Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and genetic characteristics of 29 Chinese patients with X-linked hypophosphatemia

Objective The aim of this study was to fully describe the clinical and genetic characteristics, including clinical manifestations, intact fibroblast growth factor 23 (iFGF23) levels, and presence of PHEX gene mutations, of 22 and 7 patients with familial and sporadic X-linked dominant hypophosphatemia (XLH), respectively. Methods Demographic data, clinical features, biochemical indicators, and imaging data of 29 patients were collected. All 22 exons and exon–intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The serum level of iFGF23 was measured in 15 of the patients. Results Twenty-nine patients (male/female: 13:16, juvenile/adult: 15:14) with XLH were included. The main symptoms were bowed lower extremities (89.7%), abnormal gait (89.7%), and short stature/growth retardation (78.6%). Hypophosphatemia with a high alkaline phosphatase level was the main biochemical feature and the median value of serum iFGF23 was 55.7 pg/ml (reference range: 16.1–42.2 pg/ml). Eight novel mutations in the PHEX gene were identified by Sanger sequencing, including two missense mutations (p. Gln682Leu and p. Phe312Ser), two deletions (c.350_356del and c.755_761del), one insertion (c.1985_1986insTGAC), and three splice mutations (c.1700+5G>C, c.1966-1G>T, and c.350-14_350-1del). Additionally, the recurrence rate after the first orthopedic surgery was 77.8% (7/9), and five of them had their first surgery before puberty. Conclusion Our study expanded the clinical phenotypes and gene mutation spectrum of XLH and provided a reference for the optimal timing of orthopedic surgeries.
Global proteome analyses of phosphorylation and succinylation of barley root proteins in response to phosphate starvation and recovery

Phosphate (Pi) stress is an important environmental factor that limits plant growth and development. Of various posttranslational modifications (PTMs), protein phosphorylation and succinylation are the two most important PTMs that regulate multiple biological processes in response to Pi stress. However, these PTMs have been investigated individually but their interactions with proteins in response to Pi stress remain poorly understood. In this study, to elucidate the underlying mechanisms of protein phosphorylation and succinylation in response to Pi stress, we performed a global analysis of the barley root phosphorylome and succinylome in Pi starvation and recovery stages, respectively. A total of 3,634 and 884 unique phosphorylated and succinylated proteins, respectively, corresponding to 11,538 and 2,840 phospho- and succinyl-sites, were identified; of these, 275 proteins were found to be simultaneously phosphorylated and succinylated. Gene Set Enrichment Analysis was performed with a Kyoto Encyclopedia of Genes and Genomes pathway database revealing pathways that significantly enriched in the phosphorylome and succinylome. Such pathways, were dynamically regulated by Pi starvation and recovery treatments, and could be partitioned into distinct metabolic processes. In particular, phosphorylated proteins related to purine, the mitogen-activated protein kinase (MAPK) signaling pathway, pyrimidine, and ATP-binding cassette (ABC) transporters were upregulated in both Pi deprivation and recovery stages. Succinylated proteins, significantly upregulated by both Pi starvation and recovery, were enriched in nitrogen metabolism and phenylpropanoid biosynthesis. Meanwhile, succinylated proteins that were significantly downregulated by both Pi starvation and recovery were enriched in lysine degradation and tryptophan metabolism. This highlighted the importance of these metabolic pathways in regulating Pi homeostasis. Furthermore, protein–protein interaction network analyses showed that the response of central metabolic pathways to Pi starvation and recovery was significantly modulated by phosphorylation or succinylation, both individually and together. In addition, we discovered relevant proteins involved in MAPK signaling and phenylpropanoid biosynthetic pathways existing in interactions between phosphorylated and succinylated proteins in response to Pi recovery. The current study not only provides a comprehensive analysis of phosphorylated and succinylated proteins in plant responses to Pi starvation and recovery, but also reveals detailed interactions between phosphorylated and succinylated proteins in barley roots.
Effects of wave-current interactions on sediment dynamics in Hangzhou Bay during Typhoon Mitag

The hydrodynamics and sediment characteristics of muddy estuaries and coasts during typhoons are closely related to the geomorphic evolution, ecological environment, and economic development of coastal zones. Taking the macro-tidal turbid Hangzhou Bay (HZB) as an example, the sediment characteristics and effects of wave-current interactions on sediment dynamics during Typhoon Mitag were studied using a fully-calibrated numerical model. The model considered tide-wave sediment interactions and the reconstructed typhoon wind field. Net sediment fluxes were controlled by residual currents and suspended sediment concentration (SSC). The combined interactions of currents and waves led to a high SSC during the typhoon. Under calm weather conditions, the impact of wave-current interactions (wave dissipation, form drag, wave radiation stress, mean current advection and refraction) was small, except for the combined bottom stresses. The combined bottom stress was the primary wave-current interaction that changed sediment resuspension and increased SSC, particularly in shallow waters or during storms. The advection term, which played an essential role in reducing SSC in HZB, mainly affected SSC by increasing the velocity. The wave dissipation term enhanced vertical mixing, which involved the vertical exchange of suspended sediment and currents. In the shallow waters of the southern bay, the wave dissipation term mostly led to decreased bottom stresses, increased currents, decreased SSC, and increased SSC in deep waters. The effects of form drag, wave radiation stress, and refraction terms on the suspended sediment dynamics were relatively small. These findings provide a theoretical foundation for the study of dynamic geomorphology in macro-tidal estuaries.
Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?

Polytopic cargo proteins are synthesized and exported along the secretory pathway from the endoplasmic reticulum (ER), through the Golgi apparatus, with eventual insertion into the plasma membrane (PM). While searching for proteins that could enhance cell surface expression of olfactory receptors, a new family of proteins termed “receptor expression-enhancing proteins” or REEPs were identified. These membrane-shaping hairpin proteins serve as adapters, interacting with intracellular transport machinery, to regulate cargo protein trafficking. However, REEPs belong to a larger family of proteins, the Yip (Ypt-interacting protein) family, conserved in yeast and higher eukaryotes. To date, eighteen mammalian Yip family members, divided into four subfamilies (Yipf, REEP, Yif, and PRAF), have been identified. Yeast research has revealed many intriguing aspects of yeast Yip function, functions that have not completely been explored with mammalian Yip family members. This review and analysis will clarify the different Yip family nomenclature that have encumbered prior comparisons between yeast, plants, and eukaryotic family members, to provide a more complete understanding of their interacting proteins, membrane topology, organelle localization, and role as regulators of cargo trafficking and localization. In addition, the biological role of membrane shaping and sensing hairpin and amphipathic helical domains of various Yip proteins and their potential cellular functions will be described. Lastly, this review will discuss the concept of Yip proteins as members of a larger superfamily of membrane-shaping adapter proteins (MSAPs), proteins that both shape membranes via membrane-sensing and hairpin insertion, and well as act as adapters for protein-protein interactions. MSAPs are defined by their localization to specific membranes, ability to alter membrane structure, interactions with other proteins via specific domains, and specific interactions/effects on cargo proteins.
A combination of cherry juice and cold water immersion does not enhance marathon recovery compared to either treatment in isolation: A randomized placebo-controlled trial

Purpose Cherry juice (CJ) and cold water immersion (CWI) are both effective recovery strategies following strenuous endurance exercise. However, athletes routinely combine recovery interventions and less is known about the impact of a combined CJ and CWI protocol. Therefore, this study investigated the effects of combining CWI and CJ (a “cocktail” (CT)) on inflammation and muscle damage following a marathon. Methods A total 39 endurance trained males were randomly assigned to a placebo (PL), CWI, CJ, or CT group before completing a trail marathon run. Muscle damage (creatine kinase (CK)), muscle function (maximal voluntary isometric contraction (MVIC)), and inflammation (interleukin-6 (IL-6); C-reactive protein (CRP)) were measured at baseline, immediately after marathon (only IL-6), 24 h, and 48 h after marathon. Results There were no statistically significant differences between groups and no group × time interaction effects for any of the dependent variables. Confidence intervals (CI) illustrated that CT had unclear effects on inflammation (IL-6; CRP) and MVIC, but may have increased CK to a greater extent than PL and CJ conditions. Conclusion There is no evidence of an additive effect of CJ and CWI when the treatments are used in conjunction with each other. On the contrary, combining CJ and CWI may result in slightly increased circulating CK.
The crosstalk between MYC and mTORC1 during osteoclastogenesis

Osteoclasts are bone-resorbing cells that undergo extensive changes in morphology throughout their differentiation. Altered osteoclast differentiation and activity lead to changes in pathological bone resorption. The mammalian target of rapamycin (mTOR) is a kinase, and aberrant mTOR complex 1 (mTORC1) signaling is associated with altered bone homeostasis. The activation of mTORC1 is biphasically regulated during osteoclastogenesis; however, the mechanism behind mTORC1-mediated regulation of osteoclastogenesis and bone resorption is incompletely understood. Here, we found that MYC coordinates the dynamic regulation of mTORC1 activation during osteoclastogenesis. MYC-deficiency blocked the early activation of mTORC1 and also reversed the decreased activity of mTORC1 at the late stage of osteoclastogenesis. The suppression of mTORC1 activity by rapamycin in mature osteoclasts enhances bone resorption activity despite the indispensable role of high mTORC1 activation in osteoclast formation in both mouse and human cells. Mechanistically, MYC induces Growth arrest and DNA damage-inducible protein (GADD34) expression and suppresses mTORC1 activity at the late phase of osteoclastogenesis. Taken together, our findings identify a MYC-GADD34 axis as an upstream regulator of dynamic mTORC1 activation in osteoclastogenesis and highlight the interplay between MYC and mTORC1 pathways in determining osteoclast activity.
Nexus between government debt, economic policy uncertainty, government spending, and governmental effectiveness in BRIC nations: Evidence for linear and nonlinear assessments

Quality institutions augment economic sustainability by ensuring domestic resource optimization with equitable development principles. Therefore, ensuring this equitable development and quality institutions is required. This study assessed the effects of government debt, uncertainty of economic policies, and government spending on institutional quality, as measured by governmental effectiveness in BRIC (Brazil, Russia, India, and China) nations from1990–2020. This study applied several econometrical techniques for empirical nexus assessment, including Augmented ARDL, nonlinear Autoregressive Distributed Lagged (ARDL), and Fourier Toda-Yamamoto causality tests. This study documented long-run cointegration in both symmetry and asymmetric assessments. In the long run, both government debt and uncertain economic policies were significantly negatively associated with institutional quality, while government spending and institutional quality were positively associated. Furthermore, the results of asymmetric ARDL revealed both long- and short-run asymmetric relationships between institutional quality and government debt, EPU, and government spending. The directional causality test documented bidirectional causality between debt and institutional quality in all nations, whereas mixed causalities were detected for uncertain economic policy, institutional quality, and government spending. Regarding policy, the results of this study suggested that economic stability was indispensable for efficient institutional quality in BRIC nations.
Classification of drug-naive children with attention-deficit/hyperactivity disorder from typical development controls using resting-state fMRI and graph theoretical approach

Background and objectives The study of brain functional connectivity alterations in children with Attention-Deficit/Hyperactivity Disorder (ADHD) has been the subject of considerable investigation, but the biological mechanisms underlying these changes remain poorly understood. Here, we aim to investigate the brain alterations in patients with ADHD and Typical Development (TD) children and accurately classify ADHD children from TD controls using the graph-theoretical measures obtained from resting-state fMRI (rs-fMRI). Materials and methods We investigated the performances of rs-fMRI data for classifying drug-naive children with ADHD from TD controls. Fifty six drug-naive ADHD children (average age 11.86 ± 2.21 years; 49 male) and 56 age matched TD controls (average age 11.51 ± 1.77 years, 44 male) were included in this study. The graph measures extracted from rs-fMRI functional connectivity were used as features. Extracted network-based features were fed to the RFE feature selection algorithm to select the most discriminating subset of features. We trained and tested Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting (GB) using Peking center data from ADHD-200 database to classify ADHD and TD children using discriminative features. In addition to the machine learning approach, the statistical analysis was conducted on graph measures to discover the differences in the brain network of patients with ADHD. Results An accuracy of 78.2% was achieved for classifying drug-naive children with ADHD from TD controls employing the optimal features and the GB classifier. We also performed a hub node analysis and found that the number of hubs in TD controls and ADHD children were 8 and 5, respectively, indicating that children with ADHD have disturbance of critical communication regions in their brain network. The findings of this study provide insight into the neurophysiological mechanisms underlying ADHD. Conclusion Pattern recognition and graph measures of the brain networks, based on the rs-fMRI data, can efficiently assist in the classification of ADHD children from TD controls.
Patient reported outcome measures in children and adolescents with type 1 diabetes using advanced hybrid closed loop insulin delivery

Purpose To determine the impact of advanced hybrid closed - loop (AHCL) insulin delivery on quality of life, metabolic control and time in range (TIR) in youth with type 1 diabetes mellitus (T1DM). Methods Twenty-four children and adolescents with T1DM (14 female) aged of 10 to 18 years participated in the study. Mixed methods study design was implemented. Quantitative part of the study was conducted as a longitudinal crossover study with data collection before and at the end of AHCL use. Qualitative data were obtained with modeled interviews of four focus groups before and the end of the period. Clinical data were collected from the electronic medical records. Results The use of AHCL significantly improved the quality of life in terms of decreased fear of hypoglycemia (p<0.001), decrease in diabetes-related emotional distress (p<0.001), and increased wellbeing (p=0.003). The mean A1C decreased from 8.55 ± 1.34% (69.9 ± 12.3 mmol/mol) to 7.73 ± 0.42 (61.1 ± 2.2 mmol/mol) (p=0.002) at the end of the study. Mean TIR was 68.22% (± 13.89) before and 78.26 (± 6.29) % (p<0.001) at the end of the study. Conclusion The use of advanced hybrid closed loop significantly improved the quality of life and metabolic control in children and adolescents with T1DM.
Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats

Background The brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated. Aim To analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment. Methods Healthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography. Results Compared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood. Conclusion Alterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.
Coupling the environmental impacts of reactive nitrogen losses and yield responses of staple crops in China

Cropland reactive nitrogen losses (Nr) are of the greatest challenges facing sustainable agricultural intensification to meet the increases in food demand. The environmental impacts of Nr losses and their yield responses to the mitigation strategies were not completely evaluated. We assessed the environmental impacts of Nr losses in China and decoupled the efficiency of mitigation actions with yield responses. Datasets about Nr losses in China were collected, converted into potentials of acidification (AP), global warming (GWP), and aquatic eutrophication (AEP), and analyzed by a meta-analysis program. Results showed that producing 1 Mg of rice grains had the highest AP (153 kg acid equiv.), while wheat had the highest GWP and AEP (74 kg CO2 equiv. and 0.37 kg PO4 equiv., respectively). Using the conventional rates (averagely, 200, 230, and 215 kg N ha−1) of urea as a surface application to produce 131.4, 257.2, and 212.1 Tg of wheat, maize, and rice resulted in 17–33 Tg, 7–10 Tg, and 6–87 Gg of AP, GWP, and AEP, respectively. For their balanced effect on reducing AP, GWP, and AEP while maximizing yields, inhibitors, and subsurface application could be set as the best mitigation strategies in wheat production. Inhibitors usage and biochar are strongly recommended strategies for sustainable production of maize. None of the investigated strategies had a balanced effect on rice yield and the environment, thus new mitigation technologies should be developed.
Becoming a Distance Manager: Managerial Experiences, Perceived Organizational Support, and Job Satisfaction During the COVID-19 Pandemic

Due to the COVID-19 pandemic having radically changed the way we now work, many recent studies have focused on employees’ experiences and well-being, their performance and job satisfaction (JSA), and ways to ensure the best support for them when working from home (WFH). However, less attention has been given to managers’ experiences in adapting to the new role of distance management and supporting them with this transition. This study aims to explore how managers experienced distance management, and the perceived organizational support (POS), and the effect of organizational support has on their JSA during the first year of the COVID-19 pandemic. Data from 1,016 line, middle and top managers in Danish workplaces were collected in March 2021, 1 year after the start of the COVID-19 pandemic. We applied descriptive statistics, ANOVA, and partial least square structural equation modeling to investigate the relation of perceived organizational support (POS) and the JSA of distance managers. Control variables were the respondents’ demographic characteristics, specifically gender, age, and management level. The study offers insights into the managerial experiences of becoming a distance manager, helps to understand the relationship between POS and managers’ JSA, and shows a positive relationship similarly for the managers as for employees. The study shows that most managers found their work as distance managers more demanding and worked more hours. The data demonstrate that managers received the most support from their own employees and manager peers, whereas administrative support was largely lacking. The data also show that the majority (67%) of the managers prefer to manage from the office, but similarly, they can continue managing from a distance if needed post-pandemic. The study adds to the literature on workplaces’ transitioning to distance management and hybrid work and contributes to understanding the role of POS and managers’ JSA during this transition. Consequently, if an organization aims to offer hybrid work, improving support from top management and in-house support functions would help maintain or increase managers’ JSA.