Miracle-dz/UniFAR-FTUs huggingface dataset:
Symptoms in Children Receiving Treatment for Cancer—Part I: Fatigue, Sleep Disturbance, and Nausea/Vomiting

Children and adolescents with cancer often undergo intensive chemotherapy treatment to obtain remission and long-term survival. The pursuit of successful treatment outcomes may lead to high levels of symptom distress related to treatment side effects and toxicities. The Children’s Oncology Group Nursing Discipline held a State of the Science Symposium “Symptom Assessment During Childhood Cancer Treatment” in 2018 that included reviews of evidence regarding key symptoms. The purpose of this review is to summarize and synthesize the evidence presented about the prevalence, relationships, trajectories, and associated biomarkers of selected symptoms experienced by children and adolescents during cancer treatment. Five symptoms were selected, with the focus on fatigue, sleep disturbance, and nausea/vomiting and included in Part I of the review. Using Ovid-Medline, studies published between 2008 and 2018 that focused on these specific symptoms during active chemotherapy treatment were selected. Fatigue interferes with normal developmental activities and is associated with sleep disturbances, and its pattern changes within a cycle of chemotherapy as well as across the treatment trajectory. Sleep is disrupted by the hospital environment, treatment medications, and changes in normal childhood and schedules. Disturbances of sleep persist during treatment, preventing recovery from poor quality sleep. Although pharmacologic interventions have advanced for treatment of nausea and vomiting, children and adolescents continue to struggle with this symptom. Its trajectory changes with the intensity of treatment, and over half of the patients report that they experience nausea and/or vomiting. Future research is needed to advance identification of biologic risk factors for symptoms and test effectiveness of symptom-related interventions.
Hybridization and a loss of sex shape genome-wide diversity and the origin of species in the evening primroses (Oenothera, Onagraceae).

•Hybridization is thought to promote speciation in at least two ways, by fixation of heterozygosity from diploid progenitors in allopolyploids, or by generation of transgressive phenotypes and shifting fitness optima during homoploid hybrid speciation. While recent studies support a hybrid origin for a growing number of species, the extent to which hybrid origins shape patterns of diversity in asexual species remains underexplored. •Here we employed transcriptome sequencing and population genomic analysis to describe patterns of genomic variation in the 13 species belonging to Oenothera subsection Oenothera. Eight of these species are functionally asexual, and arose by hybrid speciation from parents spanning a range of phylogenetic divergence. •We showed that genomic divergence between parents has been retained as heterozygosity in functionally asexual species, and that genome-wide levels of heterozygosity in these asexuals largely reflects the divergence of parental haplotypes coupled with a breakdown in recombination and segregation across the genome. •These results show that divergence between parental species and loss of sex in hybrids shape patterns of whole genome diversity and the origin of asexual species. This article is protected by copyright. All rights reserved.
Comparison of three frailty models and a sarcopenia model in elderly patients with chronic obstructive pulmonary disease

Frailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models – the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures – and one sarcopenia model for older patients with COPD.
Managing Uncertainty within KTD

The dilemma between exploration and exploitation is an important topic in reinforcement learning (RL). Most successful approaches in addressing this problem tend to use some uncertainty information about values estimated during learning. On another hand, scalability is known as being a lack of RL algorithms and value function approximation has become a major topic of research. Both problems arise in real-world applications, however few approaches allow approximating the value function while maintaining uncertainty information about estimates. Even fewer use this information in the purpose of addressing the exploration/exploitation dilemma. In this paper, we show how such an uncertainty information can be derived from a Kalman-based Temporal Dierences (KTD) framework and how it can be used.
Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial.

BACKGROUND Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI. METHODS Hospitalized children (≥3 months to <18 years) with cIAI were randomized 3:1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7-15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit. RESULTS Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in ≥90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits. CONCLUSIONS Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.
Plasma cytokine profile on admission related to aetiology in community‐acquired pneumonia

Potentially unnecessary antibiotic use for community‐acquired pneumonia (CAP) contributes to selection of antibiotic‐resistant pathogens. Cytokine expression at the time that treatment is started may assist in identifying patients not requiring antibiotics. We determined plasma cytokine patterns in patients retrospectively categorized as strict viral, pneumococcal or combined viral‐bacterial CAP.
Extending Structural Learning Paradigms for High-Dimensional Machine Learning and Analysis

Structure-based machine-learning techniques are frequently used in extensions of supervised learning, such as active, semi-supervised, multi-modal, and multi-task learning. A common step in many successful methods is a structure-discovery process that is made possible through the addition of new information, which can be user feedback, unlabeled data, data from similar tasks, alternate views of the problem, etc. Learning paradigms developed in the above-mentioned fields have led to some extremely flexible, scalable, and successful multivariate analysis approaches. This success and flexibility offer opportunities to expand the use of machine learning paradigms to more complex analyses. In particular, while information is often readily available concerning complex problems, the relationships among the information rarely follow the simple labeled-example-based setup that supervised learning is based upon. Even when it is possible to incorporate additional data in such forms, the result is often an explosion in the dimensionality of the input space, such that both sample complexity and computational complexity can limit real-world success. In this work, we review many of the latest structural learning approaches for dealing with sample complexity. We expand their use to generate new paradigms for combining some of these learning strategies to address more complex problem spaces. We overview extreme-scale data analysis problems where sample complexity is a much more limiting factor than computational complexity, and outline new structurallearning approaches for dealing jointly with both. We develop and demonstrate a method for dealing with sample complexity in complex systems that leads to a more
Further Results on Nyquist's Problem in Pulse Transmission

The Nyquist criterion specifies pulse shapes for a synchronous pulse amplitude modulation (PAM) signal which produce no intersymbol interference when the signal is sampled at the proper instants. For bandwidths in excess of one half the pulse repetition rate, the criterion is not uniquely satisfied. This paper considers the selection of pulse shapes for a single-sideband carrier signal which, in addition to satisfying the Nyquist criterion, will introduce minimal interference for small sampling time and carrier phase error at the receiver.
Relationships Between Diffusion Tensor Imaging and Cerebrospinal Fluid Metrics in Early Stages of the Alzheimer's Disease Continuum.

Recently, the field of Alzheimer's disease (AD) research has adopted a new framework that places the progression of Alzheimer's disease along a continuum consisting of a preclinical stage, followed by conversion to mild cognitive impairment, and ultimately dementia. Important neuropathological changes occur in the preclinical phase, necessitating the identification of metrics that can detect such early changes. While cerebrospinal fluid (CSF) measures of amyloid and tau are generally accepted as biomarkers of AD pathology, neuroimaging measures used to index white matter alterations throughout the brain remain less widely endorsed as candidate biomarkers. To explore the relationship between white matter alterations and AD pathology, we review the literature on multimodal studies that assessed both CSF markers and white matter indices, derived from diffusion tensor imaging (DTI) methods, across cohorts primarily in the early phases of AD. Our review indicates that abnormal CSF measures of Aβ42 and tau are associated with widespread alterations in white matter microstructure throughout the brain. Furthermore, white matter variability is related to individual differences in behavior and can aid in tracking longitudinal changes in cognition. Our review advocates for the utilization of DTI metrics in investigations of early AD and suggests that the combined use of DTI and CSF markers may better explain individual differences in cognition and disease progression. However, further research is needed to resolve certain mixed findings.
Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community

Abstract. A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case–control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to Leptospira and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96–10.0, P = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of Leptospira. No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu within a few years. A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.
The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
A binding site hotspot map of the FKBP12-rapamycin-FRB ternary complex by photo-affinity labeling and mass spectrometry-based proteomics.

Structural characterization of small molecule bind-ing site hotspots within the global proteome is uniquely enabled by photo-affinity labeling (PAL) coupled with chemical enrichment and unbiased analysis by mass spectrometry (MS). MS-based binding site maps provide structural resolution of interaction sites in conjunction with identification of target proteins. However, binding site hotspot mapping has been confined to relatively simple small molecules to date; extension to more com-plex compounds would enable the structural defi-nition of new binding modes in the proteome. Here, we extend PAL and MS methods to derive a binding site hotspot map for the immunosuppres-sant rapamycin, a complex macrocyclic natural product that forms a ternary complex with the pro-teins FKBP12 and FRB. Photo-rapamycin was de-veloped as a diazirine-based PAL probe for ra-pamycin, and the FKBP12-photo-rapamycin-FRB ternary complex formed readily in vitro. Photo-irradiation, digestion, and MS analysis of the ter-nary complex revealed a McLafferty rearrangement product of photo-rapamycin conjugated to specific surfaces on FKBP12 and FRB. Molecular modeling based on the binding site map revealed two distinct conformations of complex-bound photo-rapamycin, providing a 5.0 Å distance constraint between the conjugated residues and the diazirine carbon and a 9.0 Å labeling radius for the diazirine upon photo-activation. These measurements may be broadly useful in the interpretation of binding site measurements from PAL. Thus, in characteriz-ing the ternary complex of photo-rapamycin by MS, we applied binding site hotspot mapping to a macrocyclic natural product and extracted precise structural measurements for interpretation of PAL products that may enable the discovery of new binding sites in the "undruggable" proteome.
New insights on the disease contribution of neuroinflammation in amyotrophic lateral sclerosis.

PURPOSE OF REVIEW Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease with a strong neuroinflammatory component. This review summarizes how the connection between neurodegeneration and the immune system is strengthened by new discoveries from ALS genetics and the analysis of subpopulations of immune cells in ALS. RECENT FINDINGS Recent genes identified in ALS encode for proteins with direct immune roles, which when mutated lead to deregulation of immune functions, potentially influencing the disease. Although neuroinflammation in the central nervous system (CNS) of ALS patients has been well documented, new evidence suggests also direct malfunctions of immune cells in the CNS and at the periphery. Although CD4+ T-regulatory lymphocytes are protective in ALS, their number and function are altered over the disease course. CD8+ T cells are detrimental for motor neurons in the CNS but show some protective roles at the periphery. Similarly, the presence of mast cells in muscles of ALS models and patients and impairments of monocyte functions reveal potential new players in ALS disease progression. SUMMARY Although motor neuron degeneration is considered the prime event in ALS, dysfunctions in immune processes can impact the disease, highlighting that targeting specific immune components is a strategy for developing biomarkers and ultimately new drugs.
Association of IL-1 and TNF-αLevels in Endometrial Secretion and Success of Embryo Transfer in IVF/ICSI Cycles

Background In this work, we have determined the levels of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which function as cytokines in endometrial receptivity, through the endometrial secretion within the eligible individuals and thus studied their relationships with the success or failure of pregnancy in in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) cycles. Materials and Methods In this prospective study, 76 women were selected for their first IVF/ICSI and met the study inclusion criteria. All of the patients have undergone the endometrial secretion aspiration prior to performing the oocyte collection. The levels of IL-1and TNF-α were analyzed by the means of enzyme-linked immunosorbent assay method, using special standard kits. The patients were requested to undergo the serum human chorionic gonadotropin measurements and ultrasound evaluation for the purpose of detecting successful implantations and pregnancies. Results Among the 76 subjects of the study, 33 (43.4%) patients had a positive beta-human chorionic gonadotropin (β-hCG) and 44 (56.6%) resulted in a negative β-hCG. It should be also noted that through the patients with positive β-hCG, 23 (30.3%) of them displayed fetal heart rate in their transvaginal sonography (TVS). Compared to the group with failed pregnancies and their cytokine levels, we perceived a higher concentration of IL-1 in the group containing successful chemical pregnancies (P=0.00). However, there was no significant difference in terms of clinical pregnancy in the IL-1 levels between the two groups (P=0.06). In addition, there was not any notable difference in the levels of TNF-α between the two groups, neither in terms of chemical nor clinical pregnancy (P=0.8 and P=0.6, respectively). Conclusion The current study suggests that higher concentrations of IL-1 in endometrial secretions could be as- sociated with improved endometrial receptivity and IVF outcome. With regards to TNF-α, no statistically significant difference was observed between the groups of with and without successful pregnancies.
Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms. Objectives To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization. Design, Setting, and Participants Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge. Interventions Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary. Main Outcomes and Measures The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool. Results Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, -4% [95% CI, -15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, -1.47 [95% CI, -1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes. Conclusions and Relevance Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT02519725.