Miracle-dz/UniFAR-FTUs huggingface dataset:
Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

ABSTRACT Exercise may ameliorate the eventual heart failure inherent in human aging. In this study, we use zebrafish to understand how aging and exercise affect cardiomyocyte turnover and myocardial remodelling. We show that cardiomyocyte proliferation remains constant throughout life but that onset of fibrosis is associated with a late increase in apoptosis. These findings correlate with decreases in voluntary swimming activity, critical swimming speed (Ucrit), and increases in biomarkers of cardiac insufficiency. The ability to respond to severe physiological stress is also impaired with age. Although young adult fish respond with robust cardiomyocyte proliferation in response to enforced swimming, this is dramatically impaired in older fish and served by a smaller proliferation-competent cardiomyocyte population. Finally, we show that these aging responses can be improved through increased activity throughout adulthood. However, despite improvement in Ucrit and the proliferative response to stress, the size of the proliferating cardiomyocyte population remained unchanged. The zebrafish heart models human aging and reveals the important trade-off between preserving cardiovascular fitness through exercise at the expense of accelerated fibrotic change.
High-Quality Genome Reconstruction of Candida albicans CHN1 Using Nanopore and Illumina Sequencing and Hybrid Assembly

We report an improved, nearly closed, high-quality draft genome of the Candida albicans CHN1 strain (ATCC MYA-4779), a human isolate, using Illumina and Nanopore sequencing. Covering six complete and two partial nuclear chromosomes along with a partial mitochondrial genome, this assembly is 14,787,852 bases in size, with 5,935 genes. ABSTRACT We report an improved, nearly closed, high-quality draft genome reconstruction of the Candida albicans CHN1 strain (ATCC MYA-4779), a human isolate, using Illumina and Nanopore sequencing. Covering six complete and two partial nuclear chromosomes along with a partial mitochondrial genome, this assembly is 14,787,852 bases in size, with 5,935 genes.
Prevalence, Characteristics, and Prognosis of Peripheral Arterial Disease in Patients With Diabetic Charcot Foot.

Charcot foot (CF) is a rare complication of diabetes associated with foot deformities and foot ulcers. Peripheral arterial disease (PAD) is a factor of poor prognosis in patients with diabetic foot ulcers (DFUs). However, PAD has infrequently been studied in CF. We aimed to determine the prevalence, the characteristics and the prognosis of PAD in a large group of patients with diabetic CF. We retrospectively compared 56 patients with diabetic CF to 116 patients with diabetic foot without CF. The prevalence of PAD in patients with CF was 66.1%. Compared to patients without CF, patients with CF had similar risks to have PAD (OR 0.98, 95%CI 0.50-1.94, p= .97) and neuro-ischemic DFUs (OR 1.19, 95%CI 0.57-2.49, p= .65), more risk to have lesions of distal arteries (OR 4.17, 95%CI 1.76-9.94, p= .001) and less risk to need revascularization (OR 0.14, 95%CI 0.06-0.36, p< .001). In patients with CF, PAD was strongly predicted by DFUs (OR 24.55, 95%CI 1.80-334.43, p= .016) and coronary artery disease (OR 17.11, 95%CI 1.75-167.43, p =.015). Survival rate and limb salvage rate in patients with CF were not worsened by PAD and by neuro-ischemic DFUs, respectively. In conclusion, we show that PAD should not be overlooked in patients with diabetic CF, especially in those having DFUs or coronary artery disease. PAD in patients with CF differed from that of patients without CF since it predominated in distal arteries and required less often revascularization.
SULT genetic polymorphisms: physiological, pharmacological and clinical implications

Abstract Introduction Cytosolic sulfotransferases (SULTs)-mediated sulfation is critically involved in the metabolism of key endogenous compounds, such as catecholamines and thyroid/steroid hormones, as well as a variety of drugs and other xenobiotics. Studies performed in the past three decades have yielded a good understanding about the enzymology of the SULTs and their structural biology, phylogenetic relationships, tissue/organ-specific/developmental expression, as well as the regulation of the SULT gene expression. An emerging area is related to the functional impact of the SULT genetic polymorphisms. Areas covered The current review aims to summarize our current knowledge about the above-mentioned aspects of the SULT research. An emphasis is on the information concerning the effects of the polymorphisms of the SULT genes on the functional activity of the SULT allozymes and the associated physiological, pharmacological, and clinical implications. Expert opinion Elucidation of how SULT SNPs may influence the drug-sulfating activity of SULT allozymes will help understand the differential drug metabolism and eventually aid in formulating personalized drug regimens. Moreover, the information concerning the differential sulfating activities of SULT allozymes toward endogenous compounds may allow for the development of strategies for mitigating anomalies in the metabolism of these endogenous compounds in individuals with certain SULT genotypes.
Changes to the activity and sensitivity of nerves innervating subchondral bone contribute to pain in late-stage osteoarthritis

Supplemental Digital Content is Available in the Text. Electrophysiological recordings in a rat model of osteoarthritis reveal pain in late stages of osteoarthritis involves activation and sensitization of nerves that innervate subchondral bone. Abstract Although it is clear that osteoarthritis (OA) pain involves activation and/or sensitization of nociceptors that innervate knee joint articular tissues, much less is known about the role of the innervation of surrounding bone. In this study, we used monoiodoacetate (MIA)-induced OA in male rats to test the idea that pain in OA is driven by differential contributions from nerves that innervate knee joint articular tissues vs the surrounding bone. The time-course of pain behavior was assayed using the advanced dynamic weight-bearing device, and histopathology was examined using haematoxylin and eosin histology. Extracellular electrophysiological recordings of knee joint and bone afferent neurons were made early (day 3) and late (day 28) in the pathogenesis of MIA-induced OA. We observed significant changes in the function of knee joint afferent neurons, but not bone afferent neurons, at day 3 when there was histological evidence of inflammation in the joint capsule, but no damage to the articular cartilage or subchondral bone. Changes in the function of bone afferent neurons were only observed at day 28, when there was histological evidence of damage to the articular cartilage and subchondral bone. Our findings suggest that pain early in MIA-induced OA involves activation and sensitization of nerves that innervate the joint capsule but not the underlying subchondral bone, and that pain in late MIA-induced OA involves the additional recruitment of nerves that innervate the subchondral bone. Thus, nerves that innervate bone should be considered important targets for development of mechanism-based therapies to treat pain in late OA.
Comparing Mid-Term Outcomes Between ACDF and Minimally Invasive Posterior Cervical Foraminotomy in the Treatment of Cervical Radiculopathy

ACDF has become one of the most commonly performed procedures by spinal surgeons and regarded as the gold-standard surgical treatment for cervical radiculopathy. MI-PCF is a safe and effective alternative to ACDF, demonstrating substantial benefit. MI-PCF demonstrated superior improvements in VAS scores, without increased complication or revision rates. Study Design. Retrospective cohort study. Objective. To compare minimally invasive posterior cervical foraminotomy (MI-PCF) and anterior cervical discectomy and fusion (ACDF) in the treatment of unilateral cervical radiculopathy. Summary of Background Data. MI-PCF has been shown to be equally effective as ACDF in treating cervical radiculopathy due to foraminal stenosis and similar pathologies. Additionally, it has been hypothesized that preserving motion and avoiding fusion reduces risk for adjacent segment disease, but potentially increases risk for subsequent revision to an ACDF. With similar short-term outcomes and substantial advantages, MI-PCF may be an effective alternative to ACDF for addressing appropriate cervical pathology. Methods. A retrospective review was performed to identify patients between 2009 and 2013 who underwent ACDF or MI-PCF with a minimum follow-up of 7 years. Demographic data was recorded. Revision rates and average time to revision between cohorts were compared. Clinical outcomes were assessed at each follow-up visit with Neck Disability Index and Visual Analog Scale for neck and Visual Analog Scale for arm pain scores. All complications were reviewed. Standard binomial and categorical comparative analysis were performed. Results. A total of 251 consecutive patients were included (205 ACDF, 46 MI-PCF). Mean follow-ups for the ACDF and MI-PCF groups were 98.3 and 95.9 months, respectively. Complication rates were 2.9% and 2.2% for the ACDF and MI-PCF cohorts, respectively (P = 0.779). Revision rates were 7.8% for the ACDF cohort and 8.7% for the MI-PCF cohort (P = 0.840). Both cohorts experienced significant improvements in their clinical scores compared with their preoperative values. Final Visual Analog Scale for neck pain (ACDF: 2.6; MI-PCF: 1.6) and Visual Analog Scale for arm pain (ACDF: 1.1; MI-PCF: 0.4) scores differed significantly at final follow-up (P = < 0.001; P = < 0.001). Conclusion. MI-PCF is a safe and effective alternative to ACDF in the treatment of cervical radiculopathy, demonstrating substantial benefit. After final follow-up, MI-PCF demonstrated superior improvements in Visual Analog Scale scores, without increased complication or revision rates. Level of Evidence: 3
Stability of Stone–Wales defect in two-dimensional honeycomb crystals

We have studied the valence effects on the stability of Stone–Wales (SW) defect in some typical two-dimensional honeycomb crystals containing group-IV, V, and VI elements employing density functional theory. The energetics involved in an in-plane formation process of SW defects in pristine and substitutionally doped materials is simulated. The SW defects are stable and have a rotation angle about 90 degree in the group-IV materials. They may become less stable with a smaller rotation angle in the group-V materials and seem difficult to exist in the group-VI materials. Group-VI doping may help eliminate SW defects while group-IV and V doping might introduce SW defects in some group-VI compounds.
Transplantation of the Stromal Vascular Fraction (SVF) Mitigates Severe Radiation-Induced Skin Injury

Severe radiation-induced skin injury is a complication of tumor radiotherapy and nuclear accidents. Cell therapy is a potential treatment for radiation-induced skin injury. The stromal vascular fraction (SVF) is a newer material in stem cell therapy that is made up of stem cells harvested from adipose tissue, which has been shown to promote the healing of refractory wounds of different causes. In this study, SVF was isolated from patients with radiation-induced skin injury. Adipose-derived stem cells (ADSCs) accounted for approximately 10% of the SVF by flow cytometry. Compared with the control group of rats, administration with SVF attenuated the skin injury induced by electron beam radiation. The effect of SVF on the human skin fibroblast microenvironment was determined by proteomic profiling of secreted proteins in SVF-co-cultured human skin fibroblast WS1 cells. Results revealed 293 upregulated and 1,481 downregulated proteins in the supernatant of SVF-co-cultured WS1 cells. WS1 co-culture with SVF induced secretion of multiple proteins including collagen and MMP-1. In the clinic, five patients with radiation-induced skin injury were recruited to receive SVF transfer-based therapy, either alone or combined with flap transplantation. Autogenous SVF was isolated and introduced into a multi-needle precision electronic injection device, which automatically and aseptically distributed the SVF to the exact layer of the wound in an accurate amount. After SVF transfer, wound healing clearly improved and pain was significantly relieved. The patients' skin showed satisfactory texture and shape with no further wound recurrence. Our findings suggest that transplantation of SVF could be an effective countermeasure against severe radiation-induced skin injury.
Prosodic Prominence – A Cross-Linguistic Perspective

This paper is concerned with the contributions of signal-driven and expectation-driven mechanisms to a general understanding of the phenomenon of prosodic prominence from a cross-linguistic perspective. It serves as an introduction to the concept of prosodic prominence and discusses the eight papers in the Special Issue, which cover a genetically diverse range of languages. These include Djambarrpuyŋu (an Australian Pama-Nyungan language), Samoan (an Austronesian Malayo-Polynesian language), the Indo-European languages English (Germanic), French (Romance), and Russian (Slavic), Korean (Koreanic), Medumba (Bantu), and two Sino-Tibetan languages, Mandarin and Taiwanese Southern Min.
Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for childhood acute lymphoblastic leukemia

Childhood acute lymphoblastic leukemia (cALL) still represents a major cause of disease-related death in children. This study aimed to explore the prognostic value of long non-coding RNAs (lncRNAs) in cALL. We downloaded lncRNA expression profiles from the TARGET and GEO databases. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify lncRNA-based signatures. We identified an eight-lncRNA signature (LINC00630, HDAC2-AS2, LINC01278, AL356599.1, AC114490.1, AL132639.3, FUT8.AS1, and TTC28.AS1), which separated the patients into two groups with significantly different overall survival rates. A nomogram based on the signature, BCR ABL1 status and white blood cell count at diagnosis was developed and showed good accuracy for predicting the 3-, 5- and 7-year survival probability of cALL patients. The C-index values of the nomogram in the training and internal validation set reached 0.8 (95% CI, 0.757 to 0.843) and 0.806 (95% CI, 0.728 to 0.884), respectively. The nomogram proposed in this study objectively and accurately predicted the prognosis of cALL. In vitro experiments suggested that LINC01278 promoted the proliferation of leukemic cells and inhibited leukemic cell apoptosis by targeting the inhibition of miR-500b-3p in cALL, and LINC01278 may be a biological target for the treatment of cALL in the future.
Is there a role for the p75 neurotrophin receptor in mediating degeneration during oxidative stress and after hypoxia?

Cholinergic basal forebrain (cBF) neurons are particularly vulnerable to degeneration following trauma and in neurodegenerative conditions. One reason for this is their characteristic expression of the p75 neurotrophin receptor (p75NTR), which is up‐regulated and mediates neuronal death in a range of neurological and neurodegenerative conditions, including dementia, stroke and ischaemia. The signalling pathway by which p75NTR signals cell death is incompletely characterised, but typically involves activation by neurotrophic ligands and signalling through c‐Jun kinase, resulting in caspase activation via mitochondrial apoptotic signalling pathways. Less well appreciated is the link between conditions of oxidative stress and p75NTR death signalling. Here, we review the literature describing what is currently known regarding p75NTR death signalling in environments of oxidative stress and hypoxia to highlight the overlap in signalling pathways and the implications for p75NTR signalling in cBF neurons. We propose that there is a causal relationship and define key questions to test this assertion.
IPC recovery length of 45 minutes improves muscle oxygen saturation during active sprint recovery

ABSTRACT Ischemic preconditioning (IPC) involves brief, repeated bouts of limb occlusion and reperfusion capable of improving exercise performance at least partially by enhancing local skeletal muscle oxygenation. This study sought to investigate the effect of a lower limb IPC protocol, with either a 5-min or 45-min post-application delay, on vastus lateralis tissue saturation index (TSI) and systemic cardiac hemodynamics at rest and during short-duration intense cycling. Twelve young adults randomly completed four interventions: IPC (at 220 mmHg) with 5-min delay (IPC5), IPC with 45-min delay (IPC45), SHAM (at 20 mmHg) with 5-min delay (SHAM5), and SHAM with 45-min delay (SHAM45). Following IPC intervention and recovery delay, participants completed 5, 60-s high-intensity (100% W peak) cycle sprints separated by 120-sec of active recovery (30% W peak). Compared to baseline, TSI immediately following IPC5, but pre-exercise, remained lower than the equivalent for IPC45 (−5.9 ± 1.5%, p = .002). IPC, imposed at least 45-min before the completion of five 60-s sprint cycling efforts, significantly enhanced TSI during active recovery between sprint intervals compared to a 5-min delay (6.6 ± 2.4%, p = .021), and identical SHAM conditions (SHAM5: 5.8 ± 2.2%, p = .024; SHAM45: 6.2 ± 2.5%, p = .029). A 45-min delay following IPC appears to provide heightened skeletal muscle metabolic rebound prior to intense sprint cycling as compared to a 5-min delay. Furthermore, IPC followed by a 45-min delay enhanced recovery of skeletal muscle oxygenation during low intensity active sprint recovery, despite an unchanged decline in skeletal muscle oxygenation during near-maximal sprinting efforts.
Radiofrequency thermoablation (RFA) and radiotherapy (RT) combined treatment for bone metastases: a systematic review.

OBJECTIVE Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary approach. Both radiofrequency ablation (RFA) and radiation therapy (RT) were safe and effective in the management of painful metastases, even if they rely on totally different action mechanisms. A synergistic combination of RT and RFA seems to result in a better pain control. A systematic review was performed to describe the feasibility and effectiveness of the association between RFA and RT in the treatment of metastatic bone pain in oligo-metastatic patients, evaluating its role in alleviating bone pain, reducing the risk of fractures, and consequently ensuring a better quality of life. MATERIALS AND METHODS A systematic database search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review included studies that reported populations meeting the following inclusion criteria: (I) conﬁrmed bone metastases in adult patients; (II) active bone metastases pain; (III) patients treated with combined RFA-RT; (IV) Original studies. RESULTS Three papers that evaluated the combined treatment with doses ranging from moderately hypofractionated three-dimensional conformal RT (3D-CRT) and stereotactic body radiation therapy (SBRT) schedules were selected. CONCLUSIONS The RFA-RT combined strategy appears to be promising in terms of efficiency and safety with adequate pain control and quality of life improvement. Positive effects on time to local failure and overall survival increase were also observed. Further prospective studies are needed to better delineate RFA-RT treatment benefits.
Transparency in risk-disproportionate regulation of modern crop-breeding techniques

ABSTRACT Despite over 25 years of safe deployment of genetically engineered crops, the number, complexity, and scope of regulatory studies required for global approvals continue to increase devoid of adequate scientific justification. Recently, there have been calls to further expand the scope of study and data requirements to improve public acceptance. However, increased regulation can actually generate consumer distrust due to the misperception that risks are high. We believe risk-disproportionate regulation as a means to advocate for acceptance of technology is counterproductive, even though some regulatory authorities believe it part of their mandate. To help avoid public distrust, the concept of regulatory transparency to demystify regulatory decision-making should be extended to clearly justifying specific regulatory requirements as: 1) risk-driven (i.e., proportionately addressing increased risk compared with traditional breeding), or 2) advocacy-driven (i.e., primarily addressing consumer concerns and acceptance). Such transparency in the motivation for requiring risk-disproportionate studies would: 1) lessen over-prescriptive regulation, 2) save public and private resources, 3) make beneficial products and technologies available to society sooner, 4) reduce needless animal sacrifice, 5) improve regulatory decision-making regarding safety, and 6) lessen public distrust that is generated by risk-disproportionate regulation.
Developmental Network-2: The Autonomous Generation of Optimal Internal-Representation Hierarchy

It is very challenging for machine learning methods to reach the goal of general-purpose learning since there are so many complicated situations in different tasks. The learning methods need to generate flexible internal representations for all scenarios met before. The hierarchical internal representation is considered as an efficient way to build such flexible representations. By hierarchy, we mean important local features in the input can be combined to form higher level features with more context. In this work, we analyze how our proposed general-purpose learning framework—the developmental network-2 (DN-2)—autonomously generates internal hierarchy with new mechanisms. Specifically, DN-2 incrementally allocates neuronal resources to different levels of representation during learning instead of handcrafting static boundaries among different levels of representation. We present the mathematical proof to demonstrate that optimal properties in terms of maximum likelihood (ML) are established under the conditions of limited learning experience and resources. The phoneme recognition and real-world visual navigation experiments that are of different modalities and include many different situations are designed to investigate general-purpose learning capability of DN-2. The experimental results show that DN-2 successfully learns different tasks. The formed internal hierarchical representations focus on important features, and the invariant abstract arise from optimal internal representations. We believe that DN-2 is in the right way toward fully autonomous learning.