Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma

Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells. As such, this review aims to highlight the potential clinical benefits of various armed antibody-based immunotherapies, including PDT, as alternative approaches for the treatment of metastatic melanoma.
Phytochemical characterization of different yarrow species (Achillea sp.) and investigations into their antimicrobial activity

Abstract Various Achillea species are rich in bioactive compounds and are important medicinal plants in phytotherapy. In the present study, Achillea millefolium L. , Achillea moschata Wulfen, and Achillea atrata L. were compared with respect to their phenolic profile and antibacterial activity against gram-positive bacteria strains (Staphylococcus, Propionibacterium). Particular focus was given to A. atrata, which has hardly been studied so far. Based on the metabolite profile, A. atrata exhibited more similarities to A. moschata than to A. millefolium. The former two only differed in the occurrence of four compounds. The flavonols syringetin-3-O-glucoside and mearnsetin-hexoside, not reported for an Achillea species before, have been detected in A. atrata and A. moschata. All Achillea species reduced growth of the tested bacteria. A. atrata demonstrated highest activity against Propionibacterium acnes and Staphylococcus epidermidis, both being involved in the pathogenesis of acne vulgaris. Furthermore, A. atrata has a pronounced anti–methicillin-resistant Staphylococcus aureus potential. Bioassay-guided fractionation revealed that only the most polar fraction of A. moschata displayed antimicrobial activity, which was attributed to phenolics such as apigenin, centaureidin, and nevadensin, being present in high amounts in A. atrata. Thus, this alpine species shows promising antimicrobial activity and might be a potential source for developing novel dermal/topical drugs.
Obesity Measures and Dietary Parameters as Predictors of Gut Microbiota Phyla in Healthy Individuals

The dynamics and diversity of human gut microbiota that can remarkably influence the wellbeing and health of the host are constantly changing through the host’s lifetime in response to various factors. The aim of the present study was to determine a set of parameters that could have a major impact on classifying subjects into a single cluster regarding gut bacteria composition. Therefore, a set of demographical, environmental, and clinical data of healthy adults aged 25–50 years (117 female and 83 men) was collected. Fecal microbiota composition was characterized using Illumina MiSeq 16S rRNA gene amplicon sequencing. Hierarchical clustering was performed to analyze the microbiota data set, and a supervised machine learning model (SVM; Support Vector Machines) was applied for classification. Seventy variables from collected data were included in machine learning analysis. The agglomerative clustering algorithm suggested the presence of four distinct community types of most abundant bacterial phyla. Each cluster harbored a statistically significant different proportion of bacterial phyla. Regarding prediction, the most important features classifying subjects into clusters were measures of obesity (waist to hip ratio, BMI, and visceral fat index), total body water, blood pressure, energy intake, total fat, olive oil intake, total fiber intake, and water intake. In conclusion, the SVM model was shown as a valuable tool to classify healthy individuals based on their gut microbiota composition.
Comparative Behavior in Lizards of the Genus Cnemidophorus (Teiidae), with Comments on the Evolution of Parthenogenesis in Reptiles

An experiment was conducted to quantify behavioral differences between the parthenogenetic teiid lizard Cnemidophorus tesselatus and the gonochoristic species C. marmoratus in response to a predatory threat. Individuals of C. marmoratus were significantly more cautious and, unlike C. tesselatus, adjusted behavioral responses to environmental contingencies in a manner likely to enhance fitness. A review of pertinent literature suggests that fitness advantages classically ascribed to parthenogenesis have yet to be adequately demonstrated in lizards.
Highly infectious prions are not directly neurotoxic

Significance Prions are infectious agents composed of polymers of misfolded prion protein which cause fatal brain diseases such as Creutzfeldt–Jakob disease. These diseases involve progressive loss of neuronal cells, and it has been long assumed that prions are directly toxic to cells as they propagate. However, recent studies have suggested that prion infectivity and neurotoxicity can be uncoupled and involve distinct mechanisms. Using highly purified infectious prions we demonstrate that prions are not directly neurotoxic and that toxicity present in infected brain tissue can be distinguished from infectious prions. This has fundamental implications for understanding of prion diseases and how to treat them and may have wide relevance in other neurodegenerative diseases which involve propagation and spread of proteopathic seeds. Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent development of methods to obtain exceptionally pure prions from mouse brain with maintained strain characteristics, and in which defined structures—paired rod-like double helical fibers—can be definitively correlated with infectivity, allowed a direct test of this assertion. Here we report that while brain homogenates from symptomatic prion-infected mice are highly toxic to cultured neurons, exceptionally pure intact high-titer infectious prions are not directly neurotoxic. We further show that treatment of brain homogenates from prion-infected mice with sodium lauroylsarcosine destroys toxicity without diminishing infectivity. This is consistent with models in which prion propagation and toxicity can be mechanistically uncoupled.
Inflammatory Bowel Diseases Elevate the Risk of Developing Acute Pancreatitis

Supplemental digital content is available in the text. Objectives Increasing data suggest that acute pancreatitis (AP) occurs more frequently among patients with inflammatory bowel diseases (IBDs) than in the non-IBD population; however, currently no comprehensive meta-analysis is available. Methods Systematic literature search was conducted in 4 major databases. We included observational studies sampling from the general population. Basic study characteristics and crude incidences of AP were extracted. Pooled odds ratios (ORs) with 95% confidence interval (CIs) were calculated using the random-effects model. Subgroups were set up by Crohn disease and ulcerative colitis. Heterogeneity was tested with I2 statistics. Results Eight studies were eligible for the analysis. The odds of AP were 3 times higher in IBD (OR, 3.11; 95% CI, 2.93–3.30; I2, 0.0%), significantly higher in Crohn disease than in ulcerative colitis (P < 0.001; OR, 4.12 vs OR, 2.61; I2, 0.0%). The pooled annual incidence of AP in IBD was 210/100,000 person-years (95% CI, 84–392/100,000 person-years; I2, 98.66%). Conclusions We confirmed that IBD elevates the risk of AP and of 100,000 IBD patients 210 AP cases are to be expected annually. Therefore, it is important to include pancreatic enzyme level measurements and radiological investigations in the workup of IBD patients with acute abdominal pain.
Purpose-Dependent Consequences of Temporal Expectations Serving Perception and Action

Temporal expectations enable anticipatory brain states that prepare us for upcoming perception and action. We investigated the purpose-dependent nature and consequences of cued temporal expectations on brain and behavior in male and female human volunteers, using two matched visual-motor tasks that stressed either response speed or visual accuracy. We show that the consequences of temporal expectations are fundamentally purpose dependent. Temporal expectations predominantly affected response times when visual demands were low and speed was more important, but perceptual accuracy when visual demands were more challenging. Using magnetoencephalography, we further show how temporal expectations latch onto anticipatory neural states associated with concurrent spatial expectations—modulating task-specific anticipatory neural lateralization of oscillatory brain activity in a modality- and frequency-specific manner. By relating these brain states to behavior, we finally reveal how the behavioral relevance of such anticipatory brain states is similarly purpose dependent. SIGNIFICANCE STATEMENT Knowing when events may occur helps to prepare neural activity for upcoming perception and action. It is becoming increasingly clear that distinct sources of temporal expectations may facilitate performance via distinct mechanisms. Another relevant dimension to consider regards the distinct purposes that temporal expectations may serve. Here, we demonstrate that the consequences of temporal expectations on neurophysiological brain activity and behavior are fundamentally purpose dependent, and show how temporal expectations interact with task-relevant neural states in a modality- and frequency-specific manner. This brings the important insight that the ways in which temporal expectations influence brain and behavior, and how brain activity is related to behavior, are not fixed properties but rather depend on the task at hand.
COVID-19 in Somalia: Adherence to Preventive Measures and Evolution of the Disease Burden

Following the COVID-19 outbreak in Somalia, strict preventive measures were implemented by the government. We assessed adherence to the government recommendations via two consecutive online cross-sectional surveys between April and July 2020. A five-point adherence score was constructed based on self-reported observance of five preventive measures (physical distancing, face mask use, hand hygiene, mouth covering when coughing/sneezing, and avoidance of touching the face). 4124 and 4703 responses were analyzed during the first and second survey, respectively. The mean adherence score decreased from 3.54 ± 1.5 in the first survey to 3.40 ± 1.6 during the second survey; p < 0.001. More participants experienced at least one flu-like symptom during the second survey (38.2%) compared to the first (16.2%); however, the proportion of positive COVID-19 tests in the first (26.9%) and second survey (26.5%) was similar. The ordinal logistic regression model identified the following predictors for high adherence scores: female gender (odds ratio (OR) = 1.715 (1.581–1.861), p < 0.001); being a healthcare worker/student (OR = 2.180 (2.000–2.377), p < 0.001); obtaining COVID-19 information from official sources (OR = 1.460 (1.341–1.589), p < 0.001); and having postgraduate education (OR = 1.679 (1.220–2.307), p < 0.001). Conversely, obtaining COVID-19 information from social media and residing in urban settings were associated with lower adherence. Targeted and context-specific adaptations of the COVID-19 response may be required in Somalia.
Chronobiological Effects on Mountain Biking Performance

Background: the aim of this study was to analyze the chronobiology influence on the mechanical, kinematic, and physiological variables in a mountain bike (MTB) time trial. Methods: 16 mountain bike (MTB) male athletes volunteered to participate. Their characteristics were as follows: body mass 70.2 ± 5.4 kg, stature 172.7 ± 4.0 cm, body fat 9.8 ± 3.5%, and VO2max 52.3 ± 3.9 mL/kg/min. Two 20 min MTB maximal protocols were applied, the first one in the morning and a second one in the afternoon period. Results: No differences were found for all the variables studied, except for the pedaling cadence (stroke rate), which showed higher values during the morning protocol (85.06 ± 7.58 vs. 82.63 ± 7.41 rpm; p = 0.044). Significant correlations between morning and afternoon physiological and mechanical variables were observed: heart rate (r = 0.871); external mechanical power—maximum (r = 0.845), mean (r = 0.938), and relative (r = 0.933), as well as in the cadence—stroke rate (r = 0.825). Conclusions: our results reveal a similar impact and significant relationship between morning and afternoon impact concerning the majority of the physiological and mechanical variables, which indicates that the period of the day does not influence the external and internal impact associated with the MTB time trial maximal protocol.
Tetrel Bonding and Other Non-Covalent Interactions Assisted Supramolecular Aggregation in a New Pb(II) Complex of an Isonicotinohydrazide

A new supramolecular Pb(II) complex [PbL(NO2)]n was synthesized from Pb(NO3)2, N’-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL) and NaNO2. [PbL(NO2)]n is constructed from discrete [PbL(NO2)] units with an almost ideal N2O3 square pyramidal coordination environment around Pb(II). The ligand L− is coordinated through the 2-pyridyl N-atom, one aza N-atom, and the carbonyl O-atom. The nitrite ligand binds in a κ2-O,O coordination mode through both O-atoms. The Pb(II) center exhibits a hemidirected coordination geometry with a pronounced coordination gap, which allows a close approach of two additional N-atoms arising from the N=C(O) N-atom of an adjacent molecule and from the 4-pyridyl N-atom from the another adjacent molecule, yielding a N4O3 coordination, constructed from two Pb–N and three Pb–O covalent bonds, and two Pb⋯N tetrel bonds. Dimeric units in the structure of [PbL(NO2)]n are formed by the Pb⋯N=C(O) tetrel bonds and intermolecular electrostatically enforced π+⋯π− stacking interactions between the 2- and 4-pyridyl rings and further stabilized by C–H⋯π intermolecular interactions, formed by one of the methyl H-atoms and the 4-pyridyl ring. These dimers are embedded in a 2D network representing a simplified uninodal 3-connected fes (Shubnikov plane net) topology defined by the point symbol (4∙82). The Hirshfeld surface analysis of [PbL(NO2)] revealed that the intermolecular H⋯X (X = H, C, N, O) contacts occupy an overwhelming majority of the molecular surface of the [PbL(NO2)] coordination unit. Furthermore, the structure is characterized by intermolecular C⋯C and C⋯N interactions, corresponding to the intermolecular π⋯π stacking interactions. Notably, intermolecular Pb⋯N and, most interestingly, Pb⋯H interactions are remarkable contributors to the molecular surface of [PbL(NO2)]. While the former contacts are due to the Pb⋯N tetrel bonds, the latter contacts are mainly due to the interaction with the methyl H-atoms in the π⋯π stacked [PbL(NO2)] molecules. Molecular electrostatic potential (MEP) surface calculations showed marked electrostatic contributions to both the Pb⋯N tetrel bonds and the dimer forming π+⋯π− stacking interactions. Quantum theory of atoms in molecules (QTAIM) analyses underlined the tetrel bonding character of the Pb⋯N interactions. The manifold non-covalent interactions found in this supramolecular assembly are the result of the proper combination of the polyfunctional multidentate pyridine-hydrazide ligand and the small nitrito auxiliary ligand.
Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice

In an ageing society, polypharmacy has become a major public health and economic issue. Overuse of medications, especially in patients with chronic diseases, carries major health risks. One common consequence of polypharmacy is the increased emergence of adverse drug events, mainly from drug–drug interactions. The majority of currently available drugs are metabolized by CYP450 enzymes. Interactions due to shared CYP450-mediated metabolic pathways for two or more drugs are frequent, especially through reversible or irreversible CYP450 inhibition. The magnitude of these interactions depends on several factors, including varying affinity and concentration of substrates, time delay between the administration of the drugs, and mechanisms of CYP450 inhibition. Various types of CYP450 inhibition (competitive, non-competitive, mechanism-based) have been observed clinically, and interactions of these types require a distinct clinical management strategy. This review focuses on mechanism-based inhibition, which occurs when a substrate forms a reactive intermediate, creating a stable enzyme–intermediate complex that irreversibly reduces enzyme activity. This type of inhibition can cause interactions with drugs such as omeprazole, paroxetine, macrolide antibiotics, or mirabegron. A good understanding of mechanism-based inhibition and proper clinical management is needed by clinicians when such drugs are prescribed. It is important to recognize mechanism-based inhibition since it cannot be prevented by separating the time of administration of the interacting drugs. Here, we provide a comprehensive overview of the different types of mechanism-based inhibition, along with illustrative examples of how mechanism-based inhibition might affect prescribing and clinical behaviors.
CROSSING RELATIONSHIPS IN THE GENUS CARICA

I regret that, in following Heilmann (The origin of birds. Witherby, London. 1926), I unwittingly perpetuated an error concerning the relationship of H esperornis. I wish to thank Dr. Storer for drawing attention to this error, and I trust that his correction will be widely noted. Dr. Storer's interpretation invalidates the chronology of my speculative interpretation of the origin of the loon wing. Whether it upsets it in other respects is a moot point. I still feel that it is quite possible that the loons arose from a line that, although capable of flight, failed to develop a really efficient wing. In particular, I find it difficult to believe that the poorly developed loon alula is anything but primitively inefficient; for, as long as a bird of substantial size flies at all, a functional alula is very valuable, and it is hard to believe that it is detrimental in swimming or diving. I am grateful to the many correspondents who have written to me about this problem, but it must be admitted that none has yet presented a convincing alternative solution.
Breast Hematoma: An Under-Recognized and Under-Reported Female-Specific Traumatic Injury and Its Clinical Significance

Female-specific traumatic injury patterns have not been well researched and are potentially not well documented. Our aim was to examine the prevalence of breast hematomas (BHs) after blunt chest trauma, and to evaluate if there were risk factors associated with BH requiring intervention. A retrospective review from 2013 to 2018 was performed, identifying female patients ≥18 years sustaining blunt chest trauma. BH was defined as the presence of a collection of blood within the breast parenchyma, and clinically significant breast hematoma (CSBH) as BH requiring blood transfusion, surgical, or interventional radiology intervention. Univariate analysis was performed comparing CSBH with BH in terms of demographics, injury severity, antithrombotic agent use, and body mass index (BMI). Of 871 female patients meeting criteria, 59 (7%) had BH. Of these, 10 (17%) had CSBH (transfusion only, n = 3; angioembolization, n = 4; operation, n = 3). Compared to BH not requiring intervention, CSBH patients were older (mean age, 80 vs 69, P = .006), but had similar rates of motor vehicle crashes (90% vs 78%), seatbelt use (70% vs 71%), antiplatelet use (10% vs 12%), and anticoagulant use (10% vs 6%). Median Injury Severity Scores and median BMI (34 vs 34) were similar between the groups.
Parents’ Perceptions Regarding the Implementation of a Physical Therapy Stimulation Program for Children with Disabilities in Bolivia: A Qualitative Study

The purpose of this study was to explore how parents of children with neuromotor disorders in the department of Chuquisaca (Bolivia) perceive attendance to a physical therapy stimulation program and the expectations they place on the therapy and professional care provided to their children. Semi-structured interviews were conducted with the parents, related to their role in supporting the recommended exercise program for the child, generating topics such as benefits of the therapy for the child, impact on the family, and role of the project in terms of therapy and the physical therapists providing treatment, including both positive and negative aspects of the overall process. This study revealed the importance of understanding the feelings of families receiving intervention under a pioneering program in Bolivia for the detection and treatment of children with neuromotor disorders. Being able to access these types of services provides them with extensive personal, social, and economic support. Knowing their concerns, desires, and demands will allow us to continue to improve and offer the best care for children and families. The professionals involved should also be encouraged to develop effective teaching techniques to promote the inclusion of parents in the stimulation program.