Miracle-dz/UniFAR-FTUs huggingface dataset:
On the pH-dependence of α-synuclein amyloid polymorphism and the role of secondary nucleation in seeding experiments

The aggregation of the protein alpha-synuclein is closely associated with several neurodegenerative disorders and as such the structures of the amyloid fibril aggregates have high scientific and medical significance. However, it seems that there are about as many unique atomic-resolution structures of these aggregates as there are publications describing them. Obviously, this highly polymorphic nature of alpha-synuclein fibrils hampers efforts in disease-relevant in vitro studies on alpha-synuclein amyloid aggregation. In order to better understand the factors that affect polymorph selection we studied the structures of alpha-synuclein fibrils in vitro as a function of pH and buffer using cryo-EM helical reconstruction. We find that in the physiological range of pH 5.8-7.4 a pH-dependent selection between Types 1, 2 and 3 polymorphs occurs. Our results indicate that even in the presence of seeds, the polymorph selection during aggregation is highly dependent on the buffer conditions, attributed to the polymorph-unspecific nature of secondary nucleation. We also uncovered two new polymorphs that occur at pH 7.0 in phosphate-buffered saline. The first is a monofilament Type 1 fibril which highly resembles the structure of the juvenile-onset synucleinopathy polymorph found in patient-derived material. The second is a new Type 5 polymorph that resembles a polymorph that has been recently reported in a study that used diseased tissues to seed aggregation. Taken together, our results highlight the shallow amyloid energy hypersurface that can be altered by subtle changes in the environment, including the pH which is shown to play a major role in polymorph selection and in many cases appears to be the determining factor in seeded aggregation. The results also confirm the possibility of producing disease-relevant structure in vitro .
The effects of disagreement and unfriending on political polarization: a moderated-mediation model of cross-cutting discussion on affective polarization via unfriending contingent upon exposure to incivility

Cross-cutting discussion is the foundation of deliberative democracy. However, previous research has reported inconsistent results regarding the effects of exposure to dissimilar perspectives on political polarization. This study aims to extend the literature by exploring how cross-cutting discussion influences affective polarization through unfriending and how this indirect effect is contingent upon exposure to incivility. The study analyzes panel data from a two-wave online survey conducted in South Korea (N = 890). The results show a significantly positive indirect effect of unfriending, suggesting that cross-cutting discussion further reinforces affective polarization via unfriending. Furthermore, the study identifies the boundary conditions for this mediating mechanism, showing that the mediated relationship of cross-cutting discussion on affective polarization via unfriending is stronger for those who are more exposed to incivility on social media.
Real-valued localisation algorithm for near-field non-circular sources

A novel real-valued near-field localisation algorithm for non-circular sources is proposed using the uniform linear array. On the basis of non-circularity of signals, an extended real-valued covariance matrix is constructed. Then, utilising the symmetric property of the extended array manifold, the direction of arrival and range parameters are obtained by two one-dimensional rank reduction estimators. The proposed algorithm is efficient in that it only requires second-order statistics (SOS) and real-valued computations. Moreover, it can improve the estimation accuracy and resolve more sources than the conventional SOS-based methods.
Community Structure in Endorsement Social Networks

In this work, we study the community structure of endorsement networks, i.e., social networks in which a directed edge u → v is asserting an action of support from user u to user v. Examples include scenarios where a user u is favouring a photo, liking a post, or following the microblog of user v. Very often, endorsement networks are sub- networks of more complex social systems; for instance, a photo-sharing site typically includes a “favouring” function, which induces an endorsement network. We start from the hypothesis that the footprint of a community in an endorsement network is a bipartite directed clique from a set of followers to a set of leaders, and apply frequent itemset mining techniques to discover such bicliques. Our analysis of real networks indicated that, with high statistical significance, this hypothesis holds, and that the leaders of a community are endorsing each other forming a very dense nucleus. Our method produces many similar bicliques, which are different footprints of the same community. Thus, we propose a novel clustering technique in order to coalesce similar bicliques into meaningful communities. We explore different similarity measures based on set similarity and on edge density between followers and leaders, and by expressing edge density as an inner product operation we show how to make the clustering algo- rithm scalable. Our experiments demonstrate that our clustering algorithm is capable of discovering communities characterised by a set of leaders who link to each other and followers who link to the leaders.
Normal Families of Meromorphic Functions and Shared Set

For nonempty finite sets S_1 and S_2 and a domain D on C,denote by S_1,S_2_D the family of meromorphic functions f which satisfy {z∈D:f(z)∈S_1} = {z∈D:f'(z)∈S_2}. We prove that if S_1 and S_2 have totally at least 12 elements, then S_1,S_2_D is normal.In particular,when S_1 has at least three elements,we get the sharp results.
Comparative Effectiveness of Value-added Manures on Crop Productivity, Soil Mineral Nitrogen and Soil Carbon Pools under Maize-Wheat Cropping System in an Inceptisol

The effect of three value-added manures viz., vermicompost, NADEP compost and FYM was evaluated for crop production and maintaining soil mineral N and organic C pools in an Inceptisol under a maize-wheat cropping system. Vermicompost was prepared from various farm wastes using Eisenia foetida and cattle dung (5%, w/w). NADEP compost was prepared using mixed crop residues like maize, oat, berseem, jowar, lobia and seasonal grasses and cattle dung (2%, w/w) in pit, while FYM was prepared by trench method using cattle dung. Data revealed that yield and N uptake by maize and wheat due to conjoint use of valueadded manures and chemical fertilizers increased significantly over application of value-added manures alone. Mineral N and microbial biomass N (MBN) in soil improved significantly with application of 100% NPK than plots receiving organic manures alone as well as integrated use of manures and 50% NPK. Plots amended with value-added manures maintained higher soil organic carbon (SOC) pools viz., Walkley Black C (WBC), KMnO4-oxidizable labile C (LBC), microbial biomass C (MBC) and mineralizable C (Cmin) over control. The effect in improving SOC pools further enhanced in plots amended with conjoint use of valueadded manure (5 Mg ha−1) and 50% NPK fertilizers than plots amended with value-added manure alone. Pearson's correlation matrix showed significant and positive relationships between yield, N uptake by crops with soil mineral N, MBN and pools of SOC. The results demonstrated that integrated use of valueadded manures along with 50% NPK fertilizers could maintain higher mineral N and SOC pools, which may be considered as a feasible and environment-friendly option for recycling various farm wastes including crop residues and cattle dung into a value-added product, thereby effecting a 50% saving on costly chemical fertilizers.
What is the next structure? Guessing enhances L2 syntactic learning in a syntactic priming task

Previous psycholinguistic research has shown that Second Language (L2) speakers could learn from engaging in prediction. Few works have directly examined the relationship between prediction and L2 syntactic learning. Further, relatively limited attention has been paid to the effects of two linguistic factors in this area: structure type and L2 proficiency. Using a mixed experimental design, 147 L2 Arabic speakers with varying L2 proficiency levels completed two syntactic priming experiments, each targeting a different structure: (a) the dative and (b) Temporal Phrases (TP). The experimental conditions required participants to predict what the upcoming sentence’s structure would be. The experimental conditions differed in the degree of engagement in prediction error. Results suggested that Arabic L2 speakers at different proficiency levels showed enhanced priming and short-term learning for two syntactic structures (PO, fronted TP) when (a) instructed to guess only (constrained condition) as well as when (b) instructed to guess and compute the prediction error (unconstrained condition), relative to the controls. These results imply a guessing benefit for priming and short-term learning. Participants also experienced different priming effects by structure type, but there was no significant effect for proficiency. The theoretical and practical implications of these findings are discussed.
In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX’s predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.
Quality of life and wellbeing among breast cancer patients in Lahore, Pakistan

Background Breast cancer has a high incidence rate, emphasizing the necessity of enhanced information on health-related quality of life (HrQOL) in this population of patients. The aim of this study was to identify the factors influencing the QOL experienced by patients in Pakistan. Methods A cross-sectional study was conducted on women with breast cancer, and four instruments were used on a random sample of 130 Pakistani women: FACIT-B Version 4 questionnaire,WHO causality assessment scale, Naranjo’s algorithm, and a demographic/clinical characteristics section. Data analysis included descriptive analysis, independent sample t-test, and analysis of variance (ANOVA) test. Results The patients’ mean age was 49.10 (standard deviation (SD) 10.89); 98.5% were married. The mean score was 18.34 for physical wellbeing (SD 5.92; interquartile range (IQR) 11), 16.33 for social/family wellbeing (SD 6.3; IQR 11.25), 13.6 for emotional wellbeing (SD 3.55; IQR 6), 17.13 for functional wellbeing (SD 3.73; IQR 6), and 24.86 for breast cancer subscale (SD 3.64; IQR 4). The study found that the age, entitlement, recurrence, marital status, salary, number of doses, duration of cancer treatment, and chemotherapy sessions were significantly related to QOL terms in the assessment of the FACIT-B scale. The WHO causality evaluation scale determined that 78.1% of the responses were “probable” and 20.1% were “possible”. According to Naranjo’s algorithm assessment scale, 80% of adverse drug reactions (ADRs) were “probable”, whereas 18.4% were declared “possible”. Chemotherapy-induced anemia was the most often reported ADR in 64.6% of patients, followed by chemotherapy-induced nausea and vomiting (61.5%). Conclusion Healthcare practitioners must acknowledge and take into account the significance of QOL in addition to therapy for breast cancer patients in order to enhance their health. The findings of this study will aid in filling gaps in current unknown knowledge and identifying sites where patients require additional assistance. Because cancer and chemotherapy clearly have a negative impact on individuals’ QOL, oncologists must concentrate on strategies that help cancer patients during their sickness and treatment while also enhancing self-care and QOL. Those with cancer will benefit from emotional wellbeing and adaptation to their disease.
A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing

Background Aberrant DNA damage repair (DDR) is one of the hallmarks of tumors, and therapeutic approaches targeting this feature are gaining increasing attention. This study aims to develop a signature of DDR-related genes to evaluate the prognosis of cervical cancer (CC). Methods Differentially expressed genes were identified between high and low DDR groups of cells from the single-cell RNA sequencing dataset GSE168652 based on DDR scores. Using the ssGSEA and WGCNA methods, DDR-related differentially expressed genes were identified from different patients within the TCGA-CESC cohort. Using Cox analysis and LASSO regression analysis, a DDR-related gene signature was constructed based on the intersection of two groups of differentially expressed genes and DDR-related genes from WGCNA, and validated in GSE52903. Immune cell infiltration analysis, mutation analysis, survival analysis, drug sensitivity analysis, etc., were performed in different groups which were established based on the DDR gene signature scoring. A key gene affecting prognosis was selected and validated through biological experiments such as wound healing, migration, invasion, and comet assays. Results A novel DDR-related signature was constructed and the nomogram results showed this signature performed better in predicting prognosis than other clinical features for CC. The high DDR group exhibited poorer prognosis, weaker immune cell infiltration in the immune microenvironment, lower expression of immune checkpoint-related genes, lower gene mutation frequencies and more sensitivity to drugs such as BI.2536, Bleomycin and etc. ITGB1, ZC3H13, and TOMM20 were expressed at higher levels in CaSki and HeLa cells compared to ECT1 cells. Compared with the native CaSki and HeLa cells, the proliferation, migration, invasion and DDR capabilities of CaSki and HeLa cell lines with ITGB1 suppressed expression were significantly decreased. Conclusion The 7 DDR-related gene signature was an independent and powerful prognostic biomarker that might effectively evaluate the prognosis of CC and provide supplementary information for a more personalized evaluation and precision therapy. ITGB1 was a potential candidate gene that may affect the DDR capacity of CC cells, and its mechanism of action was worth further in-depth study.
Immunogenicity and contraceptive efficacy of plant-produced putative mouse-specific contraceptive peptides

Rodent population control through contraception requires species-specific oral contraceptive vaccines. Therefore, in this study, we produced putative mouse-specific contraceptive peptides, mZP2 (from oocyte) and mIzumo1 (from sperm), in plants using Agrobacterium-mediated transient expression. Peptides were produced separately in Nicotiana benthamiana using constructs encoding antigens containing three copies of each peptide. We also determined the immunogenicity and contraceptive effects of the plant-produced antigens in female BALB/c mice. Mice immunized subcutaneously with a relatively low amount of antigen (5 µg/dose of each peptide in a mixture) showed systemic immune responses against mZP2-3 and mIzumo1-3 antigens. Moreover, the mean litter size of mice treated with the plant-produced antigens was reduced by 39% compared to that of the control mice. Notably, there was a significant negative correlation between the number of pups born and individual antibody levels against both antigens. Immunofluorescence assays demonstrated the binding of induced antibodies to the oocytes of BALB/c and wild-type mice in vivo and in vitro, respectively. Our study demonstrate the feasibility of producing small contraceptive peptides in plants that can be further used to develop oral contraceptive vaccines against mouse populations.
Janus kinase inhibitors in systemic lupus erythematosus: implications for tyrosine kinase 2 inhibition

Aberrant activation of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is common in systemic lupus erythematosus (SLE), conferring immune-mediated properties in target tissues. Multiple cytokines activate different combinations of JAKs and STATs to alter the cell fate of target tissue and induce end-organ damage. Thus, the simultaneous blockade of several different cytokines by small molecules acting downstream intracellular signalling has gained traction. JAK inhibitors have been approved for the treatment of several rheumatic diseases, yet hitherto not for SLE. Nevertheless, JAK inhibitors including tofacitinib, baricitinib, and deucravacitinib have shown merit as treatments for SLE. Tofacitinib, a JAK1/3 inhibitor, reduced cholesterol levels, improved vascular function, and decreased the type I interferon signature in SLE patients. Baricitinib, a JAK1/2 inhibitor, demonstrated significant improvements in lupus rashes and arthritis in a phase 2 and a phase 3 randomised controlled trial, but the results were not replicated in another phase 3 trial. Deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, yielded greater response rates than placebo in a phase 2 trial of SLE and will be investigated in larger phase 3 trials. TYK2 is activated in response to cytokines actively involved in lupus pathogenesis; this review highlights the potential of targeting TYK2 as a promising therapy for SLE.
Women's health, hormonal balance, and personal autonomy

Hormone-based contraception disrupts hormonal balance, creating artificial states of anovulation and threatening women's health. We reviewed its main adverse effects and mechanisms on accelerated ovarian aging, mental health (emotional disruptions, depression, and suicide), sexuality (reduced libido), cardiovascular (brain stroke, myocardial infarction, hypertension, and thrombosis), and oncological (breast, cervical, and endometrial cancers). Other “collateral damage” includes negative effects on communication, scientific mistrust, poor physician–patient relationships, increased patient burden, economic drain on the healthcare system, and environmental pollution. Hormone-sensitive tumors present a dilemma owing to their potential dual effects: preventing some cancers vs. higher risk for others remains controversial, with denial or dismissal as non-relevant adverse effects, information avoidance, and modification of scientific criteria. This lack of clinical assessment poses challenges to women's health and their right to autonomy. Overcoming these challenges requires an anthropological integration of sexuality, as the focus on genital bodily union alone fails to encompass the intimate relational expression of individuals, complete sexual satisfaction, and the intertwined feelings of trust, safety, tenderness, and endorsement of women's femininity.
Visuo-spatial imagery in dreams of congenitally and early blind: a systematic review

Background The presence of visual imagery in dreams of congenitally blind people has long been a matter of substantial controversy. We set to systematically review body of published work on the presence and nature of oneiric visuo-spatial impressions in congenitally and early blind subjects across different areas of research, from experimental psychology, functional neuroimaging, sensory substitution, and sleep research. Methods Relevant studies were identified using the following databases: EMBASE, MEDLINE and PsychINFO. Results Studies using diverse imaging techniques and sensory substitution devices broadly suggest that the “blind” occipital cortex may be able to integrate non-visual sensory inputs, and thus possibly also generate visuo-spatial impressions. Visual impressions have also been reported by blind subjects who had near-death or out-of-body experiences. Conclusion Deciphering the mechanistic nature of these visual impression could open new possibility in utilization of neuroplasticity and its potential role for treatment of neurodisability.
Evaluation of the impacts of photodynamic therapy on the prognosis of patients with hrHPV infection based on BTNL8 expression

Objective The aim of this study was to evaluate the prognostic value of Butyrophilin-like protein 8 (BTNL8) expression in high-risk HPV (hrHPV) infection treated with photodynamic therapy. Methods A total of 93 patients with hrHPV infection were enrolled as research study subjects, along with 69 healthy women who served as controls. Serum samples were obtained from each participant, and BTNL8 levels were quantified. The patients were divided into high- and low-expression groups (n = 45 and n = 48, respectively), and both groups underwent photodynamic therapy. We recorded the following data: BTNL8 expression pre-treatment and at 3/6 months post-treatment, HPV negative conversion ratio, regression rate of low-grade squamous intraepithelial lesions (LSIL), incidence of adverse reactions, complication rate, serum inflammatory factors, persistence of HPV positivity, LSIL residue or recurrence, and incidence of high-grade cervical intraepithelial lesions (HCIL). Results Patients with HPV infection exhibited higher BTNL8 expression than healthy individuals. Compared to the low-expression group, the high-expression group showed increased HPV negative conversion ratios, LSIL regression rates, and levels of IL-17 and IL-23. This group also demonstrated decreased total complication rate, HPV positivity persistence, LSIL residue or recurrence, and IL-10 levels. Additionally, there was no significant difference between the two groups in terms of the number of adverse reactions and cases with LSIL residue/recurrence. Conclusion Serum BTNL8 expression may serve as a valuable tool for early screening and prognosis monitoring of patients with hrHPV infection.