Miracle-dz/UniFAR-FTUs huggingface dataset:
An overview of the Plasmodium falciparum hexose transporter and its therapeutic interventions

Despite intense elimination efforts, human malaria, caused by the infection of five Plasmodium species, remains the deadliest parasitic disease in the world. Even worse, with the emergence and spreading of the first‐line drug‐resistant Plasmodium parasites, therapeutic interventions based on novel plasmodial drug targets are more necessary than ever. Given that the blood‐stage parasites primarily rely on glycolysis for their energy supply, blocking glucose uptake, the rate‐limiting step of ATP generation, was considered a promising approach to kill these parasites. To achieve this goal, characterization of the plasmodial hexose transporter and development of selective inhibitors have been pursued for decades. Here, we review the identification and characterization of the Plasmodium falciparum hexose transporter (PfHT1) and summarize current advances in its inhibitor development.
Neglected Monteggia fracture: a review

Monteggia fracture is characterized by radial head dislocation combined with proximal ulnar fracture. If not diagnosed at an early stage, these lesions can gradually lead to forearm deformities and dysfunction, finally resulting in neglected Monteggia fracture. When the radial head is not reduced, several deformities develop at the humeroradial joint, including cubitus valgus and osteoarthritis. Adequate radiographs are crucial when the surgeons deal with forearm injuries. At present, proximal ulnar osteotomy and open reduction of chronic radial head dislocation provides satisfactory functional outcomes because of anatomic alignment reconstruction. Supplementary procedures, including transcapitellar pinning and repair or reconstruction of the annular ligament, which are performed in order to enhance stability of the humeroradial joint, should be thoroughly assessed based on joint rotational stability after reduction and on potential complications.
Impairment of the cellulose degradation machinery enhances Fusarium oxysporum virulence but limits its reproductive fitness

Fungal pathogens grow in the apoplastic space, in constant contact with the plant cell wall (CW) that hinders microbe progression while representing a source of nutrients. Although numerous fungal CW modifying proteins have been identified, their role during host colonization remains underexplored. Here, we show that the root-infecting plant pathogen Fusarium oxysporum (Fo) does not require its complete arsenal of cellulases to infect the host plant. Quite the opposite: Fo mutants impaired in cellulose degradation become hypervirulent by enhancing the secretion of virulence factors. On the other hand, the reduction in cellulase activity had a severe negative effect on saprophytic growth and microconidia production during the final stages of the Fo infection cycle. These findings enhance our understanding of the function of plant CW degradation on the outcome of host-microbe interactions and reveal an unexpected role of cellulose degradation in a pathogen’s reproductive success.
Parallel‐reaction monitoring revealed altered expression of a number of epitranscriptomic reader, writer, and eraser proteins accompanied with colorectal cancer metastasis

RNA contains more than 170 types of chemical modifications, and these modified nucleosides are recognized, installed and removed by their reader, writer, and eraser (RWE) proteins, respectively. Here, we employed a parallel‐reaction monitoring (PRM)‐based targeted proteomic method, in conjunction with stable isotope labeling by amino acids in cell culture (SILAC), to examine comprehensively the differential expression of epitranscriptomic RWE proteins in a matched pair of primary/metastatic colorectal cancer (CRC) cells, namely SW480/SW620. We were able to quantify 113 nonredundant epitranscriptomic RWE proteins; among them, 48 and 5 were up‐ and down‐regulated by >1.5‐fold in SW620 over SW480 cells, respectively. Some of those proteins with marked up‐regulation in metastatic CRC cells, including NAT10, hnRNPC, and DKC1, were documented to assume important roles in the metastasis of CRC and other types of cancer. Interrogation of the Clinical Proteomic Tumor Analysis Consortium data revealed the involvement of DUS1L in the initiation and metastatic transformation of CRC. It can be envisaged that the PRM method can be utilized, in the future, to identify epitranscriptomic RWE proteins involved in the metastatic transformations of other types of cancer.
Promoting industrial symbiosis : analysing context and network evolution during biowaste-to-resource innovations

Government and industry increasingly face challenges resulting from resource scarcity and climate change. By reducing carbon emissions whilst promoting resource efficiency and business development, industrial symbiosis has been recognised as a strategy to manage these challenges. Industrial symbiosis can be interpreted as the innovative use of waste from one company as a resource for another company, i.e. waste-to-resource innovation. These resource innovations involve the development of relations between waste producers and users, and often governmental organisations and other actors. A review of industrial symbiosis and relevant network and innovation literature concluded that empirical understanding of the implementation of industrial symbiosis, and consequently how it can be promoted by public and private organisations, needed considerable improvement. Hence, a qualitative empirical exploration was conducted to answer the question: How and why did industrial symbiosis develop over time? The exploration was carried out in the Humber region (UK) and, with several bio-based developments emerging in the area, focused on biowaste-to-resource innovation. Case studies with companies revealed: the social process through which resource partnerships developed; important contextual conditions (resource security, economic benefits, and governance); and varying network diversification and strengthening strategies. Analysing these innovations in their longer-term dynamic contexts revealed different business-responses to context-changes through their varying innovation and government-engagement strategies. Some companies were constrained by poor harmonisation of economic and various governmental drivers. In particular, since 2012, regional governance capacity for biowaste-to-resource innovation decreased while such innovations gained momentum at national government level. These findings have added to understanding of variation in factors and processes associated with implementing industrial symbiosis through company activities, strategies, and collaborations; and the relations between context dynamics, evolution of industrial symbiosis networks, and on-going business development. The level of detail revealed in this inductive empirical research contributed to identifying numerous further research directions. Moreover, practical recommendations were provided to companies and governmental organisations supporting the promotion of industrial symbiosis and contributing to the on-going transition to a more resource efficient and circular economy.
Pain Science in Practice: What Is Pain Neuroscience? Part 1.

SYNOPSIS This first article in the JOSPT "Pain Science in Practice" series explains fundamental concepts related to neuroscience: transduction, transmission, modulation, and perception. J Orthop Sports Phys Ther 2022;52(4):163-165. doi:10.2519/jospt.2022. 10995.
5‐HT2 receptor antagonism reduces human motoneuron output to antidromic activation but not to stimulation of corticospinal axons

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast‐acting excitatory ionotropic inputs. Serotonin (5‐HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5‐HT increases motoneuron excitability by activating 5‐HT2 receptors on the somato‐dendritic compartment. In the current study, we examined how antagonism of the 5‐HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5‐HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double‐blinded, placebo‐controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley to motoneurons to elicit cervicomedullary motor evoked potentials (CMEPs) in the surface electromyography (EMG) signal of the resting biceps brachii. Likewise, electrical peripheral nerve stimulation was used to generate antidromic spikes in motoneurons and cause recurrent discharges, which were recorded with surface EMG as F‐waves in a resting hand muscle. Compared with placebo, we found that 5‐HT2 antagonism reduced the amplitude and persistence of F‐waves but did not affect CMEP amplitude. 5‐HT2 antagonism also reduced maximal contraction strength. The reduced recurrent discharge of motoneurons with 5‐HT2 antagonism suggests that 5‐HT2 receptors modulate the electrical properties of the initial segment or soma to promote excitability. Conversely, as cyproheptadine did not affect motoneuron excitability to brief synaptic input, but affected maximal contractions requiring sustained input, it seems likely that the 5‐HT2‐mediated amplification of synaptic input at motoneuron dendrites is functionally significant only when excitatory input activates persistent inward currents.
Vapor Pressure, Vaping, and Corrections to Misconceptions Related to Medical Cannabis' Active Pharmaceutical Ingredients' Physical Properties and Compositions

Medical cannabis products contain dozens of active pharmaceutical ingredients (APIs) derived from the cannabis plant. However, their actual compositions and relative doses significantly change according to the production methods. Product compositions are strongly dependent on processing step conditions and on components' evaporation during those steps. Review of the documentation presented to caregivers and to patients show erroneous data or misinterpretation of data related to the evaporation, for example, cannabinoids' boiling points, as well as confusions between terms, such as boiling, vaporization, and evaporation. Clarifying these aspects is essential for caregivers, for researchers, and for developers of manufacturing processes. Original and literature data were analyzed, comparing composition changes during various processing steps and correlating the extent of change to components' vapor pressures at the corresponding temperature. Evaporation-related composition changes start at temperatures as low as those of drying and curing and become extensive during decarboxylation. The relative rate of components' evaporation is determined by their relative vapor pressure and monoterpenes are lost first. On vaping, terpenes are inhaled before cannabinoids do. Commercial medical cannabis products are deficient in terpenes, mainly monoterpenes, compared with the cannabis plants used to produce them. Terms, such as “whole plant” and “full spectrum,” are misleading since no product actually reflects the original cannabis plant composition. There are important implications for medical cannabis manufacturing and for the ability to make the most out of the terpene API contribution. Medical cannabis products' composition and product delivery are controlled by the relative vapor pressure of the various APIs. Quantitative data provided in this study can be used for improvement to reach better accuracy, reproducibility, and preferred medical cannabis compositions.
III-Nitride advanced technologies and equipment for microelectronics

Using of complex equipment SemiTEq shown in example of a closed cycle of basic technological operations for production of high-power field microwave transistors based on gallium nitride in the "Svetlana-Rost" JSC. Basic technological operations are shown: MBE growth of heterostructures, metal deposition of contacts using electron-beam evaporation system, thermal annealing of ohmic contacts, meza-isolation plasma-chemical etching and dielectric plasma deposition. The main problems during the technological route as well as ways to solve are discussed. In particular, ways to reduce the dislocation density in the active region of the transistor heterostructures grown on the mismatched substrates are described in detail. Special attention given to the homogeneity and reproducibility both after some manufacturing operations and applied to the end product.
Prevalence and risk factors of urogenital schistosomiasis among under-fives in Mtama District in the Lindi region of Tanzania

Introduction Despite the ongoing intervention for schistosomiasis control among school-age children in the Lindi region of Tanzania, urogenital schistosomiasis continues to be a public health problem, presumably because other at-risk populations are not covered in praziquantel deworming campaigns. Evidence shows that under-fives become infected in their early life hence the need to understand the disease profile and the risk factors for exposure to infection so as to plan effective control strategies in this group. This study examined the prevalence and risk factors of urogenital schistosomiasis among under-fives in the Mtama district, Lindi region of Tanzania. Methodology/Principal findings A quantitative community-based cross-sectional study was carried out among 770 participants (385 under-fives and their 385 parents/guardians) in the Mtama district to investigate the burden and the risk factors associated with S. haematobium infection. A single urine specimen was collected from the under-fives and tested for macro and microhaematuria, presence of S. haematobium ova, and intensity of infection. A structured questionnaire gathered on risk factors for S. haematobium exposure in under-fives from their parents/guardians. Data analysis was performed using descriptive statistics, chi-square test, and logistic regression. Prevalence of S. haematobium ova was 16.9%, and that of macro and microhaematuria was 6% and 17.9%, respectively. Of the 65 positive under-fives, 49 (75.4%) 95% CI 65.4–86.3 had a light infection intensity, and 16 (24.6%) 95% CI 13.7–35.5 had a heavy infection intensity. Among the assessed risk factors, the parents/guardians habit of visiting water bodies for domestic routines (AOR: 1.44, 95% CI: 1.13–1.74), especially the river (AOR: 6.00, 95% CI: 1.20–35.12), was found to be a significant risk factor for infection of S. haematobium in under-fives. Conclusion/Significance A moderate prevalence of S. haematobium was found among the under-fives conceivably with adverse health events. The infected under-fives could be a source of continuity for transmission in the community. An intervention that covers this group is necessary and should be complemented with regular screening, health education campaigns, and an adequate supply of safe water.
Frailty predicts increased risk of reintervention in the 2 years after arteriovenous fistula creation

Introduction: Frailty is associated with adverse survival and increased hospital use in patients with end-stage kidney disease (ESKD). Dialysis access failure is an important source of morbidity and mortality for these patients. There is limited evidence about the interactions between frailty and haemodialysis access failure. This population-based cohort study aimed to determine if haemodialysis access reintervention was predicted by frailty. Methods: Routinely-collected hospital data linked with death records were analyzed for all patients with ESKD who had a new arteriovenous fistula or graft (AVF) created between 2010 and 2012 in New South Wales, Australia. Frailty risk was assigned by the Hospital Frailty Risk Score. Multivariate Cox-proportional hazard ratios (HR), adjusted for patient and procedural variables, quantified if frailty was prognostic for adverse haemodialysis access outcomes in the 2 years after AVF creation. Results: Almost one quarter of the 2302 patients who had a new AVF created during the study period were classified as high frailty risk (554, 24.1%). Compared to low frailty risk patients, patients with high frailty had a significantly greater risk of reintervention for AVF failure in the 2 years after creation (HR 1.68; 95% CI 1.45–1.96), adjusted for age, sex and prior AVFs. Frailer patients were also more likely to have perioperative complications, longer hospital length of stay and readmission to hospital. Frailty was associated with a higher risk of mortality at 2 years after AVF creation (adjusted HR 2.65; 95% CI 1.72–4.10). Conclusion: Frailty predicted adverse haemodialysis access outcomes, with frailer patients having higher rates of AVF reinterventions. These results can assist clinicians engaging in shared decision-making discussions about dialysis access risks and help personalize dialysis access decisions.
Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis

Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin‐induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin‐induced renal injury, Library of Integrated Network‐based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin‐induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin‐induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin‐induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin‐induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin‐induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin‐induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.
Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.
Chiral Arene Ligand as Stereocontroller for Asymmetric C-H Activation.

Development of chiral ligands is the most fundamental task in metal-catalyzed asymmetric synthesis. In the last 60 years, various kinds of ligands have been sophisticatedly developed. However, it remains a long-standing challenge to develop practically useful chiral η6-arene ligands, thereby seriously hampered the asymmetric synthesis promoted by arene-metal catalysts. Herein, we report the design and synthesis of a class of readily tunable, C2 symmetric chiral arene ligands derived from [2.2]paracyclophane. Its ruthenium(II) complexes have been prepared and successfully applied in the enantioselective C-H activation to afford a series of axially chiral isoquinolones (up to 99% yield and 96% ee). This study not only lays chemists' longstanding doubts about whether it is possible to use chiral arene ligand to stereocontrol ruthenium(II)-catalyzed asymmetric C-H activation, but also opens up a new avenue to achieve asymmetric C-H activation.
News & information: Vectors in radar technology

In mid-November 2015 a two-day event took place at University College London (UCL), intended to be the first of a new type of professional meeting. The motivation was a realization that most of the conferences and events that we currently organize are inherently retrospective — that is to say, they are reporting on work that has already been performed. There seemed, therefore, to be a niche for an event that encourages participants to look forward, to speculate and even to argue on the advances that will need to be made over the next ten, twenty years or even further into the future, and what the key challenges might be. This should be more than an academic exercise, of course — the results would be of interest to many parties, including governments, funding agencies, and research program managers.
Is value portable? An examination of contextual and practical considerations that affect the transferability of value assessments between settings

Abstract Objectives The extent to which value assessments are uniquely deployed in any given geographic setting is variable. Increasingly, markets are seeking insights from external health technology assessments (HTAs) to assist with decisions surrounding the adoption of new technologies. We reviewed the environment, infrastructure, and practice of value assessment in six countries, with a focus on how these elements influence the transferability of value assessments between settings. Methods We reviewed the diverse settings in which six organizations conducting HTA operate, and explored how differences might affect the transferability of value assessment. We focused attention on Australia’s Pharmaceutical Benefits Advisory Committee, China’s National Center for Medicine and HTA, Germany’s Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, Japan’s Center for Outcomes Research and Economic Evaluation for Health (Core 2 Health), the National Institute for Health and Care Excellence in England and Wales, and the Institute for Clinical and Economic Review in the United States. Results HTA is adopted to address unique objectives for a given health system and is tailored to support local standards and preferences. Some elements of a value assessment, such as evidence on clinical effectiveness, may be more transferable than others. It is challenging to appropriately adjust external assessments to the local context. Conclusions Contextual differences influence both the role and application of HTA. These differences limit the transferability of value assessments from one setting to another. De novo appraisals, customized to the local decision context, are the ideal approach to determinations about value.