Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of High-Energy Milling on the Dissolution of Anti-HIV Drug Efavirenz in Different Solvents

The anti-HIV drug efavirenz (EFV) displays low and variable bioavailability because of its poor aqueous solubility. Ball milling is a simple and cost-effective alternative to traditional micronization to improve the solubility and dissolution rate of EFV. A multibody dynamics model was employed to optimize the milling process parameters, while the motion of the balls in the mill jar was monitored in operando. This led to a better understanding of the milling dynamics for efficient comminution and enhancement of EFV dissolution. The variability of results for different EFV batches was also considered. Depending on the EFV batch, there were intrinsic differences in how the milling affected the dissolution behavior and inhibition of HIV-1 infection. High-energy grinding is more effective on EFV materials containing an amorphous fraction; it helps to remove agglomeration and enhances dissolution. Polyvinylpyrrolidone (PVP) addition improves the dissolution by forming a hydrophilic layer on the EFV surface, thereby increasing the drug wettability. Polymorphism also affects the quality, dosage, and effectiveness of the drug. The mechanical stress effect and PVP addition on the EFV polymorphic transformation were monitored by X-ray powder diffraction, while the residual of ground EFV was collected after dissolution, analyzed by scanning electron microscopy, and provided insights into the morphological changes.
A Review on the Utilization of Lignin as a Fermentation Substrate to Produce Lignin-Modifying Enzymes and Other Value-Added Products

The lignocellulosic biomass is comprised of three major components: cellulose, hemicellulose, and lignin. Among these three, cellulose and hemicellulose were already used for the generation of simple sugars and subsequent value-added products. However, lignin is the least applied material in this regard because of its complex and highly variable nature. Regardless, lignin is the most abundant material, and it can be used to produce value-added products such as lignin-modifying enzymes (LMEs), polyhydroxyalkanoates (PHAs), microbial lipids, vanillin, muconic acid, and many others. This review explores the potential of lignin as the microbial substrate to produce such products. A special focus was given to the different types of lignin and how each one can be used in different microbial and biochemical pathways to produce intermediate products, which can then be used as the value-added products or base to make other products. This review paper will summarize the effectiveness of lignin as a microbial substrate to produce value-added products through microbial fermentations. First, basic structures of lignin along with its types and chemistry are discussed. The subsequent sections highlight LMEs and how such enzymes can enhance the value of lignin by microbial degradation. A major focus was also given to the value-added products that can be produced from lignin.
Improved Functional Causal Likelihood-Based Causal Discovery Method for Diabetes Risk Factors

Diabetes mellitus is a disease that has reached epidemic proportions globally in recent years. Consequently, the prevention and treatment of diabetes have become key social challenges. Most of the research on diabetes risk factors has focused on correlation analysis with little investigation into the causality of these risk factors. However, understanding the causality is also essential to preventing the disease. In this study, a causal discovery method for diabetes risk factors was developed based on an improved functional causal likelihood (IFCL) model. Firstly, the issue of excessive redundant and false edges in functional causal likelihood structures was resolved through the construction of an IFCL model using an adjustment threshold value. On this basis, an IFCL-based causal discovery algorithm was designed, and a simulation experiment was performed with the developed algorithm. The experimental results revealed that the causal structure generated using a dataset with a sample size of 2000 provided more information than that produced using a dataset with a sample size of 768. In addition, the causal structures obtained with the developed algorithm had fewer redundant and false edges. The following six causal relationships were identified: insulin→plasma glucose concentration, plasma glucose concentration→body mass index (BMI), triceps skin fold thickness→BMI and age, diastolic blood pressure→BMI, and number of times pregnant→age. Furthermore, the reasonableness of these causal relationships was investigated. The algorithm developed in this study enables the discovery of causal relationships among various diabetes risk factors and can serve as a reference for future causality studies on diabetes risk factors.
An Interaction Effect Analysis of Thermodilution-Guided Hemodynamic Optimization, Patient Condition, and Mortality after Successful Cardiopulmonary Resuscitation

Proper hemodynamic management is necessary among post-cardiac arrest patients to improve survival. We aimed to investigate the effects of PiCCO™-guided (pulse index contour cardiac output) hemodynamic management on mortality in post-resuscitation therapy. In this longitudinal analysis of 63 comatose patients after successful cardiopulmonary resuscitation cooled to 32–34 °C, 33 patients received PiCCO™, and 30 were not monitored with PiCCO™. Primary and secondary outcomes were 30 day and 1 year mortality. Kaplan–Meier curves and log-rank tests were used to assess differences in mortality among the groups. Interaction effects to disentangle the relationship between patient’s condition, PiCCO™ application, and mortality were assessed by means of Chi-square tests and logistic regression models. A 30 day mortality was significantly higher among PiCCO™ patients, while 1 year mortality was marginally higher. More severe patient condition per se was not the cause of higher mortality rate in the PiCCO™ group. Patients in better health conditions (without ST-elevation myocardial infarction, without cardiogenic shock, without intra-aortic balloon pump device, or without stroke in prior history) had worse outcomes with PiCCO™-guided therapy. Catecholamine administration worsened both 30 day and 1 year mortality among all patients. Our analysis showed that there was a complex interaction relationship between PiCCO™-guided therapy, patients’ condition, and 30 day mortality for most conditions.
The Multifunctional Role of EMP3 in the Regulation of Membrane Receptors Associated with IDH-Wild-Type Glioblastoma

Epithelial membrane protein 3 (EMP3) is a tetraspan membrane protein overexpressed in isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma (GBM). Several studies reported high EMP3 levels as a poor prognostic factor in GBM patients. Experimental findings based on glioma and non-glioma models have demonstrated the role of EMP3 in the regulation of several membrane proteins known to drive IDH-wt GBM. In this review, we summarize what is currently known about EMP3 biology. We discuss the regulatory effects that EMP3 exerts on a variety of oncogenic receptors and discuss how these mechanisms may relate to IDH-wt GBM. Lastly, we enumerate the open questions towards EMP3 function in IDH-wt GBM.
May Measurement Month 2019: an analysis of blood pressure screening results from Nepal

Abstract May Measurement Month (MMM) is a global initiative to screen high blood pressure (BP) in the community and increase awareness at the population level. High BP is the leading risk factor for mortality worldwide and in Nepal. This study presents the results of the 2019 MMM in Nepal. Opportunistic BP screening was conducted in 30 out of 77 districts across Nepal and aged ≥18 years at the community and public places. BP was measured three times in a seated position. A total of 74 205 individuals participated in the study, mean age 39.9 years, and 58% were male. BP measurements for the second and third readings were available for 69 292 (93.3%) individuals. The proportion of the population that were hypertensive was 27.5% (n = 20 429). Among those hypertensives, 46.3% were aware of their hypertensive status and of these, 37.5% were on antihypertensive medication. Only 54.3% of those on antihypertensive medication had their BP controlled. Of the community screened, those self reporting to have diabetes, current tobacco users, and current alcohol drinkers were 6.7%, 23.6%, and 31.9%, respectively; 20.6% of the participants were overweight, and 6.5% were obese. Since the first BP screening campaign, MMM 2017 in Nepal, the number of participants screened has largely increased over the years. MMM’s success in Nepal is through a coordinated mobilization of trained health science students and volunteers in the communities. The Nepal MMM data demonstrates that large community-based BP screening campaigns are possible in low resource settings.
Changes in the Small RNA Expression in Endothelial Cells in Response to Inflammatory Stimulation

Objective Endothelial cell inflammation is a common pathophysiological process in many cardiovascular and cerebrovascular diseases. Small RNA is a kind of short nonprotein coding RNA molecule. Changes in the small RNA expression in endothelial cells have been linked to the development of cardiovascular and cerebrovascular diseases. We investigated and verified differentially expressed small RNAs in endothelial cells in response to inflammatory stimulation. Methods Primary rat endothelial cells were obtained from Sprague-Dawley rats and treated with 10 ng/ml TNF-α for 24 hours. Small RNA sequencing was used to generate extensive small RNA data. Significantly differentially expressed small RNAs identified in the analysis were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we investigated the tissue-specific small RNA expression after RNA extraction from different tissues. Results Small RNA sequencing demonstrated that 17 miRNAs, 1 piRNA, 10 snoRNAs, and 7 snRNAs were significantly differentially expressed. qRT-PCR identified 3 miRNAs, 2 snoRNAs, and 2 snRNAs with significantly different expression. Analysis of the tissue-specific expression showed that rno-miR-126a-5p was predominantly expressed in the lung, rno-miR-146a-5p in the intestines, and rno-novel-178 in the heart. Rno-piR-017330 was mainly expressed in the muscle. snoR-8966.1 was predominantly expressed in the bone. snoR-6253.1 was mostly expressed in the vessels and bone. snR-29469.1 was mainly expressed in the bone, and snR-85806.1 was predominantly expressed in the vessels and bone. Conclusions We report for the first time the expression of small RNAs in endothelial cells under inflammatory conditions. TNF-α can regulate the expression of small RNAs in endothelial cells, and their expression is tissue-specific.
Assessment of a Reliable Fractional Anisotropy Cutoff in Tractography of the Corticospinal Tract for Neurosurgical Patients

Background: Tractography has become a standard technique for planning neurosurgical operations in the past decades. This technique relies on diffusion magnetic resonance imaging. The cutoff value for the fractional anisotropy (FA) has an important role in avoiding false-positive and false-negative results. However, there is a wide variation in FA cutoff values. Methods: We analyzed a prospective cohort of 14 patients (six males and eight females, 50.1 ± 4.0 years old) with intracerebral tumors that were mostly gliomas. Magnetic resonance imaging (MRI) was obtained within 7 days before and within 7 days after surgery with T1 and diffusion tensor image (DTI) sequences. We, then, reconstructed the corticospinal tract (CST) in all patients and extracted the FA values within the resulting volume. Results: The mean FA in all CSTs was 0.4406 ± 0.0003 with the fifth percentile at 0.1454. FA values in right-hemispheric CSTs were lower (p < 0.0001). Postoperatively, the FA values were more condensed around their mean (p < 0.0001). The analysis of infiltrated or compressed CSTs revealed a lower fifth percentile (0.1407 ± 0.0109 versus 0.1763 ± 0.0040, p = 0.0036). Conclusion: An FA cutoff value of 0.15 appears to be reasonable for neurosurgical patients and may shorten the tractography workflow. However, infiltrated fiber bundles must trigger vigilance and may require lower cutoffs.
Changes in Light Energy Utilization in Photosystem II and Reactive Oxygen Species Generation in Potato Leaves by the Pinworm Tuta absoluta

We evaluated photosystem II (PSII) functionality in potato plants (Solanum tuberosum L.) before and after a 15 min feeding by the leaf miner Tuta absoluta using chlorophyll a fluorescence imaging analysis combined with reactive oxygen species (ROS) detection. Fifteen minutes after feeding, we observed at the feeding zone and at the whole leaf a decrease in the effective quantum yield of photosystem II (PSII) photochemistry (ΦPSII). While at the feeding zone the quantum yield of regulated non-photochemical energy loss in PSII (ΦNPQ) did not change, at the whole leaf level there was a significant increase. As a result, at the feeding zone a significant increase in the quantum yield of non-regulated energy loss in PSII (ΦNO) occurred, but there was no change at the whole leaf level compared to that before feeding, indicating no change in singlet oxygen (1O2) formation. The decreased ΦPSII after feeding was due to a decreased fraction of open reaction centers (qp), since the efficiency of open PSII reaction centers to utilize the light energy (Fv′/Fm′) did not differ before and after feeding. The decreased fraction of open reaction centers resulted in increased excess excitation energy (EXC) at the feeding zone and at the whole leaf level, while hydrogen peroxide (H2O2) production was detected only at the feeding zone. Although the whole leaf PSII efficiency decreased compared to that before feeding, the maximum efficiency of PSII photochemistry (Fv/Fm), and the efficiency of the water-splitting complex on the donor side of PSII (Fv/Fo), did not differ to that before feeding, thus they cannot be considered as sensitive parameters to monitor biotic stress effects. Chlorophyll fluorescence imaging analysis proved to be a good indicator to monitor even short-term impacts of insect herbivory on photosynthetic function, and among the studied parameters, the reduction status of the plastoquinone pool (qp) was the most sensitive and suitable indicator to probe photosynthetic function under biotic stress.
In Vitro Antiviral Activity of α-Mangostin against Dengue Virus Serotype-2 (DENV-2)

Dengue virus (DENV), a member of the family Flaviviridae, is a threat for global health as it infects more than 100 million people yearly. Approved antiviral therapies or vaccines for the treatment or prevention of DENV infections are not available. In the present study, natural compounds were screened for their antiviral activity against DENV by in vitro cell line-based assay. α-Mangostin, a xanthanoid, was observed to exert antiviral activity against DENV-2 under pre-, co- and post-treatment testing conditions. The antiviral activity was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immunofluorescence assay (IFA). A complete inhibition of DENV-2 was observed at 8 µM under the co-treatment condition. The possible inhibitory mechanism of α-Mangostin was also determined by docking studies. The molecular docking experiments indicate that α-Mangostin can interact with multiple DENV protein targets such as the NS5 methyltransferase, NS2B-NS3 protease and the glycoprotein E. The in vitro and in silico findings suggest that α-Mangostin possesses the ability to suppress DENV-2 production at different stages of its replication cycle and might act as a prophylactic/therapeutic agent against DENV-2.
Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

Simple Summary Liver metastasis remains the major contributor in colorectal cancer-related death. It has become clear that the unique immune features of liver microenvironment take part in many steps of metastatic cascade, from pre-metastatic niche formation, tumor cell colonization to metastatic tumor establishment. Therefore, better understanding of mechanisms orchestrating the formation of a hospitable hepatic metastatic niche is necessary for the development of effective therapies. This review summarizes the current understandings of the critical role of liver immune microenvironment in metastasis development and provides therapeutic perspective on targeting the metastasis-prone microenvironment. Abstract A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.
Meta-Analytic Review of High Anxiety Comorbidity among Patients with Vitiligo

Background Vitiligo is a disfiguring skin disease with profound psychosocial impacts, such as anxiety, but the reported effect sizes of associations vary. We aimed to conduct a meta-analysis to quantify the strength of association between anxiety and vitiligo and to estimate the prevalence of anxiety among individuals with vitiligo. Methods A systematic literature search was performed in five online databases (MEDLINE, Embase, Web of Science, Cochrane Library, and PsycINFO) from inception until March 20, 2020. All of the eligible studies were comprehensively reviewed, and all of the available data were analyzed according to our predefined criteria. Results Twenty-one studies involving 3259 patients in 11 countries were included in this meta-analysis. Compared with the healthy control group, patients with vitiligo often had concomitant anxiety (OR = 6.14 [95% CI: 3.35–11.24], I2 = 30.1%). The pooled prevalence of anxiety in female patients was significantly higher than that in males (OR = 2.24 [95% CI: 1.31–3.84], I2 = 0.0%). Subgroup analysis showed that the pooled prevalence of clinical anxiety disorder and anxiety symptoms was 12% (95% CI: 7%–16%, I2 = 76.3%) and 34% (95% CI: 21%–46%, I2 = 94.7%), respectively. No publication bias has been detected by Begg's funnel plot and Egger's test. Conclusion Patients with vitiligo have high anxiety comorbidity, with female predominance. Dermatologists and psychiatrists should be vigilant to the presence of anxiety, apply appropriate interventions to reduce the psychological impacts in a timely manner, and thus promote recovery in vitiligo patients. However, due to some objective limitations (poor information about the OR and diversity in assessment tools among included studies), findings should be interpreted with caution.
Surgery for Perforated Peptic Ulcer: Is Laparoscopy a New Paradigm?

Introduction Laparoscopic repair of perforated peptic ulcer (PPU) remains controversial mainly due to its safety and applicability in critically ill patients. The aim of this study is to compare the outcomes of laparoscopy versus laparotomy in the treatment of PPU. Methods Single-institutional, retrospective study of all patients submitted to surgical repair of PPU between 2012 and 2019. Results During the study period, 169 patients underwent emergent surgery for PPU. A laparoscopic approach was tried in 60 patients and completely performed in 49 of them (conversion rate 18.3%). The open group was composed of 120 patients (included 11 conversions). Comparing the laparoscopic with the open group, there were significant differences in gender (male/female ratio 7.2/1 versus 2.2/1, respectively; p=0.009) and in the presence of sepsis criteria (12.2% versus 38.3%, respectively; p=0.001), while the Boey score showed no differences between the two groups. The operative time was longer in the laparoscopic group (median 100' versus 80', p=0.01). Laparoscopy was associated with few early postoperative complications (18.4% versus 41.7%, p=0.004), mortality (2.0% versus 14.2%; p=0.02), shorter hospital stay (median 6 versus 7 days, p=0.001), and earlier oral intake (median 3 versus 4 days, p=0.021). Conclusion Laparoscopic repair of PPU may be considered the procedure of choice in patients without sepsis criteria if expertise and resources are available. This kind of approach is associated with a shorter length of hospital stay and earlier oral intake. In patients with sepsis criteria, more data are required to access the safety of laparoscopy in the treatment of PPU.
From Melanocytes to Melanoma Cells: Characterization of the Malignant Transformation by Four Distinctly Different Melanin Fluorescence Spectra (Review) †

The melanin fluorescence emitted by pigment cells of the human skin has been a central research topic for decades, because melanin, on the one hand, protects against (solar) radiation in the near-UV range, whereas on the other hand, melanocytes are the starting point for the malignant transformation into melanoma. Until recently, however, melanin fluorescence was not accessible in the context of conventional spectroscopy, because it is ultraweak and is overshadowed by the more intense so-called autofluorescence of endogenous fluorophores. The advent of a new method of laser spectroscopy has made this melanin fluorescence measurable in vivo. A stepwise two-photon absorption with 800 nm photons is used, which more selectively excites melanin (dermatofluoroscopy). Our review summarizes the experimental results on melanin fluorescence of the four types of cutaneous pigment cells from healthy and malignant tissues. Outstanding is the finding that different types of melanocytes (i.e., melanocytes of common nevi, versus dysplastic nevi or versus melanoma cells) show characteristically different fluorescence spectra. The possibilities of using this melanin fluorescence for melanoma diagnosis are shown. Moreover, the uniform fluorescence spectra emitted by different melanoma subtypes are essential. Conclusions are drawn about the molecular processes in the melanosomes that determine fluorescence. Finally, experimental suggestions for further investigations are given.