that harmine administration improved kidney injury induced by nicotine in mice.
An Interregional, Transdisciplinary and Good Practice-Based Approach for Frailty: the Mind&Gait Project

Social facilities such residential structures and day-centres increasingly seek integrated, structured, adapted, creative, dynamic and economic strategies to prevent frailty. The arising need of an aged and frail population requires innovative interventions and products to prevent cognitive and physical decline. The interregional MIND&GAIT project aims to promote independent living in frail older adults by improving cognition and gait ability by using assistive products. This transdisciplinary strategy within a 24-months period expects as project’ deliverables: i) a structured and good practice-based combined intervention (CI) consisting of a cognitive stimulation programme and a physical exercise programme; ii) an auto-blocking mechanism for rolling walkers with biofeedback acquisition (ABMRW); iii) a randomized clinical trial to assess CI′ effectiveness; and iv) a web-platform to be used as a repository that will support and disseminate the intervention materials, covering the action-line of translational research. Positive benefits are expected in prevention and maintenance of frail older adults’ capacities. Preliminary results showed positive effects on the improvement of cognitive and physical functions, functionality and depressive symptomatology. The interregional geographical coverage induced by MIND&GAIT underlines the potential replicability of the project extension to the community in the Centro and Alentejo regions of Portugal. MIND&GAIT network supports actions and provides learning opportunities and emergence of locally-embedded support systems towards social innovation for older adults.
Post-LSCS uterocutaneous fistula-utility of magnetic resonance imaging in its diagnosis

The present report describes one of the rarest complications of cesarean section, uterocutaneous fistula, diagnosed on magnetic resonance imaging (MRI). A 37-year-old female with history of lower segment caesarean section (LSCS) four years previously presented with a chief symptom of discharge from the right end of a Pfannenstiel incision and on further evaluation was found to have uterocutaneous fistula arising from the LSCS scar to the right end of the abdominal incision. Uterocutaneous fistula is a rare delayed complication of LSCS and MRI plays a definitive role in the accurate diagnosis and delineation of the tract. The present case highlights that although rare, uterocutaneous fistulae must be kept in mind in patients presenting with discharge from the abdominal incision site and MRI evaluation should be performed in such cases for appropriate delineation of the tract.
A Study Protocol for Development and Validation of a Clinical Prediction Model for Frailty (ModulEn): a new European Commitment to Tackling Frailty

There is a growing need to implement and evaluate the technological solutions that allow the early detection of age-related frailty and enable assessment of the predictive values of frailty components. The broad use of these solutions may ensure an efficient and sustainable response of health and social care systems to the challenges related to demographic aging. In this paper, we present the protocol of the ModulEn study that aims to develop and validate a predictive model for frailty. For this purpose, the sample composed by older adults aged 65–80 years and recruited from the community will be invited to use an electronic device ACM Kronowise® 2.0. This device allows proactive and continuous monitoring of circadian health, physical activity, and sleep and eating habits. It will be used during a period of seven to ten days. The participants will also be given the questionnaires evaluating the variables of interest, including frailty level, as well as their experience and satisfaction with the device use. Data provided from these two sources will be combined and the relevant associations will be identified. In our view, the implications of this study’ findings for clinical practice include the possibility to develop and validate tools for timely prevention of frailty progress. In the long term, the ModulEn may contribute to the critical reduction of frailty burden in Europe.
Innovative Approaches to Active and Healthy Ageing: Campania Experience to Improve the Adoption of Innovative Good Practices

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level.
Association of CYP1A1 M2 (A2455G) Polymorphism with Susceptibility to Breast Cancer in Mazandaran Province, Northern Iran: A Case–control Study

Background: Breast cancer is one of the most frequent women malignancies in the world. The cytochrome P450 1A1 (CYP1A1) is a key enzyme in xenobiotics metabolism. Moreover, CYP1A1 plays a critical role in the etiology of breast cancer by involving in 2-hydroxylation of estrogen. Therefore, single-nucleotide polymorphisms (SNPs) of its coding gene have been verified to be important in cancer susceptibility. The aim of the study was to evaluate the association of CYP1A1 M2 (A2455G) includes rs1048943 of this SNP polymorphism with the risk of breast cancer in Mazandaran province. Methods: Ninety-six breast cancer patients with known clinicopathological characters and 110 healthy women as control were genotyped for CYP1A1 M2 polymorphisms by the restriction fragment length polymorphism technique. Results: The analysis of CYP1A1 gene (polymorphism M2) showed that the frequency of homozygous wild genotypes (AA), heterozygous (AG), and mutant genotype (GG) in the patient group, respectively, 78%, 22%, and 0%, and also the frequency of genotypes AA, AG, and GG in healthy included 82%, 16%, and 2%, respectively. Statistical analysis by Logistic regression model at P < 0.05 showed no significant correlation between polymorphisms in CYP1A1M2 and breast cancer risk (odds ratio = 0.84, confidence interval = 0.33–2.17). Conclusions: The results indicated that the M2 allelic genotypes were significantly associated neither with breast cancer risk nor with clinicopathological characteristics in Mazandaran province.
The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment

Background: Immunotherapies targeting immune checkpoint proteins CTLA-4, PD-1, and PD-L1 have saved lives, but these therapies have only been effective in some patients. Patients positive for expression of immune checkpoint proteins in the tumor microenvironment show better response to immune checkpoint inhibitors. Consequently, knowledge of which genes are consistently expressed in lymphocytes within the tumor microenvironment can convey potentially effective and complementary new immunotherapy targets. Results: We identified 54 genes that have higher co-expression with the pan T-cell marker CD3E than CTLA4 or PDCD1. In a dataset of 26 patients who received anti-PD-1 therapy, we observed that co-expression between CD3E and PDCD1 was higher among responders than non-responders, supporting our correlation-based approach. Conclusions: The genes highlighted in these analyses, which include CD6, TIGIT, CD96, and SLAMF6, warrant further investigation of their therapeutic potential. Methods: We analyzed and ranked genes that were co-expressed with the pan T-cell marker CD3E in 9,601 human tumors, spanning 31 cancer types. To further identify targets that may be complementary to existing PD-1 therapy, we examined and ranked genes with high CD3E co-expression and relatively low PDCD1 co-expression.
Ability of people with post-stroke hemiplegia to self-administer FES-assisted hand therapy video games at home: An exploratory case series

Introduction This article describes the development and initial clinical testing of an innovative home-based treatment for upper extremity hemiplegia that integrates contralaterally controlled functional electrical stimulation with hand therapy video games. Methods We explored the ability of seven participants with moderate-to-severe hand impairment to self-administer 12 weeks of contralaterally controlled functional electrical stimulation video game therapy at home for 10 h/week and in-lab with a therapist for four h/week. Clinical suitability was assessed by device usage logs, qualitative surveys, and clinical motor and cognitive outcomes. Results Three participants completed the study with > 95% compliance and four did not. Factors linked to incompletion included development of trigger finger in the non-paretic hand, acceptance of a new full-time job, residence relocation, and persistence of drowsiness from anti-spasticity medication. Those who completed the treatment perceived qualitative benefits and experienced gains in motor and cognitive outcomes. Conclusion Individuals with moderate-to-severe chronic post-stroke upper extremity hemiplegia can self-administer contralaterally controlled functional electrical stimulation video game therapy for up to 90 min/day at home. We also identified social and physiological factors that may preclude its use for daily home treatment. Further studies are warranted and are in progress to estimate treatment effect and optimal dose of this intervention.
Deep Mining of Complex Antibody Phage Pools Generated by Cell Panning Enables Discovery of Rare Antibodies Binding New Targets and Epitopes

Phage display technology is a common approach for discovery of therapeutic antibodies. Drug candidates are typically isolated in two steps: First, a pool of antibodies is enriched through consecutive rounds of selection on a target antigen, and then individual clones are characterized in a screening procedure. When whole cells are used as targets, as in phenotypic discovery, the output phage pool typically contains thousands of antibodies, binding, in theory, hundreds of different cell surface receptors. Clonal expansion throughout the phage display enrichment process is affected by multiple factors resulting in extremely complex output phage pools where a few antibodies are highly abundant and the majority is very rare. This is a huge challenge in the screening where only a fraction of the antibodies can be tested using a conventional binding analysis, identifying mainly the most abundant clones typically binding only one or a few targets. As the expected number of antibodies and specificities in the pool is much higher, complementing methods, to reach deeper into the pool, are required, called deep mining methods. In this study, four deep mining methods were evaluated: 1) isolation of rare sub-pools of specific antibodies through selection on recombinant proteins predicted to be expressed on the target cells, 2) isolation of a sub-pool enriched for antibodies of unknown specificities through depletion of the primary phage pool on recombinant proteins corresponding to receptors known to generate many binders, 3) isolation of a sub-pool enriched for antibodies through selection on cells blocked with antibodies dominating the primary phage pool, and 4) next-generation sequencing-based analysis of isolated antibody pools followed by antibody gene synthesis and production of rare but enriched clones. We demonstrate that antibodies binding new targets and epitopes, not discovered through screening alone, can be discovered using described deep mining methods. Overall, we demonstrate the complexity of phage pools generated through selection on cells and show that a combination of conventional screening and deep mining methods are needed to fully utilize such pools. Deep mining will be important in future phenotypic antibody drug discovery efforts to increase the diversity of identified antibodies and targets.
Microglia Express Insulin-Like Growth Factor-1 in the Hippocampus of Aged APPswe/PS1ΔE9 Transgenic Mice

Insulin-like growth factor-1 (IGF-1) is a pleiotropic molecule with neurotrophic and immunomodulatory functions. Knowing the capacity of chronically activated microglia to produce IGF-1 may therefore show essential to promote beneficial microglial functions in Alzheimer’s disease (AD). Here, we investigated the expression of IGF-1 mRNA and IGF-1 along with the expression of tumor necrosis factor (TNF) mRNA, and the amyloid-β (Aβ) plaque load in the hippocampus of 3- to 24-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (WT) mice. As IGF-1, in particular, is implicated in neurogenesis we also monitored the proliferation of cells in the subgranular zone (sgz) of the dentate gyrus. We found that the Aβ plaque load reached its maximum in aged 21- and 24-month-old APPswe/PS1ΔE9 Tg mice, and that microglial reactivity and hippocampal IGF-1 and TNF mRNA levels were significantly elevated in aged APPswe/PS1ΔE9 Tg mice. The sgz cell proliferation decreased with age, regardless of genotype and increased IGF-1/TNF mRNA levels. Interestingly, IGF-1 mRNA was expressed in subsets of sgz cells, likely neuroblasts, and neurons in both genotypes, regardless of age, as well as in glial-like cells. By double in situ hybridization these were shown to be IGF1 mRNA+ CD11b mRNA+ cells, i.e., IGF-1 mRNA-expressing microglia. Quantification showed a 2-fold increase in the number of microglia and IGF-1 mRNA-expressing microglia in the molecular layer of the dentate gyrus in aged APPswe/PS1ΔE9 Tg mice. Double-immunofluorescence showed that IGF-1 was expressed in a subset of Aβ plaque-associated CD11b+ microglia and in several subsets of neurons. Exposure of primary murine microglia and BV2 cells to Aβ42 did not affect IGF-1 mRNA expression. IGF-1 mRNA levels remained constant in WT mice with aging, unlike TNF mRNA levels which increased with aging. In conclusion, our results suggest that the increased IGF-1 mRNA levels can be ascribed to a larger number of IGF-1 mRNA-expressing microglia in the aged APPswe/PS1ΔE9 Tg mice. The finding that subsets of microglia retain the capacity to express IGF-1 mRNA and IGF-1 in the aged APPswe/PS1ΔE9 Tg mice is encouraging, considering the beneficial therapeutic potential of modulating microglial production of IGF-1 in AD.