Miracle-dz/UniFAR-FTUs huggingface dataset:
Open-wedge high tibial osteotomy associated with lipogems® intra-articular injection for the treatment of varus knee osteoarthritis – retrospective study

Background and aim: Open-wedge high tibial osteotomy (HTO) is a good choice in the treatment of varus knee medial osteoarthritis, with the restore of the correct mechanical axis of the lower limb. Autologous adipose derived stem cells (aASCs) are used in cartilage regeneration and in the treatment of early osteoarthritis. Aim of this study is to retrospectively analyze clinical (and radiological) results in two populations of patients with initial varus medial knee osteoarthritis, treated with HTO, with or without associated intra-articular injection of aASCs. Methods: In this study we analyze 85 patients treated with HTO for varus knee osteoarthritis with or without Lipogems® intra-articular injection. It was used of a single model of HTO plate. No associated procedure was performed. Results: Significant improvement in the daily life activity assessment (KOOS score) was observed in the group treated also with aASCs compared with group treated with isolated HTO. Conclusions: We suggest, in these patients, the surgical indication of an open-wedge high tibial osteotomy (HTO) and simultaneous injection with aASCs associated procedure to improve cartilage regeneration, with clinical improvement. (www.actabiomedica.it)
Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography.

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility’s Extremely Brilliant Source: the world’s first high-energy 4th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ’s structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ’s individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.
Operando unraveling photothermal-promoted dynamic active-sites generation in NiFe2O4 for markedly enhanced oxygen evolution

Significance As the electrochemical reconstruction into highly active species is anticipated to arise under the oxidative conditions, activating and tailoring the surface reconstruction via a rational and effective strategy is pivotal to improve the oxygen evolution reaction (OER) activity. In this work, we advance a robust process, that is, the photothermal effect originated from the spinel NiFe2O4 catalyst, to render its dynamic transition into active (Ni,Fe)oxyhydroxides species that triggers highly efficient oxygen evolution. Significantly, the reaction kinetics of OER are improved due to the lowered activation energy, as modulated by the photothermal energy-promoted surface reconstruction. More importantly, the operando Raman spectroelectrochemistry study and first-principle calculation collectively unveil the mechanism of photothermal-assisted enhancement in OER reaction. The ability to develop highly active and low-cost electrocatalysts represents an important endeavor toward accelerating sluggish water-oxidation kinetics. Herein, we report the implementation and unraveling of the photothermal effect of spinel nanoparticles (NPs) on promoting dynamic active-sites generation to markedly enhance their oxygen evolution reaction (OER) activity via an integrated operando Raman and density functional theory (DFT) study. Specifically, NiFe2O4 (NFO) NPs are first synthesized by capitalizing on amphiphilic star-like diblock copolymers as nanoreactors. Upon the near-infrared light irradiation, the photothermal heating of the NFO-based electrode progressively raises the temperature, accompanied by a marked decrease of overpotential. Accordingly, only an overpotential of 309 mV is required to yield a high current density of 100 mA cm−2, greatly lower than recently reported earth-abundant electrocatalysts. More importantly, the photothermal effect of NFO NPs facilitates surface reconstruction into high-active oxyhydroxides at lower potential (1.36 V) under OER conditions, as revealed by operando Raman spectroelectrochemistry. The DFT calculation corroborates that these reconstructed (Ni,Fe)oxyhydroxides are electrocatalytically active sites as the kinetics barrier is largely reduced over pure NFO without surface reconstruction. Given the diversity of materials (metal oxides, sulfides, phosphides, etc.) possessing the photo-to-thermal conversion, this effect may thus provide a unique and robust platform to boost highly active surface species in nanomaterials for a fundamental understanding of enhanced performance that may underpin future advances in electrocatalysis, photocatalysis, solar-energy conversion, and renewable-energy production.
Changes in the Organosulfur and Polyphenol Compound Profiles of Black and Fresh Onion during Simulated Gastrointestinal Digestion

This study aims to determine the changes in, and bioaccessibility of, polyphenols and organosulfur compounds (OSCs) during the simulated gastrointestinal digestion of black onion, a novel product derived from fresh onion by a combination of heat and humidity treatment, and to compare it with its fresh counterpart. Fresh and black onions were subjected to in-vitro gastrointestinal digestion, and their polyphenol and OSC profiles were determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Although to a lesser extent than in the fresh onion, the phenolic compounds in the black variety remained stable during the digestion process, presenting a higher bioaccessibility index (BI) with recovery corresponding to 41.1%, compared with that of fresh onion (23.5%). As for OSCs, apart from being more stable after the digestion process, with a BI of 83%, significantly higher quantities (21 times higher) were found in black onion than in fresh onion, suggesting that the black onion production process has a positive effect on the OSC content. Gallic acid, quercetin, isorhamnetin, and ɣ-glutamyl-S-(1-propenyl)-L-cysteine sulfoxide were the most bioaccessible compounds in fresh onion, while isorhamnetin, quercetin-diglucoside, ɣ-glutamyl-S-methyl-L-cysteine sulfoxide and methionine sulfoxide were found in black onion. These results indicate that OSCs and polyphenols are more bioaccessible in black onion than in fresh onion, indicating a positive effect of the processing treatment.
Risk factors of pleural effusion after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in late-stage and recurrent ovarian cancer.

BACKGROUND Pleural effusion (PE) is one of the most common complications of advanced recurrent ovarian cancer. However, no studies have revealed the risk factors for PE after surgery. The purpose of this study is to observe the incidence and risk factors of PE after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with late-stage and recurrent ovarian cancer. METHODS A retrospective analysis of 77 patients with late-stage and recurrent ovarian cancer after CRS + HIPEC was conducted. According to the presence of PE within 7 days after operation, two groups were formed. The basic information, surgical process, and laboratory examinations of the two groups were analyzed and compared to conduct a regression analysis. RESULTS The incidence of postoperative PE was 57.1% (44/77 patients). Among these patients, the prevalence of grade I-II and grade III-IV PE was 42.8% (33/77 patients) and 14.3% (11/77 patients), respectively. There were statistically significant differences between the two groups in terms of preoperative PE, the duration of surgery, intraoperative blood loss, postoperative level of albumin, intestinal involvement, and diaphragmatic involvement. Among these, preoperative PE and diaphragmatic involvement were identified as independent risk factors of postoperative PE. CONCLUSIONS Patients with late-stage and recurrent ovarian cancer invariably develop postoperative PE after CRS + HIPEC. Preoperative PE and diaphragmatic involvement are independent risk factors of postoperative PE. It is estimated that the incidence of postoperative PE among patients with these two independent risk factors is approximately 100%. Hence, we should promote the prevention and treatment of PE to improve its prognosis.
A Transcription Regulatory Sequence in the 5′ Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs

Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5′ ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.
Endothelial Dysfunction Is Associated with Cerebrovascular Events in Pre-Dialysis CKD Patients: A Prospective Study

Background: Patients with chronic kidney disease (CKD) have markedly increased rates of end stage renal disease, major adverse cardiovascular/cerebrovascular events (MACCEs), and mortality. Endothelial dysfunction (ED) is an early marker of atherosclerosis that is emerging as an increasingly important non-traditional cardiovascular risk factor in CKD. There is a lack of clinical studies examining the association between ED and both cardiovascular and renal endpoints in patients with CKD. Aims: We examined the association between reactive hyperemia index (RHI), a validated measure of endothelial function measured by peripheral arterial tonometry (PAT), with traditional cardiovascular risk factors in pre-dialysis CKD patients and prospectively evaluated the role of RHI as predictor of renal and cardiovascular outcomes in this population. Methods: One hundred and twenty pre-dialysis patients with CKD stages 1 to 5 (CKD group) and 18 healthy kidney donor candidates (control group) were recruited and had a successful RHI measurement by PAT. General demographic and clinical information including traditional cardiovascular risk factors were registered from all participants. Thereafter, patients were prospectively followed-up for a median time of 47 (IQR 19–66) months to determine associations of RHI with renal outcomes, MACCEs, hospitalizations or mortality. Results: In the CKD patient population, the mean age was 57.7 ± 15.5 years, the mean eGFR was 54.9 ± 36.7 mL/min/1.73 m2 (CKD-EPI) and 57 were males (47.5%). At baseline, in univariate analysis, RHI in the CKD group correlated positively with eGFR (r = 0.332, p < 0.0001) and correlated negatively with age (r = −0.469, p < 0.0001), Charlson index (r = −0.399, p < 0.0001), systolic blood pressure (r = −0.256, p = 0.005), and proteinuria (r = 0.211, p = 0.027). Reactive hyperemia index in the control group did not significantly differ from RHI observed in patients with CKD stages 1 to 5 (2.09 ± 0.40 vs. 2.01 ± 0.06, p = 0.493). In adjusted analysis, only age (β = −0.014, p = 0.003) remained independently associated with RHI at baseline. During follow-up, 8 patients suffered a MACCEs, 33 patients experienced renal function deterioration, 17 patients were hospitalized for medical reasons and 6 patients died. RHI at baseline was not significantly associated with CKD progression (1.94 vs. 2.02, p = 0.584), hospitalizations (1.90 vs. 2.04, p = 0.334), and all-cause mortality (1.65 vs. 2.01, p = 0.208) or MACCEs (1.77 vs. 2.01, p = 0.356), but was significantly associated with cerebrovascular events (1.27 vs. 2.02, p = 0.004) and with a composite cardiovascular outcome (MACCEs, hospital admissions and death; 1.73 vs. 2.07, p = 0.035). Conclusion: Our results suggest that RHI may be a predictor for the development of cerebrovascular events in pre-dialysis CKD patients who may benefit from more aggressive preventive measures.
Lessons from an International Initiative to Set and Share Good Practice on Human Health in Environmental Impact Assessment

Environmental Impact Assessment (EIA) is applied to infrastructure and other large projects. The European Union EIA Directive (2011/92/EU as amended by 2014/52/EU) requires EIAs to consider the effects that a project might have on human health. The International Association for Impact Assessment and the European Public Health Association prepared a reference paper on public health in EIA to enable the health sector to contribute to this international requirement. We present lessons from this joint action. We review literature on policy analysis, impact assessment and Health Impact Assessment (HIA). We use findings from this review and from the consultation on the reference paper to consider how population and human health should be defined; how the health sector can participate in the EIA process; the relationship between EIA and HIA; what counts as evidence; when an effect should be considered ‘likely’ and ‘significant’; how changes in health should be reported; the risks from a business-as-usual coverage of human health in EIA; and finally competencies for conducting an assessment of human health. This article is relevant for health authorities seeking to ensure that infrastructure, and other aspects of development, are not deleterious to, but indeed improve, human health.
Selenium Biofortification: Roles, Mechanisms, Responses and Prospects

The trace element selenium (Se) is a crucial element for many living organisms, including soil microorganisms, plants and animals, including humans. Generally, in Nature Se is taken up in the living cells of microorganisms, plants, animals and humans in several inorganic forms such as selenate, selenite, elemental Se and selenide. These forms are converted to organic forms by biological process, mostly as the two selenoamino acids selenocysteine (SeCys) and selenomethionine (SeMet). The biological systems of plants, animals and humans can fix these amino acids into Se-containing proteins by a modest replacement of methionine with SeMet. While the form SeCys is usually present in the active site of enzymes, which is essential for catalytic activity. Within human cells, organic forms of Se are significant for the accurate functioning of the immune and reproductive systems, the thyroid and the brain, and to enzyme activity within cells. Humans ingest Se through plant and animal foods rich in the element. The concentration of Se in foodstuffs depends on the presence of available forms of Se in soils and its uptake and accumulation by plants and herbivorous animals. Therefore, improving the availability of Se to plants is, therefore, a potential pathway to overcoming human Se deficiencies. Among these prospective pathways, the Se-biofortification of plants has already been established as a pioneering approach for producing Se-enriched agricultural products. To achieve this desirable aim of Se-biofortification, molecular breeding and genetic engineering in combination with novel agronomic and edaphic management approaches should be combined. This current review summarizes the roles, responses, prospects and mechanisms of Se in human nutrition. It also elaborates how biofortification is a plausible approach to resolving Se-deficiency in humans and other animals.
Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.
Investigation of the potential mechanism of farnesol in protecting the intestinal epithelium barrier from invasion by Candida albicans via untargeted metabolomics.

BACKGROUND This study aimed to explore the potential mechanisms of farnesol in the protection of the intestinal epithelium barrier from invasion by Candida albicans (C. albicans) via untargeted metabolomics. METHODS The C. albicans reference strain SC5314 and Caco-2 cells were used in this study. The effect of different concentrations of farnesol on the co-culture of C. albicans and Caco-2 cells was investigated using the CCK-8 assay. The effect of farnesol on C. albicans biofilm formation was also observed. There were 4 treatment groups, including the Caco-2 + C. albicans (group 1), Caco-2 (group 2), Caco-2 + C. albicans + farnesol (group 3), and a quality control (QC group) for metabolite extraction, followed by LC-MS/MS analysis and bioinformatics analysis. RESULTS Farnesol treatment significantly reduced the adhesion of C. albicans and inhibited the formation of C. albicans biofilm. A total of 22 differential metabolites were identified in group 1 vs. group 2, such as acetylcarnitine, linoleic acid, spermidine, and glutathione disulfide. These differential metabolites were involved in fatty acid biosynthesis, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and glutathione metabolism. There were 18 differential metabolites identified in group 3 vs. group 1, including acetylcarnitine, hypoxanthine, L-glutamate, and linoleic acid, which were enriched in fatty acid biosynthesis, linoleic acid metabolism, and biosynthesis of unsaturated fatty acids. CONCLUSIONS C. albicans can damage the intestinal barrier by affecting the metabolism of acetylcarnitine, linoleic acid, glutathione. Farnesol may protect the intestinal epithelium barrier from the invasion of C. albicans by regulating the metabolism of acetylcarnitine, linoleic acid, and L-glutamate.
Retinoids in the visual cycle: role of the retinal G protein-coupled receptor.

Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11- cis -retinal to the all- trans configuration. This photo-chemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensi-tive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11- cis retinal. This trans - cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11- cis -retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)-retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11- cis -retinal regeneration. The photoisomerase
Nonparametric Bayesian functional two‐part random effects model for longitudinal semicontinuous data analysis

Longitudinal semicontinuous data, characterized by repeated measures of a large portion of zeros and continuous positive values, are frequently encountered in many applications including biomedical, epidemiological, and social science studies. Two‐part random effects models (TPREM) have been used to investigate the association between such longitudinal semicontinuous data and covariates accounting for the within‐subject correlation. The existing TPREM is, however, limited to incorporate a functional covariate, which is often available in a longitudinal study. Moreover, the existing TPREM typically assumes the normality of subject‐specific random effects, which can be easily violated when there exists a subgroup structure. In this article, we propose a nonparametric Bayesian functional TPREM to assess the relationship between the longitudinal semicontinuous outcome and various types of covariates including a functional covariate. The proposed model also relaxes the normality assumption for the random effects through a Dirichlet process mixture of normals, which allows for identifying an underlying subgroup structure. The methodology is illustrated through an application to social insurance expenditure data collected by the Korean Welfare Panel Study and a simulation study.