Miracle-dz/UniFAR-FTUs huggingface dataset:
Epo pretreatment of Ecfcs enhances functional recovery after transplantation in a rat model of cerebral ischemia through an increase of their homing abilities: a Spect/ct study: Co-078

Background: endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients suffering from an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hind limb ischemia. Objective: the present study aimed to evaluate whether priming of ECFCs with erythropoietin could enhance their homing into the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effects on brain-blood barrier disruption (BBBd), cerebral apoptosis and cerebral blood flow (CBF) by Single Photon Emission/Computed Tomography (SPECT/CT) imaging. Methods: Rats underwent a 1-hour MCAO followed by reperfusion, and then received either PBS injection (control, n =10), PBS- or erythropoietin-primed ECFCs IV injection (ECFC PBS , n =13; ECFC EPO , n =10) 1 day after MCAO. ECFCs homing and their effects on BBBd, cerebral apoptosis and CBF were evaluated by SPECT/CT imaging up to 14 days after MCAO. Results were expressed as median±interquartile ipsi-/contralateral ratio of the activity in MCA-vascularized territories in each hemisphere. Histological evaluation of neuronal survival and astrocytal proliferation was performed on day 14. Results: erythropoietin priming increased ECFCs homing to the ischemic hemisphere (ECFC PBS : 111.0±16.0%; ECFC EPO : 146.5±13.3%). BBBd was significantly reduced (control: 387±153%; ECFC PBS : 151±46%, P <0.05; ECFC EPO : 112±9%, P <0.001) and negatively correlated with ECFCs homing ( Pearson r =-0.6930, P =0.0002). Cerebral apoptosis was significantly reduced (control: 161±10%; ECFC
CDKN1A upregulation and cisplatin-pemetrexed resistance in non-small cell lung cancer cells

Cisplatin-pemetrexed is a frequently adopted first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) ineligible for biological therapy, notwithstanding its limited efficacy. In the present study, the RAL cell line, an epidermal growth factor receptor (EGFR)-wild-type, p53- and KRAS-mutated model of NSCLC, was used to investigate novel biomarkers of resistance to this treatment. Cells were analyzed 96 h (96 h-post wo) and 21 days (21 days-post wo) after the combined treatment washout. Following an initial moderate sensitivity to the treatment, the cell growth proliferative capability had fully recovered. Gene expression analysis of the resistant surviving cells revealed a significant upregulation of CDKN1A expression in the cells at 96-h post-wo and, although to a lesser extent, in the cells at 21 days-post wo, accompanied by an enrichment of acetylated histone H3 in its promoter region. CDKN1A was also upregulated at the protein level, being mainly detected in the cytoplasm of the cells at 96 h-post wo. A marked increase in the number of apoptotic cells, together with a significant G1 phase block, were observed at 96-h post wo in the cells in which CDKN1A was knocked down, suggesting its involvement in the modulation of the response of RAL cells to the drug combination. On the whole, these data suggest that CDKN1A plays a role in the response to the cisplatin-pemetrexed combination in advanced KRAS-mutated NSCLC, thus suggesting that it may be used as a promising predictive marker.
Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis

A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-effects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n = 1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 × 109/L, 95% CI 0.83–1.03 × 109/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay.
Insights into the community structure and lifestyle of the fungal root endophytes of tomato by combining amplicon sequencing and isolation approaches with phytohormone profiling

ABSTRACT Little is known about the influence of host genotype and phytohormones on the composition of fungal endophytic communities. We investigated the influence of host genotype and phytohormones on the structure of the fungal endophytic communities of tomato roots by amplicon sequencing of the ITS1 region and combined this approach with isolation and functional characterization of the isolates. A significant effect of the host genotype on the dominant fungal species was found by comparing the cultivars Castlemart and UC82B and, surprisingly, root pathogens were among the most abundant taxa. In contrast, smaller changes in the relative abundance of the dominant species were found in mutants impaired in jasmonic acid biosynthesis (def1) and ethylene biosynthesis (8338) compared to the respective wild types. However, def1 showed significantly higher species richness compared to the wild type. Analysis of the phytohormone profiles of these genotypes indicates that changes in the phytohormone balance may contribute to this difference in species richness. Assessing the lifestyle of isolated fungi on tomato seedlings revealed the presence of both beneficial endophytes and latent pathogens in roots of asymptomatic plants, suggesting that the interactions between members of the microbiome maintain the equilibrium in the community preventing pathogens from causing disease.
Spanish real-world experience with fingolimod in relapsing-remitting multiple sclerosis patients: MS NEXT study

Purpose The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice. Methods This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months. Results The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%. Conclusions The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting.
Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP)

Objective The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients. Methods These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP. Results As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab’s known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0–11.6) years; median follow-up time was 5.2 (range 0–10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias. Conclusions Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab. Trial registration number NCT00493298.
Social media use disorder and alexithymia: Any association between the two? Results of a cross-sectional study among Lebanese adults.

PURPOSE To learn more about the association between social media use disorder and alexithymia among Lebanese people. DESIGN/METHODS Four hundred fifty-six residents participated in this cross-sectional study which was carried out between January and December 2018. FINDINGS The results showed that 107 (23.7%) participants were classified as having social media use disorder. Higher social media use disorder score (β = .52), higher perceived stress (β = .35), and higher depression (β = .12) were significantly associated with more alexithymia. PRACTICE IMPLICATIONS Our results have shown that social media use disorder and being depressed and stressed were associated with higher levels of alexithymia. Psychologists/health practitioners can benefit from these findings in their future prevention and intervention plans. People who negatively utilize social media platforms can then be offered with appropriate counseling and coping mechanisms.
Characterization of Vaginal Microbiota Associated with Pregnancy Outcomes of Artificial Insemination in Dairy Cows

The profitability of the dairy and beef industries is largely affected by the actually achieved reproductive efficiency. Although a large proportion of cows worldwide are bred by artificial insemination (AI) services, many potential factors affecting the outcome of pregnancy by AI remain to be addressed. In the present study, we investigated the vaginal microbiota by high-throughput sequencing of 16S rRNA gene and analyzed their association with differential pregnancy outcomes (i.e., pregnant vs. nonpregnant) of multiple AI services in dairy cows. Sequencing of the V3-V4 region totally produced 512,046 high-quality sequences that were computationally clustered into 2,584 operational taxonomic units (OTUs). All OTUs were taxonomically assigned to 10 bacterial phyla. There were statistically significant differences among the three AI service times (T1, T2 and T3) with respect to the Shannon index and number of observed OTUs (p < 0.05). Bray-Curtis distance-based PCoA analysis also revealed that T2 group could be significantly distinguished from T1 and T3. However, no significant difference between the pregnant and nonpregnant cows was found in confidence regarding both alpha diversity and beta diversity. These results could help us better understand the possible influence of vaginal microbial community on pregnancy outcomes of AI service in cows.
Race and Ethnicity and Satisfaction With Communication in the Intensive Care Unit

Purpose: Racial and ethnic minority patients receive poorer quality end-of-life (EoL) care compared with white patients. Differences in quality of communication (QOC) with clinicians may contribute to these disparities. We measured differences in satisfaction with communication in the intensive care unit (ICU) by race and ethnicity. Materials and Methods: This is a cross-sectional survey of family members of patients in ICUs of an academic medical center serving a diverse urban population using The Family Satisfaction with the ICU (FS-ICU) and QOC scales. Results: One hundred surveys were completed (18.8% white, non-Hispanic; 34.4% black, non-Hispanic; 31.3% Hispanic; 15.6% other race/ethnicity). Mean FS-ICU score was 84.2 (standard deviation [SD] 20.5) for white patients, 83.3 (SD 16.2) for black patients, 82.7 (SD 17.8) for Hispanic or Latino patients, and 80.9 (SD 18.8) for patients with other race/ethnicity (Kruskal-Wallis, P = .92). Differences remained insignificant when controlling for patient and respondent characteristics. The QOC scale was not scored due to nonresponse levels on questions about EoL communication. Conclusions: Uniformly high ratings may have been influenced by avoidance of EoL discussion. This study is inconclusive regarding whether QOC influences disparities in EoL care since quality of EoL communication was not captured.
Respiratory Syncytial Virus Prophylaxis in Immunocompromised Children

Supplemental Digital Content is available in the text. Background: Immunocompromised children are at increased risk for respiratory syncytial virus (RSV) infection with associated morbidity and mortality. Prophylaxis is usually provided to these children on a case-by-case basis. Methods: Immunocompromised children who received ≥1 injection of palivizumab were prospectively enrolled across 32 Canadian sites, between 2005 and 2017, during the RSV season. We assessed respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios (HRs) in immunocompromised children versus infants’ prophylaxed for standard indications (SI: prematurity ≤35 weeks’ gestation, bronchopulmonary dysplasia, and congenital heart disease) and complex medical disorders (CMD). Data were analyzed using t-tests, χ2 and Cox proportional hazards adjusted for confounders. Results: A total of 25,003 infants were recruited; 214 immunocompromised, 4283 CMD, 20,506 SI. On average, children received 4.4 ± 1.3 injections. A total of 16,231 children were perfectly adherent (58.4% immunodeficiency, 68.9% CMD, 64.2% SI; P < 0.0005). A higher proportion of immunocompromised children were aboriginal and exposed to smoking compared with CMD and SI. Immunocompromised children also had a higher median; gestational and enrollment age and birth weight compared with CMD and SI. Immunodeficient children had a higher RIH risk compared with SI (HR = 2.4, 95% confidence interval, 1.3–4.7, P = 0.009) but were similar to CMD (HR = 1.7, 95% confidence interval, 0.9–3.4, P = 0.118). RSVH in prophylaxed, immunocompromised children was similar to CMD (HR < 0.005, P = 0.955) and SI (HR < 0.005, P = 0.953). Conclusions: Immunocompromised children who received palivizumab had an increased RIH hazard compared with the SI group. Similar RSVH hazard between the 3 groups suggests that immunocompromised children may benefit from palivizumab during the RSV season.
Identification of client iron-sulfur proteins of the chloroplastic NFU2 transfer protein in Arabidopsis thaliana.

Iron-sulfur (Fe-S) proteins have critical functions in plastids, participating notably in the photosynthetic electron transfer, sulfur and nitrogen assimilation, chlorophyll metabolism and vitamin or amino acid biosynthesis. Their maturation relies on the so-called SUF assembly machinery. The Fe-S clusters are synthesized de novo on a scaffold protein complex and then delivered to client proteins via several transfer proteins. However, the maturation pathways of most client proteins and their specificities towards transfer proteins are mostly unknown. In order to decipher the proteins interacting with the Fe-S cluster transfer protein NFU2, one of the three plastidial representatives found in Arabidopsis thaliana, we have performed a quantitative proteomic analysis of nfu2 plants (shoots, roots and seedlings). Combined with NFU2 co-immunoprecipitation and binary yeast two-hybrid experiments, we identified 14 new targets, among which nine were validated in planta using a binary bimolecular fluorescence complementation (BiFC) assay. These analyses also revealed a possible role for NFU2 in plant response to desiccation. Altogether this study delineates better the maturation pathways of many chloroplastic Fe-S proteins, extending considerably the number of NFU2 clients. It also helps clarifying the respective roles of the three NFU paralogs, NFU1, NFU2 and NFU3.
Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.
Addressing Social Determinants of Health: Time for a Polysocial Risk Score.

What determines health? For decades, researchers have attempted to quantify the exact contribution of social factors, such as income, education, race/ethnicity, and the community environment, to health. The motivation is simple: understanding which social factors most affect health would help prioritize societal investments in those areas. However, most efforts to precisely quantify the influence of individual social determinants of health have failed, largely because the causal pathways are numerous, interconnected, and complex. Most empirical evidence has found that social factors matter in aggregate, but quantifying their individual contributions is difficult. After decades of efforts in this area, it may be time for a new approach. The challenges posed in studying social determinants of health today are similar to the challenges in studying human genetics not long ago. In 2001, many expected that sequencing the human genome would facilitate finding the causal links between individual genes and diseases. Some proponents assumed that once these links were identified, genetically customized therapies would surely follow. However, for most diseases, that has not occurred. Most efforts to identify
The Effect of Monophasic Pulsed Current with Stretching Exercise on the Heel Pain and Plantar Fascia Thickness in Plantar Fasciitis: A Randomized Controlled Trial

Plantar fasciitis (PF) is one of the most common causes of heel and foot pain. Monophasic pulsed current (MPC) is an electrical stimulation used to accelerate the healing processes. The purpose of this study was to determine the effect of MPC and MPC combined with plantar fascia stretching exercises (SE) on heel pain and plantar fascia thickness in treatment of PF and see if there is any relationship between heel pain and plantar fascia thickness after intervention. Forty-four participants diagnosed with PF were randomly assigned to two group; MPC group or MPC combined with plantar fascia SE. Plantar fascia thickness was measured with musculoskeletal ultrasound. Although no statistical differences between the two groups were found, heel pain and the plantar fascia thickness significantly decreased in both groups after the intervention (p < 0.001). No significant correlation was found between changes in heel pain and plantar fascia thickness after 4 weeks of treatment. Our results indicated that MPC can reduce heel pain and plantar fascia thickness caused by PF. However, MPC combined with plantar fascia SE is not superior to MCP only in terms of reduction in heel pain and plantar fascia thickening.
Male mice adjust courtship behavior in response to female multimodal signals

Multimodal signaling is nearly ubiquitous across animal taxa. While much research has focused on male signal production contributing to female mate-choice or preferences, females often give their own multimodal signals during intersexual communication events. Multimodal signal components are often classified based on whether they contain redundant information (e.g., the backup hypothesis) or non-redundant information (e.g., the multiple messages hypothesis) from the perspective of the receiver. We investigated the role of two different female vocalizations produced by the female house mouse (Mus musculus): the broadband, relatively low-frequency squeaks (broadband vocalizations or BBVs,), and the higher-frequency ultrasonic vocalizations (USVs). These female vocalizations may convey differently valenced information to the male receivers. We paired these vocalizations with and without female urine to examine the influence of combining information across multiple modalities. We found evidence that female urine and vocalizations act as non-redundant multimodal cues as males responded with different behaviors and vocalization rates depending on the female signal presented. Additionally, male mice responded with greater courtship effort to the multimodal combination of female USVs paired with female urine than any other signal combination. These results suggest that the olfactory information contained in female urine provides the context by which males can then evaluate potentially ambiguous female vocalizations.