Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery Pulmonary Segmentectomy

Background Uniportal video-assisted thoracoscopic surgery (VATS) has proven safe and effective for pulmonary wedge resection and lobectomy. The objective of this study was to evaluate the safety and feasibility of uniportal VATS segmentectomy by comparing its outcomes with those of the multiportal approach at a single center. Methods The records of 84 patients who underwent VATS segmentectomy from August 2010 to August 2018, including 33 in the uniportal group and 51 in the multiportal group, were retrospectively reviewed and analyzed. Results Anesthesia and operative times were similar in the uniportal and multiportal groups (215 minutes vs. 220 minutes, respectively; p=0.276 and 180 minutes vs. 198 minutes, respectively; p=0.396). Blood loss was significantly lower in the uniportal group (50 mL vs. 100 mL, p=0.013) and chest tube duration and hospital stay were significantly shorter in the uniportal group (2 days vs. 3 days, p=0.003 and 4 days [range, 1–14 days] vs. 4 days [range, 1–62 days], p=0.011). The number of dissected lymph nodes tended to be lower in the uniportal group (5 vs. 8, p=0.056). Conclusion Our preliminary experience indicates that uniportal VATS segmentectomy is safe and feasible in well-selected patients. A randomized, prospective study with a large group of patients and long-term follow-up is necessary to confirm these results.
Different isolation approaches lead to diverse glycosylated extracellular vesicle populations

ABSTRACT Extracellular vesicles (EVs) are a heterogeneous group of small secreted particles involved in intercellular communication and mediating a broad spectrum of biological functions. EVs cargo is composed of a large repertoire of molecules, including glycoconjugates. Herein, we report the first study on the impact of the isolation strategy on the EV populations’ glycosylation profile. The use of different state-of-the-art protocols, namely differential ultracentrifugation (UC), total exosome isolation (TEI), OptiPrepTM density gradient (ODG) and size exclusion chromatography (SEC) resulted in EV populations displaying different sets of glycoconjugates. The EV populations obtained by UC, ODG and SEC methods displayed similar protein and glycan profiles, whereas TEI methodology isolated the most distinct EV population. In addition, ODG and SEC isolation protocols provided an enhanced EV glycoproteins detection. Remarkably, proteins displaying the tumour-associated glycan sialyl-Tn (STn) were identified as packaged cargo into EVs independently of the isolation methodology. STn carrying EV samples isolated by UC, ODG and SEC presented a considerable set of cancer-related proteins that were not detected in EVs isolated by TEI. Our work demonstrates the impact of using different isolation methodologies in the populations of EVs that are obtained, with consequences in the glycosylation profile of the isolated population. Furthermore, our results highlight the importance of selecting adequate EV isolation protocols and cell culture conditions to determine the structural and functional complexity of the EV glycoconjugates.
Is Co-production Just a Pipe Dream for Applied Health Research Commissioning? An Exploratory Literature Review

Background and Rationale: Internationally, the idea of “co-production' has become more popular in health research because of the promise of partnership between researchers and patients to create research that focuses on patients' needs. Patient and public involvement (PPI) at an early stage in deciding what research should be funded, can improve the quality and impact of research. However, professional power over the process places limits on the public practising their participatory rights for involvement in commissioning research that affects them and can leave members of the public feeling unheard or excluded, particularly within the context of early phase applied health research. Aim: This article explores whether and how the public can be involved in the co-production of research commissioning early on in the process, with a focus on the power relations that pervade basic and early phase translational applied health research. Methods: An exploratory literature review of international peer-reviewed and gray health research literature using structured searches of electronic databases and key search terms. Results: There is very little literature that critically evaluates how PPI is embedded into the early phases of the commissioning process. The field of basic or early translational applied research appear to be particularly challenging. Four themes which emerged from the review are: reasons for PPI in research commissioning; benefits of PPI at strategic levels of research commissioning; contributions of patients and members of the public; improving PPI in research commissioning. Conclusion: Although the public are being consulted at some stages of the research commissioning process, it is evident that the process of determining research priorities and agendas is far from being widely co-produced. Moving PPI from a consultative paternalistic model to a collaborative partnership model should be a priority for commissioners. Significant changes to communication, practices, systems, structures, or cultures that exclude patients and the public from contributing in meaningful ways, are needed to fulfill the potential of co-produced models of research commissioning.
Central Venous Access Devices (CVAD) in Pediatric Oncology Patients—A Single-Center Retrospective Study Over More Than 9 Years

Background: Central venous access devices (CVAD) provide important benefits in the management of oncological pediatric patients. However, these catheters are responsible for severe complications. Methods: In this context, we aimed to analyze all patients receiving a CVAD in the Department of Pediatric Hematology and Oncology of the University hospital of Mainz over a period of 9 years, focused on CVAD related complications. Data on demographics, as well as intraoperative and postoperative complications were extracted. Results: A total of 296 patients with a mean age 93.2 ± 62.4 months were analyzed. The majority suffered from leukemia (n = 91, 30.7%), lymphomas (n = 50, 16.9%), and brain tumors (n = 48, 16.2%). In 63 (21.3) patients, complications were observed. No death caused by complications of CVADs was found in our series. Catheter-related blood stream infections (BSI) (7.4%) were most prevalent, followed by dislodgements (5.4%), occlusions (2.7%), thrombosis (2.4%), and catheter leakage (2.4%). Insertion site infections were observed in three patients (1.0%). Fifty-nine percent of all patients with catheter-related BSI suffered from Leukemia. In patients with Catheter-related BSIs we detected the condition leukemia as the underlying disease as a risk factor compared to solid tumors as the underlying disease. Overall, totally implanted devices (ports) have a lower complication rate than tunneled catheter. Conclusion: Implantation of CVADs seems to be safe and reliable in this large pediatric patient cohort. Even if complications occur in the long-term management of CVADs, they can be treated successfully and long-term catheter survival rates are excellent.
Structural Evolution of α-Fe2O3(0001) Surfaces Under Reduction Conditions Monitored by Infrared Spectroscopy

The precise determination of the surface structure of iron oxides (hematite and magnetite) is a vital prerequisite to understand their unique chemical and physical properties under different conditions. Here, the atomic structure evolution of the hematite (0001) surface under reducing conditions was tracked by polarization-resolved infrared reflection absorption spectroscopy (IRRAS) using carbon monoxide (CO) as a probe molecule. The frequency and intensity of the CO stretch vibration is extremely sensitive to the valence state and electronic environments of surface iron cations. Our comprehensive IRRAS results provide direct evidence that the monocrystalline, stoichiometric α-Fe2O3(0001) surface is single Fe-terminated. The initial reduction induced by annealing at elevated temperatures produces surface oxygen vacancies, where the excess electrons are localized at adjacent subsurface iron ions (5-fold coordinated). A massive surface restructuring occurs upon further reduction by exposing to atomic hydrogen followed by Ar+-sputtering and annealing under oxygen poor conditions. The restructured surface is identified as a Fe3O4(111)/Fe1−xO(111)-biphase exposing both, Fe3+ and Fe2+ surface species. Here the well-defined surface domains of Fe3O4(111) exhibit a Feoct2-termination, while the reduced Fe1−xO(111) is Fe2+(oct)-terminated. These findings are supported by reference IRRAS data acquired for CO adsorption on magnetite (111) and (001) monocrystalline surfaces.
Immunopathogenesis of Juvenile Systemic Sclerosis

Juvenile-onset systemic sclerosis (jSSc) is a rare and severe autoimmune disease with associated life-threatening organ inflammation and evidence of fibrosis. The organ manifestations of jSSc resemble adult SSc, but with better outcomes and survival. The etiology of jSSc appears to reflect adult-onset SSc, with similar inflammatory mediators and autoantibodies, but with a significant population of children with uncharacterized anti-nuclear antibodies. The genetics of patients with jSSc differ from women with SSc, resembling instead the genes of adult males with SSc, with additional HLA genes uniquely associated with childhood-onset disease. Current treatments are aimed at inhibiting the inflammatory aspect of disease, but important mechanisms of fibrosis regulated by dermal white adipose tissue dendritic cells may provide an avenue for targeting and potentially reversing the fibrotic stage.
Human Skin-Derived Mast Cells Spontaneously Secrete Several Angiogenesis-Related Factors

Mast cells are classically recognized as cells that cause IgE-mediated allergic reactions. However, their ability to store and secrete vascular endothelial growth factor (VEGF) suggests a role in vascular development and tumorigenesis. The current study sought to determine if other angiogenesis-related factors, in addition to VEGF, were also secreted by human tissue-derived mast cells. Using proteome array analysis and ELISA, we found that human skin-derived mast cells spontaneously secrete CXCL16, DPPIV, Endothelin-1, GM-CSF, IL-8, MCP-1, Pentraxin 3, Serpin E1, Serpin F1, TIMP-1, Thrombospondin-1, and uPA. We identified three groups based on their dependency for stem cell factor (SCF), which is required for mast cell survival: Endothelin-1, GM-CSF, IL-8, MCP-1, and VEGF (dependent); Pentraxin 3, Serpin E1, Serpin F1, TIMP-1, and Thrombospondin-1 (partly dependent); and CXCL16, DPPIV, and uPA (independent). Crosslinking of FcεRI with multivalent antigen enhanced the secretion of GM-CSF, Serpin E1, IL-8, and VEGF, and induced Amphiregulin and MMP-8 expression. Interestingly, FcεRI signals inhibited the spontaneous secretion of CXCL16, Endothelin-1, Serpin F1, Thrombospondin-1, MCP-1 and Pentraxin-3. Furthermore, IL-6, which we previously showed could induce VEGF, significantly enhanced MCP-1 secretion. Overall, this study identified several angiogenesis-related proteins that, in addition to VEGF, are spontaneously secreted at high concentrations from human skin-derived mast cells. These findings provide further evidence supporting an intrinsic role for mast cells in blood vessel formation.
A Six Week Therapeutic Ballet Intervention Improved Gait and Inhibitory Control in Children With Cerebral Palsy—A Pilot Study

Children with cerebral palsy (CP) have motor impairments that make it challenging for them to participate in standard physical activity (PA) interventions. There is a need to evaluate adapted PA interventions for this population. Dance can promote coordination, posture, muscle strength, motor learning, and executive functioning. This pilot study evaluated the feasibility and the effects of a new therapeutic ballet intervention specifically designed for children with CP. Methods: Eight children with CP (9–14 y/o; 75% female) participated in a 6-week therapeutic ballet intervention. Outcomes were measured in multiple domains, including body composition (DXA), muscle strength (hand-grip dynamometer), habitual physical activity, gait and selective motor control functions, and executive functioning. Follow-up assessments of habitual physical activity, gait, and executive functioning were completed 4 to 5 weeks post-intervention. Results: Five of the eight participants were overfat or obese based on DXA percentage of body fat. All participants were below the 50th percentile for their age and gender for bone density. Four participants showed a trend to improve hand-grip strength in one hand only, while one improved in both hands. There were significant improvements in gait across time points (pre, post, and follow-up), specifically in time of ambulation (Xpre = 4.36, Xpost = 4.22, Xfollow−up = 3.72, d = 0.056, p = 0.02), and in step length (cm) on the right: Xpre = 48.29, Xpost = 50.77, Xfollow−up = 52.11, d = 0.22, p = 0.027, and left stride: Xpre = 96.29, Xpost = 102.20, Xfollow−up = 104.20, d = 0.30, p = 0.027, indicating gait changes in bilateral lower extremities. There was improvement in inhibitory control (d = 0.78; 95% Confidence Limit = ±0.71, p < 0.05) with large individual responses primarily among those above the mean at baseline. Conclusions: Therapeutic ballet may prove to be a useful intervention to promote physiological and cognitive functions in children with CP. Results demonstrated feasibility of the physical, physiological, and cognitive assessments and suggested improvements in participants' gait and inhibitory control with large individual responses. Modifications to personalize the intervention may be needed to optimize positive outcomes. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT03681171
Middle Ear Administration of a Particulate Chitosan Gel in an in vivo Model of Cisplatin Ototoxicity

Background Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss. Aim This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity. Materials and Methods Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system. Results Both chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination. Conclusion Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.
Association Between p.R4810K Variant and Long-Term Clinical Outcome in Patients With Moyamoya Disease

Objective: To estimate the association between p. R4810K variant and clinical outcomes of patients with moyamoya disease (MMD). Methods: The p.R4810K genetic variant was genotyped among 498 Chinese patients with MMD conducted from June 1, 2012, to June 31, 2017. Data was obtained by retrospective chart review, follow-up information and outcome were obtained through clinical visits and telephone. Results: Among 498 patients, 361 (72.5%) were wild-type patients (G/G), 133 (26.7%) heterozygous patients (G/A), and 4 (0.8%) homozygotes (A/A). Compared with GG group, the patients in the G/A+A/A group were younger at diagnosis and had more familial cases, more transient ischemic attack cases, more posterior cerebral artery involved hemispheres, less unilateral lesions. After the median 53 months follow-up, strokes occurred in 9 patients in the G/A+A/A group and in 52 in the G/G group. Multivariate Cox regression analysis showed that the history of hypertension (HR, 2.294; 95% CI, 1.251–4.206; p = 0.007), the presence of TIA (HR, 0.319; 95% CI, 0.120–0.846; p = 0.022), and the Suzuki stage (HR, 1.510; 95% CI, 1.129–2.018; p = 0.005) were associated with recurrent stroke. The p.R4810K (HR, 0.601; 95% CI, 0.292–1.239; p = 0.168) was not associated with recurrent stroke. Multivariate logistic regression analysis showed that recurrent stroke (OR, 5.997; 95% CI, 2.583–13.924; p = 0.000) was the only factor associated with unfavorable neurological status. And the p.R4810K (OR, 0.885; 95% CI, 0.482–1.627; p = 0.695) was not associated with neurological status. Conclusions: Compared to the patients in G/G group, patients in G/A+A/A group exhibited different clinical features, and had a lower rate of recurrent stroke and better clinical outcome after early medical and surgical interventions. Multivariate COX and logistic regression analysis showed that p.R4810Kvariant was not related to either recurrent stroke or neurological status. The p.R4810Kvariant may not be associated with long-term clinical outcome in Chinese patients with MMD.
Health of Non-binary and Genderqueer People: A Systematic Review

Background: Non-binary and genderqueer (NBGQ) people are those who do not identify within the gender binary system (male vs. female), not falling exclusively in man/male or woman/female normative categories. A higher proportion of NBGQ people is usually found within young persons. This population is marginalized and, as such, is at risk of stigmatization and of developing negative health outcomes. As literature on the health of NBGQ people is sparse, this study aims at systematically review the limited studies on this field. Methods: The research questions which guided the systematic review were: (1) What are the differences in the health levels between NBGQ and binary transgender (BT) individuals? (2) What are the differences in the health levels between NBGQ and cisgender individuals? (3) Which medical and psychological interventions are most suitable for improving NBGQ health? According to PRISMA guidelines, a systematic search was conducted in PubMed, PsycInfo, Web of Science, and Google Scholar. Results: Eleven studies met the inclusion criteria for the current systematic review. Among them, 9 were focused on the health differences between NBGQ and BT individuals, 4 of the latter and 1 individually were focused on the health differences between NBGQ and cisgender individuals, and 1 was focused on the evaluation of health outcomes related to medical procedures. No studies assessed psychological interventions aimed at improving health in NBGQ individuals. All studies were cross-sectional, did not generally recruit a large sample of NBGQ individuals, and used non-probability sample design. Results related to the difference in health between NBGQ and BT were mixed; indeed, some found a better health status while others a worse one. Results related to the differences in health between NBGQ and cisgender highlighted higher health needs in NBGQ than in BT individuals. The only study analyzing the effects of medical interventions on health found that NBGQ female-assigned at birth individuals improved their quality of life after chest surgery. Conclusions: Although scholars are starting to pay attention to the NBGQ health, research needs to be expanded both in terms of methodology and research contents. Clinical, health-related social policies, and research recommendations in this field are reported.
Pemphigus: Current and Future Therapeutic Strategies

Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.