Miracle-dz/UniFAR-FTUs huggingface dataset:
Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation.

BACKGROUND Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation. METHODS Participants (ages 18-22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin-6 (IL-6) were measured immediately before and 24 hr after vaccination. RESULTS ELS was not associated with the magnitude of change in IL-6 from pre- to post-vaccine, however, exposure to ELS moderated the association between change in IL-6 from pre- to post-vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL-6. CONCLUSIONS Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.
Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-Antitrypsin Protein in NSCLC

High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.
Infant emotional responses to challenge predict empathic behavior in toddlerhood

Abstract Although emotional responses are theorized to be important in the development of empathy, findings regarding the prediction of early empathic behavior by infant behavioral and physiological responses are mixed. This study examined whether behavioral and physiological responses to mild emotional challenge (still face paradigm and car seat task) in 118 infants at age 6 months predicted empathic distress and empathic concern in response to an empathy‐evoking task (i.e, experimenter's distress simulation) at age 20 months. Correlation analyses, corrected for sex and baseline levels of physiological arousal, showed that stronger physiological and behavioral responses to emotional challenge at age 6 months were positively related to observed empathic distress, but not empathic concern, at age 20 months. Linear regression analyses indicated that physiological and behavioral responses to challenge at 6 months independently predicted empathic distress at 20 months, which suggests an important role for both physiological and behavioral emotional responses in empathy development. In addition, curvilinear regression analyses showed quadratic associations between behavioral responses at 6 months, and empathic distress and empathic concern at 20 months, which indicates that moderate levels of behavioral responsivity predict the highest levels of empathic distress and empathic concern.
APC/Cdh1 targets PECAM‐1 for ubiquitination and degradation in endothelial cells

Platelet endothelial cell adhesion molecule‐1 (PECAM‐1) is a member of the immunoglobulin superfamily and is expressed by hematopoietic and endothelial cells (ECs). Recent studies have shown that PECAM‐1 plays a crucial role in promoting the development of the EC inflammatory response in the context of disturbed flow. However, the mechanistic pathways that control PECAM‐1 protein stability remain largely unclear. Here, we identified PECAM‐1 as a novel substrate of the APC/Cdh1 E3 ubiquitin ligase. Specifically, lentivirus‐mediated Cdh1 depletion stabilized PECAM‐1 in ECs. Conversely, overexpression of Cdh1 destabilized PECAM‐1. The proteasome inhibitor MG132 blocked Cdh1‐mediated PECAM‐1 degradation. In addition, Cdh1 promoted K48‐linked polyubiquitination of PECAM‐1 in a destruction box‐dependent manner. Furthermore, we demonstrated that compared with pulsatile shear stress (PS), oscillatory shear stress decreased the expression of Cdh1 and the ubiquitination of PECAM‐1, therefore stabilizing PECAM‐1 to promote inflammation in ECs. Hence, our study revealed a novel mechanism by which fluid flow patterns regulate EC homeostasis via Cdh1‐dependent ubiquitination and subsequent degradation of PECAM‐1.
Outbreak of measles among persons with secondary vaccine failure, China, 2018

ABSTRACT Although the incidence of measles has been dramatically reduced by the highly effective measles vaccine, cases of measles and outbreaks continue to occur in vaccinated population because of immunization failure. We report on an outbreak in which two cases had previous evidence of measles immunity and then one of them transmitted measles infection to an unvaccinated contact. The cases and contacts exposed during the outbreak were investigated. Clinical information and epidemiological information were obtained. Serum samples were collected for measles-specific immunoglobulin M (IgM), immunoglobulin G (IgG) and IgG avidity. Throat swabs were obtained to test for measles virus RNA. Two measles cases (case 1 and case 2) who have received one dose of MCV in past 5 years, and both working at a hospital in Beijing, occurred in 18th and 20nd of January, respectively. Out of the 102 contacts, one additional case (case 3) who had a close, long-term co-exposure with case 1 was reported subsequently. No additional cases of measles occurred among 15 contacts of case 3. The index case was not ascertained through the outbreak review. All three cases had laboratory confirmation of measles infection. Both case 1 and case 2 had high-avidity IgG antibody characteristic of a secondary immune response and developed a modified clinical presentation. This report confirms that a vaccinated individual with documented secondary vaccine failure (SVF) could transmit measles and is the second report since a New York City outbreak (the first report in China). The outbreak represented a series of rare events, so we can conclude that the SVF individuals in the transmission chain of measles are unlikely to threaten measles elimination. The importance of the herd immunity in preventing transmission and sensitive surveillance activities in case of misdiagnosis is emphasized.
Sentinel Lymph Node Analysis in Colorectal Cancer Patients Using One-Step Nucleic Acid Amplification in Combination With Fluorescence and Indocyanine Green

Purpose Analysis of the sentinel lymph node (SLN) in colorectal cancer (CRC) patients was proposed for more accurate staging and tailored lymphadenectomy. The aim of this study was to assess the ability to predict lymph node (LN) involvement through analysis of the SLN with a one-step nucleic acid (OSNA) technique in combination with peritumoral injection of indocyanine green (ICG) and near-infrared (NIR) lymphangiography in CRC patients. Methods A total of 34 patients were enrolled. Overall, 51 LNs were analyzed with OSNA. LNs of 17 patients (50%) were examined simultaneously with hematoxylin and eosin (H&E) and OSNA. Results SLN analysis of 17 patients examined with H&E and OSNA revealed that OSNA had a higher sensitivity (1 vs. 0.55), higher negative predictive value (1 vs. 0.66) and higher accuracy (100% vs. 76.4%) in predicting LN involvement. Overall, OSNA showed a sensitivity of 0.69, specificity of 1, accuracy of 88.2%, and stage migration of 8.8%. Compared to those who were OSNA (−), OSNA (+) patients had a greater number of LN metastases (4.8 vs. 0.16, P = 0.04), higher G3 rate (44.4% vs. 4%, P = 0.01), more advanced stage of disease (stage III: 77.8% vs. 16%; P = 0.00) and were more rapidly subjected to adjuvant chemotherapy (39.1 days vs. 50.2 days, P = 0.01). Conclusion SLN analysis with OSNA in combination with ICG-NIR lymphangiography is feasible and can detect LN involvement in CRC patients. Furthermore, it allows for more accurate staging reducing the delay between surgery and adjuvant chemotherapy.
Dysbiotic 1‐carbon metabolism in cardiac muscle remodeling

Unless there is a genetic defect/mutation/deletion in a gene, the causation of a given disease is chronic dysregulation of gut metabolism. Most of the time, if not always, starts within the gut; that is what we eat. Recent research shows that the imbalance between good versus bad microbial population, especially in the gut, causes systemic diseases. Thus, an appropriate balance of the gut microbiota (eubiosis over dysbiosis) needs to be maintained for normal health (Veeranki and Tyagi, 2017, Journal of Cellular Physiology, 232, 2929–2930). However, during various diseases such as metabolic syndrome, inflammatory bowel disease, diabetes, obesity, and hypertension the dysbiotic gut environment tends to prevail. Our research focuses on homocysteine (Hcy) metabolism that occupies a center‐stage in many biochemically relevant epigenetic mechanisms. For example, dysbiotic bacteria methylate promoters to inhibit gene activities. Interestingly, the product of the 1‐carbon metabolism is Hcy, unequivocally. Emerging studies show that host resistance to various antibiotics occurs due to inverton promoter inhibition, presumably because of promoter methylation. This results from modification of host promoters by bacterial products leading to loss of host's ability to drug compatibility and system sensitivity. In this study, we focus on the role of high methionine diet (HMD), an ingredient rich in red meat and measure the effects of a probiotic on cardiac muscle remodeling and its functions. We employed wild type (WT) and cystathionine beta‐synthase heterozygote knockout (CBS+/−) mice with and without HMD and with and without a probiotic; PB (Lactobacillus) in drinking water for 16 weeks. Results indicate that matrix metalloproteinase‐2 (MMP‐2) activity was robust in CBS+/− fed with HMD and that it was successfully attenuated by the PB treatment. Cardiomyocyte contractility and ECHO data revealed mitigation of the cardiac dysfunction in CBS+/− + HMD mice treated with PB. In conclusion, our data suggest that probiotics can potentially reverse the Hcy‐meditated cardiac dysfunction.
Family carers’ experiences of nutritional care for people living with dementia at home: An interpretative phenomenological analysis

Objectives Few studies have captured the experiences of family carers who manage the nutritional needs of family members living with dementia at home. The identification and management of symptoms that may affect nutritional status is often reliant upon the family carer. This interpretative phenomenological study aimed to explore the experiences and perceptions of the nutritional care of people living with dementia at home from the perspectives of the family members who support them. Method Semi-structured interviews were conducted between October 2017 and February 2018. Participants were also asked to keep a diary of experiences for two weeks before the interview. An Interpretative Phenomenological Analysis approach was used throughout. Findings: Eight participants, with a mean age of 69.6 years residing in South West England were recruited and represented a range of familial roles. Following analysis, three superordinate themes were identified: ‘becoming carer and cook’, ‘changing role and relationships’ and ‘emotional eating’. Conclusion Family carers make food and drink decisions daily, and feel a duty to take on the responsibility for food shopping and cooking. They are conscious about ‘doing the right thing’ when it comes to providing nutritional care, and some feel uncertain about the food choices they are making, particularly regarding a reliance on convenience foods. Changes in appetite, food preferences and mealtime habits related to dementia can lead to disruption affecting the dyad. It is important that family carers and people living at home with dementia are provided with adequate support regarding identifying nutritional risks, making appropriate food and drink choices and preventing the risk of malnutrition in the dyad.
Radiosensitization of head and neck squamous cell carcinoma lines by DNA-PK inhibitors is more effective than PARP-1 inhibition and is enhanced by SLFN11 and hypoxia

Abstract Background and purpose: Poly(ADP-ribose)polymerase-1 (PARP1) and DNA-dependent protein kinase (DNA-PK) play key roles in the repair of radiation-induced DNA double strand breaks, but it is unclear which is the preferred therapeutic target in radiotherapy. Here we compare small molecule inhibitors of both as radiosensitizers of head and neck squamous cell carcinoma (HNSCC) cell lines. Methods: Two PARP1 inhibitors (olaparib, veliparib) and two DNA-PK inhibitors (KU57788, IC87361) were tested in 14 HNSCC cell lines and two non-tumorigenic lines (HEK-293 and WI-38/Va-13), with drug exposure for 6 or 24 h post-irradiation, using regrowth assays. For three lines (UT-SCC-54C, -74B, -76B), radiosensitization was also assessed by clonogenic assay under oxia and acute (6 h) anoxia, and for 54C cells under chronic hypoxia (0.2% O2 for 48 h). Relationships between sensitizer enhancement ratios (SER) and gene expression, assessed by RNA sequencing, were evaluated. Results: The inhibitors were minimally cytotoxic in the absence of radiation, with 74B and 54C cells the most sensitive to both olaparib and KU57788. Median SER values for each inhibitor at 1.1 µM were 1.12 (range 1.02–1.24) for olaparib, 1.08 (1.04–1.13) for veliparib, 1.35 (1.10–1.64) for IC87361 and 1.77 (1.41–2.38) for KU57788. The higher SER values for the DNA-PK inhibitors were observed with all cell lines (except HEK-293) and all concentrations tested and were confirmed by clonogenic assay. Radiosensitization by the DNA-PK inhibitors correlated with expression of SLFN11 mRNA. Radiosensitization by IC87361 and olaparib was significantly enhanced under acute anoxia and chronic hypoxia. Conclusions: The DNA-PK inhibitors KU57788 and IC87361 are more effective radiosensitizers than the PARP-1 inhibitors olaparib and veliparib at non-cytotoxic concentrations in HNSCC cell cultures and their activity is enhanced by SLFN11 and hypoxia.
Fibroblast Growth Factor 23 and Mortality in Patients With Type 2 Diabetes and Normal or Mildly Impaired Kidney Function

OBJECTIVE To study whether fibroblast growth factor 23 (FGF23) is associated with adverse outcomes in patients with type 2 diabetes and normal or mildly impaired kidney function. RESEARCH DESIGN AND METHODS We analyzed C-terminal FGF23 levels in 310 patients with type 2 diabetes and estimated glomerular filtration rate ≥60 mL/min/1.73 m2. Associations of FGF23 with all-cause mortality and major adverse cardiovascular events (MACE) were studied by Cox regression. RESULTS During a follow-up of 5.8 years (3.3–6.5), 47 patients developed MACE and 28 patients died. FGF23 was associated with an increased risk of all-cause mortality (age- and sex-adjusted hazard ratio 2.78 [95% CI 1.76–4.40]) and MACE (1.67 [1.12–2.49]). Results were similar after additional adjustment for other potential confounders and were consistent upon replication in an independent cohort. CONCLUSIONS In patients with type 2 diabetes and normal or mildly impaired kidney function, FGF23 is associated with an increased risk of cardiovascular events and mortality.
Amplicon Sequencing-Based Noninvasive Fetal Genotyping for RHD-Positive D Antigen-Negative Alleles.

BACKGROUND To avoid hemolytic disease of the fetus and newborn resulting from maternal alloantibodies against fetal Rh antigens, anti-D immunoglobulin is routinely administered to RhD-negative pregnant women in Japan. Fetal RHD genotyping using cell-free DNA may prevent unnecessary antibody administration; however, current PCR-based methods, which detect RHD deletion, do not address the higher rates of RHD-positive D antigen-negative alleles in nonwhite populations without additional inspections. METHODS We developed an amplicon-sequencing method that could estimate the type of paternally inherited fetal RHD allele from 4 major RHD alleles in the Japanese population: the D antigen-positive allele (RHD*01, 92.9%) and 3 D antigen-negative alleles (RHD*01N.01, 6.6%; RHD*01EL.01, 0.3%; RHD* 01N.04, 0.1%) using cell-free DNA obtained from the blood plasma of pregnant women. RESULTS The method correctly determined the fetal RhD type even when RhD-negative pregnant women possessed an RHD-positive D antigen-negative allele: RHD*01EL.01 or RHD*01N.04. CONCLUSIONS This method is a reliable noninvasive fetal RHD genotyping method for Japanese and other East Asian populations. The genotyping principle of amplifying 2 different regions using the same primer pair and distinguishing them by their sequence difference during the subsequent mapping procedure is also theoretically applicable to RHD-positive D antigen-negative alleles prevalent in Africans. Therefore, this method offers an opportunity to consider targeted administration of anti-D immunoglobulin to RhD-negative pregnant women in East Asian and African countries and to increase the specificity of the fetal RHD genotyping implemented nationwide in several European countries.
Methods for analysis of circular RNAs

Eukaryotic cells express a myriad of circular RNAs (circRNAs), many of them displaying tissue‐specific expression patterns. They arise from linear precursor RNAs in which 5′ and 3′ ends become covalently ligated. Given these features, biochemical and computational approaches traditionally used to study linear RNA must be adapted for analysis of circular RNAs. Such circRNA‐specific methodologies are allowing the systematic identification of circRNAs and the analysis of their biological functions. Here, we review the resources and molecular methods currently utilized to quantify circRNAs, visualize their distribution, identify interacting partners, and elucidate their function. We discuss the challenges of analyzing circRNAs and propose alternative approaches for studying this unique class of transcripts.
Electrodeposited PEDOT:Nafion Composite for Neural Recording and Stimulation

Microelectrode arrays are used for recording and stimulation in neurosciences both in vitro and in vivo. The electrodeposition of conductive polymers, such as poly(3,4‐ethylene dioxythiophene) (PEDOT), is widely adopted to improve both the in vivo recording and the charge injection limit of metallic microelectrodes. The workhorse of conductive polymers in the neurosciences is PEDOT:PSS, where PSS represents polystyrene‐sulfonate. In this paper, the counterion is the fluorinated polymer Nafion, so the composite PEDOT:Nafion is deposited onto a flexible neural microelectrode array. PEDOT:Nafion coated electrodes exhibit comparable in vivo recording capability to the reference PEDOT:PSS, providing a large signal‐to‐noise ratio in a murine animal model. Importantly, PEDOT:Nafion exhibits a minimized polarization during electrical stimulation, thereby resulting in an improved charge injection limit equal to 4.4 mC cm−2, almost 80% larger than the 2.5 mC cm−2 that is observed for PEDOT:PSS.
DREB/CBF expression in wheat and barley using the stress‐inducible promoters of HD‐Zip I genes: impact on plant development, stress tolerance and yield

Summary Networks of transcription factors regulate diverse physiological processes in plants to ensure that plants respond to abiotic stresses rapidly and efficiently. In this study, expression of two DREB/CBF genes, TaDREB3 and TaCBF5L, was modulated in transgenic wheat and barley, by using stress‐responsive promoters HDZI‐3 and HDZI‐4. The promoters were derived from the durum wheat genes encoding the γ‐clade TFs of the HD‐Zip class I subfamily. The activities of tested promoters were induced by drought and cold in leaves of both transgenic species. Differences in sensitivity of promoters to drought strength were dependent on drought tolerance levels of cultivars used for generation of transgenic lines. Expression of the DREB/CBF genes under both promoters improved drought and frost tolerance of transgenic barley, and frost tolerance of transgenic wheat seedlings. Expression levels of the putative TaCBF5L downstream genes in leaves of transgenic wheat seedlings were up‐regulated under severe drought, and up‐ or down‐regulated under frost, compared to those of control seedlings. The application of TaCBF5L driven by the HDZI‐4 promoter led to the significant increase of the grain yield of transgenic wheat, compared to that of the control wild‐type plants, when severe drought was applied during flowering; although no yield improvements were observed when plants grew under well‐watered conditions or moderate drought. Our findings suggest that the studied HDZI promoters combined with the DREB/CBF factors could be used in transgenic cereal plants for improvement of abiotic stress tolerance, and the reduction of negative influence of transgenes on plant development and grain yields.
Biofabrication of neural microphysiological systems using magnetic spheroid bioprinting

The high attrition rate of neuro-pharmaceuticals as they proceed to market necessitates the development of clinically-relevant in vitro neural microphysiological systems that can be utilized during the preclinical screening phase to assess the safety and efficacy of potential compounds. Historically, proposed models have adhered to two distinct approaches; those that are biologically relevant (e.g.—organoids, spheroids) or those that provide engineering control (e.g.—bioprinting, microfluidics). Separately, these approaches fail to fully recapitulate the complex hierarchical structure of the nervous system, limiting their clinical applications. Furthermore, the reliance on manual implementation present in many models fails to effectively scale up or satisfy the consistency standards required for widespread industry adoption. This work serves as a proof-of-concept for merging the two approaches to create a neural microphysiological system that overcomes their individual limitations. Spinal cord spheroids, fabricated using magnetic nanoparticles, are positioned in a three-dimensional hydrogel construct using magnetic bioprinting. Resulting constructs demonstrate both localized cell–cell interactions and long-distance projections that mimic in vivo structure. The use of magnetic nanoparticles for spheroid formation provides batch-to-batch consistency in size and shape and reduces the reliance on trained experimenters for accurate placing for culture. Taken together, this combination approach provides the first steps towards developing a simple approach for integrating spheroid, hydrogel culture, and bioprinting as an alternative to more specialized and expensive processes.