A bridge between trust and control: computational workflows meet automated battery cycling.

Compliance with good research data management practices means trust in the integrity of the data, and it is achievable by full control of the data gathering process. In this work, we demonstrate tooling which bridges these two aspects, and illustrate its use in a case study of automated battery cycling. We successfully interface off-the-shelf battery cycling hardware with the computational workflow management software AiiDA, allowing us to control experiments, while ensuring trust in the data by tracking its provenance. We design user interfaces compatible with this tooling, which span the inventory, experiment design, and result analysis stages. Other features, including monitoring of workflows and import of externally generated and legacy data are also implemented. Finally, the full software stack required for this work is made available in a set of open-source packages.

Modeling tropical tuna shifts: An inflated power logit regression approach.

We introduce a new class of zero-or-one inflated power logit (IPL) regression models, which serve as a versatile tool for analyzing bounded continuous data with observations at a boundary. These models are applied to explore the effects of climate changes on the distribution of tropical tuna within the North Atlantic Ocean. Our findings suggest that our modeling approach is adequate and capable of handling the outliers in the data. It exhibited superior performance compared to rival models in both diagnostic analysis and regarding the inference robustness. We offer a user-friendly method for fitting IPL regression models in practical applications.

The distinct cell physiology of Bradyrhizobium at the population and cellular level.

The α-Proteobacteria belonging to Bradyrhizobium genus are microorganisms of extreme slow growth. Despite their extended use as inoculants in soybean production, their physiology remains poorly characterized. In this work, we produced quantitative data on four different isolates: B. diazoefficens USDA110, B. diazoefficiens USDA122, B. japonicum E109 and B. japonicum USDA6 which are representative of specific genomic profiles. Notably, we found conserved physiological traits conserved in all the studied isolates: (i) the lag and initial exponential growth phases display cell aggregation; (ii) the increase in specific nutrient concentration such as yeast extract and gluconate hinders growth; (iii) cell size does not correlate with culture age; and (iv) cell cycle presents polar growth. Meanwhile, fitness, cell size and in vitro growth widely vary across isolates correlating to ribosomal RNA operon number. In summary, this study provides novel empirical data that enriches the comprehension of the Bradyrhizobium (slow) growth dynamics and cell cycle.

Tofacitinib and peficitinib inhibitors of Janus kinase for autoimmune disease treatment: a quantum biochemistry approach.

Autoimmune inflammatory diseases, such as rheumatoid arthritis (RA) and ulcerative colitis, are associated with an uncontrolled production of cytokines leading to the pronounced inflammatory response of these disorders. Their therapy is currently focused on the inhibition of cytokine receptors, such as the Janus kinase (JAK) protein family. Tofacitinib and peficitinib are JAK inhibitors that have been recently approved to treat rheumatoid arthritis. In this study, an in-depth analysis was carried out through quantum biochemistry to understand the interactions involved in the complexes formed by JAK1 and tofacitinib or peficitinib. Computational analyses provided new insights into the binding mechanisms between tofacitinib or peficitinib and JAK1. The essential amino acid residues that support the complex are also identified and reported. Additionally, we report new interactions, such as van der Waals; hydrogen bonds; and alkyl, pi-alkyl, and pi-sulfur forces, that stabilize the complexes. The computational results revealed that peficitinib presents a similar affinity to JAK1 compared to tofacitinib based on their interaction energies.

Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental-Theoretical Study.

Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.

Blastomycosis Complicated by Adult Respiratory Distress Syndrome in an Immunocompetent Adult: A Case Report and Literature Review.

Blastomycosis is an endemic mycotic infection caused by inhalation of thermally dimorphic fungi from the genus Blastomyces. Blastomyces dermatitidis is the species most related to human infection in the USA and North America. Adult respiratory distress syndrome (ARDS) is a rare complication of blastomycosis and is associated with high mortality. Due to its rarity, evidence-based guidelines for diagnosing and treating ARDS associated with blastomycosis are scarce. In this case presentation, a 22-year-old male with a history of chronic cannabis use presented with severe respiratory symptoms, initially treated as community-acquired pneumonia. Despite antibiotic treatment, his condition deteriorated, necessitating intubation and resulting in the development of ARDS. A delayed diagnosis of pulmonary blastomycosis was confirmed through polymerase chain reaction testing. Treatment with amphotericin B and corticosteroids proved successful in addressing the fungal infection, leading to the recovery of the patient from his severe clinical condition. This case highlights the challenges associated with diagnosing and treating blastomycosis, particularly when complicated by ARDS, emphasizing the importance of considering fungal infections in the differential diagnosis of non-responsive pulmonary infections. Additionally, it suggests the potential utility of corticosteroids in severe cases and emphasizes the crucial role of early diagnosis and a combination of diagnostic modalities for the timely management of this rare and potentially life-threatening condition.

Understanding species-specific and conserved RNA-protein interactions in vivo and in vitro.

While evolution is often considered from a DNA- and protein-centric view, RNA-based regulation can also impact gene expression and protein sequences. Here we examined interspecies differences in RNA-protein interactions using the conserved neuronal RNA binding protein, Unkempt (UNK) as model. We find that roughly half of mRNAs bound in human are also bound in mouse. Unexpectedly, even when transcript-level binding was conserved across species differential motif usage was prevalent. To understand the biochemical basis of UNK-RNA interactions, we reconstituted the human and mouse UNK-RNA interactomes using a high-throughput biochemical assay. We uncover detailed features driving binding, show that in vivo patterns are captured in vitro, find that highly conserved sites are the strongest bound, and associate binding strength with downstream regulation. Furthermore, subtle sequence differences surrounding motifs are key determinants of species-specific binding. We highlight the complex features driving protein-RNA interactions and how these evolve to confer species-specific regulation.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

BACKGROUND AND OBJECTIVES: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. METHODS: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. RESULTS: IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). DISCUSSION: Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

Inhibitory effects against SARSCoV-2 main protease (Mpro) of biflavonoids and benzophenones from the fruit of Platonia insignis.

The SARS-CoV-2 mutation and the limitation of the approved drug against COVID-19 are still a challenge in many country healthcare systems and need to be affronted despite the set of vaccines to prevent this viral infection. To contribute to the identification of new antiviral agents, the present study focused on natural products from an edible fruit with potential inhibitory effects against the SARS-CoV-2 main protease (Mpro). First, LC-ESIMS analysis of Platonia insignis fruits was performed and showed the presence of biflavonoids and benzophenones in the seed and pulp, respectively. Then, maceration and chromatographic purification led to the identification of two triglycerides (1 and 2) alongside chamaejasmine (3) and volkensiflavone (4) from the seed and isogarcinol (5) and cycloxanthochymol (6), from the pulp. Compounds 1-6 after evaluating their inhibitory against Mpro, displayed from no to significant activity. Compound 5 was the most potent with an IC50 value of 0.72 µM and was more active than the positive control, Ebselen (IC50 of 3.4 µM). It displayed weak and no cytotoxicity against THP-1 (CC50 of 116.2 µM) and Vero cell lines, respectively. Other active compounds showed no cytotoxicity against THP-1. and Vero cell lines. Molecular docking studies revealed interactions in the catalytic pocket between compound 5 and amino acid residues that composed the catalytic dyads (His 41 and Cyst 145).

Records of the non-native alga Acanthophoraspicifera (Rhodophyta) and their colonial epibionts in La Paz Bay, Gulf of California.

Acanthophoraspicifera, a red alga considered an alien species, was discovered for the first time on the Pacific coast of Mexico in 2006 from a locality inside La Paz Bay, Gulf of California. Since then, more records have shown its presence, 17 localities having been added up to 2015. A two-year field study (2020-2022) visiting 31 sites along the coast of La Paz Bay, complemented with data from literature and citizen science, resulted in a database of 709 entries that spans the data from 2004 to 2023. These data showed a distribution that goes from Punta Coyote, close to Boca Grande, the northern entrance to the Bay to Playa Tecolote in the south, more than 100 km of coastline, including Espiritu Santo Archipelago, an area considered a natural reserve since 2007. Anthropogenic activity and environmental variables did not present statistical differences that explain A.spicifera spreading. It represents a naturalised alien species without evidence of a negative impact. Still, it soon could acquire the status of invasive species together with its epibionts Bryozoa and Hydrozoa detected in this study.

New polymorphic phase of arachidic acid crystal: structure, intermolecular interactions, low-temperature stability and Raman spectroscopy combined with DFT calculations.

Saturated monocarboxylic fatty acids with long carbon chains are organic compounds widely used in several applied fields, such as energy production, thermal energy storage, antibactericidal, antimicrobial, among others. In this research, a new polymorphic phase of arachidic acid (AA) crystal was synthesized and its structural and vibrational properties were studied by single-crystal X-ray diffraction (XRD) and polarized Raman scattering. The new structure of AA was solved at two different temperature conditions (100 and 300 K). XRD analysis indicated that this polymorph belongs to the monoclinic space group P21/c (C2h5), with four molecules per unit cell (Z = 4). All molecules in the crystal lattice adopt a gauche configuration, exhibiting a R22(8) hydrogen bond pattern. Consequently, this new polymorphic phase, labeled as B form, is a polytype belonging to the monoclinic symmetry, i.e., Bm form. Complementarily, Hirshfeld's surfaces were employed to analyze the intermolecular interactions within the crystal lattice of this polymorph at temperatures of 100 and 300 K. Additionally, density functional theory (DFT) calculations were performed to assign all intramolecular vibration modes related to experimental Raman-active bands, which were properly calculated using a dimer model, considering a pair of AA molecules in the gauche configuration, according to the solved-crystal structure.

Diagnosis and referral of patients with AL amyloidosis in Portugal: results from a Delphi panel.

Light chain amyloidosis (AL) is a complex disorder defined by the extracellular deposition of insoluble amyloid fibrils formed by intact or fragmented immunoglobulin light chains, leading to cell dysfunction, rapid organ deterioration, and, ultimately, death. Although the clinical presentation of AL is directly connected to organ involvement, signs and symptoms of AL are frequently nonspecific, misinterpreted, and late recognized. Thus, an early diagnosis combined with effective therapies to cease disease progression and rescue organ function is essential. The aim of this study was to assess the knowledge and characterize the current clinical practice regarding AL diagnosis and referral among Portuguese physicians. A Delphi-like panel (one round only) with a group of national experts from different medical specialties (cardiology, hematology, internal medicine, nephrology, and neurology) was carried out online, in which 30 statements were classified using a 4-point Likert scale. For each statement, the consensus level was set at 70% for "fully agree/disagree" and the majority level was defined as >70% in agreement or disagreement. Although the results suggest the existence of adequate general knowledge of AL amyloidosis, they also disclosed the necessity to raise awareness for this disease. Overall, this Delphi panel revealed a high lack of consensus regarding the diagnosis and early management of patients with AL among different specialties despite the qualified majority obtained in 26 statements. An optimized strategy for AL early diagnosis, transversal to several medical fields, is urgently needed. Moreover, referral centers with access to diagnostic technology and a network of diverse specialties should be established to foster an early diagnosis and better disease approach to boost the possibility of a better outcome for patients with AL.

Polysaccharide/Silica Microcapsules Prepared via Ionic Gelation Combined with Spray Drying: Application in the Release of Hydrophilic Substances and Catalysis.

Polysaccharide/silica hybrid microcapsules were prepared using ionic gelation followed by spray-drying. Chitosan and alginate were used as biopolymer matrices, and in situ prepared silica was used as a structuring additive. The prepared microparticles were used in two very different applications: the encapsulation of hydrophilic molecules, and as a support for palladium nanoparticles used as catalysts for a model organic reaction, namely the reduction of p-nitrophenol by sodium borhydride. In the first application, erioglaucine disodium salt, taken as a model hydrophilic substance, was encapsulated in situ during the preparation of the microparticles. The results indicate that the presence of silica nanostructures, integrated within the polymer matrix, affect the morphology and the stability of the particles, retarding the release of the encapsulated substance. In the second application, chloropalladate was complexed on the surface of chitosan microparticles, and palladium(II) was subsequently reduced to palladium(0) to obtain heterogeneous catalysts with an excellent performance.

Metabolomic Profile, Plasmatic Levels of Losartan and EXP3174, Blood Pressure Control in Hypertensive Patients and Their Correlation with COVID-19.

Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and is related to serious health complications. It has been pointed out as a major risk factor for COVID-19. This study aimed to determine the impact of COVID-19 on the metabolomic profile, the correlation with the plasmatic levels of losartan and its active metabolite (EXP3174), biochemical markers, and blood pressure (BP) control in hypertensive patients. 1H NMR metabolomic profiles of hypertensive and normotensive patients with and without previous COVID-19 diagnosis were identified. Plasmatic levels of LOS and EXP3174 were correlated with BP, biochemical markers, and the metabolomic fingerprint of the groups. Biomarkers linked to important aspects of SAH and COVID-19 were identified, such as glucose, glutamine, arginine, creatinine, alanine, choline, erythritol, homogentisate, 0-tyrosine, and 2-hydroxybutyrate. Those metabolites are indicative of metabolic alterations, kidney damage, pulmonary dysfunction, and persistent inflammation, which can be found in both diseases. Some hypertensive patients did not reach the therapeutic levels of LOS and EXP3174, while the BP control was also limited among the normotensive patients with previous COVID-19 diagnoses. Metabolomics proved to be an important tool for assessing the effectiveness of losartan pharmacotherapy and the damage caused by SAH and COVID-19 in hypertensive patients.

Single laboratory evaluation of umbilical cord blood units processing methodologies for banking.

OBJECTIVE: To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. METHODS: Historical data were compiled and the analytical results obtained for the 3 different methods were compared. RESULTS: The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. CONCLUSION: These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality.

Sudden Cardiac Arrest: A Rare Clinical Presentation of Primary Aldosteronism.

Sudden cardiac arrest (SCA) may be related to reversible causes in up to 50% of cases, such as electrolyte imbalances. Primary aldosteronism (PA) is characterized by excessive autonomic aldosterone production and can present with hypokalemia. We present an uncommon case of a 36-year-old woman who was diagnosed with PA after two episodes of ventricular fibrillation, secondary to severe hypokalemia.

Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions.

An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ-RhS. Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er).

[Stress injuries of bone in children and adolescents]. / Stressverletzungen des Knochens bei Kindern und Jugendlichen.

Stress injuries of bone in childhood and adolescence are the result of an imbalance between physical stress on the growing musculoskeletal system and its intrinsic resilience. Children who are very active in sports are particularly affected. The classical stress injuries mainly occur in the area of the lower leg, the metatarsus and the lower lumbar spine due to the disproportionate load on healthy bone; however, overuse syndromes can also occur in the area of the growth plates and possibly lead to growth plate disorders. The anamnesis usually shows stress-related pain that has existed for a long time without trauma. As part of the differential diagnosis, a stress injury must first be included in the considerations due to it being a rare entity. An X­ray examination can show the first signs of a stress reaction. In the event of a conspicuous periosteal reaction, a malignant event must also be considered. As a rule, the MRI examination is then groundbreaking and in some rare cases biopsies have to be considered. The treatment of stress injuries is usually conservative. Recurrences should be counteracted by exercise control.

Spontaneous Proteus mirabilis Meningitis in Adults Requiring an Extended Antibiotic Course: Case Report and Literature Review.

Most cases of gram-negative bacillary meningitis occur in neonates and infants. Meningitis in adults caused by Proteus mirabilis has been reported rarely. Evidence-based guidelines for the treatment of adult patients with gram-negative bacillus meningitis are scarce. The optimal duration of antibiotic therapy for these patients is an unanswered question in the medical literature. This article outlines a case of community-acquired meningitis caused by P. mirabilis in an adult patient who required an extended antimicrobial treatment, after failing to a three-week antibiotic regime. Our patient, a 66-year-old man with a history of neurogenic bladder, remote spinal cord trauma, and recurrent urinary tract infections presented to the emergency department reporting a two-day history of severe headache, fever, and confusion. Cerebrospinal fluid (CSF) revealed significant neutrophil-predominant pleocytosis, low glucose level, and elevated protein level. CSF culture grew few pan-susceptible P. mirabilis. The patient initially completed 21 days of ceftriaxone guided by susceptibility testing. Nine days after finishing antibiotic therapy, the patient was readmitted with recurrent headache, fever, and neck rigidity. A new CSF study again revealed pleocytosis, elevated polymorphonuclear cells, low glucose level, and elevated protein level, but with a negative CSF culture. The patient became afebrile, and his symptoms improved after two days of ceftriaxone. He completed an additional six-week regime of ceftriaxone. On the one-month follow-up visit, the patient remained afebrile, with no recurrent symptoms. Spontaneous community-acquired P. mirabilis meningitis is rare among adult patients. Experiences in the treatment of gram-negative bacillus meningitis in adults must be shared with the scientific community to build up a better understanding of this condition. In the context of this case, sterilization of the CSF, extended antibiotic therapy, and a close post-treatment follow-up are crucial for treating this life-threatening condition.