Miracle-dz/UniFAR-FTUs huggingface dataset:
The rs216009 single-nucleotide polymorphism of the CACNA1C gene is associated with phantom tooth pain

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. The present study focused on the CACNA1C gene, which encodes the α1C subunit of the Cav1.2 L-type Ca2+ channel (LTCC) that has been reported to be associated with neuropathic pain in previous studies. We investigated genetic polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 33 patients with PTP and 118 patients without PTP but with pain or dysesthesia in the orofacial region. From within and around the CACNA1C gene, 155 polymorphisms were selected and analyzed for associations with clinical data. We found that the rs216009 single-nucleotide polymorphism (SNP) of the CACNA1C gene in the recessive model was significantly associated with the vulnerability to PTP. Homozygote carriers of the minor C allele of rs216009 had a higher rate of PTP. Nociceptive transmission in neuropathic pain has been reported to involve Ca2+ influx from LTCCs, and the rs216009 polymorphism may be involved in CACNA1C expression, which regulates intracellular Ca2+ levels, leading to the vulnerability to PTP. Furthermore, psychological factors may lead to the development of PTP by modulating the descending pain inhibitory system. Altogether, homozygous C-allele carriers of the rs216009 SNP were more likely to be vulnerable to PTP, possibly through the regulation of intracellular Ca2+ levels and affective pain systems, such as those that mediate fear memory recall.
THE IMPACT OF INNOVATION PERFORMANCE ON THE COMPETITIVENESS OF THE VISEGRAD 4 COUNTRIES

The economic development of world economies accompanied by their growing openness and stronger integration processes put pressure on mutual confrontation of their economic power based on its determinant sources. International comparison requires determining a complex of factors that affect the success of developed economies; factors that, given their multiplier effects, influence the social productivity of labor in a country and create a competitive advantage in an international comparison. A key factor of the states’ increasing competitiveness is assumed to be the innovation performance of enterprises, which is projected through innovative business processes into the innovation performance of the economy as a whole. This paper determines the impact of their innovation performance on their international competitiveness position observed by the Global Economic Forum based on the Global Competitiveness Index (GCI). To assess the impact, the following economic-statistical methods were used: comparative and correlation analyses and logical deduction. Data from the World Economic Forum (WEF), European Innovation Scoreboard (EIS), and Eurostat database were used to process the assessment. The results of the research have led to the conclusion that the Visegrad 4 (V4) countries as transition economies in terms of their economic development are quite similar, but in the ranking of global competitiveness, their position varies depending on the innovative performance. The Czech economy is the best performing of the four, while the worst indicators are attributed to the economies of Slovakia and Hungary. The economy of Poland has a relatively balanced development. The results of these analyses have led to the creation of a discussion platform focused on the evaluation of the innovation potential status and its determinants in Slovakia, with the aim of pointing out critical areas in the country’s competitiveness growth on an international scale.
Long-Wave High-Frequency Oscillations in Ionic Crystals with Two Atoms in Elementary Cell

Long-wave high-frequency electromagnetic oscillations in an ionic crystal with two atoms in an elementary cell have been considered in the framework of a self-consistent model for free point charges in the electromagnetic field in a dielectric medium. The frequency of longitudinal phonons is shown to equal the ionic plasma frequency divided by the square root of the high-frequency dielectric permittivity. The standard dispersion law for the upper phonon-polariton branch is obtained.
In Vitro Antiproliferative Effects and Phytochemical Characterization of Carissa edulis ((Forssk) Vahl) and Pappea capensis (Eckyl and Zeyh) Extracts

Cancer mortality is a global concern. The current therapeutic approaches despite showing efficacy are characterized by several limitations. Search for alternatives has led to the use of herbal plants including C. edulis and P. capensis. However, there is limited research on antiproliferative effects of these medicinal plants. The study sought to evaluate antiproliferative effects of the plants against human breast and prostate cancers using cell viability, and gene expression assays to determine modulation of apoptotic genes. Further, Liquid Chromatography Mass Spectrophotometer (LC-MS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses were performed to confirm phytocompounds in the extracts. The results indicated that ethylacetate extracts of C. edulis and P. capensis had the highest activity against cancer cells with IC50 values of 2.12 ± 0.02, and 6.57 ± 0.03 μg/ml on HCC 1395 and 2.92 ± 0.17 and 5.00 ± 0.17 μg/ml on DU145, respectively. Moreover, the plants extracts exhibited relatively less cytotoxic activities against Vero cell lines (IC50 > 20 μg/ml). The extracts also exhibit selectivity against the cancer cells (SI > 3). Further, mRNA expression of p53 in the treated HCC 1395 was increased by 7 and 3-fold, whereas by 3 and 2-fold in DU145 cells, upon treatment with ethylacetate extracts of C. edulis and P. capensis, respectively. Similarly, several-fold increases were observed in the number of transcripts of Bax in HCC 1395 and HOXB13 in DU145 cells. Phytochemical analyses detected presence of phytocompounds including flavonoids, phenolics, tocopherols and terpenoids which are associated with anticancer activity. Findings from this study provide a scientific validation for the folklore use of these plants in management of cancer.
Ageing reduces persistent inward current contribution to motor neurone firing: Potential mechanisms and the role of exercise

Nervous system deterioration is a primary driver of age‐related motor impairment. The motor neurones, which act as the interface between the central nervous system and the muscles, play a crucial role in amplifying excitatory synaptic input to produce the desired motor neuronal firing output. For this, they utilise their ability to generate persistent (long‐lasting) depolarising currents that increase cell excitability, and both amplify and prolong the output activity of motor neurones for a given synaptic input. Modulation of these persistent inward currents (PICs) contributes to the motor neurones’ capacities to attain the required firing frequencies and rapidly modulate them to competently complete most tasks. Thus, PICs are crucial for adequate movement generation. Impairments in intrinsic motor neurone properties can impact motor unit firing capacity, with convincing evidence indicating that the PIC contribution to motor neurone firing is reduced in older adults. Indeed, this could be an important mechanism underpinning the age‐related reductions in strength and physical function. Furthermore, resistance training has emerged as a promising intervention to counteract age‐associated PIC impairments, with changes in PICs being correlated with improvements in muscular strength and physical function after training. In this review, we present the current knowledge of the PIC magnitude decline during ageing and discuss whether reduced serotonergic and noradrenergic input onto the motor neurones, voltage‐gated calcium channel dysfunction or inhibitory input impairments are candidates that: (i) explain age‐related reductions in the PIC contribution to motor neurone firing and (ii) underpin the enhanced PIC contribution to motor neurone firing following resistance training in older adults.
Reminders, but not monetary incentives, increase COVID-19 booster uptake

Significance COVID-19 booster vaccination rates around the world are low, despite being the best source of protection against serious disease or death. In a preregistered randomized controlled trial with 57,893 patients, we found that a one-time personal reminder message increased booster vaccination rates by nearly 33% but small financial incentives of $25 had no additional impact.
Photocatalytic chlorine atom production on mineral dust–sea spray aerosols over the North Atlantic

Significance Using a combination of field data and global modeling, we demonstrate a mechanism in which a mix of Sahara dust and sea spray aerosol activated by sunlight produces large amounts of active chlorine. This mechanism resolves a number of unexplained observations and significantly revises our understanding of atmospheric chlorine, reducing uncertainties in the source budget. The chlorine formed by this mechanism impacts two important greenhouse gasses, methane and tropospheric ozone, with an estimated catalytic efficiency of removing ca. 45 methane molecules per iron atom per day. The inclusion of Cl. made from the photocatalytic oxidation of ocean chloride in models will reduce critical uncertainties in estimates of methane emissions and improve our ability to predict future climate change.
NOD1 cooperates with HAX‐1 to promote cell migration in a RIPK2‐ and NF‐ĸB‐independent manner

The human Nod‐like receptor protein NOD1 is a well‐described pattern‐recognition receptor (PRR) with diverse functions. NOD1 associates with F‐actin and its protein levels are upregulated in metastatic cancer cells. A hallmark of cancer cells is their ability to migrate, which involves actin remodelling. Using chemotaxis and wound healing assays, we show that NOD1 expression correlated with the migration rate and chemotactic index in the cervical carcinoma cell line HeLa. The effect of NOD1 in cell migration was independent of the downstream kinase RIPK2 and NF‐ĸB activity. Additionally, NOD1 negatively regulated the phosphorylation status of cofilin, which inhibits actin turnover. Co‐immunoprecipitation assays identified HCLS1‐associated protein X‐1 (HAX‐1) as a previously unknown interaction partner of NOD1. Silencing of HAX‐1 expression reduced the migration behaviour to similar levels as NOD1 knockdown, and simultaneous knockdown of NOD1 and HAX‐1 showed no additive effect, suggesting that both proteins act in the same pathway. In conclusion, our data revealed an important role of the PRR NOD1 in regulating cell migration as well as chemotaxis in human cervical cancer cells and identified HAX‐1 as a protein that interacts with NOD1 and is involved in this signalling pathway.
Relative singular locus and matrix factorizations

We introduce the notion of the relative singular locus Sing$(T/S)$ of a closed subscheme $T$ of a Noetherian scheme $S$, and for a separated Noetherian scheme $X$ with an ample family of line bundles and a non-zero-divisor $W\in\Gamma(X,L)$ of a line bundle $L$ on $X$, we classify certain thick subcategories of the derived matrix factorization category DMF$(X,L,W)$ by means of specialization-closed subsets of the relative singular locus Sing$(X_0/X)$ of the zero scheme $X_0:=W^{-1}(0)\subset X$. Furthermore, we show that the spectrum of the tensor triangulated category (DMF$(X,L,W)$, $\otimes^{\frac{1}{2}}$) is homeomorphic to the relative singular locus Sing$(X_0/X)$ by using the classification result and the theory of Balmer's tensor triangular geometry.
Tubulin Alpha-1b as a Potential Biomarker for Lung Adenocarcinoma Diagnosis and Prognosis

Background: Because lung cancer is the main cause of cancer deaths and lung adenocarcinoma (LUAD) accounts for more than 40% of all lung malignancies, it is essential to develop clinically useful biomarkers for the disease. The aim of this investigation is to assess the potential application of tubulin alpha-1b (TUBA1B) as a biomarker for diagnosing and monitoring the outcome of LUAD. Methods: The clinical data of the LUAD patients was retrospectively analyzed. Immunohistochemistry (IHC) analysis of a tissue microarray containing 90 LUAD cases was implemented to examine the expression of TUBA1B. The protein and mRNA levels of TUBA1B in serum were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) analysis respectively. UALCAN was employed to confirm the expression levels and survival probability of TUBA1B in LUAD patients. Results: Compared to adjacent non-cancerous tissues in the microarray, the expression of TUBA1B in LUAD tissues was much higher. The expression of TUBA1B in LUAD was statistically correlated with lymph node status (P = .031). Moreover, patients with higher TUBA1B expression had shorter overall survival (P < .0001). Furthermore, cox multi-factor analysis also suggested that TUBA1B may be an independent predictor for LUAD prognosis (P = .030). The results of TCGA data analysis by UALCAN were consistent with the microarray results, except for that TUBA1B was also significantly correlated with clinical tumor stages. Protein levels of TUBA1B in serum were obviously elevated in LUAD patients than control (P < .0001), and the area under the ROC curve was 0.99. TUBA1B also showed better sensitivity of 92.9% for LUAD than common clinical biomarkers. Conclusion: TUBA1B may be a non-invasive prognostic and diagnostic biomarker for LUAD patients.
Implementing Preeclampsia Screening in Switzerland (IPSISS): First Results from a Multicentre Registry

Introduction: The Fetal Medicine Foundation (FMF) London developed a first trimester combined screening algorithm for preterm preeclampsia (pPE) that allows a significantly higher detection of pregnancies at risk compared to conventional screening by maternal risk factors only. The aim of this trial is to validate this screening model in the Swiss population in order to implement this screening into routine first trimester ultrasound and to prescribe low-dose aspirin 150 mg (LDA) in patients at risk for pPE. Therefore, a multicentre registry study collecting and screening pregnancy outcome data was initiated in 2020; these are the preliminary results. Methods: Between June 1, 2020, and May 31, 2021, we included all singleton pregnancies with pPE screening at the hospitals of Basel, Lucerne, and Bern. Multiple of medians of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) as well as risks were analysed as calculated by each centre’s software and recalculated on the FMF online calculator for comparative reasons. Statistical analyses were performed by GraphPad Version 9.1. Results: During the study period, 1,027 patients with singleton pregnancies were included. 174 (16.9%) had a risk >1:100 at first trimester combined screening. Combining the background risk, MAP, UtA-PI, and PlGF only, the cut-off to obtain a screen positive rate (SPR) of 11% is ≥1:75. Outcomes were available for 968/1,027 (94.3%) of all patients; 951 resulted in live birth. Fifteen (1.58%) developed classical preeclampsia (PE), 23 (2.42%) developed PE according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) definition. Conclusion: First trimester combined screening for PE and prevention with LDA results in a low prevalence of PE. The screening algorithm performs according to expectations; however, the cut-off of >1:100 results in a SPR above the accepted range and a cut-off of ≥1:75 should be considered for screening. More data are needed to evaluate, if these results are representative for the general Swiss population.
Discovery of novel TRPV1 modulators through machine learning‐based molecular docking and molecular similarity searching

The transient receptor potential vanilloid 1 (TRPV1) channel belongs to the transient receptor potential channel superfamily and participates in many physiological processes. TRPV1 modulators (both agonists and antagonists) can effectively inhibit pain caused by various factors and have curative effects in various diseases, such as itch, cancer, and cardiovascular diseases. Therefore, the development of TRPV1 channel modulators is of great importance. In this study, the structure‐based virtual screening and ligand‐based virtual screening methods were used to screen compound databases respectively. In the structure‐based virtual screening route, a full‐length human TRPV1 protein was first constructed, three molecular docking methods with different precisions were performed based on the hTRPV1 structure, and a machine learning‐based rescoring model by the XGBoost algorithm was constructed to enrich active compounds. In the ligand‐based virtual screening route, the ROCS program was used for 3D shape similarity searching and the EON program was used for electrostatic similarity searching. Final 77 compounds were selected from two routes for in vitro assays. The results showed that 8 of them were identified as active compounds, including three hits with IC50 values close to capsazepine. In addition, one hit is a partial agonist with both agonistic and antagonistic activity. The mechanisms of some active compounds were investigated by molecular dynamics simulation, which explained their agonism or antagonism.
Low‐dose decitabine promotes M2 macrophage polarization in patients with primary immune thrombocytopenia via enhancing KLF4 binding to PPARγ promoter

Background The first‐line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long‐term responses remains challenging. Low‐dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP. Methods The M2 monocytes were identified by flow cytometry from peripheral blood mononuclear cells in healthy controls (HCs) and ITP patients. The expression of PPARγ, Arg‐1, DNMT3b and NLRP3, together with IL‐10 plasma levels was measured to examine its function. Bisulfite‐sequencing PCR was used to evaluate the methylation status of PPARγ promoter, and the binding affinity of KLF4 was measured by Cut&Tag. A sh‐PPARγ THP‐1 cell line was created to verify if low‐dose DAC‐modulated M2 macrophage polarization was PPARγ‐dependent. The passive ITP models were used to investigate the therapeutic effects of low‐dose DAC and its role in modulating polarization and immunomodulatory function of macrophages. NLRP3 inflammasome and reactive oxygen species were also tested to understand the downstream of PPARγ. Results The M2 monocytes with impaired immunoregulation were observed in ITP. After high‐dose dexamethasone (HD‐DXM) treatment, M2 monocytes increased significantly with the elevated expression of PPARγ, Arg‐1 and IL‐10 in CR patients. Low‐dose DAC promoted M2 macrophage polarization in a PPARγ‐dependent way via demethylating the promoter of PPARγ, especially the KLF4 binding sites. Low‐dose DAC alleviated ITP mice by restoring the M1/M2 balance and fine‐tuning immunomodulatory function of macrophages. The downstream of the PPARγ modulation of M2 macrophage polarization might physiologically antagonize NLRP3 inflammasome. Conclusions Low‐dose DAC promoted M2 macrophage polarization due to the demethylation within the promoter of PPARγ, thus enhanced the KLF4 binding affinity in ITP.
Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero

Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre‐pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population.
Doppler Examination of the Testicular Artery of Beagle-Breed Dogs from Birth to Puberty

The objectives were (a) the study of haemodynamic parameters of blood flow within the testicular artery, (b) the assessment of differences in these parameters at different segments of the artery (i.e., sequentially, as the artery flows through different regions of the testis), and (c) the identification of potential associations with measures of testicular maturation. Eight healthy beagle-breed male dogs were monitored at fortnightly intervals from the 4th to the 40th week of life, by using clinical, seminological, and ultrasonographic (B-mode, pulsed-wave Doppler) examinations. Haemodynamic parameters were assessed at four different segments of the testicular artery: at the distal supra-testicular, the marginal testicular at the cranial pole of the testis, the marginal testicular at the caudal pole of the testis, and the intratesticular. The study period was divided into three time slots (pre-puberty, puberty, and post-puberty) depending on testicular maturation and sperm production. No clinically evident abnormalities were seen in any animal throughout the study. Semen ejaculates were first collected on the 28th week, and spermatozoa were first seen on the 30th week of life. The results of B-mode examination indicated that in all dogs, the echogenicity of the testicular parenchyma was homogeneous. The waveforms of the blood flow in the testicular artery were monophasic with systolic peaks, low diastolic flow, and low vascular resistance. Most cases of significant differences between the three age periods were noted for the comparison of the pre-pubertal to pubertal periods (n = 11); among the parameters studied, the blood volume (n = 9) showed most instances of significant differences; finally, most cases of significant differences were noted in the distal supra-testicular artery (n = 12). Correlations were mainly seen for the end diastolic velocity, the peak systolic velocity and the blood volume (each with two semen evaluation parameters). The distal supra-testicular and the marginal artery at the cranial pole of the testis are recommended as the most appropriate segments of the vessel for performing a Doppler examination in the testicular artery due to the adequate size and the clear spectral waveforms as early as the 12th week of age of the animals.