Miracle-dz/UniFAR-FTUs huggingface dataset:
Biofilms in Periprosthetic Joint Infections: A Review of Diagnostic Modalities, Current Treatments, and Future Directions

Abstract As the number of total joint arthroplasties continues to rise, periprosthetic joint infection (PJI), a significant and devastating complication of total joint arthroplasty, may also increase. In PJI, bacterial biofilms are formed by causative pathogens surrounded by extracellular matrix with relatively dormant cells that can persist, resulting in a barrier against the host immune system and antibiotics. These biofilms not only contribute to the pathogenesis of PJI but also result in diagnostic challenges, antibiotic resistance, and PJI treatment failure. This review discusses the development of biofilms and key features associated with biofilm pathogenicity in PJI, current PJI diagnostic methods and their limitations, and current treatment options. Additionally, this article explores novel approaches to treat PJI, including targeting persister bacteria, immunotherapy, antimicrobial peptides, nanoparticles, and bacteriophage therapy. Biofilm eradication can also be achieved through enzymatic therapy, photodynamic therapy, and ultrasound. Finally, this review discusses novel techniques to prevent PJI, including improved irrigation solutions, smart implants with antimicrobial properties, inhibition of quorum sensing, and vaccines, which may revolutionize PJI management in the future by eradicating a devastating problem.
Practice-Based Research in Complementary Medicine: Could N-of-1 Trials Become the New Gold Standard?

Complementary medicines and therapies are popular forms of healthcare with a long history of traditional use. Yet, despite increasing consumer demand, there is an ongoing exclusion of complementary medicines from mainstream healthcare systems. A lack of evidence is often cited as justification. Until recently, high-quality evidence of treatment efficacy was defined as findings from well-conducted systematic reviews and meta-analyses of randomized controlled trials. In a recent and welcome move by the Oxford Centre for Evidence-Based Practice, however, the N-of-1 trial design has also been elevated to the highest level of evidence for treatment efficacy of an individual, placing this research design on par with the meta-analysis. N-of-1 trial designs are experimental research methods that can be implemented in clinical practice. They incorporate much of the rigor of group clinical trials, but are designed for individual patients. Individualizing treatment interventions and outcomes in research designs is consistent with the movement towards patient-centered care and aligns well with the principles of holism as practiced by naturopaths and many other complementary medicine practitioners. This paper explores whether rigorously designed and conducted N-of-1 trials could become a new ‘gold standard’ for demonstrating treatment efficacy for complementary medicine interventions in individual patients in clinical practice.
Traditional healers’ and biomedical practitioners’ perceptions of collaborative mental healthcare in low- and middle-income countries: A systematic review

Access to mental healthcare in low- and middle-income countries (LMICs) is one of the greatest challenges in public health today. One suggestion for improving accessibility is through collaboration between biomedical practitioners and traditional healers. This paper reviews studies of traditional healers’ and biomedical practitioners’ perceptions of collaboration. We conducted a systematic review of online databases, selected journals, and reference lists for relevant studies. Eligible papers were assessed using a tool designed for this review for quality and study characteristics, and qualitative data demonstrating participants’ views were extracted. A total of 14 papers from seven countries were included. The published literature on this topic is relatively homogenous and studies are of variable quality. The findings suggest that, despite differing conceptualisations of mental illness causation, both traditional healers and biomedical practitioners recognise that patients can benefit from a combination of both practices and demonstrate a clear willingness to work together. There are concerns about patients’ safety and human rights regarding traditional methods and some healers are sceptical about the effectiveness of Western psychiatric medication. Despite keeping the inclusion criteria open to all LMICs, 13 of the studies were conducted in Africa, seven of which were in South Africa. This limits the applicability of the findings of this review to the wider LMIC context. The paper concludes with recommendations for research and practice.
Temperature and Light-Quality-Dependent Regulation of Freezing Tolerance in Barley

It is established that, besides the cold, incident light also has a crucial role in the cold acclimation process. To elucidate the interaction between these two external hardening factors, barley plantlets were grown under different light conditions with low, normal, and high light intensities at 5 and 15 °C. The expression of the HvCBF14 gene and two well-characterized members of the C-repeat binding factor (CBF)-regulon HvCOR14b and HvDHN5 were studied. In general, the expression level of the studied genes was several fold higher at 5 °C than that at 15 °C independently of the applied light intensity or the spectra. The complementary far-red (FR) illumination induced the expression of HvCBF14 and also its target gene HvCOR14b at both temperatures. However, this supplementation did not affect significantly the expression of HvDHN5. To test the physiological effects of these changes in environmental conditions, freezing tests were also performed. In all the cases, we found that the reduced R:FR ratio increased the frost tolerance of barley at every incident light intensity. These results show that the combined effects of cold, light intensity, and the modification of the R:FR light ratio can greatly influence the gene expression pattern of the plants, which can result in increased plant frost tolerance.
The Link between Polyphenol Structure, Antioxidant Capacity and Shelf-Life Stability in the Presence of Fructose and Ascorbic Acid

Polyphenols play an important role in the sensorial and health-promoting properties of fruits and vegetables and display varying structure-dependent stability during processing and shelf-life. The current work aimed to increase the fundamental understanding of the link between the stability of polyphenols as a function of their structure, presence of ascorbic acid and fructose and total antioxidant capacity (TAC), using a multi-component model system. Polyphenol extract, used as the multi-component model system, was obtained from freeze-dried, high polyphenol content strawberry (Fragaria × ananassa ‘Nerina’) and twenty-one compounds were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The TAC and the first-order degradation kinetics were obtained, linking the polyphenol stability to its chemical structure, with and without the presence of fructose and ascorbic acid. The TAC (measured by oxygen radical absorption capacity (ORAC) and ferric reducing antioxidant potential (FRAP) assays) was not dramatically affected by storage temperatures and formulation, while polyphenol stability was significantly and structure dependently affected by temperature and the presence of ascorbic acid and fructose. Anthocyanins and phenolic acids were more unstable in the presence of ascorbic acid, while flavonol stability was enhanced by its presence. Shelf life study performed at 37 °C revealed significantly higher stability of purified polyphenols vs. the stability of the same polyphenols in the strawberry extract (multi-component system).
Spatial Arrangement Drastically Changes the Neural Representation of Multiple Visual Stimuli That Compete in More Than One Feature Domain

Natural scenes often contain multiple objects and surfaces. However, how neurons in the visual cortex represent multiple visual stimuli is not well understood. Previous studies have shown that, when multiple stimuli compete in one feature domain, the evoked neuronal response is biased toward the stimulus that has a stronger signal strength. Natural scenes often contain multiple objects and surfaces. However, how neurons in the visual cortex represent multiple visual stimuli is not well understood. Previous studies have shown that, when multiple stimuli compete in one feature domain, the evoked neuronal response is biased toward the stimulus that has a stronger signal strength. We recorded from two male macaques to investigate how neurons in the middle temporal cortex (MT) represent multiple stimuli that compete in more than one feature domain. Visual stimuli were two random-dot patches moving in different directions. One stimulus had low luminance contrast and moved with high coherence, whereas the other had high contrast and moved with low coherence. We found that how MT neurons represent multiple stimuli depended on the spatial arrangement. When two stimuli were overlapping, MT responses were dominated by the stimulus component that had high contrast. When two stimuli were spatially separated within the receptive fields, the contrast dominance was abolished. We found the same results when using contrast to compete with motion speed. Our neural data and computer simulations using a V1-MT model suggest that the contrast dominance found with overlapping stimuli is due to normalization occurring at an input stage fed to MT, and MT neurons cannot overturn this bias based on their own feature selectivity. The interaction between spatially separated stimuli can largely be explained by normalization within MT. Our results revealed new rules on stimulus competition and highlighted the impact of hierarchical processing on representing multiple stimuli in the visual cortex. SIGNIFICANCE STATEMENT Previous studies have shown that the neural representation of multiple visual stimuli can be accounted for by a divisive normalization model. By using multiple stimuli that compete in more than one feature domain, we found that luminance contrast has a dominant effect in determining competition between multiple stimuli when they are overlapping but not spatially separated. Our results revealed that neuronal responses to multiple stimuli in a given cortical area cannot be simply predicted by the population neural responses elicited in that area by the individual stimulus components. To understand the neural representation of multiple stimuli, rather than considering response normalization only within the area of interest, one must consider the computations including normalization occurring along the hierarchical visual pathway.
Factors That Govern the Induction of Long-Lived Antibody Responses

The induction of long-lasting, high-titer antibody responses is critical to the efficacy of many vaccines. The ability to produce durable antibody responses is governed by the generation of the terminally differentiated antibody-secreting B cells known as long-lived plasma cells (LLPCs). Once induced, LLPCs likely persist for decades, providing long-term protection against infection. The factors that control the generation of this important class of B cells are beginning to emerge. In particular, antigens with highly dense, multivalent structures are especially effective. Here we describe some pathogens for which the induction of long-lived antibodies is particularly important, and discuss the basis for the extraordinary ability of multivalent antigens to drive differentiation of naïve B cells to LLPCs.
Neuroprotective γ-Pyrones from Fusarium Solani JS-0169: Cell-Based Identification of Active Compounds and an Informatics Approach to Predict the Mechanism of Action

Glutamate toxicity has been implicated in neuronal cell death in both acute CNS injury and in chronic diseases. In our search for neuroprotective agents obtained from natural sources that inhibit glutamate toxicity, an endophytic fungus, Fusarium solani JS-0169 isolated from the leaves of Morus alba, was found to show potent inhibitory activity. Chemical investigation of the cultures of the fungus JS-0169 afforded isolation of six compounds, including one new γ-pyrone (1), a known γ-pyrone, fusarester D (2), and four known naphthoquinones: karuquinone B (3), javanicin (4), solaniol (5), and fusarubin (6). To identify the protective effects of the isolated compounds (1–6), we assessed their inhibitory effect against glutamate-induced cytotoxicity in HT22 cells. Among the isolates, compound 6 showed significant neuroprotective activity on glutamate-mediated HT22 cell death. In addition, the informatics approach using in silico systems pharmacology identified that compound 6 may exert its neuroprotective effect by controlling the amount of ubiquinone. The results suggest that the metabolites produced by the endophyte Fusarium solani JS-0169 might be related to the neuroprotective activity of its host plant, M. alba.
Cost-Effective Wearable Indoor Localization and Motion Analysis via the Integration of UWB and IMU

Wearable indoor localization can now find applications in a wide spectrum of fields, including the care of children and the elderly, sports motion analysis, rehabilitation medicine, robotics navigation, etc. Conventional inertial measurement unit (IMU)-based position estimation and radio signal indoor localization methods based on WiFi, Bluetooth, ultra-wide band (UWB), and radio frequency identification (RFID) all have their limitations regarding cost, accuracy, or usability, and a combination of the techniques has been considered a promising way to improve the accuracy. This investigation aims to provide a cost-effective wearable sensing solution with data fusion algorithms for indoor localization and real-time motion analysis. The main contributions of this investigation are: (1) the design of a wireless, battery-powered, and light-weight wearable sensing device integrating a low-cost UWB module-DWM1000 and micro-electromechanical system (MEMS) IMU-MPU9250 for synchronized measurement; (2) the implementation of a Mahony complementary filter for noise cancellation and attitude calculation, and quaternions for frame rotation to obtain the continuous attitude for displacement estimation; (3) the development of a data fusion model integrating the IMU and UWB data to enhance the measurement accuracy using Kalman-filter-based time-domain iterative compensations; and (4) evaluation of the developed sensor module by comparing it with UWB- and IMU-only solutions. The test results demonstrate that the average error of the integrated module reached 7.58 cm for an arbitrary walking path, which outperformed the IMU- and UWB-only localization solutions. The module could recognize lateral roll rotations during normal walking, which could be potentially used for abnormal gait recognition.
Establishment of A Reversibly Inducible Porcine Granulosa Cell Line

Granulosa cells (GCs) are the key components of ovarian follicles for regulating oocyte maturation. Previous established GC lines have allowed prolonged proliferation, but lost some physiological features owing to long-term immortalization. This study was to establish an induced immortal porcine GC line with reversible proliferation status by the tetracycline inducible (Tet-on) 3G system. Our conditional immortal porcine GCs (CIPGCs) line steadily propagated for at least six months and displayed primary GC morphology when cultured in the presence of 50 ng/mL doxycycline [Dox (+)]. Upon Dox withdrawal [Dox (–)], Large T-antigen expression, reflected by mCherry fluorescence, gradually became undetectable within 48 h, accompanied by less proliferation and size increase. The levels of estradiol and progesterone, and the expression of genes associated with steroid production, such as CYP11A1 (cytochrome P450 family 11), 3β-HSD (3β-hydroxysteroid dehydrogenase), StAR (steroidogenic acute regulatory protein), and CYP19A1 (cytochrome P450 family 19 subfamily a member 1), were all significantly higher in the Dox (–) group than Dox (+) group. The CIPGCs could switch into a proliferative state upon Dox induction. Interestingly, the expression of StAR and CYP19A1 in the CIPGCs (–Dox) was significantly increased by adding porcine follicular fluid (PFF) to mimic an ovary follicle environment. Moreover, PFF priming the CIPGCs in Dox (–) group resulted in similar estradiol production as that of primary GC, and enabled this cell line to respond to gonadotrophins in estradiol production. Collectively, we have established an inducible immortal porcine GC line, which offers a unique and valuable model for future research on the regulation of ovarian functions.
Glabralysins, Potential New β-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata

Biomphalaria glabrata is a freshwater Planorbidae snail. In its environment, this mollusk faces numerous microorganisms or pathogens, and has developed sophisticated innate immune mechanisms to survive. The mechanisms of recognition are quite well understood in Biomphalaria glabrata, but immune effectors have been seldom described. In this study, we analyzed a new family of potential immune effectors and characterized five new genes that were named Glabralysins. The five Glabralysin genes showed different genomic structures and the high degree of amino acid identity between the Glabralysins, and the presence of the conserved ETX/MTX2 domain, support the hypothesis that they are pore-forming toxins. In addition, tertiary structure prediction confirms that they are structurally related to a subset of Cry toxins from Bacillus thuringiensis, including Cry23, Cry45, and Cry51. Finally, we investigated their gene expression profiles in snail tissues and demonstrated a mosaic transcription. We highlight the specificity in Glabralysin expression following immune stimulation with bacteria, yeast or trematode parasites. Interestingly, one Glabralysin was found to be expressed in immune-specialized hemocytes, and two others were induced following parasite exposure.
Expression and clinical significance of HOXA5, E-cadherin, and β-catenin in cervical squamous cell carcinoma.

OBJECTIVES HOXA5 has been identified as a biomarker in pathogenesis of several cancers, such as non-small cell lung cancer (NSCLC) and breast cancer cells. The role has not been explored in cervical squamous cell carcinoma (CSCC). METHODS Tissues of 120 cases with CSCC and 30 controls with chronic cervicitis were constructed from our archived surgical pathology files and staining with HOXA5. Additional antibodies to E-cadherin and β-catenin were stained for comparison. For each marker, low expression was defined as staining score 0 to 3 points, whereas high expression referred to 4 points and above. Fifty-four patients in this research with cervical cancer were followed up for prognostic assessment. RESULT HOXA5 had high expression in chronic cervicitis and low in CSCC (P=0.004). The positivity rates of HOXA5 in patients without muscular layer invasion (MLI) and lymphatic invasion (LI) was higher than that in metastasis (113 vs. 17; 117 vs. 3). Consistently, low expression of HOXA5 was more common in poorly differentiated carcinoma, CSCC subjects without MLI and LI. Expression of E-cadherin and β-catenin was parallel with the expression of HOXA5. Additionally, patients with higher expression of HOXA5 had much more favorable prognosis than those with lower expression among follow up of the 54 patients. CONCLUSION In parallel with E-cadherin and β-catenin, low expression of HOXA5 was more common in CSCC patients with poor differentiation, without MLI and LI, among those which showed poor prognosis.
Differential Expression of CD31 and Von Willebrand Factor on Endothelial Cells in Different Regions of the Human Brain: Potential Implications for Cerebral Malaria Pathogenesis

Cerebral microvascular endothelial cells (CMVECs) line the vascular system of the brain and are the chief cells in the formation and function of the blood brain barrier (BBB). These cells are heterogeneous along the cerebral vasculature and any dysfunctional state in these cells can result in a local loss of function of the BBB in any region of the brain. There is currently no report on the distribution and variation of the CMVECs in different brain regions in humans. This study investigated microcirculation in the adult human brain by the characterization of the expression pattern of brain endothelial cell markers in different brain regions. Five different brain regions consisting of the visual cortex, the hippocampus, the precentral gyrus, the postcentral gyrus, and the rhinal cortex obtained from three normal adult human brain specimens were studied and analyzed for the expression of the endothelial cell markers: cluster of differentiation 31 (CD31) and von-Willebrand-Factor (vWF) through immunohistochemistry. We observed differences in the expression pattern of CD31 and vWF between the gray matter and the white matter in the brain regions. Furthermore, there were also regional variations in the pattern of expression of the endothelial cell biomarkers. Thus, this suggests differences in the nature of vascularization in various regions of the human brain. These observations also suggest the existence of variation in structure and function of different brain regions, which could reflect in the pathophysiological outcomes in a diseased state.
Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells

Medical treatments for corticotrophinomas are limited, and we therefore investigated the effects of epigenetic modulators, a new class of anti-tumour drugs, on the murine adrenocorticotropic hormone (ACTH)-secreting corticotrophinoma cell line AtT20. We found that AtT20 cells express members of the bromo and extra-terminal (BET) protein family, which bind acetylated histones, and therefore, studied the anti-proliferative and pro-apoptotic effects of two BET inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, using CellTiter Blue and Caspase Glo assays, respectively. JQ1 and PFI-1 significantly decreased proliferation by 95% (P < 0.0005) and 43% (P < 0.0005), respectively, but only JQ1 significantly increased apoptosis by >50-fold (P < 0.0005), when compared to untreated control cells. The anti-proliferative effects of JQ1 and PFI-1 remained for 96 h after removal of the respective compound. JQ1, but not PFI-1, affected the cell cycle, as assessed by propidium iodide staining and flow cytometry, and resulted in a higher number of AtT20 cells in the sub G1 phase. RNA-sequence analysis, which was confirmed by qRT-PCR and Western blot analyses, revealed that JQ1 treatment significantly altered expression of genes involved in apoptosis, such as NFκB, and the somatostatin receptor 2 (SSTR2) anti-proliferative signalling pathway, including SSTR2. JQ1 treatment also significantly reduced transcription and protein expression of the ACTH precursor pro-opiomelanocortin (POMC) and ACTH secretion by AtT20 cells. Thus, JQ1 treatment has anti-proliferative and pro-apoptotic effects on AtT20 cells and reduces ACTH secretion, thereby indicating that BET inhibition may provide a novel approach for treatment of corticotrophinomas.