Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults

The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.
Mycorrhizal Switching and the Role of Fungal Abundance in Seed Germination in a Fully Mycoheterotrophic Orchid, Gastrodia confusoides

Mycorrhizal associations are essential for orchid germination and seedling establishment, and thus may constrain the distribution and abundance of orchids under natural conditions. Previous studies have shown that germination and seedling establishment in several orchids often decline with increasing distance from adult plants, resulting in non-random spatial patterns of seedling establishment. In contrast, individuals of the fully mycoheterotrophic orchid Gastrodia confusoides often tend to have random aboveground spatial patterns of distribution within bamboo forests. Since G. confusoides is parasitic on litter-decaying fungi, its random spatial patterns of distribution may be due to highly scattered patterns of litter-decaying fungi within bamboo forests. To test this hypothesis, we first identified the main mycorrhizal fungi associating with developing seeds and adult plants at a bamboo forest site in Taiwan using Miseq high-throughput DNA sequencing. Next, we combined seed germination experiments with quantitative PCR (qPCR) analyses to investigate to what extent the abundance of mycorrhizal fungi affected spatial patterns of seed germination. Our results show that seed germination and subsequent growth to an adult stage in G. confusoides required a distinct switch in mycorrhizal partners, in which protocorms associated with a single Mycena OTU, while adults mainly associated with an OTU from the genus Gymnopus. A strong, positive relationship was observed between germination and Mycena abundance in the litter, but not between germination and Gymnopus abundance. Fungal abundance was not significantly related to the distance from the adult plants, and consequently germination was also not significantly related to the distance from adult plants. Our results provide the first evidence that the abundance of litter-decaying fungi varies randomly within the bamboo forest and independently from G. confusoides adults.
Computational Modeling Intervertebral Disc Pathophysiology: A Review

Lower back pain is a medical condition of epidemic proportion, and the degeneration of the intervertebral disc has been identified as a major contributor. The etiology of intervertebral disc (IVD) degeneration is multifactorial, depending on age, cell-mediated molecular degradation processes and genetics, which is accelerated by traumatic or gradual mechanical factors. The complexity of such intertwined biochemical and mechanical processes leading to degeneration makes it difficult to quantitatively identify cause–effect relationships through experiments. Computational modeling of the IVD is a powerful investigative tool since it offers the opportunity to vary, observe and isolate the effects of a wide range of phenomena involved in the degenerative process of discs. This review aims at discussing the main findings of finite element models of IVD pathophysiology with a special focus on the different factors contributing to physical changes typical of degenerative phenomena. Models presented are subdivided into those addressing role of nutritional supply, progressive biochemical alterations stemming from an imbalance between anabolic and catabolic processes, aging and those considering mechanical factors as the primary source that induces morphological change within the disc. Limitations of the current models, as well as opportunities for future computational modeling work are also discussed.
Chronic Exposure to Cigarette Smoke Affects the Ileum and Colon of Guinea Pigs Differently. Relaxin (RLX-2, Serelaxin) Prevents Most Local Damage

Cigarette smoking (CS) is the cause of several organ and apparatus diseases. The effects of smoke in the gut are partially known. Accumulating evidence has shown a relationship between smoking and inflammatory bowel disease, prompting us to investigate the mechanisms of action of smoking in animal models. Despite the role played by neuropeptides in gut inflammation, there are no reports on their role in animal models of smoking exposure. The hormone relaxin has shown anti-inflammatory properties in the intestine, and it might represent a putative therapy to prevent gut damage caused by smoking. Presently, we investigate the effects of chronic smoke exposure on inflammation, mucosal secretion, and vasoactive intestinal peptide (VIP) and substance P (SP) expressions in the ileum and colon of guinea pigs. We also verify the ability of relaxin to counter the smoke-induced effects. Smoke impacted plasma carbon monoxide (CO). In the ileum, it induced inflammatory infiltrates, fibrosis, and acidic mucin production; reduced the blood vessel area; decreased c-kit-positive mast cells and VIP-positive neurons; and increased the SP-positive nerve fibers. In the colon, it reduced the blood vessel area and the goblet cell area and decreased c-kit-positive mast cells, VIP-positive neurons, and SP-positive nerve fibers. Relaxin prevented most of the smoking-induced changes in the ileum, while it was less effective in the colon. This study shows the diverse sensitivity to CS between the ileum and the colon and demonstrates that both VIP and SP are affected by smoking. The efficacy of relaxin proposes this hormone as a potential anti-inflammatory therapeutic to counteract gut damage in humans affected by inflammatory bowel diseases.
Driving Forces of the Changes in Vegetation Phenology in the Qinghai-Tibet Plateau

Phenological change is an emerging hot topic in ecology and climate change research. Existing phenological studies in the Qinghai–Tibet Plateau (QTP) have focused on overall changes, while ignoring the different characteristics of changes in different regions. Here, we use the Global Inventory Modeling and Mapping Studies (GIMMS3g) normalized difference vegetation index (NDVI) dataset as a basis to discuss the temporal and spatial changes in vegetation phenology in the Qinghai–Tibet Plateau from 1982 to 2015. We also analyze the response mechanisms of pre-season climate factor and vegetation phenology and reveal the driving forces of the changes in vegetation phenology. The results show that: (1) the start of the growing season (SOS) and the length of the growing season (LOS) in the QTP fluctuate greatly year by year; (2) in the study area, the change in pre-season precipitation significantly affects the SOS in the northeast (p < 0.05), while, the delay in the end of the growing season (EOS) in the northeast is determined by pre-season air temperature and precipitation; (3) pre-season precipitation in April or May is the main driving force of the SOS of different vegetation, while air temperature and precipitation in the pre-season jointly affect the EOS of different vegetation. The differences in and the diversity of vegetation types together lead to complex changes in vegetation phenology across different regions within the QTP. Therefore, addressing the characteristics and impacts of changes in vegetation phenology across different regions plays an important role in ecological protection in this region.
Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies–From Discovery to Knowledge-Guided Platforms for Better Patient Management

Comprehensive molecular landscaping studies reveal a potentially brighter future for pancreatic ductal adenocarcinoma (PDAC) patients. Blood-borne biomarkers obtained from minimally invasive “liquid biopsies” are now being trialled for early disease detection and to track responses to therapy. Integrated genomic and transcriptomic studies using resectable tumour material have defined intrinsic patient subtypes and actionable genomic segments that promise a shift towards genome-guided patient management. Multimodal mapping of PDAC using spatially resolved single cell transcriptomics and imaging techniques has identified new potentially therapeutically actionable cellular targets and is providing new insights into PDAC tumour heterogeneity. Despite these rapid advances, defining biomarkers for patient selection remain limited. This review examines the current PDAC cancer biomarker ecosystem (identified in tumour and blood) and explores how advances in single cell sequencing and spatially resolved imaging modalities are being used to uncover new targets for therapeutic intervention and are transforming our understanding of this difficult to treat disease.
Multiple Cases of Bacterial Sequence Erroneously Incorporated Into Publicly Available Chloroplast Genomes

Public sequencing databases are invaluable resources to biological researchers, but assessing data veracity as well as the curation and maintenance of such large collections of data can be challenging. Genomes of eukaryotic organelles, such as chloroplasts and other plastids, are particularly susceptible to assembly errors and misrepresentations in these databases due to their close evolutionary relationships with bacteria, which may co-occur within the same environment, as can be the case when sequencing plants. Here, based on sequence similarities with bacterial genomes, we identified several suspicious chloroplast assemblies present in the National Institutes of Health (NIH) Reference Sequence (RefSeq) collection. Investigations into these chloroplast assemblies reveal examples of erroneous integration of bacterial sequences into chloroplast ribosomal RNA (rRNA) loci, often within the rRNA genes, presumably due to the high similarity between plastid and bacterial rRNAs. The bacterial lineages identified within the examined chloroplasts as the most likely source of contamination are either known associates of plants, or co-occur in the same environmental niches as the examined plants. Modifications to the methods used to process untargeted ‘raw’ shotgun sequencing data from whole genome sequencing efforts, such as the identification and removal of bacterial reads prior to plastome assembly, could eliminate similar errors in the future.
The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation

The first intracellular loop (ICL1) of G protein-coupled receptors (GPCRs) has received little attention, although there is evidence that, with the 8th helix (H8), it is involved in early conformational changes following receptor activation as well as contacting the G protein β subunit. In class B1 GPCRs, the distal part of ICL1 contains a conserved R12.48KLRCxR2. 46b motif that extends into the base of the second transmembrane helix; this is weakly conserved as a [R/H]12.48KL[R/H] motif in class A GPCRs. In the current study, the role of ICL1 and H8 in signaling through cAMP, iCa2+ and ERK1/2 has been examined in two class B1 GPCRs, using mutagenesis and molecular dynamics. Mutations throughout ICL1 can either enhance or disrupt cAMP production by CGRP at the CGRP receptor. Alanine mutagenesis identified subtle differences with regard elevation of iCa2+, with the distal end of the loop being particularly sensitive. ERK1/2 activation displayed little sensitivity to ICL1 mutation. A broadly similar pattern was observed with the glucagon receptor, although there were differences in significance of individual residues. Extending the study revealed that at the CRF1 receptor, an insertion in ICL1 switched signaling bias between iCa2+ and cAMP. Molecular dynamics suggested that changes in ICL1 altered the conformation of ICL2 and the H8/TM7 junction (ICL4). For H8, alanine mutagenesis showed the importance of E3908.49b for all three signal transduction pathways, for the CGRP receptor, but mutations of other residues largely just altered ERK1/2 activation. Thus, ICL1 may modulate GPCR bias via interactions with ICL2, ICL4 and the Gβ subunit.
Biofortified Diets Containing Algae and Selenised Yeast: Effects on Growth Performance, Nutrient Utilization, and Tissue Composition of Gilthead Seabream (Sparus aurata)

Efforts have been made to find natural, highly nutritious alternatives to replace fish meal (FM) and fish oil (FO), which can simultaneously promote fish health and improve the nutritional quality of filets for human consumption. This study evaluated the impact of biofortified diets containing microalgae (as replacement for FM and FO), macroalgae (as natural source of iodine) and selenised yeast (organic source of selenium) on gilthead seabream growth, nutrient utilization, tissue composition and gene expression. A control diet (CTRL) with 15% FM and 5.5% FO was compared with three experimental diets (AD1, AD2, and AD3), where a microalgae blend (Chlorella sp., Tetraselmis sp., and DHA-rich Schizochytrium sp.) replaced 33% of FM. Diet AD1 contained 20% less FO. Diets were supplemented with Laminaria digitata (0.4% AD1 and AD2; 0.8% AD3) and selenised yeast (0.02% AD1 and AD2; 0.04% AD3). After feeding the experimental diets for 12 weeks, growth was similar in fish fed AD1, AD2, and CTRL, indicating that microalgae meal can partially replace both FM and FO in diets for seabream. But AD3 suppressed fish growth, suggesting that L. digitata and selenised yeast supplementation should be kept under 0.8 and 0.04%, respectively. Despite lower lipid intake and decreased PUFAs bioavailability in fish fed AD3, compared to CTRL, hepatic elovl5 was upregulated resulting in a significant increase of muscle EPA + DHA. Indeed, filets of fish fed AD2 and AD3 provided the highest EPA + DHA contents (0.7 g 100 g–1), that are well above the minimum recommended values for human consumption. Fish consuming the AD diets had a higher retention and gain of selenium, while iodine gain remained similar among diets. Upregulation of selenoproteins (gpx1, selk, and dio2) was observed in liver of fish fed AD1, but diets had limited impact on fish antioxidant status. Overall, results indicate that the tested microalgae are good sources of protein and lipids, with their LC-PUFAs being effectively accumulated in seabream muscle. Selenised yeast is a good fortification vehicle to increase selenium levels in fish, but efforts should be placed to find new strategies to fortify fish in iodine.
The Efficacy of Adjuvant Corticosteroids in Surgical Management of Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis

Objective: This systematic review aimed to assess the efficacy of adjuvant corticosteroids in managing patients with chronic subdural hematoma (CSDH) undergoing surgical intervention. Methods: We searched for eligible studies electronically on the databases of PubMed, Embase, and Google Scholar. The last date of the search was 15th Jun 2021. Outcomes were pooled to calculate risk ratios (RR) with 95% confidence intervals (CI). Results: Eleven studies were included. Four of them were randomized controlled trials (RCTs). Six studies reported data on good neurological outcomes but with variable definitions. Combining all studies, we noted no statistically significant difference in good neurological outcome with the use of adjuvant corticosteroids (RR: 0.91 95% CI: 0.74, 1.12 I2 = 92% p = 0.39). Similar results were obtained on subgroup analysis based on definition and study type. However, the use of adjuvant corticosteroids was associated with a significantly reduced risk of recurrence (RR: 0.51 95% CI: 0.40, 0.64 I2 = 0% p < 0.0001). The meta-analysis also demonstrated no statistically significant difference in mortality rates with the use of adjuvant corticosteroids (RR: 1.01 95% CI: 0.47, 2.21 I2 = 76% p = 0.97). The results did not differ between RCTs and non-RCTs. Limited studies reported data on complications, and pooled analysis indicated no significant increase in infectious, gastrointestinal, and neurological complications with the use of adjuvant corticosteroids. Conclusion: The use of corticosteroids with surgery for CSDH might be associated with a reduction in recurrence rate. However, corticosteroids do not improve functional outcomes or mortality rates. Future studies should assess the impact of different corticosteroid regimens on patient outcomes, and should use standardized reporting of neurological outcomes with uniform follow-up duration.
Experimental Designs to Study the Aggregation and Colonization of Biofilms by Video Microscopy With Statistical Confidence

The goal of this study was to quantify the variability of confocal laser scanning microscopy (CLSM) time-lapse images of early colonizing biofilms to aid in the design of future imaging experiments. To accomplish this a large imaging dataset consisting of 16 independent CLSM microscopy experiments was leveraged. These experiments were designed to study interactions between human neutrophils and single cells or aggregates of Staphylococcus aureus (S. aureus) during the initial stages of biofilm formation. Results suggest that in untreated control experiments, variability differed substantially between growth phases (i.e., lag or exponential). When studying the effect of an antimicrobial treatment (in this case, neutrophil challenge), regardless of the inoculation level or of growth phase, variability changed as a frown-shaped function of treatment efficacy (i.e., the reduction in biofilm surface coverage). These findings were used to predict the best experimental designs for future imaging studies of early biofilms by considering differing (i) numbers of independent experiments; (ii) numbers of fields of view (FOV) per experiment; and (iii) frame capture rates per hour. A spreadsheet capable of assessing any user-specified design is included that requires the expected mean log reduction and variance components from user-generated experimental results. The methodology outlined in this study can assist researchers in designing their CLSM studies of antimicrobial treatments with a high level of statistical confidence.
Does It Pay to Treat Patients With Coronavirus Disease 2019? Social Perception of Physicians Treating Patients With Coronavirus Disease 2019

During the coronavirus disease 2019 (COVID-19) pandemic, the public has often expressed great appreciation toward medical personnel who were often shown in the media expressing strong emotions about the situation. To examine whether the perception of people on a physician is in fact influenced by whether the physician treats patients with COVID-19 and the emotions they expressed in response to the situation, 454 participants were recruited in May 2020. Participants saw facial expressions of anger, sadness, happiness, and neutrality which supposedly were shown by physicians who were presented as working either in COVID-19 wards or in an internal medicine ward. Participants rated how competent, empathetic, caring, and likable each physician was, to what degree they would wish to be treated by each physician, and what salary each physician deserved. Physicians treating patients with COVID-19 were seen more positively and as deserving higher pay; they appeared more competent, caring, likable, and were more likely to be chosen as a caregiver compared to physicians not treating patients with COVID-19. The expressed emotions of physicians had a strong impact on how they were perceived, yet this effect was largely unrelated to whether they treated patients with COVID-19 or not such that happy physicians seemed more empathetic, caring, and likable than the physicians who showed negative emotions. Positive regard toward physicians treating patients with COVID-19 was associated with the fact that they were seen as saving lives and not due to the risk imposed by their work.
Responses of Phosphate-Solubilizing Microorganisms Mediated Phosphorus Cycling to Drought-Flood Abrupt Alternation in Summer Maize Field Soil

Soil microbial communities are essential to phosphorus (P) cycling, especially in the process of insoluble phosphorus solubilization for plant P uptake. Phosphate-solubilizing microorganisms (PSM) are the dominant driving forces. The PSM mediated soil P cycling is easily affected by water condition changes due to extreme hydrological events. Previous studies basically focused on the effects of droughts, floods, or drying-rewetting on P cycling, while few focused on drought-flood abrupt alternation (DFAA), especially through microbial activities. This study explored the DFAA effects on P cycling mediated by PSM and P metabolism-related genes in summer maize field soil. Field control experiments were conducted to simulate two levels of DFAA (light drought-moderate flood, moderate drought-moderate flood) during two summer maize growing periods (seeding-jointing stage, tasseling-grain filling stage). Results showed that the relative abundance of phosphate-solubilizing bacteria (PSB) and phosphate-solubilizing fungi (PSF) increased after DFAA compared to the control system (CS), and PSF has lower resistance but higher resilience to DFAA than PSB. Significant differences can be found on the genera Pseudomonas, Arthrobacter, and Penicillium, and the P metabolism-related gene K21195 under DFAA. The DFAA also led to unstable and dispersed structure of the farmland ecosystem network related to P cycling, with persistent influences until the mature stage of summer maize. This study provides references for understanding the micro process on P cycling under DFAA in topsoil, which could further guide the DFAA regulations.