Miracle-dz/UniFAR-FTUs huggingface dataset:
The interplay of climate and land use change affects the distribution of EU bumblebees

Bumblebees in Europe have been in steady decline since the 1900s. This decline is expected to continue with climate change as the main driver. However, at the local scale, land use and land cover (LULC) change strongly affects the occurrence of bumblebees. At present, LULC change is rarely included in models of future distributions of species. This study's objective is to compare the roles of dynamic LULC change and climate change on the projected distribution patterns of 48 European bumblebee species for three change scenarios until 2100 at the scales of Europe, and Belgium, Netherlands and Luxembourg (BENELUX). We compared three types of models: (1) only climate covariates, (2) climate and static LULC covariates and (3) climate and dynamic LULC covariates. The climate and LULC change scenarios used in the models include, extreme growth applied strategy (GRAS), business as might be usual and sustainable European development goals. We analysed model performance, range gain/loss and the shift in range limits for all bumblebees. Overall, model performance improved with the introduction of LULC covariates. Dynamic models projected less range loss and gain than climate‐only projections, and greater range loss and gain than static models. Overall, there is considerable variation in species responses and effects were most pronounced at the BENELUX scale. The majority of species were predicted to lose considerable range, particularly under the extreme growth scenario (GRAS; overall mean: 64% ± 34). Model simulations project a number of local extinctions and considerable range loss at the BENELUX scale (overall mean: 56% ± 39). Therefore, we recommend species‐specific modelling to understand how LULC and climate interact in future modelling. The efficacy of dynamic LULC change should improve with higher thematic and spatial resolution. Nevertheless, current broad scale representations of change in major land use classes impact modelled future distribution patterns.
Treatment of autoinflammatory syndromes

Purpose of review Inherited autoinflammatory diseases are experiments in nature in which mutations of proteins playing a pivotal role in the regulation of the innate immunity lead to unprovoked episodes of inflammation. The understanding of the molecular pathways involved in these disorders has shed a new light on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets. In this review, we outline the more recent novelties in the treatment of autoinflammatory diseases and their possible implications for some multifactorial pediatric conditions. Recent findings Cryopyrin-associated periodic syndrome (CAPS) represents the prototype of autoinflammatory diseases. The study of the pathophysiological consequence of mutations of the cryopyrin gene (NLRP3) allowed the identification of the intracellular pathways thought to play a pivotal part in the activation and secretion of the potent inflammatory cytokine interleukin (IL)-1β. The dramatic effect of IL-1 blockade in CAPS opens new perspectives for the treatment of other inherited and multifactorial inflammatory disorders. A number of IL-1 blockers are now available on the market. Summary Studies on the pathogenesis and treatment of inherited autoinflammatory diseases are also changing the approach to some multifactorial inflammatory conditions.
The guanine nucleotide exchange factor Arhgef5 plays crucial roles in Src-induced podosome formation

Podosomes and invadopodia are actin-rich membrane protrusions that play a crucial role in cell adhesion and migration, and extracellular matrix remodeling in normal and cancer cells. The formation of podosomes and invadopodia is promoted by upregulation of some oncogenic molecules and is closely related to the invasive potential of cancer cells. However, the molecular mechanisms underlying the podosome and invadopodium formation still remain unclear. Here, we show that a guanine nucleotide exchange factor (GEF) for Rho family GTPases (Arhgef5) is crucial for Src-induced podosome formation. Using an inducible system for Src activation, we found that Src-induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3-binding protein. RNA interference (RNAi)-mediated depletion of Arhgef5 caused robust inhibition of Src-dependent podosome formation. Overexpression of Arhgef5 promoted actin stress fiber remodeling through activating RhoA, and the activation of RhoA or Cdc42 was required for Src-induced podosome formation. Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity. Furthermore, the pleckstrin homology (PH) domain of Arhgef5 was required for podosome formation, and Arhgef5 formed a ternary complex with Src and phosphoinositide 3-kinase when Src and/or Arhgef5 were upregulated. These findings provide novel insights into the molecular mechanisms of podosome and invadopodium formation induced by Src upregulation.
Regulación del flujo de lodo en tuberías

El desarrollo de lodos de liquido en las tuberias multifase es un importante -y costoso- quebradero de cabeza para los productores de petroleo. En el yacimiento petrolifero de Hod, explotado por BP en el Mar del Norte, los problemas causados por un descenso de la produccion de petroleo han dado lugar a un flujo de lodo inducido por el material del terreno en la tuberia situada entre la plataforma de la cabeza de pozo y la plataforma de produccion. El flujo irregular da lugar a una mala separacion del petroleo y del agua, limita la capacidad de produccion y origina combustiones de gases. Un algoritmo prototipo de control anticipativo, desarrollado de forma conjunta por ABB y BP para eliminar el flujo de lodo inducido por el material del terreno en las tuberias, ha estado siendo utilizado in situ desde enero de 2000 con interesantes resultados.
When open access might not work: Understanding patient attitudes in appointment scheduling

Background: Open-access (OA) systems aim to reduce delays to care. However, recent evidence suggests that OA systems might reduce patient satisfaction and result in poorer patient experiences due to patients’ inability to obtain appointments with their usual care provider. We conducted a series of experiments to explore the role of risk attitudes, an individual difference variable that measures preferences for risky options, in patients’ perception of OA systems. Purpose: The aim of the study was to investigate the relationship between patient’s risk attitudes and attitudes toward OA systems and demonstrate whether patients’ attitudes toward OA systems will vary as a function of their risk attitudes. Methodology: Three separate experiments were conducted to assess the relationship between patient risk attitudes and their attitudes about OA systems. Study 1 (patient population) explored the aforementioned relationship. We explored two potential moderators for this effect: how salient the tradeoff is between delays to care and quality of care (Study 2; online population) and the severity of the patient’s health condition (Study 3; patient population). Results: Compared to risk-averse patients, risk-seeking patients have more favorable attitudes toward OA systems (a 1-point increase in risk attitudes on a 7-point scale resulted in a 0.44-point boost in attitudes toward OA systems on a 7-point scale). This relationship holds even when the tradeoff between access to care and quality of care is made salient (e.g., a practice informs patients they can have a same-day appointment but are unlikely to see their regular provider) and when people consider having a minor health condition. This relationship is attenuated when patients imagine having a serious medical condition because speedy access to care becomes a top priority. Conclusion: Risk-seeking patients have more favorable attitudes toward OA systems. Practice Implications: Risk-seeking patients are primarily driven by speed to access at the potential expense of continuity of care. Organizations that better understand patient motives in scheduling medical appointments can introduce more effective interventions and positively impact patient experiences of care.
The Expanding Spectrum of Herpesvirus Infections of the Nervous System

Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV‐1), and less frequently HSV‐2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV‐2, and benign recurrent meningitis with HSV‐2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV‐2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV‐6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV‐mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV‐associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75‐year‐old male on steroid treatment for chronic lung disease with fatal HSV‐2 meningitis and an 81‐year‐old male with myasthenia gravis, long‐term azathioprine use, and an EBV‐associated primary CNS lymphoma.
Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort

Objectives To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. Design Prospective multinational population based observational study. Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. Participants 7336 infants born between 24+0 and 31+6 weeks’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. Main outcome measures Combined use of four evidence based practices for infants born before 28 weeks’ gestation using an “all or none” approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. Results Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. Conclusions More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.
Caffeine intake and the risk of first-trimester spontaneous abortion.

BACKGROUND Some epidemiologic studies have suggested that the ingestion of caffeine increases the risk of spontaneous abortion, but the results have been inconsistent. METHODS We performed a population-based, case-control study of early spontaneous abortion in Uppsala County, Sweden. The subjects were 562 women who had spontaneous abortion at 6 to 12 completed weeks of gestation (the case patients) and 953 women who did not have spontaneous abortion and were matched to the case patients according to the week of gestation (controls). Information on the ingestion of caffeine was obtained from in-person interviews. Plasma cotinine was measured as an indicator of cigarette smoking, and fetal karyotypes were determined from tissue samples. Multivariate analysis was used to estimate the relative risks associated with caffeine ingestion after adjustment for smoking and symptoms of pregnancy such as nausea, vomiting, and tiredness. RESULTS Among nonsmokers, more spontaneous abortions occurred in women who ingested at least 100 mg of caffeine per day than in women who ingested less than 100 mg per day, with the increase in risk related to the amount ingested (100 to 299 mg per day: odds ratio, 1.3; 95 percent confidence interval, 0.9 to 1.8; 300 to 499 mg per day: odds ratio, 1.4; 95 percent confidence interval, 0.9 to 2.0; and 500 mg or more per day: odds ratio, 2.2; 95 percent confidence interval, 1.3 to 3.8). Among smokers, caffeine ingestion was not associated with an excess risk of spontaneous abortion. When the analyses were stratified according to the results of karyotyping, the ingestion of moderate or high levels of caffeine was found to be associated with an excess risk of spontaneous abortion when the fetus had a normal or unknown karyotype but not when the fetal karyotype was abnormal. CONCLUSIONS The ingestion of caffeine may increase the risk of an early spontaneous abortion among non-smoking women carrying fetuses with normal karyotypes.
Production of reagents and optimization of methods for studying calmodulin-binding proteins.

Owing to subtle but potentially crucial structural and functional differences between calmodulin (CaM) of different species, the biochemical study of low-affinity CaM-binding proteins from Dictyostelium discoideum likely necessitates the use of CaM from the same organism. In addition, most of the methods used for identification and purification of CaM-binding proteins require native CaM in nonlimiting biochemical quantities. The gene encoding D. discoideum CaM has previously been cloned allowing production of recombinant protein. The present study describes the expression of D. discoideum CaM in Escherichia coli and its straightforward and rapid purification. Furthermore, we describe the optimization of a complete palette of assays to detect as little as nanogram quantities of proteins binding CaM with middle to low affinities. Purified CaM was used to raise high-affinity polyclonal antibodies suitable for immunoblotting, immunofluorescence, and immunoprecipitation experiments. The purified CaM was also used to optimize a specific and sensitive nonradioactive CaM overlay assay as well as to produce a high-capacity CaM affinity chromatography matrix. The effectiveness of this methods is illustrated by the detection of potentially novel D. discoideum CaM-binding proteins and the preparatory purification of one of these proteins, a short tail myosin I.
Candida albicans Pmr1p, a Secretory Pathway P-type Ca2+/Mn2+-ATPase, Is Required for Glycosylation and Virulence*

The cell surface of Candida albicans is the immediate point of contact with the host. The outer layer of the cell wall is enriched in highly glycosylated mannoproteins that are implicated in many aspects of the host-fungus interaction. Glycosylation of cell wall proteins is initiated in the endoplasmic reticulum and then elaborated in the Golgi as the protein passes through the secretory pathway. Golgi-bound mannosyltransferases require Mn2+ as an essential cofactor. In Saccharomyces cerevisiae, the P-type ATPase Pmr1p transports Ca2+ and Mn2+ ions into the Golgi. To determine the effect of a gross defect in glycosylation on host-fungus interactions of C. albicans, we disrupted the PMR1 homolog, CaPMR1. This mutation would simultaneously inhibit many Golgi-located, Mn2+-dependent mannosyltransferases. The Capmr1Δ null mutant was viable in vitro and had no growth defect even on media containing low Ca2+/Mn2+ ion concentrations. However, cells grown in these media progressively lost viability upon entering stationary phase. Phosphomannan was almost completely absent, and O-mannan was severely truncated in the null mutant. A defect in N-linked outer chain glycosylation was also apparent, demonstrated by the underglycosylation of surface acid phosphatase. Consistent with the glycosylation defect, the null mutant had a weakened cell wall, exemplified by hypersensitivity to Calcofluor white, Congo red, and hygromycin B and constitutive activation of the cell integrity pathway. In a murine model of systemic infection, the null mutant was severely attenuated in virulence. These results demonstrate the importance of glycosylation for cell wall structure and virulence of C. albicans.
A comparative study of the transhiatal laparoscopic approach versus laparoscopic gastric mobilisation and right open transthoracic esophagectomy for esophageal cancer management.

AIM Regarding the surgical treatment of esophageal cancer, a question was raised by the introduction of minimally invasive surgery, because of the technical complexity of the techniques involved and its uncertain benefits. We evaluated the impact of laparoscopic esophagectomy on the surgical approach to esophageal cancer. PATIENTS AND METHODS From January 2002 to March 2006, 22 non-randomized patients were recruited to undergo esophagectomy for neoplastic disease. The esophagectomy and esophagogastroplasty were performed using the laparoscopic transhiatal technique (THE) in 9 cases, while a combined laparoscopic gastric mobilisation and right transthoracic incision (TT/LE) was performed in the other 13. RESULTS Mean follow up was 21+/-3.23 months, range 2-46 months. Overall cumulative survival was 84.0% at 12 months, 61.3% at 24 months, 51.0% at 36 months. THE achieved better results than TT/LE on the ground with regard to the time it took to complete the procedure (p=0.046) and the hospital stay times (p=0.039), and the time in ICU, postoperative oral feeding resumption, number of retrieved lymph nodes. CONCLUSION The clinical benefits of minimally invasive techniques regard the time it takes to complete the procedure, the time in ICU, postoperative oral feeding resumption and the hospital stay times. Minimally invasive surgery might be not less curative and effective than open surgical procedures, as found in our small non-randomzed series of patients. Larger series should confirm these results.
Trans-arterial chemoembolization of metastatic colorectal carcinoma to the liver adopting DC Bead®, drug-eluting bead loaded with irinotecan: results of a phase II clinical study.

UNLABELLED Trans-arterial chemoembolization (TACE) is a promising locoregional therapy for the treatment of primary hepatic tumors and liver metastases. The aim of the study was to define the activity and outcome of using DC Bead, drug-eluting bead, a spherical embolic device capable of being loaded with irinotecan. PATIENTS AND METHODS We conducted a double institutional, single arm, phase II clinical study to evaluate TACE adopting this device in 82 patients presenting with metastatic colorectal carcinoma to the liver after failing chemotherapy. The primary endpoints were tumor shrinkage, safety, feasibility, compliance, and overall survival. RECIST criteria were used to assess responses. Quality of life (QoL) was addressed using Edmonton SAS improvement scale. RESULTS Out of 103 patients considered, 82 were enrolled and underwent a total of 185 treatments of TACE. The median number of TACE was 2.2 (1-4). A post-embolization syndrome was frequently observed. Adverse observed effects were: right upper quadrant pain (40%), fever (80%), nausea (27%) and increased transaminases (70%). The median follow-up was 29 months. Within one month after treatment, each patient received a computed tomograpic scan. It showed reduction of metastatic contrast enhancement in all patients. Responses were 78% at 3 months. After the first treatment, 75 out 82 patients declared an improvement of their well being lasting more than 18 weeks. The median duration of response was 6 (range 3-10) months; the median follow up was 29 (range 7-48) months. The median survival was 25 (range 6-34) months, with progression free survival at 8 (range 4-16) months. CONCLUSION We suggest that TACE adopting DC Bead®, drug-eluting bead loaded with irinotecan could be proposed as palliative therapy for unresectable and chemotherapy resistant liver metastases from CRC.
CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: a follow-up study.

BACKGROUND Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and Abeta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD. METHODS We determined the ratio of CSF tau/Abeta(42) (T/Abeta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12). RESULTS We identified 16% of the control group with abnormally elevated CSF T/Abeta; all were 53 years or older. Using age-matched controls with normal CSF T/Abeta we showed that the high CSF T/Abeta subgroup of controls had significantly increased frequency of the epsilon4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture. CONCLUSIONS These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.