Miracle-dz/UniFAR-FTUs huggingface dataset:
Clostridioides difficile Infection, Still a Long Way to Go

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.
KRAS‐Mutated, Estrogen Receptor‐Positive Low‐Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery

Abstract We report on a woman with aggressive estrogen receptor‐positive, KRAS‐mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor (trametinib) and the aromatase inhibitor (letrozole), even though the disease had failed to respond to a combination of a PI3K inhibitor and different MEK inhibitor, as well as to trametinib and the estrogen modulator, tamoxifen, and to letrozole by itself. The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. Our current observations indicate that subtle variations in mechanisms of action of outwardly similar regimens may have a major impact on outcome and that such translational knowledge is critical for optimizing a precision medicine strategy. Key Points This report describes the remarkable response of a patient with KRAS‐mutated, estrogen receptor‐positive low‐grade serous ovarian cancer treated with trametinib (MEK inhibitor) and letrozole (aromatase inhibitor), despite prior progression on similar agents including tamoxifen (estrogen modulator). In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason for the patient not responding to the combination of trametinib and tamoxifen. The current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anticancer activity when used in combinations.
Association of Physical Activity and Physical Functioning Phenotypes With Fall Risk Among Women

Objective: Physical activity (PA) may slow aging-related declines in physical functioning (PF), but the relationship of PA and falls is not well understood. This study examined the association of PA and PF with falls. Methods: The Study of Women’s Health Across the Nation participants (n = 1597; age: 65.1 years ± 2.7) reported PF and PA in 2012–2013 and falls in 2016–2017. Four phenotypes were identified: high PA–high PF, high PA–low PF, low PA–high PF, and low PA–low PF. Results: One-third (29.3%) reported ≥1 fall. Women with low PA–low PF (RR = 1.32; 95% CI: 1.06, 1.66) and with high PA–low PF (RR = 1.37; 95% CI: 1.07, 1.74) were more likely to fall than high PA–high PF. Over time, women with worsening PF had increased fall risk (RR = 1.43; 95% CI: 1.17, 1.74), but women who increased PA did not. Discussion: Poor PF increases the risk of falls, regardless of PA. However, increasing PA does not necessarily increase fall risk, reinforcing the importance of PA engagement.
Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of HOXD1 for Horn Patterning in Bovidae

Abstract In the course of evolution, pecorans (i.e., higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as “headgear,” which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae.
How Do Pharmaceutical Companies Overcome a Corporate Productivity Crisis? Business Diversification into Medical Devices for Growth Potential

The purpose of this study was to analyze the performance of pharmaceutical companies’ business diversification into medical devices in terms of their technical efficiency (TE) as compared to that of traditional pharmaceutical companies. For a total of 174 externally audited pharmaceutical companies engaged in the drug product business between 2008 and 2019, pharmaceutical companies were classified into two groups according to medical device business diversification. The TE of pharmaceutical companies that diversify the medical device business was lower than that of traditional pharmaceutical companies. However, in terms of the meta-technology ratio (MTR) calculated using meta-frontier analysis, pharmaceutical companies diversified into medical devices showed higher MTR than the traditional pharmaceutical company group. The results imply that the corporate performance growth potential of traditional pharmaceutical companies is lower than that of pharmaceutical companies that have diversified into the medical device business.
The Use of Telehealth Technology to Support Health Coaching for Older Adults: Literature Review

Background Health coaching is an intervention process for driving behavior change through goal-setting, education, encouragement, and feedback on health-related behaviors. Telehealth systems that include health coaching and remote monitoring are making inroads in managing chronic conditions and may be especially suited for older populations. Objective This literature review aimed to investigate the current status of health coaching interventions incorporating telehealth technology and the associated effectiveness of this intervention to deliver health care with an emphasis on older adults (aged 65 and older). Methods A literature review was conducted to identify the research conducted on health coaching combined with remote monitoring for delivering health care to older adults. The Ovid MEDLINE and CINAHL databases were queried using a combination of relevant search terms (including middle aged, aged, older adult, elderly, health coaching, and wellness coaching). The search retrieved 196 papers published from January 2010 to September 2019 in English. Following a systematic review process, the titles and abstracts of the papers retrieved were screened for applicability to health coaching for older adults to define a subset for further review. Papers were excluded if the studied population did not include older adults. The full text of the 42 papers in this subset was then reviewed, and 13 papers related to health coaching combined with remote monitoring for older adults were included in this review. Results Of the 13 studies reviewed, 10 found coaching supported by telehealth technology to provide effective outcomes. Effectiveness outcomes assessed in the studies included hospital admissions/re-admissions, mortality, hemoglobin A1c (HbA1c) level, body weight, blood pressure, physical activity level, fatigue, quality of life, and user acceptance of the coaching program and technology. Conclusions Telehealth systems that include health coaching have been implemented in older populations as a viable intervention method for managing chronic conditions with mixed results. Health coaching combined with telehealth may be an effective solution for providing health care to older adults. However, health coaching is predominantly performed by human coaches with limited use of technology to augment or replace the human coach. The opportunity exists to expand health coaching to include automated coaching.
Microbial, environmental and anthropogenic factors influencing the indoor microbiome of the built environment

A built environment is a human‐made environment providing surroundings for human occupancy, activities, and settlement. It is supposed to safeguard humans from all undesirable and harmful pollutants; however, indoor concentrations of some pollutants are much greater than that of the outdoors. Bioaerosols infiltrate from the outdoors in addition to many indoor sources of bioaerosols including the use of various chemicals as well as activities like cooking, smoking, cleaning, or even normal movement. They are also associated with a number of serious health concerns. Various ecological factors associated with the generation, the persistence as well as the dispersal of these microbial components of indoor bioaerosols, are discussed in this review, that have not been considered all together till now. The factors like microbial taxa, environmental factors, and anthropogenic activities (human occupancy, activities, and impact of urbanization) are addressed in the review. Effects of both indoor environmental factors like architectural design, lighting, ventilation, temperature, humidity, indoor/outdoor ratio, particulate matter, indoor chemistry as well as outdoor environmental factors like geography, seasons, and meteorology on the microbial concentrations have been discussed. Efforts are underway to design selective pressures for microbes to create a healthy symbiotic built microbiome as the “right” indoor microbiome is a “healthy” indoor microbiome.
Bayesian Network as a Decision Tool for Predicting ALS Disease

Clinical diagnosis of amyotrophic lateral sclerosis (ALS) is difficult in the early period. But blood tests are less time consuming and low cost methods compared to other methods for the diagnosis. The ALS researchers have been used machine learning methods to predict the genetic architecture of disease. In this study we take advantages of Bayesian networks and machine learning methods to predict the ALS patients with blood plasma protein level and independent personal features. According to the comparison results, Bayesian Networks produced best results with accuracy (0.887), area under the curve (AUC) (0.970) and other comparison metrics. We confirmed that sex and age are effective variables on the ALS. In addition, we found that the probability of onset involvement in the ALS patients is very high. Also, a person’s other chronic or neurological diseases are associated with the ALS disease. Finally, we confirmed that the Parkin level may also have an effect on the ALS disease. While this protein is at very low levels in Parkinson’s patients, it is higher in the ALS patients than all control groups.
Syntheses, Crystal Structures, and Physico‐Chemical Studies of Sodium and Potassium Alcoholates Bearing Thienyl Substituents and their Derived Luminescent Samarium(III) Alkoxides

The synthesis, structural characterisation, electrochemistry, and luminescence properties of a series of alkali metal alcoholates and samarium(III) alkoxides with thiophene-based OR substituents are presented. The alkali metal alcoholates 7–15 were obtained by deprotonation of the carbinol with NaH or KH. Their molecular structures consist of tetranuclear alkali metal alcoholates with a distorted cubane-like M4O4 core (X-ray structure analyses). Each alkali metal is surrounded by three carbinolate ligands and (depending on the derivative) by additional tetrahydrofuran molecules. The mononuclear samarium alkoxides {Sm[OC(C4H3S)3]3(thf)3}·thf (16) and {Sm[OC(C16H13S)]3(thf)3}·thf (17) were synthesised by the salt metathesis reactions between {[KOC(C4H3S)3]4(thf)2}·thf (7), [NaOC(C4H3S)3]4(thf)2 (8) or {[KOC(C16H13S)]4(thf)3}·1/2thf (11), respectively, and SmCl3 in thf solution. The molecular structures of these air-sensitive base adducts have been determined by single crystal X-ray crystallography and reveal an approximately octahedral coordination sphere around the samarium metal atoms with three methoxido ligands and three facially arranged tetrahydrofuran molecules. The electrochemical properties are essentially dominated by the oxidation of the thienyl units. The emission spectra of the carbinols and their derived potassium and sodium compounds display broad bands attributed to the π* π transitions of the aromatic ligands. Luminescence studies performed on complexes 16 and 17 reveal the typical f–f transitions of the SmIII ion. The photophysical data suggest that an energy transfer from the ligand to the metal atom operates.
Annals of Warsaw University of Life Sciences – SGGW

The possibility to use a side-timber in glulam beams manufacturing for structural applications. The aim of presented study was to determine the mechanical properties of three-layered glued structural beams manufactured with the use of side-timber pieces as an outer layers and the fragmented main yield as an inner layer. Four types of beams were pressed and tested in terms of four-point bending strength and modulus of elasticity. Variants differed from each other in the direction of the fibers in the inner layer and in the presence of adhesive layer between the fragmented wood. Studies have shown that the bending strength of the beams depended on the calculation method. Moreover, no significant effect of the inner layer arranging method on the bending strength of the beams was found. The values of modulus of elasticity (MOE) were low. The presented study is a starting point for further investigations concerning the possible way of the rational application of fragmented timber pieces and the side-timber for structural applications.
Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis

Today, more than a billion people—one-sixth of the world’s population—are suffering from neglected tropical diseases. Human African trypanosomiasis, Chagas disease, and leishmaniasis are neglected tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. ABSTRACT Today, more than a billion people—one-sixth of the world’s population—are suffering from neglected tropical diseases. Human African trypanosomiasis, Chagas disease, and leishmaniasis are neglected tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. About half a million people living in tropical and subtropical regions of the world are at risk of contracting one of these three infections. Kinetoplastids have complex life cycles with different morphologies and unique physiological requirements at each life cycle stage. This review covers the latest findings on metabolic pathways impacting disease pathogenesis of kinetoplastids within the mammalian host. Nutrient availability is a key factor shaping in vivo parasite metabolism; thus, kinetoplastids display significant metabolic flexibility. Proteomic and transcriptomic profiles show that intracellular trypanosomatids are able to switch to an energy-efficient metabolism within the mammalian host system. Host metabolic changes can also favor parasite persistence, and contribute to symptom development, in a location-specific fashion. Ultimately, targeted and untargeted metabolomics studies have been a valuable approach to elucidate the specific biochemical pathways affected by infection within the host, leading to translational drug development and diagnostic insights.
The international temperature scale of 1990 (ITS-90)

On 1st January 1990 the International Temperature Scale of 1990 (ITS-90) will come into force. This brief article describes the new scale and gives the differences between temperatures measured on ITS-90 and those measured on the current international scale, the International Practical Temperature Scale of 1968 (IPTS-68).
Healthcare costs before and after stroke in patients with non-valvular atrial fibrillation who initiated treatment with rivaroxaban or warfarin

Abstract Aims Rivaroxaban reduces stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF). This study compared healthcare costs before and after stroke in NVAF patients treated with rivaroxaban or warfarin. Materials and methods Using de-identified IBM MarketScan Commercial and Medicare databases, this retrospective cohort study (from 2011 to 2019) included patients with NVAF who initiated rivaroxaban or warfarin within 30 days after initial NVAF diagnosis. Patients who developed stroke were identified, and stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) score, imputed by a random forest method. Total all-cause per-patient per-year (PPPY) costs of care were determined for patients: (1) who developed stroke during the pre- and post-stroke periods and (2) who remained stroke-free during the follow-up period. Treatment groups were balanced using inverse probability of treatment weighting. Results A total of 13,599 patients initiated rivaroxaban and 39,861 initiated warfarin, of which 272 (2.0%) and 1,303 (3.3%), respectively, developed stroke during a mean follow-up of 28 months. Among patients who developed stroke, PPPY costs increased from the pre-stroke to post-stroke period, with greater increases in the warfarin cohort relative to the rivaroxaban cohort. Overall, the costs increased by 1.78-fold for rivaroxaban vs 3.07-fold for warfarin; for less severe strokes (NIHSS < 5), costs increased 0.88-fold and 1.05-fold, respectively. Cost increases for more severe strokes (NIHSS ≥ 5) among rivaroxaban patients were half those for warfarin patients (3.19-fold vs 6.37-fold, respectively). Among patients without stroke, costs were similar during the follow-up period between the two treatment groups. Conclusions Total all-cause costs of care increased in the post-stroke period, and particularly in the patients treated with warfarin relative to those treated with rivaroxaban. The lower rate of stroke in the rivaroxaban cohort suggests that greater pre- to post-stroke cost increases result from more strokes occurring in the warfarin cohort.
The impact of exercise training versus caloric restriction on inflammation markers: a systemic review and meta-analysis

Abstract Obesity is associated with an increased risk of chronic, low-grade systematic inflammation for which exercise training (EX) and caloric restriction (CR) are potential treatments. We therefore performed a systematic meta-analysis to compare the effect of EX vs. CR and EX + CR vs. CR on inflammation markers in overweight and obese individuals. PubMed, Scopus, Web of Science and the Cochrane were searched up to April 2020 for EX vs. CR or EX + CR vs. CR interventions studies on inflammatory makers i.e. CRP, IL-6 and TNF-α in overweight and obese individuals. Standardized mean differences and 95% confidence intervals were calculated. Thirty two articles (reporting 38 trials) involving 2108 participants were included in the meta-analysis. Based on studies that directly compared EX and CR, there were no evidence for an effect of EX on IL-6 (p = 0.20) and TNF-α (p = 0.58), when compared with a CR. However, when compared to EX, CR has a statistically greater benefit on CRP (p = 0.01). In those studies, directly comparing EX + CR and CR, EX + CR caused a larger decrease in TNF-α (p = 0.002) and IL-6 (p = 0.02) and tended to decrease CRP (p = 0.06) when compared with CR. These results suggest that a combination of EX and CR may be more effective than CR alone at reducing inflammatory cytokines and CRP in overweight and obese individuals.
Current and Future Trends in the Laboratory Diagnosis of Sexually Transmitted Infections

Sexually transmitted infections (STIs) continue to exert a considerable public health and social burden globally, particularly for developing countries. Due to the high prevalence of asymptomatic infections and the limitations of symptom-based (syndromic) diagnosis, confirmation of infection using laboratory tools is essential to choose the most appropriate course of treatment and to screen at-risk groups. Numerous laboratory tests and platforms have been developed for gonorrhea, chlamydia, syphilis, trichomoniasis, genital mycoplasmas, herpesviruses, and human papillomavirus. Point-of-care testing is now a possibility, and microfluidic and high-throughput omics technologies promise to revolutionize the diagnosis of STIs. The scope of this paper is to provide an updated overview of the current laboratory diagnostic tools for these infections, highlighting their advantages, limitations, and point-of-care adaptability. The diagnostic applicability of the latest molecular and biochemical approaches is also discussed.