Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of type 2 diabetes mellitus models using streptozotocin after 3 months high-fat diet in Bama minipigs

Abstract In the past twenty years, the number of adults with diabetes has tripled. Most studies have been conducted using rodent models of type 2 diabetes mellitus (T2DM), and the developed drugs have low clinical conversion efficiency. Therefore, it is urgent to establish a more human-like large animal model to explore T2DM pathogenesis and formulate new disease prevention and control strategies. This study was designed to establish and validate a T2DM model using minipigs fed a high-fat or high-cholesterol/high-fat diet and injected with low-dose streptozotocin (STZ). We examined the influence of the STZ injection timing with a diet high in fat (HFD) compared with one high in cholesterol and fat (HCFD) on the atherosclerotic lesions accelerated by T2DM. Male Bama minipigs (n = 24) were randomly divided into five groups. The control group was fed a normal diet for 9 months. The STZ + HFD and STZ + HCFD groups were infused with 90 mg/kg STZ and then fed a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively. The HFD + STZ and HCFD + STZ groups were fed a high-fat diet or a high-cholesterol and high-fat diet, respectively, for 9 months (after 3 months, these pigs were injected intravenously with 90 mg/kg STZ). During the induction period, animal body weight, BMI, and serum GLU, INS, TG, TC, HDL-C, LDL-C, FFA, ALT, AST, CRE, and BUN were detected monthly intervals. IVGTT and insulin release tests were performed at 3-month intervals. At the end of the test, the coronary artery and abdominal aorta were examined by computed tomography and pathological observations, and the thickness of the basement membrane of the capillary of the retina and kidney glomerulus was measured under a transmission electron microscope. The serum glucose concentrations were normal in all groups except the HFD + STZ and HCFD + STZ groups. Animals fed an HFD for 9 months did not develop apparent atherosclerotic lesions, but atherosclerotic lesions were seen in the animals fed an HCFD. Hyperglycemia accelerated the formation of atherosclerotic lesions on the intimal surface of the abdominal aorta. Low-dose STZ after 3 months of HFD or HCFD successfully established a T2DM model in minipigs. The HFD did not induce apparent atherosclerotic lesions, but these were seen with the HCFD. Hyperglycemia accelerated atherosclerosis in the minipigs.
Riociguat attenuates the changes in left ventricular proteome and microRNA profile after experimental aortic stenosis in mice

Development and progression of heart failure involve endothelial and myocardial dysfunction as well as a dysregulation of the NO‐sGC‐cGMP signalling pathway. Recently, we reported that the sGC stimulator riociguat has beneficial effects on cardiac remodelling and progression of heart failure in response to chronic pressure overload. Here, we examined if these beneficial effects of riociguat were also reflected in alterations of the myocardial proteome and microRNA profiles.
Geometrizing Local Rates of Convergence for High-Dimensional Linear Inverse Problems

This paper presents a unified theoretical framework for the analysis of a general ill-posed linear inverse model which includes as special cases noisy compressed sensing, sign vector recovery, trace regression, orthogonal matrix estimation, and noisy matrix completion. We propose a computationally feasible convex program for the linear inverse problem and develop a theoretical framework to characterize the local rate of convergence. The unified theory is built based on the local conic geometry and duality. The difficulty of estimation is captured by the geometric characterization of the local tangent cone through the complexity measures -- the Gaussian width and covering entropy.
Forecasting spot electricity prices Deep learning approaches and empirical comparison of traditional algorithms

(cid:129) A novel deep learning framework to forecast electricity prices is proposed. (cid:129) The framework leads to accuracy improvements that are statistically signi ﬁ cant. (cid:129) The largest benchmark to date in electricity price forecasting is presented. (cid:129) 27 state-of-the-art methods for predicting electricity prices are compared. (cid:129) Machine learning models are shown to, in general, outperform statistical methods. In this paper, a novel modeling framework for forecasting electricity prices is proposed. While many predictive models have been already proposed to perform this task, the area of deep learning algorithms remains yet unexplored. To ﬁ ll this scienti ﬁ c gap, we propose four di ﬀ erent deep learning models for predicting electricity prices and we show how they lead to improvements in predictive accuracy. In addition, we also consider that, despite the large number of proposed methods for predicting electricity prices, an extensive benchmark is still missing. To tackle that, we compare and analyze the accuracy of 27 common approaches for electricity price forecasting. Based on the benchmark results, we show how the proposed deep learning models outperform the state-of-the-art methods and obtain results that are statistically signi ﬁ cant. Finally, using the same results, we also show that: (i) machine learning methods yield, in general, a better accuracy than statistical models; (ii) moving average terms do not improve the predictive accuracy; (iii) hybrid models do not outperform their simpler counterparts.
Neurofilament light chain: a new marker for neuronal decay in the anterior chamber fluid of patients with glaucoma

Background/Aims Neurofilament light chain (NfL) levels in cerebrospinal fluid and serum are reliable indicators for neuroaxonal damage in a broad spectrum of neurodegenerative diseases. Herein, we investigate NfL levels in serum and anterior chamber fluid of patients with glaucoma. Methods Patients scheduled for routine glaucoma or cataract surgery were recruited for this study. Retinal nerve fibre layer thickness was measured by optical coherence tomography (OCT, Heidelberg Spectralis). NfL levels in serum and in anterior chamber fluid were analysed with Simoa SR-X Analyzer (Quanterix; NFLIGHT, Lexington, Massachusetts, USA). T-test was used for parametric data and Mann-Whitney-U test for nonparametric data. Spearman’s rank-order correlation was used to investigate correlations. P values<0.05 were considered as statistically significant. Results Sixty patients with glaucoma and 58 controls were enrolled. Serum NfL concentration of patients with glaucoma was similar to serum NfL concentration in controls (median (IQR); 22.7 (18.9) pg/mL vs 22.5 (24.0) pg/mL; p=0.763). A positive correlation of serum NfL with age was observed in both patients with glaucoma (r=0.77; p<0.001) and in the control group (r=0.82, p<0.001). In the anterior chamber fluid, the NfL concentration was substantially increased in patients with glaucoma compared with controls (20.7 (101.3) pg/mL vs 3.1 (2.9) pg/mL; p<0.001). Furthermore, we found a positive correlation of anterior chamber fluid NfL with preoperative intraocular pressure (r=0.39, p=0.003) and with retinal nerve fibre layer thickness (r=0.58, p<0.001). Conclusion NfL levels in anterior chamber fluid are elevated in patients with glaucoma and correlate with intraocular pressure and retinal nerve fibre layer thickness. The presented data strongly support anterior chamber fluid NfL as a new marker for glaucoma.
Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial

ABSTRACT Background We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment. Methods NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250–1500 mg/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders. Results In the intention-to-treat population (NAMR: n = 539; placebo: n = 183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40 ± 1.55 versus 5.79 ± 1.37 mg/dl, P < .001) with a mean difference of −0.39 mg/dl [95% confidence interval (CI) −0.66 to −0.13], but was comparable between the groups at week 52 [mean difference −0.08 (95% CI −0.36–0.20)]. In the completer population (n = 358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR. Conclusions NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation.
Graft aberrant hepatic arteries in deceased donor liver transplantation: The “one liver, one artery” approach

In liver transplantation (LT), graft aberrant hepatic arteries (aHAs) frequently require complex arterial reconstructions, potentially increasing the risk of post‐operative complications. However, intrahepatic hilar arterial shunts are physiologically present and may allow selective aHA ligation. Thus, we performed a retrospective study from a single‐center cohort of 618 deceased donor LTs where a selective reconstruction policy of aHAs was prospectively applied. In the presence of any aHA, the vessel with the largest caliber was first reconstructed. In case of adequate bilobar arterial perfusion assessed on intraparenchymal Doppler ultrasound, the remnant vessel was ligated; otherwise, it was reconstructed. Consequently, outcomes of three patient groups were compared: the “no aHAs” group (n = 499), the “reconstructed aHA” group (n = 25), and the “ligated aHA” group (n = 94). Primary endpoint was rate of biliary complications. Only 38.4% of right aHAs and 3.1% of left aHAs were reconstructed. Rates of biliary complications in the no aHA, reconstructed aHA, and ligated aHA groups were 23.4%, 28%, and 20.2% (p = 0.667), respectively. The prevalence rates of primary non‐function (p = 0.534), early allograft dysfunction (p = 0.832), and arterial complications (p = 0.271), as well as patient survival (p = 0.266) were comparable among the three groups. Retransplantation rates were 3.8%, 4%, and 5.3% (p = 0.685), respectively. In conclusion, a selective reconstruction policy of aHAs based on Doppler assessment of bilobar intraparenchymal arterial flow did not increase post‐operative morbidity and avoided unnecessary and complex arterial reconstructions.
13CO2 labeling kinetics in maize reveal impaired efficiency of C4 photosynthesis under low irradiance

Abstract C4 photosynthesis allows faster photosynthetic rates and higher water and nitrogen use efficiency than C3 photosynthesis, but at the cost of lower quantum yield due to the energy requirement of its biochemical carbon concentration mechanism. It has also been suspected that its operation may be impaired in low irradiance. To investigate fluxes under moderate and low irradiance, maize (Zea mays) was grown at 550 µmol photons m−2 s−l and 13CO2 pulse-labeling was performed at growth irradiance or several hours after transfer to 160 µmol photons m−2 s−1. Analysis by liquid chromatography/tandem mass spectrometry or gas chromatography/mass spectrometry provided information about pool size and labeling kinetics for 32 metabolites and allowed estimation of flux at many steps in C4 photosynthesis. The results highlighted several sources of inefficiency in low light. These included excess flux at phosphoenolpyruvate carboxylase, restriction of decarboxylation by NADP-malic enzyme, and a shift to increased CO2 incorporation into aspartate, less effective use of metabolite pools to drive intercellular shuttles, and higher relative and absolute rates of photorespiration. The latter provides evidence for a lower bundle sheath CO2 concentration in low irradiance, implying that operation of the CO2 concentration mechanism is impaired in this condition. The analyses also revealed rapid exchange of carbon between the Calvin–Benson cycle and the CO2-concentration shuttle, which allows rapid adjustment of the balance between CO2 concentration and assimilation, and accumulation of large amounts of photorespiratory intermediates in low light that provides a major carbon reservoir to build up C4 metabolite pools when irradiance increases.
Reliability of biological maturation analyses performed by equations predicting skeletal age and peak height velocity with hand and wrist X‐ray results

Hand‐wrist radiography is the gold standard for the assessment of skeletal age (SA) and the assignment of biological maturation (BM) status. However, its practical use in the field is questioned, prompting the development of anthropometric equations to estimate BM. However, there is no consensus on the reliability of these equations in relation to hand‐wrist X‐rays.
Effects of selective attention on the C1 ERP component: A systematic review and meta-analysis.

The C1 event-related potential (ERP) captures the earliest stage of feedforward processing in the primary visual cortex (V1). An ongoing debate is whether top-down selective attention can modulate the C1. One side of the debate pointed out that null findings appear to outnumber positive findings; thus, selective attention does not seem to influence the C1. However, this suggestion is not based on a valid approach to summarizing evidence across studies. Therefore, we conducted a systematic review and meta-analysis investigating the effects of selective attention on the C1, involving 47 experiments and 794 subjects in total. Despite heterogeneity across studies, results suggested that attention has a moderate effect on the C1 (Cohen's d z $$ {d}_z $$ = 0.33, p < .0001); that is, C1 amplitude is larger for visual stimuli that are attended than unattended. These results suggest that C1 is affected by top-down selective attention.
Punica Granatum Linn.: A phytochemical and pharmacological review

The pharmacochemistry of the pomegranate ( Punica granatum Linn .) was mentioned in the literatures. The natural chemicals and the biological attributes of the plant were determined. The interested properties include the wound healing effect, anti-diarrhoeal, anti-parasitic and antioxidant capacities of the seed and rind, or fruit peel extracts. Biotechnological research was also focused on the potentially natural dye colourant from the pomegranate. The pomegranate peel, producible as flour, could as well, be a promising antibacterial agent. Per the publications, therapeutic applications of pomegranate were reviewed. Manufacturers utilize this plant to produce supplements and cosmetics. Advances in pharmacological studies include the clinical trial to investigate the efficiency of a Punica -contained traditional mouthwash, to control gingivitis among the diabetic patients. From the phytochemical screening, the phenolic, alkaloid and terpenoid constituents were detected. The separation of alkaloids was performed by utilising the bulk liquid membrane technique, using rotating discs’ contactor. Latest discovery includes the identification of punigratane, a novel pyrrolidine alkaloid with putative efflux inhibition activity. It is anticipated that P. granatum fruit peels and seeds could offer potential benefits and medicinal uses for human. The bio-waste of the rind is also appreciated and could possess significant values in the agricultural, biotechnological, chemical and food industries.
Associations of Guillain‐Barré syndrome with coronavirus disease 2019 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database

Vaccinations against the severe acute respiratory syndrome coronavirus 2 which causes COVID‐19 have been administered worldwide. We aimed to investigate associations of COVID‐19 vaccination with the occurrence of Guillain‐Barré syndrome (GBS). We explored potential safety signals regarding the development of GBS using disproportionality analyses to compare COVID‐19 vaccination with all adverse drug reaction (ADR) reports and influenza vaccines reported to VigiBase. As of October 15, 2021, a total of 2163 cases (0.13%) of GBS and its variants (including 46 cases of Miller‐Fisher syndrome and 13 cases of Bickerstaff's encephalitis) were identified in entire ADR database after vaccination with the ChAdOx1 nCoV‐19 (AstraZeneca, Cambridge, UK) or the two messenger RNA‐based COVID‐19 (BNT162b2; Pfizer and BioNTech) or mRNA‐1273; Moderna) vaccines. The median time to onset of GBS after vaccination was around 2 weeks. The ChAdOx1 nCoV‐19 and two messenger RNA‐based COVID‐19 vaccines demonstrated a higher risk for GBS against entire database (information component [IC]025 = 1.73 reporting odds ratio [ROR]025 = 3.51; IC025 = 1.07, ROR025 = 2.22, respectively). When compared with influenza vaccines, neither the ChAdOx1 nCoV‐19 nor mRNA‐based vaccines were found to be associated with greater risks of GBS (IC025 = −1.84, ROR025 = 0.11; IC025 = −1.86, ROR025 = 0.06, respectively). Although potential safety signals associated with GBS COVID‐19 vaccines have been identified, the risk of GBS from COVID‐19 vaccines were low and did not surpass those of influenza vaccines; however, because of the heterogeneity of the sources of information in the WHO pharmacovigilance database, further epidemiological studies are warranted to confirm these observations.
The functional diversity of tissue‐resident natural killer cells against infection

For decades, studies of natural killer (NK) cells have focused on those found in peripheral blood (PBNK cells) as the prototype for NK cell biology. Only recently have researchers begun to explore the diversity of tissue‐resident NK (tr‐NK) cells. While tr‐NK cells were initially identified from mice parabiosis and intravascular staining experiments, they can also be identified by tissue retention markers such as CD69, CD103 and others. More importantly, tr‐NK cells have distinct functions compared to PBNK cells. Within the liver, there are diverse subsets of tr‐NK cells expressing different combinations of tissue‐retention markers and transcription factors, the clinical relevance of which are still unclear. Functionally, liver tr‐NK are primed with immediate responsiveness to infection and equipped with regulatory mechanisms to prevent liver damage. When decidual NK (dNK) cells were first discovered, they were mainly characterized by their reduced cytotoxicity and functions related to placental development. Recent studies, however, revealed different mechanisms by which dNK cells prevent uterine infections. The lungs are one of the most highly exposed sites for infection due to their role in oxygen exchange. Upon influenza infection, lung tr‐NK cells can degranulate and produce more inflammatory cytokines than PBNK cells. Less understood are gut tr‐NK cells which were recently characterized in infants and adults for their functional differences. In this mini‐review, we aim to provide a brief overview of the most recent discoveries on how several tr‐NK cells are implicated in the immune response against infection.
Comparability of skeletal fibulae surfaces generated by different source scanning (dual‐energy CT scan vs. high resolution laser scanning) and 3D geometric morphometric validation

This work aims to test accuracy and comparability of 3D models of human skeletal fibulae generated by clinical CT and laser scanner virtual acquisitions. Mesh topology, segmentation and smoothing protocols were tested to assess variation among meshes generated with different scanning methods and procedures, and to evaluate meshes‐interchangeability in 3D geometric morphometric analysis. A sample of 13 left human fibulae were scanned separately with Revolution Discovery CT dual energy (0.625 mm resolution) and ARTEC Space Spider 3D structured light laser scanner (0.1 mm resolution). Different segmentation methods, including half‐maximum height (HMH) and MIA‐clustering protocols, were compared to their high‐resolution standard generated with laser‐scanner by calculating topological surface deviations. Different smoothing algorithms were also evaluated, such as Laplacian and Taubin smoothing. A total of 142 semilandmarks were used to capture the shape of both proximal and distal fibular epiphyses. After Generalized Procrustes superimposition, the Procrustes coordinates of the proximal and distal fibular epiphyses were used separately to assess variation due to scanning methods and the operator error. Smoothing algorithms at low iteration do not provide significant variation among reconstructions, but segmentation protocol may influence final mesh quality (0.09–0.24 mm). Mean deviation among CT‐generated meshes that were segmented with MIA‐clustering protocol, and laser scanner‐generated ones, is optimal (0.42 mm, ranging 0.35–0.56 mm). Principal component analysis reveals that homologous samples scanned with the two methods cluster together for both the proximal and distal fibular epiphyses. Similarly, Procrustes ANOVA reveals no shape differences between scanning methods and replicates, and only 1.38–1.43% of shape variation is due to scanning device. Topological similarities support the comparability of CT‐ and laser scanner‐generated meshes and validate its simultaneous use in shape analysis with potential clinical relevance. We precautionarily suggest that dedicated trials should be performed in each study when merging different data sources prior to analyses.
Antibody-based therapy for acute myeloid leukemia: a review of phase 2 and 3 trials

ABSTRACT Introduction Despite recent advances in the treatment of adult acute myeloid leukemia (AML), the clinical outcome of patients continues to be unsatisfactory especially among older patients, those with a high-risk profile, and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel therapeutic agents either used alone or in combination with intensive chemotherapy or low-intensity treatments. Areas covered The current paper reviews the clinical development of monoclonal antibody-based therapies in AML, their current status and phases 2 and 3 prospective trials. Expert opinion Monoclonal antibody-based therapies demonstrated efficacy and tolerability in several clinical trials, especially when used in combination either with ‘3 + 7’ chemotherapy or with low-intensity treatments. Additional studies are needed to determine new antigens for antibody-based therapies that target leukemia stem cells and spare normal hematopoiesis. Phase 2 and 3 additional clinical trial data are needed to assess the promise of first trials, especially regarding chimeric antigen receptor T cells redirected against myeloid antigens and immune checkpoint inhibitor therapies.