Miracle-dz/UniFAR-FTUs huggingface dataset:
Prepubertal Dietary and Plasma Phospholipid Fatty Acids Related to Puberty Timing: Longitudinal Cohort and Mendelian Randomization Analyses

Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3–7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8–17 years, and age at peak height velocity (PHV) from repeated height measurements at 5–20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls (n = 3872) but not boys (n = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.
Predicting Protein–Protein Interactions via Gated Graph Attention Signed Network

Protein–protein interactions (PPIs) play a key role in signal transduction and pharmacogenomics, and hence, accurate PPI prediction is crucial. Graph structures have received increasing attention owing to their outstanding performance in machine learning. In practice, PPIs can be expressed as a signed network (i.e., graph structure), wherein the nodes in the network represent proteins, and edges represent the interactions (positive or negative effects) of protein nodes. PPI predictions can be realized by predicting the links of the signed network; therefore, the use of gated graph attention for signed networks (SN-GGAT) is proposed herein. First, the concept of graph attention network (GAT) is applied to signed networks, in which “attention” represents the weight of neighbor nodes, and GAT updates the node features through the weighted aggregation of neighbor nodes. Then, the gating mechanism is defined and combined with the balance theory to obtain the high-order relations of protein nodes to improve the attention effect, making the attention mechanism follow the principle of “low-order high attention, high-order low attention, different signs opposite”. PPIs are subsequently predicted on the Saccharomyces cerevisiae core dataset and the Human dataset. The test results demonstrate that the proposed method exhibits strong competitiveness.
Treatment Patterns and Pharmacoutilization in Patients Affected by Rheumatoid Arthritis in Italian Settings

This study aimed to evaluate the treatment patterns and pharmacoutilization of patients with rheumatoid arthritis (RA) in real-world settings in Italy. This retrospective observational analysis was based on administrative databases of selected Italian entities. All adult patients with RA diagnosis confirmed by ≥1 discharge diagnosis of RA (ICD-9-CM code = 714.0) or an active exemption code (006.714.0) were enrolled in 2019. Two cohorts were created: one included patients prescribed baricitinib, the other those prescribed biological disease-modifying antirheumatic drugs (bDMARDs). Overall, 47,711 RA patients were identified, most of them without DMARD prescription. As a first-line prescription, 43.2% of patients were prescribed conventional synthetic DMARDs (csDMARDs), 5.2% bDMARDs and 0.3% baricitinib. In 2019, 82.6% of csDMARD users continued with the same DMARD category, 15.9% had a bDMARD, while 1.5% had baricitinib as second-line therapy. Overall, 445 patients used baricitinib during 2019. During follow-up, baricitinib was prescribed as monotherapy to 31% of patients, as cotreatment with csDMARDs and corticosteroids to 27% of patients, with corticosteroids to 28% of patients and with csDMARDs to 14% of patients. In line with previous findings, a trend of bDMARD undertreatment was observed. The treatment patterns of baricitinib patients could help to better characterize patients eligible for new therapeutic options that will be available in the future.
Targeted Therapeutic Approach Based on Understanding of Aberrant Molecular Pathways Leading to Leukemic Proliferation in Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogenous hematopoietic neoplasm with various genetic abnormalities in myeloid stem cells leading to differentiation arrest and accumulation of leukemic cells in bone marrow (BM). The multiple genetic alterations identified in leukemic cells at diagnosis are the mainstay of World Health Organization classification for AML and have important prognostic implications. Recently, understanding of heterogeneous and complicated molecular abnormalities of the disease could lead to the development of novel targeted therapeutic agents. In the past years, gemtuzumab ozogamicin, BCL-2 inhibitors (venetovlax), IDH 1/2 inhibitors (ivosidenib and enasidenib) FLT3 inhibitors (midostaurin, gilteritinib, and enasidenib), and hedgehog signaling pathway inhibitors (gladegib) have received US Food and Drug Administration (FDA) approval for the treatment of AML. Especially, AML patients with elderly age and/or significant comorbidities are not currently suitable for intensive chemotherapy. Thus, novel therapeutic planning including the abovementioned target therapies could lead to improve clinical outcomes in the patients. In the review, we will present various important and frequent molecular abnormalities of AML and introduce the targeted agents of AML that received FDA approval based on the previous studies.
Getting hit by the bus around the world – a global perspective on goal directed treatment of massive hemorrhage in trauma

Purpose of review Major trauma remains one of the leading causes of death worldwide with traumatic brain injury and uncontrolled traumatic bleeding as the main determinants of fatal outcome. Interestingly, the therapeutic approach to trauma-associated bleeding and coagulopathy shows differences between geographic regions, that are reflected in different guidelines and protocols. Recent findings This article summarizes main principles in coagulation diagnostics and compares different strategies for treatment of massive hemorrhage after trauma in different regions of the world. How would a bleeding trauma patient be managed if they got hit by the bus in the United States, United Kingdom, Germany, Switzerland, Austria, Denmark, Australia, or in Japan? Summary There are multiple coexistent treatment standards for trauma-induced coagulopathy in different countries and different trauma centers. Most of them initially follow a protocol-based approach and subsequently focus on predefined clinical and laboratory targets.
The Influence of Hyaluronic Acid Biofunctionalization of a Bovine Bone Substitute on Osteoblast Activity In Vitro

Bovine bone substitute materials (BSMs) are used for oral bone regeneration. The objective was to analyze the influence of BSM biofunctionalization via hyaluronic acid (HA) on human osteoblasts (HOBs). BSMs with ± HA were incubated with HOBs including HOBs alone as a negative control. On days 3, 7 and 10, cell viability, migration and proliferation were analyzed by fluorescence staining, scratch wound assay and MTT assay. On days 3, 7 and 10, an increased cell viability was demonstrated for BSM+ compared with BSM− and the control (each p ≤ 0.05). The cell migration was enhanced for BSM+ compared with BSM− and the control after day 3 and day 7 (each p ≤ 0.05). At day 10, an accelerated wound closure was found for the control compared with BSM+/− (each p < 0.05). The highest proliferation rate was observed for BSM+ on day 3 (p ≤ 0.05) followed by BSM− and the control (each p ≤ 0.05). At day 7, a non-significantly increased proliferation was shown for BSM+ while the control was higher than BSM− (each p < 0.05). The least proliferation activity was observed for BSM− (p < 0.05) at day 10. HA biofunctionalization of the BSMs caused an increased HOB activity and might represent a promising alternative to BSM− in oral bone regeneration.
Phase Diagram of Binary Alloy Nanoparticles under High Pressure

CALPHAD (CALculation of PHAse Diagram) is a useful tool to construct phase diagrams of various materials under different thermodynamic conditions. Researchers have extended the use of the CALPHAD method to nanophase diagrams and pressure phase diagrams. In this study, the phase diagram of an arbitrary A–B nanoparticle system under pressure was investigated. The effects of the interaction parameter and excess volume were investigated with increasing pressure. The eutectic temperature was found to decrease in most cases, except when the interaction parameter in the liquid was zero and that in the solid was positive, while the excess volume parameter of the liquid was positive. Under these conditions, the eutectic temperature increased with increasing pressure.
60-S Retrogated Compressed Sensing 2D Cine of the Heart: Sharper Borders and Accurate Quantification

Background and objective: Real-time compressed sensing cine (CSrt) provides reliable quantification for both ventricles but may alter image quality. The aim of this study was to assess image quality and the accuracy of left (LV) and right ventricular (RV) volumes, ejection fraction and mass quantifications based on a retrogated segmented compressed sensing 2D cine sequence (CSrg). Methods: Thirty patients were enrolled. Each patient underwent the reference retrogated segmented steady-state free precession cine sequence (SSFPref), the real-time CSrt cine and the segmented retrogated prototype CSrg sequence providing the same slices. Functional parameters quantification and image quality rating were performed on SSFPref and CSrg images sets. The edge sharpness, which is an estimate of the edge spread function, was assessed for the three sequences. Results: The mean scan time was: SSFPref = 485.4 ± 83.3 (SD) s (95% CI: 454.3–516.5) and CSrg = 58.3 ± 15.1 (SD) s (95% CI: 53.7–64.2) (p < 0.0001). CSrg subjective image quality score (median: 4; range: 2–4) was higher than the one provided by CSrt (median: 3; range: 2–4; p = 0.0008) and not different from SSFPref overall quality score (median: 4; range: 2–4; p = 0.31). CSrg provided similar LV and RV functional parameters to those assessed with SSFPref (p > 0.05). Edge sharpness was significantly better with CSrg (0.083 ± 0.013 (SD) pixel−1; 95% CI: 0.078–0.087) than with CSrt (0.070 ± 0.011 (SD) pixel−1; 95% CI: 0.066–0.074; p = 0.0004) and not different from the reference technique (0.075 ± 0.016 (SD) pixel−1; 95% CI: 0.069–0.081; p = 0.0516). Conclusions: CSrg cine provides in one minute an accurate quantification of LV and RV functional parameters without compromising subjective and objective image quality.
Stimulating the Involvement of Family Members in the Medication Management Activities of Older Adults Through Ambient Displays

Little attention has been paid to how medication management technologies, designed for older adults, modify the participation of family caregivers. We developed a tablet-based ambient display that provides external cues to remind and motivate older adults to take their medications. This study aimed to understand the effect of ambient displays on the involvement of family members in the elderly's medication management. We conducted a 10-week study consisting of interviews administered weekly to nine elderly-caregivers. We identify that new involvement patterns of the family caregivers were provoked through external cues, which made them aware of older adults' medication adherence and encouraged younger relatives to help older adults.
Affordable Magnetic Hydrogels Prepared from Biocompatible and Biodegradable Sources

Magnetic hydrogels composed of poly(vinyl alcohol) (PVA)/water-soluble tricarboxy cellulose (CO)/magnetic fluids (MFs) have been prepared by a freeze–thaw cycle technique. The system designed here combines the renewability and biocompatibility aspects of PVA and CO, as well as the magnetic properties of MFs, thereby offering special properties to the final product with potential applications in medicine. In the first step, the water-soluble CO is synthesized using a one-shot oxidation procedure and then the aqueous solutions of CO are mixed with PVA solutions and magnetic fluids in the absence of any additional cross-linking agent. The magnetic hydrogels were thoroughly investigated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), magnetometry (VSM), and thermogravimetric analysis. The morphological results show an excellent distribution of magnetic particles and CO inside the PVA matrix. The VSM results show that the magnetic hydrogels possess superparamagnetic properties.
Deep Learning Methods for Heart Sounds Classification: A Systematic Review

The automated classification of heart sounds plays a significant role in the diagnosis of cardiovascular diseases (CVDs). With the recent introduction of medical big data and artificial intelligence technology, there has been an increased focus on the development of deep learning approaches for heart sound classification. However, despite significant achievements in this field, there are still limitations due to insufficient data, inefficient training, and the unavailability of effective models. With the aim of improving the accuracy of heart sounds classification, an in-depth systematic review and an analysis of existing deep learning methods were performed in the present study, with an emphasis on the convolutional neural network (CNN) and recurrent neural network (RNN) methods developed over the last five years. This paper also discusses the challenges and expected future trends in the application of deep learning to heart sounds classification with the objective of providing an essential reference for further study.
Metatranscriptomic Analysis Reveals an Imbalance of Hepatopancreatic Flora of Chinese Mitten Crab Eriocheir sinensis with Hepatopancreatic Necrosis Disease

Simple Summary The cause of Chinese mitten crab Eriocheir sinensis hepatopancreas necrosis disease (HPND) remains a mystery. In this study, metatranscriptomics sequencing was conducted to characterize the changes in the structure and gene expression of hepatopancreatic flora of crabs with and without typical symptoms of HPND; an imbalance of hepatopancreatic flora can be found in the crab with HPND, and the detected microbial taxa decreased, whereas the prevalence of Spiroplasma eriocheiris significantly increased in the hepatopancreatic flora of crabs with typical symptoms of HPND, and the relative abundances of the virus and microsporidia in crabs with HPND were very low and did not increase with disease progression. The differentially-expressed genes (DEGs) in hepatopancreatic flora between crabs with and without HPND were enriched ribosome, retinol metabolism, and biosynthesis of unsaturated fatty acid KEGG pathways. These results suggested that an imbalance of hepatopancreatic flora was associated with crab HPND, and the enriched pathways of DEGs were associated with the pathological mechanism of HPND. Abstract Hepatopancreas necrosis disease (HPND) of the Chinese mitten crab Eriocheir sinensis causes huge economic loss in China. However, the pathogenic factors and pathogenesis are still a matter of dissension. To search for potential pathogens, the hepatopancreatic flora of diseased crabs with mild symptoms, diseased crabs with severe symptoms, and crabs without visible symptoms were investigated using metatranscriptomics sequencing. The prevalence of Absidia glauca and Candidatus Synechococcus spongiarum decreased, whereas the prevalence of Spiroplasma eriocheiris increased in the hepatopancreatic flora of crabs with HPND. Homologous sequences of 34 viral species and 4 Microsporidian species were found in the crab hepatopancreas without any significant differences between crabs with and without HPND. Moreover, DEGs in the hepatopancreatic flora between crabs with severe symptoms and without visible symptoms were enriched in the ribosome, retinol metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism—cytochrome P450, biosynthesis of unsaturated fatty acids, and other glycan degradation. Moreover, the relative abundance of functions of DEDs in the hepatopancreatic flora changed with the pathogenesis process. These results suggested that imbalance of hepatopancreatic flora was associated with crab HPND. The identified DEGs were perhaps involved in the pathological mechanism of HPND; nonetheless, HPND did not occur due to virus or microsporidia infection.
Usefulness of a Colonoscopy Cap with an External Grid for the Measurement of Small-Sized Colorectal Polyps: A Prospective Randomized Trial

Accurate measurement of polyp size during colonoscopy is crucial. The usefulness of cap-assisted colonoscopy and external grid application on monitor (gCAP) was evaluated for polyp size measurement in this 3-year, single-center, single-blind, randomized trial. Using the endoscopic forceps width as reference, the discrepancy percent (DP), error rate (ER), and measurement time were compared between gCAP and visual estimation (VE) after randomization. ER was calculated within a 20% and 33% limit. From the 111 patients, 280 polyps were measured. The mean polyp sizes were 4.0 ± 1.7 mm and 4.2 ± 1.8 mm with gCAP and VE, respectively (p = 0.368). Compared with that by the forceps method, DP was significantly lower in the gCAP group than in the VE group. Moreover, ER was significantly lower in the gCAP group within its preset limit. The measurement time was 4 s longer in the gCAP group than in the VE group (8.2 ± 4.8 s vs. 4.2 ± 1.5 s; p < 0.001). However, the forceps method lasted 28 s longer than the others. On subgroup analysis by size, gCAP was more accurate for polyp size ≥ 5 mm. The gCAP method was more accurate for polyp size measurement than VE, especially for polyps ≥ 5 mm, and was more convenient than the forceps method.
Proteomic Analyses of Vitreous in Proliferative Diabetic Retinopathy: Prior Studies and Future Outlook

Vitreous fluid is becoming an increasingly popular medium for the study of retinal disease. Numerous studies have demonstrated that proteomic analysis of the vitreous from patients with proliferative diabetic retinopathy yields valuable molecular information regarding known and novel proteins and pathways involved in this disease. However, there is no standardized methodology for vitreous proteomic studies. Here, we share a suggested protocol for such studies and outline the various experimental and analytic methods that are currently available. We also review prior mass spectrometry-based proteomic studies of the vitreous from patients with proliferative diabetic retinopathy, discuss common pitfalls of these studies, and propose next steps for moving the field forward.
Enhanced Monitoring of Sleep Position in Sleep Apnea Patients: Smartphone Triaxial Accelerometry Compared with Video-Validated Position from Polysomnography

Poor sleep quality is a risk factor for multiple mental, cardiovascular, and cerebrovascular diseases. Certain sleep positions or excessive position changes can be related to some diseases and poor sleep quality. Nevertheless, sleep position is usually classified into four discrete values: supine, prone, left and right. An increase in sleep position resolution is necessary to better assess sleep position dynamics and to interpret more accurately intermediate sleep positions. This research aims to study the feasibility of smartphones as sleep position monitors by (1) developing algorithms to retrieve the sleep position angle from smartphone accelerometry; (2) monitoring the sleep position angle in patients with obstructive sleep apnea (OSA); (3) comparing the discretized sleep angle versus the four classic sleep positions obtained by the video-validated polysomnography (PSG); and (4) analyzing the presence of positional OSA (pOSA) related to its sleep angle of occurrence. Results from 19 OSA patients reveal that a higher resolution sleep position would help to better diagnose and treat patients with position-dependent diseases such as pOSA. They also show that smartphones are promising mHealth tools for enhanced position monitoring at hospitals and home, as they can provide sleep position with higher resolution than the gold-standard video-validated PSG.
Fabrication of Piezoelectric ZnO Nanowires Energy Harvester on Flexible Substrate Coated with Various Seed Layer Structures

Flexible piezoelectric nanogenerators (PENGs) are very attractive for mechanical energy harvesting due to their high potential for realizing self-powered sensors and low-power electronics. In this paper, a PENG that is based on zinc oxide (ZnO) nanowires (NWs) is fabricated on flexible and transparent Polydimethylsiloxane (PDMS) substrate. The ZnO NWs were deposited on two different seed layer structures, i.e., gold (Au)/ZnO and tin-doped indium-oxide (ITO)/ZnO, using hydrothermal synthesis. Along with the structural and morphological analyses of ZnO NWs, the electrical characterization was also investigated for ZnO NWs-based flexible PENGs. In order to evaluate the suitability of the PENG device structure, the electrical output performance was studied. By applying a periodic mechanical force of 3 N, the ZnO NWs-based flexible PENG generated a maximum root mean square (RMS) voltage and average power of 2.7 V and 64 nW, respectively. Moreover, the comparison between the fabricated device performances shows that a higher electrical output can be obtained when ITO/ZnO seed layer structure is adopted. The proposed ZnO NWs-based PENG structure can provide a flexible and cost-effective device for supplying portable electronics.
NutriCatt Protocol Improves Body Composition and Clinical Outcomes in Elderly Patients Undergoing Colorectal Surgery in ERAS Program: A Retrospective Cohort Study

Background: A poor body composition, often found in elderly patients, negatively impacts perioperative outcomes. We evaluated the effect of a perioperative nutritional protocol (NutriCatt) on body composition and clinical outcomes in a cohort of elderly patients undergoing colorectal surgery in a high-volume center adopting the ERAS program. Methods: 302 out of 332 elderly (>75 years) patients from 2015 to 2020 were identified. Patients were divided according to their adherence, into “NutriCatt + ERAS” (n = 166) or “standard ERAS” patients (n = 136). Anthropometric and bioelectrical impedance analysis data were evaluated for NutriCatt + ERAS patients. Complications, length of hospital stay (LOS), and other postoperative outcomes were compared between both groups. Results: In NutriCatt + ERAS patients, significant improvements of phase angle (pre-admission vs. admission 4.61 ± 0.79 vs. 4.84 ± 0.85; p = 0.001; pre-admission vs. discharge 4.61 ± 0.79 vs. 5.85 ± 0.73; p = 0.0002) and body cell mass (pre-admission vs. admission 22.4 ± 5.6 vs. 23.2 ± 5.7; p = 0.03; pre-admission vs. discharge 22.4 ± 5.6 vs. 23.1 ± 5.8; p = 0.02) were shown. NutriCatt + ERAS patients reported reduced LOS (p = 0.03) and severe complications (p = 0.03) compared to standard ERAS patients. A regression analysis confirmed the protective effect of the NutriCatt protocol on severe complications (OR 0.10, 95% CI 0.01–0.56; p = 0.009). Conclusions: The NutriCatt protocol improves clinical outcomes in elderly patients and should be recommended in ERAS colorectal surgery.