Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Randomized Controlled Cancer Chemoprevention Trials on the Evolution of Regulatory Assessments

This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high (er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs. Cancer Prev Res; 4(3); 311–23. 2011 AACR. An ounce of prevention is worth a pound of cure.
AAC barriers and facilitators for children with Koolen de Vries syndrome and childhood apraxia of speech: parent perceptions

Abstract Despite the potential positive impact of augmentative and alternative communication, the literature suggests that many individuals with disabilities experience barriers in developing communication skills and access to appropriate supports. Parents can provide valuable insight into the barriers and facilitators experienced by their children with complex communication needs. Previous studies exploring parent perspectives of the complex communication needs of children with various disabilities have revealed similarities and differences in experiences. This supports the need to examine the barriers and facilitators experienced by different populations, including individuals with Koolen de Vries syndrome (KdVS). As a newly identified syndrome, information on individuals with KdVS is limited, and studies examining parent experiences in supporting the communication needs of children with KdVS have not been conducted. This study obtained parents' perspectives regarding the communication barriers and facilitators experienced by their children with KdVS. Fifteen parents participated in one of two focus group sessions. The data were analyzed through qualitative content analysis, resulting in 13 categories discussed in relation to previous research and conceptual frameworks. Research and practical implications for developing a deeper understanding of the barriers experienced by children with KdVS are proposed.
Quercetin in Tonglong Qibi decoction ameliorates testosterone‐induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress

Benign prostatic hyperplasia (BPH) is a common urological disease in older males. Existing pharmacotherapy shows several side effects, and the exploration of new therapeutic strategies is of high significance. Tonglong Qibi (TQ) decoction was proved to ameliorate BPH, while the underlying mechanisms are still unclear. In the current study, we explored the anti‐BPH effects of TQ in vivo and identified its main therapeutic component and the underlying mechanisms in vitro. We demonstrated that TQ mitigated BPH in rats and showed no toxicity to the liver and reproductive system. Network pharmacology identified quercetin as the main component in TQ treating BPH. Quercetin reduced proliferation, oxidative stress, and increased Nrf2 expression in hyperplastic prostate epithelial cells. These findings indicate that quercetin in TQ alleviates BPH via inhibiting oxidative stress and activating the Nrf2 signalling pathway.
The pulsatile 3D-Hemodynamics in a doubly afflicted human descending abdominal artery with iliac branching

Abstract The study of patient-specific human arterial flow dynamics is well known to face challenges like a) apt geometric modelling, b) bifurcation zone meshing, and c) capturing the hemodynamic prone to variations with multiple disease complications. Due to aneurysms and stenosis in the same arterial network, the blood flow dynamics get affected, which needs to be explored. This study develops a new protocol for accurate geometric modelling, bifurcation zone meshing and numerically investigates the arterial network with abdominal aortic aneurysms (AAA) and right internal iliac stenosis (RIIAS). A realistic arterial model is reconstructed from the computed tomography (CT) data of a human subject. To understand the combined effect of the aneurysm and aortoiliac occlusive diseases in a patient, an arterial network with AAA, RIIAS, multiple branches tapering, and curvature has been considered. Clinically significant pulsatile blood flow simulations have been carried out to trace the alteration in the flow dynamics with multiple pathological complications under consideration. The transient blood flow dynamics are investigated via wall shear stress, wall pressure, velocity contour, streamlines, vorticity, and swirling strength. During the systolic deceleration phase, the rhythmic nested rapid secondary oscillatory WSS, adverse pressure gradients, high WSS, and high WP bands are noticed. Also, the above studies will help researchers, clinicians, and doctors understand the influence of morphological changes on hemodynamics in cardiovascular studies.
Systematic identification of molecular mediators of interspecies sensing in a community of two frequently coinfecting bacterial pathogens

Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these interactions is critical for understanding and modulating bacterial behavior in natural environments. While bacterial responses to foreign species are frequently characterized at the molecular and phenotypic level, the exogenous molecules that elicit these responses are understudied. Here, we outline a systematic strategy based on transcriptomics combined with genetic and biochemical screens of promoter-reporters to identify the molecules from one species that are sensed by another. We utilized this method to study interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus that are frequently found in coinfections. We discovered that P. aeruginosa senses diverse staphylococcal exoproducts including the metallophore staphylopine (StP), intermediate metabolites citrate and acetoin, and multiple molecules that modulate its iron starvation response. We observed that StP inhibits biofilm formation and that P. aeruginosa can utilize citrate and acetoin for growth, revealing that these interactions have both antagonistic and beneficial effects. Due to the unbiased nature of our approach, we also identified on a genome scale the genes in S. aureus that affect production of each sensed exoproduct, providing possible targets to modify multispecies community dynamics. Further, a combination of these identified S. aureus products recapitulated a majority of the transcriptional response of P. aeruginosa to S. aureus supernatant, validating our screening strategy. Cystic fibrosis (CF) clinical isolates of both S. aureus and P. aeruginosa also showed varying degrees of induction or responses, respectively, which suggests that these interactions are widespread among pathogenic strains. Our screening approach thus identified multiple S. aureus secreted molecules that are sensed by P. aeruginosa and affect its physiology, demonstrating the efficacy of this approach, and yielding new insight into the molecular basis of interactions between these two species.
Previous surgery for instability is a risk factor for a worse patient-reported outcome after anatomical shoulder arthroplasty for osteoarthritis: a Danish nationwide cohort study of 3,743 arthroplasties

Background and purpose Although most patients have good outcomes after shoulder arthroplasty for osteoarthritis, certain risk factors may lead to disappointing outcomes. We assessed risk factors for a worse outcome after anatomical shoulder arthroplasty for osteoarthritis. Our hypothesis was that previous surgery for instability would be a risk factor for a worse outcome independent of age, sex, and arthroplasty type. Patients and methods We included arthroplasties reported to the Danish Shoulder Arthroplasty Registry between 2006 and 2018 (n = 3,743). The Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year was used as outcome. The total score was converted to a percentage of a maximum score. The general linear model was used to analyze differences in WOOS. Age, sex, arthroplasty type, and previous surgery were included in the multivariate model. Estimates were given with 95% confidence intervals (CI). Results The mean WOOS score was 78 for patients with no previous surgery and 55 for patients with surgery for instability. The mean difference was –16 (CI –10 to –22) in the multivariate model. Hemiarthroplasty had a worse outcome compared with total shoulder arthroplasty and young patients had a worse outcome compared with older patients. The mean differences in the multivariate model were –12 (CI –10 to –14) and –11 (CI –8 to –14) respectively. Interpretation Patients with previous surgery for instability had worse results independent of age, sex, and arthroplasty type and should be informed about their individual risk of a worse outcome.
Contextual influence of reinforcement learning performance of depression: evidence for a negativity bias?

Abstract Backgrounds Value-based decision-making impairment in depression is a complex phenomenon: while some studies did find evidence of blunted reward learning and reward-related signals in the brain, others indicate no effect. Here we test whether such reward sensitivity deficits are dependent on the overall value of the decision problem. Methods We used a two-armed bandit task with two different contexts: one ‘rich’, one ‘poor’ where both options were associated with an overall positive, negative expected value, respectively. We tested patients (N = 30) undergoing a major depressive episode and age, gender and socio-economically matched controls (N = 26). Learning performance followed by a transfer phase, without feedback, were analyzed to distangle between a decision or a value-update process mechanism. Finally, we used computational model simulation and fitting to link behavioral patterns to learning biases. Results Control subjects showed similar learning performance in the ‘rich’ and the ‘poor’ contexts, while patients displayed reduced learning in the ‘poor’ context. Analysis of the transfer phase showed that the context-dependent impairment in patients generalized, suggesting that the effect of depression has to be traced to the outcome encoding. Computational model-based results showed that patients displayed a higher learning rate for negative compared to positive outcomes (the opposite was true in controls). Conclusions Our results illustrate that reinforcement learning performances in depression depend on the value of the context. We show that depressive patients have a specific trouble in contexts with an overall negative state value, which in our task is consistent with a negativity bias at the learning rates level.
Mechanical cassava harvesting as influenced by seedbed preparation and cassava variety

A BSTRACT . Cassava ( Manihot esculenta Crantz ) is the world’s third most important crop and an essential source of food and income throughout the tropics providing livelihood for over 500 million farmers and countless processors and traders. In Ghana, cassava contributes 22% of Agricultural Gross Domestic Product (AGDP) and is an emerging profitable industry crop. Large-scale cassava harvesting especially during the dry season is the greatest constraint to its industrial demand and commercial production. Manual harvesting is slow and associated with drudgery and high root damage in the dry season. A mechanical harvester is needed to break the labor bottleneck associated with cassava harvesting. Research on mechanization of cassava production however is very low, especially in the area of harvesting and currently there exists no known mechanical cassava harvesters in Ghana. The main objective of this study was to assess the response of five different cassava varieties to mechanical harvesting on ridged and flat landforms. Results from field trials using the tek mechanical cassava harvester showed that best performance was achieved on ridged landforms, which have better tuber yields and root tuber orientation. Among all the cassava varieties, “Nkabom” was generally found to more easily lend itself to mechanical harvesting due to its bunchy nature. The tek mechanical harvester worked best on fields with minimal trash or weeds and relatively dry soils with moisture content from 12%-16% d.b. and requires drafts of up to 10.33 kN with penetration depth from 23 to 29 cm. Best harvesting performance was achieved at a tractor speed of 5 km/h giving a field capacity of 1.9 to 2.5 h/ha. After mechanical harvesting, the field is left plowed with savings on fuel, time and cost. However, it is recommended to field evaluate the harvester in all agro-ecological zones and through a wide range of soil moisture regimes in Ghana to determine suitable areas for mechanical harvesting and to promote nationwide adoption.
New Cytochalasin Derivatives from Deep‐Sea Cold Seep‐Derived Endozoic Fungus Curvularia verruculosa CS‐129

Two new antimicrobial cytochalasin derivatives, 6β,7β‐epoxydeoxaphomin C (1) and 12‐hydroxydeoxaphomin C (2), a new natural occurring product 24‐nor‐cytochalasin B (3), together with two related known analogs (4–5) were isolated and identified from an endozoic fungus Curvularia verruculosa CS‐129, isolated from the deep‐sea squat lobster Shinkaia crosnieri which was collected in cold seep region of south China sea. The structures of new compounds were elucidated on the basis of detailed spectroscopic analysis and ECD calculation. The spectroscopic data of 24‐nor‐cytochalasin B (3) were reported for the first time. All compounds were tested for their antibacterial activities against human and aquatic pathogenic bacteria.
Does intensive blood pressure control benefit type B aortic dissection patients who undergoing surgical repair?

Objectives The aim of this research is to determine the optimum blood pressure (BP) control goal for hypertensive type B aortic dissection (TBAD) patients undergoing surgery. Methods Between January 2019 and April 2021, 259 hypertensive TBAD patients undergoing surgery were included in the research. 98 patients received intensive BP control with a target of systolic BP (SBP) < 120 mmHg, and 161 received standard BP control targeting SBP between 120 and 140 mmHg. Clinical data from two groups were compared. Results Patients who received intensive BP control experienced a significantly higher incidence of acute kidney injury (AKI) postoperatively (21/98, 21.4% vs 14/161, 8.7%, p = 0.004). The intensive group took more anti-hypertensive drugs per day compared with the standard group (1.9 vs 1.5, p < 0.001). Triple-drug combination treatment was more frequent in the intensive group (38.8% vs 14.3%, p < 0.001), as were angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB; 67.3% vs 44.7%, p 0.001), and thiazide-like diuretic (44.9% vs 18.0%, p < 0.001). Conclusions Intensive BP control treatment increases the incidence of AKI and raises the utilization of the anti-hypertensive drug, but did not reduce the operative mortality and late mortality in TBAD patients undergoing surgical repair.
Lumbar Giant Disk Herniations Treated With a Unilateral Approach for Bilateral Decompression

BACKGROUND: Disk herniations that obstruct the spinal canal by more than 50% are named “giant disk herniations” (GDHs). GDHs are challenging to treat from a surgical perspective because of their size and the risk of iatrogenic manipulation during resection resulting in additional neurological compromise. As a result, the appropriateness of minimally invasive tubular approaches for the treatment of lumbar GDHs remains controversial. OBJECTIVE: To report our experience in treating lumbar GDHs using tubular minimally invasive surgery. METHODS: A total number of 228 disk herniations were evaluated for the criteria of GDH. In addition, the presence of neurological deficits such as cauda equina syndrome, pain as measured by a visual analog scale, operating time, complications, estimated intraoperative blood loss, and number of surgical revisions were assessed. The standard tubular diskectomy technique was modified to include unilateral laminectomy for bilateral decompression before the diskectomy to create a sufficient working space for removal of the disk fragments. RESULTS: Twenty-three (10%) patients met the criteria for GDH. Clinically significant motor weakness was present in 21 patients (91.3%) before surgery, and 3 patients (13%) presented with cauda equina syndrome. The average mean visual analog scale (±SD) for the preoperative pain score was 8.3 and decreased to 2.4 at follow-up after surgery. All cases of cauda equina syndrome resolved postoperatively. CONCLUSION: Unilateral tubular minimally invasive surgery diskectomy seems to be a safe and effective treatment alternative for lumbar GDHs, combined with the “over-the-top” decompression, which provides bilateral decompression and working space.
Caregiving stress and burden associated with cardiometabolic risk in family caregivers of individuals with cancer

Abstract Chronic stress is a well-established risk factor for cardiometabolic disease. Caregiving for individuals with cancer is perceived as a chronic stressor yet research on the risk for cardiometabolic disease in this population, opposed to the elderly and those with Alzheimer’s disease, is limited. Additionally, few studies have explored the early physiological changes that occur in family caregivers suggesting an elevated risk for illness. This cross-sectional study was designed to examine levels of cardiometabolic risk biomarkers and their correlates in caregivers of patients with colorectal cancer. Caregivers completed questionnaires that measure exposures to stress and vulnerability factors, psychological distress, and health habits as potential correlates. Traditional lipid and nontraditional lipoprotein particle biomarkers (e.g. concentration and size for all lipoprotein classes) were assayed from blood serum. Caregivers (N = 83, mean age = 49.8, 73% female) displayed levels of cardiometabolic biomarkers that suggest an elevated risk for cardiometabolic disease. Caregivers who were Hispanic, married, highly educated, employed, reported more hours spent caregiving daily, experienced higher caregiver burden associated with the lack of family support and impact on schedule, and psychological distress, demonstrated an elevated risk for cardiometabolic disease; primarily determined by nontraditional lipid biomarkers – large TRL-P, LDL-P, small HDL-P, large HDL-P, TRL-Z, LDL-Z and HDL-Z. These findings suggest that traditional lipid biomarkers may not be robust enough to detect early physiological changes associated with cardiometabolic disease risk in family caregivers. Moreover, findings reiterate the importance of assessing caregiver burden and providing evidence-based interventions to manage caregiving stress with the potential to improve caregivers’ cardiometabolic health.
Numerical Analysis of the Contact Pressure in a Quasi-Static Elastomeric Reciprocating Sealing System

In this technical brief, we present detailed finite element simulations of a sealing system operating in quasi-static conditions, in the framework of the real piston actuator of a landing gear braking system. Numerical results show two peaks of the contact pressure on the rod, and demonstrate that this contact pressure remains larger than that in the fluid chamber. These numerical results are qualitatively validated by scanning electron microscopy (SEM) observations of a worn sealing system. Overall, this study shows the benefits of numerical simulation in geometrical design of sealing systems targeting a given contact pressure at the rod/seal interface. [DOI: 10.1115/1.4040154]
Assessing the immunosuppressive activity of alginate-encapsulated mesenchymal stromal cells on splenocytes

Abstract Mesenchymal stromal cells (MSCs) show immunosuppressive effects both via cell-to-cell contact (direct) with immune cells and by producing paracrine factors and extracellular vesicles (indirect). A key challenge in delivering this therapeutic effect in vivo is retaining the MSCs at the site of injection. One way to address this is by encapsulating the MSCs within suitable biomaterial scaffolds. Here, we assess the immunosuppressive effect of alginate-encapsulated murine MSCs on proliferating murine splenocytes. Our results show that MSCs are able to significantly suppress splenocyte proliferation by ∼50% via the indirect mechanism and almost completely (∼98%) via the direct mechanism. We also show for the first time that MSCs as monolayers on tissue culture plastic or encapsulated within alginate, when physically isolated from the splenocytes via transwells, are able to sustain immunosuppressive activity with repeated exposure to fresh splenocytes, for as long as 9 days. These results indicate the need to identify design strategies to simultaneously deliver both modes of MSC immunosuppression. By designing cell-biomaterial constructs with tailored degradation profiles, we can achieve a more sustained (avoiding MSCs migration and apoptosis) and controlled release of both the paracrine signals and eventually the cells themselves enabling efficient MSC-based immunosuppressive therapies for wound healing.
Based on network pharmacology and in vitro experiments to prove the effective inhibition of myocardial fibrosis by Buyang Huanwu decoction

ABSTRACT Among cardiovascular diseases, myocardial fibrosis (MF) is a major pathological change underlying heart failure and is associated with a high mortality rate. However, the molecular mechanism underlying MF has remained elusive. Buyang Huanwu decoction (BYHWD), a traditional Chinese medicine (TCM) formula for cardiovascular diseases, exhibits good anti-inflammatory and blood-activating properties. In the present study, we studied the MF inhibitory effect of BYHWD using network pharmacology and experimental validation. We used several databases to collect information on MF and related drugs and finally obtained cross-targets for BYHWD and MF. After that we got protein-protein interaction (PPI) network and performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses to obtain key signaling pathways for further study. After screening, interleukin (IL)-6, IL-1β, and matrix metallopeptidase 9 (MMP9) were selected for in vitro experiments, which included cell cycle studies, cell migration rate, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB). Finally, molecular docking was performed to validate the results. We found 299 common targets between BYHWD and MF. In total, 75 core targets of the PPI core network were selected for enrichment analysis, and the IL-17 signaling pathway, which is intricately linked to inflammation, was speculated to be involved. Accordingly, in vitro experiments were performed. Altogether, our findings indicated that BYHWD can affect the function of cardiac fibroblasts and reduce the expression of inflammatory factors in rats. In summary, BYHWD can inhibit MF by reducing the expression of inflammatory factors and affecting the IL-17 signaling pathway. GRAPHICAL ABSTRACT