Tailoring the efficiency of porphyrin molecular frameworks for the electroactivation of molecular N2.

The combination of compositional versatility and topological diversity for the integration of electroactive species into high-porosity molecular architectures is perhaps one of the main appeals of metal-organic frameworks (MOFs) in the field of electrocatalysis. This premise has attracted much interest in recent years, and the results generated have also revealed one of the main limitations of molecular materials in this context: low stability under electrocatalytic conditions. Using zirconium MOFs as a starting point, in this work, we use this stability as a variable to discriminate between the most suitable electrocatalytic reaction and specific topologies within this family. Our results revealed that the PCN-224 family is particularly suitable for the electroreduction of molecular nitrogen for the formation of ammonia with faradaic efficiencies above 30% in the presence of Ni2+ sites, an activity that improves most of the catalysts described. We also introduce the fluorination of porphyrin at the meso position as a good alternative to improve both the activity and stability of this material under electrocatalytic conditions.

Photoproperties of favipiravir and its 6-substituted analogues: fluorescence controlled through halogen substitution and tautomerism.

Herein, we have showed the photophysical properties of favipiravir and its 6-substituted analogues. Also, we interpreted the origin of fluorescence of favipiravir and its 6-substituted analogues as a function of tautomerism modulation in ground and excited states. Favipiravir, the 6-fluorine derivative, showed the best photophysical profile, exhibiting a dominant emission wavelength of 430 nm, a high quantum yield (Q.Y.) of 1.0 and a long-lived state (10 ns). Its analogues also showed a maximum emission at 430 nm, but their Q.Y. values were 5-fold lower than that found for favipiravir, decreasing as a function of 6-substitution as follows: F > Cl > Br > I > H. Pyrazines bearing the least electronegative 6-substituent (X = Br, I, H) showed an extra lifetime, which was shorter (0.2-0.3 ns) and less abundant (>15%) than the main lifetime (10 ns, 85%). Further 2D excitation-emission matrix and solvent studies supported that these 3-hydroxy-2-pyrazinecarboxamides present two emissive states. The first of them (λem = 430 nm), which was the most abundant, most fluorescent and long-lived state, was characterized as "locally excited" (LE). Its fluorescence was favored with an increase of the hydrogen-donor nature of the solvent and for pyrazines having a high enolic characteristic. Thus, the high LE-fluorescence of these types of pyrazines depends on the keto-tautomerization of the ground state using a protic solvent and its feasible enol-tautomerization upon excitation. Finally, the second excited state (λem = 536 nm) was suggested as an excited-state intramolecular proton-transfer (ESIPT), and it was observed only, although discretely, for pyrazines bearing the least electronegative 6-substituent.

Effects of multicomponent training and HMB supplementation on disability, cognitive and physical function in institutionalized older adults aged over 70 years: a cluster-randomized controlled trial.

OBJECTIVES: To investigate the synergist effects of exercise and ß-hydroxy ß-methylbutyrate (HMB) supplementation on disability, cognitive and physical function, and muscle power in institutionalized older people. DESIGN: Cluster-randomized controlled trial. PARTICIPANTS: Seventy-two institutionalized older adults (age = 83 ± 10 years old; 63% women) were randomized in four groups: exercise plus placebo (EX), HMB supplementation, EX plus HMB supplementation (EX + HMB), and control (CT). INTERVENTION: The exercising participants completed a 12-week tailored multicomponent exercise intervention (Vivifrail; 5 days/week of an individualized resistance, cardiovascular, balance and flexibility program), whereas the HMB groups received a drink containing 3 g/day of HMB. MEASUREMENTS: Participants were assessed Pre and Post intervention for disability and cognitive function (validated questionnaires), physical function (short physical performance battery, SPPB), handgrip strength and sit-to-stand relative muscle power. Linear mixed-effect models were used to compare changes among groups. RESULTS: Compared to baseline, both EX and EX + HMB improved cognitive function (+2.9 and +1.9 points; p < 0.001), SPPB score (+2.9 points and +2.4 points; p < 0.001) and relative muscle power (+0.64 and +0.48 W·kg-1; p < 0.001), while CT and HMB remained unchanged (p > 0.05). Significant between-group differences were noted between CT, EX and EX + HMB for cognitive function (p < 0.01), between CT and EX + HMB for physical function (p = 0.043), and between CT, EX and EX + HMB for relative muscle power (p < 0.001). CONCLUSION: The Vivifrail exercise program was effective in improving cognitive and physical function, and muscle power in nursing home residents, while HMB supplementation did not provide additional benefits when combined with exercise. These results emphasize the importance of physical exercise interventions in very old people as an essential basis for improving their overall health and quality of life.

Torque-Cadence Profile and Maximal Dynamic Force in Cyclists: A Novel Approach.

We aimed to determine the feasibility, test-retest reliability and long-term stability of a novel method for assessing the force (torque)-velocity (cadence) profile and maximal dynamic force (MDF) during leg-pedaling using a friction-loaded isoinertial cycle ergometer and a high-precision power-meter device. Fifty-two trained male cyclists completed a progressive loading test up to the one-repetition maximum (1RM) on a cycle ergometer. The MDF was defined as the force attained at the cycle performed with the 1RM-load. To examine the test-retest reliability and long-term stability of torque-cadence values, the progressive test was repeated after 72 h and also after 10 weeks of aerobic and strength training. The participants' MDF averaged 13.4 ± 1.3 N·kg-1, which was attained with an average pedal cadence of 21 ± 3 rpm. Participants' highest power output value was attained with a cadence of 110 ± 16 rpm (52 ± 5% MDF). The relationship between the MDF and cadence proved to be very strong (R2 = 0.978) and independent of the cyclists' MDF (p = 0.66). Cadence values derived from this relationship revealed a very high test-retest repeatability (mean SEM = 4 rpm, 3.3%) and long-term stability (SEM = 3 rpm, 2.3%); despite increases in the MDF following the 10-week period. Our findings support the validity, reliability and long-term stability of this method for the assessment of the torque-cadence profile and MDF in cyclists.

Load-velocity Relationship of the Bench Press Exercise is not Affected by Breast Cancer Surgery and Adjuvant Therapy.

We examined the effect of breast cancer surgery and adjuvant therapy on the relationship between bar velocity and relative intensity (load-velocity [L-V] relationship) of the bench press (BP) exercise. Twenty-two breast cancer survivors (age: 48.0±8.2 yr., relative strength: 0.40±0.08) completed a loading test up to the one-repetition maximum (1RM) in the BP using a lightweight carbon bar. General and individual relationships between relative intensity (%1RM) and mean propulsive velocity (MPV) were studied. Furthermore, the mean test velocity (MPVTest) and velocity attained to the 1RM (MPV1RM) were analyzed. These procedures and analyses were also conducted in 22 healthy women (age: 47.8±7.1 yr., relative strength: 0.41±0.09) to examine the differences in velocity parameters derived from these L-V relationships. Polynomial regressions showed very close relationships (R2≥0.965) and reduced estimation errors (≤4.9% 1RM) for both groups. Between-group differences in MPV attained to each %1RM were small (≤0.01 m·s-1) and not significant (p≥0.685). Similarly, the MPVTest (0.59±0.06 m·s-1) and MPV1RM (0.17±0.03 m·s-1) were identical for breast cancer survivors and healthy women. These results suggest that practitioners could use the same velocity parameters derived from the BP L-V relationship to prescribe this exercise in middle-aged women, regardless of whether they have suffered from breast cancer.

How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study.

Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues. This is crucial, as it hampers the research and commercialization of affected MOFs. Here, it presents the first-ever interlaboratory study of the synthetic reproducibility of two Zr-porphyrin MOFs, PCN-222 and PCN-224, to investigate the scope of this problem. For PCN-222, only one sample out of ten was phase pure and of the correct symmetry, while for PCN-224, three are phase pure, although none of these show the spatial linker order characteristic of PCN-224. Instead, these samples resemble dPCN-224 (disordered PCN-224), which has recently been reported. The variability in thermal behavior, defect content, and surface area of the synthesised samples are also studied. The results have important ramifications for field of metal-organic frameworks and their crystallization, by highlighting the synthetic challenges associated with a multi-variable synthesis space and flat energy landscapes characteristic of MOFs.

In vitro antiviral activity of favipiravir and its 6- and 3-O-substituted derivatives against coronavirus: Acetylation leads to improvement of antiviral activity.

Favipiravir is currently approved for the treatment of the influenza virus and has shown encouraging results in terms of antiviral capacity in clinical studies against severe acute respiratory syndrome coronavirus 2. Favipiravir is a prodrug, where its favipiravir-ribofuranosyl-5B-triphosphate metabolite is capable of blocking RNA replication of the virus. However, the antiviral efficiency of favipiravir is limited by two factors: (i) low accumulation in plasma and rapid excretion/elimination post-administration and (ii) low conversion rate into the active metabolite. To tackle these problems, herein, we have designed new favipiravir analogues focusing on the replacement of the fluorine atom at the 6-position by halogen or hydrogen atoms and 3-O-functionalization with labile groups. The first type of functionalization seeks to increase the antiviral activity because of the better ability of the keto-tautomer as a function of the halogen, and it is hypothesized that the keto-tautomer tends to promote the formation of the ribofuranosyl-5B-triphosphate (RTP) metabolite. Meanwhile, the second type of functionalization seeks to promote lipophilicity and increase accumulation in cells. From the in vitro antiviral activity against two coronavirus models (bovine and human 229E), it was identified that the replacement did not improve the antiviral activity against both the models, which seems to be attributable to the low water solubility of these new 6-functionalized analogues. Meanwhile, with 3-O-functionalization, acetylation provided the most active compounds with higher half-maximal inhibitory concentration and selectivity than favipiravir, whereas benzylation/methanosulfonation yielded the least active compounds. In summary, acetylation is found to be a convenient functionalization to enhance the antiviral profile of favipiravir.

Optimization of the 2-arylquinazoline-4(3H)one scaffold for a selective and potent antitrypanosomal agent: modulation of the mechanism of action through chemical functionalization.

We sought to identify a potent and selective antitrypanosomal agent through modulation of the mechanism of action of a 2-arylquinazoline scaffold as an antitrypanosomal agent via chemical functionalization at the 4-position. We wished to use the: (i) susceptibility of trypanosomatids towards nitric oxide (NO) and reactive oxygen species (ROS); (ii) capacity of the 4-substituted quinazoline system to act as an antifolate agent. Three quinazolin-based moieties that differed from each other by having at the 4-position key pharmacophores targeting the induction of NO and ROS production were evaluated in vitro against Leishmania infantum and Trypanosoma cruzi parasites and their modes of action were explored. Replacement of an oxygen moiety at the 4-position of the antifolate 2-arylquinazolin-4(3H)one by hydrazinyl and 5-nitrofuryl-hydrazinyl pharmacophores enhanced antitrypanosomatid activity significantly due to promotion of an additional mechanism beyond the antifolate response such as NO or ROS production, respectively. Among the three types of chemical functionalization, the 5-nitrofuryl-hydrazinyl moiety generated the most potent compounds. Compound 3b was a potential candidate thanks to its sub-micromolar response against the promastigotes/amastigotes of L. infantum and epimastigote of T. cruzi, moderate toxicity on macrophages (J774.1), good selectivity index (∼15.1-17.6) and, importantly, non-mutagenic effects. 2-Arylquinazoline could be an attractive platform to design new anti-trypanosomatid agents with the use of key pharmacophores.

C-H Bond Functionalization of N-Heteroarenes Mediated by Selectfluor.

Herein, recent developments for Selectfluor-mediated C-H functionalization of N-heteroarenes are described. This type of C-H bond activation is an attractive and competitive alternative to traditional methodologies, allowing the functionalization of a variety of chemical functions. In addition, Selectfluor is a more sustainable and economically accessible oxidant compared with expensive/toxic metals or hazardous peroxides. For a practical understanding, the current review classified systematically the reported strategies in four subsections as follows: (1) carbon-carbon formation, (2) carbon-nitrogen bond formation, (3) carbon-chalcogen bond, and (4) carbon-halogen bond formation. Mechanistic aspects and reaction conditions are fully discussed to provide an understanding of the aspects that govern C-H functionalization in N-heteroarenes mediated by Selectfluor.

Reaching the limit in autonomous racing: Optimal control versus reinforcement learning.

A central question in robotics is how to design a control system for an agile mobile robot. This paper studies this question systematically, focusing on a challenging setting: autonomous drone racing. We show that a neural network controller trained with reinforcement learning (RL) outperformed optimal control (OC) methods in this setting. We then investigated which fundamental factors have contributed to the success of RL or have limited OC. Our study indicates that the fundamental advantage of RL over OC is not that it optimizes its objective better but that it optimizes a better objective. OC decomposes the problem into planning and control with an explicit intermediate representation, such as a trajectory, that serves as an interface. This decomposition limits the range of behaviors that can be expressed by the controller, leading to inferior control performance when facing unmodeled effects. In contrast, RL can directly optimize a task-level objective and can leverage domain randomization to cope with model uncertainty, allowing the discovery of more robust control responses. Our findings allowed us to push an agile drone to its maximum performance, achieving a peak acceleration greater than 12 times the gravitational acceleration and a peak velocity of 108 kilometers per hour. Our policy achieved superhuman control within minutes of training on a standard workstation. This work presents a milestone in agile robotics and sheds light on the role of RL and OC in robot control.

Free-Weight and Machine-Based Training Are Equally Effective on Strength and Hypertrophy: Challenging a Traditional Myth.

PURPOSE: This study aimed to compare the effects of free-weight and machine-based resistance training on strength, hypertrophy, and joint discomfort. METHODS: Thirty-eight resistance-trained men participated in an 8-wk resistance program allocated into free-weight ( n = 19) or machine-based ( n = 19) groups. Training variables were identical for both modalities, so they only differed in the use of barbells or machines to execute the full squat, bench press, prone bench pull, and shoulder press exercises. The velocity-based method was implemented to accurately adjust the intensity throughout the program. Strength changes were evaluated using eight velocity-monitored loading tests (four exercises × two modalities) and included the relative one-repetition maximum (1RM Rel ), as well as the mean propulsive velocity against low (MPV Low ) and high (MPV High ) loads. Ultrasound-derived cross-sectional area of quadriceps (proximal and distal regions), pectoralis major, and rectus abdominis was measured to examine hypertrophy. Complementarily, Western Ontario and McMaster Universities and Disabilities of the Arm, Shoulder and Hand questionnaires were administrated to assess changes in lower- and upper-limb joint discomfort. Outcomes were compared using ANCOVA and percentage of change (∆) statistics. RESULTS: Each group significantly ( P < 0.001) increased 1RM Rel , MPV Low , and MPV High for both modalities tested, but especially in the one they trained. When considering together the eight exercises tested, strength changes for both modalities were similar (∆ differences ≤1.8%, P ≥ 0.216). Likewise, the cross-sectional area of all the muscles evaluated was significantly increased by both modalities, with no significant differences between them (∆ difference ≤2.0%, P ≥ 0.208). No between-group differences ( P ≥ 0.144) were found for changes in stiffness, pain, and functional disability levels, which were reduced by both modalities. CONCLUSIONS: Free-weight and machine-based modalities are similarly effective to promote strength and hypertrophy without increasing joint discomfort.

Refractive Error Changes Due to COVID-19 Pandemic Confinement in Children from Puerto Rico: A Retrospective Study.

SIGNIFICANCE: The progression of myopia increased in children after the pandemic confinement. A myopic shift in the refractive error of the Hispanic population was found regardless of the refractive status of the school-aged children studied. PURPOSE: This study aimed to evaluate the refractive error in Puerto Rican children before and after the COVID-19 pandemic. We were interested in whether there was a significant change in refractive error attributed to online learning during the pandemic lockdown. METHODS: A retrospective record review of children aged 7 to 18 years who underwent a comprehensive visual evaluation between 2018 and 2021 at the Inter American Eye Institute in Puerto Rico was performed. The spherical equivalent pre- and post-lockdown was compared. The study excluded the best-corrected visual acuities worse than 20/40, any corneal or retinal disease, and amblyopia. RESULTS: In total, 801 records were included in this study. The mean age was 12.7 ± 3.2 years, with 50.3% male and 49.7% female children. The mean spherical equivalent for the right and left eyes was similar ( r = 0.93, P ≤ .001). A significant difference in the mean spherical equivalent was found pre- and post- lockdown (0.22 ± 0.59 D, t800 = 10.44, P ≤ .001). A myopic shift post-lockdown was significant for all ages except those in the 7- (0.13 ± 0.79 D, t28 = 0.84, P = .40) and 8-year-old range (0.12 ± 0.65 D, t40 = 1.22, P = .23), respectively. No significant change was found between sexes before (0.16 ± 0.12 D; t799 = 1.38, P = .16) and after (0.15 ± 0.13 D; t799 = 1.19, P = .23) confinement. CONCLUSIONS: The current study revealed a significant myopic shift in Hispanic school-aged children as a result of the pandemic confinement.

Tautomerism and Rotamerism of Favipiravir and Halogenated Analogues in Solution and in the Solid State.

Favipiravir is an important selective antiviral against RNA-based viruses, and currently, it is being repurposed as a potential drug for the treatment of COVID-19. This type of chemical system presents different carboxamide-rotameric and hydroxyl-tautomeric states, which could be essential for interpreting its selective antiviral activity. Herein, the tautomeric 3-hydroxypyrazine/3-pyrazinone pair of favipiravir and its 6-substituted analogues, 6-Cl, 6-Br, 6-I, and 6-H, were fully investigated in solution and in the solid state through ultraviolet-visible, 1H nuclear magnetic resonance, infrared spectroscopy, and X-ray diffraction techniques. Also, a study of the gas phase was performed using density functional theory calculations. In general, the keto-enol balance in these 3-hydroxy-2-pyrazinecarboxamides is finely modulated by external and internal electrical variations via changes in solvent polarity or by replacement of substituents at position 6. The enol tautomer was prevalent in an apolar environment, whereas an increase in the level of the keto tautomer was favored by an increase in solvent polarity and, even moreso, with a strong hydrogen-donor solvent. Keto tautomerization was favored either in solution or in the solid state with a decrease in 6-substituent electronegativity as follows: H ≫ I ≈ Br > Cl ≥ F. Specific rotameric states based on carboxamide, "cisoide" and "transoide", were identified for the enol and keto tautomer, respectively; their rotamerism is dependent on the tautomerism and not the aggregation state.

A novel scale based on biomarkers associated with COVID-19 severity can predict the need for hospitalization and intensive care, as well as enhanced probabilities for mortality.

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.

Exploring binding chemistry of alkali/alkaline earth cations in solution through modulation of intramolecular charge-transfer in an excited ambidentate organic fluorophore.

Studying the metal-ligand monoligation of alkali/alkaline earth metals (AMs) in solution represents a significant challenge due to the low stabilization of their complexes and the absence of an effective strategy to identify this type of weak binding. Herein, we show that the modulation of the intramolecular charge-transfer (ICT) in an excited ambidentate organic fluorophore is a convenient strategy to characterize the binding chemistry of AM cations in solution through simple steady-state fluorescence and fluorescence lifetime measurements. The key points of the fluorophore as a metal-binding probe were the location of diverse coordination functionalities with different binding abilities (ionic-, pseudo-covalent- and non-covalent-probes) along the donor-acceptor (D-A) chain and the occurrence of an intramolecular charge-transfer (ICT) mechanism upon excitation. The binding of these functionalities with AM-cations generated selective and specific fluorescence responses, which were quantifiable and allowed us to recognize the primary, secondary and tertiary interactions for all the AM cations in the solution. The relative binding affinities for each one of the functionalities with AM cations was estimated, and a general and consistent perspective of the binding of AMs as a function of their location in the Periodic Table, hardness property and ionic radius was established. The binding preferences of the AM cations were supported by DFT calculations. Our strategy allowed us to validate the binding dynamics of AMs in solution for three types of key ligations, which opens a new perspective to recognize weak intermolecular interactions derived from acidic species and rationally design selective AM-cation probes using an ICT-based ambidentate organic fluorophore.

Cracking double-blind review: Authorship attribution with deep learning.

Double-blind peer review is considered a pillar of academic research because it is perceived to ensure a fair, unbiased, and fact-centered scientific discussion. Yet, experienced researchers can often correctly guess from which research group an anonymous submission originates, biasing the peer-review process. In this work, we present a transformer-based, neural-network architecture that only uses the text content and the author names in the bibliography to attribute an anonymous manuscript to an author. To train and evaluate our method, we created the largest authorship-identification dataset to date. It leverages all research papers publicly available on arXiv amounting to over 2 million manuscripts. In arXiv-subsets with up to 2,000 different authors, our method achieves an unprecedented authorship attribution accuracy, where up to 73% of papers are attributed correctly. We present a scaling analysis to highlight the applicability of the proposed method to even larger datasets when sufficient compute capabilities are more widely available to the academic community. Furthermore, we analyze the attribution accuracy in settings where the goal is to identify all authors of an anonymous manuscript. Thanks to our method, we are not only able to predict the author of an anonymous work but we also provide empirical evidence of the key aspects that make a paper attributable. We have open-sourced the necessary tools to reproduce our experiments.

Adaptations in athletic performance and muscle architecture are not meaningfully conditioned by training free-weight versus machine-based exercises: Challenging a traditional assumption using the velocity-based method.

BACKGROUND: Although the superior effectiveness of free-weight over machine-based training has been a traditionally widespread assumption, longitudinal studies comparing these training modalities were scarce and heterogeneous. OBJECTIVE: This research used the velocity-based method to compare the effects of free-weight and machine-based resistance training on athletic performance and muscle architecture. METHODS: Thirty-four resistance-trained men participated in an 8-week resistance training program allocated into free-weight (n = 17) or machine-based (n = 17) groups. Training variables (intensity, intraset fatigue, and recovery) were identical for both groups, so they only differed in the use of a barbell or specific machines to execute the full squat, bench press, prone bench pull, and shoulder press exercises. The velocity-based method was implemented to accurately adjust the planned intensity. Analysis of covariance and effect size (ES) statistics were used to compare both training modalities on a comprehensive set of athletic and muscle architecture parameters. RESULTS: No between-group differences were found for any athletic (p ≥ 0.146) and muscle architecture (p ≥ 0.184) variable. Both training modalities significantly and similarly improved vertical jump (Free-weight: ES ≥ 0.45, p ≤ 0.001; Machine-based: ES ≥ 0.41, p ≤ 0.001) and lower limb anaerobic capacity (Free-weight: ES ≥ 0.39, p ≤ 0.007; Machine-based: ES ≥ 0.31, p ≤ 0.003). Additionally, the machine-based group meaningfully enhanced upper limb anaerobic power (ES = 0.41, p = 0.021), whereas the free-weight group significantly improved the change of direction (ES = -0.54, p = 0.003) and 2/6 balance conditions analyzed (p ≤ 0.012). Changes in sprint capacity (ES ≥ -0.13, p ≥ 0.274), fascicle length, and pennation angle (ES ≤ 0.19, p ≥ 0.129) were not significant for either training modality. CONCLUSION: Adaptations in athletic performance and muscle architecture would not be meaningfully influenced by the resistance modality trained.

One-step synthesis of favipiravir from Selectfluor® and 3-hydroxy-2-pyrazinecarboxamide in an ionic liquid.

Favipiravir is an important selective antiviral that emerged as an alternative against COVID-19 during the pandemic. Its synthesis has gained great interest and the conventional strategies proceed through multiple-step protocols (6-7 reaction steps), which involve, in addition, several drawbacks with global yields, lower than 34%. Herein, a simple, economical, eco-friendly and scalable (1 g) one-step protocol for the synthesis of favipiravir from the direct fluorination of the available 3-hydroxy-2-pyrazinecarboxamide with Selectfluor® is reported. The reaction proceeds easily in BF4-BMIM through a simple operational work-up, affording the favipiravir with a yield of 50% without the need of a special catalyst/additive. The key point of the present strategy was the use of the ionic liquid of BF4-BMIM, which helps to minimize the several chemical limitations derived from 3-hydroxy-2-pyrazinecarboxamide as a substrate for the direct Selectfluor-mediated fluorination. All these chemical reactivity aspects are also discussed in detail.

Velocity-Based Method in Free-Weight and Machine-Based Training Modalities: The Degree of Freedom Matters.

ABSTRACT: Hernández-Belmonte, A, Buendía-Romero, Á, Pallares, JG, and Martínez-Cava, A. Velocity-based method in free-weight and machine-based training modalities: the degree of freedom matters. J Strength Cond Res 37(9): e500-e509, 2023-This study aimed to analyze and compare the load-velocity relationships of free-weight and machine-based modalities of 4 resistance exercises. Moreover, we examined the influence of the subject's strength level on these load-velocity relationships. Fifty men completed a loading test in the free-weight and machine-based modalities of the bench press, full squat, shoulder press, and prone bench pull exercises. General and individual relationships between relative intensity (%1RM) and velocity variables were studied through the coefficient of determination ( R2 ) and standard error of the estimate ( SEE ). Moreover, the velocity attained to each %1RM was compared between both modalities. Subjects were divided into stronger and weaker to study whether the subject's strength level influences the mean test (mean propulsive velocity [MPV Test ]) and 1RM (MPV 1RM ) velocities. For both modalities, very close relationships ( R2 ≥ 0.95) and reduced estimation errors were found when velocity was analyzed as a dependent ( SEE ≤ 0.086 m·s -1 ) and independent ( SEE ≤ 5.7% 1RM) variable concerning the %1RM. Fits were found to be higher ( R2 ≥ 0.995) for individual load-velocity relationships. Concerning the between-modality comparison, the velocity attained at each intensity (from 30 to 100% 1RM) was significantly faster for the free-weight variant. Finally, nonsignificant differences were found when comparing MPV Test (differences ≤ 0.02 m·s -1 ) and MPV 1RM (differences ≤ 0.01 m·s -1 ) between stronger and weaker subjects. These findings prove the accuracy and stability of the velocity-based method in the free-weight and machine-based variants but highlight the need to use the load-velocity relationship (preferably the individual one) specific to each training modality.

Effects of a concurrent training, respiratory muscle exercise, and self-management recommendations on recovery from post-COVID-19 conditions: the RECOVE trial.

The aim of this study was to determine the effectiveness of physical exercise, respiratory muscle training, and the self-management World Health Organization (WHO) recommendations leaflet on the recovery of physical fitness, quality of life, and symptom status in people with post-COVID-19 conditions. Eighty nonhospitalized adults with a post-COVID-19 condition were randomly assigned to one of four 8-wk parallel intervention groups: 1) multicomponent exercise program based on concurrent training (CT, number of subjects (n) = 20; 3 resistance and endurance supervised sessions per week at low-moderate intensity); 2) inspiratory muscle training (RM, n = 17; 2 standardized daily sessions); 3) a combination of both of the above (CTRM, n = 23); and 4) control group (CON, n = 20; following the WHO guidelines for post-COVID-19-related illness rehabilitation). No significant differences between groups were detected at baseline. Although no significant differences between interventions were detected in the V̇o2max, significant individual improvements were identified in the CT (7.5%; effect size, ES = 0.28) and CTRM (7.8%; ES = 0.36) groups. Lower body muscle strength significantly improved in the CT and CTRM (14.5%-32.6%; ES = 0.27-1.13) groups compared with RM and CON (-0.3% to 11.3%; ES = 0.10-0.19). The CT and CTRM groups improved significantly for dyspnea and fatigue, as did the health status. In addition, significant differences between interventions were described in fatigue and depression scales favoring CT and CTRM interventions. An individualized and supervised concurrent training with or without inspiratory muscle training was safe and more effective than self-care recommendations and inspiratory muscle training alone, to regain cardiovascular and muscular fitness, improve symptom severity, and health status in outpatients with post-COVID-19 conditions.NEW & NOTEWORTHY Eight weeks of concurrent training, with or without inspiratory muscle exercise, was better than WHO "Support for Rehabilitation: Self-Management after COVID-19-Related Illness" recommendations or inspiratory muscle training alone to improve cardiopulmonary fitness, strength, and symptom severity, in a safe and effective manner. The RECOVE trial proved the benefits and utility of a supervised exercise program in people with post-COVID-19 conditions after mild COVID-19 in an ambulatory setting.