Miracle-dz/UniFAR-FTUs huggingface dataset:
Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study

Significance Statement In vivo cleavage of IgG by an endopeptidase is a novel therapeutic strategy for anti-GBM disease. Despite plasma exchange, most patients become dependent on dialysis, especially those with AKI at diagnosis. In an encouraging pilot study, two thirds of 15 patients selected because of poor prognosis exhibited kidney survival at 6 months without major safety issues after receiving a single infusion of imlifidase. The drug has been used in patients who have undergone a transplant with multiple HLA antibodies. Our study supports further use of the drug in clinical situations in which IgG autoantibodies threaten vital organ function. However, randomized trials are necessary to confirm the findings. Visual Abstract Background The prognosis for kidney survival is poor in patients presenting with circulating anti–glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treatment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis. Methods An investigator-driven phase 2a one-arm study (EudraCT 2016–004082–39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR <15 ml/min per 1.73m2. All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months. Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m2. The median age was 61 years (range 19–77), six were women, and six were also positive for anti–neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P<0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug. Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial. Clinical Trial registration number: EUDRACT 2016–004082–39 https://www.clinicaltrialsregister. eu/ctr-search/trial/2007-001377-28/results
Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer

Key Points Question Does hyperthermic intraperitoneal chemotherapy (HIPEC) after primary or interval cytoreductive surgery increase survival in patients with ovarian cancer? Findings In this randomized clinical trial of 184 women with ovarian cancer, among those who underwent interval cytoreductive surgery after neoadjuvant chemotherapy, the addition of HIPEC decreased recurrence and increased overall survival; however, in patients undergoing primary cytoreductive surgery, progression-free survival and overall survival were not improved. No unresolved serious HIPEC-related adverse events were found in either group. Meaning These results suggest that HIPEC after interval cytoreductive surgery may increase progression-free and overall survival in patients with ovarian cancer who receive neoadjuvant chemotherapy.
Analyzing Effect of Multi-Modality in Predicting Protein-Protein Interactions

Nowadays, multiple sources of information about proteins are available such as protein sequences, 3D structures, Gene Ontology (GO), etc. Most of the works on protein-protein interaction (PPI) identification had utilized these information about proteins, mainly sequence-based, but individually. The new advances in deep learning techniques allow us to leverage multiple sources/modalities of proteins, which complement each other. Some recent works have shown that multi-modal PPI models perform better than uni-modal approaches. This paper aims to investigate whether the performance of multi-modal PPI models is always consistent or depends on other factors such as dataset distribution, algorithms used to learn features, etc. We have used three modalities for this study: Protein sequence, 3D structure, and GO. Various techniques, including deep learning algorithms, are employed to extract features from multiple sources of proteins. These feature vectors from different modalities are then integrated in several combinations (bi-modal and tri-modal) to predict PPI. To conduct this study, we have used Human and S. cerevisiae PPI datasets. The obtained results demonstrate the potentiality of a multi-modal approach and deep learning techniques in predicting protein interactions. However, the predictive capability of a model for PPI depends on feature extraction methods as well. Also, increasing the modality does not always ensure performance improvement. In this study, the PPI model integrating two modalities outperforms the designed uni-modal and tri-modal PPI models.
Sleep and eye disease: A review

There is a growing body of literature on the effects of sleep disorders, in particular obstructive sleep apnoea (OSA), on ocular health, with consistent evidence of an increased risk of floppy eyelid syndrome, non‐arteritic anterior ischaemic optic neuropathy, diabetic macular oedema, and other retinal vasculature changes in individuals with OSA. However, reports on OSA's associations with glaucoma, papilloedema, diabetic retinopathy, central serous chorioretinopathy, and keratoconus have been conflicting, while links between OSA and age‐related macular degeneration have only been described fairly recently. Despite numerous suggestions that OSA treatment may reduce risk of these eye diseases, well‐designed studies to support these claims are lacking. In particular, the ocular hypertensive effects of continuous positive airway pressure (CPAP) therapy for OSA requires further investigation into its potential impact on glaucoma risk and management. Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit. Poor sleep habits have also been linked with increased myopia risk; however, the evidence on this association remains weak.
Animal agency in wildlife conservation and management

Wildlife conservation and management (WCM) practices have been historically drawn from a wide variety of academic fields, yet practitioners have been slow to engage with emerging conversations about animals as complex beings, whose individuality and sociality influence their relationships with humans. We propose an explicit acknowledgement of wild, nonhuman animals as active participants in WCM. We examined 190 studies of WCM interventions and outcomes to highlight 3 common assumptions that underpin many present approaches to WCM: animal behaviors are rigid and homogeneous; wildlife exhibit idealized wild behavior and prefer pristine habitats; and human–wildlife relationships are of marginal or secondary importance relative to nonhuman interactions. We found that these management interventions insufficiently considered animal learning, decision‐making, individuality, sociality, and relationships with humans and led to unanticipated detrimental outcomes. To address these shortcomings, we synthesized theoretical advances in animal behavioral sciences, animal geographies, and animal legal theory that may help conservation professionals reconceptualize animals and their relationships with humans. Based on advances in these fields, we constructed the concept of animal agency, which we define as the ability of animals to actively influence conservation and management outcomes through their adaptive, context‐specific, and complex behaviors that are predicated on their sentience, individuality, lived experiences, cognition, sociality, and cultures in ways that shape and reshape shared human–wildlife cultures, spaces, and histories. Conservation practices, such as compassionate conservation, convivial conservation, and ecological justice, incorporate facets of animal agency. Animal agency can be incorporated in conservation problem‐solving by assessing the ways in which agency contributes to species’ survival and by encouraging more adaptive and collaborative decision‐making among human and nonhuman stakeholders.
How to explain the sensitivity of DNA double-strand breaks yield to 125I position?

Abstract Purpose Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 Å–12 Å, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail. Materials and methods Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage. Results The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder. Conclusions Explaining variations in DSBs yields with 125I position should consider the probability of inducing damage in the proximal strand (nearest to the 125I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.
Resolving the subtle details of human DNA alkyltransferase lesion search and repair mechanism by single-molecule studies

Significance We directly visualize DNA translocation and lesion recognition by the O6-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn2+ occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed. Surprisingly, our data show no enhancement of DNA translocation speed by AGT cluster formation, suggesting that AGT clusters may serve a different role in AGT function. Our data support preferential cluster formation by AGT at alkyl lesions, suggesting a role of these clusters in stabilizing lesion-bound complexes. From our data, we derive a new model for the lesion search and repair mechanism of AGT.
Results of routine inspections in restaurants and institutional catering establishments associated with foodborne outbreaks in Finland

ABSTRACT Official food control is intended to ensure food safety in the food business. In Finland, inspections of food service are performed using a 4-point risk-based grading system. This study compared routine inspection results of outbreak and nonoutbreak establishments in restaurants and institutional catering to investigate whether certain inspection results were associated with the occurrence of foodborne outbreaks. Also a more specific sample of outbreak establishments was defined using strength of evidence registered for each outbreak. Grade distributions of specific inspected items were compared separately. No significant differences were seen in restaurants but in institutional catering significantly poorer inspection results (p < 0.05) were detected in items concerning the order and cleanliness of facilities, surfaces and equipment in outbreak establishments. Effective correction of noncompliances in cleanliness of the food handling environment and equipment and constant maintenance of a favourable situation is essential in ensuring a high level of consumer safety in food service.
Identification of a conserved chemokine receptor motif that enables ligand discrimination

Extensive ligand-receptor promiscuity in the chemokine signaling system balances beneficial redundancy and specificity. However, this feature poses a major challenge to selectively modulate the system pharmacologically. Here, we identified a conserved cluster of three aromatic receptor residues that anchors the second extracellular loop (ECL2) to the top of receptor transmembrane helices (TM) 4 and 5 and enables recognition of both shared and specific characteristics of interacting chemokines. This cluster was essential for the activation of several chemokine receptors. Furthermore, characteristic motifs of the ß1 strand and 30s loop make the two main CC-chemokine subgroups—the macrophage inflammatory proteins (MIPs) and monocyte chemoattractant proteins (MCPs)—differentially dependent on this cluster in the promiscuous receptors CCR1, CCR2, and CCR5. The cluster additionally enabled CCR1 and CCR5 to discriminate between closely related MIPs based on the N terminus of the chemokine. G protein signaling and β-arrestin2 recruitment assays confirmed the importance of the conserved cluster in receptor discrimination of chemokine ligands. This extracellular site may facilitate the development of chemokine-related therapeutics. Description A cluster of aromatic residues in some chemokine receptors creates ligand-specific contact points. A cluster to decipher chemokines Chemokines direct immune cell migration during development, homeostasis, and beneficial as well as pathological inflammation. However, targeting chemokine signaling in a selective manner is challenging, in part, because of the promiscuous pairing of chemokine ligands with multiple receptors. Larsen et al. identified a structure in a group of chemokine receptors that enables them to discriminate between closely related chemokines. A trio of aromatic residues on their extracellular terminus enabled the receptors CCR1, CCR2, and CCR5 to distinguish between chemokine subgroups and specific chemokines in these subgroups through common and unique contact points with the chemokine N terminus. The findings may inform drug development to more selectively modulate chemokine signaling.
Precarious employment and migrant workers’ mental health: a systematic review of quantitative and qualitative studies

Objectives Evidence suggests that precarious employment can have detrimental effects on workers’ health, including mental health. Migrant workers are discussed to be especially vulnerable to such effects. Thus, we systematically reviewed existing research on the association between precarious employment and migrant workers’ mental health. Methods Three electronic databases (Web of Science, PsycINFO and PubMed/Medline) were searched for original articles on quantitative and qualitative studies published from January 1970 to February 2022 in English, German, Turkish and Spanish. Multiple dimensions of precarious employment were considered as exposure, with mental health problems as outcomes. Narrative synthesis and thematic analyses were performed to summarize the findings of the included studies along with risk of bias and quality assessment. Results The literature search resulted in 1557 original articles, 66 of which met the inclusion criteria – 43 were of high quality and 22 were of moderate quality. The most common exposure dimensions analyzed in the studies included temporariness, vulnerability, poor interpersonal relationships, disempowerment, lacking workers’ rights and low income. The outcome measures included stress, depression, anxiety and poor general mental health. The prevalence of these outcomes varied between 10–75% among the included quantitative studies. All qualitative studies reported one or more dimensions of precarious employment as an underlying factor of the development of mental health problems among migrants. Of 33 quantitative studies, 23 reported evidence for an association between dimensions of precarious employment and mental health. Conclusion The results of this review support the hypothesis that precarious employment is associated with migrant workers’ mental health.
Does group size matter during collaborative skills learning? A randomised study

Collaborative skills learning in the form of dyad learning compared with individual learning has been shown to lead to non‐inferior skills retention and transfer. However, we have limited knowledge on which learning activities improve collaborative skills training and how the number of collaborators may impact skills transfer. We explored the effects of skills training individually, in dyads, triads or tetrads on learning activities during training and on subsequent skills transfer.
Commentary on Livingston et al.: Do reductions in adolescent drinking really maintain into adulthood?

policies reported that the decline in adolescent heavy episodic drinking in Finland, Norway and Sweden was associated with a decline in adolescent daily smoking, a decline in perceived access to alcohol and an increase in parental control [8]. While parental control and access control may be powerful during adolescence, they gradu-ally lose their effect on drinking behaviour when adolescents transi-tion into adulthood and become less dependent on their parents. As the preventive effect fades, other factors need to take their place to keep consumption levels low. Unfortunately, while prevention measures and their effects on drinking in adolescents have been studied intensively [9], there seems to be a lack of knowledge on effective alcohol prevention measures targeting adolescents during their transi-tion to young and older adulthood. The working hypothesis of Livingston and colleagues [1] is that alcohol-related harm would reduce if the observed reductions were maintained into adulthood and continued into older age. Research suggesting links between heavy drinking in adolescence and heavy drinking and increased risk of abuse and dependence in adulthood [10] imply that persistent reductions in alcohol use in all parts of the population will result in less alcohol harm, morbidity and mortality [11]. level have the may and by the the the age terms of reduced risks of harm is Lower and risky levels in adolescence certainly lower the likelihood of acute harm, such as becoming however, even after a period of – 10 years, they reach the higher level of previous generations, no major impact upon chronic conditions, such as cancer, high blood pressure or dependence, is to be expected. This suggests that we may only expect short-term rather than long-term public health benefits.
An experimental protocol for molecular biology lab at an Amazonian University

Laboratory‐based practical classes are an essential component in teaching molecular biology for undergraduate students. Universidad Regional Amazonica Ikiam is a higher education institution located in the Ecuadorian Amazon rainforest, a high biodiversity place, including amphibians. Based on this, we have established a practical molecular biology program with eight sessions that contextualize the biodiverse surroundings of the University. This program stimulates synchronization of information between theory and practice and improves research skills. During these sessions, students are motivated to identify and characterize antimicrobial peptides from Ecuadorian frog skin secretions, using molecular biology techniques and biochemistry and microbiology knowledge. This practical course was held twice with a total of 56 students from the fifth semester of the biotechnology engineering. The evaluation of the practical program was carried out through a questionnaire applied to students using the Likert scale. Overall, this form of teaching had high receptivity and presented benefits for student learning. Interestingly, 80% of respondents strongly agreed that this course provided tools and knowledge for the development of their undergraduate dissertation. Therefore, practical courses tailored to the student's context can stimulate student learning and interest. Additionally, this experimental methodology is interdisciplinary and can be applied to other research fields and subjects.
Evaluation of In Situ Antiaging Activity in Saccharomyces cerevisiae BY611 Yeast Cells Treated with Polyalthia longifolia Leaf Methanolic Extract (PLME) Using Different Microscopic Approaches: A Morphology-Based Evaluation

Abstract Abstract Polyalthia longifolia is known for its anti-oxidative properties, which might contribute to the antiaging action. Hence, the current research was conducted to evaluate the antiaging activity of P. longifolia leaf methanolic extract (PLME) in a yeast model based on morphology using microscopic approaches. Saccharomyces cerevisiae BY611 strain yeast cells were treated with 1.00 mg/mL of PLME. The antiaging activity was assessed by determining the replicative lifespan, total lifespan, vacuole morphology by light microscopy, extra-morphology by scanning (SEM), and intra-morphology by transmission (TEM) electron microscopy. The findings demonstrated that PLME treatment significantly accelerated the replicative and total lifespan of the yeast cells. PLME treatment also delays the formation of large apoptotic-like type 3 yeast cell vacuoles. The untreated yeast cells demonstrated aging morphology via SEM analysis, such as shrinking, regional invaginations, and wrinkled cell surface. The TEM analysis revealed the quintessential aging intracellular morphology such as swollen, wrinkled, or damaged vacuole formation of the circular endoplasmic reticulum, a rupture in the nuclear membrane, fragmentation of the nucleus, and complete damaged cytoplasm. Decisively, the present study revealed the vital role of PLME in the induction of antiaging activity in a yeast model using three microscopic approaches—SEM, TEM, and bright-field light microscope.