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Enterprises face significant growth and survival challenges in highly competitive markets. Many companies fail to meet their tax obligations, which deprives society of essential resources and often results in tax penalties. This article examines whether companies that receive tax fines for evasion have a longer or shorter life expectancy compared to those that consistently comply with tax regulations. To analyze survival rates, the Kaplan–Meier estimator and Cox regression model were applied, considering factors such company size, sector, location, and tax evasion fines. The study included data from 11,297 firms established in 2017, in Rio Grande do Sul, Brazil. The findings indicate that companies fined for tax evasion had a higher survival rate (69%) compared to those without fines (38%) by 2023. This suggests that fines might serve as a corrective measure, helping companies realign and improve their chances of survival. Additionally, the study shows that medium-sized enterprises face significant challenges, possibly due to exceeding the limits of a simplified tax regime. This study highlights the importance of continued research across different regions and countries to validate these findings and enhance tax administration strategies.

The impact of COVID-19 on the economy was devastating. Small businesses typically have few resources to fight against such adversity. Many businesses remained closed for some time during the pandemic period, resulting in significant consequences for people in terms of jobs, income and life. The objective of this research is to identify the factors that contributed to increasing company failures during the pandemic. Furthermore, this study aims to verify whether the size of the companies, the sectors of economic activity in which they operate and their geographic location influence enterprise failure. This article analyzes the survival of 8931 small businesses from 2017 to 2023, in Rio Grande do Sul, Brazil. The study applied a survival analysis using the Kaplan–Meier procedure, complemented with the Cox procedure, to determine the effects of the size of companies, sector activity and location on the survival time. The results indicate that survival is much higher in small companies with large revenues that are located in the Campaign and West Frontier regions, as well as in the Northeast, North, Production, South, Taquari, and Rio Pardo Valleys regions, whereas the survival rates were extremely lower in the commercial sector and in financial intermediation activities. In the second analysis restricted to the commerce sector, the data highlighted the retail activities, accommodation and food activities sectors as the most affected in terms of overall survival. The results indicated that the survival of small business remained relatively strong during the COVID-19 pandemic, signaling the pertinent support from the government. The smallest business with revenues under USD 15,576 (BRL 81,000) per year were the most affected, with only 39% survival after 7 years. Some activities and some regions suffered more than others, emphasizing the need for special attention from authorities in future catastrophes.

To further extend the structure-activity relationships (SARs) of 5-aminopyrazoles (5APs) and identify novel compounds able to interfere with inflammation, oxidative stress, and tumorigenesis, 5APs 1–4 have been designed and prepared. Some chemical modifications have been inserted on cathecol function or in aminopyrazole central core; in detail: (i) smaller, bigger, and more lipophilic substituents were introduced in meta and para positions of catechol portion (5APs 1); (ii) a methyl group was inserted on C3 of the pyrazole scaffold (5APs 2); (iii) a more flexible alkyl chain was inserted on N1 position (5APs 3); (iv) the acylhydrazonic linker was moved from position 4 to position 3 of the pyrazole scaffold (5APs 4). All new derivatives 1–4 have been tested for radical scavenging (DPPH assay), anti-aggregating/antioxidant (in human platelets) and cell growth inhibitory activity (MTT assay) properties. In addition, in silico pharmacokinetics, drug-likeness properties, and toxicity have been calculated. 5APs 1 emerged to be promising anti-proliferative agents, able to suppress the growth of specific cancer cell lines. Furthermore, derivatives 3 remarkably inhibited ROS production in platelets and 5APs 4 showed interesting in vitro radical scavenging properties. Overall, the collected results further confirm the pharmaceutical potentials of this class of compounds and support future studies for the development of novel anti-proliferative and antioxidant agents.

We recall the classical tree-cotree technique in magnetostatics. (1) We extend it in the frame of high-order finite elements in general domains. (2) We focus on its connection with the question of the invertibility of the final algebraic system arising from a high-order edge finite element discretization of the magnetostatic problem formulated in terms of the magnetic vector potential. With the same purpose of invertibility, we analyse another classically used condition, the Coulomb gauge. (3) We conclude by underlying that the two gauges can be naturally considered in a high order framework without any restriction on the topology of the domain.

Injury in sports is an occurrence that prevents athletes from participating in training and competitions and has an incidence of 8.1 injuries/1000 h of practice. This translates into a cost and also into danger, especially if the event is repeated, for the health of the athlete; the injury certainly has a multifactorial causality. On the other hand, having instruments that can represent an alarm could be helpful for those involved in sports science. We used a specifically designed instrument, presented in a previous work, which shows excellent reliability and repeatability in measuring the strength of the knee flexors and extensors to test 107 players belonging to three different teams playing in the Italian Serie A. We took three measurements, beginning of the season, mid-season, and close to the end of the season. This retrospective study on 107 professional soccer players demonstrates that isometric force-related parameters of the knee extensors and flexors are associated with the risk of injury to lower limbs. Logistic regression evidenced a significant correlation between the parameter indicating the imbalance of the force between the flexors of the two limbs (p≤0.05, OR = 1.089) and the occurrence of injuries. Survival analyses (p≤0.001) evidenced a correlation between the population survival time and the injury incidence. We demonstrated that the analysis of the strength imbalance is correlated with injury occurrence, but it is well known that sports injuries are a multifactorial event; so, they cannot be predicted by only one parameter. However, the method proposed in this paper could represent a useful tool for sport scientists.

This paper proposes a novel method to reliably calibrate a pair of sensorized insoles utilizing an array of capacitive tactile pixels (taxels). A new calibration setup is introduced that is scalable and suitable for multiple kinds of wearable sensors and a procedure for the simultaneous calibration of each of the sensors in the insoles is presented. The calibration relies on a two-step optimization algorithm that, firstly, enables determination of a relevant set of mathematical models based on the instantaneous measurement of the taxels alone, and, then, expands these models to include the relevant portion of the time history of the system. By comparing the resulting models with our previous work on the same hardware, we demonstrate the effectiveness of the novel method both in terms of increased ability to cope with the non-linear characteristics of the sensors and increased pressure ranges achieved during the experiments performed.

Gastrointestinal nematodes (GINs) is a limiting health factor for dairy goats, and the integration of the diet with fodder containing condensed tannins (CT) is becoming increasingly important to control GINs. To preliminary evaluate their potential role as part of GIN control in goat breeding, the in vitro anthelmintic efficacy of the CTs of Silvafeed BYPRO (SBP), Silvafeed Q powder (SQ), and sainfoin hay (SH) was evaluated, and the untargeted metabolomics profiling of the selected formulations was performed. CTs were extracted in water and in ethanol, their concentration was determined, and their chemical characterization was conducted using High-Performance Liquid Chromatography (HPLC) coupled to High-Resolution Mass Spectrometry (HRMS) platform. The in vitro anthelmintic activity of the extracts was evaluated using the Eggs Hatch Test (EHT) and the Larval Migration Inhibition Test (LMIT) using different extract concentrations (150, 300, 600, and 1200 μg/mL). The metabolomic profile of the ethanol extract showed a high number of flavonoids, while the water extract showed higher levels of hydrolysable tannins. The ethanol extracts were effective on both eggs hatching and larvae migration at low concentrations (150 μg/mL) for the three analyzed samples, while the water extracts showed more varied results: SH showed the greatest ovicidal efficacy (concentration 150 μg/mL, %IH = 40.9), while SBP and SQ were more effective against the larvae migration (concentration 600 μg/mL, %LMI = 69.7% and 88%), respectively. The integration of CT-rich fodder into the diet may be considered for the control of GIN infection in goats.

Background: Assessing lower limb strength in the field is problematic, as the “gold standard assessment” with isokinetic strength is cumbersome, and the device is costly and not transportable and keeps the angle of the hip at around 90°. Methods: We evaluated isometric muscle strength in a standing position with the help of an exoskeleton that holds the subject and makes the test easily repeatable. Results: The optimal device angles for hip and knee were, respectively, 20° and 80° for flexor tests and 30° and 40° for extensor tests. Test–retest reliability was very high for the right knee extensor (ICC 0.96–0.98), left knee extensor (ICC 0.96–0.97), right knee flexor (ICC 0.91–0.96), and left knee flexor (ICC 0.96–0.97). Furthermore, the typical error in percent (T.E.%) ranged from 2.50 to 5.50%, and the change in the mean in percent ranged from 0.84 to 7.72%, making it possible to determine even a slight variation in force. Conclusions: this new method could represent a valid alternative for assessing strength, due to the high reliability and the favorable joint position, particularly in football.

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence.

The current nutrient recommendations focus on pigs fed ad libitum up to 140 kg in body weight (BW). It remains unclear whether this applies to pigs weighing above 140 kg in BW under different rearing conditions. This study aimed to estimate protein (Pd) and lipid (Ld) depositions and the metabolizable energy (ME), standardized ileal digestible lysine (SID lysine) requirement and partitioning in 224 C21 Goland pigs (90–200 kg in BW). The control pigs (C) received diets limiting ME up to 170 kg in slaughter weight (SW) at 9 months of age (SA); older (OA) pigs had restricted diets limiting ME and SID lysine up to 170 kg in SW at >9 months SA; younger (YA) pigs were fed nonlimited amounts of ME and SID lysine up to 170 kg in SW at 170 kg in SW. The estimated MEm averaged 1.03 MJ/kg0.60. An 11% increase in MEm was observed in OA pigs compared to the controls. Energy restriction had negligible effects on the estimated MEm. The marginal efficiency of SID lysine utilization for Pd averaged 0.725, corresponding to a SID lysine requirement of 9.8 g/100 g Pd.

This study was carried out to compare bunch weight determination in relation to the source-sink balance in a selection of 12 Cavendish banana cultivars. Fruit number and individual fruit weight are the main bunch weight components. The fruit number depended on the growth potential during floral induction, which we estimated according to the active leaf area at floral induction (ALAfi). We studied fruit weight determination by measuring the source-sink balance during bunch growth, carbohydrate reserves and bunch-sucker biomass partitioning. Throughout the experiment, we monitored the global radiation (Rg), which exhibited seasonal variations. We noted a source variation from the first to the second cycle during bunch growth because of a decrease in the Rg and active leaf area. Our results showed significant differences between Cavendish cultivars regarding bunch weight, fruit number and susceptibility to source variations. There was an overall positive linear relation between ALAfi and fruit number, but the ALAfi/fruit number ratio varied between cultivars. We also found that the bunch weight was mainly determined by the fruit number rather than the fruit weight when the source was not limited. Finally, we assessed the cultivar susceptibility to source decreases, thereby revealing some cultivars of interest for agroecological cropping systems.

The weaning period is a stressful period for the gastrointestinal tract (GIT) of piglets. This work aims to evaluate the effects of the commercial polyphenol-based product GreenFIS® on: (1) GIT health and performance of 60 weaned piglets; (2) digestibility in 18 growing pigs. Three diets were tested: a control diet (C), C plus 2.5 g of GreenFIS®/kg C (T1), and C plus 5 g of GreenFIS®/kg C (T2). After the post-weaning trial three piglets per treatment were sacrificed for the GIT histological analysis. No differences between diets were recorded in terms of growing performance or clinical and biochemical blood parameters. The GIT histological analysis did not show any indicators of inflammation for any of the groups. The feces of the two extreme treatments (C and T2) were analyzed for microbiota, revealing a greater presence of the Ruminococcus bromii group, positively associated with starch degradation, in T2. In the second experiment six pigs per treatment were randomly chosen for the digestibility study. The inclusion of GreenFIS® at both levels led to a higher fecal digestibility of gross energy (86.2%, 89.1%, and 89.5%, for C, T1, and T2, respectively) and crude protein (87.0%, 90.2%, and 90.0%). In conclusion, the additive did not improve, in the excellent experimental hygienic conditions, the gut health, but it did increase nutrient digestibility.

The effect of whole linseeds or hemp seeds on milk production, energy and nitrogen balance, and methane emission was studied in 12 Alpine goats using respiration chambers. Diets tested were a control diet (C) and two diets supplemented with whole linseeds (L) or hemp seeds (H) at 9.3% on a dry matter (DM) basis. DM intake was similar among treatments, whereas DM and organic matter digestibility were lower for L compared to C. Milk yield (2.30 kg/d on average) and rumen fermentation profile were not affected by treatments. Treatment also did not affect the milk composition, with the exception of fat, which was higher in H and L compared to C (4.21, 3.94, and 3.20%, respectively). Oilseed supplementation caused a reduction in the concentration of de novo fatty acids (FA) (41.1, 48.8, and 64.1% of FA, for L, H, and C, respectively). Moreover, L and H diets reduced the sum of saturated FA, and increased monounsaturated FA, whereas only the L diet increased the concentration of polyunsaturated FA. Regarding methane production, and nitrogen and energy balances, no differences were registered among the diets. Our research indicates that including whole linseeds and hemp seeds in the dairy goat diet is an effective strategy for increasing milk fat content and positively modifying the milk FA composition, without a change in nitrogen and energy balances, but also without a reduction in enteric methane emission.

(1) Background: different previously synthesized pyrazoles and imidazo-pyrazoles showed interesting anti-angiogenic action, being able to interfere with ERK1/2, AKT and p38MAPK phosphorylation in different manners and with different potency; (2) Methods: here, a new small compound library, endowed with the same differently decorated chemical scaffolds, has been synthetized to obtain new agents able to inhibit different pathways involved in inflammation, cancer and human platelet aggregation. (3) Results: most of the new synthesized derivatives resulted able to block ROS production, platelet aggregation and p38MAPK phosphorylation both in platelets and Human Umbilical Vein Endothelial cells (HUVEC). This paves the way for the development of new agents with anti-angiogenic activity.

Alternative treatment strategies are necessary to reduce the severity of glaucoma, a group of eye conditions that progressively damage the optic nerve and impair vision. The aim of this review is to gain insight into potentially exploitable molecular mechanisms to slow down the death of retinal ganglion cells (RGCs), a fundamental element in the pathophysiology of all forms of glaucoma, and to stimulate adult optic nerve repair. For this purpose, we focus our analysis on both visible and far-red to near-infrared light photobiomodulation (PBM) as phototherapeutic agents, which were recently proposed in RGCs, and on the nerve lamina region neural progenitor cell (ONLR-NPC) niche. Both are suggested as potential strategies in glaucoma neuroprotection. We discuss the impact of beneficial molecular effects of PBM on both mitochondrial derangement and the alteration of ion fluxes that are considered important causes of RGC damage, as well as on the stimulation of progenitor cells. We suggest these are the most promising approaches to prevent excessive neuronal cell loss. We describe the experimental evidence supporting the validity of PBM therapy which, despite being a safe, non-invasive, inexpensive, and easy to administer procedure, has not yet been fully explored in the clinical practice of glaucoma treatment.

This paper contributes towards the development of motion tracking algorithms for time-critical applications, proposing an infrastructure for dynamically solving the inverse kinematics of highly articulate systems such as humans. The method presented is model-based, it makes use of velocity correction and differential kinematics integration in order to compute the system configuration. The convergence of the model towards the measurements is proved using Lyapunov analysis. An experimental scenario, where the motion of a human subject is tracked in static and dynamic configurations, is used to validate the inverse kinematics method performance on human and humanoid models. Moreover, the method is tested on a human-humanoid retargeting scenario, verifying the usability of the computed solution in real-time robotics applications. Our approach is evaluated both in terms of accuracy and computational load, and compared to iterative optimization algorithms.

Undigested neutral detergent fibre (uNDF) is commonly used as an internal marker for the estimation of diet digestibility in ruminants. This work aimed to verify (i) whether the in vivo method with uNDF could be used to evaluate diet digestibility in growing pigs, and (ii) whether pre-treating the samples with neutral detergent solution (NDS) and α-amylase improves the accuracy of the estimates. Samples from a previously published work of two diets with known in vivo digestibility values estimated by the total faecal collection method and 16 individual samples of faeces were used. For each sample, four Ankom F57 bags were weighed. Before the incubation, two F57 bags were pre-treated with NDS and α-amylase. All the samples were incubated for 240 h in the Ankom DaisyII incubator and then analysed for their uNDF contents. Dry matter, organic matter, and neutral detergent fibre digestibilities were estimated using the uNDF contents, and the results were compared with those of the former study. The digestibility values obtained using the uNDF method with pre-treatment were not statistically different from those determined with the total faecal collection. On the contrary, the uNDF method without the pre-treatment could not satisfactorily predict the digestibilities of pig diets.

The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed as potential drugs, this review is focused on molecules characterized by a urea function directly linked to the pyrazole nucleus in a different position. In the last 20 years, the interest of numerous researchers has been especially attracted by pyrazolyl-ureas showing a wide spectrum of biological activities, ranging from the antipathogenic activities (bacteria, plasmodium, toxoplasma, and others) to the anticarcinogenic activities. In particular, in the anticancer field, pyrazolyl-ureas have been shown to interact at the intracellular level on many pathways, in particular on different kinases such as Src, p38-MAPK, TrKa, and others. In addition, some of them evidenced an antiangiogenic potential that deserves to be explored. This review therefore summarizes all these biological data (from 2000 to date), including patented compounds.

Alzheimer’s disease is the most common type of dementia, affecting millions of people worldwide. One of its main consequences is memory loss, which is related to downstream effectors of cyclic adenosine monophosphate (cAMP). A well-established strategy to avoid cAMP degradation is the inhibition of phosphodiesterase (PDE). In recent years, GEBR-32a has been shown to possess selective inhibitory properties against PDE type 4 family members, resulting in an improvement in spatial memory processes without the typical side effects that are usually correlated with this mechanism of action. In this work, we performed the HPLC chiral resolution and absolute configuration assignment of GEBR-32a. We developed an efficient analytical and semipreparative chromatographic method exploiting an amylose-based stationary phase, we studied the chiroptical properties of both enantiomers and we assigned their absolute configuration by 1H-NMR (nuclear magnetic resonance). Lastly, we measured the IC50 values of both enantiomers against both the PDE4D catalytic domain and the long PDE4D3 isoform. Results strongly support the notion that GEBR-32a inhibits the PDE4D enzyme by interacting with both the catalytic pocket and the regulatory domains.

Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure−activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets.

In view of better environmental sustainability, livestock diets must not exceed protein requirements, as often happens with lactating goats reared in semi-intensive systems. The aim of this experiment was to verify in real-breeding conditions the influence of two diets with different protein contents (% crude protein (CP) on dry matter (DM)): 16.0 (high-protein diet; HP) vs 12.2 (low-protein diet; LP) on milk production in dairy goats. The diets differed only in the replacement—in the LP diet—of 250 g soybean meal with 250 g maize grain meal. Twenty-three Alpine goats were divided into two groups and used in a cross-over feeding trial for 2 months. Animals were weighed at the beginning of each month of the trial, and feed intake and milk yield and composition were recorded weekly. HP and LP did not differ statistically for milk yield and composition (3.32 vs 3.42 kg milk/d, 3.21% vs 3.27% fat, 3.31% vs 3.27% protein for HP and LP, respectively), but the HP diet determined a higher milk urea content (51.2 vs 36.6 mg/dL, p < 0.001) and a worse efficiency of nitrogen utilization (28.0% vs 37.2%). In conclusion, the LP diet resulted in a reduction of urinary nitrogen excretion by 28% and of the feed cost by about 10%.

Wearable sensors are gaining in popularity because they enable outdoor experimental monitoring. This paper presents a cost-effective sensorised insole based on a mesh of tactile capacitive sensors. Each sensor’s spatial resolution is about 4 taxels/cm 2 in order to have an accurate reconstruction of the contact pressure distribution. As a consequence, the insole provides information such as contact forces, moments, and centre of pressure. To retrieve this information, a calibration technique that fuses measurements from a vacuum chamber and shoes equipped with force/torque sensors is proposed. The validation analysis shows that the best performance achieved a root mean square error (RMSE) of about 7 N for the contact forces and 2 N m for the contact moments when using the force/torque shoe data as ground truth. Thus, the insole may be an alternative to force/torque sensors for certain applications, with a considerably more cost-effective and less invasive hardware.

Cow faeces have been investigated as alternative inoculum to replace rumen fluid to determine neutral detergent fibre (NDF) digestibility (NDFD). Aims of this study were to estimate: (1) the NDFD (48 h) of feed ingredients using a rumen inoculum in comparison with faecal inocula from cows fed diets with different forage basis; (2) the undigestible NDF (uNDF) at 240 and 360 h with ruminal fluid and faecal inocula from lactating cows fed two different diets. At 48 h incubation, the NDFD was affected both by feed and type of inoculum (p < 0.01) and by their interaction (p = 0.03). Overall, the mean NDFD was higher for rumen inoculum than for faecal inocula (585 vs. 389 g/kg NDF, p < 0.05), and faecal inoculum obtained from cows fed hay-based diets gave lower NDFD than those from cows fed maize silage (367 vs. 440 g/kg, p < 0.05). At long incubation times, the average uNDF was affected by substrate, inoculum and incubation time (p < 0.01), but not by their interactions. For each inoculum, significantly lower values were obtained at 360 than at 240 h. Regressions between uNDF with rumen and with the tested faecal inocula resulted in r2 ≥ 0.98. Despite the differences at 48 h, the uNDF showed that faecal inoculum could replace rumen fluid at longer incubation times.

Nowadays, the incidence of neurodegenerative diseases is increasing, and these disorders will become one of the main challenges for medicine and public health in future years. Particularly, memory loss characterizes many neurodegenerative pathologies, and it is often related to low levels of cyclic adenosine monophosphate (cAMP). [...]

The paper presents a stochastic methodology for the simultaneous floating-base estimation of the human whole-body kinematics and dynamics (i.e., joint torques, internal and external forces). The paper builds upon our former work where a fixed-base formulation had been developed for the human estimation problem. The presented approach is validated by presenting experimental results of a health subject equipped with a wearable motion tracking system and a pair of shoes sensorized with force/torque sensors while performing different motion tasks, e.g., walking on a treadmill. The results show that joint torque estimates obtained by using floating-base and fixed-base approaches match satisfactorily, thus validating the present approach.