Miracle-dz/UniFAR-FTUs huggingface dataset:
ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.
Preliminary Psychometrics for the Executive Function Challenge Task: A Novel, “Hot” Flexibility, and Planning Task for Youth

Abstract Objective: Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task. Method: We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth. Results: The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children. Conclusions: The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.
FASN Is a Biomarker Enriched in Malignant Glioma-Derived Extracellular Vesicles

Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.
The expression of cytokines in aqueous humor of high myopic patients with cataracts

Purpose To analyze the expression of 440 human cytokines in aqueous humor of high myopic patients with cataracts. Methods Eighty-five patients with cataracts were recruited in this study. In the screening stage, the RayBio G-Series Human Cytokine Antibody Array 440 was used to assay the aqueous humor samples collected from nine high myopic patients with cataracts and eight non-myopic patients with cataracts right before the surgery. The array was further used for verification of the screened cytokines, with aqueous humor samples obtained from 34 eyes of high myopic patients with cataracts and 34 eyes of non-myopic patients with cataracts. Results Compared with the non-myopic patients with cataracts, the expression levels of decorin, receptor activator of NF-kB (RANK), angiopoietin-1 (ANG-1), C-X-C motif ligand 16 (CXCL16), β-inducible gene-h3 (bIG-H3), insulin-like growth factor-binding protein 2 (IGFBP-2), and interleukin-17B (IL-17B) were statistically significantly higher in high myopic patients with cataracts (all p<0.000114). The matrix metalloproteinase-2 (MMP-2) level also increased in the aqueous humor of high myopic patients with cataracts (p = 0.0034). The concentrations of ANG-1 and MMP-2 were also increased in the aqueous humor of the confirmatory stage (all p<0.05). Conclusions In this study, numerous cytokines in aqueous humor were detected in high myopic patients with cataracts and non-myopic patients with cataracts, and it was confirmed that the MMP-2 level in the aqueous humor of patients with high myopia was statistically significantly increased. Further verification also revealed the elevation of ANG-1 in the aqueous humor of high myopic patients with cataracts, which suggests that ANG-1 may be related to the pathogenesis of high myopia.
Altered gray matter volume and structural co-variance in adolescents with social anxiety disorder: evidence for a delayed and unsynchronized development of the fronto-limbic system

Abstract Background Social anxiety disorder (SAD) is a prevalent mental disorder diagnosed in childhood and adolescence. Theories regarding brain development and SAD suggest a close link between neurodevelopmental dysfunction at the adolescent juncture and SAD, but direct evidence is rare. This study aims to examine brain structural abnormalities in adolescents with SAD. Methods High-resolution T1-weighted images were obtained from 31 adolescents with SAD (15–17 years) and 42 matching healthy controls (HC). We evaluated symptom severity with the Social Anxiety Scale for Children (SASC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). We used voxel-based morphometry analysis to detect regional gray matter volume abnormalities and structural co-variance analysis to investigate inter-regional coordination patterns. Results We found significantly higher gray matter volume in the orbitofrontal cortex (OFC) and the insula in adolescents with SAD compared to HC. We also observed significant co-variance of the gray matter volume between the OFC and amygdala, and the OFC and insula in HC, but these co-variance relationships diminished in SAD. Conclusions These findings provide the first evidence that the brain structural deficits in adolescents with SAD are not only in the core regions of the fronto-limbic system, but also represented by the diminished coordination in the development of these regions. The delayed and unsynchronized development pattern of the fronto-limbic system supports SAD as an adolescent-sensitive developmental mental disorder.
A better Amazon road network for people and the environment

Significance In the next 5 y, more than 10 thousand kilometers of roads will be built or improved in the Amazon. Well-designed projects can increase employment opportunities, reduce transport costs, and support regional development. However, roads will also drive deforestation, threatening biodiversity and ecosystem services, jeopardizing the welfare of indigenous people, and moving the biome toward irreversible shifts in vegetation. Data to support good decisions are remarkably scarce. Typical feasibility studies, where they exist, inadequately address environmental and social impacts and do not facilitate comparison across projects. This study contributes to informed decision-making by quantifying the environmental, social and economic effects of 75 planned projects. It demonstrates that fewer projects in carefully chosen locations would dramatically improve outcomes of all types. The rapidly expanding network of roads into the Amazon is permanently altering the world’s largest tropical forest. Most proposed road projects lack rigorous impact assessments or even basic economic justification. This study analyzes the expected environmental, social and economic impacts of 75 road projects, totaling 12 thousand kilometers of planned roads, in the region. We find that all projects, although in different magnitudes, will negatively impact the environment. Forty-five percent will also generate economic losses, even without accounting for social and environmental externalities. Canceling economically unjustified projects would avoid 1.1 million hectares of deforestation and US$ 7.6 billion in wasted funding for development projects. For projects that exceed a basic economic viability threshold, we identify the ones that are comparatively better not only in terms of economic return but also have lower social and environmental impacts. We find that a smaller set of carefully chosen projects could deliver 77% of the economic benefit at 10% of the environmental and social damage, showing that it is possible to have efficient tradeoff decisions informed by legitimately determined national priorities.
Primary cutaneous localized/clearly‐outlined true histiocytic sarcoma: Two long‐term follow‐up cases

Histiocytic sarcoma (HS) is a rare hematopoietic tumor that mainly involves extranodal sites, including the intestinal tract, skin, soft tissues and other organs. It is well known as an aggressive neoplasm that shows a poor response to therapy. However, a subset of patients with resectable disease has shown a favorable outcome with surgical treatment. Primary cutaneous HS is exceedingly rare and, to date, its long‐term prognosis has thus not been well described. Here, we highlight two cases of primary cutaneous HS that showed long‐term survival. Case 1 was a healthy 47‐year‐old woman who found a 12‐mm tumor on her forehead. Case 2 was a 66‐year‐old woman, under follow up of a myxoid liposarcoma in her leg, who presented with a 25‐mm tumor in her hypothenar eminence. Histologically, the tumors in both cases had a smooth outline with proliferating atypical tumor cells that showed histiocytic differentiation as revealed by immunohistochemistry with antibodies to CD68 (KP‐1) and lysozyme in case 1; and CD68, lysozyme and CD163 in case 2. Tumor cells in case 1 had a monotonous appearance. After complete resection, cases 1 and 2 have survived for 10 and 4 years, respectively, without recurrence. To date, such patients are relatively long follow‐up cases of survival from HS and highlight how a clear outline of the primary cutaneous HS tumor may be associated with its resectability and be an important factor in the assessment of its curability.
Asymptomatic Bacteriuria and Pyuria in Premenopausal Women.

BACKGROUND Asymptomatic bacteriuria and pyuria in healthy women often trigger inappropriate antimicrobial treatment, but there is a paucity of data on their prevalence and persistence. METHODS To evaluate the prevalence and persistence of asymptomatic bacteriuria and pyuria in women at high risk for recurrent urinary tract infection, we conducted an observational cohort study of 104 healthy premenopausal women with a history of recurrent urinary tract infection with daily assessments of bacteriuria, pyuria and urinary symptoms over a 3-month period. RESULTS The mean age of participants was 22 and 74% were white. Asymptomatic bacteriuria events (urine cultures with colony count ≥105 CFU/mL of a uropathogen on days with no symptomatic urinary tract infection diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6283 days. Asymptomatic bacteriuria events were most commonly caused by E. coli, which was present on 1.4% of days with median duration one day (range, 1-10). Pyuria occurred in 70 (78%) of 90 evaluable subjects on at least one day and 25% of all days on which no symptomatic urinary tract infection was diagnosed. The positive predictive value of pyuria for E. coli asymptomatic bacteriuria was 4%. CONCLUSIONS In this population of healthy women at high risk for recurrent urinary tract infection, asymptomatic bacteriuria is uncommon and when present rarely lasts more than two days. Pyuria, on the other hand, is common but infrequently associated with bacteriuria or symptoms. These data strongly support recommendations not to screen for or treat asymptomatic bacteriuria or pyuria in healthy, non-pregnant women.
Novel finite element‐based plate design for bridging mandibular defects: Reducing mechanical failure

Abstract Introduction When the application of a free vascularised flap is not possible, a segmental mandibular defect is often reconstructed using a conventional reconstruction plate. Mechanical failure of such reconstructions is mostly caused by plate fracture and screw pull‐out. This study aims to develop a reliable, mechanically superior, yet slender patient‐specific reconstruction plate that reduces failure due to these causes. Patients and Methods Eight patients were included in the study. Indications were as follows: fractured reconstruction plate (2), loosened screws (1) and primary reconstruction of a mandibular continuity defect (5). Failed conventional reconstructions were studied using finite element analysis (FEA). A 3D virtual surgical plan (3D‐VSP) with a novel patient‐specific (PS) titanium plate was developed for each patient. Postoperative CBCT scanning was performed to validate reconstruction accuracy. Results All PS plates were placed accurately according to the 3D‐VSP. Mean 3D screw entry point deviation was 1.54 mm (SD: 0.85, R: 0.10–3.19), and mean screw angular deviation was 5.76° (SD: 3.27, R: 1.26–16.62). FEA indicated decreased stress and screw pull‐out inducing forces. No mechanical failures appeared (mean follow‐up: 16 months, R: 7–29). Conclusion Reconstructing mandibular continuity defects with bookshelf‐reconstruction plates with FEA underpinning the design seems to reduce the risk of screw pull‐out and plate fractures.
The Effects of Fibrin–icariin Nanoparticle Loaded in Poly (lactic-co-glycolic) Acid Scaffold as a Localized Delivery System on Chondrogenesis of Human Adipose-derived Stem Cells

Background: Nowadays, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. This study evaluates the effect of fibrin/icariin (ICA) nanoparticles (F/I NPs) on chondrogenesis of stem cells. Materials and Methods: F/I NPs were characterized by Dynamic Light Scattering DLS. Poly (lactic-co-glycolic) acid (PLGA)-F/I NP scaffold was fabricated and assessed by scanning electron microscope. Human adipose-derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene expression were analyzed by the 3-(4, 5- dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. MTT assay and real-time polymerase chain reaction (RT-PCR). Results: The size and surface charge of F/I NP were about 28–30 nm and − 17, respectively. The average of pore size of PLGA and PLGA–fibrin/ICA was 230 and 340 μm, respectively. Cell viability of differentiated cells in P/F group was higher than others significantly (P ≤ 0.05). Furthermore, quantitative RT-PCR analysis demonstrated that ICA upregulated cartilaginous-specific gene expression. Furthermore, the results of the expression of type I collagen revealed that ICA downregulated this gene significantly (P < 0.01). Conclusions: The results indicated that F/I NP could be a potential factor for chondrogenesis of stem cells and downregulation of fibrocartilage marker.
Distribution and Antifungal Susceptibility of Candida Species Causing Candidemia in China: An Update From the CHIF-NET Study.

BACKGROUND Candidemia is the most common, serious fungal infection and Candida antifungal resistance is a challenge. We report recent surveillance of candidemia in China. METHODS The study encompassed 77 Chinese hospitals over 3 years. Identification of Candida species was by mass spectrometry and DNA sequencing. Antifungal susceptibility was determined using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS In total, 4010 isolates were collected from candidemia patients. Although C. albicans was the most common species, non-albicans Candida species accounted for over two-thirds of isolates, predominated C. parapsilosis complex (27.1%), C. tropicalis (18.7%), and C. glabrata complex (12.0%). Most C. albicans and C. parapsilosis complex isolates were susceptible to all antifungal agents (resistance rate <5%). However, there was a decrease in voriconazole susceptibility to C. glabrata sensu stricto over the 3 years and fluconazole resistance rate in C. tropicalis tripled. Amongst less common Candida species, over one-third of C. pelliculosa isolates were coresistant to fluconazole and 5-flucytocine, and >56% of C. haemulonii isolates were multidrug resistance. CONCLUSIONS Non-albicans Candida species are the predominant cause of candidemia in China. Azole resistance is notable amongst C. tropicalis and C. glabrata. Coresistance and multidrug resistance has emerged in less common Candida species.
Citrus flavonoids, β-Glucan and organic acid feed additives decrease relative risk during Yersinia ruckeri O1 biotype 2 infection of rainbow trout (Oncorhynchus mykiss)

Whether through direct supplementation of bacteria or by prebiotic supplementation thought to favour subsets of bacteria, modulation of gut microbiota constitutes an important and promising alternative to the use of prophylactic and growth promoting antibiotics in worldwide aquaculture. We fed a commercial base feed, alone or supplemented with either proprietary β-glucan, β-glucan and organic acids, citrus flavonoid or yeast cell wall supplements, to rainbow trout over a period of four weeks. Fish from each feed group were then subjected to experimental, waterborne infection with Yersinia ruckeri O1 biotype 2. Following experimental feeding, the β-glucan and organic acids supplemented group showed significantly improved feed conversion and lipid efficiency ratios. Furthermore, the β-glucan, β-glucan and organic acids and citrus flavonoid supplements proved to significantly reduce the risk of mortality in rainbow trout during experimental infection as shown by hazard ratio analysis. Resulting in 33.2%, 30.6% and 30.5% reduction in risk relative to the non-supplemented base feed, respectively, these three supplements show a promising potential either as stand-alone feed supplements, or as components in complex feed formulations.
The positive impact of lockdown in Wuhan on containing the COVID-19 outbreak in China

Abstract Background With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). Consequently, many countries have implemented flight restrictions to China. China itself has imposed a lockdown of the population of Wuhan as well as the entire Hubei province. However, whether these two enormous measures have led to significant changes in the spread of COVID-19 cases remains unclear. Methods We analyzed available data on the development of confirmed domestic and international COVID-19 cases before and after lockdown measures. We evaluated the correlation of domestic air traffic to the number of confirmed COVID-19 cases and determined the growth curves of COVID-19 cases within China before and after lockdown as well as after changes in COVID-19 diagnostic criteria. Results Our findings indicate a significant increase in doubling time from 2 days (95% Confidence Interval, CI): 1.9–2.6), to 4 days (95% CI: 3.5–4.3), after imposing lockdown. A further increase is detected after changing diagnostic and testing methodology to 19.3 (95% CI: 15.1–26.3), respectively. Moreover, the correlation between domestic air traffic and COVID-19 spread became weaker following lockdown (before lockdown: r = 0.98, p < 0.05 vs. after lockdown: r = 0.91, p = NS). Conclusions A significantly decreased growth rate and increased doubling time of cases was observed, which is most likely due to Chinese lockdown measures. A more stringent confinement of people in high risk areas seem to have a potential to slow down the spread of COVID-19.
Socio-economic impact of Foot-and-Mouth Disease outbreaks and control measures: An analysis of Mongolian outbreaks in 2017.

Mongolia is a large landlocked country in central Asia and has one of the highest per capita livestock ratios in the world. During 2017 reported Foot and Mouth disease (FMD) outbreaks in Mongolia increased considerably, prompting widespread disease control measures. This study estimates the socio-economic impact of FMD and subsequent control measures on Mongolian herders. The analysis encompassed quantification of the impact on subsistence farmers' livelihoods and food security and estimation of the national level gross losses due to reaction and expenditure during 2017. Data were collected from 112 herders across eight Provinces that reported disease. Seventy of these herders had cases of FMD, while 42 did not have FMD in their animals but were within quarantine zones. Overall, 86/112 herders reported not drinking milk for a period of time and 38/112 reduced their meat consumption. Furthermore, 55 herders (49.1%) had to borrow money to buy food, medicines and/or pay bills or bank loans. Among herders with FMD cases, the median attack rate was 31.7%, 3.8% and 0.59% in cattle, sheep and goats respectively, with important differences across Provinces. Herders with clinical cases before the winter had higher odds of reporting a reduction in their meat consumption. National level gross losses due to FMD in 2017 were estimated using government data. The estimate of gross economic loss was 18.4 billion Mongolian-tugriks (US$7.35 million) which equates to approximately 0.65% of the Mongolian GDP. The FMD outbreaks combined with current control measures has negatively impacted herders' livelihoods (including herders with and without cases of FMD) which is likely to reduce stakeholder advocacy. Possible strategies that could be employed to ameliorate the negative effects of the current control policy were identified. The findings and approach are relevant to other FMD endemic regions aiming to control the disease.