Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media

The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
Engineering Microneedles for Therapy and Diagnosis: A Survey

Microneedle (MN) technology is a rising star in the point-of-care (POC) field, which has gained increasing attention from scientists and clinics. MN-based POC devices show great potential for detecting various analytes of clinical interests and transdermal drug delivery in a minimally invasive manner owing to MNs’ micro-size sharp tips and ease of use. This review aims to go through the recent achievements in MN-based devices by investigating the selection of materials, fabrication techniques, classification, and application, respectively. We further highlight critical aspects of MN platforms for transdermal biofluids extraction, diagnosis, and drug delivery assisted disease therapy. Moreover, multifunctional MNs for stimulus-responsive drug delivery systems were discussed, which show incredible potential for accurate and efficient disease treatment in dynamic environments for a long period of time. In addition, we also discuss the remaining challenges and emerging trend of MN-based POC devices from the bench to the bedside.
Current State and Perspectives in Population Genomics of the Common Bean

Population genomics integrates advances in sequencing technologies, bioinformatics tools, statistical methods and software into research on evolutionary and population genetics. Its application has provided novel approaches that have significantly advanced our understanding of new and long-standing questions in evolutionary processes. This has allowed the disentangling of locus-specific effects from genome-wide effects and has shed light on the genomic basis of fitness, local adaptation and phenotypes. “-Omics” tools have provided a comprehensive genome-wide view of the action of evolution. The specific features of the Phaseolus genus have made it a unique example for the study of crop evolution. The well-documented history of multiple domestications in Phaseolus vulgaris L. (common bean) and its further adaptation to different environments have provided the opportunity to investigate evolutionary issues, such as convergent evolution in the same species across different domestication events. Moreover, the availability of the P. vulgaris reference genome now allows adaptive variations to be easily mapped across the entire genome. Here, we provide an overview of the most significant outcomes obtained in common bean through the use of different computational tools for analysis of population genomics data.
A Systematic Test of Receptor Binding Kinetics for Ligands in Tumor Necrosis Factor Superfamily by Computational Simulations

Ligands in the tumor necrosis factor (TNF) superfamily are one major class of cytokines that bind to their corresponding receptors in the tumor necrosis factor receptor (TNFR) superfamily and initiate multiple intracellular signaling pathways during inflammation, tissue homeostasis, and cell differentiation. Mutations in the genes that encode TNF ligands or TNFR receptors result in a large variety of diseases. The development of therapeutic treatment for these diseases can be greatly benefitted from the knowledge on binding properties of these ligand–receptor interactions. In order to complement the limitations in the current experimental methods that measure the binding constants of TNF/TNFR interactions, we developed a new simulation strategy to computationally estimate the association and dissociation between a ligand and its receptor. We systematically tested this strategy to a comprehensive dataset that contained structures of diverse complexes between TNF ligands and their corresponding receptors in the TNFR superfamily. We demonstrated that the binding stabilities inferred from our simulation results were compatible with existing experimental data. We further compared the binding kinetics of different TNF/TNFR systems, and explored their potential functional implication. We suggest that the transient binding between ligands and cell surface receptors leads into a dynamic nature of cross-membrane signal transduction, whereas the slow but strong binding of these ligands to the soluble decoy receptors is naturally designed to fulfill their functions as inhibitors of signal activation. Therefore, our computational approach serves as a useful addition to current experimental techniques for the quantitatively comparison of interactions across different members in the TNF and TNFR superfamily. It also provides a mechanistic understanding to the functions of TNF-associated cell signaling pathways.
Poji: a Fiji-based tool for analysis of podosomes and associated proteins

ABSTRACT Podosomes are actin-based adhesion and invasion structures in a variety of cell types, with podosome-forming cells displaying up to several hundreds of these structures. Podosome number, distribution and composition can be affected by experimental treatments or during regular turnover, necessitating a tool that is able to detect even subtle differences in podosomal properties. Here, we present a Fiji-based macro code termed ‘Poji’ (‘podosome analysis by Fiji’), which serves as an easy-to-use tool to characterize a variety of cellular and podosomal parameters, including area, fluorescence intensity, relative enrichment of associated proteins and radial podosome intensity profiles. This tool should be useful to gain more detailed insight into the regulation, architecture and functions of podosomes. Moreover, we show that Poji is easily adaptable for the analysis of invadopodia and associated extracellular matrix degradation, and likely also of other micron-size punctate structures. This article describes the workflow of the Poji macro, presents several examples of its applications, and also points out limitations, as well as respective solutions, and adaptable features to streamline the analysis. This article has an associated First Person interview with the first author of the paper. Summary: Poji is a Fiji-based macro for the characterization of cellular and podosomal parameters, including area, fluorescence intensity, relative protein enrichment and radial podosome intensity profiles.
Added Value of Diffusion Weighted Imaging for Detecting Pancreatic Abnormality in Patients with Clinically Suspected Acute Pancreatitis

Acute pancreatitis (AP) is a series of acute inflammatory reactions of the pancreatic parenchyma and can range from clinically mild to lethal. In the United States, the annual incidence of AP ranges from 13 to 45/100,000 people (1). In Korea, the annual incidence of AP per 100,000 people has increased from 15.6 in 1995 to 19.4 in 2000 (2). Although AP has a 10% of median mortality, the mortality rate is increased with age and co-morbidities and reaches up to 30-50% particularly in necrotizing pancreatitis (1-5). AP is clinically defined by at least the first two of the following three features: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: November 29, 2016 Revised: December 22, 2016 Accepted: December 26, 2016
Comparison of 1-Repetition-Maximum Performance Across 3 Weightlifting Overhead Pressing Exercises and Sport Groups.

OBJECTIVE To (1) compare the 1-repetition-maximum (1RM) performance between the push press, push jerk, and split jerk and (2) explore these differences between weightlifters, CrossFit athletes, and a mixed group of athletes. METHODS Forty-six resistance-trained males (age 28.8 [6.4] y; height 180.0 [6.0] cm; body mass 84.1 [10.2] kg; weightlifting training experience 3.64 [3.14] y) participated in this study. The 1RM performance of the push press, push jerk, and split jerk was assessed during the same session in a sequential order (ie, combined 1RM assessment method). Thirty-six participants were retested to determine between-sessions reliability of the 1RM values. RESULTS Intraclass correlation coefficients (ICCs) and associated 95% confidence intervals (CIs) showed a high between-sessions reliability for the push press (ICC = .98; 95% CI, .95-.99), push jerk (ICC = .99; 95% CI, .98-1.00), and split jerk (ICC = .99; 95% CI, .98-1.00). There was a significant main effect of exercise (η2 = .101) and exercise × group interaction (η2 = .012) on 1RM performance (P < .001), whereas the main effect of group did not reach statistical significance (P = .175). CONCLUSIONS This study provides evidence that the weightlifting overhead press derivatives affect 1RM performance. In addition, the interaction of exercise and sport group was caused by the higher differences in 1RM performance between exercises for weightlifters compared with CrossFit and a mixed group of athletes. Therefore, strength and conditioning professionals should be aware that the differences in 1RM performance between weightlifting overhead-press derivatives may be affected by sport group.
Sleep and Circadian Rhythm Disturbance in Remitted Schizophrenia and Bipolar Disorder: A Systematic Review and Meta-analysis

Abstract Background Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder. Methods EMBASE, Medline, and PsycINFO were searched for case–control studies reporting actigraphic parameters in remitted schizophrenia or bipolar disorder. Standardized and absolute mean differences between patients and controls were quantified using Hedges’ g, and patient–control differences in variability were quantified using the mean-scaled coefficient of variation ratio (CVR). A wald-type test compared effect sizes between disorders. Results Thirty studies reporting on 967 patients and 803 controls were included. Compared with controls, both schizophrenia and bipolar groups had significantly longer total sleep time (mean difference [minutes] [95% confidence interval {CI}] = 99.9 [66.8, 133.1] and 31.1 [19.3, 42.9], respectively), time in bed (mean difference = 77.8 [13.7, 142.0] and 50.3 [20.3, 80.3]), but also greater sleep latency (16.5 [6.1, 27.0] and 2.6 [0.5, 4.6]) and reduced motor activity (standardized mean difference [95% CI] = −0.86 [−1.22, −0.51] and −0.75 [−1.20, −0.29]). Effect sizes were significantly greater in schizophrenia compared with the bipolar disorder group for total sleep time, sleep latency, and wake after sleep onset. CVR was significantly elevated in both diagnoses for total sleep time, time in bed, and relative amplitude. Conclusions In both disorders, longer overall sleep duration, but also disturbed initiation, continuity, and reduced motor activity were found. Common, modifiable factors may be associated with these sleep-circadian phenotypes and advocate for further development of transdiagnostic interventions that target them.
Clinical Applications of Ultrasonography in Neurocritically Ill Patients

Ultrasonography is part of the multimodal monitoring of the neurocritical patient. Through transcranial color Doppler ultrasound, carotid-color Doppler ultrasound, and ocular ultrasound it is possible to diagnose and monitor a multitude of pathological conditions, such as cerebrovascular events, vasospasm, Terson syndrome, carotid atheromatosis, and brain death. Furthermore, these techniques enable the monitoring of the intracranial pressure, the cerebral perfusion pressure, and the midline deviation, which allows us to understand the patient’s neurocritical pathology at their bedside, in a noninvasive way. Although none of these tools have yet been shown to improve patient prognosis, the dissemination of knowledge and management of neurovascular ultrasonography could significantly improve the comprehensive management of neurocritical patients.
Implementing Technology-Supported Care for Depression and Alcohol Use Disorder in Primary Care in Colombia: Preliminary Findings.

OBJECTIVE Depression and alcohol use disorder are among the most common causes of disability and death worldwide. Health care systems are seeking ways to leverage technology to screen, evaluate, and treat these conditions, because workforce interventions alone, particularly in low- and middle-income countries, are insufficient. This article reports data from the first year of implementation of a technology-supported, systematic approach to identify and care for persons with these disorders in primary care in Colombia. METHODS A care process that includes waiting room kiosks to screen primary care patients, decision support tablets to guide doctors in diagnosis and treatment, and access to digital therapeutics as a treatment option was implemented in two primary care clinics, one urban and one in a small town. The project collected data on the number of people screened, diagnosed, and engaged in the research and their demographic characteristics. RESULTS In the first year, 2,656 individuals were screened for depression and unhealthy alcohol use in the two clinics. Primary care doctors increased the percentage of patients diagnosed as having depression and alcohol use disorder from next to 0% to 17% and 2%, respectively. CONCLUSIONS Early experience with implementing technology-supported screening and decision support for depression and alcohol use disorder into the workflow of busy primary care clinics in Colombia indicates that this care model is feasible and leads to dramatically higher rates of diagnoses of these conditions. Diagnosis in these settings appeared to be easier for depression than for alcohol use disorder.
Fate of Grape-derived Terpenoids in Model Systems Containing Active Yeast Cells.

Terpenes are important contributors wine aroma. Free and glycosidically bound terpenes are primarily formed in grapes. During fermentation they undergo to important transformation catalysed by yeast, so that the terpenes profile of grape is substantially different from that of the corresponding wine. The present paper assessed the ability of a Saccharomyces cerevisiae strain to biotransform 17 different terpenes. Biotransformation was performed by placing target compounds in incubation with resting cells. Volatile compounds produced were extracted by solid phase extraction (SPE) and analysed by GC-MS. Geranyl acetate, neryl acetate, citronellyl acetate and menthyl acetate were formed from the corresponding terpene alcohols. β-Citronellol was the main product of geraniol biotransformation; geranial, an intermediate of this pathway, has also been detected. Limonene was hydroxylated by yeast to form carveol, trans-2,8-menthadien-1-ol and cis-2,8-menthadien-1-ol. Moreover, yeast cells were found to be able to adsorb a significant portion of the terpenes present in the reaction batches, the extent of this phenomenon being linked to terpenes hydrophobicity.
DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes

Significance Human RNA polymerase II (Pol II) transcribes messenger RNA from underlying DNA sequences for the purpose of generating proteins for proper biological functions. One of the key steps of Pol II-driven transcription is elongation, which is directly stimulated by transcription factors such as ELL and affects expression of vast number of genes. However, mechanisms by which the overall functions of ELL are regulated through its stabilization are completely unknown. In this study, we decipher a mechanism of regulation of ELL stability, and thus its functions through multiple factors involving DBC1, HDAC3, p300, and Siah1 for regulation of expression of diverse sets of genes that are required for several physiological processes, including maintenance of glucose homeostasis in human. Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis.
Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation

Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1–V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome.
The UK NCRI study of chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced stage follicular lymphoma: molecular response strongly predicts prolonged overall survival

We present a long‐term follow‐up of the UK chlorambucil, mitoxantrone and dexamethasone (CMD) versus fludarabine, mitoxantrone and dexamethasone (FMD) for untreated advanced, symptomatic follicular lymphoma (FL). This trial was the first to prospectively assess molecular response and the impact on outcomes for 400 patients. The median progression‐free survival (PFS) and overall survival (OS) for CMD were 3·6 and 14·6 years vs. 3·0 and 15·7 years for FMD, respectively. Estimates for Restricted Mean Survival Time (RMST) suggested no difference in PFS or OS. For the whole cohort there was a highly significant difference in survival by POD24, with a median OS from a risk‐defining event of 3·9 years compared to 13·7 years for all others (RMST P < 0·001). Molecular remission was achieved in 25/46 patients (54·3%) in the CMD arm and 20/41 (48·8%) in the FMD arm (P = 0·6). Molecular negativity resulted in median PFS of 5·6 years vs. 2·3 years for molecularly positive (log‐rank P < 0·001) and median OS not reached versus 12·5 years (log‐rank P < 0·01). No cases of progression occurred in minimal residual disease (MRD) negative patients after six years of follow‐up. Although there was no difference in outcomes between arms, this is the first prospective study to report MRD negativity resulting in significantly improved OS.
Can Hybrid Na–Air Batteries Outperform Nonaqueous Na–O2 Batteries?

In recent years, there has been an upsurge in the study of novel and alternative energy storage devices beyond lithium‐based systems due to the exponential increase in price of lithium. Sodium (Na) metal‐based batteries can be a possible alternative to lithium‐based batteries due to the similar electrochemical voltage of Na and Li together with the thousand times higher natural abundance of Na compared to Li. Though two different kinds of Na–O2 batteries have been studied specifically based on electrolytes until now, very recently, a hybrid Na–air cell has shown distinctive advantage over nonaqueous cell systems. Hybrid Na–air batteries provide a fundamental advantage due to the formation of highly soluble discharge product (sodium hydroxide) which leads to low overpotentials for charge and discharge processes, high electrical energy efficiency, and good cyclic stability. Herein, the current status and challenges associated with hybrid Na–air batteries are reported. Also, a brief description of nonaqueous Na–O2 batteries and its close competition with hybrid Na–air batteries are provided.