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This study examines the relative contributions to dietary diversity of the diversity of plant and domesticated animal species which rural households produce or collect, i.e., nonmarket food sources, versus the diversity of foods purchased in markets. Although opinions differ in the literature as to their relative importance, clarifying how different sources of food contribute to the dietary diversity of rural households in the developing world is important to inform policies and interventions to improve their food security and dietary quality. This case study was carried out among a random sample of 654 rural households in southern Benin during two seasons: when food is plentiful after harvest; and when food is scarcer between harvests. We collected data on crops, wild plants, and domesticated animals utilized by households, the number of markets they visited, and the diet of a mother in the household, with a structured 24-hour food frequency questionnaire. We hypothesize that the number of markets visited is an indicator of the diversity of foods available in the markets they have access to, and thus shows the contribution of markets as food sources. Results support this hypothesis and show that households that produced more plant and domesticated animal species and those that visited more markets had more diversified diets. Obtaining diverse foods from multiple sources provides households with more options to achieve better diets. These results suggest a need for a more holistic approach that recognizes the complementarities between market and nonmarket sources of foods. This approach should build on the diversity of species rural households already utilize, and on the ways they interact with markets.

Background Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC). Methods pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence. pAXLxCD3ε mediated T-cell infiltration, activation and proliferation were assessed by immunofluorescence microscopy and by flow cytometry. Activity of pAXLxCD3ε was also investigated in combination with poly-ADP ribose polymerase inhibitors (PARPi). In vivo antitumor activity of pAXLxCD3ε was evaluated in immunocompromised (NSG) mice bearing intraperitoneal or subcutaneous EOC xenografts and immunologically reconstituted with human peripheral blood mononuclear cells (PBMC). Results pAXLxCD3ε induced dose-dependent cytotoxicity by activation of T lymphocytes against EOC cells, regardless of their histologic origin. The addition of PARPi to cell cultures enhanced pAXLxCD3ε cytotoxicity. Importantly, in vivo, pAXLxCD3ε was highly effective against EOC xenografts in two different NSG mouse models, by inhibiting the growth of tumor cells in ascites and subcutaneous xenografts. This effect translated into a significantly prolonged survival of treated animals. Conclusion pAXLxCD3ε is an active therapeutics against EOC cells providing a rational for its development as a novel agent in this still incurable disease. The preclinical validation of a first-in-class agent opens the way to the development of a new 14Fn3-based scaffold platform for the generation of innovative immune therapeutics against cancer.

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging pediatric and adult haematologic disease still associated with an unsatisfactory cure rate. Unlike B-ALL, the availability of novel therapeutic options to definitively improve the life expectancy for relapsed/resistant patients is poor. Indeed, the shared expression of surface targets among normal and neoplastic T-cells still limits the efficacy and may induce fratricide effects, hampering the use of innovative immunotherapeutic strategies. However, novel monoclonal antibodies, bispecific T-cell engagers (BTCEs), and chimeric antigen receptors (CAR) T-cells recently showed encouraging results and some of them are in an advanced stage of pre-clinical development or are currently under investigation in clinical trials. Here, we review this exciting scenario focusing on most relevant advances, challenges, and perspectives of the emerging landscape of immunotherapy of T-cell malignancies.

BackgroundDNA ligases are crucial for DNA repair and cell replication since they catalyze the final steps in which DNA breaks are joined. DNA Ligase III (LIG3) exerts a pivotal role in Alternative-Non-Homologous End Joining Repair (Alt-NHEJ), an error-prone DNA repair pathway often up-regulated in genomically unstable cancer, such as Multiple Myeloma (MM). Based on the three-dimensional (3D) LIG3 structure, we performed a computational screening to identify LIG3-targeting natural compounds as potential candidates to counteract Alt-NHEJ activity in MM.MethodsVirtual screening was conducted by interrogating the Phenol Explorer database. Validation of binding to LIG3 recombinant protein was performed by Saturation Transfer Difference (STD)—nuclear magnetic resonance (NMR) experiments. Cell viability was analyzed by Cell Titer-Glo assay; apoptosis was evaluated by flow cytometric analysis following Annexin V-7AAD staining. Alt-NHEJ repair modulation was evaluated using plasmid re-joining assay and Cytoscan HD. DNA Damage Response protein levels were analyzed by Western blot of whole and fractionated protein extracts and immunofluorescence analysis. The mitochondrial DNA (mtDNA) copy number was determined by qPCR. In vivo activity was evaluated in NOD-SCID mice subcutaneously engrafted with MM cells.ResultsHere, we provide evidence that a natural flavonoid Rhamnetin (RHM), selected by a computational approach, counteracts LIG3 activity and killed Alt-NHEJ-dependent MM cells. Indeed, Nuclear Magnetic Resonance (NMR) showed binding of RHM to LIG3 protein and functional experiments revealed that RHM interferes with LIG3-driven nuclear and mitochondrial DNA repair, leading to significant anti-MM activity in vitro and in vivo.ConclusionTaken together, our findings provide proof of concept that RHM targets LIG3 addiction in MM and may represent therefore a novel promising anti-tumor natural agent to be investigated in an early clinical setting.

Although biomedical devices have greatly evolved, none of the materials that have been used to date are able to meet all the hemocompatibility criteria. The rapid accumulation of proteins at the implant surface and the subsequent physiological response are the main causes of failure. Thus, the appropriate design of antithrombotic materials is of the utmost importance. In this work, we employed Carbothane® electrospun matrices (PCU) for lysine surface modification, using oligomers obtained from allyl glycidyl ether (AGE) reaction as spacers. This technique enables the binding of several lysine molecules per urethane linkage, which, along with the large surface-to-volume ratio of the electrospun membranes, leads to high e-amino free lysine grafting (29 ± 2 nmol cm−2). The incorporation of AGE oligomers significantly reduced the nonspecific protein adsorption, while further modification with lysine led to a more pronounced decrease (25% for BSA, 35% for fibrinogen, and 30% for PNP proteins, with respect to PCU membranes). The lysine-modified matrices presented increased plasminogen adsorption capacity and in vitro clot lysis ability after incubation in pooled normal human plasma and tissue plasminogen activator, confirming the plasminogen adsorption selectivity and thus improving the hemocompatibility behavior of these matrices. Therefore, the obtained electrospun membranes are promising coatings for biomedical devices with fibrinolytic activity. In this work, we employed Carbothane® electrospun matrices (PCU) for lysine surface modification, using oligomers obtained from allyl glycidyl ether (AGE) reaction as spacers. The incorporation of AGE oligomers significantly reduced the nonspecific protein adsorption, while further modification with lysine led to a more pronounced decrease. The lysine-modified matrices presented increased plasminogen adsorption capacity and in vitro clot lysis ability, confirming the plasminogen adsorption selectivity and thus improving the hemocompatibility behavior of these matrices.

A set of four magnitude Ml ≥ 3.0 earthquakes including the magnitude Ml = 3.7 mainshock of the seismic sequence hitting the Lake Constance, Southern Germany, area in July–August 2019 was studied by means of bulletin and waveform data collected from 86 seismic stations of the Central Europe-Alpine region. The first single-event locations obtained using a uniform 1-D velocity model, and both fixed and free depths, showed residuals of the order of up ± 2.0 s, systematically affecting stations located in different areas of the study region. Namely, German stations to the northeast of the epicenters and French stations to the west exhibit negative residuals, while Italian stations located to the southeast are characterized by similarly large positive residuals. As a consequence, the epicentral coordinates were affected by a significant bias of the order of 4–5 km to the NNE. The locations were repeated applying a method that uses different velocity models for three groups of stations situated in different geological environments, obtaining more accurate locations. Moreover, the application of two methods of relative locations and joint hypocentral determination, without improving the absolute location of the master event, has shown that the sources of the four considered events are separated by distances of the order of one km both in horizontal coordinates and in depths. A particular attention has been paid to the geographical positions of the seismic stations used in the locations and their relationship with the known crustal features, such as the Moho depth and velocity anomalies in the studied region. Significant correlations between the observed travel time residuals and the crustal structure were obtained.

This study analyzes the influence of livelihood assets on Ugandan farmers’ decisions to control Banana Xanthomonas Wilt (BXW), a disease that has threatened banana production and the livelihoods of Ugandan farmers since 2001. The BXW control strategy is based on the simultaneous implementation of four cultural practices: de-budding, infected plant removal, disinfecting tools, and using clean planting materials. The Sustainable Rural Livelihood (SRL) framework represents a very useful theoretical architecture for examining the interplay between livelihood systems of rural Ugandan households and the external context. Empirically, this study applies a double-hurdle model with the base assumption that the two adoption decision processes (whether to adopt and the intensity of adoption of the cultural practices) are separate. Results indicate that the vulnerability context and the human, social, natural, and physical capitals are the factors that drive farmers to adopt the identified strategy. Farmers’ decisions about the extent of adoption are instead negatively influenced by natural capital and positively associated with social capital. These findings highlight the importance of supporting the improvement of livelihood assets to enable tailored support to farmers. It is particularly important to support the social and natural capitals that facilitate information exchange and provide critical resources for the adoption of the BXW control strategy.

The aim of the present study was to evaluate the inter- and intra-rater reliability of the PERFECT scheme assessed by uni- and bidigital vaginal palpation in young nulligravid women. Forty healthy women [median age 22 (19–34) years] were evaluated by unidigital vaginal palpation by both Examiners A and C, while the other 40 participants [median age 23.5 (19–35) years] were assessed by Examiners B and C by bidigital vaginal palpation. Inter- and intra-rater reliability of all items of the PERFECT scheme were evaluated: P = power (Modified Oxford Scale); E = endurance; R = repetitions; F = fast contractions. Cohenʼs linear weighted kappa (κw) was used to assess the reliability of the power, while the intraclass correlation coefficient (ICC) was applied for the other items. A priori sample size calculation found that 40 participants would be adequate. Inter-rater reliability of unidigital palpation was considered fair for power (κw = 0.34) and poor for other items (ICC

The global number of megacities is projected to increase from 33 to 43 by 2030. Megacities are critical for the world’s economy; however, their resource management is particularly challenging. The increase of energy demand, in parallel to population growth and climate change, requires urgent investment in sustainable energies. We examine the megacities of Bogotá, Los Angeles, and Jakarta and reveal that the potential geothermal resource base is enough to cover the residential electricity demand by 1.14, 4.25, 1.84 times, respectively. Geothermal energy, a clean baseload resource independent from weather conditions, could significantly contribute to energy needs, improved air quality, and the decarbonization of the world’s megacities. We conclude that it is critical that governments and public are educated about the benefits of geothermal. Moreover, those energy policies coupled with investment in research and development are needed to ensure geothermal is successfully integrated into the future energy mix.

An empirical approach for the analysis of treatment effect at various quantiles in the case of multiple treatment conditions is here proposed. Outcome changes under multiple treatment conditions are computed using (a) inverse propensity score weights and (b) unconditional outcome distribution within each group. Through (a) and (b), the standard double robust estimator is extended to evaluate treatment effect not only on average but also in the tails (quantiles). A Monte Carlo study designed to examine and assess the performance of the proposed approach and two empirical applications conclude the analysis.

Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability. Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA expression in MM patients correlates with shorter survival and even increases with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we investigated the post-transcriptional regulation. We identified miR-22-3p as effective negative regulator of LIG3 in MM. Enforced expression of miR-22 in MM cells downregulated LIG3 protein, which in turn increased DNA damage inhibiting in vitro and in vivo cell growth. Taken together, our findings demonstrate that myeloma cells are addicted to LIG3, which can be effectively inhibited by miR-22, promoting a novel axis of genome stability regulation.

Purpose The knee stiffness acquired following an Anterior Cruciate Ligament (ACL) injury might affect clinical knee tests, i.e., the pivot-shift maneuver. In contrast, the motor effects of spinal anesthesia could favor the identification of rotatory knee deficiencies prior to ACL reconstruction. Hence, we hypothesized that the intra-operative pivot-shift maneuver under spinal anesthesia generates more acceleration in the lateral tibial plateau of patients with an injured ACL than without. Methods Seventy patients with unilateral and acute ACL rupture (62 men and 8 women, IKDC of 55.1 ± 13.8 pts) were assessed using the pivot-shift maneuver before and after receiving spinal anesthesia. A triaxial accelerometer was attached to the skin between Gerdys’ tubercle and the anterior tuberosity to measure the subluxation and reduction phases. Mixed ANOVA and multiple comparisons were performed considering the anesthesia and leg as factors (alpha = 5%). Results We found a higher acceleration in the injured leg measured under anesthesia compared to without anesthesia (5.12 ± 1.56 m.s− 2 vs. 2.73 ± 1.19 m.s− 2, p − 2 vs. 3.45 ± 1.35 m.s− 2, p p Conclusions The pivot-shift maneuver performed under anesthesia identifies better rotatory instability than without anesthesia because testing the pivot-shift without anesthesia underestimates the rotatory subluxation of the knee by an increased knee stiffness. Thus, testing under anesthesia provides a unique opportunity to determine the rotational instability prior to ACL reconstruction.

The identification of the primary products and the determination of their branching ratios as a function of translational energy (temperature) for multi-channel elementary (bimolecular) reactions of importance in combustion flames and plasma-assisted combustion still represent a challenge for traditional kinetics experiments. On the other hand, this kind of information is central for the detailed modeling of combustion/plasma systems. In this short review, the significant contribution provided in this area by the crossed molecular beam (CMB) scattering method with “universal” mass-spectrometric detection and time-of-flight analysis is illustrated. In particular, we describe the basics of the CMB technique empowered with “soft” electron-impact ionization as recently implemented in our laboratory, and report on its application to the study of the multi-channel elementary reactions of ground state atomic oxygen, O(3P), with unsaturated hydrocarbons containing two carbon atoms (acetylene and ethylene), three carbon atoms (propyne, propene, and allene), and also four carbon atoms (1-butene, 1,2-butadiene, and 1,3-butadiene), which are of paramount interest in combustion flames and plasma-assisted combustion of hydrocarbons. These studies are usually complemented in a synergistic manner by high-level electronic structure calculations of the underlying potential energy surfaces and related statistical (and dynamical when feasible) calculations of product branching ratios. The complementarity to kinetics studies and the implications of the dynamics results for the modeling of combustion/plasma chemistry will be commented on.

Hidradenitis suppurativa/acne inversa (HS) is one of the most debilitating inflammatory chronic skin diseases and it heavily impairs the emotional and relational life of the patients. Despite its clinical and epidemiological relevance, its psychological correlates are still largely unexplored. The aim of the present study was to investigate the psychological and emotional impact of HS, with a specific focus on psychiatric symptoms, particularly depression, suicidal ideation, self-esteem, anger, and some personality traits. Thirty eight patients diagnosed with HS (HS Group) were compared with a control group of 28 outpatients diagnosed with nevi (N Group) and assessed with psychometric questionnaires (GHQ-28, STAXI-2, BDI-II, BHS, RSES, EF Questionnaire, and I-R Questionnaire). Results showed significant differences between the two groups, with more psychiatric symptoms, lower self-esteem, and higher levels of state anger and of emotional fragility in HS patients. These findings suggest the evidence of a significant psychiatric comorbidity in HS and of a strong emotional impact of the disease.

Runoff is expected to change due to climate and land use change. Because it constitutes a large component of the terrestrial water budget, we need to develop new policies for managing regional water resources. To do so, we must first attribute changes in the natural flow regime to either climate or land use change. In this context, the Budyko’s curve has previously been adopted to separate the impacts of climate and land use change on runoff by using long term hydrological variables. In this study, a framework based on Fu’s equation (which describes Budyko’s curve) is used to separate the impacts of climate and land use change on annual runoff distributions. Specifically, this framework is based on a recently developed method to obtain annual runoff probability density function (pdf) in seasonally dry basins—such as those in Mediterranean regions—from climate statistics and Fu’s equation parameter ω. The effect of climate change is captured through variations in the first order statistics of annual rainfall and potential evapotranspiration, while land use change is represented by changes in Fu’s equation parameter ω. The effects of these two drivers (i.e., climate and land use change) are analyzed by reconstructing the annual runoff pdfs for the current period and for likely future scenarios, based on predictions from global circulation models and urbanization trajectories. The results show that climate change can lead to a strong reduction in mean annual runoff, a shift of the runoff pdf toward lower values, and a decrease in its variance. Concurrent changes in climate and land use almost always result in a reduction in the mean annual runoff, due to the greater impact of climate change on the runoff pdf.

The half-life of $^{212}$Po was measured with the highest up-to-date accuracy as $T_{1/2}=295.1(4)$ ns by using thorium-loaded liquid scintillator., Comment: 28 pages, 13 figures, 4 tables