Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin Regulates Alveolar Macrophage Polarization to Protect Against Acute Lung Injury in Rats Caused by Paraquat Poisoning

This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.
The Effect of Bangerter Filters on Visual Acuity and Contrast Sensitivity With External Noise

It is critical to address the relationship between density label of Bangerter filters and expected visual acuity, and how filters modulate contrast sensitivity (CS) at different spatial frequency and external noise levels. In the current study, the monocular visual acuity and CS at ten spatial frequencies and three noise levels were measured in normal subjects wearing no filters, 0.8, 0.4, or 0.2 Bangerter filters. Compared with the baseline condition (no filter worn), Bangerter filters degraded both visual acuity and contrast sensitivity function (CSF) in zero-noise conditions, but the reduction of both visual functions did not correlate with each other at any filter level. In addition, the stronger the filter was, the worse both visual functions became. In contrast, when external noise was present, filters improved the contrast sensitivity at low frequencies but deteriorated it at intermediate and high spatial frequencies. The perceptual template model was used to reveal the corresponding mechanism accounted for filter-induced visual function changes. Although the internal process in visual system should not be affected by the filters, the measurement of parameters was biased. To be specific, (1) the internal additive noise was elevated at all frequencies; (2) the perceptual template was improved at low spatial frequencies but impaired at intermediate spatial frequencies; and (3) the changes in both factors were highly dependent on filter intensity. We conclude that Bangerter filters influence visual acuity and contrast sensitivity differently and that their effect on contrast sensitivity depends on spatial frequency and noise.
Targeting the Homologous Recombination Pathway in Cancer With a Novel Class of RAD51 Inhibitors

Targeting DNA damage response (DDR) pathway has been proposed as an approach for amplifying tumor-specific replicative lesions. RAD51 plays a central role in the DDR process, and thus represents a promising anti-tumor target. We here report the discovery of a series of next generation RAD51 inhibitors that can prevent RAD51 foci formation. The lead compounds dramatically impaired human cancer cell growth, induced cell cycle arrest in S-phase, and resulted in elevated γH2AX. Furthermore, cancer cells became sensitized to chemotherapy and other DDR inhibitors. Dosed either as a single agent or in combination with cisplatin, the compounds significantly inhibited tumor growth in vivo. By upregulating ATR-CHK1 signaling, the RAD51 inhibitors increased surface PD-L1 levels in various tumor cells, suggesting a potential combination of RAD51 inhibitors with PD-1/PD-L1 blockade. Overall, our findings provide the preclinical rationale to explore RAD51 inhibitors as monotherapy or in combination with chemotherapy, immunotherapy or DDR-targeting therapy in cancer treatment.
Survival Benefit of Metformin as an Adjuvant Treatment for Head and Neck Cancer: A Systematic Review and Meta-Analysis

Background/Aims: The relationship between the efficacy of metformin and the prognosis of patients with head and neck cancer (HNC) was still unclear. This study aims to clarify the prognostic value of metformin treatment using meta-analysis. Methods: Studies related to HNC prognosis and metformin were searched in Cochrane Library, Embase, LILACS, MEDLINE and PubMed databases. A meta-analysis was performed to evaluate the association between metformin therapy and the prognosis of HNC on overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and whether article quality, comorbidities, age, region or smoking had an influence on the prognosis of metformin treatment. Pooled hazard ratio (HR) and 95% confidence interval (CI) were analyzed to assess the effect. Results: Eleven eligible studies involving 14,694 participants were included. Metformin increased the OS (HR = 0.87, 95% CI: 0.76–0.99), but failed on DFS (HR = 0.67, 95% CI: 0.40–1.09) or DSS (HR = 0.69, 95% CI: 0.41–1.14) in HNC patients. Subgroup analysis showed metformin was associated with improved OS (HR = 0.66, 95% CI: 0.49–0.88), DFS (HR = 0.49, 95% CI: 0.26–0.92) and DSS (HR = 0.38, 95% CI: 0.22–0.65) in studies with higher Newcastle-Ottawa Scale (NOS) scores. Subgroup analysis of age indicated that patients younger than 65 years (OS, HR = 0.67, 95% CI: 0.49–0.92) were more likely to benefit from metformin treatment. Subgroup analysis of comorbidities showed metformin significantly improved patient outcomes in studies without adjusted for comorbidities (OS, HR = 0.66, 95% CI: 0.51–0.85; DSS, HR = 0.38, 95% CI: 0.22–0.65), but not in studies that adjusted for comorbidities. Conclusions: Metformin improved the prognosis of HNC patients as an adjuvant therapy, especially in those with higher NOS scores. Age and comorbidities of HNC patients influenced the therapeutic effect of metformin. Further well-conducted investigations are needed.
Body Image Scale: Evaluation of the Psychometric Properties in Three Indian Head and Neck Cancer Language Groups

Background Body image is a subjective concept encompassing a person’s views and emotions about their body. Head and neck cancer (HNC) diagnosis and treatment affects several psychosocial concepts including body image. Large numbers of HNC patients are diagnosed each year in India but there are no suitable measures in regional languages to assess their body image. This study assessed the psychometric properties of the Body Image Scale (BIS), a measure suitable for clinical and research use in HNC populations, translated into Tamil, Telugu and Hindi and compared body image distress between language groups. Methods Translated versions of BIS were completed by HNC patients recruited from three cancer centers across India one time only. Psychometric evaluation was conducted including factor analysis using principal component analysis and internal consistency reliability using Cronbach’s alpha. Patients completed the EORTC Quality of Life Questionnaire (QLQ) C-30 and EORTC QLQ HN-35 measures to enable exploration of convergent and discriminant validity. ANOVA was used to calculate difference in mean values for body image. Results Our sample included 621 HNC patients (Tamil = 205, Telugu = 216, Hindi = 200). Factor analysis revealed a one-factor solution and Cronbach’s alpha coefficients ranged between 0.891 and 0.969 indicating good reliability. Hypothesized correlations between similar and different constructs were as expected, supporting construct validity. On the BIS, we found a statistically significant difference (F = 11.0954, P < 0.05) between means of Tamil, Telugu, and Hindi groups, with higher body image scores in Telugu (M = 12.86; SD = 7.65) and Hindi groups (M = 12.52; SD = 7.36) indicating more symptoms/body image distress, when compared to Tamil population (M = 9.28; SD = 10.04). Conclusion The reliability and validity of the three translated Indian versions of the BIS were maintained, providing a method for assessing body image of HNC population worldwide speaking Tamil, Telugu, and Hindi across the illness trajectory.
Modulating the Immune Response in Periodontitis

Periodontitis is a chronic inflammatory condition initiated by the accumulation of bacterial biofilm. It is highly prevalent and when left untreated can lead to tooth loss. The presence of bacterial biofilm is essential for the initiation of the inflammatory response but is not the sole initiator. Currently it is unknown which mechanisms drive the dysbiosis of the bacterial biofilm leading to the dysregulation of the inflammatory response. Other players in this equation include environmental, systemic, and genetic factors which can play a role in exacerbating the inflammatory response. Treatment of periodontal disease consists of removal of the bacterial biofilm with the goal of resolving the inflammatory response; however, this does not occur in every case. Understanding the way the inflammatory response does not return to a state of homeostasis has led investigators to consider both systemic and local pharmacological interventions. Nonetheless, a better understanding of the impact that genetics and environmental factors may have on the inflammatory response could be key to helping identify how inflammation can be modulated therefore stopping the destruction of the periodontium. In this article, we will explore the current evidence associating the microbial dysbiosis and the dysregulation of the immune response, potential mechanisms or pathways that may be targeted for the modulation of the inflammatory response, and discuss the advantages and drawbacks associated with local and systemic inflammatory modulation in the management of periodontal disease. This information will be valuable for those interested in understanding potential adjunct methods for managing periodontal diseases, but not limited to, dental professionals, clinical researchers and the public at large.
Social Interaction With an Anonymous Opponent Requires Increased Involvement of the Theory of Mind Neural System: An fMRI Study

An anonymous interaction might facilitate provoking behavior and modify the engagement of theory of mind (TOM) brain mechanisms. However, the effect of anonymity when processing unfair behavior of an opponent remains largely unknown. The current functional magnetic resonance imaging (fMRI) study applied the Taylor aggression paradigm, introducing an anonymous opponent to this task. Thirty-nine healthy right-handed subjects were included in the statistical analysis (13 males/26 females, mean age 24.5 ± 3.6 years). A player winning the reaction-time game could subtract money from the opponent during the task. Participants behaved similarly to both introduced and anonymous opponents. However, when an anonymous opponent (when compared to the introduced opponent) subtracted money, the right inferior frontal gyrus (IFG) demonstrated an increased BOLD signal and increased functional connectivity with the left IFG. Further, increased functional connectivity between the right IFG, the right temporal parietal junction and precuneus was observed during the perception of high provocation (subtracting a large amount of money) from the anonymous compared to the introduced opponent. We speculate that the neural changes may underlie different inferences about the opponents’ mental states. The idea that this reorganization of the TOM network reflects the attempt to understand the opponent by “completing” socially relevant details requires further investigation.
Evaluation of the Major Seed Storage Proteins, the Conglutins, Across Genetically Diverse Narrow-Leafed Lupin Varieties

Lupin seeds have an excellent nutritional profile, including a high proportion of protein and dietary fiber. These qualities make lupin seeds an ideal candidate to help meet the growing global demand for complementary sources of protein. Of consequence to this application, there are nutritional and antinutritional properties assigned to the major lupin seed storage proteins—referred to as α-, β-, δ- and γ-conglutins The variation in the abundance of these protein families can impact the nutritional and bioactive properties of different lupin varieties. Hence, exploring the conglutin protein profiles across a diverse range of lupin varieties will yield knowledge that can facilitate the selection of superior genotypes for food applications or lupin crop improvement. To support this knowledge generation, discovery proteomics was applied for the identification of the 16 known conglutin subfamilies from 46 domestic and wild narrow-leafed lupin (NLL) genotypes. Consequently, the diversity of abundance of these proteins was evaluated using liquid chromatography–multiple reaction monitoring-mass spectrometry (LC–MRM-MS). This comparative study revealed a larger variability for the β- and δ-conglutin content across the lines under study. The absence/lower abundance of the β2- to β6-conglutin subfamilies in a subset of the domesticated cultivars led to substantially lower overall levels of the allergenic β-conglutin content in these NLLs, for which the elevation of the other conglutin families were observed. The diversity of the conglutin profiles revealed through this study—and the identification of potential hypoallergenic genotypes—will have great significance for lupin allergic consumers, food manufactures as well as grain breeders through the future development of lupin varieties with higher levels of desirable bioactive proteins and lower allergen content.
Soleus H and Lower Limb Posterior Root Muscle Reflexes During Stepping After Incomplete SCI

The goal of this study was to examine and compare the step cycle related modulation of the soleus H and posterior root muscle (PRM) reflexes in subjects with and without spinal cord injury. Ten subjects without neurological injury and fifteen subjects with spinal cord injury (SCI) underwent soleus H reflex and lower limb PRM reflex testing while standing and stepping in a robotic gait orthosis. Reflex amplitudes were evaluated during standing, mid stance and mid swing to determine if speed and/or injury altered step cycle related neuromodulation. H and PRM reflexes in the soleus underwent step cycle related modulation in injured and uninjured subjects though the degree of modulation differed between the two reflexes with the H reflex showing more step cycle related modulation. We found in the SCI group that both the soleus H and soleus PRM reflex amplitudes were higher relative to the non-injured group and modulated less during the step cycle. We also found that modulation of the soleus H reflex, but not soleus PRM reflex, correlated to the lower extremity motor scores in individuals with SCI. Our evidence suggests that the inability to provide appropriate step cycle related reflex modulation may be due to decreased supra-spinal regulation of motoneuron and spinal excitability and could be an indicator of the severity of injury as it relates to clinically measured lower extremity motor scores.
Pan-Cancer Single-Cell Analysis Reveals the Core Factors and Pathway in Specific Cancer Stem Cells of Upper Gastrointestinal Cancer

Upper gastrointestinal cancer (UGIC) is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Here, we collected 39,057 cells, and they were annotated into nine cell types. By clustering cancer stem cells (CSCs), we discovered the ubiquitous existence of sub-cluster CSCs in all UGICs, which is named upper gastrointestinal cancer stem cells (UGCSCs). The identification of UGCSC function is coincident with the carcinogen of UGICs. We compared the UGCSC expression profile with 215,291 single cells from six other cancers and discovered that UGCSCs are specific tumor stem cells in UGIC. Exploration of the expression network indicated that inflammatory genes (CXCL8, CXCL3, PIGR, and RNASE1) and Wnt pathway genes (GAST, REG1A, TFF3, and ZG16B) are upregulated in tumor stem cells of UGICs. These results suggest a new mechanism for carcinogenesis in UGIC: mucosa damage and repair caused by poor eating habits lead to chronic inflammation, and the persistent chronic inflammation triggers the Wnt pathway; ultimately, this process induces UGICs. These findings establish the core signal pathway that connects poor eating habits and UGIC. Our system provides deeper insights into UGIC carcinogens and a platform to promote gastrointestinal cancer diagnosis and therapy.
Understanding the Role of Stigma and Misconceptions in the Experience of Epilepsy in India: Findings From a Mixed-Methods Study

It is surprising that although 12 million people in India suffer from epilepsy this remains a thoroughly under-researched area in the sociology of health and practice. We address this intellectual and policy neglect by reviewing the social, psychological and legal challenges governing the lives of people living with epilepsy (PWE) by paying particular attention to negotiations in arranged marriages and employment. Drawing on the analytical frameworks of the sociological study of stigma, critical race theory and paying attention to the cultural models of health and suffering, this study utilized a combination of (online) survey data (N = 100) and in-depth qualitative interviews (N = 10) with PWE and their families. The online survey was administered to map the level of awareness about epilepsy and its clinical management among the general population, whereas the in-depth interviews were conducted to understand the experience, self-perception and everyday struggles of those diagnosed with the condition. Findings from the survey on non-PWE suggest a general lack of awareness and fearful misconceptions around epilepsy related seizures. In-depth interviews with PWEs revealed concealment (of the illness) as a dominant coping strategy to attenuate the social alienation and rejection associated with epilepsy. Further, PWE participants reported persistent discrimination, harassment and prejudiced understanding of diminished cognitive capacities at workplaces as a result of cultural myths and popular representations of epilepsy-related seizures. The study also demonstrated the significance of institutional support groups in assisting PWE to cope with symbolic violence and forge solidarities. We conclude with reflections on the ethical dilemmas faced by medical practitioners while dealing with social-medical interventions of epilepsy treatment. Overall, results from this study undergird the significance to revisit the social-moral as well as legal frameworks that persistently restrict opportunities for PWE in India. In an attempt to reimagine inclusive futures regardless of disease, disability and affliction, we attempt to move beyond the biomedical gaze and instead privilege stories of individual personhood, struggles and aspirations.
Transcriptomic Evidence of the Immune Response Activation in Individuals With Limb Girdle Muscular Dystrophy Dominant 2 (LGMDD2) Contributes to Resistance to HIV-1 Infection

LGMDD2 is a rare form of muscular dystrophy characterized by one of the three heterozygous deletions described within the TNPO3 gene that result in the addition of a 15-amino acid tail in the C-terminus.TNPO3 is involved in the nuclear import of splicing factors and acts as a host cofactor for HIV-1 infection by mechanisms not yet deciphered. Further characterization of the crosstalk between HIV-1 infection and LGMDD2 disease may contribute to a better understanding of both the cellular alterations occurring in LGMDD2 patients and the role of TNPO3 in the HIV-1 cycle. To this regard, transcriptome profiling of PBMCs from LGMDD2 patients carrying the deletion c.2771delA in the TNPO3 gene was compared to healthy controls. A total of 545 differentially expressed genes were detected between LGMDD2 patients and healthy controls, with a high representation of G protein-coupled receptor binding chemokines and metallopeptidases among the most upregulated genes in LGMDD2 patients. Plasma levels of IFN-β and IFN-γ were 4.7- and 2.7-fold higher in LGMDD2 patients, respectively. An increase of 2.3-fold in the expression of the interferon-stimulated gene MxA was observed in activated PBMCs from LGMDD2 patients after ex vivo HIV-1 pseudovirus infection. Thus, the analysis suggests a pro-inflammatory state in LGMDD2 patients also described for other muscular dystrophies, that is characterized by the alteration of IL-17 signaling pathway and the consequent increase of metallopeptidases activity and TNF response. In summary, the increase in interferons and inflammatory mediators suggests an antiviral environment and resistance to HIV-1 infection but that could also impair muscular function in LGMDD2 patients, worsening disease evolution. Biomarkers of disease progression and therapeutic strategies based on these genes and mechanisms should be further investigated for this type of muscular dystrophy.
3D Organisation of Cells in Pseudostratified Epithelia

Pseudostratified epithelia have smooth apical and basal surfaces, yet along the apical-basal axis, cells assume highly irregular shapes, which we introduce as punakoids. They interact dynamically with many more cells than visible at the surface. Here, we review a recently developed new perspective on epithelial cell organisation. Seemingly random at first sight, the cell packing configurations along the entire apical-basal axis follow fundamental geometrical relationships, which minimise the lateral cell-cell contact energy for a given cross-sectional cell area variability. The complex 3D cell neighbour relationships in pseudostratified epithelia thus emerge from a simple physical principle. This paves the way for the development of data-driven 3D simulation frameworks that will be invaluable in the simulation of epithelial dynamics in development and disease.
Modulation of Motor Cortex Activity After Intrathecal Baclofen Delivery in Chronic Thoracic Spinal Cord Injury

Objectives Intrathecal baclofen (ITB) is commonly used for reduction of spasticity in chronic spinal cord injury (SCI). Its clinical effect is well-known; however, exact mechanisms of long-term effect of continuous ITB administration (cITBa) on modulation of cortical processes have not been elucidated. The aim of this study was to evaluate changes in motor cortex activation for healthy upper limbs in comparison to impaired lower limbs by functional magnetic resonance imaging (fMRI). Methods Ten subjects (eight males, 20–69 years) with thoracic SCI presenting no voluntary movements of lower limbs (except one) were enrolled in the fMRI study. fMRI at 1.5T with a finger tapping paradigm and mental movement simulating foot flexion on the dominant side were performed before, 3 months, and 1 year after start of cITBa. fMRI data processing was carried out using FMRI Expert Analysis Tool (FEAT), part of FSL. A second-level analysis was carried out using FLAME stages 1 and 2. The level of spasticity was assessed with the Modified Ashworth scale (MAS). Results Continuous ITB significantly decreased limb spasticity in all the subjects (group MAS spasticity dropped from 3 to 0.3). The second-level analysis (Z > 1.6, cluster significance threshold p =0.05) revealed increased activation of the primary sensorimotor cortex of the foot between baseline and 3 months, and 3 months and 1 year. Conclusion Increased sensorimotor cortex activation with spasticity reduction after cITBa may reflect distant functional reorganization because of long-term mediated neuroplastic changes in the sensorimotor cortex. Better understanding of modulation of brain function in SCI after cITBa may influence the field of neurorehabilitation.