Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of precision medicine in clinical routine in haematology—Challenges and opportunities

Precision medicine is revolutionising patient care in cancer. As more knowledge is gained about the impact of specific genetic lesions on diagnosis, prognosis and treatment response, diagnostic precision and the possibility for optimal individual treatment choice have improved. Identification of hallmark genetic aberrations such as the BCR::ABL1 gene fusion in chronic myeloid leukaemia (CML) led to the rapid development of efficient targeted therapy and molecular follow‐up, vastly improving survival for patients with CML during recent decades. The assessment of translocations, copy number changes and point mutations are crucial for the diagnosis and risk stratification of acute myeloid leukaemia and myelodysplastic syndromes. Still, the often heterogeneous and complex genetic landscape of haematological malignancies presents several challenges for the implementation of precision medicine to guide diagnosis, prognosis and treatment choice. This review provides an introduction and overview of the important molecular characteristics and methods currently applied in clinical practice to guide clinical decision making in haematological malignancies of myeloid and lymphoid origin. Further, experimental ways to guide the choice of targeted therapy for refractory patients are reviewed, such as functional precision medicine using drug profiling. An example of the use of pipeline studies where the treatment is chosen according to the molecular characteristics in rare solid malignancies is also provided. Finally, the future opportunities and remaining challenges of precision medicine in the real world are discussed.
Elevated CO2 Increases Overwintering Mortality of Varroa destructor (Mesostigmata: Varroidae) in Honey Bee (Hymenoptera: Apidae) Colonies

Abstract Indoor storage of honey bees (Apis mellifera L.) during winter months has been practiced for decades to protect colonies from the adverse effects of long, harsh winter months. Beekeepers have recently employed indoor storage to reduce labor, feeding costs, theft, and woodenware degradation. Despite the growing number of colonies stored indoors, national survey results still reveal high losses. Varroa mites (Varroa destructor Anderson and Trueman) are the most critical threat to colony winter survival and health of colonies because they contribute to the transmission of viruses and colony mortality. To investigate the effect of high CO2 on varroa mites during the indoor storage of honey bees, 8-frame single deep colonies were stored in two separate environmental chambers at 4°C each. One environmental chamber was set at 8.5% CO2 (high CO2), while the other was set at low CO2 (0.12%). Dead and falling mites were collected and counted from the bottom of individual colonies weekly during the experiment. There was a significant difference in mite mortality of colonies with high CO2 compared to colonies held at low CO2. These results indicated that high CO2 could increase mite mortality during the period of indoor storage, potentially improving honey bee health coming out of the winter months. Our research offers a critical addition to beekeepers' tools for managing varroa mite populations.
Mechanobiology of indirect bone fracture healing under conditions of relative stability: a narrative review for the practicing clinician

Background and aim: Mechanical influence on secondary fracture healing remains an incompletely understood phenomenon. This is of special importance in biological osteosynthesis, where sility is sacrificed for the sake of an optimal biological fracture environment. Under condition of relative stability, a wide range of biomechanical conditions can be achieved. Mechanobiology, which studies mechanical influences on biological systems has become a large, interdisciplinary field. The aim of this article is to present a comprehensive synthesis of the literature for the practicing clinician, with insights relevant to their practice of fracture care. Methods: The MEDLINE online database (Pubmed) was searched in September 2021 for relevant articles. Results: The search provided 816 results, which were scanned by the first author by the title and abstract. With relevance to the research topic, 59 articles were chosen and read in detail. Another 70 articles were added by screening the references of relevant articles. A total of 129 articles were read and analysed Conclusions: Mechanical environment plays a crucial role in the fracture healing process. The definition of an optimal mechanical environment still evades us, due to the complexity of the problem. Computational models could replicate the complex mechanical environment of bone healing in humans but require detailed knowledge of mechano-transduction and material properties of healing tissues. The literature reminds us of the importance of adequate stiffness of constructs used under conditions of relative stability. Hopefully, further research in this field will result in not only empirical but more accurate and evidence-based assessments of osteosynthesis fixations. (www.actabiomedica.it)
Electrocommunication signals and aggressive behavior vary among male morphs in an apteronotid fish, Compsaraia samueli.

Within-species variation in male morphology is common among vertebrates and is often characterized by dramatic differences in behavior and hormonal profiles. Males with divergent morphs also often use communication signals in a status-dependent way. Weakly electric knifefish are an excellent system for studying variation in male morphology and communication and its hormonal control. Knifefish transiently modulate the frequency of their electric organ discharge (EOD) during social encounters to produce chirps and rises. In the knifefish Compsaraia samueli, males vary extensively in jaw length. EODs and their modulations (chirps and rises) have never been investigated in this species, so it is unclear whether jaw length is related to the function of these signals. We used three behavioral assays to analyze EOD modulations in male C. samueli: (1) artificial playbacks, (2) relatively brief, live agonistic dyadic encounters, and (3) long-term overnight recordings. We also measured circulating levels of two androgens, 11-ketotestosterone and testosterone. Chirp structure varied within and across individuals in response to artificial playback, but was unrelated to jaw length. Males with longer jaws were more often dominant in dyadic interactions. Chirps and rises were correlated with and preceded attacks regardless of status, suggesting these signals function in aggression. In longer-term interactions, chirp rate declined after one week of pairing, but was unrelated to male morphology. Levels of circulating androgens were low and not predictive of jaw length or EOD signal parameters. These results suggest that communication signals and variation in male morphology are linked to outcomes of non-breeding agonistic contests.
Association between dietary creatine and visuospatial short-term memory in older adults

Aims: The purpose was to examine the relationship between habitual dietary creatine intake obtained in food and visuospatial short-term memory (VSSM). Methods: Forty-two participants (32 females, 10 males; > 60 yrs of age) completed a 5-day dietary recall to estimate creatine intake and performed a cognitive assessment which included a visuospatial short-term memory test (forward and reverse corsi block test) and a mini-mental state examination (MMSE). Pearson correlation coefficients were determined. Further, cohorts were derived based on the median creatine intake. Results: There was a significant correlation between the forward Corsi (r = 0.703, P < 0.001), reverse Corsi (r = 0.715, P < 0.001), and the memory sub-component of the MMSE (r = 0.406, P = 0.004). A median creatine intake of 0.382 g/day was found. Participants consuming greater than the median had a significantly higher Corsi (P = 0.005) and reverse Corsi (P < 0.001) scores compared to participants ingesting less than the median. Conclusions: Dietary creatine intake is positively associated with measures of memory in older adults. Clinical Implications: Older adults should consider food sources containing creatine (i.e. red meat, seafood) due to the positive association with visuospatial short-term memory.
High static gain single-phase PFC based on a hybrid boost converter

ABSTRACT In this paper, a single-phase unity power factor rectifier, based on a hybrid boost converter, resulting from the integration of a conventional dc–dc boost converter and a switched-capacitor voltage doubler is proposed, analysed, designed and tested. The high-power rectifier is controlled by two feedback loops with the same control strategy employed in the conventional boost-based rectifier. The main feature of the proposed rectifier is its ability to output a dc voltage larger than the double of the peak value of the input line voltage, while subjecting the power switches to half of the dc-link voltage, which contributes to reducing the cost and increasing the efficiency. Experimental data were obtained from a laboratory prototype with an input voltage of 220 Vrms, line frequency of 60 Hz, output voltage of 800 Vdc, load power of 1000 W and switching frequency of 50 kHz. The efficiency of the prototype, measured in the laboratory, was 96.5% for full load and 97% for half load.
Prevalence and Odds of Anxiety Disorders and Anxiety Symptoms in Children and Adults with Psoriasis: Systematic Review and Meta-analysis

The magnitude of the association between psoriasis and depression has been evaluated, but not that between psoriasis and anxiety. The aim of this systematic review and meta-analysis was to examine the prevalence and odds of anxiety disorders and symptoms in patients with psoriasis. Five medical databases (Cochrane Database, EMBASE, PubMed, PsychINFO, ScienceDirect) were searched for relevant literature. A total of 101 eligible articles were identified. Meta-analysis revealed different prevalence rates depending on the type of anxiety disorder: 15% [95% confidence interval [CI] 9–21] for social anxiety disorder, 11% [9–14] for generalized anxiety disorder, and 9% [95% CI 8–10] for unspecified anxiety disorder. There were insufficient studies assessing other anxiety disorders to be able to draw any conclusions on their true prevalence. Meta-analysis also showed a high prevalence of anxiety symptoms (34% [95% CI 32–37]). Case-control studies showed a positive association between psoriasis and unspecified anxiety disorder (odds ratio 1.48 [1.18; 1.85]) and between psoriasis and anxiety symptoms (odds ratio 2.51 [2.02; 3.12]). All meta-analyses revealed an important heterogeneity, which could be explained in each case by methodological factors. The results of this study raise the necessity of screening for the presence of anxiety disorders, as previously recommended for depressive disorders, in patients with psoriasis and, if necessary, to refer such patients for evaluation by a mental health professional and appropriate treatment.
Importance of Non-Newtonian Computational Fluid Modeling on Severely Calcified Aortic Valve Geometries - Insights from Quasi-Steady State Simulations.

The Newtonian model has commonly been used to represent the viscosity of blood in the aorta, despite blood itself being a non-Newtonian fluid. This is justified where shear rates tend to be large. However, we hypothesized that using the Newtonian model to predict the hemodynamics on the aortic valve, particularly in those with severe calcifications, is inaccurate owing to valve leaflet geometry irregularities inducing multiple regions of low shear rates, <100 s-1, where a Newtonian model is invalid. We investigated the use of three fluid models: Newtonian, Carreau, and Quemada on a healthy and calcified valve and compared their ability to capture important hemodynamic parameters of time averaged wall shear stress (TAWSS) and the oscillatory shear index (OSI). Our findings indicate that when the shear rates were large enough, >100 s-1, use of a Newtonian model was justified for the ventricularis side of the leaflet. However, in spatial regions of low shear rates, <100 s-1, specifically on the inner cusps of the fibrosa side of the valve, TAWSS calculations under a Newtonian model were found to be much lower when compared with their non-Newtonian Carreau and Quemada counterparts. We hereby conclude that in order to facilitate more accurate computational flow simulations in severe aortic valve calcification which is subjected to relatively large spatial regions of low shear (<100 s-1), a non-Newtonian model should be applied.
Genomic Characterization of a Tomato Yellow Mottle-Associated Virus Collected from a Field Tomato Plant in Chengdu, Southwestern China

Here, we report the genomic sequence and genetic variations of a Tomato yellow mottle-associated virus. The virus isolated from a field tomato (Solanum lycopersicum) plant in Chengdu, southwestern China, was sequenced via both Illumina and Sanger technologies. Phylogeny indicates that its genome is close to the reported virus sequence from S. lycopersicum collected in 2013 but far from Solanum nigrum collected in 2020. ABSTRACT Here, we report the genomic sequence and genetic variations of a Tomato yellow mottle-associated virus. The virus isolated from a field tomato (Solanum lycopersicum) plant in Chengdu, southwestern China, was sequenced via both Illumina and Sanger technologies. Phylogeny indicates that its genome is close to the reported virus sequence from S. lycopersicum collected in 2013 but far from Solanum nigrum collected in 2020.
Potential mechanism of hepatic lipid accumulation during a long-term rest phase restricted feeding in mice

ABSTRACT Eating during a rest phase disrupts the biological clock system and leads to obesity and metabolic diseases. Although a rest phase restricted feeding (RF) is reported to enhance hepatic lipid accumulation, the mechanism(s) of the phenomenon is still unknown. This study evaluated the potential involvement of the CD36-related transport of lipids into the liver in mice with the RF procedure. This study showed that hepatic lipid accumulation was more significant in the RF group compared with mice under an active phase restricted feeding (AF). The RF procedure also elevated the expression of CD36 mRNA and its protein on the cellular membrane throughout the day. The transcription factor profiling array revealed that the RF activated the proliferator-activated receptor-γ (PPARγ), one of the CD36 transcript enhancers. In the liver of RF mice, the expression of miR-27b-3p, which is known to interfere with PPARγ gene expression, significantly decreased. These results suggest that the RF procedure inhibits the expression of miR-27b-3p in the liver and subsequently elevates PPARγ activity. Activated PPARγ might lead to CD36 upregulation, which, in turn, stimulates the transport of lipids into the liver.
Exploring the medical cannabis prescribing behaviours of New Zealand physicians

Abstract Introduction Many countries are changing their regulations for prescribing medical cannabis. As gatekeepers, physicians significantly impact patient access to cannabis treatments. It is important to explore how physicians view prescribing cannabis in terms of their existing beliefs, knowledge, possible concerns and personal perceptions. Methods Individual, semi‐structured telephone interviews were undertaken with 14 New Zealand physicians from various specialties. The interviews were thematically analysed using a phenomenological approach. Results The physician–patient relationship was of extreme importance in making prescription decisions, driven largely by trust in the patient. Barriers to prescribing included concern over possible side effects, the quality and standardisation of medication, uncertainty about indications and equity concerns from the high cost for lower socio‐economic patients. Some physicians held concerns over their liability and risks to their reputation if issues arose for patients. Discussion and Conclusion The way physicians regard prescribing medical cannabis is based on their personal beliefs and knowledge built up over their medical career. It is important that these are taken into consideration in the design of future guidelines to help alleviate uncertainties and reduce barriers for informed prescribing. While our research and previous research find that physicians generally will follow clinical guidelines based on institutional logics (i.e. the standardised approach to medicine), we find that physicians often allow their personal construals to determine their perceptions and prescribing behaviour to a considerable extent when they practice medicine. Our findings have implications for Continuing Medical Education, marketing and regulation for medical cannabis, especially about the wording of guideline adherence.
Expression profile of CYP402C1 and its role in resistance to imidacloprid in the whitefly, Bemisia tabaci

Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cosmopolitan insect pest causing serious damage to crop production. Cytochromes P450 (CYPs) of B. tabaci are widely known to be involved in the metabolic resistance to a variety of insecticides, continuously increasing the difficulty in controlling this pest. In this study, four P450 genes (CYP6CM1, CYP6CX1, CYP6CX3, and CYP402C1) in B. tabaci exhibited correlations with the resistance to imidacloprid. We have focused on trying to understand the function and metabolism capacity of CYP402C1. The expression profiles of CYP402C1 were examined by reverse transcription quantitative real‐time PCR and fluorescence in situ hybridizations. Its role in resistance to imidacloprid was investigated by RNA interference, transgenic Drosophila melanogaster, and heterologous expression. The results showed that CYP402C1 was highly expressed in the active feeding stages of B. tabaci, such as nymphs and female adults. CYP402C1 was mainly expressed in midguts of nymphs and adults, especially in the filter chamber. Knockdown of CYP402C1 significantly decreased the resistance of B. tabaci to imidacloprid by 3.96‐fold (50% lethal concentration: 186.46 versus 47.08 mg/L). Overexpression of CYP402C1 in a transgenic D. melanogaster line (Gal4 > UAS‐CYP402C1) significantly increased the resistance to imidacloprid from 12.68‐ to 14.92‐fold (129.01 and 151.80 mg/L versus 1925.14 mg/L). The heterologous expression of CYP402C1 showed a metabolism ability of imidacloprid (imidacloprid decreased by 12.51% within 2 h). This study provides new insights for CYP402C1 function in B. tabaci and will help develop new strategies in B. tabaci control and its insecticide resistance.
Neural Reinstatement of Overlapping Memories in Young and Older Adults

Abstract When we update our episodic memories with new information, mnemonic competition between old and new memories may result because of the presence of shared features. Behavioral studies suggest that this competition can lead to proactive interference, resulting in unsuccessful memory updating, particularly for older adults. It is difficult with behavioral data alone to measure the reactivation of old, overlapping memories during retrieval and its impact on memory for new memories. Here, we applied encoding–retrieval representational similarity (ERS) analysis to EEG data to estimate event-specific encoding-related neural reinstatement of old associations during the retrieval of new ones and its impact on memory for new associations in young and older adults. Our results showed that older adults' new associative memory performance was more negatively impacted by proactive interference from old memories than that of young adults. In both age groups, ERS for old associative memories was greater for trials for which new associative memories were forgotten than remembered. In contrast, ERS for new associative memories was greater when they were remembered than forgotten. In addition, older adults showed relatively attenuated target (i.e., new associates) and lure (i.e., old associates) ERS effects compared to younger adults. Collectively, these results suggest that the neural reinstatement of interfering memories during retrieval contributes to proactive interference across age, whereas overall attenuated ERS effect in older adults might reflect their reduced memory fidelity.
Key Drivers and Facilitators of the Choice to Use mHealth Technology in People With Neurological Conditions: Observational Study

Background There is increasing interest in the potential uses of mobile health (mHealth) technologies, such as wearable biosensors, as supplements for the care of people with neurological conditions. However, adherence is low, especially over long periods. If people are to benefit from these resources, we need a better long-term understanding of what influences patient engagement. Previous research suggests that engagement is moderated by several barriers and facilitators, but their relative importance is unknown. Objective To determine preferences and the relative importance of user-generated factors influencing engagement with mHealth technologies for 2 common neurological conditions with a relapsing-remitting course: multiple sclerosis (MS) and epilepsy. Methods In a discrete choice experiment, people with a diagnosis of MS (n=141) or epilepsy (n=175) were asked to select their preferred technology from a series of 8 vignettes with 4 characteristics: privacy, clinical support, established benefit, and device accuracy; each of these characteristics was greater or lower in each vignette. These characteristics had previously been emphasized by people with MS and or epilepsy as influencing engagement with technology. Mixed multinomial logistic regression models were used to establish which characteristics were most likely to affect engagement. Subgroup analyses explored the effects of demographic factors (such as age, gender, and education), acceptance of and familiarity with mobile technology, neurological diagnosis (MS or epilepsy), and symptoms that could influence motivation (such as depression). Results Analysis of the responses to the discrete choice experiment validated previous qualitative findings that a higher level of privacy, greater clinical support, increased perceived benefit, and better device accuracy are important to people with a neurological condition. Accuracy was perceived as the most important factor, followed by privacy. Clinical support was the least valued of the attributes. People were prepared to trade a modest amount of accuracy to achieve an improvement in privacy, but less likely to make this compromise for other factors. The type of neurological condition (epilepsy or MS) did not influence these preferences, nor did the age, gender, or mental health status of the participants. Those who were less accepting of technology were the most concerned about privacy and those with a lower level of education were prepared to trade accuracy for more clinical support. Conclusions For people with neurological conditions such as epilepsy and MS, accuracy (ie, the ability to detect symptoms) is of the greatest interest. However, there are individual differences, and people who are less accepting of technology may need far greater reassurance about data privacy. People with lower levels of education value greater clinician involvement. These patient preferences should be considered when designing mHealth technologies.