Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimisation of cDNA microarray tumour profiling and molecular analysis of epithelial ovarian cancer

The advent of microarray technology has allowed the study of diseases such as epithelial ovarian cancer (EOC) to occur at an unprecedented level of molecular resolution. EOC is fifth leading cause of female cancer death world wide. The prognosis of women diagnosed with this disease is often extremely poor, partially due to the difficulty of detection in its early and most treatable stages. It is hypothesised that gene expression profiling can shed light on the molecular events responsible for EOC development and progression. This information could one day be used to develop novel screening methods and therapeutic approaches based on individual tumour profiling. This thesis first describes the optimisation of several aspects of the microarray work flow and demonstrates their impact on the sensitivity and robustness of cDNA microarray data. An evaluation of reference RNA options was conducted, in which gene expression data generated using either a pool of RNA sourced from a diverse range of cell lines, or from a cohort of EOC specimens was compared. The cell line RNA was found to be the most suitable choice for a large-scale tumour profiling study based on the diverse criteria applied. A number of factors with the potential to impact on the spatial distribution of gene expression are also described and a novel method for quantification of this type of systematic bias is proposed. The findings from these comparisons are then used to create and analyse two clinically annotated dataset of EOC specimens. These data are interrogated to identify gene expression patterns related to overall length of patient survival and the phenotypic differences between the invasive and low malignant potential EOC subtypes. These analyses generated several validated sets of differentially regulated genes, many of which were clinically relevant or previously implicated in other cancer types. The molecular signatures identified were technically and biologically validated before bioinformatic analyses to identify the key biological processes and functional relationships they represent. Comparison of the gene expression signatures deduced for patient survival and serous low malignant potential vs. invasive cancer to studies of similar and disparate cancer types was carried out. The universality of the molecular events regulated by these genes in order to mediate survival and/or the malignant potential of EOC was evaluated. A significant relationship involving the altered expression of interacting calcium-dependant cell adhesion molecules was found to be important for both aspects of this disease.
Stabilization of DNA by sodium and magnesium ions during the synthesis of DNA-bridged gold nanoparticles

Nanostructures synthesized using DNA-conjugated gold nanoparticles have a wide range of applications in the field of biosensorics. The stability of the DNA duplex plays a critical role as it determines the final geometry of these nanostructures. The main way to control DNA stability is to maintain a high ionic strength of the buffer solution; at the same time, high salt concentrations lead to an aggregation of nanoparticles. In this study, by means of the instrumentality of DNA-bridged seeds using tris(hydroxymethyl)aminomethane as a soft reducing agent the dumbbell-like gold nanoparticles up to 35 nm were synthesized with a high concentration of sodium ions of up to 100 mM and magnesium ions up to 1 mM. We also examined at the atomic level the details of the effect of the gold nanoparticle surface, as well as Na+ and Mg2+ ions, on the stability of nucleotide pairs located in close proximity to the grafting site.
Acceptance, grief and adaptation amongst caregivers of partners with acquired brain injury: an interpretative phenomenological enquiry

Abstract Purpose Families provide vital support to relatives with brain injury yet shoulder significant stress and anxiety with little help threatening family cohesion and rehabilitative outcomes. This paper analyses the accounts of people caring for a long-term partner with brain injury to identify coping mechanisms and support systems that enhanced well-being. Materials and method: This study used semi-structured interviews with eight participants and interpretative phenomenological analysis. Results Three themes are reported—“moving through denial toward acceptance”; “confronting and managing ambiguous loss”; and “becoming an expert carer”. Theme one describes participants’ struggles to accept the longevity of brain injury and use of strenuous care practices to deny or fight disability; this proved counterproductive and was later remedied by individuals embracing change and making adaptations. Theme two reports how participants split their partners’ identities -before and after brain injury- to help grieve for the marital relationships they lost. Theme three looks at participants’ development of self-reliant attitudes to caregiving due to perceived limited state help, while embracing peer support that enhanced information and emotion-based coping. Conclusions Findings support therapeutic practices that help family members confront the permanence of brain injury, and target feelings of complex and unresolved grief. Future research proposals are discussed. IMPLICATIONS FOR REHABILITATION: Caregivers typically provide considerable rehabilitative support to spouses living with Acquired Brain Injury to manage the physical and psychosocial burdens of long-term disability. Therapeutic interventions should reconcile notions of hope and acceptance in order to help carers confront the permanence of brain injury and develop sustainable care practices. We recommend that interventions address feelings of unresolved grief and ambiguous loss and develop tailored support for caregivers which targets pertinent psychological concerns.
Studies on the achene morphology of Turkish species of Scorzonera L. (Asteraceae) using light and scanning electron microscopy

Macro- and micromorphological features of achenes belonging to 59 taxa from Turkey were observed via light and scanning electron microscopy. The findings agree with the traditional subdivision of Scorzonera into S. subg. Scorzonera, S. subg. Podospermum and S. subg. Pseudopodospermum. Members of S. subg. Podospermum were distinguished by achenes with a distinct carpopodium and horizontally striped epidermal cell surface; members of S. subg. Pseudopodospermum were distinguished by achenes with a conspicuous carpopodium and often ruminate and sometimes rugose-granulate or smooth epidermal surface, and members of Scorzonera s.str were distinguished by achenes without a carpopodium and with various combinations of surface patterns . The results also showed that the length, pubescence and surface pattern of achenes, as well as the carpopodium and anticlinal and periclinal walls of the epidermal cells are valuable for delimiting the examined species within the genus.
Extracellular clusterin limits the uptake of α‐synuclein fibrils by murine and human astrocytes

The progressive neuropathological damage seen in Parkinson's disease (PD) is thought to be related to the spreading of aggregated forms of α‐synuclein. Clearance of extracellular α‐synuclein released by degenerating neurons may be therefore a key mechanism to control the concentration of α‐synuclein in the extracellular space. Several molecular chaperones control misfolded protein accumulation in the extracellular compartment. Among these, clusterin, a glycoprotein associated with Alzheimer's disease, binds α‐synuclein aggregated species and is present in Lewy bodies, intraneuronal aggregates mainly composed by fibrillary α‐synuclein. In this study, using murine primary astrocytes with clusterin genetic deletion, human‐induced pluripotent stem cell (iPSC)‐derived astrocytes with clusterin silencing and two animal models relevant for PD we explore how clusterin affects the clearance of α‐synuclein aggregates by astrocytes. Our findings showed that astrocytes take up α‐synuclein preformed fibrils (pffs) through dynamin‐dependent endocytosis and that clusterin levels are modulated in the culture media of cells upon α‐synuclein pffs exposure. Specifically, we found that clusterin interacts with α‐synuclein pffs in the extracellular compartment and the clusterin/α‐synuclein complex can be internalized by astrocytes. Mechanistically, using clusterin knock‐out primary astrocytes and clusterin knock‐down hiPSC‐derived astrocytes we observed that clusterin limits the uptake of α‐synuclein pffs by cells. Interestingly, we detected increased levels of clusterin in the adeno‐associated virus‐ and the α‐synuclein pffs‐ injected mouse model, suggesting a crucial role of this chaperone in the pathogenesis of PD. Overall, our observations indicate that clusterin can limit the uptake of extracellular α‐synuclein aggregates by astrocytes and, hence, contribute to the spreading of Parkinson pathology.
Cysteine focused covalent inhibitors against the main protease of SARS-CoV-2

Abstract In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys–His catalytic dyad, and ligands that interact with the Cys145 assumed to be an effective approach to inhibit the Mpro. In this study, approximately 1400 cysteine-focused ligands were screened to identify the best candidates that can act as potent inhibitors against Mpro. Our results show that the selected ligands strongly interact with the key Cys145 and His41 residues. Covalent docking was performed for the selected candidates containing the acrylonitrile group, which can form a covalent bond with Cys145. All atoms molecular dynamics (MD) simulation was performed on the selected four inhibitors including L1, L2, L3 and L4 to validate the docking interactions. Our results were also compared with a control ligand, α-ketoamide (11r). Principal component analysis on structural and energy data obtained from the MD trajectories shows that L1, L3, L4 and α-ketoamide (11r) have structural similarity with the apo-form of the Mpro. Quantitative structure-activity relationship method was employed for pattern recognition of the best ligands, which discloses that ligands containing acrylonitrile and amide warheads can show better performance. ADMET analysis displays that our selected candidates appear to be safer inhibitors. Our combined studies suggest that the best cysteine focused ligands can help to design an effective lead drug for COVID-19 treatment. Communicated by Ramaswamy H. Sarma Graphical Abstract
Cytotoxic T cells swarm by homotypic chemokine signalling

Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. CTLs engaging cognate targets accelerate the recruitment of distant T cells through long-range homotypic signalling, in part mediated via the diffusion of chemokines CCL3 and CCL4. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Activated effector human T cells and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Thus, CTLs recognising a cognate target can induce a localised mass response by amplifying the direct recruitment of additional T cells independently of other leukocytes.
Multicentric endocrine mucin‐producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report

Endocrine mucin‐producing sweat gland carcinoma (EMPSGC) is a rare low‐grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71‐year‐old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.
Spatially resolved mass spectrometry analysis of amyloid plaque‐associated lipids

Over the last 10 years, considerable technical advances in mass spectrometry (MS)‐based bioanalysis have enabled the investigation of lipid signatures in neuropathological structures. In Alzheimer´s Disease (AD) research, it is now well accepted that lipid dysregulation plays a key role in AD pathogenesis and progression. This review summarizes current MS‐based strategies, notably MALDI and ToF‐SIMS imaging as well as laser capture microdissection combined with LC‐ESI‐MS. It also presents recent advances to assess lipid alterations associated with Amyloid‐β plaques, one of the hallmarks of AD. Collectively, these methodologies offer new opportunities for the study of lipids, thus pushing forward our understanding of their role in such a complex and still untreatable disease as AD.
Helminths of urban gray squirrels in Florida

lengths of 14 setae from so-called ear mites (P. cuniculi) that were collected from the various hosts. The lengths of the 14 setae of mites from mule deer of Colorado were similar to those of rabbits of New Mexico and goats of Texas, but were significantly different from all other P. cuniculi mites. The mites collected from bighorn sheep would be classified as P. cuniculi according to Sweatman because he first used body location (ear) and then the setal length ranges. The mean lengths of the 14 setae of these mites (137 Am) fall within the range for P. cuniculi (64-164 j,m). However, had these mites been taken from the body rather than ear locations, they would, by Sweatman's key, be classified as P. ovis (74-258 ,Am). The mites taken from the bighorn sheep in New Mexico were taken from both ear and body locations, but the predominant infestation areas were the ears of the hosts. Even though the method of Sweatman (1958, loc. cit.) for distinguishing between species of Psoroptes is widely used, our findings indicate that it is inadequate and alternate methods to identify the various species need to be found. The overlap of setal lengths mentioned by Sweatman (1958, loc. cit.) and confirmed by our data makes this point evident. Also, there are too many significant differences in lengths of the 14 setae between the same species of mites within the same host. The various species of Psoroptes are so similar morphologically that it is extremely difficult to find distinguishing characteristics. However, with the advent of the scanning electron microscope, the exoskeletons of arthropods are much easier to examine. By the use of this or different techniques, additional differences may be found to aid in the proper identification of the various species of Psoroptes. We thank the following for providing some of the psoroptic mites used in this study: Dr. Durr Bezuidenhout, Onderstepoort, Republic of South Africa; Dr. Robert L. Glaze, Kerrville, Texas; Dr. Gordon Hubell, Miami, Florida; Dr. Grant Kinzer, New Mexico State University, Las Cruces, New Mexico; Mr. Allan Kirkwood, Weybridge, England; Mr. Leonard Roundtree, Denver, Colorado; Dr. Stephen M. Schmitt, East Lansing, Michigan; and Dr. Juan Solis, Sao Paulo, Brazil.
CATCH RATES AND SUSTAINABLE YIELD OF THE KUWAIT'S TRAWL FISHERY

The catch rate and sustainable yield of the Kuwait's trawl fishery was estimated from the Research Vessel sea survey data from 1979 to 1987. The mean monthly and annual catch rate for mixed fish, mixed shrimp and catfish varied among months and between years. The annual variations in the mean catch rate of mixed shrimp and catfish were larger than that of mixed fish. The Maximum Sustainable Yield (MSY) obtained from Schaefer model was reliable for mixed fish and mixed shrimp, whereas Fox model gave better results for catfish. An MSY value of 20,800 t/yr at an effort level of 12,000 days per year coincides with the present level of fishing effort expended in the trawl fishery. On the contrary an MSY value of 2,080 t/yr at 6,000 days per year were obtained for mixed shrimp showing that the sustainable yield could be obtained at half of the present fishing effort level expended in the fishery. The MSY value of yield 3,250 t/yr at 6,600 days per year obtained from the Fox model could be treated as a preliminary estimate for catfish in Kuwait waters.
Social media use and health promoting lifestyle: an exploration among Indian nursing students

Abstract Objective. To evaluate the use of social media and the health promoting lifestyle profile of indian nursing students. Methods. A cross-sectional study was carried out with 125 students (89 undergraduate and 36 graduate) from various Nursing universities in India, who provided information on their sociodemographic data, the Bergen Social Media Addiction Scale (BSMAS) and the Health Promoting Lifestyle Profile (HPLP-II). Results. Regarding the BSMAS, the participants had an average of 12.8 (maximum possible = 30); 42% reported they frequently delayed their sleep due to using social media; 9% had excessive use of social media; by gender, men had higher total score than women. With respect to the health promoting lifestyle profile, the total average was 126.9 (maximum possible = 208); no difference was observed by gender in the total score and men scored better in the domain of physical activity; students living with their families had higher scores in the domain of health responsibility than those living alone; and graduate students had better scores than undergraduate students in the scale total and in the domains of health responsibility, spiritual relations, and interpersonal relations. Conclusion: There is excessive use of social media, especially among male students. This study also revealed lower scores than those desired in the domains of Health Promoting Lifestyle, especially for physical activity, health responsibility, stress management, and nutrition. Thereby, the findings may be used to improve health literacy on social media, as well as promote a positive lifestyle among nursing students.
Global impact of mcr-1-positive Enterobacteriaceae bacteria on “one health”

Abstract Polymyxins, especially polymyxin B and polymyxin E (colistin), are considered to be the last line of defence against infections caused by multi-drug-resistant (MDR) gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae (CRE). However, the recent emergence and dissemination of the plasmid-mediated colistin resistance gene mcr-1 and its variants pose a serious challenge to public health and the livestock industry. This review describes the prevalence and dissemination of mcr-1-positive isolates from different sources, including animals (food animals, pet animals and wildlife), humans (healthy populations and patients) and the environment (farms, urban and rural communities and natural environments) based on existing epidemiological studies of mcr-1 and MCR-1-producing Enterobacteriaceae bacteria around the world. The major mechanisms of mcr-1 transmission across humans, animals and the environment are discussed.
Denosumab induced atypical fracture of free vascularized fibular graft 20 years after tumour reconstruction

A 67-year-old female developed sudden, severe pain and an inability to weight bear on her right leg upon standing from a chair. She had a tibial adamantinoma, treated with wide resection and reconstruction with a free vascularized fibular graft (VFG) 21 years earlier (Fig. 1). Eighteen months prior to her current presentation, she was diagnosed with osteoporosis and the treatment was initiated with an antiresorptive agent, denosumab, 60 mg subcutaneously every 6 months. She had received a total of three injections, the last dose being 1 month prior to this presentation. There was no other history of fragility fractures or any other previous antiresorptive therapy.
Decoding of voluntary and involuntary upper-limb motor imagery based on graph fourier transform and cross-frequency coupling coefficients

Objective. Brain-computer interface (BCI) technology based on motor imagery (MI) control has become a research hotspot but continues to encounter numerous challenges. BCI can assist in the recovery of stroke patients and serve as a key technology in robot control. Current research on MI almost exclusively focuses on the hands, feet, and tongue. Therefore, the purpose of this paper is to establish a four-class MI BCI system, in which the four types are the four articulations within the right upper limbs, involving the shoulder, elbow, wrist, and hand. Approach. Ten subjects were chosen to perform nine upper-limb analytic movements, after which the differences were compared in P300, movement-related potentials(MRPS), and event-related desynchronization/event-related synchronization under voluntary MI (V-MI) and involuntary MI (INV-MI). Next, the cross-frequency coupling (CFC) coefficient based on mutual information was extracted from the electrodes and frequency bands with interest. Combined with the image Fourier transform and twin bounded support vector machine classifier, four kinds of electroencephalography data were classified, and the classifier’s parameters were optimized using a genetic algorithm. Main results. The results were shown to be encouraging, with an average accuracy of 93.2% and 92.2% for V-MI and INV-MI, respectively, and over 95% for any three classes and any two classes. In most cases, the accuracy of feature extraction using the proximal articulations as the basis was found to be relatively high and had better performance. Significance. This paper discussed four types of MI according to three aspects under two modes and classed them by combining graph Fourier transform and CFC. Accordingly, the theoretical discussion and classification methods may provide a fundamental theoretical basis for BCI interface applications.