Miracle-dz/UniFAR-FTUs huggingface dataset:
Integration of RNA-seq and RNAi reveals the contribution of znuA gene to the pathogenicity of Pseudomonas plecoglossicida and to the immune response of Epinephelus coioides.

Pseudomonas plecoglossicida is an important pathogen in aquaculture and causes serious economic losses. Our previous study indicated that znuA gene might play an important role in the pathogenicity of P. plecoglossicida. Five shRNAs were designed and synthesized to silence the znuA gene of P. plecoglossicida. Two of the five mutants of P. plecoglossicida exhibited significant reduction in the expression level of znuA mRNA with different efficiencies. The mutant with the highest silencing efficiency of 89.2% was chosen for further studies. Intrapleural injection of the znuA-RNAi strain at a dose of 105 cfu/fish did not cause the death of Epinephelus coioides, and no significant signs were observed at the spleen surface of infected E. coioides, while the counterpart E. coioides infected by the same dose of wild-type strain of P. plecoglossicida all died in 5 days post-infection (dpi). The expression of znuA gene of znuA-RNAi strain in E. coioides was always lower than that in wild-type strain of P. plecoglossicida. The pathogen load in the early stage of infection was higher than that in the later stage of infection. Although the infection of the znuA-RNAi strain of P. plecoglossicida could induce the production of antibodies in E. coioides, it failed to produce a good immune protection against the infection of wild-type strain of P. plecoglossicida. Compared with the transcriptome data of E. coioides infected by the wild-type strain of P. plecoglossicida, the transcriptome data of E. coioides infected by the znuA-RNAi strain of P. plecoglossicida have altered significantly. Among them, KEGG enrichment analysis showed that the focal adhesion pathway was significantly enriched and exhibited the largest number of 302 DEMs (differentially expressed mRNAs). These results showed that the immune response of E. coioides to P. plecoglossicida infection was significantly affected by the RNAi of znuA gene.
Role of supplemental teriparatide therapy in management of osteoporotic intertrochanteric femur fractures.

BACKGROUND Despite the surgical advances, obtaining the desired outcome in osteoporotic intertrochanteric femur fractures is still a tough row to hoe for the surgeons. Consequently, the interest of the researchers has shifted towards establishing a holistic approach for managing such injuries. Teriparatide, a recombinant form of human parathyroid hormone, is a novel drug that has been proved to hasten fracture healing and in both animals and humans. We attempted to evaluate the influence of Teriparatide therapy in surgically fixed osteoporotic intertrochanteric femur fractures and provide the groundwork for further research in this area. METHODS The results of osteoporotic patients who underwent only Proximal Femur Nailing [PFN] for intertrochanteric femur fractures were prospectively compared to the patients who received an additional Teriparatide therapy. We aimed to identify the effect of Teriparatide on the time to fracture union, bone mineral density [BMD], and other fracture related post-operative complications. The functional outcome was assessed using the Lower extremity functional scale [LEFS]. RESULTS All patients were followed up for 6 months by which time all the fractures united. However, in the Teriparatide group, time to fracture union was shortened by about 2 weeks and improvement in BMD and functional outcome were significantly better. The rate of migration of the helical, varus collapse, and femoral shortening did not show any relevant difference. CONCLUSION Our preliminary attempt shows that early union coupled with better functional improvement and a substantial increase in BMD tips the balance in favour of the Teriparatide therapy in osteoporotic patients with intertrochanteric femur fractures. Well-designed clinical trials conducted in a similar vein are further required to support our claim.
Effects of sevoflurane and adenosine receptor antagonist on the sugammadex‐induced recovery from rocuronium‐induced neuromuscular blockade in rodent phrenic nerve–hemidiaphragm tissue specimens

Sevoflurane affects on the A1 receptor in the central nervous system and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. In this study, phrenic nerve–hemidiaphragm tissue specimens were obtained from 40 Sprague–Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train‐of‐four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2‐chloroadenosine (CADO), SEVO, or SLV320 + SEVO groups. In the CADO and SLV320 + SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium‐induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320 + SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400–500 μM for 10 min. Sugammadex‐induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. T1 recovery in the SEVO and CADO groups was significantly delayed compared with the control and SLV320 + SEVO groups (p < .05). In conclusion, sevoflurane affects on the A1 receptor at the neuromuscular junction and delays sugammadex‐induced recovery from neuromuscular blockade.
The effectiveness of arthroscopy assisted fixation of Schatzker types I-III tibial plateau fractures: our experience at a tertiary centre.

BACKGROUND Tibial condyle fractures are high energy injuries which require anatomical reduction and stable fixation for early mobilisation of the knee joint. Arthroscopy assisted fixation of these fractures provide additional benefits of minimal dissection, accurate visualisation of the articular surface and faster rehabilitation. The present study describes our experience with this technique. MATERIALS & METHODS Patients in the age group 15-65 years, presenting with closed tibial plateau fractures (Schatzker types I, II, III) at the advanced trauma centre of our institute within 3 weeks of injury, were recruited for this prospective case series. Open fractures, fractures of types IV, V and VI, fractures with associated knee dislocation, fractures presenting after 3 weeks and polytrauma patients with head injuries and/or blunt trauma to chest/abdomen, were excluded. Patients were evaluated according to Rasmussen numerical subjective evaluation chart at a minimum follow up of 6 months. RESULTS There were 5 fractures of Schatzker type I, 8 of type II and 2 of type III, which were scoped and fixed percutaneously. The mean age of the 15 patients was 34.2 years with male to female ratio of 4:1. Diagnostic arthroscopy detected co existent lateral meniscal tears (peripheral) in 2 cases, while 1 case had a contused anterior cruciate ligament. Fixation of the fractures were done by 1 or 2 percutaneous screws in 9/15 cases; buttress plating in 4/15 cases and combination of plate and screw in 2/15 cases. The average overall Rasmussen score was 28.2/30 (range 22-30) and there were 1 patient each with postoperative stiffness and screw prominence while 3 cases had extensor lags. CONCLUSION The aim of this combination procedure is stable fixation by minimally invasive methods; this reduces surgical insult, improves articular surface visualisation, allows management of concomitant ligament injuries, and patients can be rapidly mobilised. Case selection is extremely important for good results.
PyCO2SYS v1.7: marine carbonate system calculations in Python

Oceanic dissolved inorganic carbon (TC) is the largest pool of carbon that interacts considerably with the atmosphere on human timescales. Oceanic TC is increasing through uptake of anthropogenic carbon dioxide (CO2), and seawater pH is decreasing as a consequence. Both the exchange of CO2 between ocean and atmosphere and the pH response are governed by a set of parameters that interact through chemical equilibria, collectively known as the marine carbonate system. To investigate these processes, at least two of the marine carbonate system’s parameters are typically measured — most commonly, two from 5 TC, total alkalinity (AT), pH, and seawater CO2 fugacity (fCO2 ; or its partial pressure, pCO2 , or its dry-air mole fraction, xCO2 ) — from which the remaining parameters can be calculated and the equilibrium state of seawater solved. Several software tools exist to carry out these calculations, but no fully functional and rigorously validated tool was previously available for Python, a popular scientific programming language. Here, we present PyCO2SYS, a Python package intended to fill this capability gap. We describe the elements of PyCO2SYS that have been inherited from the existing CO2SYS family of software and explain 10 subsequent adjustments and improvements. For example, PyCO2SYS uses automatic differentiation to solve the marine carbonate system and calculate chemical buffer factors, ensuring that the effect of every solute and reaction is accurately included in all its results. We validate PyCO2SYS with internal consistency tests and comparisons against other software, showing that PyCO2SYS produces results that are either virtually identical or different for known reasons, with the differences negligible for all practical purposes. We discuss new insights that arose during the development process, for example that the marine car15 bonate system cannot be unambiguously solved from the total alkalinity and carbonate ion parameter pair. Finally, we consider potential future developments to PyCO2SYS and discuss the outlook for this and other software for solving the marine carbonate system. The code for PyCO2SYS is distributed via GitHub (https://github.com/mvdh7/PyCO2SYS) under the GNU General Public License v3, archived on Zenodo (Humphreys et al., 2021), and documented online (https://PyCO2SYS.readthedocs.io). 1 20 https://doi.org/10.5194/gmd-2021-159 Preprint. Discussion started: 8 June 2021 c © Author(s) 2021. CC BY 4.0 License.
A Practical Approach for Multi-Scale Performance Analysis of Internet Traffic

: Recent studies suggest that long-memory property in nowadays internet traffic shows a complicated scaling behavior: unlike the unchanged Hurst parameter of a self-similar process, scaling exponents of such processes change over time or scale ranges. In this paper, we propose a practical method, which uses the simple FBM process, to model long-range dependent traffic with changing scaling exponents over time scales. By using multiple self-similar processes to capture the statistical properties in different time scales, queueing performance of the multi-scale natured traffic can be presented by a composed performance curve produced by each self-similar process. Simulation results using traffic data measured from a backbone network is used to show the efficiency of our method.
Sequential Halving Applied to Trees Tristan Cazenave

Monte Carlo Tree Search (MCTS) is state of the art for multiple games and problems. The base algorithm currently used for Monte Carlo Tree Search is UCT. We propose an alternative Monte Carlo Tree Search algorithm: Sequential Halving applied to Trees (SHOT). It has multiple advantages over UCT: it spends less time in the tree, it uses less memory, it is parameter free, at equal time settings it beats UCT for a complex combinatorial game and it can be efficiently parallelized.
Being in a queer time: Exploring the influence of the COVID‐19 pandemic on LGBTQ+ body image

Abstract Aim The isolating public health measures mandated during the COVID‐19 pandemic had complex influences on the lives and body image of lesbian, gay, bisexual, trans, and queer individuals (LGBTQ+) in Canada. The aim of this study was to explore the impact the COVID‐19 pandemic had on body image for LGBTQ+ Canadians. Methods The qualitative research process was guided by queer theory and poststructuralism and consisted of an online survey with open‐ended questions and semi‐structured virtual interviews. A total of 70 self‐identifying LGBTQ+ individuals completed the survey, and eight individuals partook in the interviews. Responses were analysed using Foucauldian discourse analysis. Results Four major discursive considerations were found to shape participants' experiences, including, (a) time for reflection, (b) time away from social surveillance, (c) time to work on oneself, and (d) time to (dis)connect. Woven through these considerations were social discourses of hetero‐cis‐normativity, healthism, and resistance. Discussion The COVID‐19 pandemic was a ‘queer time’ for LGBTQ+ people. Competing social discourses created complex and often contradictory meanings of bodies and body image. COVID‐19‐related self‐isolation was for some participants a reprieve from constant body monitoring while for others it was a time of continued pressure to embody body ideals. Participants suggested that nutritional messages during such times be ones of compassion and non‐judgement of bodies.
A ferroptosis-related gene signature for graft loss prediction following renal allograft

ABSTRACT Allogeneic kidney transplantation (renal allograft) is the most effective treatment for advanced kidney disease. Previous studies have indicated that ferroptosis participates in the progression of acute kidney injury and renal transplant failure. However, few studies have evaluated the prognostic value of ferroptosis on renal transplantation outcomes. In this study, a total of 22 differentially expressed ferroptosis-related genes (DFGs) were identified, which were mainly enriched in infection-related pathways. Next, a ferroptosis-related gene signature, including GA-binding protein transcription factor subunit beta 1 (GABPB1), cyclin-dependent kinase inhibitor 1A (CDKN1A), Toll-like receptor 4 (TLR4), C-X-C motif chemokine ligand 2 (CXCL2), caveolin 1 (CAV1), and ribonucleotide reductase subunit M2 (RRM2), was constructed to predict graft loss following renal allograft. Moreover, receiver operating characteristic (ROC) curves (area under the ROC curve [AUC] > 0.8) demonstrated the accuracy of the gene signature and univariate Cox analysis suggested that the gene signature could play an independent role in graft loss (p < 0.05). Furthermore, the nomogram and calibration plots also indicated the good prognostic capability of the gene signature. Finally, immune-related and cytokine signaling pathways were mostly enriched in renal allograft patients with poor outcomes. Considered together, a ferroptosis-related gene signature and nomogram based on DFGs were created to predict the 1-, 2- and 3- year graft loss probability of renal allograft patients.The gene signature could serve as a valuable biomarker for predicting graft loss, contributing to improving the outcome of allogeneic kidney transplantation. GRAPHICAL ABSTRACT
Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas

A mathematical model successfully estimates malignant transformation-free survival and reveals a link between genetic alterations and progression, identifying precision medicine approaches for optimal treatment of IDH-mutant low-grade gliomas. Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDHmut/1p19qcodel and IDHmut/1p19qnoncodel) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data. These analyses showed that tumor mutational burden correlated positively with malignant transformation rate, and chemotherapy and radiotherapy significantly suppressed tumor growth but increased malignant transformation rate per cell by 1.8 to 2.8 times compared with before treatment. This model revealed that prompt adjuvant chemoradiotherapy prolonged malignant transformation-free survival in small IDHmut-LGGs (≤ 50 cm3). Furthermore, optimal treatment differed according to genetic alterations for large IDHmut-LGGs (> 50 cm3); adjuvant therapies delayed malignant transformation in IDHmut/1p19qnoncodel but often accelerated it in IDHmut/1p19qcodel. Notably, PI3K mutation was not associated with malignant transformation but increased net postoperative proliferation rate and decreased malignant transformation-free survival, prompting the need for adjuvant therapy in IDHmut/1p19qcodel. Overall, this model uncovered therapeutic strategies that could prevent malignant transformation and, consequently, improve overall survival in patients with IDHmut-LGGs. Significance: A mathematical model successfully estimates malignant transformation-free survival and reveals a link between genetic alterations and progression, identifying precision medicine approaches for optimal treatment of IDH-mutant low-grade gliomas.
An in silico scientific basis for LL‐37 as a therapeutic for Covid‐19

A multi‐pronged approach with help in all forms possible is essential to completely overcome the Covid‐19 pandemic. There is a requirement to research as many new and different types of approaches as possible to cater to the entire world population, complementing the vaccines with promising results. The need is also because SARS‐CoV‐2 has several unknown or variable facets which get revealed from time to time. In this work, in silico scientific findings are presented, which are indicative of the potential for the use of the LL‐37 human anti‐microbial peptide as a therapeutic against SARS‐CoV‐2. This indication is based on the high structural similarity of LL‐37 to the N‐terminal helix, with which the virus interacts, of the receptor for SARS‐CoV‐2, Angiotensin Converting Enzyme 2. Moreover, there is positive prediction of binding of LL‐37 to the receptor‐binding domain of SARS‐CoV‐2; this is the first study to have described this interaction. In silico data on the safety of LL‐37 are also reported. As Vitamin D is known to upregulate the expression of LL‐37, the vitamin is a candidate preventive molecule. This work provides the possible basis for an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid‐19, as widely reported in literature. With the scientific link put forth herein, Vitamin D could be used at an effective, medically prescribed, safe dose as a preventive. The information in this report would be valuable in bolstering the worldwide efforts to eliminate the pandemic as early as possible.
Caspase-3 dependent peritubular capillary dysfunction is pivotal for transition from acute to chronic kidney disease after acute ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Caspase-3, an effector responsible for apoptosis execution, is activated within peritubular capillary (PTC) in the early stage of IRI-induced acute kidney injury (AKI). Recently, we showed that caspase-3-dependent microvascular rarefaction plays a key role in fibrosis development after mild renal IRI. Here, we further characterize the role of caspase-3 in microvascular dysfunction and progressive renal failure in both mild and severe AKI, by performing unilateral renal artery clamping for 30/60 minutes with contralateral nephrectomy in wild-type (C57BL/6) or caspase-3-/- mice. In both forms of AKI, caspase-3-/- mice showed better long-term outcomes in spite of worse initial tubular injury. After 3 weeks, they showed reduced PTC injury, decreased PTC collagen deposition and α-SMA expression, and lower tubular injury scores when compared to wild-type animals. Caspase-3-/- mice with severe IRI also showed better preservation of long-term renal function. Intra-vital imaging and micro Computed Tomography (microCT) revealed preserved PTCs permeability and better terminal capillary density in caspase-3-/- mice. Collectively, these results demonstrate the pivotal importance of caspase-3 in regulating long-term renal function after IRI and establish the predominant role of PTCs dysfunction as a major contributor to progressive renal dysfunction.
Plasma Exchange Did Not Reduce Viral Load in a Recovered Case of Severe Fever with Thrombocytopenia Syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). There is no specific treatment for SFTS, although several reports have indicated that plasma exchange (PE) can be an effective therapy for severe SFTS. However, whether or not PE can reduce the viral load is unclear. We herein report a woman with SFTS who had her SFTSV viral load measured just before and after PE. While the patient recovered, there was no significant difference in the SFTSV viral load after PE. Our results confirmed that PE itself does not reduce the SFTSV viral load.