Miracle-dz/UniFAR-FTUs huggingface dataset:
Age of first infection across a range of parasite taxa in a wild mammalian population

Newborn mammals have an immature immune system that cannot sufficiently protect them against infectious diseases. However, variation in the effectiveness of maternal immunity against different parasites may couple with temporal trends in parasite exposure to influence disparities in the timing of infection risk. Determining the relationship between age and infection risk is critical in identifying the portion of a host population that contributes to parasite dynamics, as well as the parasites that regulate host recruitment. However, there are no data directly identifying timing of first infection among parasites in wildlife. Here, we took advantage of a longitudinal dataset, tracking infection status by viruses, bacteria, protists and gastro-intestinal worms in a herd of African buffalo (Syncerus caffer) to ask: how does age of first infection differ among parasite taxa? We found distinct differences in the age of first infection among parasites that aligned with the mode of transmission and parasite taxonomy. Specifically, we found that tick-borne and environmentally transmitted protists were acquired earlier than directly transmitted bacteria and viruses. These results emphasize the importance of understanding infection risk in juveniles, especially in host species where juveniles are purported to sustain parasite persistence and/or where mortality rates of juveniles influence population dynamics.
May Failure to Thrive in Infants Be a Clinical Marker for the Early Diagnosis of Cow’s Milk Allergy?

Objectives—Failure to thrive (FTT) in infants is characterized by growth failure. Although, cow’s milk allergy (CMA) may have an impact on growth and leads to FTT, data are still limited. We focused on FTT as a possible clinical marker for an early diagnosis of CMA. The aim of the present study was to evaluate the implications of cow’s milk hypersensitivity in infants with FTT and the growth catch-up after a cow’s milk-free diet (CMFD). Methods—A cross-sectional study of all consecutive infants evaluated at the Pediatric Nutrition and Allergy Unit of the University Hospital of Bari (Italy) from January 2016 to April 2018 with a medical-driven diagnosis of FTT. Eligible infants were investigated for possible IgE mediated or non-IgE mediated CMA. Results—43 infants were included, mean age 5.7 months. 33/43 (77%) FTT presented a CMA related disease: 3/43 (7%) were diagnosed as presenting an IgE mediated CMA, 30 (93%) had a non IgE-mediated CMA, confirmed by the elimination diet for diagnostic purposes, that led to a significant improvement of symptoms and recrudescence after milk reintroduction. A total of 29 out of 30 patients (one patient was lost at follow-up) moved up to their original growth percentile after dietary changes. Growth z-scores were computed based on WHO anthropometric data. In 10 out of 43 patients (23%) were diagnosed with gastro-esophageal reflux disease (GERD). Conclusions—when evaluating an infant with FTT, physicians should include in their evaluation an extensive search for IgE mediated and non IgE mediated CMA. When in vivo and in vitro analysis are not conclusive, a 4- to 8-weeks trial of CMFD and a consecutive re-introduction of milk proteins may be helpful in less common diagnoses.
Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer

The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.
Medical Authority under Siege: How Clinicians Transform Patient Resistance into Acceptance

Over the past decades, professional medical authority has been transformed due to internal and external pressures, including weakened institutional support and patient-centered care. Today’s patients are more likely to resist treatment recommendations. We examine how patient resistance to treatment recommendations indexes the strength of contemporary professional authority. Using conversation analytic methods, we analyze 39 video recordings of patient-clinician encounters involving pediatric epilepsy patients in which parents resist recommended treatments. We identify three distinct grounds for parental resistance to treatments: preference-, fear-, and experience-based resistance. Clinicians meet these grounds with three corresponding persuasion strategies ranging from pressuring, to coaxing, to accommodating. Rather than giving parents what they want, physicians preserve their professional authority, adjusting responses based on whether the resistance threatens their prerogative to prescribe. While physicians are able to convert most resistance into acceptance, resistance has the potential to change the treatment recommendation and may lead to changed communication styles.
Percutaneous drainage of retroperitoneal abscesses: variables for success, failure, and recurrence.

PURPOSE We aimed to evaluate the success and failure rates and minor and major complications of percutaneous drainage of retroperitoneal abscesses. METHODS Between 1990 and 2010, percutaneously drained 170 retroperitoneal abscesses in 150 patients (83 males, 67 females, median age 44.2 years, age range, 1-86 years) were included retrospectively. Percutaneous drainage of retroperitoneal abscesses was performed under the guidance of ultrasonography and fluoroscopy or computed tomography. Six abscesses were drained via single needle aspiration whereas 164 abscesses were drained via catheters of 6-14 F calibre using the Seldinger technique. RESULTS When all retroperitoneal abscesses are considered, success rates were found as follows: 75.3% cure (128/170), 7.7% temporization (13/170), 4.1% palliation (7/170). Failure rate was 12.9% (22/170). Recurrence rate was 10.6% (18/170), and 13 of the recurred abscesses were treated via second session percutaneous drainage. Mortality rate was 2.7% (4/150). CONCLUSION Percutaneous drainage is the first treatment option for retroperitoneal abscesses due to procedural reliability, elimination of need for general anesthesia, better tolerability, and lower morbidity and mortality rates compared with the surgical methods. High cure, temporization, or palliation rates can be obtained via imaging-guided percutaneous drainage for all retroperitoneal abscesses with a safe access route.
Challenging the Status Quo of Physician Attire in the Palliative Care Setting.

BACKGROUND, AIM, AND HYPOTHESIS This randomized controlled trial aimed to compare the impact of a physician's attire on the perceptions of patients with cancer of compassion, professionalism, and physician preference. Our hypothesis was that patients would perceive the physician with formal attire as more compassionate than the physician wearing casual attire. MATERIALS AND METHODS One hundred five adult follow-up patients with advanced cancer were randomized to watch two standardized, 3-minute video vignettes with the same script, depicting a routine physician-patient clinic encounter. Videos included a physician in formal attire with tie and buttoned-up white coat and casual attire without a tie or white coat. Actors, patients, and investigators were all blinded to the purpose and videos watched, respectively. After each video, patients completed validated questionnaires rating their perception of physician compassion, professionalism, and their overall preference for the physician. RESULTS There were no significant differences between formal and casual attire for compassion (median [interquartile range], 25 [10-31] vs. 20 [8-27]; p = .31) and professionalism (17 [13-21] vs. 18 [14-22]; p = .42). Thirty percent of patients preferred formal attire, 31% preferred casual attire, and 38% had no preference. Subgroup analysis did not show statistically significant differences among different cohorts of age, sex, marital status, and education level. CONCLUSION Doctors' attire did not affect the perceptions of patients with cancer of physician's level of compassion and professionalism, nor did it influence the patients' preference for their doctor or their trust and confidence in the doctor's ability to provide care. There is a need for more studies in this area of communications skills. Clinical trial identification number. NCT03168763 IMPLICATIONS FOR PRACTICE: The significance of physician attire as a means of nonverbal communication has not been well characterized. It is an important element to consider, as patient preferences vary geographically, are influenced by cultural beliefs, and may vary based on particular care settings. Previous studies consisted of nonblinded surveys and found increasing confidence in physicians wearing a professional white coat. Unfortunately, there are no randomized controlled trials, to the authors' knowledge, to confirm the survey findings. In this randomized, blinded clinical trial the researchers found that physician's attire did not affect patients' perception of the physician's level of compassion and professionalism. Attire also did not influence the patients' preferences for their doctor or their trust and confidence in the doctor's ability to provide care.
The Operant Plantar Thermal Assay: A Novel Device for Assessing Thermal Pain Tolerance in Mice

Abstract Pain is a multidimensional experience of sensory-discriminative, cognitive, and affective processes; however, current basic research methods rely heavily on response to threshold stimuli, bypassing the supraspinal processing that ultimately gives rise to the pain experience. We developed the operant plantar thermal assay (OPTA), which utilizes a novel, conflict-based operant task requiring evaluation and active decision-making to obtain reward under thermally aversive conditions to quantify thermal pain tolerance. In baseline measures, male and female mice exhibited similar temperature preferences, however in the OPTA, female mice exhibited greater temperature-dependent tolerance, as defined by choice time spent in an adverse thermal condition to obtain reward. Increasing reward salience (4% vs 10% sucrose solution) led to increased thermal tolerance for males but not females. To determine whether neuropathic and inflammatory pain models alter thermal tolerance, animals with chronic constriction injury (CCI) or complete Freund’s adjuvant (CFA), respectively, were tested in the OPTA. Surprisingly, neuropathic animals exhibited increased thermal tolerance, as shown by greater time spent in the reward zone in an adverse thermal condition, compared with sham animals. There was no effect of inflammation on thermal tolerance. Administration of clonidine in the CCI model led to increased thermal tolerance in both injured and sham animals. In contrast, the non-steroidal anti-inflammatory meloxicam was anti-hyperalgesic in the CFA model, but reduced thermal pain tolerance. These data support the feasibility of using the OPTA to assess thermal pain tolerance to gain new insights into complex pain behaviors and to investigate novel aspects of analgesic efficacy.
Virtual Screening Approach to Identify High-Affinity Inhibitors of Serum and Glucocorticoid-Regulated Kinase 1 among Bioactive Natural Products: Combined Molecular Docking and Simulation Studies

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine kinase that works under acute transcriptional control by several stimuli, including serum and glucocorticoids. It plays a significant role in the cancer progression and metastasis, as it regulates inflammation, apoptosis, hormone release, neuro-excitability, and cell proliferation. SGK1 has recently been considered as a potential drug target for cancer, diabetes, and neurodegenerative diseases. In the present study, we have performed structure-based virtual high-throughput screening of natural compounds from the ZINC database to find potential inhibitors of SGK1. Initially, hits were selected based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and other drug-like properties. Afterwards, PAINS filter, binding affinities estimation, and interaction analysis were performed to find safe and effective hits. We found four compounds bearing appreciable binding affinity and specificity towards the binding pocket of SGK1. The docking results were complemented by all-atom molecular dynamics simulation for 100 ns, followed by MM/PBSA, and principal component analysis to investigate the conformational changes, stability, and interaction mechanism of SGK1 in-complex with the selected compound ZINC00319000. Molecular dynamics simulation results suggested that the binding of ZINC00319000 stabilizes the SGK1 structure, and it leads to fewer conformational changes. In conclusion, the identified compound ZINC00319000 might be further exploited as a scaffold to develop promising inhibitors of SGK1 for the therapeutic management of associated diseases, including cancer.
Significant gender differences according to the Problematic and Risky Internet Use Screening Scale among 15‐year‐olds in Sweden

According to recent national data on media use in 13-16 year olds from Sweden (https://statensmedierad.se/download/18.126747f416d00e1ba946903a/1568041620554/Ungar%20och%20medier%202019%20tillganglighetsanpassad.pdf), 72% use internet more than 3 hours daily. Excessive internet use can be seen as a non-drug form of addiction. Data from a meta-analysis, investigating the relationship between internet addiction and psychiatric co-morbidity in different age-groups, including adolescents, suggested that internet addiction is associated with alcohol abuse, ADHD, depression and anxiety (1).
Antimicrobial Activity of Essential Oils against Staphylococcus and Malassezia Strains Isolated from Canine Dermatitis

Staphylococcus spp. bacteria are the most frequently involved agents in canine cutaneous infections. Treatment of these infections is based on antibiotic therapy, that often is not effective because of the antibiotic-resistance of the bacterial strains. Cutaneous staphylococcal infections are often complicated by Malassezia yeasts, that may be resistant to the conventional antifungal drugs. The present investigation was aimed to evaluate the in vitro antimicrobial activity of some essential oils (EOs) in view of a potential cutaneous application. In detail, EOs obtained from lemon verbena (Aloysia triphylla L’Hèr. Britton), cinnamon (Cinnamomum zeylanicum J. Presl), myrrh (Commiphora myrrha (Nees) Engl. var. molmol), lemongrass (Cymbopogon citratus (DC.) Stapf), litsea (Litsea cubeba (Lour.) Pers. ), lemon balm (Melissa officinalis L.), oregano (Origanum vulgare L.), savory (Satureja montana L.), and thyme (Thymus vulgaris L.) were assayed against Staphylococcus spp. and Malassezia pachydermatis strains previously isolated from dogs with dermatitis. All EOs were tested by agar disk diffusion and minimum inhibitory concentration methods to verify the antistaphylococcal activity, and by a microdilution method to evaluate the activity against M. pachydermatis. O. vulgare, T. vulgaris, and S. montana showed the best antibacterial activity against all the selected strains, with MICs ranging from 0.29 to 0.58 mg/mL, from 0.58 to 1.16 mg/mL, and from 0.56 to 1.12 mg/mL, respectively, whereas A. triphylla (1.03 mg/mL) and S. montana (1.8 mg/mL) were the most active against M. pachydermatis. After a proper in vivo evaluation, O. vulgare, T. vulgaris, and S. montana EOs could be a promising treatment to combat canine cutaneous mixed infections.
Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1

Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein phosphatase 2A (CIP2A), protein phosphatase methylesterase 1 (PME-1), and SET nuclear proto-oncogene (SET) that often are deregulated in cancers. However, how they impact cellular phosphorylation and how redundant they are in cellular regulation is poorly understood. Here, we conducted a systematic phosphoproteomics screen for phosphotargets modulated by siRNA-mediated depletion of CIP2A, PME-1, and SET (to reactivate PP2A) or the scaffolding A-subunit of PP2A (PPP2R1A) (to inhibit PP2A) in HeLa cells. We identified PP2A-modulated targets in diverse cellular pathways, including kinase signaling, cytoskeleton, RNA splicing, DNA repair, and nuclear lamina. The results indicate nonredundancy among CIP2A, PME-1, and SET in phosphotarget regulation. Notably, PP2A inhibition or reactivation affected largely distinct phosphopeptides, introducing a concept of nonoverlapping phosphatase inhibition- and activation-responsive sites (PIRS and PARS, respectively). This phenomenon is explained by the PPP2R1A inhibition impacting primarily dephosphorylated threonines, whereas PP2A reactivation results in dephosphorylation of clustered and acidophilic sites. Using comprehensive drug-sensitivity screening in PP2A-modulated cells to evaluate the functional impact of PP2A across diverse cellular pathways targeted by these drugs, we found that consistent with global phosphoproteome effects, PP2A modulations broadly affect responses to more than 200 drugs inhibiting a broad spectrum of cancer-relevant targets. These findings advance our understanding of the phosphoproteins, pharmacological responses, and cellular processes regulated by PP2A modulation and may enable the development of combination therapies.
Phylogeographic and population genetic analyses of Cucurbita moschata reveal divergence of two mitochondrial lineages linked to an elevational gradient.

PREMISE Domestication usually involves local adaptation to environmental conditions. Cucurbita species are a promising model for studying these processes. Cucurbita moschata is the third major crop in the genus because of its economic value and because it displays high landrace diversity, but research about its genetic diversity, population structure, and phylogeography is limited. We aimed at understanding how geography and elevation shape the distribution of genetic diversity in C. moschata landraces in Mexico. METHODS We sampled fruits from 24 localities throughout Mexico. We assessed 11 nuclear microsatellite loci, one mtDNA region, and three cpDNA regions but found no variation in cpDNA. We explored genetic structure with cluster analysis, and phylogeographic relationships with haplotype network analysis. RESULTS Mitochondrial genetic diversity was high, and nuclear genetic differentiation among localities was intermediate compared to other domesticated Cucurbita. We found high levels of inbreeding. We recovered two mitochondrial lineages: highland (associated with the Trans-Mexican Volcanic Belt) and lowland. Nuclear microsatellites show that localities from the Yucatan Peninsula constitute a well-differentiated group. CONCLUSIONS Mexico is an area of high diversity for C. moschata, and these landraces represent important plant genetic resources. In Mexico this species is characterized by divergence processes linked to an elevational gradient, which could be related to adaptation and may be of value for applications in agriculture. The Isthmus of Tehuantepec may be a partial barrier to gene flow. Morphological variation, agricultural management, and cultural differences may be related to this pattern of genetic structure, but further studies are needed.
Phosphate excess increases susceptibility to pathogen infection in rice

Abstract Phosphorus (P) is an essential nutrient for plant growth and productivity. Due to soil fixation, however, phosphorus availability in soil is rarely sufficient to sustain high crop yields. The overuse of fertilizers to circumvent the limited bioavailability of phosphate (Pi) has led to a scenario of excessive soil P in agricultural soils. Whereas adaptive responses to Pi deficiency have been deeply studied, less is known about how plants adapt to Pi excess and how Pi excess might affect disease resistance. We show that high Pi fertilization, and subsequent Pi accumulation, enhances susceptibility to infection by the fungal pathogen Magnaporthe oryzae in rice. This fungus is the causal agent of the blast disease, one of the most damaging diseases of cultivated rice worldwide. Equally, MIR399f overexpression causes an increase in Pi content in rice leaves, which results in enhanced susceptibility to M. oryzae. During pathogen infection, a weaker activation of defence‐related genes occurs in rice plants over‐accumulating Pi in leaves, which is in agreement with the phenotype of blast susceptibility observed in these plants. These data support that Pi, when in excess, compromises defence mechanisms in rice while demonstrating that miR399 functions as a negative regulator of rice immunity. The two signalling pathways, Pi signalling and defence signalling, must operate in a coordinated manner in controlling disease resistance. This information provides a basis to understand the molecular mechanisms involved in immunity in rice plants under high Pi fertilization, an aspect that should be considered in management of the rice blast disease.
Prognostic Effects of Treatment Strategies for Left Main Versus Non-Left Main Bifurcation Percutaneous Coronary Intervention With Current-Generation Drug-Eluting Stent

Supplemental Digital Content is available in the text. Background: Although 1-stent with provisional approach is the preferred strategy for the treatment of bifurcation lesions, the optimal treatment strategy according to lesion location is still debatable. This study aimed to identify whether clinical outcomes according to treatment strategy differed between left main (LM) and non-LM bifurcation lesions in the second-generation drug-eluting stent era. Methods: The Coronary Bifurcation Stenting registry III is a retrospective multicenter registry of 2648 patients with bifurcation lesions who underwent percutaneous coronary intervention with second-generation drug-eluting stent. Among the study population, 935 (35.3%) patients had an LM bifurcation lesion. The primary outcome was target lesion failure, a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Median follow-up duration was 53 months. LM bifurcation was associated with a higher risk of target lesion failure (HRadj, 1.846 [95% CI, 1.317–2.588]; P<0.001) than non-LM bifurcation. Two-stent strategy was more frequently applied in patients with LM bifurcation than in patients with non-LM bifurcation (27.1% versus 11.7%; P<0.001). In the LM bifurcation group, compared with the 1-stent strategy, the 2-stent strategy showed a significantly higher risk of target lesion failure (2-stent versus 1-stent, 17.4% versus 10.6%; HRadj, 1.848 [95% CI, 1.045–3.266]; P=0.035), mainly driven by the higher rate of target lesion revascularization (15.3% versus 5.5%; HRadj, 2.698 [95% CI, 1.276–5.706]; P=0.009). However, the risk of cardiac death or myocardial infarction did not differ between the 2 groups (4.4% versus 6.6%; HRadj, 0.694 [95% CI, 0.306–1.572]; P=0.381). For patients with non-LM-bifurcation, there was no significant difference in the rate of target lesion failure between 1-stent and 2-stent strategies (5.6% versus 6.3%; HRadj, 0.925 [95% CI, 0.428–2.001]; P=0.843). Conclusions: Even in the second-generation drug-eluting stent era, the 1-stent strategy, if possible, should initially be considered the preferred approach for the treatment of LM bifurcation lesions. Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT03068494.