Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges in the Assessment and Diagnosis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS)7 is a complex endocrine-mediated disorder in women with a prevalence of 8% to 13%. Women with PCOS typically present with heterogeneous clinical signs and symptoms such as excess hair growth, irregular menstrual cycles, infertility, and metabolic issues. PCOS is associated with cardiometabolic risk factors such as type 2 diabetes, and it may increase risks for other comorbidities like endometrial cancer and nonalcoholic fatty liver disease. PCOS is also associated with anxiety, depression, and other psychosocial manifestations. To date, there are no universal criteria for PCOS diagnosis. As a result, women with the disorder often report significant delays (>2 years) in diagnosis and poor follow-up care. Three sets of diagnostic criteria currently exist to define PCOS: ( a ) NIH, ( b ) Rotterdam, and ( c ) Androgen Excess Society criteria. Recently the International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018 endorsed the use of the Rotterdam criteria in adult women. To diagnose PCOS using the Rotterdam criteria, women must meet at least 2 of the following: ovulatory abnormalities, hyperandrogenism (clinical, biochemical, or both), or polycystic ovary morphology (PCOM). The clinician must also exclude several disorders with similar manifestations before a diagnosis can be finalized. In this article, 5 experts discuss the challenges surrounding the current diagnostic criteria, available biomarkers, and the timely diagnosis and treatment of women with PCOS. Who should be screened or tested for PCOS and, despite the high prevalence, why is PCOS often overlooked? Chris McCartney: PCOS should be considered in reproductive-aged women with clinical hyperandrogenism (e.g., hirsutism, acne, male-pattern hair loss), abnormal menstrual bleeding (oligo/amenorrhea, irregular bleeding patterns), or subfertility. Early recognition of PCOS is important for several reasons. For example, accurate attribution of patient symptoms and initiation of appropriate treatments are expected to improve patient well-being. PCOS is also associated …
The relationship between separation anxiety and intolerance of uncertainty in pregnant women

Abstract Background and aim: Pregnancy is a risky period to develop Adult Separation Anxiety Disorder (ASAD). The aim of this study was to investigate the frequency of separation anxiety in pregnant women, and the relationship of separation anxiety with sociodemographic variables and intolerance of uncertainty. Methods: This study included 310 pregnant women and used the Adult Separation Anxiety Questionnaire (ASAQ) and Intolerance of Uncertainty Scale-Short Form (IUS-12). Results: The average age in pregnant women with ASAD was lower. IUS-12 total score, prospective anxiety, and inhibitory anxiety subscale scores were significantly higher in the ASAD group. There were moderate and statistically significant positive correlations between the ASAD score and the IUS-12 total, prospective anxiety and inhibitory anxiety subscale scores. Conclusion: Intolerance of uncertainty may be an important factor in the mental processes of individuals with separation anxiety. Pregnancy period can be a risky period for developing ASAD. Cognitive behavioral treatments including intolerance of uncertainty may be effective in the treatment of ASAD. There is a need for follow-up studies on the effects of separation anxiety during pregnancy on maternal–fetal health.
Association between miRNAs expression and cognitive performances of Pediatric Multiple Sclerosis patients: A pilot study

The Pediatric onset of Multiple Sclerosis (PedMS) occurs in up to 10% of all cases. Cognitive impairment is one of the frequent symptoms, exerting severe impact in patients’ quality of life and school performances. The underlying pathogenic mechanisms are not fully understood, and molecular markers predictive of cognitive dysfunctions need to be identified. On these grounds, we searched for molecular signature/s (i.e., miRNAs and target genes) associated with cognitive impairment in a selected population of PedMS patients. Additionally, changes of their regional brain volumes associated with the miRNAs of interest were investigated.
‘I went back to being myself’: acceptability of a culturally adapted task-shifted cognitive-behavioural therapy (CBT) treatment for depression (Ziphamandla) for South African HIV care settings

ABSTRACT There is a need for a culturally adapted, evidence-based, psychotherapy treatment that is effective, acceptable, and feasible for integration into primary care in South Africa. This qualitative study used exit interviews to examine participants’ experiences of an adapted cognitive-behavioural therapy treatment for adherence and depression, task-shifted and delivered by nurses in two peri-urban HIV clinics near Cape Town. Nine semi-structured exit interviews were conducted with isiXhosa-speaking females and analysed using thematic analysis. Overall, participants responded positively to the treatment, viewing it as acceptable and beneficial and as a catalyst to returning to normalcy. Results indicated that participants viewed the treatment as being effective in ameliorating their depressive symptoms and improving their adherence to ART . Additional benefits described included improvements in subjective wellbeing and social and occupational functioning. Several began or resumed employment, an important behavioural indicator of the treatment’s capacity to facilitate positive change and cost saving. Recommendations to improve the treatment included using video material and educating others about depression. These findings have positive implications regarding the acceptability and cultural applicability of the treatment for use in South Africa.
On Diophantine quintuples

The Greek mathematician Diophantus of Alexandria noted that the set { 1 16 , 33 16 , 17 4 , 105 16 } has the following property: the product of any two of its distinct elements increased by 1 is a square of a rational number (see [5]). Fermat first found a set of four positive integers with the above property, and it was {1, 3, 8, 120}. Let n be an integer. A set of positive integers {x1, x2, . , xm} is said to have the property D(n) if for all 1 ≤ i < j ≤ m the following holds: xixj + n = y 2 ij , where yij is an integer. Such a set is called a Diophantine m-tuple. Davenport and Baker [4] showed that if d is a positive integer such that the set {1, 3, 8, d} has the property of Diophantus, then d has to be 120. This implies that the Diophantine quadruple {1, 3, 8, 120} cannot be extended to the Diophantine quintuple with the propertyD(1). Analogous result was proved for the Diophantine quadruple {2, 4, 12, 420} with the property D(1) [17], for the Diophantine quadruple {1, 5, 12, 96} with the propertyD(4) [15] and for the Diophantine quadruples {k−1, k+1, 4k, 16k3−4k} with the property D(1) for almost all positive integers k [9]. Euler proved that every Diophantine pair {x1, x2} with the property D(1) can be extended in infinitely many ways to the Diophantine quadruple with the same property (see [12]). In [6] it was proved that the same conclusion is valid for the pair with the property D(l2) if the additional condition that x1x2 is not a perfect square is fulfilled. Arkin, Hoggatt and Strauss [3] proved that every Diophantine triple with the property D(1) can be extended to the Diophantine quadruple. More precisely, if xixj + 1 = y 2 ij , then we can set x4 = x1 + x2 + x3 + 2x1x2x3+2y12y13y23. For the Diophantine quadruple obtained in this way, they proved the existence of a positive rational number x5 with the property that xix5 + 1 is a square of a rational number for i = 1, 2, 3, 4. Using this construction, in [2, 7, 8, 11] some formulas for Diophantine
Aggregation of the nucleic acid–binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation

TAR DNA-binding protein 43 (TDP-43) is a nucleic acid–binding protein, and its aggregation represents the defining pathology in amyotrophic lateral sclerosis (ALS) and related proteinopathies. Recent studies implicate cytoplasmic stress granules (SGs) as hubs that may facilitate TDP-43 aggregation. Here, using cellular fractionation, biochemical analyses, and histological assays, we show that TDP-43 targeted to the cytoplasm has multiple fates. Whereas a TDP-43 subpopulation is indeed recruited to SGs, mature aggregated TDP-43, produced with aggregate-prone TDP-43 variants or exposure to oxidative stress, generates distinct TDP-43 inclusions that are surprisingly devoid of SGs. Consistent with this observation, we found that SG components are predominantly excluded from TDP-43 pathology in motor neurons from individuals with ALS. We generated de novo SGs by expressing the fragile X protein (FMRP) and found that rather than directly engaging TDP-43 aggregates, SGs can sequester the proteostasis factor histone deacetylase 6 (HDAC6) and thereby impede TDP-43 clearance from cells. These findings indicate that SGs form distinct cytoplasmic structures that can indirectly enhance TDP-43 aggregation. Therapeutic approaches that inhibit SG formation may therefore be effective at suppressing TDP-43–mediated toxicity in patients with ALS and related TDP-43 proteinopathies.
DNA barcoding and morphological taxonomy: identification of lanternfish (Myctophidae) larvae in the Gulf of Mexico

Abstract Accurate identification of fish larval stages is complicated and time-consuming due to the lack of diagnostic morphological characters, especially during early developmental stages. The distribution of lanternfish (Myctophidae) has been described based on the morphological identification of adult stages. Larvae of only a few species of Myctophidae have been described, and the description is not always precise. In this study, larvae were collected and morphologically identified as Diaphus mollis, Hygophum hygomii, H. reinhardtii, H. taaningi, Myctophum obtusirostre and M. selenops. The DNA barcode region of the mitochondrial cytochrome oxidase I gene (COI) was determined for all larvae. The COI sequences matched reference barcodes available in GenBank for 14 of the identified larvae. The remaining COI sequences matched reference barcodes for different species of Myctophidae including Centrobranchus nigroocellatus, Diogenichthys atlanticus and Lepidophanes guentheri. This effort demonstrated the importance of integrated morphological and molecular analysis of species diversity and distribution of the Myctophidae in the Gulf of México.
Microbial uptake by the respiratory epithelium: outcomes for host and pathogen

Intracellular occupancy of the respiratory epithelium is a useful pathogenic strategy facilitating microbial replication and evasion of professional phagocytes or circulating antimicrobial drugs. A less appreciated but growing body of evidence indicates that the airway epithelium also plays a crucial role in host defence against inhaled pathogens, by promoting ingestion and quelling of microorganisms, processes that become subverted to favour pathogen activities and promote respiratory disease. To achieve a deeper understanding of beneficial and deleterious activities of respiratory epithelia during antimicrobial defence, we have comprehensively surveyed all current knowledge on airway epithelial uptake of bacterial and fungal pathogens. We find that microbial uptake by airway epithelial cells (AECs) is a common feature of respiratory host-microbe interactions whose stepwise execution, and impacts upon the host, vary by pathogen. Amidst the diversity of underlying mechanisms and disease outcomes, we identify four key infection scenarios and use best-characterised host-pathogen interactions as prototypical examples of each. The emergent view is one in which effi-ciency of AEC-mediated pathogen clearance correlates directly with severity of disease outcome, therefore highlighting an important unmet need to broaden our understanding of the antimicrobial properties of respiratory epithelia and associated drivers of pathogen entry and intracellular fate.
Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms

Fucoidan is a natural derived compound found in different species of brown algae and in some animals, that has gained attention for its anticancer properties. However, the exact mechanism of action is currently unknown. Therefore, this review will address fucoidans structure, the bioavailability, and all known different pathways affected by fucoidan, in order to formulate fucoidans structure and activity in relation to its anti-cancer mechanisms. The general bioactivity of fucoidan is difficult to establish due to factors like species-related structural diversity, growth conditions, and the extraction method. The main pathways influenced by fucoidan are the PI3K/AKT, the MAPK pathway, and the caspase pathway. PTEN seems to be important in the fucoidan-mediated effect on the AKT pathway. Furthermore, the interaction with VEGF, BMP, TGF-β, and estrogen receptors are discussed. Also, fucoidan as an adjunct seems to have beneficial effects, for both the enhanced effectiveness of chemotherapy and reduced toxicity in healthy cells. In conclusion, the multipotent character of fucoidan is promising in future anti-cancer treatment. However, there is a need for more specified studies of the structure–activity relationship of fucoidan from the most promising seaweed species.
Plagiarism-Requiring a Holistic Approach

Plagiarism is the concept of checking intruding matter from other workers’ research or writing. It refers to use of another’s information, language, or writing , when done without proper acknowledgment of the original source . Plagiarism in text documents happens in several forms, i.e., plagiarized text may be copied as such, passages may be modified or they may be translated. Plagiarism has been around for as long as humans have produced work of art and research. Easy access to web, large data bases and telecommunication has made it a reality more obvious than ever. Key factors leading to plagiarism are unawareness of citing ethics, inadequate writing skills and pressing deadlines to get published. Plagiarism can be managed by its prevention detection by plagiarism detection soft wares, and educating researchers about ethical writing. Plagiarism can not be dealt with as a simple black and white issue, the prevention of which can be achieved via threats, warnings and admonitions. The notion of ownership of text and learning is becoming complex, day by day . It needs to be understood in terms of complex relationships between text, memory, and learning borrowing.
Microfluidic enrichment, isolation and characterization of disseminated melanoma cells from lymph node samples

For the first time in melanoma, novel therapies have recently shown efficacy in the adjuvant therapy setting, which makes companion diagnostics to guide treatment decisions a desideratum. Early spread of disseminated cancer cells (DCC) to sentinel lymph nodes (SLN) is indicative of poor prognosis in melanoma and early DCCs could therefore provide important information about the malignant seed. Here, we present a strategy for enrichment of DCCs from SLN suspensions using a microfluidic device (Parsortix™, Angle plc). This approach enables the detection and isolation of viable DCCs, followed by molecular analysis and identification of genetic changes. By optimizing the workflow, the established protocol allows a high recovery of DCC from melanoma patient‐derived lymph node (LN) suspensions with harvest rates above 60%. We then assessed the integrity of the transcriptome and genome of individual, isolated DCCs. In LNs of melanoma patients, we detected the expression of melanoma‐associated transcripts including MLANA (encoding for MelanA protein), analyzed the BRAF and NRAS mutational status and confirmed the malignant origin of isolated melanoma DCCs by comparative genomic hybridization. We demonstrate the feasibility of epitope‐independent isolation of LN DCCs using Parsortix™ for subsequent molecular characterization of isolated single DCCs with ample application fields including the use for companion diagnostics or subsequent cellular studies in personalized medicine.
Verbal working memory training in older adults: an investigation of dose response

Abstract The WM training protocol proposed by Borella et al. found specific and transfer effects among seniors, however, the studies were carried out in the same socio-cultural context and variations in the procedure were never tested. The present study aimed at analyzing the efficacy of Borella et al.’s training, in terms of short and long-term benefits, in a different socio-cultural context (Study 1), and the effect of change in the training's length (duplicating the number of sessions (Study 2). Participants were randomly assigned to a trained group (N = 18 for Study 1, and N = 23 for Study 2) and active control group (N = 28 for Study 1, and N = 27 for Study 2), and evaluated at pre, post-test and six-month follow-up for verbal WM task (criterion task), and for visuospatial and verbal WM, inhibition, processing speed, executive function, and fluid intelligence measures (transfer tasks). The trained groups had higher performance in all tasks when compared with active control groups after training and at 6 month follow-up. The longer training (Study 2) generated similar gains as the original protocol, with some advantage in far transfer tasks at post-test and follow-up. Study limitations include the small sample sizes. In conclusion, this training was effective in a different socio-cultural context and adding three sessions to the protocol did not significantly change training impact.
Influence of Fiber Distribution and Orientation in the Fracture Behavior of Polyolefin Fiber-Reinforced Concrete

Polyolefin fiber-reinforced concrete (PFRC) has become an attractive alternative to steel for the reinforcement of concrete elements, mainly due to its chemical stability and the residual strengths that can be reached with lower weights. The use of polyolefin fibers can meet the requirements of standards, although the main constitutive relations are based on experience with steel fibers. Therefore, the structural contributions of the fibers should be assessed by inverse analysis. In this study, the fiber dosage was fixed at 6 kg/m3, and both self-compacting concrete and conventional concrete were used to compare the influence of the positioning of the fibers. An idealized homogeneous distribution of the fibers with such fibers crossing from side to side of the specimen was added to self-compacting concrete. The experimental results of three-point bending tests on notched specimens were reproduced by using the cohesive crack approach. Hence, constitutive relations were found. The significance of this research relies on the verification of the formulations found to build constitutive relations. Moreover, with these results, it is possible to establish a higher threshold for the performance of PFRC and the difficulties of limiting the first unloading branch typical of fracture tests of PFRC.
Accurate, fast, data efficient and interpretable glaucoma diagnosis with automated spatial analysis of the whole cup to disc profile

BACKGROUND Glaucoma is the leading cause of irreversible blindness worldwide. It is a heterogeneous group of conditions with a common optic neuropathy and associated loss of peripheral vision. Both over and under-diagnosis carry high costs in terms of healthcare spending and preventable blindness. The characteristic clinical feature of glaucoma is asymmetrical optic nerve rim narrowing, which is difficult for humans to quantify reliably. Strategies to improve and automate optic disc assessment are therefore needed to prevent sight loss. METHODS We developed a novel glaucoma detection algorithm that segments and analyses colour photographs to quantify optic nerve rim consistency around the whole disc at 15-degree intervals. This provides a profile of the cup/disc ratio, in contrast to the vertical cup/disc ratio in common use. We introduce a spatial probabilistic model, to account for the optic nerve shape, we then use this model to derive a disc deformation index and a decision rule for glaucoma. We tested our algorithm on two separate image datasets (ORIGA and RIM-ONE). RESULTS The spatial algorithm accurately distinguished glaucomatous and healthy discs on internal and external validation (AUROC 99.6% and 91.0% respectively). It achieves this using a dataset 100-times smaller than that required for deep learning algorithms, is flexible to the type of cup and disc segmentation (automated or semi-automated), utilises images with missing data, and is correlated with the disc size (p = 0.02) and the rim-to-disc at the narrowest rim (p<0.001, in external validation). DISCUSSION The spatial probabilistic algorithm is highly accurate, highly data efficient and it extends to any imaging hardware in which the boundaries of cup and disc can be segmented, thus making the algorithm particularly applicable to research into disease mechanisms, and also glaucoma screening in low resource settings.
Osa‐miR398b boosts H2O2 production and rice blast disease‐resistance via multiple superoxide dismutases

Summary miRNAs contribute to plant resistance against pathogens. Previously, we found that the function of miR398b in immunity in rice differs from that in Arabidopsis. However, the underlying mechanisms are unclear. In this study, we characterized the mutants of miR398b target genes and demonstrated that multiple superoxide dismutase genes contribute to miR398b‐regulated rice immunity against the blast fungus Magnaporthe oryzae. Out of the four target genes of miR398b, mutations in Cu/Zn‐Superoxidase Dismutase1 (CSD1), CSD2 and Os11g09780 (Superoxide DismutaseX,SODX) led to enhanced resistance to M. oryzae and increased hydrogen peroxide (H2O2) accumulation. By contrast, mutations in Copper Chaperone for Superoxide Dismutase (CCSD) resulted in enhanced susceptibility. Biochemical studies revealed that csd1, csd2 and sodx displayed altered expression of CSDs and other superoxide dismutase (SOD) family members, leading to increased total SOD enzyme activity that positively contributed to higher H2O2 production. By contrast, the ccsd mutant showed CSD protein deletion, resulting in decreased CSD and total SOD enzyme activity. Our results demonstrate the roles of different SODs in miR398b‐regulated resistance to rice blast disease, and uncover an integrative regulatory network in which miR398b boosts total SOD activity to upregulate H2O2 concentration and thereby improve disease resistance.
Inhibition of Stat3‐mediated astrogliosis ameliorates pathology in an Alzheimer's disease model

Reactive astrogliosis is a hallmark of Alzheimer's disease (AD), but its role for disease initiation and progression has remained incompletely understood. We here show that the transcription factor Stat3 (signal transducer and activator of transcription 3), a canonical inducer of astrogliosis, is activated in an AD mouse model and human AD. Therefore, using a conditional knockout approach, we deleted Stat3 specifically in astrocytes in the APP/PS1 model of AD. We found that Stat3‐deficient APP/PS1 mice show decreased β‐amyloid levels and plaque burden. Plaque‐close microglia displayed a more complex morphology, internalized more β‐amyloid, and upregulated amyloid clearance pathways in Stat3‐deficient mice. Moreover, astrocyte‐specific Stat3‐deficient APP/PS1 mice showed decreased pro‐inflammatory cytokine activation and lower dystrophic neurite burden, and were largely protected from cerebral network imbalance. Finally, Stat3 deletion in astrocytes also strongly ameliorated spatial learning and memory decline in APP/PS1 mice. Importantly, these protective effects on network dysfunction and cognition were recapitulated in APP/PS1 mice systemically treated with a preclinical Stat3 inhibitor drug. In summary, our data implicate Stat3‐mediated astrogliosis as an important therapeutic target in AD.