Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses

Introduction: Although chemotherapy combining 5-fluorouracil (5FU)-dacarbazine (DTIC) or temozolomide (TEM)-capecitabine (CAP) is extensively used in patients with neuroendocrine tumors (NET), they were never compared. We compared their tolerance and efficacy in advanced NET. Methods: We evaluated the records of consecutive patients with pancreatic or small-intestine advanced NET who received 5FU-DTIC or TEM-CAP between July 2004 and December 2017 in 5 French centers. Tolerance, tumor response and progression-free survival (PFS) were compared. Factors associated with PFS were analyzed using Cox multivariate regression model. To reduce the confounding bias of the nonrandomized design, PFS was compared using propensity score analyses. Results: Ninety-four (5FU-DTIC) patients and 153 (TEM-CAP) patients were included. Pancreatic NET represented 82.3% of cases and 17.1, 61.8 and 10.9% of patients had G1, G2 or G3 NET respectively. Progression at baseline was reported in 92.7% of patients with available data. Grades 3–4 adverse events occurred in 24.7 and 8.5% of TEM-CAP and 5FU-DTIC patients respectively (p = 0.002). The overall response rate was 38.3 and 39.2% respectively (p = 0.596). Median PFS on raw analysis was similar to 5FU-DTIC and TEM-CAP (13.9 vs. 18.3 months, respectively p = 0.86). TEM-CAP was associated with an increased risk of progression on the raw multivariate analysis (hazard ratio [HR] 1.90, 95% CI [1.32–2.73], p = 0.001) and when adjusted on propensity score (HR 1.65, 95% CI [1.18–2.31], p = 0.004). Conclusion: PFS may be longer with 5FU-DTIC than TEM-CAP in patients with advanced NET. Although patients often prefer oral chemotherapy, 5FU-DTIC is a relevant alternative. A randomized comparison is needed to confirm these results.
The Malleable Morality of Conspicuous Consumption

Conspicuous consumption has often been decried as immoral by many philosophers and scholars, yet it is ubiquitous and widely embraced. This research sheds light on the apparent paradox by proposing that the perceived morality of conspicuous consumption is malleable, contingent upon how different moral lenses highlight the different characteristics embedded in the behavior. Utilizing the Moral Foundations Theory, we demonstrate that the individualizing values (i.e., equality and welfare) make people focus on the self-enhancing characteristics of conspicuous consumption, making it seem morally objectionable. However, the binding values (i.e., deference to authority, in-group loyalty, and purity) make people focus on the social identity signaling characteristic of conspicuous consumption, making it seem morally permissible. First, an archival dataset shows that the prevalence of the different moral values predicts per-capita spending on luxury goods across different countries. Then, 6 studies (N = 2903) show that the trait endorsement and the momentary salience of the different moral foundations can influence the moral judgment of conspicuous consumption as well as the propensity to engage in conspicuous consumption. Further, analyses show that the effect of the binding values (individualizing values) is mediated by heightened sensitivity to the social identity signaling (self-enhancing) aspects of conspicuous consumption. Finally, the studies demonstrate that the effect is moderated by the extent of social visibility during consumption. Thus, this research suggests that some moral values can, somewhat paradoxically, increase conspicuous consumption. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The E3-ligases SCFPpa and APC/CCdh1 co-operate to regulate CENP-ACID expression across the cell cycle

Abstract Centromere identity is determined by the specific deposition of CENP-A, a histone H3 variant localizing exclusively at centromeres. Increased CENP-A expression, which is a frequent event in cancer, causes mislocalization, ectopic kinetochore assembly and genomic instability. Proteolysis regulates CENP-A expression and prevents its misincorporation across chromatin. How proteolysis restricts CENP-A localization to centromeres is not well understood. Here we report that, in Drosophila, CENP-ACID expression levels are regulated throughout the cell cycle by the combined action of SCFPpa and APC/CCdh1. We show that SCFPpa regulates CENP-ACID expression in G1 and, importantly, in S-phase preventing its promiscuous incorporation across chromatin during replication. In G1, CENP-ACID expression is also regulated by APC/CCdh1. We also show that Cal1, the specific chaperone that deposits CENP-ACID at centromeres, protects CENP-ACID from SCFPpa-mediated degradation but not from APC/CCdh1-mediated degradation. These results suggest that, whereas SCFPpa targets the fraction of CENP-ACID that is not in complex with Cal1, APC/CCdh1 mediates also degradation of the Cal1-CENP-ACID complex and, thus, likely contributes to the regulation of centromeric CENP-ACID deposition.
ADAM10 sheddase activation is controlled by cell membrane asymmetry

Abstract Dysregulation of the disintegrin-metalloproteinase ADAM10 may contribute to the development of diseases including tumorigenesis and Alzheimer’s disease. The mechanisms underlying ADAM10 sheddase activation are incompletely understood. Here, we show that transient exposure of the negatively charged phospholipid phosphatidylserine (PS) is necessarily required. The soluble PS headgroup was found to act as competitive inhibitor of substrate cleavage. Overexpression of the Ca2+-dependent phospholipid scramblase Anoctamin-6 (ANO6) led to increased PS externalization and substrate release. Transfection with a constitutively active form of ANO6 resulted in maximum sheddase activity in the absence of any stimulus. Calcium-dependent ADAM10 activation could not be induced in lymphocytes of patients with Scott syndrome harbouring a missense mutation in ANO6. A putative PS-binding motif was identified in the conserved stalk region. Replacement of this motif resulted in strong reduction of sheddase activity. In conjunction with the recently described 3D structure of the ADAM10 extracellular domain, a model is advanced to explain how surface-exposed PS triggers ADAM10 sheddase function.
Mal Secco Disease Caused by Phoma tracheiphila: A Potential Threat to Lemon Production Worldwide.

Lemon ( Citrus limon (L.) Burm. f) is the most popular acid citrus fruit because of its appealing color, odor, and flavor. World production of lemons was about 7 to 8 million metric tons in 2007. Major producers and exporters of lemon in the world include Argentina, Spain, Iran, the United States, Italy, Turkey, Egypt, Greece, South Africa, Cyprus, Morocco, and Israel (www.cga.co.za). Argentina and Italy are major suppliers of lemon juice, and Spain, Argentina, Turkey, the United States, South Africa, Italy, Chile, Egypt, Uruguay, India, Jordan, Cyprus, China, and Iran are the leading exporting countries of fresh fruit. Mal secco of citrus is a highly destructive vascular disease of lemon, presently confined to the Mediterranean basin, which has a relevant economic impact on the lemon industry in this geographic region. Mal secco is caused by the mitosporic fungus Phoma tracheiphila (Petri) Kantschaveli & Gikachvili (syn. Deuterophoma tracheiphila Petri). The name of the disease stems from the Italian words male (disease) and secco (dry). The term “malsecco,” referring to nonspecific symptoms, was initially used in a broad sense to indicate citrus diseases of various origins. Later, Petri used the term “mal secco of citrus” in a more strict sense to indicate the tracheomycotic disease that was spreading in lemon orchards in Sicily. Mal secco first appeared affecting lemon trees on the islands of Chios and Poros (Greece) near the end of the nineteenth century. In 1929, Petri described the fungus causing mal secco as a new species and named it Deuterophoma tracheiphila , which he proposed as the type-species of the new genus Deuterophoma Petri. The species was transferred to Phoma by Kantschaveli and Gikachvili in 1948. Later, Ciccarone and Russo and Ciccarone, who amended the description of the fungus, confirmed this binomial as the correct name.
Relationships Between Vein Repairs, Postoperative Transfusions, and Survival in Single Digit Replantation

Background: The general teaching is that increased number of vein repairs in digit replantation leads to improved venous outflow, resulting in lower need for iatrogenic bleeding, lower postoperative transfusion requirements, and better survival rates. The purpose of this study was to determine whether the traditional teaching that emphasizes the repair of multiple veins per arterial anastomosis results in superior survival rates. Methods: A retrospective review of a single urban replant center’s single-digit replants distal to the mid-metacarpal level in adult patients from 2007 to 2017 was performed. Data on patient demographics, mechanism and level of injury, veins repaired, iatrogenic bleeding, postoperative transfusions, and replant survival were obtained. Results: There were a total of 54 single-digit replants. The most common mechanism was lacerations (N = 38), and the most common injury level was at the proximal phalanx (N = 21). All digits were replanted with a single arterial anastomosis—44% via grafting. In all, 0 to 3 veins were repaired per digit (mean = 1.5 veins). The mean transfusion requirement was 1.7 units. The survival rate was 50%. Digits with 1 or 2 veins repaired had lower transfusion requirements (1.1-1.3 units) and higher survival rates (56%-61%) compared with those replanted with 0 or 3 veins repaired (2.9-3.5 transfused units, 25%-29% survival). There were no differences between those digits replanted with either 1 or 2 veins repaired for transfusion requirements or survival. Conclusions: More veins repaired do not necessarily improve survival or possibly venous outflow, calling into question the traditional teaching that 2 veins should be repaired for every arterial anastomosis.
Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.
Sodium fluoride regulates the osteo/odontogenic differentiation of stem cells from apical papilla by modulating autophagy

Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit‐8, EdU staining, and flow cytometry were performed to detected the proliferation activity. Alkaline phosphatase (ALP) activity, Alizarin Red staining, Western blot assay, and real‐time reverse‐transcription polymerase chain reaction were applied to assess the osteo/odontogenic differentiation NaF‐treated SCAPs. Western blot assay and transmission electron microscope were used to evaluate the autophagy involved in the differentiation of SCAPs. ALP activity, ALP protein, and messenger RNA (mRNA) expression showed that 0.5 mM was the optimal concentration for the induction of SCAPs by NaF. 0.5 mM NaF‐treated SCAPs induced more mineralized nodules as compared with untreated cells. Moreover, the osteo/odontogenic markers (RUNX2, OSX, DSP, and OCN) in mRNA levels were upregulated while the protein levels of these markers increased considerably in 0.5 mM NaF‐treated SCAPs. Furthermore, the autophagy‐related proteins (LC3, ATG5, and Beclin1) increased in NaF‐treated SCAPs, and the osteo/odontogenic makers significantly decreased while silencing ATG5 to block autophagy. In all, sodium fluoride can regulate the osteo/odontogenic differentiation of SCAPs by modulating autophagy.
Neutrophil‐to‐lymphocyte ratio and its relation with pro‐inflammatory mediators, visceral adiposity and carotid intima‐media thickness in population with obesity

Atherosclerosis represents a cardiovascular risk. Chronic inflammation is a key factor for atherogenic progression. Neutrophil‐to‐lymphocyte ratio (NLR) has been proposed as a novel biomarker for cardiovascular risks. We aimed to explore whether NLR was related to surrogate pro‐atherogenic promoters driving atherogenic progression, as measured by carotid intima‐media thickness (CIMT).
Pathogenicity and immunosuppressive potential of fowl adenovirus in specific pathogen free chickens

ABSTRACT To elucidate the effect of fowl adenovirus (FAdV)‐C in specific‐pathogen‐free (SPF) chickens, we investigated the pathogenicity, body weights, enzymatic systems, and immune organs of chickens in response to Newcastle disease virus (NDV) and avian influenza virus subtype H9 (AIV‐H9) vaccination. Chickens were divided randomly into four groups, which included injection groups (FAdV‐C, vaccination, and FAdV‐C plus vaccination) and a negative control group. The results indicated that FAdV‐C was highly pathogenic in SPF chickens and led to a 40% mortality rate and growth retardation, compared with the control birds. Significant changes in clinical chemical markers of all infected birds, together with histopathological lesions, indicated impairment of the liver and heart integrity and function. Furthermore, chickens in the FAdV‐C plus vaccination group had significantly lower titers of antibodies against NDV and AIV‐H9 than the uninfected and vaccinated chickens. The results of this study provide new insights into the pathogenesis of hydropericardium syndrome, a disease that progresses to a metabolic disorder and causes serious growth retardation and immunosuppression.
The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer

Abstract Objective: Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated colorectal cancer (CAC). Previous studies have indicated that the composition of gut microflora may be involved in CAC induction and progress. Bacteroides fragilis (BF) is a Gram-negative anaerobe belonging to colonic symbiotic bacteria of the host. This study was aimed to investigate the protective role of BF in a colorectal cancer (CRC) model induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in germ-free (GF) mice. Materials and methods: Total 22 GF mice were divided into two groups: GF and BF group. Half of the GF mice were colonized with BF for 28 days before CRC induction by AOM/DSS. Results: BF colonization increased animal survival (100%). Cecum weight and cecum/body weight ratio significantly decreased in BF/AOM/DSS group. Interestingly, there was a significant decrease in tumor number and tumor incidence in the BF/AOM/DSS group as compared to the GF/AOM/DSS group. The adenocarcinoma/adenoma incidence and histologic score were also decreased in the BF/AOM/DSS group. In addition, immunohistochemistry staining found decreased numbers of cell proliferation (PCNA) and inflammatory cell (granulocytes) infiltration in the colon mucosa of the BF group. The β-catenin staining in the BF/AOM/DSS group had fewer and weaker positive signal expressions. Taking together, the BF colonization significantly ameliorated AOM/DSS-induced CRC by suppressing the activity of cell proliferation-related molecules and reducing the number of inflammatory cells. Conclusions: Symbiotic BF may play a pivotal role in maintaining the gastrointestinal immunophysiologic balance and regulating anti-tumorigenesis responses.
Social threat learning transfers to decision making in humans

Significance In today’s world, indirect exposure to threatening situations is more common than ever, as illustrated by footage of terror and disaster in social media. How do such social threat learning experiences shape our decisions? We found that learning about threats from both observation and verbal information strongly influenced decision making. As with learning from our own experience, this influence could be either adaptive or maladaptive depending on whether the social information provided accurate expectations about the environment. Our findings can help explain both adaptive and pathological behaviors resulting from the indirect exposure to threatening events. In today’s world, mass-media and online social networks present us with unprecedented exposure to second-hand, vicarious experiences and thereby the chance of forming associations between previously innocuous events (e.g., being in a subway station) and aversive outcomes (e.g., footage or verbal reports from a violent terrorist attack) without direct experience. Such social threat, or fear, learning can have dramatic consequences, as manifested in acute stress symptoms and maladaptive fears. However, most research has so far focused on socially acquired threat responses that are expressed as increased arousal rather than active behavior. In three experiments (n = 120), we examined the effect of indirect experiences on behaviors by establishing a link between social threat learning and instrumental decision making. We contrasted learning from direct experience (i.e., Pavlovian conditioning) (experiment 1) against two common forms of social threat learning—social observation (experiment 2) and verbal instruction (experiment 3)—and how this learning transferred to subsequent instrumental decision making using behavioral experiments and computational modeling. We found that both types of social threat learning transfer to decision making in a strong and surprisingly inflexible manner. Notably, computational modeling indicated that the transfer of observational and instructed threat learning involved different computational mechanisms. Our results demonstrate the strong influence of others’ expressions of fear on one’s own decisions and have important implications for understanding both healthy and pathological human behaviors resulting from the indirect exposure to threatening events.
Prospective memories and working memory: shared resources or distinct mechanisms?

Abstract Prospective memory (PM) is a complex process involving multiple cognitive abilities. Several studies demonstrated the role of working memory (WM) in PM. However, to date, the extent to which PM and WM shared resources or, rather, they are distinct mechanisms is still debated. With the aim to investigate the role of WM in PM, we developed two experiments manipulating the WM load required by ongoing tasks to examine a patient with PM difficulties and dysexecutive syndrome following brain damage. Experiment 1 required a simple arithmetic activity together with a PM switching-task to be performed at a given time (time-based condition) or following cue presentation (event-based condition). In Experiment 2, we varied the complexity of the ongoing task (PASAT test). Patient MB’s performance in PM tasks significantly differs from the controls only in the PASAT time-based condition. We demonstrated a partial independence between WM and PM in tasks involving automatic retrieval.
Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!

Artemisinin-based combination therapies (ACTs) have become the mainstay for malaria treatment in almost all malaria endemic settings. Artemisinin derivatives are highly potent and fast acting antimalarials; but they have a short half-life and need to be combined with partner drugs with a longer half-life to clear the remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased susceptibility to artemisinins have emerged in the Greater Mekong Subregion (GMS), followed by ACTs’ failure, due to both decreased susceptibility to artemisinin and partner drug resistance. Therefore, there is an urgent need to strengthen and expand current resistance surveillance systems beyond the GMS to track the emergence or spread of artemisinin resistance. Great attention has been paid to the spread of artemisinin resistance over the last five years, since molecular markers of decreased susceptibility to artemisinin in the GMS have been discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious partner drug. This review outlines the different mechanisms of resistance and molecular markers associated with resistance to partner drugs for the currently used ACTs. Strategies to improve surveillance and potential solutions to extend the useful therapeutic lifespan of the currently available malaria medicines are proposed.