Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional lung imaging in thoracic tumor radiotherapy: Application and progress

Radiotherapy plays an irreplaceable and unique role in treating thoracic tumors, but the occurrence of radiation-induced lung injury has limited the increase in tumor target doses and has influenced patients’ quality of life. However, the introduction of functional lung imaging has been incorporating functional lungs into radiotherapy planning. The design of the functional lung protection plan, while meeting the target dose requirements and dose limitations of the organs at risk (OARs), minimizes the radiation dose to the functional lung, thus reducing the occurrence of radiation-induced lung injury. In this manuscript, we mainly reviewed the lung ventilation or/and perfusion functional imaging modalities, application, and progress, as well as the results based on the functional lung protection planning in thoracic tumors. In addition, we also discussed the problems that should be explored and further studied in the practical application based on functional lung radiotherapy planning.
Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management

Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms. Global control of tuberculosis will require interventions that effectively address these and related aspects. Interrupting tuberculosis transmission is dependent on the availability of novel rapid diagnostics which provide accurate results, as near-patient as is possible, together with appropriate linkage to care. Contact tracing, longitudinal follow-up for symptoms and active mapping of social contacts are essential elements to curb further community-wide spread of drug resistant strains. Appropriate prophylaxis for contacts of drug resistant index cases is imperative to limit disease progression and subsequent transmission. Preventing the evolution of drug resistant strains will require the development of shorter regimens that rapidly eliminate all populations of mycobacteria, whilst concurrently limiting bacterial metabolic processes that drive drug tolerance, mutagenesis and the ultimate emergence of resistance. Drug discovery programs that specifically target bacterial genetic determinants associated with these processes will be paramount to tuberculosis eradication. In addition, the development of appropriate clinical endpoints that quantify drug tolerant organisms in sputum, such as differentially culturable/detectable tubercle bacteria is necessary to accurately assess the potential of new therapies to effectively shorten treatment duration. When combined, this holistic approach to addressing the critical problems associated with drug resistance will support delivery of quality care to patients suffering from tuberculosis and bolster efforts to eradicate this disease.
Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs

Tuberculosis (TB) is a lethal disease and remains one of the top ten causes of mortality by an infectious disease worldwide. It can also result in significant morbidity related to persistent inflammation and tissue damage. Pulmonary TB treatment depends on the prolonged use of multiple drugs ranging from 6 months for drug-susceptible TB to 6–20 months in cases of multi-drug resistant disease, with limited patient tolerance resulting from side effects. Treatment success rates remain low and thus represent a barrier to TB control. Adjunct host-directed therapy (HDT) is an emerging strategy in TB treatment that aims to target the host immune response to Mycobacterium tuberculosis in addition to antimycobacterial drugs. Combined multi-drug treatment with HDT could potentially result in more effective therapies by shortening treatment duration, improving cure success rates and reducing residual tissue damage. This review explores the rationale and challenges to the development and implementation of HDTs through a succinct report of the medications that have completed or are currently being evaluated in ongoing clinical trials.
The relationship between negative life events and quality of life in adolescents: Mediated by resilience and social support

Background Quality of life has become an important indicator for assessing the health care of adolescents. This study aimed to explore the relationship between negative life events and quality of life in adolescents and the potential mediating roles of resilience and social support. Methods A stratified cluster sampling technique was used to select 3,860 adolescents as study participants. The Adolescent Self-Rating Life Events Checklist, the Resilience Scale for Chinese Adolescents, the Social Support Rating Scale, and the Adolescent Quality of Life Scale were used by participants to rate their negative life events, resilience, social support, quality of life, respectively. The correlations between study variables were analyzed by the Pearson correlation analyses. The AMOS 26.0 software was used to explore the mediating roles of resilience and social support in negative life events and quality of life. Results There was a negative correlation between negative life events and quality of life (β=-0.745, P < 0.05); resilience and social support played an important mediating role in the relationship between negative life events and quality of life (βResilience = −0.287, P < 0.05; βSocial support = −0.124, P < 0.05). The emotional adjustment dimension of resilience (β = −0.285, P < 0.05) and the subjective support dimension of social support (β = −0.100, P < 0.05) played the largest mediating roles, respectively. Conclusion Negative life events were negatively correlated with adolescents' quality of life. Strengthening resilience and social support is expected to weaken and reduce the adverse effects of negative life events on adolescents and further maintain and improve their quality of life.
First genetic maps development and QTL mining in Ranunculus asiaticus L. through ddRADseq

Persian Buttercup (Ranunculus asiaticus L.; 2x=2n=16; estimated genome size: 7.6Gb) is an ornamental and perennial crop native of Asia Minor and Mediterranean basin, marketed both as cut flower or potted plant. Currently new varieties are developed by selecting plants carrying desirable traits in segregating progenies obtained by controlled mating, which are propagated through rhizomes or micro-propagated in vitro. In order to escalate selection efficiency and respond to market requests, more knowledge of buttercup genetics would facilitate the identification of markers associated with loci and genes controlling key ornamental traits, opening the way for molecular assisted breeding programs. Reduced-representation sequencing (RRS) represents a powerful tool for plant genotyping, especially in case of large genomes such as the one of buttercup, and have been applied for the development of high-density genetic maps in several species. We report on the development of the first molecular-genetic maps in R. asiaticus based on of a two-way pseudo-testcross strategy. A double digest restriction-site associated DNA (ddRAD) approach was applied for genotyping two F1 mapping populations, whose female parents were a genotype of a so called ‘ponpon’ and of a ‘double flower’ varieties, while the common male parental (‘Cipro’) was a genotype producing a simple flower. The ddRAD generated a total of ~2Gb demultiplexed reads, resulting in an average of 8,3M reads per line. The sstacks pipeline was applied for the construction of a mock reference genome based on sequencing data, and SNP markers segregating in only one of the parents were retained for map construction by treating the F1 population as a backcross. The four parental maps (two of the female parents and two of the common male parent) were aligned with 106 common markers and 8 linkage groups were identified, corresponding to the haploid chromosome number of the species. An average of 586 markers were associated with each parental map, with a marker density ranging from 1 marker/cM to 4.4 markers/cM. The developed maps were used for QTL analysis for flower color, leading to the identification of major QTLs for purple pigmentation. These results contribute to dissect on the genetics of Persian buttercup, enabling the development of new approaches for future varietal development.
Dietary supplementation with a mixture of herbal extracts during late gestation and lactation improves performance of sows and nursing piglets through regulation of maternal metabolism and transmission of antibodies

The dietary inclusion of phytogenic feed additives to improve the performance and health of sows is considered to be safe, effective and environmentally friendly, thus gaining growing popularity among new strategies. This study was designed with three trials aimed to determine the effective supplemental levels of Scutellaria baicalensis and Lonicera japonica mixed extracts (SLE) in sow diets based on production performance and explore its related mechanisms of action based on serum metabolites, antioxidant capacity, and immune profile of sows and nursing piglets. Trials 1 and 2 were conducted to determine the effective dose and ratio of SLE by supplementation of various proportions and doses of SLE to sows diets from the late pregnancy to weaning, with litter performance at farrowing and weaning and disease conditions being evaluated. Trial 3 was conducted to further explore the mechanisms of action of SLE as evaluated by serum immunity and antioxidants indices in late gestation and lactation sows. The results of trials 1 and 2 showed that dietary supplementation of 1.0 g/kg SLE (50% S. baicalensis extract, 30% L. japonica extract, and 20% wheat bran fiber as carrier) enhanced the number of piglets born alive, litter birth weight, litter weight gain, and average daily feed intake of sows during lactation, while decreased diarrhea of suckling piglets. In Trial 3, compared with the control group, dietary SLE supplementation increased (P < 0.05) sow serum glucose (GLU), triglyceride (TG), total cholesterol (TC), prolactin (PRL) and interleukin-10 (IL-10) concentrations, and total superoxide dismutase (T-SOD) activities at the farrowing, and increased (P < 0.05) sow serum prolactin, leptin, and insulin concentrations at d 14 of lactation. Fat concentrations in sow colostrum and in milk on day 14 of lactation, both IgA and IgG concentrations in colostrum, and both IL-10 and IgA concentrations in piglet serum at d 14 of lactation were all increased (P < 0.05) following dietary SLE supplementation. Altogether, dietary supplementation with the appropriate levels of SLE promoted health and growth of suckling piglets, which was associated with the improvement of maternal metabolism and transmission of antibodies.
Genome sequencing and analysis of the raccoon variant rabies lyssaviruses directly from clinical samples, Connecticut, 2017–2019

COPYRIGHT © 2022 Chung, Helal, Desiato, McGinnis, Sims, Hunt, Kim, Risatti and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Genome sequencing and analysis of the raccoon variant rabies lyssaviruses directly from clinical samples, Connecticut, 2017–2019
Modeling the effect of environmental cytokines, nutrient conditions and hypoxia on CD4+ T cell differentiation

Upon antigen stimulation and co-stimulation, CD4+ T lymphocytes produce soluble factors that promote the activity of other immune cells against pathogens or modified tissues; this task must be performed in presence of a variety of environmental cytokines, nutrient, and oxygen conditions, which necessarily impact T cell function. The complexity of the early intracellular processes taking place upon lymphocyte stimulation is addressed by means of a mathematical model based on a network that integrates variable microenvironmental conditions with intracellular activating, regulatory, and metabolic signals. Besides the phenotype subsets considered in previous works (Th1, Th2, Th17, and Treg) the model includes the main early events in differentiation to the T FH phenotype. The model describes how cytokines, nutrients and oxygen availability regulate the differentiation of naïve CD4+ T cells into distinct subsets. Particularly, it shows that elevated amounts of an all-type mixture of effector cytokines under optimal nutrient and oxygen availability conduces the system towards a highly-polarized Th1 or Th2 state, while reduced cytokine levels allow the expression of the Th17, Treg or T FH subsets, or even hybrid phenotypes. On the other hand, optimal levels of an all-type cytokine mixture in combination with glutamine or tryptophan restriction implies a shift from Th1 to Th2 expression, while decreased levels of the Th2-inducing cytokine IL-4 leads to the rupture of the Th1-Th2 axis, allowing the manifestation of different (or hybrid) subsets. Modeling proposes that, even under reduced levels of pro-inflammatory cytokines, the sole action of hypoxia boost Th17 expression.
PCL strut-like scaffolds appear superior to gyroid in terms of bone regeneration within a long bone large defect: An in silico study

The treatment of large bone defects represents a major clinical challenge. 3D printed scaffolds appear as a promising strategy to support bone defect regeneration. The 3D design of such scaffolds impacts the healing path and thus defect regeneration potential. Among others, scaffold architecture has been shown to influence the healing outcome. Gyroid architecture, characterized by a zero mean surface curvature, has been discussed as a promising scaffold design for bone regeneration. However, whether gyroid scaffolds are favourable for bone regeneration in large bone defects over traditional strut-like architecture scaffolds remains unknown. Therefore, the aim of this study was to investigate whether gyroid scaffolds present advantages over more traditional strut-like scaffolds in terms of their bone regeneration potential. Validated bone defect regeneration principles were applied in an in silico modeling approach that allows to predict bone formation in defect regeneration. Towards this aim, the mechano-biological bone regeneration principles were adapted to allow simulating bone regeneration within both gyroid and strut-like scaffolds. We found that the large surface curvatures of the gyroid scaffold led to a slower tissue formation dynamic and conclusively reduced bone regeneration. The initial claim, that an overall reduced zero mean surface curvature would enhance bone formation, could not be confirmed. The here presented approach illustrates the potential of in silico tools to evaluate in pre-clinical studies scaffold designs and eventually lead to optimized architectures of 3D printed implants for bone regeneration.
Basin-scale control on N2O loss rate and emission in the Changjiang River network, China

Global riverine N2O emissions have been made by several studies with great uncertainty. However, the regional N2O budgets and patterns in large river networks is still unclear, due to the lacking understanding of in-river N2O emission rate and well-classified river network water areas. Furthermore, the mass ratio of N2O emission against nitrogen(N) load in river networks remains controversial. Here we report N2O emissions from the largest river of China, the Changjiang River network, emphasizing the basin-scale control on riverine N2O loss rate in response to increasing N loads and river size. We find the N2O emission rate is negatively related to Strahler river orders, and positively related to N loading. The velocity (Vf) of N conversion into N2O was 0.131-0.436 m yr-1, and N2O loss rate (ζ) was 0.27-37.64 ×10-4 d-1 and declined exponentially with water discharge. Both the loss rate and the mass ratio of N conversion into N2O varied significantly at basin scale, indicating the diminishing capacity of river ecosystems to convert excess DIN into N2O when N load increased as a direct result of human activities. Our study shows N2O emission was 0.66 Gg N2O-N (1Gg=109g) in 1986 and increased to 10.3 Gg N2O-N in 2014 for the whole Changjiang River network. We identified the headwater streams are hotspots of N2O emission across the headwater stream to the estuary aquatic continuum. N2O emission was about 0.82% - 5.31% of global riverine N2O budget during 2010-2014. Our study suggested that an integrated approach in view of the riverine N loads and river hydrology is needed to improve estimates of riverine N2O emissions.
Synergetic reorganization of the contralateral structure and function in patients with unilateral frontal glioma

Objective This study aimed to investigate the contralateral structural and functional plasticity induced by frontal gliomas. Methods Patients with left (n = 49) or right (n = 52) frontal diffuse glioma were enrolled along with 35 age- matched healthy controls (HCs). The gray-matter volumes (GMVs) of the contralesional region were measured using the voxel-based morphometry (VBM) analysis. Additionally, the amplitude of low-frequency fluctuation (ALFF) of the contralesional region was calculated via resting state functional magnetic resonance imaging (MRI) to assess functional alterations. Result The GMV of the contralateral orbitofrontal cortex of the right or left frontal gliomas was significantly larger than the corresponding GMV in the controls. In the patients with right frontal glioma, the GMV and ALFF in the left inferior frontal gyrus were significantly increased compared with those in the controls. Conclusion Glioma invasion of the frontal lobe can induce contralateral structural compensation and functional compensation, which show synergy in the left inferior frontal gyrus. Our findings explain why patients with unilateral frontal glioma can have functional balance, and offer the possibility of preserving the brain function while maximizing tumor removal.
Effects of moderate-intensity exercise on social health and physical and mental health of methamphetamine-dependent individuals: A randomized controlled trial

Objective Methamphetamine (MA)-dependent individuals’ health problems are widespread and need to be solved urgently. Exercise is considered a potential treatment for MA dependents. The study aimed to determine the effects of a 12-week aerobic exercise on the social, physical, and mental health of MA-dependent individuals. Materials and methods Sixty MA-dependent individuals were randomly assigned into two groups. Subjects in the exercise group (n = 30) received an exercise intervention five days a week for 60 min each for 12 weeks. Subjects in the control group (n = 30) received regular corrective rehabilitation without exercise in the same setting. Outcome measures, including questionnaires [quality of life scale for drug addiction (QOL-DA), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Pittsburgh sleep quality index (PSQI)] and physical fitness, were arranged the day before the start of the intervention and the day after the end of the intervention. Two-factor repeated measures ANOVA was used to compare the treatment differences between the two groups. Results After 12 weeks of the intervention period, social health was significantly improved in the exercise group (P < 0.01), and there was a statistically significant difference in mental health scores between exercise group and control group, with a greater impact in exercise group. (Psychology: P < 0.01; SAS: P < 0.01; SDS: P < 0.01; PSQI: P < 0.01), physical health improved in the exercise group, physiology (P < 0.01), symptom (P < 0.01), heart rate (P < 0.01), systolic blood pressure (P < 0.01), systolic blood pressure (P < 0.01), vital capacity (P < 0.05), grip (P < 0.01), vertical jump (P < 0.001), sit and reach (P < 0.01), 50-meter run (P < 0.01), and reaction time (P < 0.01). Conclusion Aerobic exercise intervention is an effective treatment for MA-dependent individuals, and the 12-week intervention improved the social, physical, and mental health of MA-dependent individuals. We recommend that future studies focus more on drug-dependent individuals’ overall health status rather than just relapse.Clinical trial registration: [https://www.chictr. org.cn/hvshowproject.aspx? id=131048], identifier [ChiCTR2200055348].
Meglumine antimoniate was associated with a higher cure rate than liposomal amphotericin B in the treatment of American tegumentary leishmaniasis: A retrospective cohort study from a Leishmania braziliensis-endemic area

Background Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established. Objective This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates. Methods This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results. Results Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61). Conclusions We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis.