Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychometric properties of the Italian version of the Experience in Close Relationship Scale 12 (ECR-12): an exploratory structural equation modeling study

The Experiences in Close Relationship Scale (ECR) is one of the most commonly used self-report instruments of adult attachment and has been widely adopted in psychotherapy research. Composed of two subscales, namely Attachment Avoidance and Anxiety, the ECR was recently shortened to a 12-items version, called the ECR-12. Given the importance of extending knowledge on its applicability in understudied populations, our aim was to validate the ECR-12 in a large sample of Italian native-speakers. A total of 1197 participants (73.2% females; mean age=28.53±11.37 years) completed the ECR-12. Each participant also completed other measures of attachment, psychopathology, interpersonal distress, coping strategies, and well-being. An Exploratory Structural Equation Modeling analysis showed an excellent fit of the data, providing support for the two-dimensional orthogonal structure of the ECR-12. In addition, the measurement model was invariant across genders. Both attachment anxiety and attachment avoidance subscales demonstrated good internal reliability, with McDonald’s Omegas and Cronbach’s Alphas above the suggested 0.8 cut-off. Finally, the Italian version of ECR-12 showed adequate convergent, concurrent, and divergent validity. Highly anxious individuals reported the highest levels of maladaptive interpersonal functioning and coping strategies, resulting in lower well-being. Interestingly, both attachment insecurity dimensions predicted higher levels of psychopathology, even after controlling for demographic variables and levels of self-reported relational difficulties. Given the good psychometric properties of the ECR-12, researchers and practitioners in Italy are encouraged to adopt the ECR-12 in their future research on adult attachment in psychotherapy.
Characterization of the apicoplast-localized enzyme TgUroD in Toxoplasma gondii reveals a key role of the apicoplast in heme biosynthesis

Apicomplexan parasites such as Toxoplasma gondii possess an unusual heme biosynthesis pathway whose enzymes localize to the mitochondrion, cytosol, or apicoplast, a nonphotosynthetic plastid present in most apicomplexans. To characterize the involvement of the apicoplast in the T. gondii heme biosynthesis pathway, we investigated the role of the apicoplast-localized enzyme uroporphyrinogen III decarboxylase (TgUroD). We found that TgUroD knockdown impaired parasite proliferation, decreased free heme levels in the parasite, and decreased the abundance of heme-containing c-type cytochrome proteins in the parasite mitochondrion. We validated the effects of heme loss on mitochondrial cytochromes by knocking down cytochrome c/c1 heme lyase 1 (TgCCHL1), a mitochondrial enzyme that catalyzes the covalent attachment of heme to c-type cytochromes. TgCCHL1 depletion reduced parasite proliferation and decreased the abundance of c-type cytochromes. We further sought to characterize the overall importance of TgUroD and TgCCHL1 for both mitochondrial and general parasite metabolism. TgUroD depletion decreased cellular ATP levels, mitochondrial oxygen consumption, and extracellular acidification rates. By contrast, depletion of TgCCHL1 neither diminished ATP levels in the parasite nor impaired extracellular acidification rate, but resulted in specific defects in mitochondrial oxygen consumption. Together, our results indicate that the apicoplast has a key role in heme biology in T. gondii and is important for both mitochondrial and general parasite metabolism. Our study highlights the importance of heme and its synthesis in these parasites.
Sleep quality and sex modify the relationships between trait energy and fatigue on state energy and fatigue

The objective of this study was to identify the associations between trait energy and fatigue with state energy fatigue, as well as exploring if these relationships interacted with sex and/or sleep quality. The study population included a convenience sample of adults and college students (n ranges from 687 to 694). Key measures were state and trait mental and physical energy and fatigue scales, PSQI (a measure of sleep quality), and sex. Multiple regression models included age, polyphenol consumption, POMS scores, physical activity, mental load, and caffeine consumption as covariates. Analyses yielded a strong (r = .65) positive association between each trait and state variable. Overall, several statistically significant interactions were identified. First, the relationship between state and trait physical fatigue was particularly strong for women with high trait scores. There were also interactions with sleep quality. In the case of physical fatigue, poor sleep quality magnified the association between physical fatigue trait and state among those with low trait physical fatigue, while sleep quality did not make a difference for those with high trait physical fatigue. Conversely, in the case of physical energy and mental fatigue, good sleep quality was associated with both higher “highs” and lower “lows” of their respective traits; both interactions were present only among males. Our analyses suggest that sleep quality and sex could influence the effects of trait physical and mental energy and fatigue on state. Findings were more complex than initially assumed, suggesting that the interrelationship between trait and state may be modified by how males and females react and adapt to their trait.
Muscle Sympathetic Reactivity to Apneic and Exercise Stress in High-Altitude Sherpa.

Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that alter vascular function. High altitude populations, such as Sherpa, have previously exhibited greater peripheral blood flow in response to acute stress than Lowlanders which may be explained through lower sympathetic activity. Our purpose was to determine if Sherpa exhibit lower sympathetic activity and reactivity to stress than Lowlanders. Muscle sympathetic activity (MSNA; microneurography) was measured at rest in Lowlanders (n=14; age=27±6yrs) at 344m and following 8-9 days at 5050m. Sherpa (age=32±11yrs) were tested at 5050m (n=8). Neurovascular reactivity (ie. change in MSNA patterns) was measured during maximal end-expiratory apnea, isometric hand-grip (IHG; 30% maximal voluntary contraction for 2-minutes) and post-exercise circulatory occlusion (PECO; 3-minutes). Burst frequency (bursts/min), incidence (bursts/100HB), and total normalized SNA (au/min) was analyzed at rest, immediately prior to apnea breakpoint, and during the last minute of IHG and PECO. Vascular responses to apnea, IHG, and PECO were also measured. MSNA reactivity to apnea was lower in Sherpa than Lowlanders at 5050m, though blood pressure responses were similar between groups. MSNA increases in Lowlanders during apnea at 5050m were significantly lower than at 344m (P<0.05), indicating possible sympathetic ceiling was reached in Lowlanders at 5050m. MSNA increased similarly during IHG/PECO in Lowlanders at both 334m and 5050m, and Sherpa at 5050m, while vascular changes (mean brachial arterial pressure, contralateral brachial flow/resistance) were similar between groups. Sherpa demonstrate overall lower sympathetic activity and reactivity which may be a result of heightened vascular responsiveness to potential apneic stress at altitude.
Mitochondrial thermo-sensitivity in invasive and native freshwater mussels

ABSTRACT Climate change is impacting many, if not all, forms of life. Increases in extreme temperature fluctuations and average temperatures can cause stress, particularly in aquatic sessile ectotherms such as freshwater mussels. However, some species seem to thrive more than others in face of temperature-related stressors. Thermal tolerance may, for example, explain the success of invasive species. It is also known that mitochondria can play a key role in setting an ectothermic species' thermal tolerance. In this study, we aimed to characterize the mitochondrial thermo-tolerance in invasive and endemic freshwater mussels. With the use of high-resolution respirometry, we analyzed the mitochondrial respiration of two freshwater bivalve species exposed to a broad range of temperatures. We noticed that the invasive dreissenid Dreissena bugensis possessed a less thermo-tolerant mitochondrial metabolism than the endemic unionid Elliptio complanata. This lack of tolerance was linked with a more noticeable aerobic metabolic depression at elevated temperatures. This decrease in mitochondrial metabolic activity was also linked with an increase in leak oxygen consumption as well as a stable maintenance of the activity of cytochrome c oxidase in both species. These findings may be associated both with the species' life history characteristics, as D. bugensis is more adapted to unstable habitats, in which selection pressures for resistance adaptations are reduced. Our findings add to the growing body of literature characterizing the mitochondrial metabolism of many aquatic ectotherms in our changing world. Summary: Contrary to previous beliefs, invasive aquatic ectotherms do not always possess more thermo-tolerant mitochondria than their endemic counterparts.
Acalabrutinib Plus Obinutuzumab in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia.

Acalabrutinib is a selective irreversible Bruton tyrosine kinase inhibitor that does not affect interleukin-2 associated tyrosine kinase or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combination therapy with anti-CD20 antibodies. We investigated acalabrutinib plus obinutuzumab in a phase 1b/2 study (NCT02296918) of patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia (CLL). Nineteen treatment-naive and 26 relapsed/refractory patients were treated with acalabrutinib (100 mg twice daily) until progression and obinutuzumab (cycle 1: 100 mg day 1, 900 mg day 2, 1000 mg days 8 and 15; cycles 2-6: 1000 mg day 1). Grade 3/4 adverse events occurred in 71% of patients. Overall response rates were 95% (treatment-naive) and 92% (relapsed/refractory). Thirty-two percent of treatment-naive and 8% of relapsed/refractory patients achieved complete remission. At 36 months, 94% (treatment-naive) and 88% (relapsed/refractory) were progression free. Acalabrutinib plus obinutuzumab was well tolerated, producing high and durable responses in treatment-naive and relapsed/refractory CLL.
The Influence of Donor Milk Supplementation on Duration of Parenteral Nutrition in Preterm Infants

Background Data are limited on the association between the use of donor human milk and improvements in feeding tolerance. Objective To determine the influence of the duration of parenteral nutrition on the growth and morbidity of the breastfed newborn when using donated human milk in the absence of mother’s own milk. Methods We conducted a retrospective study before and after the intervention that compared two groups of newborns (N = 284; each group n = 142). We used a convenience sample of all newborns ≤32 weeks gestation consecutively admitted in a single unit before (Group 1 between December 2012 and May 2014) or after (Group 2 between October 2014 and December 2016) the availability of donor human milk. In Group 2, donor human milk was administered at least 3 to 4 weeks or until the baby weighed 1,500 g. Weight was recorded daily and length and head circumference weekly. Parenteral nutrition was continued until enteral feeding volume reached 120 ml/kg/day. Additional variables measured were the number of days with a central venous catheter, age that the enteral feeding volume reached 150 ml/kg/day, and duration of stay. Results The duration of parenteral feeding was the same before and after: 12 (8.23) and 11 (7.19) days (p = .822). The z scores for weight and height of newborns was lower in Group 2 = −1.8 (1.0) and −2.3 (1.1) and Group 1 = −1.2 (1.1) (p < .001) and −1.8 (1.4) (p = .005). Conclusion We did not find an association between the administration of donor human milk as a supplement to mother’s own milk and reduced number of days of parenteral nutrition. Back translation by Laurence Grummer-Strawn
The Orphan Immune Receptor LILRB3 Modulates Fc Receptor–Mediated Functions of Neutrophils

Key Points Neutrophils express LILRB3, which is released in a soluble form upon activation. LILRB3 inhibits FcαR-mediated neutrophil activation and effector functions. Neutrophils are critical to the generation of effective immune responses and for killing invading microbes. Paired immune receptors provide important mechanisms to modulate neutrophil activation thresholds and effector functions. Expression of the leukocyte Ig-like receptor (LILR)A6 (ILT8/CD85b) and LILRB3 (ILT5/CD85a) paired-receptor system on human neutrophils has remained unclear because of the lack of specific molecular tools. Additionally, there is little known of their possible functions in neutrophil biology. The objective of this study was to characterize expression of LILRA6/LILRB3 receptors during human neutrophil differentiation and activation, and to assess their roles in modulating Fc receptor–mediated effector functions. LILRB3, but not LILRA6, was detected in human neutrophil lysates following immunoprecipitation by mass spectrometry. We demonstrate high LILRB3 expression on the surface of resting neutrophils and release from the surface following neutrophil activation. Surface expression was recapitulated in a human PLB-985 cell model of neutrophil-like differentiation. Continuous ligation of LILRB3 inhibited key IgA-mediated effector functions, including production of reactive oxygen species, phagocytic uptake, and microbial killing. This suggests that LILRB3 provides an important checkpoint to control human neutrophil activation and their antimicrobial effector functions during resting and early-activation stages of the neutrophil life cycle.
Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.

BACKGROUND Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study. METHODS In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. RESULTS Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time. CONCLUSIONS Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).
A prophylaxis study of acute exacerbation of interstitial pneumonia after lung cancer surgery.

INTRODUCTION Acute exacerbation of interstitial pneumonia (AE-IP) is a lethal complication after lung surgery. We conducted a prospective, multi-institutional phase II trial to assess the efficacy and safety of prophylactic measures. METHOD Patients with lung cancer with dorsal subpleural fibrotic changes occupying three or more segments of both lower lobes and planned anatomical lung resection were enrolled. Prior to surgery, patients received a 125-mg bolus injection of methylprednisolone and continuous intravenous infusion of sivelestat sodium hydrate (sivelestat) for 2 days. RESULTS Sixty-nine patients were analysed. Preoperative high-resolution computed tomography (HRCT) showed 37 (53.6%) cases presented with usual interstitial pneumonia (UIP) and possible UIP pattern. There were 60 lobectomies and 9 segmentectomies. Thirty-eight cases were in clinical stage I. No adverse events associated with prophylaxis were observed. There were four cases of AE-IP (5.8%), higher than the expected 2.0%. Three of the four cases showed inconsistencies with the UIP pattern in preoperative HRCT and were pathologically diagnosed as UIP. All patients died of respiratory failure. Overall, 89.9% were diagnosed as idiopathic interstitial pneumonias; UIP was found in 48 patients (69.6%). Severe post-operative complications occurred in 11.6% of the cases. There were 35 deaths, 17 cases of lung cancer and 11 cases related to interstitial pneumonias. The overall survival rate at 3 years was 41.8% of the total and 47.2% of cases with clinical stage I. CONCLUSIONS Perioperative use of sivelestat and low-dose methylprednisolone in patients with anatomical lung resection was safe but did not prove to be a prophylactic effect for AE-IP.
Evaluation and validation of 2D biomechanical models of the knee for radiograph-based preoperative planning in total knee arthroplasty

Thorough preoperative planning in total knee arthroplasty is essential to reduce implant failure by proper implant sizing and alignment. The “gold standard” in conventional preoperative planning is based on anterior-posterior long-leg radiographs. However, the coronal component alignment is still an open discussion in literature, since studies have reported contradictory outcomes on survivorship, indicating that optimal individual alignment goals still need to be defined. Two-dimensional biomechanical models of the knee have the potential to predict joint forces and, therefore, objectify therapy planning. Previously published two-dimensional biomechanical models were evaluated and validated for the first time in this study by comparison of model predictions to corresponding in vivo measurements obtained from telemetric implants for a one- and two-leg stance. Model input parameters were acquired from weight-bearing anterior-posterior long-leg radiographs and statistical assumptions for patient-specific model adaptation. The overall time from initialization to load prediction was in the range of 7–8 minutes per patient for all models. However, no model could accurately predict the correct trend of knee joint forces over patients. Two dimensional biomechanical models of the knee have the potential to improve preoperative planning in total knee arthroplasty by providing additional individual biomechanical information to the surgeon. Although integration into the clinical workflow might be performed with acceptable costs, the models’ accuracy is insufficient for the moment. Future work is needed for model optimization and more sophisticated modelling approaches.
Grief and Survival in the Era of HIV Treatment Advances

Since the beginning of the epidemic, AIDS has been associated with a high mortality rate, and consequently, the literature has focused on grief and bereavement as key elements of the psychosocial impact of HIV infection (Dane and Miller 1992; Mead and Willemsen 1995). There has been a clear attempt to describe the unique characteristics of AIDSrelated grief, and it has been suggested that those who experience AIDS-related deaths are at greater risk for complicated grieving (Fawzy, Fawzy, and Pasnau 1991; Houseman and Pheifer 1988; Catalan 1995; Siegel and Gorey 1994). Factors complicating the mourning of an AIDSrelated death include the social stigma attached to AIDS, the young age of the deceased as well as the bereaved, reduced material resources of the bereaved, the HIV status of the bereaved, lack of social support, bereavement overload, and multiple loss (Sherr 1995; Siegel and Gorey 1994; Mallinson 1999). Kelly et al. (1996) compared a group of individuals bereaved by an AIDS death with a group bereaved by a cancer death, and they found that those bereaved by AIDS reported a greater number of losses, less social support, stigma, and less open disclosure of the cause of death. HIV has been described as a “disease of loss” (Mead and Willemsen 1995). Being HIV positive or diagnosed with AIDS means that the individual must confront a variety of losses such as the loss of health and changes in physical appearance, possible loss of mental functioning, loss of employment and changes in financial status, loss of sexual relationships, loss of friends and loved ones to the disease, loss of self-esteem, and loss of meaningfulness in life (Mead and Willemsen 1995). All of these factors have led clinicians to recommend the development of mental
Enhancer of zeste homolog 2 modulates oxidative stress‐mediated pyroptosis in vitro and in a mouse kidney ischemia‐reperfusion injury model

Enhancer of zeste homolog 2 (EZH2), a well‐known methyltransferase, mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays a crucial role in several kidney disease models. However, its role in renal ischemia/reperfusion (I/R) injury still remains unclear. In this study, we found that EZH2 was positively related to renal I/R injury and inhibition of EZH2 with DZNeP alleviated I/R injury and blocked the activation of oxidative stress and pyroptosis in vivo. Similarly, inhibition of EZH2 with either DZNeP or si‐RNA also exerted an inhibitory effect on hypoxia/reoxygenation (H/R)‐induced oxidative stress and pyroptosis in vitro. Moreover, further study revealed that ablation of reactive oxygen species (ROS) with N‐acetyl‐cysteine (NAC) suppressed pyroptosis in human renal proximal tubular epithelial cell line cells exposed to H/R stimulation. Furthermore, Nox4, which was positively related to the generation of ROS, was upregulated during H/R process, while it could be reversed by EZH2 inhibition. Consistently, Nox4‐mediated ROS generation was attenuated upon inhibition of EZH2 with DZNeP or si‐RNA. Additionally, the transcriptional activity of Nox4 was enhanced by the activation of ALK5/Smad2/3 signaling pathway, which was abolished by ALK5 knockdown in vitro. Finally, EZH2 inhibition blocked H/R and I/R‐activated ALK5/Smad2/3 pathway and also resulted in an obvious decrease in the transcriptional activity and protein expression levels of Nox4. In conclusion, our results proved that EZH2 inhibition alleviated renal pyroptosis by blocking Nox4‐dependent ROS generation through ALK5/Smad2/3 signaling pathway, indicating that EZH2 could be a potential therapeutic target for renal I/R injury.