Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of intrathecal bupivacaine/morphine on quality of recovery in robot‐assisted radical prostatectomy: a randomised controlled trial[Link]

Robot‐assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty‐five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 μg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg−1 morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery‐15 (QoR‐15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR‐15 on postoperative day 1; median (IQR [range]) 10% (1–8 [−60% to 50%]) vs. 13% (5–24 [−6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1–7 [0–41 mg]) vs. 15 mg (12–20 [8–61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1–6 [0–9]) vs. 5 (3–7 [0–9]), p = 0.001; less bladder spasms (NRS 1 (0–2 [0–10]) vs. 2 (0–5 [0–10]), p = 0.001 and less sedation; NRS 2 (0–3 [0–10]) vs. 3 (2–6 [0–10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1–7 [0–10]) vs. 0 (0–1 [0–10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot‐assisted radical prostatectomy.
Early Recovery of Height Velocity in Prepubertal Children With Acute Lymphoblastic Leukemia Treated by a Short Intensive Phase Without Cranial Radiation Therapy

Supplemental Digital Content is available in the text. Purpose: There have been few reports on height disturbance in childhood acute lymphoblastic leukemia (ALL) patients treated without cranial radiation therapy (CRT). Our study aimed to clarify the critical period of growth in pediatric patients who were treated by the Japan Childhood Leukemia Study (JACLS) ALL-02 protocol, which involved short-term intensive treatment without CRT. Patients and Methods: A retrospective, cohort study was conducted for prepubertal children with B-precursor ALL who were diagnosed from July 2002 to November 2011 and treated by the JACLS ALL-02 protocol at Oita University Hospital. The heights were chronologically measured at pretreatment, after the intensive phase (INT), at the end of treatment (END), and at 1 to 5 year(s) posttreatment (POST 1 to 5). Results: Nine boys and 4 girls were enrolled. Z score of the height was reduced at INT and END. Delta Z scores of the height and Z score of height velocity were reduced from pretreatment to INT, and they demonstrated an early recovery during maintenance treatment in INT to END. Conclusions: Early recovery of delta Z scores of the height and Z score of height velocity was observed during the INT to END period. The shortened intensive phase without CRT may result in an adequate height in prepubertal ALL patients.
The emergence of classical BSE from atypical/Nor98 scrapie

Significance The origin of transmissible BSE in cattle remains unestablished. Sheep scrapie is a potential source of this known zoonotic. Here we investigated the capacity of sheep scrapie to propagate in bovine PrP transgenic mice. Unexpectedly, transmission of atypical but not classical scrapie in bovine PrP mice resulted in propagation of classical BSE prions. Detection of prion seeding activity by in vitro protein misfolding cyclic amplification demonstrated BSE prions in the original atypical scrapie isolates. BSE prion seeding activity was also detected in ovine PrP mice inoculated with limiting dilutions of atypical scrapie. Our data demonstrate that classical BSE prions can emerge during intra- and interspecies passage of atypical scrapie and provide an unprecedented insight into the evolution of mammalian prions. Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE.
Single amino acid mutation altered substrate specificity for L-glucose and inositol in scyllo-inositol dehydrogenase isolated from Paracoccus laeviglucosivorans

ABSTRACT scyllo-inositol dehydrogenase, isolated from Paracoccus laeviglucosivorans (Pl-sIDH), exhibits a broad substrate specificity: it oxidizes scyllo- and myo-inositols as well as L-glucose, converting L-glucose to L-glucono-1,5-lactone. Based on the crystal structures previously reported, Arg178 residue, located at the entry port of the catalytic site, seemed to be important for accepting substrates. Here, we report the role of Arg178 by using an alanine-substituted mutant for kinetic analysis as well as to determine the crystal structures. The wild-type Pl-sIDH exhibits the activity for scyllo-inositol most preferably followed by myo-inositol and L-glucose. On the contrary, the R178A mutant abolished the activities for both inositols, but remained active for L-glucose to the same extent as its wild-type. Based on the crystal structures of the mutant, the side chain of Asp191 flipped out of the substrate binding site. Therefore, Arg178 is important in positioning Asp191 correctly to exert its catalytic activities. Abbreviations: IDH: inositol dehydrogenase; LB: Luria-Bertani; kcat: catalyst rate constant; Km: Michaelis constant; NAD: nicotinamide dinucleotide; NADH: nicotinamide dinucleotide reduced form; PDB; Protein Data Bank; PDB entry: 6KTJ, 6KTK, 6KTL Graphical abstract R178A mutation of scyllo-inositol dehydrogenase (isolated from Paracoccus laeviglucosivorans) turned it to an L-glucose substrate-specific enzyme.
Photoreceptor disc membranes are formed through an Arp2/3-dependent lamellipodium-like mechanism

Significance Vertebrate photoreceptor cells contain a specialized organelle, the outer segment, which produces electrical responses to light. To maximize light capture efficiency, the outer segment is filled with hundreds of stacked membrane “discs” containing the molecular machinery responsible for performing visual signaling. Importantly, discs undergo continuous renewal throughout the lifetime of a photoreceptor. Our data suggest that new discs are formed through a mechanism analogous to the formation of lamellipodia in migrating cells. Each new disc is born as an evagination of the outer segment membrane driven by the expanding branched actin network. This work contributes to our understanding of the molecular mechanisms responsible for disc formation and guides future therapies directed at correcting defects in this process. The light-sensitive outer segment of the vertebrate photoreceptor is a highly modified primary cilium filled with disc-shaped membranes that provide a vast surface for efficient photon capture. The formation of each disc is initiated by a ciliary membrane evagination driven by an unknown molecular mechanism reportedly requiring actin polymerization. Since a distinct F-actin network resides precisely at the site of disc morphogenesis, we employed a unique proteomic approach to identify components of this network potentially driving disc morphogenesis. The only identified actin nucleator was the Arp2/3 complex, which induces the polymerization of branched actin networks. To investigate the potential involvement of Arp2/3 in the formation of new discs, we generated a conditional knockout mouse lacking its essential ArpC3 subunit in rod photoreceptors. This knockout resulted in the complete loss of the F-actin network specifically at the site of disc morphogenesis, with the time course of ArpC3 depletion correlating with the time course of F-actin loss. Without the actin network at this site, the initiation of new disc formation is completely halted, forcing all newly synthesized membrane material to be delivered to the several nascent discs whose morphogenesis had already been in progress. As a result, these discs undergo uncontrolled expansion instead of normal enclosure, which leads to formation of unusual, large membrane whorls. These data suggest a model of photoreceptor disc morphogenesis in which Arp2/3 initiates disc formation in a “lamellipodium-like” mechanism.
I/V BOLUS DEXMEDETOMIDINE ATTENUATES THE AIRWAY REFLEXES AND HEMODYNAMIC RESPONSES DURING EXTUBATION FOLLOWING GENERAL ANAESTHESIA

AIM: Aim of our study was to assess airway and hemodynamic changes during endotracheal extubation. OBJECTIVE: To evaluate the efficacy of IV dexmedetomidine in attenuating airway reflexes and hemodynamic responses during endotracheal extubation. MATERIAL AND METHODS: 60 patients of ASA grade I, II, & III, divided into two groups, of age between 20-50 years of both sexes, scheduled for receiving general anaesthesia in Gandhi Medical College and Hamidia Hospital, Bhopal (M.P.) Group I (n= 30) (Control Group): 10 ml of normal saline was given 15 min. before the end of surgery. Group II (n= 30): Injection Dexmedetomidine 0. 7µg/kg of body weight diluted in normal saline to prepare 10 ml of drug solution was given 15 min. before the end of surgery. Heart rate (HR) was recorded by ECG monitoring; Blood pressure (SBP and DBP) was recorded by non-invasive blood pressure monitoring, Respiratory rate (RR), Oxygen saturation. The pre-operative parameters were recorded before the induction of general anaesthesia. All the patients were observed for airway reflexes (coughing, breath-holding, laryngospasm and bronchospasm at extubation), Hemodynamic responses - HR, SBP DBP and arrythmias, Respiratory monitoring - RR and SpO2.HR, SBP, and DBP were recorded just before drug administration/basal value (T0) and 1 min. (T1), 3 min. (T2), and 5 min. (T3) after drug administration, at extubation (T4) and at 1 min. (T5), 5 min. (T6), 10 min. (T7), and 30 min. (T8), after extubation. RESULT: Analysis revealed that there was initially insignificant change in mean (±SD) HR, SBP, DBP in both the groups which became highly significant during extubation and remained significantly higher till the end of surgery. Change in the mean (±SD) respiratory rate and spo2of the both the groups were statistically insignificant throughout the study period. CONCLUSION: IV bolus dexmedetomidine is found very effective in attenuating these airway and hemodynamic reflexes without causing any un towards side effect or
Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma

Significance PDAC epithelial (E) and quasi-mesenchymal (QM) subtypes can be modulated by different therapies demonstrating the plasticity of PDAC cells that contributes to the heterogeneity of PDAC tumors and their intrinsic resistance to a broad spectrum of therapies. Understanding and monitoring the fluidity of PDAC E and QM states are critical to the development of improved clinical trial design to target these different subpopulations. Transcriptional profiling has defined pancreatic ductal adenocarcinoma (PDAC) into distinct subtypes with the majority being classical epithelial (E) or quasi-mesenchymal (QM). Despite clear differences in clinical behavior, growing evidence indicates these subtypes exist on a continuum with features of both subtypes present and suggestive of interconverting cell states. Here, we investigated the impact of different therapies being evaluated in PDAC on the phenotypic spectrum of the E/QM state. We demonstrate using RNA-sequencing and RNA-in situ hybridization (RNA-ISH) that FOLFIRINOX combination chemotherapy induces a common shift of both E and QM PDAC toward a more QM state in cell lines and patient tumors. In contrast, Vitamin D, another drug under clinical investigation in PDAC, induces distinct transcriptional responses in each PDAC subtype, with augmentation of the baseline E and QM state. Importantly, this translates to functional changes that increase metastatic propensity in QM PDAC, but decrease dissemination in E PDAC in vivo models. These data exemplify the importance of both the initial E/QM subtype and the plasticity of E/QM states in PDAC in influencing response to therapy, which highlights their relevance in guiding clinical trials.
Resurgence of an apex marine predator and the decline in prey body size

Significance Recent recoveries of marine mammal populations worldwide have heightened concerns for their potential impacts on global fisheries. While predator-induced reductions in prey abundance have been documented, trait-mediated changes in life-history characteristics are rarely considered. Here we provide a striking example of the impact of a resurging apex marine predator on a commercially important fish species through changes in prey life-history traits. We find that widespread declines in the body size of Chinook salmon over the past 50 y can be explained by intensified predation by growing populations of resident killer whales that selectively feed on large Chinook salmon, thus revealing a potential conflict between salmon fisheries and marine mammal conservation objectives. In light of recent recoveries of marine mammal populations worldwide and heightened concern about their impacts on marine food webs and global fisheries, it has become increasingly important to understand the potential impacts of large marine mammal predators on prey populations and their life-history traits. In coastal waters of the northeast Pacific Ocean, marine mammals have increased in abundance over the past 40 to 50 y, including fish-eating killer whales that feed primarily on Chinook salmon. Chinook salmon, a species of high cultural and economic value, have exhibited marked declines in average size and age throughout most of their North American range. This raises the question of whether size-selective predation by marine mammals is generating these trends in life-history characteristics. Here we show that increased predation since the 1970s, but not fishery selection alone, can explain the changes in age and size structure observed for Chinook salmon populations along the west coast of North America. Simulations suggest that the decline in mean size results from the selective removal of large fish and an evolutionary shift toward faster growth and earlier maturation caused by selection. Our conclusion that intensifying predation by fish-eating killer whales contributes to the continuing decline in Chinook salmon body size points to conflicting management and conservation objectives for these two iconic species.
Glucagon-Like Peptide-1 Receptors in the Kidney: Impact on renal autoregulation.

Glucagon-like peptide-1 (GLP-1) and strategies based on this blood sugar-reducing and appetite-suppressing hormone are used to treat obesity and type-2 diabetes. However, the GLP-1 receptor (GLP-1R) is also present in the kidney where it influences renal function. The effect of GLP-1 on the kidney varies between humans and rodents. The effect of GLP-1 on kidney function also seems to vary depending on its concentration and the physiological or pathological state of the kidney. In studies with rodents or humans, acute infusion of pharmacological doses of GLP-1 stimulates natriuresis and diuresis. However, the effect on the renal vasculature is less clear. In rodents, GLP-1 infusion increases renal plasma flow (RPF) and glomerular filtration rate (GFR), suggesting renal vasodilation. In humans, only a subset of the subjects exhibits increased RPF and GFR. Differential status of kidney function and changes renal vascular resistance of the preglomerular arterioles, may account for the different responses of the human subjects. Because renal function in type-2 diabetic patients is already at risk or compromised, understanding the effects of GLP-1R activation on kidney function in these patients is particularly important. This review examines the distribution of GLP-1R in the kidney and the effects elicited by GLP-1 or GLP-1R agonists. By integrating results from acute and chronic studies in healthy individuals and type-2 diabetic patients along with those from rodent studies, we provide insight into how GLP-1R activation affects renal function and autoregulation.
Doxorubicin concentration in brain remains high for one day after triolein emulsion infusion induced BBB opening

Abstract Aim: The purpose of this study was to assess changes in doxorubicin concentration in rabbit brain with respect to time after BBB opening induced by triolein emulsion infusion via a carotid artery and the mechanism of BBB opening. Materials and Methods: Doxorubicin (2.4 mg/kg) was infused immediately after triolein emulsion (1%) into rabbit carotid arteries. Bilateral hemispheres were harvested 2, 4, 6 12 and 24 h later and doxorubicin concentrations were measured fluorometrically. Doxorubicin concentration ratios of ipsilateral versus contralateral hemispheres were calculated, and a TEM study was performed to investigate the mechanism responsible for the increased vascular permeability induced by triolein. Results: Doxorubicin concentrations were higher in ipsilateral hemispheres at all time points, and peaked at 2 h after treatment. Doxorubicin was still detected in ipsilateral hemispheres at 24 h after treatment. TEM showed tight junction opening by triolein emulsion with lanthanum tracer spillage into neural interstitium and transcytotic vesicles. Conclusion: Doxorubicin was delivered into neural interstitium because of the increased vascular permeability of the BBB induced by triolein emulsion. Doxorubicin concentrations in brain peaked within 2 h of triolein and doxorubicin administration and remained high for 24 h. The study shows increased vascular permeability induced by triolein emulsion may involve paracellular and transcellular pathways.
An Online Database for Exploring Over 2,000 Arabidopsis Small RNA Libraries1[OPEN]

The Arabidopsis Small RNA Database is a user-friendly, web-based tool for exploring over 2,000 Arabidopsis sRNA-seq libraries. Small RNAs (sRNAs) play a wide range of important roles in plants, from maintaining genome stability and enhancing disease resistance to regulating developmental processes. Over the past decade, next-generation sequencing technologies have allowed us to explore the sRNA populations with unprecedented depth and accuracy. The community has accumulated a tremendous amount of sRNA sequencing (sRNA-seq) data from various genotypes, tissues, and treatments. However, it has become increasingly challenging to access these “big data” and extract useful information, particularly for researchers lacking sophisticated bioinformatics tools and expensive computational resources. Here, we constructed an online website, Arabidopsis Small RNA Database (ASRD, http://ipf.sustech.edu.cn/pub/asrd), that allows users to easily explore the information from publicly available Arabidopsis (Arabidopsis thaliana) sRNA libraries. Our database contains ∼2.3 billion sRNA reads, representing ∼250 million unique sequences from 2,024 sRNA-seq libraries. We downloaded the raw data for all libraries and reprocessed them with a unified pipeline so that the normalized abundance of any particular sRNA or the sum of abundances of sRNAs from a genic or transposable element region can be compared across all libraries. We also integrated an online Integrative Genomics Viewer browser into our Web site for convenient visualization. ASRD is a free, web-accessible, and user-friendly database that supports the direct query of over 2,000 Arabidopsis sRNA-seq libraries. We believe this resource will help plant researchers take advantage of the vast next-generation sequencing datasets available in the public domain.
Bi-Layered Polymer Carriers with Surface Modification by Electrospinning for Potential Wound Care Applications

Polymeric wound dressings with advanced properties are highly preferred formulations to promote the tissue healing process in wound care. In this study, a combinational technique was investigated for the fabrication of bi-layered carriers from a blend of polyvinyl alcohol (PVA) and sodium alginate (SA). The bi-layered carriers were prepared by solvent casting in combination with two surface modification approaches: electrospinning or three-dimensional (3D) printing. The bi-layered carriers were characterized and evaluated in terms of physical, physicochemical, adhesive properties and for the safety and biological cell behavior. In addition, an initial inkjet printing trial for the incorporation of bioactive substances for drug delivery purposes was performed. The solvent cast (SC) film served as a robust base layer. The bi-layered carriers with electrospun nanofibers (NFs) as the surface layer showed improved physical durability and decreased adhesiveness compared to the SC film and bi-layered carriers with patterned 3D printed layer. Thus, these bi-layered carriers presented favorable properties for dermal use with minimal tissue damage. In addition, electrospun NFs on SC films (bi-layered SC/NF carrier) provided the best physical structure for the cell adhesion and proliferation as the highest cell viability was measured compared to the SC film and the carrier with patterned 3D printed layer (bi-layered SC/3D carrier). The surface properties of the bi-layered carriers with electrospun NFs showed great potential to be utilized in advanced technical approach with inkjet printing for the fabrication of bioactive wound dressings.