Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of dietary polyphenols in alternating DNA methylation in cancer

Abstract Natural products such as curcumin, quercetin, and resveratrol have been shown to have antitumor effectsand several studies have examined their role in treating cancer, either alone or in combination with other chemotherapeutic drugs. These compounds are capable of affecting different cancer-related mechanisms, such as proliferation, inflammation, invasion, and metastasis. Along with all of the benefits of these agents, affecting epigenetic processes is one of the most important aspects of their impact. Epigenetic modifications can be categorized into three main processes that include DNA methylation, histone modification, and regulation of small non-coding RNAs. Therefore, targeting DNA methylation can be used as a cancer treatment strategy by identifying or developing methylation modulators. Herein, we take a look into the studies investigating the role of natural products (e.g. curcumin, resveratrol, epigallocatechin gallate (EGCG), and quercetin) in alternating the DNA methylation status of various cancer cells. We discuss how these compounds reduce the expression of enzymes mediating the methylation of tumor suppressor genes and thereby, increasing the expression of tumor suppressors while reactivating antitumor signaling pathways.
A compact arbitrary power division coupler with nonstandard phase-difference

Abstract This paper presents a new coupler configuration which can be designed with both arbitrary power division and nonstandard phase difference at the output ports. The planar coupler ring is composed of four section microstrip lines and an open stub resulting in ease of fabrication. Its circuit parameters can be easily determined by the derived closed-form equations and the corresponding performance in terms of power division ratio, output phase difference, and the tunable parameters is mainly analyzed. Compared with the previous counterparts, its bandwidth and area have obvious superiority. For experimental verification, two prototypes, operating at 1 GHz, have been designed and implemented in microstrip process. One demonstrates a 45° phase difference with equal outputs and the other is designed for a 105° phase difference with 6.02 dB power division ratio. The design theory has been supported with good agreement between the simulated and measured responses.
Timing of gestational weight gain in association with birth weight outcomes: a prospective cohort study

Abstract Maternal gestational weight gain (GWG) is an important determinant of infant birth weight, and having adequate total GWG has been widely recommended. However, the association of timing of GWG with birth weight remains controversial. We aimed to evaluate this association, especially among women with adequate total GWG. In a prospective cohort study, pregnant women’s weight was routinely measured during pregnancy, and their GWG was calculated for the ten intervals: the first 13, 14–18, 19–23, 24–28, 29–30, 31–32, 33–34, 35–36, 37–38 and 39–40 weeks. Birth weight was measured, and small-for-gestational-age (SGA) and large-for-gestational-age were assessed. Generalized linear and Poisson models were used to evaluate the associations of GWG with birth weight and its outcomes after multivariate adjustment, respectively. Of the 5049 women, increased GWG in the first 30 weeks was associated with increased birth weight for male infants, and increased GWG in the first 28 weeks was associated with increased birth weight for females. Among 1713 women with adequate total GWG, increased GWG percent between 14 and 23 weeks was associated with increased birth weight. Moreover, inadequate GWG between 14 and 23 weeks, compared with the adequate GWG, was associated with an increased risk of SGA (43 (13·7 %) v. 42 (7·2 %); relative risk 1·83, 95 % CI 1·21, 2·76). Timing of GWG may influence infant birth weight differentially, and women with inadequate GWG between 14 and 23 weeks may be at higher risk of delivering SGA infants, despite having adequate total GWG.
Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis

Abstract RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.
Leptin mediates the regulation of muscle mass and strength by adipose tissue

Adipose tissue secretes numerous cytokines (termed ‘adipokines’) that have known or hypothesized actions on skeletal muscle. The majority of adipokines have been implicated in the pathological link between excess adipose and muscle insulin resistance, but approximately half also have documented in vitro effects on myogenesis and/or hypertrophy. This complexity suggests a potential dual role for adipokines in the regulation of muscle mass in homeostasis and the development of pathology. In this study, we used lipodystrophic ‘fat‐free’ mice to demonstrate that adipose tissue is indeed necessary for the development of normal muscle mass and strength. Fat‐free mice had significantly reduced mass (∼15%) and peak contractile tension (∼20%) of fast‐twitch muscles, a slowing of contractile dynamics and decreased cross‐sectional area of fast twitch fibres compared to wild‐type littermates. These deficits in mass and contractile tension were fully rescued by reconstitution of ∼10% of normal adipose mass, indicating that this phenotype is the direct consequence of absent adipose. We then showed that the rescue is solely mediated by the adipokine leptin, as similar reconstitution of adipose from leptin‐knockout mice fails to rescue mass or strength. Together, these data indicate that the development of muscle mass and strength in wild‐type mice is dependent on adipose‐secreted leptin. This finding extends our current understanding of the multiple roles of adipokines in physiology as well as disease pathophysiology to include a critical role for the adipokine leptin in muscle homeostasis.
Evaluation of human papillomavirus (HPV) knowledge among healthcare professionals: A study of conference attendees in Angola

ABSTRACT Human papillomavirus (HPV) plays an essential role in cervical cancer development. Angola has a high cervical cancer incidence rate (36.1 per 100,000); therefore, knowledge of HPV among clinicians is essential for the prevention of cervical cancer and educating at-risk individuals. This study aimed to evaluate knowledge of HPV among healthcare professionals in Angola. A 44-item questionnaire was distributed to 65 healthcare professionals who attended a conference on the cancer burden in Angola. Non-parametric and multiple regression analyses were conducted. Of the participants (55.6%) were male, and 33.3% were aged 31–40 years, 56.3% had an undergraduate degree, and 35.9% had a postgraduate degree. All participants worked in healthcare in academic and/or clinical settings, with 36.7% in joint contracts. Most (62.2%) knew that early sexual debut increases the risk of contracting HPV, and HPV vaccines are most effective if administered before sexual debut. However, there was limited knowledge regarding the virus transmission. The mean HPV knowledge score was 11.08 ± 8.76 and knowledge was higher among older healthcare workers (>50 years) with a postgraduate degree and working in a clinical role. Overall, HPV knowledge was limited among the respondents. Policymakers should consider promoting knowledge and targeted public health initiatives among healthcare professionals in Angola.
Tilmanocept as a novel tracer for lymphatic mapping and sentinel lymph node biopsy in melanoma and oral cancer

Sentinel lymph node biopsy (SLNB) has been pivotal for pathological assessment of nodal status in cutaneous melanoma (CM) and oral cavity squamous cell carcinoma (OCSCC) thus crucial for staging. An ideal agent for lymphatic mapping should have a standardized preparation, appropriate accumulation in first‐echelon nodes and no side effects. Tilmanocept, a CD206‐receptor targeted novel radiotracer fulfils these properties. This study investigated Tilmanocept for lymphoscintigraphy and intraoperative identification of sentinel lymph nodes (SLN) in CM and OCSCC.
Preliminary results of P-wave and S-wave measurements by seismic dilatometer test (SPDMT) in Mirandola (Italy)

A trial seismic dilatometer-VP (SPDMT) has been recently developed to measure the compressional wave velocity VP, in addition to the shear wave velocity VS and to the DMT geotechnical parameters. The new SPDMT is the combination of the traditional mechanical flat dilatometer (DMT) with an appropriate seismic module placed above the DMT blade. The SPDMT module consist in a probe outfitted with two receivers for measuring the P-wave velocity, along with two receivers for measuring the S-wave velocity. The paper describes the SPDMT equipment, the test procedure and the interpretation of VP and VS measurements, together with some considerations on the potential geotechnical applications which can benefit from the contemporary measurement of the two propagation velocities. Finally, the paper illustrates preliminary results of P-wave and S-wave measurements by SPDMT compared to several cross-hole, down-hole and suspension logging data at the Mirandola test site (Italy), a soft alluvial site which was investigated within the InterPACIFIC (Intercomparison of methods for site parameter and velocity profile characterization) project.
Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension

INTRODUCTION: We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease. METHODS: In this retrospective cohort study, we identified 5849 US veterans who underwent LS measurement from May 01, 2014 to June 30, 2019, and laboratory tests enabling FIB-4 calculation within 6 months of LS measurement. Patients were followed up from the LS measurement date until February 05, 2020, for incident complications of PH. We combined LS values and the individual components of the FIB-4 score (i.e. age, aspartate aminotransferase, alanine aminotransferase, and platelet count) using multivariable Cox proportional hazards modeling and the machine learning algorithm eXtreme gradient boosting to develop the C-FIB-5 and X-FIB-5 models, respectively. Models were internally validated using optimism-corrected measures. RESULTS: Among 5,849 patients, the mean age was 62.8 years, 95.9% were men, and the mean follow-up time was 2.14 ± 1.21 years. Within 3 years after LS measurement date, 116 (2.0%) patients developed complications of PH. The X-FIB-5 (area under the receiver operating characteristic [AUROC] 0.845) and C-FIB-5 scores (AUROC 0.868) demonstrated superior discrimination over LS (AUROC 0.688) and FIB-4 (AUROC 0.672) for predicting incident complications of PH. Both the X-FIB-5 and C-FIB-5 models demonstrated higher classification accuracy across all sensitivity cutoffs when compared with LS or FIB-4 alone. DISCUSSION: We combined LS and the individual components of the FIB-4 into a single scoring system (FIB-5, www.fib5.net), which can help identify patients with compensated liver disease at risk of developing complications of PH.
Does the timing of antibiotic exposure in pregnancy impact the risk of development of pediatric asthma?: A systematic review and meta-analysis

Abstract Objective Maternal exposure to antibiotics has been linked to the development of pediatric asthma. However, the impact of the timing of exposure is unclear. We aimed to explore if the risk of pediatric asthma varies with trimester-specific exposure to antibiotics through a systematic review and meta-analysis. Methods PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for studies reporting an association between trimester-specific maternal exposure to antibiotics and risk of asthma in the offspring. Results Eleven studies were included. The total sample size of the included studies was 2,160,216. Meta-analysis revealed a statistically significant increased risk of asthma with first (RR: 1.13 95% CI: 1.10, 1.17 I 2 = 59% p < 0.00001), second (RR: 1.14 95% CI: 1.07, 1.21 I 2 = 92% p < 0.0001), and third (RR: 1.14 95% CI: 1.08, 1.20 I 2=86% p < 0.00001) trimester exposure of antibiotics. The results were stable on sensitivity analysis. On subgroup analysis, we noted that the association for the first and second trimester was significant for studies on children >5 years but not for those on children <5 years of age. The certainty of evidence based on GRADE was low. Conclusion Our results indicate that antibiotics administered during any trimester of pregnancy lead to an increased risk of childhood asthma. The overall risk is small and could be due to confounding. Further studies rigorously adjusting for important confounding variables are needed for stronger evidence.
Who is seeking help for psychological distress associated with the COVID-19 pandemic? Characterization of risk factors in 1269 participants accessing low-threshold psychological help

Background The COVID-19 pandemic and accompanying restrictions are associated with substantial psychological distress. However, it is unclear how this increased strain translates into help-seeking behavior. Here, we aim to characterize those individuals who seek help for COVID-19 related psychological distress, and examine which factors are associated with their levels of distress in order to better characterize vulnerable groups. Methods We report data from 1269 help-seeking participants subscribing to a stepped-care program targeted at mental health problems due to the COVID-19 pandemic. Sample characteristics were compared to population data, and linear regression analyses were used to examine which risk factors and stressors were associated with current symptom levels. Results Seeking for help for COVID-19 related psychological distress was characterized by female gender, younger age, and better education compared to the general population. The majority reported mental health problems already before the pandemic. 74.5% of this help-seeking sample also exceeded clinical thresholds for depression, anxiety, or somatization. Higher individual symptom levels were associated with higher overall levels of pandemic stress, younger age, and pre-existing mental health problems, but were buffered by functional emotion regulation strategies. Conclusions Results suggest a considerable increase in demand for mental-healthcare in the pandemic aftermath. Comparisons with the general population indicate diverging patterns in help-seeking behavior: while some individuals seek help themselves, others should be addressed directly. Individuals that are young, have pre-existing mental health problems and experience a high level of pandemic stress are particularly at-risk for considerable symptom load. Mental-healthcare providers should use these results to prepare for the significant increase in demand during the broader aftermath of the COVID-19 pandemic as well as allocate limited resources more effectively.
Feasibility Study of High-speed Ultrasonic Vibration Cutting Titanium Alloy

Abstract For a series of unique properties, titanium alloy has been widely applied in aviation and aerospace fields. However, the poor machinability makes high-speed machining titanium alloy hardly perform as expected even with advanced tool materials due to the high cutting temperature. Intermittent cutting could be an effective method to decrease the cutting temperature and improve the cutting performance. As typical intermittent cutting methods, traditional ultrasonic vibration cutting (UVC) and elliptical ultrasonic vibration cutting (EUVC) have achieved significant advancements. However, the critical cutting speed confines them to the field of low speed machining. This article proposed a new type of ultrasonic vibration cutting, i.e. high-speed ultrasonic vibration cutting (HUVC), in which the vibration is always along with the feed direction. The separation of the tool and workpiece can be realized under some certain conditions although the cutting speed exceeds far away from the critical speed of the traditional UVC and EUVC methods. As a consequence, it realized high speed cutting on a macro level and intermittent cutting in the micro, and improved the machinability of titanium alloy. Firstly, a theoretical model of HUVC process was established and both of the separation criteria and the duty cycle of HUVC were fully analyzed. Then the feasibility of HUVC method for cutting Ti-6Al-4 V was verified experimentally compared with conventional cutting (CC) and traditional ultrasonic vibration cutting (UVC). The results demonstrated that tool life in HUVC were extended by 300% in an optimal situation due to the significantly tool wear reduction. Besides, the cutting efficiency increased by 90% compared with CC method obviously. Furthermore, significant cutting force reduction about 50% and better surface roughness improvement in a successive cutting process were also achieved.
Olfactory placode generates a diverse population of neurons expressing GnRH, somatostatin mRNA, neuropeptide Y, or calbindin in the chick forebrain

The olfactory placode (OP) of vertebrates generates several classes of migrating cells, including hypothalamic gonadotropin‐releasing hormone (GnRH)‐producing neurons, which play essential roles in the reproduction system. Previous studies using OP cell labeling have demonstrated that OP‐derived non‐GnRH cells enter the developing forebrain; however, their final fates and phenotypes are less well understood. In chick embryos, a subpopulation of migratory cells from the OP that is distinct from GnRH neurons transiently expresses somatostatin (SS). We postulated that these cells are destined to develop into brain neurons. In this study, we examined the expression pattern of SS mRNA in the olfactory‐forebrain region during development, as well as the destination of OP‐derived migratory cells, including SS mRNA‐expressing cells. Utilizing the Tol2 genomic integration system to induce long‐term fluorescent protein expression in OP cells, we found that OP‐derived migratory cells labeled at embryonic day (E) 3 resided in the olfactory nerve and medial forebrain at E17–19. A subpopulation of green fluorescent protein (GFP)‐labeled GnRH neurons that remained in the olfactory nerve was considered to comprise terminal nerve neurons. In the forebrain, GFP‐labeled cells showed a distribution pattern similar to that of GnRH neurons. A large proportion of GFP‐labeled cells expressed the mature neuronal marker NeuN. Among the GFP‐labeled cells, the percentage of GnRH neurons was low, while the remaining GnRH‐negative neurons either expressed SS mRNA, neuropeptide Y, or calbindin D‐28k or did not express any of them. These results indicate that a diverse population of OP‐derived neuronal cells, other than GnRH neurons, integrates into the chick medial forebrain.
Comprehensive detrimental effects of a simulated frequently shifting schedule on diurnal rhythms and vigilance

ABSTRACT Accumulating data have demonstrated that shift work causes a disturbance in circadian rhythms, which is detrimental to physiology and performance. However, the detailed effects of shift work and especially the underlying mechanisms remain to be further investigated. Frequently shifting schedules are widely used in industries, e.g., maritime tasks, oil mining, and aviation. In this work, we investigated the physiological changes and vigilance of 12 subjects who lived on a 30-day frequent shift working schedule in a confined environment, which mimics the common maritime schedules. Elevated and decreased cortisol levels were observed at different stages during the shift, suggesting the occurrence of stress and fatigue. The results of the Karolinska Sleepiness Scale (KSS) indicate increased sleepiness and a changed pattern of the rhythmicity of sleepiness during the shift. The tests of the Psychomotor Vigilance Task (PVT) reveal that the shift led to a continuously decreasing alertness as the shift working schedule progressed, which is prevalently due to the increasingly slower reaction speed. The PVT time-out errors were significantly increased in the early period but decreased in the late period. In addition, we found recoupling of the correlations between multiple physiological and cognitive variables. For instance, heartbeat rate (HR) and breath rate (BR) showed moderate correlations in the control and early periods but little in the late period. Together, these results reveal substantial alterations in diurnal rhythms, affected vigilance and changed coupling of the correlations of diurnal rhythms, physiology and cognition caused by a shift schedule. Our findings may help in the recognition of the detrimental effects of such working schedules and provide clues for the development of potential mitigations.
Limitations of microbial iron reduction under extreme conditions

Abstract Microbial iron reduction is a widespread and ancient metabolism on Earth, and may plausibly support microbial life on Mars and beyond. Yet, the extreme limits of this metabolism are yet to be defined. To investigate this, we surveyed the recorded limits to microbial iron reduction in a wide range of characterized iron-reducing microorganisms (n = 141), with a focus on pH and temperature. We then calculated Gibbs free energy of common microbially mediated iron reduction reactions across the pH–temperature habitability space to identify thermodynamic limits. Comparing predicted and observed limits, we show that microbial iron reduction is generally reported at extremes of pH or temperature alone, but not when these extremes are combined (with the exception of a small number of acidophilic hyperthermophiles). These patterns leave thermodynamically favourable combinations of pH and temperature apparently unoccupied. The empty spaces could be explained by experimental bias, but they could also be explained by energetic and biochemical limits to iron reduction at combined extremes. Our data allow for a review of our current understanding of the limits to microbial iron reduction at extremes and provide a basis to test more general hypotheses about the extent to which biochemistry establishes the limits to life.