Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochar and Rhizobacteria Amendments Improve Several Soil Properties and Bacterial Diversity

In the current context, there is a growing interest in reducing the use of chemical fertilizers and pesticides to promote ecological agriculture. The use of biochar and plant growth-promoting rhizobacteria (PGPR) is an environmentally friendly alternative that can improve soil conditions and increase ecosystem productivity. However, the effects of biochar and PGPR amendments on forest plantations are not well known. The aim of this study is to investigate the effects of biochar and PGPR applications on soil nutrients and bacterial community. To achieve this goal, we applied amendments of (i) biochar at 20 t hm−2, (ii) PGPR at 5 × 1010 CFU mL−1, and (iii) biochar at 20 t hm−2 + PGPR at 5 × 1010 CFU mL−1 in a eucalyptus seedling plantation in Guangxi, China. Three months after applying the amendments, we collected six soil samples from each treatment and from control plots. From each soil sample, we analyzed several physicochemical properties (pH, electrical conductivity, total N, inorganic N, NO3−-N, NH4+-N, total P, total K, and soil water content), and we determined the bacterial community composition by sequencing the ribosomal 16S rRNA. Results indicated that co-application of biochar and PGPR amendments significantly decreased concentrations of soil total P and NH4+-N, whereas they increased NO3-N, total K, and soil water content. Biochar and PGPR treatments increased the richness and diversity of soil bacteria and the relative abundance of specific bacterial taxa such as Actinobacteria, Gemmatimonadetes, and Cyanobacteria. In general, the microbial composition was similar in the two treatments with PGPR. We also found that soil physicochemical properties had no significant influence on the soil composition of bacterial phyla, but soil NH4+-N was significantly related to the soil community composition of dominant bacterial genus. Thus, our findings suggest that biochar and PGPR amendments could be useful to maintain soil sustainability in eucalyptus plantations.
Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ’s exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics.
A Novel DBS Paradigm for Axial Features in Parkinson's Disease: A Randomized Crossover Study

High‐frequency (130–185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low‐frequency (60–80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a “dual‐frequency” programming paradigm (interleave‐interlink, IL‐IL) to address both axial and appendicular symptoms. In IL‐IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high‐frequency stimulation, HFS) aims to control appendicular symptoms.
Parallels of Resistance between Angiogenesis and Lymphangiogenesis Inhibition in Cancer Therapy

Metastasis is the primary cause of cancer-related mortality. Cancer cells primarily metastasize via blood and lymphatic vessels to colonize lymph nodes and distant organs, leading to worse prognosis. Thus, strategies to limit blood and lymphatic spread of cancer have been a focal point of cancer research for several decades. Resistance to FDA-approved anti-angiogenic therapies designed to limit blood vessel growth has emerged as a significant clinical challenge. However, there are no FDA-approved drugs that target tumor lymphangiogenesis, despite the consequences of metastasis through the lymphatic system. This review highlights several of the key resistance mechanisms to anti-angiogenic therapy and potential challenges facing anti-lymphangiogenic therapy. Blood and lymphatic vessels are more than just conduits for nutrient, fluid, and cancer cell transport. Recent studies have elucidated how these vasculatures often regulate immune responses. Vessels that are abnormal or compromised by tumor cells can lead to immunosuppression. Therapies designed to improve lymphatic vessel function while limiting metastasis may represent a viable approach to enhance immunotherapy and limit cancer progression.
Effectiveness and Costs Associated to Adding Cetuximab or Bevacizumab to Chemotherapy as Initial Treatment in Metastatic Colorectal Cancer: Results from the Observational FABIO Project

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan–Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.
Yield Performance, Laying Behaviour Traits and Egg Quality of Purebred and Hybrid Hens Reared under Outdoor Conditions

Simple Summary Nowadays, the consumer has a choice of table eggs depending on rearing system, egg size, eggshell and yolk colour, produced by a few worldwide hybrid strains. Many countries have a historic poultry tradition, with breeds used for domestic egg production. In Northern Italy, in the Po river plain, a relevant part of the maize production was used also for poultry feeding and many breeds existed in the last centuries. At present, the Veneto region shows an important poultry biodiversity with many breeds, whose egg production traits are not well known. A comparison between purebred and hybrid hens throughout the laying period was carried out in order to study yield performance, laying behavioural traits and egg quality. The knowledge of the variation of these traits is useful for managing the breeding of these genotypes and the offer to the consumers. The local breeds showed differences from hybrid hens both for yield performance and laying behaviour and for both egg size and external and internal quality. Abstract This study compared the yield performance, laying behavioural traits and egg quality of purebred and hybrid hens (from 28 until 44 weeks of age, considering four periods) reared under outdoor conditions. The four genotypes were reared on the same trial station, on four areas (one genotype/area), and under the same environmental conditions from hatching until the end of the trial. Italian dual-purpose purebred (Ermellinata di Rovigo—ER and Robusta maculata—RM) and hybrid (Hy-Line Brown—HB and Hy-Line White 36—HW) hens (flock size: 70 birds/genotype) were allowed outdoors (4 m2/bird, good pasture during the growing period and poor pasture throughout the laying period, according to the season) and indoors (0.20 m2/bird, five birds/individual nest) and fed commercial feed. Significant (p < 0.01) differences among genotypes were found. The hybrids showed a higher laying rate and hen-day edible egg mass, and a lower body weight than the purebreds. Broken and out-of-nest egg% were higher in RM and HW than ER and HB, respectively. Double-yolk egg% was higher in hybrids than in purebreds. The eggshell colour varied among brown eggshell ER, RM, and HB. The ER showed the lowest shape index. With aging, the yolk to albumen ratio linearly increased in all groups, eggshell% changed in ER, HW, RM (cubic) and in HB (linear). The purebreds showed meat spots% higher than blood spots; HW showed the lowest total inclusion%. In conclusion, according to an egg scoring evaluation (egg weight = medium-large size, yolk to albumen ratio = 0.5, total inclusions = none), HW showed a higher quality than HB and RM, and ER was intermediate. The RM hens showed the highest% of defective eggs, especially for overcrowding at nest, HB showed the lowest. Under outdoor conditions the laying behaviour of the purebred hens and the nest management are important factors for the saleable egg rate.
Phenolic Profile, Antioxidant, and Antidiabetic Potential Exerted by Millet Grain Varieties

This study evaluated the potential antioxidant and antidiabetic properties in vitro of four millet grain varieties cultivated in South Korea. The free fractions were tested for their total antioxidant capacity using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays, followed by α-glucosidase, α-amylase, and advanced glycation endproducts (AGEs) formation inhibition assays. The total phenolics, flavonoids, and condensed tannins in the free fractions ranged from 107.8 to 136.4 mg ferulic acid equivalent (FAE)/100 g, 101.3 to 115.8 mg catechin equivalent (CE)/100 g, and 17.65 to 59.54 mg catechin equivalent (CE)/100 g, respectively. Finger Italian millet had the highest total phenolic content (136.4 mg FAE/100 g) and flavonoid content (115.8 mg CE/100 g). Barnyard and finger Italian millet showed the highest DPPH (IC50 = 359.6 µg/mL and 436.25 µg/mL, respectively) and ABTS radical scavenging activity (IC50 = 362.40 µg/mL and 381.65 µg/mL, respectively). Similarly, finger Italian millet also exhibited significantly lower IC50 values for the percentage inhibition of α-glucosidase (18.07 µg/mL) and α-amylase (10.56 µg/mL) as compared with acarbose (IC50 = 59.34 µg/mL and 27.73 µg/mL, respectively) and AGEs formation (33.68 µg/mL) as compared with aminoguanidine (AG) (52.30 µg/mL). All eight phenolic compounds identified in finger Italian millet were flavonoids, with flavanols being the predominant subclass. Taken together, millet flavonoids play important roles in the prevention and management of type 2 diabetes, and hence finger Italian millet has the potential to be developed as a functional food.
NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias

Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab. Although a clear NK activation has been demonstrated for Elotuzumab, the effect of anti-CD38 mAbs on NK system is controversial. As a matter of fact, an initial reduction of NK cells number characterizes Daratumumab therapy, limiting the potential role of this subset on myeloma immunotherapy. In this paper we discuss the role of NK cells along with anti-CD38 therapy and their implication in plasma cell dyscrasias, showing that mechanisms triggered by anti-CD38 mAbs ultimately lead to the activation of the immune system against myeloma cell growth.
Tie-2 Cre-Mediated Deficiency of Extracellular Signal-Regulated Kinase 2 Potentiates Experimental Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension in Neonatal Mice

Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a significant lung morbidity of infants, and disrupted lung angiogenesis is a hallmark of this disease. We observed that extracellular signal-regulated kinases (ERK) 1/2 support angiogenesis in vitro, and hyperoxia activates ERK1/2 in fetal human pulmonary microvascular endothelial cells (HPMECs) and in neonatal murine lungs; however, their role in experimental BPD and PH is unknown. Therefore, we hypothesized that Tie2 Cre-mediated deficiency of ERK2 in the endothelial cells of neonatal murine lungs would potentiate hyperoxia-induced BPD and PH. We initially determined the role of ERK2 in in vitro angiogenesis using fetal HPMECs. To disrupt endothelial ERK2 signaling in the lungs, we decreased ERK2 expression by breeding ERK2flox/flox mice with Tie-Cre mice. One-day-old endothelial ERK2-sufficient (eERK2+/+) or –deficient (eERK2+/−) mice were exposed to normoxia or hyperoxia (FiO2 70%) for 14 d. We then performed lung morphometry, gene and protein expression studies, and echocardiography to determine the extent of inflammation, oxidative stress, and development of lungs and PH. The knockdown of ERK2 in HPMECs decreased in vitro angiogenesis. Hyperoxia increased lung inflammation and oxidative stress, decreased lung angiogenesis and alveolarization, and induced PH in neonatal mice; however, these effects were augmented in the presence of Tie2-Cre mediated endothelial ERK2 deficiency. Therefore, we conclude that endothelial ERK2 signaling is necessary to mitigate hyperoxia-induced experimental BPD and PH in neonatal mice. Our results indicate that endothelial ERK2 is a potential therapeutic target for the management of BPD and PH in infants.
The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response

Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, understanding therapy resistance and the mechanisms of tumor immune evasion is crucial to increase the frequency of patients benefiting from treatment. The PTEN gene is thought to promote immune evasion and is frequently mutated in cancer and melanoma. Another feature of melanoma tumors that may affect the capacity of escaping T-cell recognition is melanoma cell dedifferentiation characterized by decreased expression of the microphtalmia-associated transcription factor (MITF) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of MITF expression using immunostaining and genomic data from a large cohort of metastatic melanoma. We confirmed in our cohort that PTEN alterations promote immune evasion highlighted by decreased frequency of T-cell infiltration in such tumors, resulting in a worse patient survival. More importantly, our results suggest that dedifferentiated PTEN negative melanoma tumors have poor patient outcome, no T-cell infiltration, and transcriptional properties rendering them resistant to targeted- and immuno-therapy.
Inter-Lineage Variation of Lassa Virus Glycoprotein Epitopes: A Challenge to Lassa Virus Vaccine Development

Lassa virus (LASV), which causes considerable morbidity and mortality annually, has a high genetic diversity across West Africa. LASV glycoprotein (GP) expresses this diversity, but most LASV vaccine candidates utilize only the Lineage IV LASV Josiah strain GP antigen as an immunogen and homologous challenge with Lineage IV LASV. In addition to the sequence variation amongst the LASV lineages, these lineages are also distinguished in their presentations. Inter-lineage variations within previously mapped B-cell and T-cell LASV GP epitopes and the breadth of protection in LASV vaccine/challenge studies were examined critically. Multiple alignments of the GP primary sequence of strains from each LASV lineage showed that LASV GP has diverging degrees of amino acid conservation within known epitopes among LASV lineages. Conformational B-cell epitopes spanning different sites in GP subunits were less impacted by LASV diversity. LASV GP diversity should influence the approach used for LASV vaccine design. Expression of LASV GP on viral vectors, especially in its prefusion configuration, has shown potential for protective LASV vaccines that can overcome LASV diversity. Advanced vaccine candidates should demonstrate efficacy against all LASV lineages for evidence of a pan-LASV vaccine.
Clinician Mental Health and Well-Being During Global Healthcare Crises: Evidence Learned From Prior Epidemics for COVID-19 Pandemic.

Novel coronavirus disease 2019 (COVID-19) is sweeping across the globe, having sickened more than 640,000 people and claimed over 30,000 lives in approximately 202 countries at the time of writing with no sign of slowing down (World Health Organization, 2020). Each time a pandemic or an epidemic disease occurs, such as measles, scarlet fever, HIV/AIDS, Ebola, or the flu of 2013, healthcare professionals are on the front lines, battling diseases and caring for sick and dying patients, even while knowingly putting themselves at risk (Borghese, Di Donato, Ruotolo, & Fiegender, 2020).
The Use of Electrospun Organic and Carbon Nanofibers in Bone Regeneration

There has been an increasing amount of research on regenerative medicine for the treatment of bone defects. Scaffolds are needed for the formation of new bone, and various scaffolding materials have been evaluated for bone regeneration. Materials with pores that allow cells to differentiate into osteocytes are preferred in scaffolds for bone regeneration, and porous materials and fibers are well suited for this application. Electrospinning is an effective method for producing a nanosized fiber by applying a high voltage to the needle tip containing a polymer solution. The use of electrospun nanofibers is being studied in the medical field, and its use as a scaffold for bone regeneration therapy has become a topic of growing interest. In this review, we will introduce the potential use of electrospun nanofiber as a scaffold for bone regenerative medicine with a focus on carbon nanofibers produced by the electrospinning method.
Grip Stabilization through Independent Finger Tactile Feedback Control

Grip force control during robotic in-hand manipulation is usually modeled as a monolithic task, where complex controllers consider the placement of all fingers and the contact states between each finger and the gripped object in order to compute the necessary forces to be applied by each finger. Such approaches normally rely on object and contact models and do not generalize well to novel manipulation tasks. Here, we propose a modular grip stabilization method based on a proposition that explains how humans achieve grasp stability. In this biomimetic approach, independent tactile grip stabilization controllers ensure that slip does not occur locally at the engaged robot fingers. Local slip is predicted from the tactile signals of each fingertip sensor i.e., BioTac and BioTac SP by Syntouch. We show that stable grasps emerge without any form of central communication when such independent controllers are engaged in the control of multi-digit robotic hands. The resulting grasps are resistant to external perturbations while ensuring stable grips on a wide variety of objects.
Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects

As one of the most frequent skeletal anomalies, developmental dysplasia of the hip (DDH) is characterized by a considerable range of pathology, from minor laxity of ligaments in the hip joint to complete luxation. Multifactorial etiology, of which the candidate genes have been studied the most, poses a challenge in understanding this disorder. Candidate gene association studies (CGASs) along with genome-wide association studies (GWASs) and genome-wide linkage analyses (GWLAs) have found numerous genes and loci with susceptible DDH association. Studies put major importance on candidate genes associated with the formation of connective tissue (COL1A1), osteogenesis (PAPPA2, GDF5), chondrogenesis (UQCC1, ASPN) and cell growth, proliferation and differentiation (TGFB1). Recent studies show that epigenetic factors, such as DNA methylation affect gene expression and therefore could play an important role in DDH pathogenesis. This paper reviews all existing risk factors affecting DDH incidence, along with candidate genes associated with genetic or epigenetic etiology of DDH in various studies.
For Peer Review Fluvastatin does not exhibit an add -on effect on pegylated - interferon/ribavirin/telaprevir therapy for HCV genotype 1b-infected chronic hepatitis C

Complete List of Authors: Atsukawa, Masanori; Nippon Medical School Chiba Hokusoh Hospital, Division of Gastroenterology Tsubota, Akihito; Jikei University, Clinical Medicine and Research Shimada, Noritomo; Shinmatsudo Central General Hospital, Gastroenterology and Hepatology Kondo, Chisa; Nippon Medical School Chiba Hokusoh Hospital, Division of Gastroenterology Itokawa, Norio; Nippon Medical School Chiba Hokusoh Hospital, Division of Gastroenterology Nakagawa, Ai; Nippon Medical School Chiba Hokusoh Hospital, Division of Gastroenterology Fukuda, Takeshi; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology Matsushita, Yoko; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology Narahara, Yoshiyuki; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology Osada, Yuji; Hakujikai Memorial Hospital, Division of Gastroenterology Yamaguchi, Hiroki; Nippon Medical School, Department of Internal Medicine, Division of Hematology Nakatsuka, Katsuhisa; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology Iwakiri, Katsuhiko; Nippon Medical School Chiba Hokusoh Hospital, Division of Gastroenterology Kawamoto, Chiaki; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology Sakamoto, Choitsu; Nippon Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology