Miracle-dz/UniFAR-FTUs huggingface dataset:
Editorial Comment: Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control

There is increasing evidence for a possible causal association between the chronic use of anticholinergics and the risk of developing dementia. The inherent limitation for establishing such causal nexus is precisely the fact that the prevalence of overactive bladder (OAB) symptoms and the prescription of antimuscarinics tends to increase in older individuals, exactly in the same age groups in which the incidence of dementia is higher (1). Coupland et al. carried out a nested case-control study based on the QResearch primary care database from England, including 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Primary exposure was defined as the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95%CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95%CI, 1.162.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95%CI, 1.561.75), and antiepileptic drugs (AOR, 1.39; 95%CI, 1.22-1.57) all for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. Despite attempts to control for confounding variables, the results of case-control studies should be viewed with caution. Even so, this is not the first study to suggest an association between the chronic use of anticholinergics and the development of dementia. Physicians should be aware of new evidences and attempt to reduce exposure to anticholinergic drugs in middle-aged and older people. One question still needs to be answered: are all antimuscarinics alike? Vol. 46 (2): 283-284, March April, 2020
Präventive Geriatrie: kognitiven Abbau verhindern

Was ist neu? Prävention des kognitiven Abbaus Maßnahmen zur Früherkennung und zur Prävention des kognitiven Abbaus stehen im Vordergrund der Therapie. Im Gegensatz zur früheren Trennung zwischen neurodegenerativen und vaskulären Formen der Demenz wird aktuell die konsequente Therapie und Einstellung von kardiovaskulären Risikofaktoren angestrebt, um das Fortschreiten von möglicherweise allen Demenzformen zu verlangsamen. Die im Mai dieses Jahres von der Weltgesundheitsorganisation veröffentlichten Leitlinien geben Anhaltspunkte, wie dem Nachlassen der kognitiven Funktion mit zunehmendem Alter begegnet werden kann. Zu den Säulen der Prävention gehören eine ausgewogene Ernährung (für die Substitution einzelner, künstlicher Nährstoffe gibt es keine Evidenz), körperliche Aktivität (vor allem aerobes Training), ausreichender Schlaf, Konvivialität und soziale Interaktion (sensorische Störungen, gerade eine Beeinträchtigung des Hörens, dürfen nicht unterschätzt werden) sowie kognitive Aktivitäten und Übungen, die die allgemeinen, exekutiven und logischen Funktionen, die Denkgeschwindigkeit und das Arbeitsgedächtnis unterstützen. Konsequenz für den klinischen Alltag Obwohl alle o. g. Bereiche des Lebensstils für die Prävention des kognitiven Abbaus wichtig sind, sind multidimensionale Interventionen nur dann für den Erhalt der Funktionen wirksam, wenn diese auf die Bedürfnisse jedes einzelnen Patienten zugeschnitten werden (die sogenannten personalized tailored interventions) und mit persönlichem Interesse, guter Lebensqualität und adäquatem Wohlbefinden verbunden sind.
Coiling for an unruptured saccular aneurysm at the non-branching segment of the distal anterior cerebral artery: Case report and literature review

Background Saccular aneurysms in the non-branching segment of the distal anterior cerebral artery (DACA) are extremely rare. Here, we describe the first case of coil embolization using a simple, non-adjunctive technique for an aneurysm at this rare location. Case description A 74-year-old man with an asymptomatic, unruptured aneurysm of the right DACA was followed up annually for 3 years by medical checkup. Endovascular treatment was proposed because of a slight angiographic change in the shape of the aneurysm in the past year. The aneurysm at the non-branching site of the right calloso-marginal artery was 2 mm distal to the origin, and measured 3 mm in height and 3.3 mm in width, with a neck measuring 1.7 mm wide; the calloso-marginal artery diameter was 1.6 mm. The aneurysm was successfully embolized with a simple technique using a Pre-Shaped S Microcatheter and two coils. Conclusions The simple, non-adjunctive technique for coil embolization of saccular side-wall type aneurysm in the non-branching segment of the DACA could be performed using the appropriate catheter and a softer coil.
Evaluating and expanding the European Union's protected‐area network toward potential post‐2020 coverage targets

The Convention on Biological Diversity's (CBD) strategic plan will expire in 2020, but biodiversity loss is ongoing. Scientists call for more ambitious targets in the next agreement. The nature‐needs‐half movement, for example, has advocated conserving half of Earth to solve the biodiversity crisis, which has been translated to protecting 50% of each ecoregion. We evaluated current protection levels of ecoregions in the territory of one of the CBD's signatories, the European Union (EU). We also explored the possible enlargement of the Natura 2000 network to implement 30% or 50% ecoregion coverage in the EU member states’ protected area (PA) network. Based on the most recent land‐use data, we examined whether ecoregions have enough natural area left to reach such high coverage targets. We used a spatially explicit mixed integer programing model to estimate the least‐cost expansion of the PA network based on 3 scenarios that put different emphasis on total conservation cost, ecological representation of ecosystems, or emphasize an equal share of the burden among member states. To realize 30% and 50% ecoregion coverage, the EU would need to add 6.6% and 24.2%, respectively, of its terrestrial area to its PA network. For all 3 scenarios, the EU would need to designate most recommended new PAs in seminatural forests and other semi‐ or natural ecosystems. Because 15 ecoregions did not have enough natural area left to implement the ecoregion‐coverage targets, some member states would also need to establish new PAs on productive land, allocating the largest share to arable land. Thirty percent ecoregion coverage was met by protecting remaining natural areas in all ecoregions except 3, where productive land would also need to be included. Our results support discussions of higher ecoregions protection targets for post‐2020 biodiversity frameworks.
Comorbidity of congenital heart defects and holoprosencephaly is likely genetically driven and gene‐specific

Comorbidity of holoprosencephaly (HPE) and congenital heart disease (CHD) in individuals with genetic variants in known HPE‐related genes has been recurrently observed. Morphogenesis of the brain and heart from very early stages are regulated by several biological pathways, some of them involved in both heart and brain development as evidenced by genetic studies on model organisms. For instance, downregulation of Hedgehog or Nodal signaling pathways, both known as major triggers of HPE, has been shown to play a role in the pathogenesis of CHD, including structural defects and left–right asymmetry defects. In this study, individuals with various types of HPE were investigated clinically and by genomic sequencing. Cardiac phenotypes were assessed in 434 individuals with HPE who underwent targeted sequencing. CHDs were identified in 8% (n = 33) of individuals, including 10 (30%) cases of complex heart disease. Only four individuals (4/33) had damaging variants in the known HPE genes STAG2, SIX3, and SHH. Interestingly, no CHD was identified in the 37 individuals of our cohort with pathogenic variants in ZIC2. These findings suggest that CHD occurs more frequently in HPE‐affected individuals with or without identifiable genetic variants, and this co‐occurrence may be genetically driven and gene‐specific.
Association between galectin-3 levels and isolated coronary artery ectasia.

BACKGROUND Coronary artery ectasia (CAE) is a well-recognised disorder characterised by abnormal dilation of the coronary arteries. Underlying mechanisms associated with abnormal luminal dilation in CAE remain to be elucidated. However, histopathological features resemble those of coronary atherosclerosis. Galectin-3 (Gal-3) is a valuable biomarker for both progression and destabilisation of atherosclerotic lesions. To the best of our knowledge, there is no study in the literature examining serum Gal-3 levels in patients with isolated CAE. In the present study, therefore, we aimed to investigate the possible relationship between serum Gal-3 levels and isolated CAE. METHODS Between March 2016 and March 2017 this prospective, case-controlled study included a total of 49 consecutive isolated CAE patients (31 males, 18 females) diagnosed with CAE by coronary angiography at the catheter laboratory of Medeniyet University, Goztepe Training and Research Hospital, and 43 individuals (19 males, 24 females) with normal coronary arteries. Physical examination, medical history, blood biochemistry and transthoracic echocardiography were performed in both groups. Serum concentrations of Gal-3 were measured using blood samples. RESULTS Median Gal-3 levels were significantly higher in isolated CAE patients than in the controls [23.2 (23.9 ± 7.1) vs 16.8 ng/ml (17.8 ± 7.3); p < 0.001]. According to the Markis classification, the extent of CAE was not correlated with Gal-3 levels (p = 0.41). Multivariate regression analysis revealed that Gal-3 concentration was an independent predictor of isolated CAE. CONCLUSIONS Our study results suggest that Gal-3 serum concentrations significantly increased in patients with isolated CAE, indicating that Gal-3 may be involved in the pathogenesis of isolated CAE.
Controlling the Electronic Properties of a Nanoporous Carbon Surface by Modifying the Pores with Alkali Metal Atoms

We investigate a process of controlling the electronic properties of a surface of nanoporous carbon glass-like thin films when the surface pores are filled with potassium atoms. The presence of impurities on the surface in the form of chemically adsorbed hydrogen and oxygen atoms, and also in the form of hydroxyl (OH) groups, is taken into account. It is found that even in the presence of impurities, the work function of a carbon nanoporous glass-like film can be reduced by several tenths of an electron volt when the nanopores are filled with potassium atoms. At the same time, almost all potassium atoms are ionized, losing one electron, which passes to the carbon framework of the film. This is due to the nanosizes of the pores in which the electron clouds of the potassium atom interact maximally with the electrons of the carbon framework. As a result, this leads to an improvement in the electrical conductivity and an increase in the electron density at the Fermi level. Thus, we conclude that an increase in the number of nanosized pores on the film surface makes it possible to effectively modify it, providing an effective control of the electronic structure and emission properties.
Carbon metabolic profiling of Trichoderma strains provides insight into potential ecological niches

ABSTRACT Many Trichoderma species are cosmopolitan and widespread free-living fungi in various ecological environment, and many are economically important in the fields of agriculture and industry. However, carbon metabolism profiles of Trichoderma species have not been characterized in detail. In this study, Biolog FF MicroPlates were used to contrast carbon utilization and the differences among five Trichoderma species, each representing a unique phenotype. Their metabolic abilities varied greatly. Species producing cellulases and chitinases and with phosphate-solubilizing activities exhibited high efficiency of substrate utilization, whereas low efficiency was shown by saline-alkaline-tolerant species that metabolized simple carbon sources. Species producing cellulases at high levels may be specified to decompose and assimilate cellulose and hemicellulose in woody substrates, and those producing chitinases may have mycoparasitic roles. Species with plant growth–promoting traits are good at uptake of exudates from plant roots. Overall, metabolic models reflect nutritional adaptation of Trichoderma to diverse niches in nature.
Characterizing the role of Zn cluster family transcription factor ZcfA in governing development in two Aspergillus species

Filamentous fungi reproduce asexually or sexually, and the processes of asexual and sexual development are tightly regulated by a variety of transcription factors. In this study, we characterized a Zn2Cys6 transcription factor in two Aspergillus species, A. nidulans (AN5859) and A. flavus (AFLA_046870). AN5859 encodes a Zn2Cys6 transcription factor, called ZcfA. In A. nidulans, ΔzcfA mutants exhibit decreased fungal growth, a reduction in cleistothecia production, and increased asexual reproduction. Overexpression of zcfA results in increased conidial production, suggesting that ZcfA is required for proper asexual and sexual development in A. nidulans. In conidia, deletion of zcfA causes decreased trehalose levels and decreased spore viability but increased thermal sensitivity. In A. flavus, the deletion of the zcfA homolog AFLA_046870 causes increased conidial production but decreased sclerotia production; these effects are similar to those of zcfA deletion in A. nidulans development. Overall, these results demonstrate that ZcfA is essential for maintaining a balance between asexual and sexual development and that some roles of ZcfA are conserved in Aspergillus spp.
Abundance, size, and survival of recruits of the reef coral Pocillopora acuta under ocean warming and acidification

Ocean warming and acidification are among the greatest threats to coral reefs. Massive coral bleaching events are becoming increasingly common and are predicted to be more severe and frequent in the near future, putting corals reefs in danger of ecological collapse. This study quantified the abundance, size, and survival of the coral Pocillopora acuta under future projections of ocean warming and acidification. Flow-through mesocosms were exposed to current and future projections of ocean warming and acidification in a factorial design for 22 months. Neither ocean warming or acidification, nor their combination, influenced the size or abundance of P. acuta recruits, but heating impacted subsequent health and survival of the recruits. During annual maximum temperatures, coral recruits in heated tanks experienced higher levels of bleaching and subsequent mortality. Results of this study indicate that P. acuta is able to recruit under projected levels of ocean warming and acidification but are susceptible to bleaching and mortality during the warmest months.
Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning

Aims Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores – for example, the Dutch Lipid Score – are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a “virtual” genetic test using machine-learning approaches. Methods and results We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data (N = 174) and internal test (N = 74)) and the FH-CEGP Milan cohort (external test, N = 364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machine-learning algorithms performed better (AUROC 0.79 (CT), 0.83 (GBM), and 0.83 (NN) on the Gothenburg cohort, and 0.70 (CT), 0.78 (GBM), and 0.76 (NN) on the Milan cohort) than the clinical Dutch Lipid Score (AUROC 0.68 and 0.64 on the Gothenburg and Milan cohorts, respectively) in predicting carriers of FH-causative mutations. Conclusion In the diagnosis of FH-causative genetic mutations, all three machine-learning approaches we have tested outperform the Dutch Lipid Score, which is the clinical standard. We expect these machine-learning algorithms to provide the tools to implement a virtual genetic test of FH. These tools might prove particularly important for lipid clinics without access to genetic testing.
Visual spatial learning outcomes for clinical trials in neurofibromatosis type 1

Cognitive problems are common in children with neurofibromatosis type 1, representing a significant source of lifelong morbidity. Assessment of cognitive function has been challenging in the setting of clinical trials. Spatial learning deficits may be an important target for cognitive interventions. We leveraged a large, international cognitive study in affected children with NF1 treated with lovastatin to assess spatial learning using the “Arena Maze”, a portable, computerized task that allows for retesting in the same environment. As with the parent study, spatial learning assessed with this task did not improve with lovastatin treatment.
Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy.

BACKGROUND This multicenter randomized trial compared oral capecitabine with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer. PATIENTS AND METHODS Patients were assigned to 24 weeks of capecitabine 1250 mg/m2 twice daily on days 1-14 every 3 weeks or 5-FU/FA (Mayo Clinic regimen). The primary end point was disease-free survival (DFS). RESULTS The intent-to-treat population received capecitabine (n = 1004) or 5-FU/FA (n = 983). With a median follow-up of 6.9 years, capecitabine was at least equivalent to 5-FU/FA in terms of DFS [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.77-1.01] and overall survival (OS) (HR = 0.86; 95% CI 0.74-1.01); the 95% CI upper limits were significantly less than the predefined noninferiority margins of 1.20 (P < 0.0001) and 1.14 (P < 0.001), respectively. This pattern was maintained in all subgroups, including patients aged ≥70 years. Preplanned multivariate analyses showed that capecitabine had statistically significant beneficial effects on DFS (P = 0.021) and OS (P = 0.020) versus 5-FU/FA. A post hoc analysis suggested that the occurrence of hand-foot syndrome may be associated with better outcomes in capecitabine recipients. CONCLUSION Oral capecitabine is an effective alternative to bolus 5-FU/FA as adjuvant treatment of patients with stage III colon cancer with efficacy benefits maintained at 5 years and in older patients.
Validation of a counseling guide for adherence to antiretroviral therapy using implementation science*

Objective: to determine the contents that must be included in the usual counseling to improve the adherence to antiretroviral therapy (ART) of HIV patients, according to their different levels of alcohol consumption, and to determine the validity of the Counseling Guide in improving the adherence to ART in patients who consume alcohol using Implementation Science. Method: this is an observational study with formative and validation phases. The formative phase defined the content, approach and structure of the counseling. Validation included focus groups with patients and nurses, trial process by an expert and a pilot test. The criteria evaluated based on Implementation Science were: intervention source, evidence strength and quality, relative advantage, and complexity. The following criteria were also evaluated: usefulness, practicality, acceptability, sustainability, effectiveness; content consistency and congruence; procedural compliance and difficulties, and time spent in counseling. Results: the strength of evidence of the counseling is High-IIA, with strong level of recommendation and presenting usefulness, practicality, acceptability, sustainability and effectiveness. Eight in 11 experts argued that the Guide is clear, consistent and congruent. Initial counseling takes around 24 minutes; and follow-up counseling, 21. The instruments of the Guide present reliability levels between good and high (0.65 ≥ alpha ≤ 0.92). Conclusion: the Counseling Guide is valid to improve the adherence to antiretroviral therapy in patients who consume alcohol.
Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh

Background In Bangladesh, pneumonia has a higher mortality among malnourished children aged <5 years. Evaluating pneumonia etiology among malnourished children may help improve empiric treatment guidelines. Methods During April 2015—December 2017, we conducted a case-control study among severe acute malnourished (SAM) children aged <5 years admitted to the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). We enrolled hospital admitted SAM children with clinical or radiological pneumonia as cases (during April 2015 to March 2017) and hospital admitted SAM children without any respiratory symptom in the past 10 days before admission as controls (during February 2016 to December 2017). We tested nasopharyngeal wash from both case and control for respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza viruses, human parainfluenza viruses (HPIV), rhinovirus and adenovirus by singleplex real-time reverse transcriptase polymerase chain reaction. To identify the independent association of pneumonia with viral pathogens during February 2016 to March 2017, we used multivariable logistic regression for calculating adjusted odds ratios. Results We enrolled 360 cases and 334 controls. For case and control the median age was 8 months (IQR: 5–13) and 11 months (IQR: 6–18) (p = 0.001) respectively. Weight/age Z-score was -4.3 (SD ±0.7) for cases and -4.1 (SD ±1.1) for controls (p = 0.01). Among cases 68% had both clinical and radiological pneumonia, 1% had clinical pneumonia and 31% had only radiological pneumonia. Respiratory virus detection was high in cases compared to controls [69.9% (251) vs. 44.8% (148), p = 0.0001]. The most frequently detected viruses among cases were rhinoviruses (79, 22.0%) followed by RSV (32, 8.9%), adenovirus (23, 6.4%), HPIV (22, 6.1%), influenza virus (16, 4.5%), and HMPV (16, 4.5%). Among the controls, rhinoviruses (82, 24.8%) were most commonly detected one followed by adenovirus (26,7.9%), HMPV (5, 1.5%), HPIV (4, 1.2%), RSV (3, 0.9%), and influenza virus (2, 0.6%). RSV (OR 13.1; 95% CI: 1.6, 106.1), influenza virus (OR 8.7; 95% CI: 1.0, 78.9), HPIV (3.8; 95% CI: 1.0, 14.8), and HMPV (2.7; 95% CI: 1.3, 5.5) were independently associated with pneumonia while compared between 178 cases and 174 controls. Conclusion Viral etiology of pneumonia in SAM children were mainly attributable to RSV, influenza, HPIV and HMPV. Our study findings may help in planning further studies targeting vaccines or drugs against common respiratory viruses responsible for pneumonia among SAM children.