Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of Clinical Questions Submitted to Norwegian Drug Information Centres Concerning Administration and Dosage to Older Patients of Relevance to Patient-Centric Care

Patient-centric care entails optimising healthcare provision to patients based on their perspective and opinion. It involves appropriate treatment at a reasonable cost and a focus on patient characteristics in the decision-making process to make it more personally useful. The optimisation of medicines in the older population is a challenge due to physiological changes, comorbidity, and polypharmacy. Furthermore, patient-centric care is difficult to achieve due to the high proportion of patients with dementia and frailty. Decision support concerning the appropriateness of indication, formulation, dose, administration, co-prescribing, and length of treatment to older patients is frequently in demand. In the current study, we aimed to review clinical questions concerning administration and dosage to older patients of relevance to patient-centric care. We analysed questions concerning medicines to patients 65 years or older in the database of the network of Norwegian drug information centres from 2010 to 2020. The analysis included the distribution of drugs, diseases, and recurring topics among the questions. Through a Boolean search that combined the indexed categories of “older” and “administration and dosage”, we retrieved 84 question-answer pairs. Questions about psychotropic and cardiovascular drugs in relation to therapy, adverse drug reactions, and pharmacokinetics dominated, and more than 60% of the questions came from physicians. Topics relevant to patient-centric pharmacotherapy were drug withdrawal (10 questions), drug formulation (8 questions), drug initiation (8 questions), and switching drugs (5 questions). One question concerned drug withdrawal and switching, and one question drug formulation and switching. Answers provided decision support regarding appropriate formulations of drugs to patients with dementia who chew capsules or tablets, the use of parenteral administration in patients who refuse to take oral formulations, and the pharmacokinetics of transdermal or rectal drug administration. The results highlight the importance of including pharmacological factors in the assessment of the acceptability and appropriateness of oral and parenteral medicine to older patients.
Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus

Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here.
Study on functional sites in human multidrug resistance protein 1 (hMRP1)

Human multidrug resistance protein 1 (hMRP1) is an important member of the ATP‐binding cassette (ABC) transporter superfamily. It can extrude a variety of anticancer drugs and physiological organic anions across the plasma membrane, which is activated by substrate binding, and is accompanied by large‐scale cooperative movements between different domains. Currently, it remains unclear completely about how the specific interactions between hMRP1 and its substrate are and which critical residues are responsible for allosteric signal transduction. To the end, we first construct an inward‐facing state of hMRP1 using homology modeling method, and then dock substrate proinflammatory agent leukotriene C4 (LTC4) to hMRP1 pocket. The result manifests LTC4 interacts with two parts of hMRP1 pocket, namely the positively charged pocket (P pocket) and hydrophobic pocket (H pocket), similar to its binding mode with bMRP1 (bovine MRP1). Additionally, we use the Gaussian network model (GNM)‐based thermodynamic method proposed by us to identify the key residues whose perturbations markedly alter their binding free energy. Here the conventional GNM is improved with covalent/non‐covalent interactions and secondary structure information considered (denoted as sscGNM). In the result, sscGNM improves the flexibility prediction, especially for the nucleotide binding domains with rich kinds of secondary structures. The 46 key residue clusters located in different subdomains are identified which are highly consistent with experimental observations. Furtherly, we explore the long‐range cooperation within the transporter. This study is helpful for strengthening the understanding of the work mechanism in ABC exporters and can provide important information to scientists in drug design studies.
DNAModAnnot: a R toolbox for DNA modification filtering and annotation

Abstract Motivation Long-read sequencing technologies can be employed to detect and map DNA modifications at the nucleotide resolution on a genome-wide scale. However, published software packages neglect the integration of genomic annotation and comprehensive filtering when analyzing patterns of modified bases detected using Pacific Biosciences (PacBio) or Oxford Nanopore Technologies (ONT) data. Here, we present DNA Modification Annotation (DNAModAnnot), a R package designed for the global analysis of DNA modification patterns using adapted filtering and visualization tools. Results We tested our package using PacBio sequencing data to analyze patterns of the 6-methyladenine (6mA) in the ciliate Paramecium tetraurelia, in which high 6mA amounts were previously reported. We found P. tetraurelia 6mA genome-wide distribution to be similar to other ciliates. We also performed 5-methylcytosine (5mC) analysis in human lymphoblastoid cells using ONT data and confirmed previously known patterns of 5mC. DNAModAnnot provides a toolbox for the genome-wide analysis of different DNA modifications using PacBio and ONT long-read sequencing data. Availability and implementation DNAModAnnot is distributed as a R package available via GitHub (https://github.com/AlexisHardy/DNAModAnnot). Supplementary information Supplementary data are available at Bioinformatics online.
Effects of Exercise Interventions on Inflammatory Parameters in Acutely Hospitalized Older Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The purpose of this systematic review and meta-analysis was to appraise the acute effects of exercise training on inflammatory parameters in hospitalized older adults. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, Medline and PubMed were searched for studies published until August 2020. The review included all randomized controlled trials (RCTs) that evaluated and compared the effect of exercise versus usual care on inflammatory parameters in acutely hospitalized older adults. Two reviewers independently assessed the studies. The quality of all the included studies was assessed using the DerSimonian–Laird random-effects inverse-variance model. Five studies (275 participants) met the inclusion criteria. The exercise interventions included resistance or multicomponent intervention programs. The results indicate that, compared with usual care, exercise interventions have a positive impact on overall inflammatory parameters, including C-reactive protein (CRP) and insulin-like growth factor-I (IGF-1) (Hedge’s g = −0.19, 95% confidence interval [CI] −0.33 to −0.04, p = 0.011, I2 = 0%). However, analyses of individual inflammatory parameters revealed a non-significant trend for reductions in CRP (Hedge’s g = −0.20, 95% CI −0.47 to 0.07, p = 0.151, I2 = 31.2%) and IGF-I (Hedge’s g = −0.34, 95% CI −0.79 to 0.11, p = 0.138, I2 = 0%). On the basis of this review, we conclude that exercise during acute hospitalization offers a mild improvement in the inflammatory profile over usual care in older patients. Nevertheless, due to limited number of RCTs, our findings must be interpreted with caution and confirmed in future studies.
Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.
Effects of application technique and anaerobic digestion on gaseous nitrogen loss from animal slurry applied to ryegrass (Lolium perenne)

SUMMARY Ammonia volatilization and denitrification were measured in a ryegrass field in Denmark after direct injection and application with trail hoses of an untreated cattle slurry and an anaerobically digested slurry in late May-early June 1993 and 1994. Ammonia volatilization was measured using a windtunnel system for a period of 8 days after slurry application. Denitrification was measured for a period of 21 days after slurry application. In an adjacent field experiment, nitrogen-uptake (N-uptake) was determined in the first two cuts of the ryegrass harvested after slurry application. N losses through ammonia volatilization were larger in 1993 than in 1994 due to differences in climatic conditions. Ammonia volatilization was lowered substantially (47–72%), when slurry was injected compared with surface application. In 1993 the loss from surface-applied digested slurry was only 35% of total ammoniacal nitrogen (TAN), while the loss from the raw slurry was 47%. There were no significant differences in ammonia volatilization from the two slurry types in the other experiments. N losses through denitrification were low (< 2% of TAN), but there were clear differences in the losses, depending on slurry type, application method and experimental year. Injection of the slurry gave a larger N-uptake in the first cut of grass compared to the trail-hose application. In 1993 N-uptake from the digested slurry treatment gave significantly larger N-uptake compared to the raw slurry in the first cut.
Cardiac arrhythmia during early‐week and mid‐week dialysis in hemodialysis patients

Data on cardiac arrhythmia and electrolyte changes during the dialysis cycle have been limited. Fifty‐two hemodialysis (HD) patients underwent 48‐h Holter monitoring during early‐week and mid‐week HD sessions. Pre‐HD and post‐HD blood samples were collected in both HD sessions. The 48‐h Holter data were divided into five phases: (1) 4‐h during the early‐week HD (HD1), (2) 12‐h post‐HD1, (3) 16‐h period between Phases 2 and 4 (used as the patient's baseline electrocardiography [ECG]), (4) 12‐h pre‐HD2 phase, and (5) 4‐h during the mid‐week HD (HD2). The patients' mean age was 68.54 ± 13.37 years. We found that the dialysate‐to‐serum[K] gradient and changes of S[K] were significantly higher in HD1 than in HD2, as well as changes of S[Mg]. There were no significant ECG changes during the 4‐h HD1 and HD2 when compared with the baseline ECG. Phase 2 of Holter ECG was the most common phase that showed significant changes (increased QT interval dispersion (QTD), increased ventricular events, increased number of premature ventricular contractions, ST elevation and ST depression), which was contributed from the dialysate[K] 2 mmol/L subgroup, but not the dialysate[K] 3 mmol/L subgroup. In the subgroup of patients with a high ultrafiltration rate (UFR; mean UFR ≥10 mL/kg/h), there were significantly increased ventricular events and ST‐segment changes in Phase 2. In conclusion, ECG changes were associated with the dialysis cycle, significantly in the 12‐h after early‐week HD sessions. These may be associated with low dialysate[K] or high dialysate‐to‐S[K] gradient, high ultrafiltration rate and duration of the interdialytic interval.
New amino acid substitution matrix brings sequence alignments into agreement with structure matches

Protein sequence matching presently fails to identify many structures that are highly similar, even when they are known to have the same function. The high packing densities in globular proteins lead to interdependent substitutions, which have not previously been considered for amino acid similarities. At present, sequence matching compares sequences based only upon the similarities of single amino acids, ignoring the fact that in densely packed protein, there are additional conservative substitutions representing exchanges between two interacting amino acids, such as a small‐large pair changing to a large‐small pair substitutions that are not individually so conservative. Here we show that including information for such pairs of substitutions yields improved sequence matches, and that these yield significant gains in the agreements between sequence alignments and structure matches of the same protein pair. The result shows sequence segments matched where structure segments are aligned. There are gains for all 2002 collected cases where the sequence alignments that were not previously congruent with the structure matches. Our results also demonstrate a significant gain in detecting homology for “twilight zone” protein sequences. The amino acid substitution metrics derived have many other potential applications, for annotations, protein design, mutagenesis design, and empirical potential derivation.
Factors affecting the uptake of preventive chemotherapy treatment for schistosomiasis in Sub-Saharan Africa: A systematic review

Background Schistosomiasis affects nearly 220 million people worldwide, mainly in Sub-Saharan Africa (SSA). Preventive chemotherapy (PC) treatment, through regular mass-drug administration (MDA) of Praziquantel tablets remains the control measure of choice by Ministries of Health. Current guidelines recommend that 75% of school-aged children receive treatment. Many programmes, however, struggle to achieve this target. Given the risk of high reinfection rates, attaining sustained high levels of treatment coverage is essential. This study provides a comprehensive review of the barriers and facilitators operating at different levels of analysis, from the individual to the policy level, conditioning the uptake of PC for schistosomiasis in SSA. Methodology/Principal findings A systematic literature search was conducted in several databases for publications released between January 2002 and 2019 that examined factors conditioning the uptake of Praziquantel in the context of MDA campaigns in SSA. A total of 2,258 unique abstracts were identified, of which 65 were selected for full text review and 30 met all eligibility criteria. Joanna Briggs Institute’s Critical Appraisal and the Mixed-Methods Assessment tools were used to assess the strength of the evidence. This review was registered with PROSPERO (CRD42017058525). A meta-synthesis approach was used. Results indicated publication bias, with the literature focusing on East African rural settings and evidence at the individual and programmatic levels. The main influencing factors identified included material wellbeing, drug properties, knowledge and attitudes towards schistosomiasis and MDAs, fears of side effects, gender values, community and health systems support, alongside programme design features, like training, sensitisation, and provision of incentives for drug-distributors. The effect of these factors on determining Praziquantel uptake were explored in detail. Conclusions/Significance Multiple determinants of treatment uptake were found in each level of analysis examined. Some of them interact with each other, thus affecting outcomes directly and indirectly. The promotion of context-based transdisciplinary research on the complex dynamics of treatment uptake is not only desirable, but essential, to design effective strategies to attain high levels of treatment coverage.
Characterization of CNT/TiO 2 Electrode Prepared Through Impregnation with TNB and Their Photoelectrocatalytic Properties

In this study, we have prepared three kinds of carbon nanometer tube (CNT)/TiO2 electrodes through impregnation with different concentration titanium n-butoxide (TNB) solution. The prepared electrodes were characterized with surface properties, structural crystallinity, elemental identification and photoelectrocatalytic activity. The N2 adsorption data showed that the composites had decreased surface area compared with the pristine CNT. This indicated the blocking of micropores on the surface of CNT, which was further supported by observation via SEM. XRD results showed patterns for the composites and a typical single and clear anatase crystal structure. The main elements such as C, O and Ti were existed for all samples from the EDX data. The catalytic efficiency of the developed electrode was evaluated by the photoelectrodegradation of methylene blue (MB). The positive potential applied in photoelectrocatalytic (PEC) oxidation was studied. It was found that photoelectrocatalytic (PEC) decomposition of MB solution could be attributed to combination effects between TiO2 photocatalytic and CNT electro-assisted. Through the comparison between photocatalytic (PC) oxidation and photoelectrocatalytic (PEC) oxidation, it was found that the PEC oxidation efficiency for MB is higher than that of PC oxidation.
Neck pain and associated factors in a sample of high school students in the city of Bauru, São Paulo, Brazil: cross-sectional study.

BACKGROUND Neck pain is a major public health problem. OBJECTIVE The aim of the present study was to determine the prevalence of neck pain among high school students and to analyze associations with sociodemographic variables, use of electronic devices, habitual physical activity practices and mental health problems. DESIGN AND SETTING Cross-sectional epidemiological study on a sample of high school students in the city of Bauru, São Paulo, Brazil. METHOD Participants were selected through cluster sampling in two stages and data were collected via face-to-face interviews. Data collection comprised the following steps: 1. sociodemographic characteristics; 2. use of electronic devices; 3. habitual physical activity levels; 3. mental health; and 4. neck pain. RESULTS A total of 1,628 participants were interviewed. The prevalence of neck pain was 49.1% (95% confidence interval, CI 46.7 to 51.5), with 40.4% (95% CI 37.0 to 43.7) in men and 57.5% (95% CI 54.2 to 60.9) in women. The variables associated with in neck pain were: female (prevalence ratio, PR = 2.04), use of cell phone in standing posture (PR = 1.47), use of tablet in sitting posture (PR = 1.72), length of computer use greater than 3 hours/day (PR = 1.54), length of cell phone use greater than 3 hours/day (PR = 1.54), length of tablet use greater than 3 hours/ day (PR = 1.34) and mental health problems (PR = 1.56). CONCLUSION There is high prevalence of neck pain among students and striking associations with female sex, use of electronic devices and mental health problems.
Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism Saccharomyces cerevisiae facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in S. cerevisiae. Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various S. cerevisiae strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes.
Comparative Proteomic Analysis of the Mesenchymal Stem Cells Secretome from Adipose, Bone Marrow, Placenta and Wharton’s Jelly

Mesenchymal stem cells (MSCs) have the potential to be a viable therapy against various diseases due to their paracrine effects, such as secretion of immunomodulatory, trophic and protective factors. These cells are known to be distributed within various organs and tissues. Although they possess the same characteristics, MSCs from different sources are believed to have different secretion potentials and patterns, which may influence their therapeutic effects in disease environments. We characterized the protein secretome of adipose (AD), bone marrow (BM), placenta (PL), and Wharton’s jelly (WJ)-derived human MSCs by using conditioned media and analyzing the secretome by mass spectrometry and follow-up bioinformatics. Each MSC secretome profile had distinct characteristics depending on the source. However, the functional analyses of the secretome from different sources showed that they share similar characteristics, such as cell migration and negative regulation of programmed cell death, even though differences in the composition of the secretome exist. This study shows that the secretome of fetal-derived MSCs, such as PL and WJ, had a more diverse composition than that of AD and BM-derived MSCs, and it was assumed that their therapeutic potential was greater because of these properties.