Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types

ABSTRACT Checkpoint inhibitors targeting the PD-1/PD-L1 axis are promising immunotherapies shown to elicit objective responses against multiple tumor types, yet these agents fail to benefit most patients with carcinomas. This highlights the need to develop effective therapeutic strategies to increase responses to PD-1/PD-L1 blockade. Histone deacetylase (HDAC) inhibitors in combination with immunotherapies have provided preliminary evidence of anti-tumor effects. We investigated here whether exposure of either natural killer (NK) cells and/or tumor cells to two different classes of HDAC inhibitors would augment (a) NK cell‒mediated direct tumor cell killing and/or (b) antibody-dependent cellular cytotoxicity (ADCC) using avelumab, a fully human IgG1 monoclonal antibody targeting PD-L1. Treatment of a diverse array of human carcinoma cells with a clinically relevant dose of either the pan-HDAC inhibitor vorinostat or the class I HDAC inhibitor entinostat significantly enhanced the expression of multiple NK ligands and death receptors resulting in enhanced NK cell‒mediated lysis. Moreover, HDAC inhibition enhanced tumor cell PD-L1 expression both in vitro and in carcinoma xenografts. These data demonstrate that treatment of a diverse array of carcinoma cells with two different classes of HDAC inhibitors results in enhanced NK cell tumor cell lysis and avelumab-mediated ADCC. Furthermore, entinostat treatment of NK cells from healthy donors and PBMCs from cancer patients induced an activated NK cell phenotype, and heightened direct and ADCC-mediated healthy donor NK lysis of multiple carcinoma types. This study thus extends the mechanism and provides a rationale for combining HDAC inhibitors with PD-1/PD-L1 checkpoint blockade to increase patient responses to anti-PD-1/PD-L1 therapies.
SURFACE: Semantically Rich Fact Validation with Explanations

Judging the veracity of a sentence making one or more claims is an important and challenging problem with many dimensions. The recent FEVER task asked participants to classify input sentences as either SUPPORTED, REFUTED or NotEnoughInfo using Wikipedia as a source of true facts. SURFACE does this task and explains its decision through a selection of sentences from the trusted source. Our multi-task neural approach uses semantic lexical frames from FrameNet to jointly (i) find relevant evidential sentences in the trusted source and (ii) use them to classify the input sentence's veracity. An evaluation of our efficient three-parameter model on the FEVER dataset showed an improvement of 90% over the state-of-the-art baseline on retrieving relevant sentences and a 70% relative improvement in classification.
Loss of Correction After Chevron Osteotomy for Hallux Valgus as a Function of Preoperative Deformity

Background: Recurrence is relatively common after surgical correction of hallux valgus. Multiple factors are discussed that could have an influence in the loss of correction. The aim of this study was to determine preoperative radiological factors with an influence on loss of correction after distal chevron osteotomy for hallux valgus. Methods: Five hundred twenty-four patients who underwent the correction of a hallux valgus by means of distal chevron osteotomy at our institution between 2002 and 2012 were included. We assessed weightbearing x-rays at 4 time points: preoperatively, postoperatively, and after 6 weeks and 3 months. We investigated the intermetatarsal angle (IMA), the hallux valgus angle (HVA), the distal metatarsal articular angle (DMAA), joint congruity, and the position of the sesamoids. Results: At all points of the survey, significant correction of the IMA and HVA was detected. The IMA improved from 12.9 (± 2.8) to 4.5 (± 2.4) degrees and the HVA from 27.5 (± 6.9) to 9.1 (± 5.3) degrees. Loss of correction was found in both HVA and IMA during follow-up with a mean of 4.5 and 1.9 degrees, respectively. Loss of correction showed a linear correlation with preoperative IMA and HVA, and a correlation between preoperative DMAA and sesamoid position. Conclusion: The chevron osteotomy showed significant correction for HVA, IMA, and DMAA. Preoperative deformity, in terms of IMA, HVA, DMAA, and sesamoid position, correlated with the loss of correction and could be assessed preoperatively for HVA and IMA. Loss of correction at 3 months persisted during the follow-up period. Level of Evidence: Level IV, retrospective case series.
Bispectral Index Monitoring During Anesthesia Promotes Early Postoperative Recovery of Cognitive Function and Reduces Acute Delirium in Elderly Patients with Colon Carcinoma: A Prospective Controlled Study using the Attention Network Test

Background Bispectral index (BIS) monitoring can reduce the duration of anesthesia. This study aimed to evaluate the effects of BIS monitoring during surgery for resection of colon carcinoma in elderly patients using the Attention Network Test (ANT) to study alerting, orienting, and executive functions, and the Confusion Assessment Method (CAM). Material/Methods Eighty-one patients (65–75 years) underwent radical surgery for colon carcinoma with general intravenous anesthesia, propofol (6–8 mg/kg/h), vecuronium (0.03–0.05 mg/kg/min), and remifentanil (0.1–0.2 μg/kg/min). The BIS group (n=41) underwent adjustment of anesthesia to maintain a BIS value between 40–60; the non-BIS group (N=40) underwent standard intraoperative hemodynamic monitoring. Primary endpoints were alerting, orienting, and executive functions assessed pre-operatively and on postoperative days 1 and 5 using the ANT; the secondary endpoint was delirium during the first five postoperative days, assessed using the CAM. Results Propofol and remifentanil doses were significantly lower in the BIS group compared with the non-BIS group (P<0.001). Alerting, orienting, and executive functions showed no differences between the two groups pre-operatively but were impaired in both groups on postoperative day 1 compared with pre-operative levels (P<0.001). On postoperative day 5, alerting (P=0.607) and orienting (P=0.851) functions recovered in the BIS group but remained impaired in the non-BIS group (P<0.001). Delirium was significantly lower in the BIS group compared with the non-BIS group (17.5% vs. 27.5%) (P<0.001). Conclusions BIS-guided anesthesia was associated with reduced anesthetic exposure, early postoperative recovery of alerting and orienting functions, and reduced postoperative delirium.
How Do I Narrate My Marriage: The Relationship Between Attachment Orientation and Quality of Autobiographical Memory

Attachment orientations play important roles in the generation of emotional autobiographical memory (AM). However, little research has considered the quality of autographical narratives, which may reflect the structure and content of internal working models (IWMs) of attachment. The purpose of the current study was to investigate the relationship between attachment orientations and narrative quality of marriage-related autobiographical memories. Ninety-four married adults were asked to retrieve two episodes of emotional autobiographical memories. The coherence and vividness of their narratives were then coded. Results indicated that adults who were highly avoidant were more likely to present their memories in a less coherent way and to describe negative memories with more perceptual details. In contrast, attachment anxiety was associated with lower vividness of negative memories. The current findings suggest that an attachment schematic-processing strategy was used in narrating the attachment-related experiences.
ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication

Significance Alphaviruses are mosquito-borne RNA viruses that cause encephalitis, rash, and arthritis. Alphavirus nonstructural protein 3 (nsP3) has a highly conserved macrodomain that can bind and remove ADP-ribose (ADPr) residues from ADP-ribosylated proteins, but its role in virus replication was not known. We show that alphavirus replication in neural cells depends on protein ADP ribosylation and that nsP3s with mutations that eliminate ADPr binding cannot form a functional replicase. Mutations that decrease ADPr binding result in fewer infected cells, while mutations that increase binding but decrease hydrolase activity infect cells normally but amplify replication complexes less well. Therefore, alphavirus replication requires nsP3 macrodomain interaction with one or more ADP-ribosylated proteins, as is consistent with the observed high conservation of this region. Alphaviruses are plus-strand RNA viruses that cause encephalitis, rash, and arthritis. The nonstructural protein (nsP) precursor polyprotein is translated from genomic RNA and processed into four nsPs. nsP3 has a highly conserved macrodomain (MD) that binds ADP-ribose (ADPr), which can be conjugated to protein as a posttranslational modification involving transfer of ADPr from NAD+ by poly ADPr polymerases (PARPs). The nsP3MD also removes ADPr from mono ADP-ribosylated (MARylated) substrates. To determine which aspects of alphavirus replication require nsP3MD ADPr-binding and/or hydrolysis function, we studied NSC34 neuronal cells infected with chikungunya virus (CHIKV). Infection induced ADP-ribosylation of cellular proteins without increasing PARP expression, and inhibition of MARylation decreased virus replication. CHIKV with a G32S mutation that reduced ADPr-binding and hydrolase activities was less efficient than WT CHIKV in establishing infection and in producing nsPs, dsRNA, viral RNA, and infectious virus. CHIKV with a Y114A mutation that increased ADPr binding but reduced hydrolase activity, established infection like WT CHIKV, rapidly induced nsP translation, and shut off host protein synthesis with reduced amplification of dsRNA. To assess replicase function independent of virus infection, a transreplicase system was used. Mutant nsP3MDs D10A, G32E, and G112E with no binding or hydrolase activity had no replicase activity, G32S had little, and Y114A was intermediate to WT. Therefore, ADP ribosylation of proteins and nsP3MD ADPr binding are necessary for initiation of alphavirus replication, while hydrolase activity facilitates amplification of replication complexes. These observations are consistent with observed nsP3MD conservation and limited tolerance for mutation.
Inflammatory breast cancer outcomes by breast cancer subtype: a population-based study.

AIM To assess the outcomes of breast cancer subtype in inflammatory breast cancer (IBC). METHODS We retrospectively assessed IBC patients from the SEER program. RESULTS We identified 626 patients, including 230 (36.7%),100 (17.6%), 113 (18.1%), and 173 (27.6%) patients with HoR+/HER2-, HoR+/HER2+, HoR-/HER2+, and HoR-/HER2- subtype disease, respectively. Multivariate analysis demonstrated that, using HoR+/HER2- subtype as reference, patients with HoR+/HER2+ subtype had better breast cancer-specific survival (BCSS) and overall survival (OS), and patients with HoR-/HER2- subtype had worse BCSS and OS, while BCSS and OS were comparable for HoR-/HER2+ subtype. Similar trends were observed in patients who received surgery, radiotherapy, chemotherapy or trimodality therapy. CONCLUSION Breast cancer subtype is clinically useful for predicting survival outcome in IBC. The HoR+/HER2- subtype shows poorer survival outcome than HoR+/HER2+ subtype.
An Individual‐Level Assessment of the Relationship between Spin‐Off Activities and Research Performance in Universities

One of the most problematic aspects in the creation of spin‐offs by university personnel concerns the relationship between entrepreneurial activity and research activity by researcher‐entrepreneurs. The literature has expressed varying and opposing views as to the nature of the relationship, but very little has been produced to empirically legitimate one position or another. The present work proposes to address this shortcoming by exploring the relationship existing between academic spin‐off generation and the research performance of enterprise founders. The study investigates whether, and to what extent, scientific performance by academic entrepreneurs is different than that of their colleagues, and if the involvement in entrepreneurial activity has an influence on the individual's research activity. The research questions are answered by considering all spin‐offs generated by Italian universities over the period 2001–2008 and evaluating, through a bibliometric approach, the scientific performance of founders relative to that of their colleagues who carry out research in the same field. The data show better scientific performance by the researcher‐entrepreneurs than that of their colleagues, and in addition, although there are some variations across fields, the creation of a spin‐off does not seem, on average, to have negative effects on the scientific performance of the founders.
Efficacy of Amphotericin B Against Fusarium and Aspergillus in Corneal Storage Medium

Purpose: The incidence of postkeratoplasty fungal infection is increasing in the United States, and our most commonly used corneal storage medium, Optisol-GS, contains antibiotics but no antifungal agents. We previously demonstrated the efficacy of amphotericin B additives in eliminating Candida albicans contaminants in Optisol-GS. The purpose of this study was to determine whether amphotericin B would also be efficacious against Fusarium solani and Aspergillus fumigatus. Methods: Vials of Optisol-GS were supplemented with 0.255 &mgr;g/mL of amphotericin B. Half of the vials were inoculated with F. solani and half with A. fumigatus. Positive control vials were inoculated with the fungi but no amphotericin B. The vials were refrigerated, sampled, and plated at different time points. The plates were then incubated at 36°C for 48 hr after which fungal colony counts were performed. Results: There was an average reduction in the growth of F. solani in the amphotericin B–supplemented vials of 44% on day 2, 79% on day 7, and 80% on day 14 when compared with the positive control vials. There was an average reduction in the growth of A. fumigatus in the amphotericin B–supplemented vials of 40% on day 2 and 14% on day 7 when compared with the positive control vials. Both amphotericin B–supplemented and control vials grew less than 2 colonies of A. fumigatus on day 14. Conclusions: This study suggests that amphotericin B additives in Optisol-GS reduce the growth of F. solani and A. fumigatus.
Investigation of Physiological and Behavioral Responses in Dogs Participating in Animal-Assisted Therapy with Children Diagnosed with Attention-Deficit Hyperactivity Disorder

ABSTRACT This study evaluated the impact that participation in sessions with children with Attention-Deficit Hyperactivity Disorder (ADHD) has on therapy dogs. Nine certified therapy dogs were paired for 6 sessions with groups of 3–4 children. Sessions consisted of 5 different activities. Activities 1 and 5 involved interactions solely with each dog and their owner, as a control. Activities 2–4 consisted of interactions with the dogs and the children which included social skills training, dog training, and reading in the company of dogs. One-zero interval sampling of stress-associated behaviors was conducted at 20-second intervals for a 10-minute duration during each of the 5 activities. At the end of each activity, heart rate was monitored, and a saliva sample was obtained for cortisol analysis. Dogs demonstrated only occasional behavioral responses and no significant findings related to cortisol or heart rate when the different activities were compared. The results indicate that with proper supervision and well-trained therapy staff, including suitable therapy dogs and their handlers, canine stress can be minimal in a therapy setting.
Ionospheric activity prediction using convolutional recurrent neural networks

The ionosphere electromagnetic activity is a major factor of the quality of satellite telecommunications, Global Navigation Satellite Systems (GNSS) and other vital space applications. Being able to forecast globally the Total Electron Content (TEC) would enable a better anticipation of potential performance degradations. A few studies have proposed models able to predict the TEC locally, but not worldwide for most of them. Thanks to a large record of past TEC maps publicly available, we propose a method based on Deep Neural Networks (DNN) to forecast a sequence of global TEC maps consecutive to an input sequence of TEC maps, without introducing any prior knowledge other than Earth rotation periodicity. By combining several state-of-the-art architectures, the proposed approach is competitive with previous works on TEC forecasting while predicting the TEC globally.
S-Locus F-Box Proteins Are Solely Responsible for S-RNase-Based Self-Incompatibility of Petunia Pollen

CRISPR/Cas9-mediated knockout of S2-SLFI of Petunia inflata established the essential role of SLF proteins in self-compatibility and reveals their complex interactions with S-RNases. Self-incompatibility (SI) in Petunia is regulated by a polymorphic S-locus. For each S-haplotype, the S-locus contains a pistil-specific S-RNase gene and multiple pollen-specific S-locus F-box (SLF) genes. Both gain-of-function and loss-of-function experiments have shown that S-RNase alone regulates pistil specificity in SI. Gain-of-function experiments on SLF genes suggest that the entire suite of encoded proteins constitute the pollen specificity determinant. However, clear-cut loss-of-function experiments must be performed to determine if SLF proteins are essential for SI of pollen. Here, we used CRISPR/Cas9 to generate two frame-shift indel alleles of S2-SLF1 (SLF1 of S2-haplotype) in S2S3 plants of P. inflata and examined the effect on the SI behavior of S2 pollen. In the absence of a functional S2-SLF1, S2 pollen was either rejected by or remained compatible with pistils carrying one of eight normally compatible S-haplotypes. All results are consistent with interaction relationships between the 17 SLF proteins of S2-haplotype and these eight S-RNases that had been determined by gain-of-function experiments performed previously or in this work. Our loss-of-function results provide definitive evidence that SLF proteins are solely responsible for SI of pollen, and they reveal their diverse and complex interaction relationships with S-RNases to maintain SI while ensuring cross-compatibility.
Evaluation of total phenolic content in virgin olive oil using fluorescence excitation-emission spectroscopy coupled with chemometrics.

BACKGROUND Determination of the total phenolic content (TPC) in olive oils is of great interest, as phenolic compounds affect the health benefits, sensory attributes and oxidative stability of olive oils. The aim of this study was to explore the feasibility of direct front-face fluorescence measurements coupled with chemometrics for developing multivatiate models for discrimination between virgin olive oils with low and high TPC and determination of TPC concentration. RESULTS Parallel factor analysis and principal component analysis of fluorescence excitation-emission matrices (EEMs) of virgin olive oils revealed different fluorescent properties for samples with low and high TPC. A perfect discrimination of oils with low and high TPC was achieved using partial least squares (PLS) discriminant analysis. The best regression model for the prediction of TPC was based on the PLS analysis of the unfolded entire EEMs (R2 = 0.951, RPD = 4.0). CONCLUSIONS The results show the potential of fluorescence spectroscopy for direct screening of virgin olive oils for TPC. This may contribute to the development of fast screening methods for TPC assessment, providing an alternative to conventional assays. The procedure is environmentally friendly and fulfils the requirements for green analytical chemistry. © 2018 Society of Chemical Industry.
Liver transplantation for hepatitis C virus (HCV) non‐viremic recipients with HCV viremic donors

In the context of organ shortage, the opioid epidemic, and effective direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV‐infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor‐derived HCV in previously non‐viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor‐derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non‐viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA‐based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20–59). There have been no instances of graft loss or death, with median follow‐up of 380 days (IQR 263–434) posttransplant. Transplantation of HCV‐viremic livers into non‐viremic recipients results in acceptable short‐term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.
The effect of exogenous activation of protease-activated receptor 2 on cutaneous vasodilatation and sweating in young males during rest and exercise in the heat

ABSTRACT Protease-activated receptor 2 (PAR2) exists in the endothelial cells of skin vessels and eccrine sweat glands. We evaluated the hypothesis that exogeneous activation of PAR2 augments cutaneous vasodilatation and sweating during rest and exercise in the heat. In 10 young males (23 ± 5 y), cutaneous vascular conductance (CVC) and sweat rate were measured at four forearm skin sites treated with either 1) lactated Ringer (Control), 2) 0.05 mM, 3) 0.5 mM, or 4) 5 mM SLIGKV-NH2 (PAR2 agonist). Participants initially rested in a semi-recumbent posture under a normothermic ambient condition (25°C) for ~60 min. Thereafter, ambient temperature was increased to 35°C while the participants rested for an additional 60 min. Participants then performed a 50-min bout of cycling (~55% of their pre-determined peak oxygen uptake) followed by a 30-min recovery period. Administration of 5 mM SLIGKV-NH2 increased cutaneous vascular conductance relative to the Control site during normothermic resting (P ≤ 0.05). However, we showed that relative to the Control site, no effect on CVC was observed for any administered dose of SLIGKV-NH2 (0.05-5 mM) during rest (33–39%max CVC), end-exercise (68–70%max CVC), and postexercise recovery (49–53%max CVC) in the heat (all P > 0.05). There were no differences in sweat rate between the Control and all SLIGKV-NH2-treated sites throughout the protocol (0.21–0.23, 1.20–1.27, and 0.32–0.33 mg∙min−1∙cm−2 for rest, end-exercise, and postexercise in the heat, respectively, all P > 0.05). We show that while exogeneous PAR2 activation induces cutaneous vasodilatation during normothermic rest, it does not influence the cutaneous blood flow and sweating responses during rest, exercise or recovery in the heat.