Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre‐treatment metabolic tumour volume and total lesion glycolysis are superior to conventional positron‐emission tomography/computed tomography variables for outcome prediction in patients with newly diagnosed multiple myeloma in clinical practice

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are positron‐emission tomography/computed tomography (PET/CT) variables for predicting multiple myeloma’s (MM) outcome. We retrospectively investigated and compared the predictive value of MTV, TLG and high‐risk PET/CT variables in clinical practice in 185 patients with newly diagnosed symptomatic MM. High‐risk PET/CT findings were defined as the presence of at least one of the following: more than three focal lesions, maximum standardised uptake value (SUVmax) >4·2 and extramedullary disease. MTV was defined as the volume of myeloma lesions visualised on PET/CT with SUV ≥ 2·5. TLG was calculated as the sum of the product of the average SUV and MTV of all lesions. The mortality prediction optimal cut‐off values for MTV and TLG were 56·4 cm3 and 166·4 g, respectively. High‐burden MTV (≥56·4 cm3), TLG (≥166·4 g) and high‐risk PET/CT findings differed significantly in progression‐free survival (PFS) and overall survival (OS). High‐burden MTV and TLG findings also predicted survival outcomes in young patients (age <75 years) and patients with high‐risk chromosomal abnormalities. High‐burden MTV and TLG independently predicted both worse PFS and OS. Pre‐treatment MTV and TLG independently predicted survival outcomes in clinical practice and may be more useful than high‐risk PET/CT variables.
Wearable Cardiorespiratory Monitoring Employing a Multimodal Digital Patch Stethoscope: Estimation of ECG, PEP, LVET and Respiration Using a 55 mm Single-Lead ECG and Phonocardiogram

Cardiovascular diseases are the main cause of death worldwide, with sleep disordered breathing being a further aggravating factor. Respiratory illnesses are the third leading cause of death amongst the noncommunicable diseases. The current COVID-19 pandemic, however, also highlights the impact of communicable respiratory syndromes. In the clinical routine, prolonged postanesthetic respiratory instability worsens the patient outcome. Even though early and continuous, long-term cardiorespiratory monitoring has been proposed or even proven to be beneficial in several situations, implementations thereof are sparse. We employed our recently presented, multimodal patch stethoscope to estimate Einthoven electrocardiogram (ECG) Lead I and II from a single 55 mm ECG lead. Using the stethoscope and ECG subsystems, the pre-ejection period (PEP) and left ventricular ejection time (LVET) were estimated. ECG-derived respiration techniques were used in conjunction with a novel, phonocardiogram-derived respiration approach to extract respiratory parameters. Medical-grade references were the SOMNOmedics SOMNO HDTM and Osypka ICON-CoreTM. In a study including 10 healthy subjects, we analyzed the performances in the supine, lateral, and prone position. Einthoven I and II estimations yielded correlations exceeding 0.97. LVET and PEP estimation errors were 10% and 21%, respectively. Respiratory rates were estimated with mean absolute errors below 1.2 bpm, and the respiratory signal yielded a correlation of 0.66. We conclude that the estimation of ECG, PEP, LVET, and respiratory parameters is feasible using a wearable, multimodal acquisition device and encourage further research in multimodal signal fusion for respiratory signal estimation.
Bovistol B, bovistol D and strossmayerin: Sesquiterpene metabolites from the culture filtrate of the basidiomycete Coprinopsis strossmayeri

Basidiomycete fungi are a rich source of natural products with a diverse array of potentially exploitable bioactivities. Two dimeric sesquiterpenes, bovistol B (1) and D (2), and one monomeric sesquiterpene, strossmayerin (7), were isolated from the culture filtrate of the basidiomycete fungus Coprinopsis strossmayeri. The structures were determined through a combination of MS and 1D/2D NMR spectroscopic techniques. Likely monomeric precursors, identified on the basis of HRMS analysis, allow a plausible biosynthetic pathway to be proposed for the biosynthesis of 1 and 2, involving the dimerisation of the monomer through a hetero-Diels-Alder mechanism. A gene cluster, including a putative sesquiterpene 1–11 cyclase, was identified through phylogenetic and RNA-seq analysis, and is proposed to be responsible for the biosynthesis of 1 and 2.
Length of Clinical Shift on Quality of Care, Learning Outcomes, and Satisfaction in Prelicensure Nursing Programs

Supplemental digital content is available in the text. Background Some schools and nursing care organizations have implemented 12-hour shifts for students' clinical experiences. Purpose The aim of this review was to identify how student 12-hour shifts compared to shifts of less than 12 hours influence patient safety, care quality, learning outcomes, and student, faculty, and staff satisfaction. Methods Searches for academic literature using electronic databases resulted in 13 primary research articles covering the period between 1982 and 2018. Results During longer clinical shifts, no change in patient safety events occurred. Students and clinical staff perceived care quality was maintained or influenced positively. Faculty were undecided or minimally did not believe care quality improved. While students perceived meeting learning outcomes, faculty perceptions were divided. Students were satisfied with longer shifts; however, the satisfaction of faculty and clinical staff was mixed. Conclusions Within realms of patient safety, care quality, learning outcomes, and student, faculty, and clinical staff satisfaction, research has been insufficient and inconclusive regarding 12-hour student shifts.
Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions

We report the in vivo regulation of Inosine-5´-monophosphate dehydrogenase 1 (IMPDH1) in the retina. IMPDH1 catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides, impacting the cellular pools of GMP, GDP and GTP. Guanine nucleotide homeostasis is central to photoreceptor cells, where cGMP is the signal transducing molecule in the light response. Mutations in IMPDH1 lead to inherited blindness. We unveil a light-dependent phosphorylation of retinal IMPDH1 at Thr159/Ser160 in the Bateman domain that desensitizes the enzyme to allosteric inhibition by GDP/GTP. When exposed to bright light, living mice increase the rate of GTP and ATP synthesis in their retinas; concomitant with IMPDH1 aggregate formation at the outer segment layer. Inhibiting IMPDH activity in living mice delays rod mass recovery. We unveil a novel mechanism of regulation of IMPDH1 in vivo, important for understanding GTP homeostasis in the retina and the pathogenesis of adRP10 IMPDH1 mutations.
Fetal bone development in the lowland paca (Cuniculus paca, Rodentia, Cuniculidae) determined using ultrasonography

Studying the timing of the main events of embryonic and fetal development may clarify the strategies adopted by species to maximize neonatal survival and the consequences of these events for their life history. This study describes bone development during the fetal phase of the lowland paca (Cuniculus paca), comparing it with other precocial or altricial species, and its relationship with the species’ adaptive strategies. A total of 102 embryos/fetuses obtained over the course of 17 years through collaboration with local subsistence hunters in the Amazon were analyzed. Measurements of mineralization of the axial and appendicular skeletons were performed by ultrasonography using a 10–18‐MHz linear transducer. The chronological order of occurrence of mineralization in relation to the total dorsal length (TDL) was: skull (TDL = 4.1 cm); vertebral bodies (TDL = 4.6 cm); scapula, humerus, radius, ulna, ilium, ischium, femur, tibia, and fibula (TDL = 6.7 cm); ribs (TDL = 7.8 cm); clavicle (TDL = 8.5 cm); metacarpi/metatarsi (TDL = 11 cm); phalanges (TDL = 15 cm); tarsus (TDL = 18 cm); patella (TDL = 23 cm); and carpus (TDL = 27.2 cm). Secondary ossification centers first appeared in the femoral distal epiphysis (TDL = 16.6 cm) and tibial proximal epiphysis (TDL = 18.4 cm). Advanced fetuses (TDL > 30 cm, 97% gestational period) presented mineralization in all primary and most secondary centers. Compared to other species, paca neonates have a well‐developed skeletal system at birth, which is important for their independent postnatal locomotion. Our results may contribute to the monitoring of bone development in other wild species, helping us to understand their life history, and serving as parameters for comparisons between precocial and altricial mammals.
Microstructure Simulation and Constitutive Modelling of Magnetorheological Fluids Based on the Hexagonal Close-packed Structure

This paper presents a new constitutive model of high particles concentrated magnetorheological fluids (MRFs) that is based on the hexagonal close-packed structure, which can reflect the micro-structures of the particles under the magnetic field. Firstly, the particle dynamic simulations for the forces sustained by carbonyl iron powder (CIP) particles of MRFs are performed in order to investigate the particles chain-forming process at different time nodes. Subsequently, according to the force analyses, a hexagonal close-packed structure, which differs from the existing single-chain structure and body-cantered cubic structure, is adopted to formulate a constitutive model of MRFs with high concentration of the magnetic-responsive particles. Several experiments are performed while considering crucial factors that influence on the chain-forming mechanism and, hence, change the field-dependent shear yield stress in order to validate the proposed model. These factors include the magnetic induction intensity, volume fraction and radius of CIP particles, and surfactant coating thickness. It is shown that the proposed modeling approach can predict the field-dependent shear yield stress much better than the single-chain model. In addition, it is identified that the shear yield stress is increased as the particle volume fraction increases and surfactant coating thickness decreases. It is believed that the proposed constitutive model can be effectively used to estimate the field-dependent shear yield stress of MRFs with a high concentration of iron particles.
Study on the Influence of Social Capital on Farmers’ Participation in Rural Domestic Sewage Treatment in Nanjing, China

Rural domestic sewage treatment is not only an important part of the renovation of rural human settlements, but also a major measure to revitalize those areas. In the absence of extensive participation by farmers, it is difficult to achieve desired results. From the theoretical analysis of the influence of social capital on farmers’ participation, and based on the survey data of farmers in Nanjing, Jiangsu Province, this study used a logistic model to analyze the influence of social capital and personal, family, and awareness characteristics of farmers on their participation levels. Social capital plays a significant role in promoting farmers’ participation, and the contribution of its core variables is in the following order: social norms > social trust > social networks. Among the control variables, the need for domestic sewage treatment, participation in environmental training, educational level, and participation in a village cadre significantly enhance farmers’ participation levels. Consequently, promotion of rural domestic sewage treatment should include improvement of farmers’ social trust, social norms, and social networks, to enhance social capital. Publicity and education should be reinforced, and environmental training should be carried out to improve farmers’ awareness and sense of responsibility, leading them to active participation.
Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells

Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5–1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.
Comparison of semirigid ureteroscopy, flexible ureteroscopy, and shock wave lithotripsy for initial treatment of 11-20 mm proximal ureteral stones.

OBJECTIVE We aimed to retrospectively evaluate the effectiveness and safety of flexible ureteroscopy (f-URS), semirigid ureteroscopy (sr-URS), and shock wave lithotripsy (SWL) to treat single 11-20 mm stones in the proximal ureter. MATERIALS AND METHODS Patients treated at our clinic for 11-20 mm single stones in the proximal ureter who underwent f-URS, sr-URS or SWL as initial lithotripsy methods were compared in terms of their clinical characteristics and treatment outcomes. RESULTS A comparison among 201 patients who had undergone f-URS, 119 patients who had undergone sr-URS, and 162 patients who had undergone SWL showed no significant baseline differences in patients' demographic and stone characteristics. Stone-free rates on the 15th day and 3rd month were higher with f-URS (89.6% and 97%, respectively) than with sr-URS (67.2% and 94.1%, respectively) and SWL (41.4% and 79.0%, respectively; all p < 0.001). Retreatment rates were significantly higher with SWL than with the other two modalities (p < 0.001); auxiliary procedure rates were significantly lower with f-URS than with the other two modalities (p < 0.001). Treatment-related complication rate at the end of the 3rd month was lower with f-URS than with SWL (p = 0.022). Furthermore, f-URS was more effective than sr-URS for treating impacted stones. CONCLUSIONS We found that f-URS was highly successful as an initial lithotripsy procedure for medium-sized proximal ureteral stones, and it helped achieve early stone-free outcomes with a lower need for retreatment and auxiliary procedures, lower complication rates, and higher effectiveness on the impacted stones compared with sr-URS and SWL.
HMGB1 in nasal inflammatory diseases: a reappraisal 30 years after its discovery

ABSTRACT Introduction High mobility group protein box 1 (HMGB1) is a protein belonging to the alarmin family. HMGB1 has a relevant role in starting the inflammatory cascade by means of receptors, such as RAGE and TLR. HMGB1 supports transcription of many genes in interactions with many transcription factors, including NF-kB. The axis HMGB1-RAGE-NF-kB has, therefore, a pivotal role in the inflammatory cascade. HMGB1 controls the production of several pro-inflammatory cytokines and the proliferation and activation of many inflammatory cells. Areas covered The present report concerns the role of HMGB1 in nasal inflammatory disorders, including allergic and non-allergic rhinitis, and chronic rhinosinusitis with nasal polyps. HMGB1 modulation has been the aim of several studies. The literature search included recent papers that covered this topic. Expert opinion As HMGB1 has a pivotal role in inflammatory events, its modulation could be attractive for designing new therapeutic strategies. In this regard, glycyrrhetic acid (GA), the active component of Glycyrrhiza glabra, can efficiently block HMGB1. Promising reports seem to suggest that GA could exert favorable anti-inflammatory activity in patients with nasal inflammatory disorders.
Ontogenetic changes of tissue compartmentalization and bone type distribution in the humerus of Soay sheep

We studied ontogenetic changes of histomorphological features and bone type distribution in the humeral midshaft region of Soay sheep from three postnatal age classes (13, 25, and 33 months). Our study demonstrated a marked change of bone type distribution in the humeri with age. In the cortical midshaft region of 13‐month‐old individuals, periosteal fibrolamellar bone was the dominating bone type. This indicates a rapid bone growth during the first year of life, which was only interrupted by a seasonal growth arrest in the animals’ first winter. In individuals from the two older age classes, periosteal lamellar‐zonal bone and intermediate fibrolamellar bone had been formed at the periosteal surface, and endosteal lamellar‐zonal bone at the endosteal surface. These bone types are indicative of a reduced bone growth rate. A marked reduction in radial growth was already recorded in the 25‐month‐old individuals. Distribution and extent of secondary bone showed a marked bilateral symmetry in the humeri of individual sheep. The presence of secondary bone was largely restricted to the anterior (cranial) and the medial cortical areas. This characteristic distribution of remodeling activity within the humeral cortex of sheep is consistent with the view that remodeling activity is largely caused by compressive stress. Our study further demonstrated the presence of a considerable cortical drift in the sheep humeri over the study period, with endosteal resorption occurring predominantly in the posterior (caudal) quadrant and formation of a prominent endosteal lamellar pocket in the anterior (cranial) and medial cortical quadrants.
Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets

Translation of transplanted alginate‐encapsulated pancreatic islets to treat type 1 diabetes has been hindered by inconsistent long‐term efficacy. This loss of graft function can be partially attributed to islet dysfunction associated with the destruction of extracellular matrix (ECM) interactions during the islet isolation process as well as immunosuppression‐associated side effects. This study aims at recapitulating islet‐ECM interactions by the direct functionalization of alginate with the ECM‐derived peptides RGD, LRE, YIGSR, PDGEA, and PDSGR. Peptide functionalization is controlled in a concentration‐dependent manner and its presentation is found to be homogeneous across the microcapsule environment. Preweaned porcine islets are encapsulated in peptide‐functionalized alginate microcapsules, and those encapsulated in RGD‐functionalized alginate displays enhanced viability and glucose‐stimulated insulin release. Effects are RGD‐specific and not observed with its scrambled control RDG nor with LRE, YIGSR, PDGEA, and PDSGR. This study supports the sustained presentation of ECM‐derived peptides in helping to maintain health of encapsulated pancreatic islets and may aid in prolonging longevity of encapsulated islet grafts.
A New Anatomy Finding of Levator Aponeurosis and Müller Muscle at Pretarsal Plate in Asian Males

Purpose: To examine the fine anatomic structures between levator aponeurosis and Müller muscle in front of the tarsus. Materials and Methods: Postmortem specimens of 6 Chinese males (5 elderly men, aging from 68 to 86 years; 1 child, 10 years old) were used. A 3-μm thickness sagittal section of the central part of the upper eyelid was prepared, and the samples were examined microscopically by using hematoxylin–eosin, Masson trichrome, and anti-smooth muscle actin antibodies staining. Results: There are 2 new findings in this study, one is the posterior layer of the levator aponeurosis and the other is the extensions of Müller muscle. The posterior levator aponeurosis had different insertion patterns that approximately paralleled the extension line of the levator aponeurosis at the confluence of attachment site of the orbital septum on the levator superioris. Below the confluence, it took the form of a layered insertion, and then extended to the orbicularis oculi muscle and subcutaneous tissue rather than inserting directly into tarsus. The Müller muscle was a multilayered structure at the upper border of tarsus. The superior Müller muscle extended above the peripheral arcade, and the inferior Müller muscle tendon was attached to the surface of tarsus with an Umbrella-shaped fiber. Conclusions: The authors discovered that the levator aponeurosis had different insertion patterns of the posterior layers. The Müller muscle gave branches at the peripheral arcade: the anterior one crossed the peripheral arcade and extended to the tarsus, and the posterior one attached and extended to the tarsus. This study found that the posterior layer of levator aponeurosis had different extensions at the attachment site of the orbital septum on the levator superioris; and we found that Müller muscle was a multilayer structure at the upper border of tarsus.
Male sterile 305 Mutation Leads the Misregulation of Anther Cuticle Formation by Disrupting Lipid Metabolism in Maize

The anther cuticle, which is mainly composed of lipid polymers, functions as physical barriers to protect genetic material intact; however, the mechanism of lipid biosynthesis in maize (Zea mays. L.) anther remains unclear. Herein, we report a male sterile mutant, male sterile 305 (ms305), in maize. It was shown that the mutant displayed a defective anther tapetum development and premature microspore degradation. Three pathways that are associated with the development of male sterile, including phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, as well as cutin, suberine, and wax biosynthesis, were identified by transcriptome analysis. Gas chromatography-mass spectrometry disclosed that the content of cutin in ms305 anther was significantly lower than that of fertile siblings during the abortion stage, so did the total fatty acids, which indicated that ms305 mutation might lead to blocked synthesis of cutin and fatty acids in anther. Lipidome analysis uncovered that the content of phosphatidylcholine, phosphatidylserine, diacylglycerol, monogalactosyldiacylglycerol, and digalactosyldiacylglycerol in ms305 anther was significantly lower when compared with its fertile siblings, which suggested that ms305 mutation disrupted lipid synthesis. In conclusion, our findings indicated that ms305 might affect anther cuticle and microspore development by regulating the temporal progression of the lipidome in maize.