Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower nutritional state and foraging success in an Arctic seabird despite behaviorally flexible responses to environmental change

Abstract The degree to which individuals adjust foraging behavior in response to environmental variability can impact foraging success, leading to downstream impacts on fitness and population dynamics. We examined the foraging flexibility, average daily energy expenditure, and foraging success of an ice‐associated Arctic seabird, the thick‐billed murre (Uria lomvia) in response to broad‐scale environmental conditions at two different‐sized, low Arctic colonies located <300 km apart. First, we compared foraging behavior (measured via GPS units), average daily energy expenditure (estimated from GPS derived activity budgets), and foraging success (nutritional state measured via nutritional biomarkers pre‐ and post‐ GPS deployment) of murres at two colonies, which differ greatly in size: 30,000 pairs breed on Coats Island, Nunavut, and 400,000 pairs breed on Digges Island, Nunavut. Second, we tested whether colony size within the same marine ecosystem altered foraging behavior in response to broad‐scale environmental variability. Third, we tested whether environmentally induced foraging flexibility influenced the foraging success of murres. Murres at the larger colony foraged farther and longer but made fewer trips, resulting in a lower nutritional state and lower foraging success compared to birds at the smaller colony. Foraging behavior and foraging success varied in response to environmental variation, with murres at both colonies making longer, more distant foraging trips in high ice regimes during incubation, suggesting flexibility in responding to environmental variability. However, only birds at the larger colony showed this same flexibility during chick rearing. Foraging success at both colonies was higher during high ice regimes, suggesting greater prey availability. Overall, murres from the larger colony exhibited lower foraging success, and their foraging behavior showed stronger responses to changes in broad‐scale conditions such as sea ice regime. Taken together, this suggests that larger Arctic seabird colonies have higher behavioral and demographic sensitivity to environmental change.
Influence of Water Hyacinth (Eichhornia crassipes) on Concentration and Distribution of Escherichia coli in Water Surrounding an Informal Floating Community in Iquitos, Peru

Floating communities exist throughout the world. Many live on water with a high pathogen load due to difficulties associated with sewage management. In Claverito, an informal floating community in Iquitos, Peru, we conducted a controlled experiment to test the ability of water hyacinth (Eichhornia crassipes) to remove Escherichia coli from water. When river E. coli concentrations were at or below ∼1,500 CFU 100 mL−1, water hyacinth reduced shallow concentrations (8 cm depth) down to levels deemed safe by U.S. EPA for recreational use. Above this threshold, plants were able to reduce E. coli levels within shallow water, but not down to “safe” levels. At deeper depths (>25 cm), there was evidence that plants increased E. coli concentrations. Water hyacinth removed E. coli from shallow water by providing a surface (i.e., submerged roots) onto which E. coli sorbed and by protecting organisms that can potentially consume E. coli. Unfortunately, because of root association, the total E. coli load within the water column was greater with water hyacinth present. The use of water hyacinth to keep surface water around floating communities low in E. coli could be beneficial as this is the water layer with which people most likely interact. Aquatic vegetation naturally proliferates in and around Claverito. While this study was based on curating aquatic plants in order to achieve a water‐quality outcome, it nonetheless supports concrete actions for Claverito residents under non‐curated conditions, which are outlined at the end of the manuscript.
Towards causal mechanisms of consciousness through focused transcranial brain stimulation

Abstract Conscious experience represents one of the most elusive problems of empirical science, namely neuroscience. The main objective of empirical studies of consciousness has been to describe the minimal sets of neural events necessary for a specific neuronal state to become consciously experienced. The current state of the art still does not meet this objective but rather consists of highly speculative theories based on correlates of consciousness and an ever-growing list of knowledge gaps. The current state of the art is defined by the limitations of past stimulation techniques and the emphasis on the observational approach. However, looking at the current stimulation technologies that are becoming more accurate, it is time to consider an alternative approach to studying consciousness, which builds on the methodology of causal explanations via causal alterations. The aim of this methodology is to move beyond the correlates of consciousness and focus directly on the mechanisms of consciousness with the help of the currently focused brain stimulation techniques, such as geodesic transcranial electric neuromodulation. This approach not only overcomes the limitations of the correlational methodology but will also become another firm step in the following science of consciousness.
Tropical Cloud Heating Profiles: Analysis from KWAJEX

Diabatic heating (or Q1) profiles associated with specific cloud types are produced by matching synoptic cloud observations with a sounding budget analysis during the Tropical Rainfall Measuring Mission (TRMM) Kwajalein Experiment (KWAJEX), which took place in the Marshall Islands from late July through mid-September 1999. Fair-weather cumulus clouds produce up to 1 K day 1 of heating below 850 hPa and are associated with cooling throughout much of the rest of the troposphere. Cumulus congestus clouds produce heating on the order of 1 K day 1 up to 575 hPa and cooling in the mid- to upper troposphere. Cumulonimbus clouds produce heating through the depth of the troposphere, with a maximum of 3.7 K day 1 near 550 hPa. Cloud types indicating widespread rain (stratus or cumulus fractus of bad weather at low levels and nimbostratus at midlevels) have the largest and most elevated heating, with values 10 K day 1 above 600 hPa. Other mid- and high-level cloud types are shown to be consistent with area-averaged rain rates and Q1 profiles. Profiles of the divergence and apparent moisture sink (or Q2) for convective clouds are also analyzed and are shown to be consistent with the physics of the heating profiles just described.
Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?

ABSTRACT Introduction Despite there being a wide range of medicines available for the treatment of type 2 diabetes, the high rate of mortality suggests treatment needs to be improved. Only a few medicines have shown long-term effectiveness in obesity, and new medicines are urgently needed. Areas covered A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes. Retatrutide was relatively safe and pharmacokinetics support once-weekly dosing. Expert opinion The role of stimulating glucagon receptors in the treatment of type 2 diabetes and/or obesity is poorly defined and needs to be clarified. Although retatrutide may be superior to the GLP-1 receptor agonist dulaglutide in reducing plasma glucose and body weight, this is not a meaningful comparison, as another GLP-1 receptor agonist (semaglutide) is more potent than dulaglutide at this and may have similar efficacy to retatrutide. Retatrutide also needs to be compared to another Eli Lilly and Company drug, the combined GLP-1 and GIP receptor agonist, tirzepatide. The safety of retatrutide needs to be determined in larger and longer trials.
The orexin story and orexin receptor antagonists for the treatment of insomnia

Insomnia is present in up to one third of the adult population worldwide, and it can present independently or with other medical conditions such as mental, metabolic, or cardiovascular diseases, which highlights the importance of treating this multifaceted disorder. Insomnia is associated with an abnormal state of hyperarousal (increased somatic, cognitive, and cortical activation) and orexin has been identified as a key promotor of arousal and vigilance. The current standards of care for the treatment of insomnia recommend non‐pharmacological interventions (cognitive behavioural therapy) as first‐line treatment and, if behavioural interventions are not effective or available, pharmacotherapy. In contrast to most sleep medications used for decades (benzodiazepines and ‘Z‐drugs’), the new orexin receptor antagonists do not modulate the activity of γ‐aminobutyric acid receptors, the main inhibitory mechanism of the central nervous system. Instead, they temporarily block the orexin pathway, causing a different pattern of effects, e.g., less morning or next‐day effects, motor dyscoordination, and cognitive impairment. The pharmacokinetic/pharmacodynamic properties of these drugs are the basis of the different characteristics explained in the package inserts, including the recommended starting dose. Orexin receptor antagonists seem to be devoid of any dependence and tolerance‐inducing effects, rendering them a viable option for longer‐term treatment. Safety studies did not show exacerbation of existing respiratory problems, but more real‐world safety and pharmacovigilance experience is needed. This review provides an overview of the orexin history, the mechanism of action, the relation to insomnia, and key features of available drugs mediating orexin signalling.
The black hole candidate IGR J17091-3624 going to quiescence

We report preliminary results on our Swift/XRT monitoring observations of the current outburst of the black hole candidate IGR J17091-3624 (e.g. Altamirano et al. 2011, ApJL, 742, 17, and references therein). Since our last report on 31 Jan 2013 (ATEL #4773), the X-ray flux as measured from Swift/XRT pointed observations has only varied by a factor not larger than 5. However, in the the last Swift/XRT pointed observation IGR J17091-3624 is barely detected, if detected at all.
Benefits of an Early Mobility Program for Hospitalized Patients With Cancer

PURPOSE Patients with cancer are often hospitalized with complications from cancer and cancer treatment. Many experience a decline in physical functioning, including loss of mobility, which likely contributes to increased length of stay (LOS) and increased readmissions. We aimed to determine whether a mobility program would improve quality of care and decrease health care utilization. METHODS We implemented a mobility aide program on an oncology unit in a large academic medical center for all patients without bedrest orders between October 1, 2018, and February 28, 2021. The program consisted of nursing evaluation using the Activity Measure for Post-Acute Care (AMPAC), an ordinal scale ranging from bed rest to ambulating ≥ 250 feet, to quantify mobility. Plan of care was determined in a multidisciplinary manner with physical therapy (PT), nursing, and a mobility aide, who is a medical assistant with enhanced rehabilitation training. Patients were then mobilized two times per day 7 days a week. Using descriptive statistics and mixed effects logistic regression, we evaluated the programs impact on LOS, readmissions, and changes in mobility during this time period compared with the 6-month interval before implementation. RESULTS A total of 1,496 hospitalized patients were identified. The odds of hospital readmission within 30 days of discharge was significantly less for those who received the intervention (OR, 0.53; 95% CI, 0.37 to 0.78; P = .001). The odds ratio (OR) of having a final AMPAC score at or above the median was significantly higher for those who received the intervention (OR, 1.60; 95% CI, 1.04 to 2.45; P < .05). There was no significant difference in LOS. CONCLUSION Use of this mobility program resulted in a significant decrease in readmissions and maintained or improved patients' mobility. This demonstrates that non-PT professionals can effectively mobilize hospitalized patients with cancer, thereby decreasing the burden on PT and nursing resources. Future work will evaluate the sustainability of the program and evaluate association with health care costs.
Kaempferol induces mitochondrial dysfunction and mitophagy by activating the LKB1/AMPK/MFF pathway in breast precancerous lesions

Kaempferol has been suggested to be an effective anticancer agent in several malignant tumors. However, its function and mechanisms in breast precancerous lesions remain largely elusive. Here, we showed that kaempferol induced excessive mitochondrial fission and mitochondrial damage with activated mitochondrial fission factor (MFF)‐mediated dynamin‐related protein (DRP) 1 mitochondrial translocation. As a result, the PTEN‐induced putative kinase 1 (PINK1)/Parkin signaling pathway was activated, accompanied by excessive mitophagy and reduced mitochondrial mass in cells. We also revealed that kaempferol‐induced lethal mitophagy contributed to inhibiting breast precancerous lesion growth in vitro and in vivo. Furthermore, we verified serine/threonine kinase 11 (STK11/LKB1)/AMP‐activated protein kinase (AMPK) pathway deficiency in breast precancerous lesions. Moreover, LKB1/AMPK pathway reactivation by kaempferol was required for excessive mitochondrial fission and lethal mitophagy. Taken together, our findings shed new light on the molecular mechanisms related to breast cancer prevention by kaempferol and provide evidence for its potential clinical application.
Effects of different phenylcapsaicin doses on resistance training performance, muscle damage, protein breakdown, metabolic response, ratings of perceived exertion, and recovery: a randomized, triple-blinded, placebo-controlled, crossover trial

ABSTRACT Background The aim of this study was to explore the effects of a low dose (LD) of 0.625 mg and a high dose (HD) of 2.5 mg of phenylcapsaicin (PC) on full squat (SQ) performance, active muscle (RPE-AM) and overall body (RPE-OB) ratings of perceived exertion, muscle damage, protein breakdown, metabolic response, and 24-h recovery in comparison to placebo (PLA). Method Twenty-five resistance-trained males (age = 21.00 ± 2.15 years, SQ 1-repetition maximum [1RM] normalized = 1.66 ± 0.22 kg) were enrolled in this randomized, triple-blinded, placebo-controlled, crossover trial. Participants completed 2 weekly sessions per condition (LD, HD, and PLA). The first session consisted of pre-blood testing of lactate, urea, and aspartate aminotransferases (AST) and 2 SQ repetitions with 60% 1RM followed by the resistance exercise protocol, which consisted of SQ sets of 3 × 8 × 70% 1RM monitoring lifting velocity. RPE-OB and RPE-AM were assessed after each set. After the first session, 2 SQ repetitions with 60% 1RM were performed, and blood lactate and urea posttests were collected. After 24 h, AST posttest and 1 × 2 × 60% 1RM were determined as biochemical and mechanical fatigue outcomes. Results HD reported significant differences for RPE-AM, AST, and SQ performance compared to LD and PLA. Post-hoc analyses revealed that HD attained faster velocities in SQ than LD (p = 0.008). HD induced a lower RPE-AM when compared with LD (p = 0.02) and PLA (p = 0.004). PLA resulted in higher AST concentrations at 24-h post than HD (p = 0.02). No significant differences were observed for the rest of the comparisons. Conclusions This study suggests that PC may favorably influence SQ performance, RPE-AM, and muscle damage compared to PLA. However, HD exhibited most of the biochemical and mechanical anti-fatigue effects instead of LD.
Evaluation of therapeutic potential of ivermectin against complete Freund's adjuvant‐induced arthritis in rats: Involvement of inflammatory mediators

Rheumatoid arthritis is a chronic systemic inflammatory disease with genetic manifestations. According to recently published case reports, patients taking corticosteroid medication for the management of rheumatoid arthritis develop strongloidiasis and are at high risk of developing associated infections. This study explored the antiarthritic role of ivermectin, a drug used in the treatment of strongyloides and to compare its results with dexamethasone. Thirty‐two male Wistar rats were randomly divided into four groups: control, diseased, dexamethasone, and ivermectin groups. Rheumatoid arthritis in all rats except the control group was induced by using complete Freund's adjuvant. After 7 days of rheumatoid arthritis induction, animals were treated with dexamethasone 5 mg/kg and ivermectin 6 mg/kg. Body weight, visual arthritic score, total leukocyte count, differential leukocyte count, proinflammatory genes, and histopathological findings were used to assess the effects of ivermectin on rheumatoid arthritis. Treatment with ivermectin showed a significant reduction in inflammatory cells levels, body weight, and visual arthritic score, indicating an improvement in the degree of inflammation as compared with the diseased group. Treatment with ivermectin and dexamethasone significantly reduced the augmentation in the mRNA expression levels of IL‐17, TLR‐2, TNF, and NF‐κB as a result of arthritic development. Ivermectin treatment also showed a significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to dexamethasone, a corticosteroid used for the treatment of rheumatoid arthritis. Ivermectin has significant antiarthritic properties and can be a novel treatment agent for the management of rheumatoid arthritis patients suffering from strongyloidiasis.
Treatment and Outcome of Osteoporotic Thoracolumbar Vertebral Body Fractures With Deformation of Both Endplates With or Without Posterior Wall Involvement (OF 4): Short-Term Results from the Prospective EOFTT Multicenter Study

Study Design Multicenter prospective cohort study Objective To analyse therapeutical strategies applied to osteoporotic thoracolumbar OF 4 injuries, to assess related complications and clinical outcome. Methods A multicenter prospective cohort study (EOFTT) including 518 consecutive patients who were treated for an Osteoporotic vertebral compression fracture (OVCF). For the present study, only patients with OF 4 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5L, and Barthel Index after a minimum follow-up of 6 weeks. Results A total of 152 (29%) patients presented with OF 4 fractures with a mean age of 76 years (range 41-97). The most common treatment was short-segment posterior stabilization (51%; hybrid stabilization in 36%). Mean follow up was 208 days (±131 days), mean ODI was 30 ± 21. Dorsoventral stabilized patients were younger compared to the other groups (P < .001) and had significant better TuG compared to hybrid stabilization (P = .049). The other clinical outcomes did not differ in the therapy strategies (VAS pain: P = 1.000, ODI: P > .602, Barthel: P > .252, EQ-5D 5L index value: P > .610, VAS-EQ-5D 5L: P = 1.000). The inpatient complication rate was 8% after conservative and 16% after surgical treatment. During follow-up period 14% of conservatively treated patients and 3% of surgical treated patients experienced neurological deficits. Conclusions Conservative therapy of OF 4 injuries seems to be viable option in patients with only moderate symptoms. Hybrid stabilization was the dominant treatment strategy leading to promising clinical short-term results. Stand-alone cement augmentation seems to be a valid alternative in selected cases.
Discovery and Validation of the Binding Poses of Allosteric Fragment Hits to Protein Tyrosine Phosphatase 1b: From Molecular Dynamics Simulations to X-ray Crystallography

Fragment-based drug discovery has led to six approved drugs, but the small sizes of the chemical fragments used in such methods typically result in only weak interactions between the fragment and its target molecule, which makes it challenging to experimentally determine the three-dimensional poses fragments assume in the bound state. One computational approach that could help address this difficulty is long-timescale molecular dynamics (MD) simulations, which have been used in retrospective studies to recover experimentally known binding poses of fragments. Here, we present the results of long-timescale MD simulations that we used to prospectively discover binding poses for two series of fragments in allosteric pockets on a difficult and important pharmaceutical target, protein tyrosine phosphatase 1b (PTP1b). Our simulations reversibly sampled the fragment association and dissociation process. One of the binding pockets found in the simulations has not to our knowledge been previously observed with a bound fragment, and the other pocket adopted a very rare conformation. We subsequently obtained high-resolution crystal structures of members of each fragment series bound to PTP1b, and the experimentally observed poses confirmed the simulation results. To the best of our knowledge, our findings provide the first demonstration that MD simulations can be used prospectively to determine fragment binding poses to previously unidentified pockets.
Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe‐induced contractions were observed in endothelium‐intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP‐2) were observed in Sevo, but not in the Iso group. While reduced IL‐10 and IL‐1β were observed in Sevo, increases in IL‐1β in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP‐2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.