Miracle-dz/UniFAR-FTUs huggingface dataset:
The evidence base for psychotropic drugs approved by the European Medicines Agency: a meta-assessment of all European Public Assessment Reports

Abstract Aims To systematically assess the level of evidence for psychotropic drugs approved by the European Medicines Agency (EMA). Methods Cross-sectional analysis of all European Public Assessment Reports (EPARs) and meta-analyses of the many studies reported in these EPARs. Eligible EPARs were identified from the EMA's website and individual study reports were requested from the Agency when necessary. All marketing authorisation applications (defined by the drug, the route of administration and given indications) for psychotropic medications for adults (including drugs used in psychiatry and addictology) were considered. EPARs solely based on bioequivalence studies were excluded. Our primary outcome measure was the presence of robust evidence of comparative effectiveness, defined as at least two ‘positive’ superiority studies against an active comparator. Various other features of the approvals were assessed, such as evidence of non-inferiority v. active comparator and superiority v. placebo. For studies with available data, effect sizes were computed and pooled using a random effect meta-analysis for each dose of each drug in each indication. Results Twenty-seven marketing authorisations were identified. For one, comparative effectiveness was explicitly considered as not needed in the EPAR. Of those remaining, 21/26 (81%) did not provide any evidence of superiority against an active comparator, 2/26 (8%) were based on at least two trials showing superiority against active comparator and three (11%) were based on one positive trial; 1/26 provided evidence for two positive non-inferiority analyses v. active comparator and seven (26%) provided evidence for one. In total, 20/27 (74%) evaluations reported evidence of superiority v. placebo with two or more trials. Among the meta-analyses of initiation studies against active comparator (57 available comparisons), the median effect size was 0.051 (range −0.503; 0.318). Twenty approved evaluations (74%) reported evidence of superiority v. placebo on the basis of two or more initiation trials and seven based on a single trial. Among meta-analyses of initiation studies against placebo (125 available comparisons), the median effect size was −0.283 (range −0.820; 0.091). Importantly, among the 89 study reports requested on the EMA website, only 19 were made available 1 year after our requests. Conclusions The evidence for psychiatric drug approved by the EMA was in general poor. Small to modest effects v. placebo were considered sufficient in indications where an earlier drug exists. Data retrieval was incomplete after 1 year despite EMA's commitment to transparency. Improvements are needed.
Integrative taxonomy of the genus Dyscolus (Coleoptera, Carabidae, Platynini) in Ecuadorian Andes

The genus Dyscolus Dejean, 1831 is a highly speciose taxon of neotropical Carabidae and the major component of high-altitude ground beetle communities in the tropical Andes. The aim of this study is threefold: (i) refine the taxonomic position of the equatorial members of Dyscolus using molecular data, (ii) provide a delimitation of the species found in Ecuador in páramo and montane forest environments based on a robust combination of molecular and morphological data, (iii) describe the new species and take the nomenclatural decisions made necessary by the results of this study. The seclusion of Dyscolus from more basal platynine clades including Platynus, Batenus and Glyptolenus, is supported by a phylogenetic analysis of the COI marker. Twenty-five new species of Dyscolus, most of them microendemic, are described and illustrated: D. aquator Moret sp. nov. (Tandayapa, Pichincha), D. arauzae Moret sp. nov. (Mt Cayambe, Pichincha), D. arborarius Moret sp. nov. (Parque Nacional Yacuri, Loja), D. barragani Moret sp. nov. (Mt Ayapungu, Chimborazo), D. crespoae Moret sp. nov. (Parque Nacional Podocarpus, Zamora-Chinchipe), D. danglesi Moret sp. nov. (Parque Nacional Yacuri, Loja), D. donosoi Moret sp. nov. (Parque Nacional Podocarpus, Zamora-Chinchipe), D. eleonorae Moret sp. nov. (Cotopaxi and Pichincha provinces), D. famelicus Moret sp. nov. (Papallacta, Napo), D. giselae Moret sp. nov. (Reserva Otonga, Cotopaxi), D. globoculus Moret sp. nov. (Parque Nacional Podocarpus, Zamora-Chinchipe), D. gobbii Moret sp. nov. (Guamaní and Mt Antisana, Pichincha), D. incommunis Moret sp. nov. (Tandayapa, Pichincha), D. marini Moret sp. nov. (Parque Nacional Podocarpus, Loja), D. piscator Moret sp. nov. (Guamaní, Napo), D. placitus Moret sp. nov. (Guamaní, Napo), D. ravidus Moret sp. nov. (Parque Nacional Podocarpus, Loja), D. rivinus Moret sp. nov. (Reserva Otonga, Cotopaxi), D. rugitarsis Moret sp. nov. (Parque Nacional Yacuri, Loja), D. ruizi Moret sp. nov. (Parque Nacional Podocarpus, Loja and Zamora), D. salazarae Moret sp. nov. (Parque Nacional Podocarpus, Loja), D. silvestris Moret sp. nov. (Papallacta, Napo), D. sulcipedis Moret sp. nov. (Parque Nacional Yacuri, Loja), D. verecundior Moret sp. nov. (Mt Illiniza and Mt Corazón, Pichincha) and D. verecundissimus Moret sp. nov. (Mt Chimborazo, Chimborazo). Dyscolus palatus Moret, 1998 is newly synonymized with D. denigratus (Bates, 1891). We demonstrate the subgenus Hydrodyscolus Moret, 1996 to be polyphyletic and therefore consider it a junior synonym of Dyscolus Dejean, 1831.
Risk of herpes zoster with IL-17 inhibitor therapy for psoriasis and other inflammatory conditions

Abstract Background: Psoriasis is a chronic inflammatory skin disease that has been associated with a significantly higher risk of herpes zoster (HZ). Several newer biologics such as secukinumab, ixekizumab, and brodalumab inhibit IL-17 and have been highly effective for treatment of psoriasis. However, adverse events related to the immunosuppressive properties of these biologics have been observed. Methods: This review aims to synthesize and evaluate the literature investigating the risk of HZ in patients treated with IL-17 inhibitors, with a focus on psoriasis patients. We performed searches using the PubMED database with the following search terms: ‘psoriasis,’ ‘herpes zoster,’ ‘secukinumab,’ ‘ixekizumab,’ ‘brodalumab,’ ‘IL-17,’ ‘anti-IL-17,’ and ‘safety. ’ Clinical trials, cohort studies, review articles, and meta-analyses were evaluated. Results: Studies did not detect a higher risk of HZ infections in psoriasis patients treated with IL-17 inhibitors when compared to those treated with placebo or other therapies. Studies of IL-17 inhibitors for other indications including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and asthma yielded similar results. Conclusion: IL-17 inhibitors do not appear to increase risk of HZ. However, IL-17 inhibitors are relatively new medications, and further long-term data may be necessary to confirm this finding. Nevertheless, HZ vaccination should be considered on a case-bycase basis prior to initiating IL-17 therapy.
Spatial variation of water temperature characteristics and behavior in a Devon river system

SUMMARY. 1. The results of 5 years of continuous monitoring of river water temperatures at seventeen stations within the Exe basin, Devon, U.K., are presented and discussed. 2. Systematic spatial variation in mean annual water temperature was evident and was strongly related to the topographic variable of elevation. Deviations from this relationship reflect local influences of vegetation shading, runoff source and channel character. 3. Considerable spatial variation in temperature extremes was also apparent, and the Exe basin differs from several other British river systems in exhibiting highest peak temperatures at downstream sites on the mainstream. Discharge from Wimbleball Reservoir exerted a significant influence on annual maxima and minima. 4. A clear seasonal cycle characterized all stations and was objectively defined by second-order harmonic functions which varied in amplitude and phase across the study area. Marked spatial variability in the magnitude and timing of diurnal temperature fluctuations, in temperature duration curves and in accumulated temperatures was also recorded. 5. The implications of the spatial variation in thermal regime for the growth of brown trout was also investigated.
Enhancement of the Molecular and Serological Assessment of Hepatitis E Virus in Milk Samples

Hepatitis E virus (HEV) infection is endemic in developing and developed countries. HEV was reported to be excreted in the milk of ruminants, raising the possibility of transmission of HEV infection through the ingestion of contaminated milk. Therefore, the detection of HEV markers in milk samples becomes pivotal. However, milk includes inhibitory components that affect HEV detection assays. Previously it was reported that dilution of milk matrix improves the performance of HEV molecular assay, however, the dilution of milk samples is not the best strategy especially when the contaminated milk sample has a low HEV load. Therefore, the objective of this study is to compare the effect of extraction procedures on the efficiency of HEV RNA detection in undiluted milk samples. In addition, we assessed the effect of the removal of milk components such as fats and casein on the performance of the molecular and serological assays of HEV. Phosphate buffered saline (PBS) and different milk matrices (such as whole milk, skim milk, and milk serum) were inoculated with different HEV inoculums and subjected to two different extraction procedures. Method A includes manual extraction using spin column-based extraction, while method B includes silica-based automated extraction. Method A was more sensitive than method B in the whole milk and skim milk matrices with a LoD95% of 300 IU/mL, and virus recovery yield of 47%. While the sensitivity and performance of method B were significantly improved using the milk serum matrix, with LoD95% of 96 IU/mL. Interestingly, retesting HEV positive milk samples using the high sensitivity assay based on method B extraction and milk serum matrix increased the HEV RNA detection rate to 2-fold. Additionally, the performance of HEV serological assays such as anti-HEV IgG and HEV Ag in the milk samples was improved after the removal of the fat globules from the milk matrix. In conclusion, HEV RNA assay is affected by the components of milk and the extraction procedure. Removal of inhibitory substances, such as fat and casein from the milk sample increased the performance of HEV molecular and serological assays which will be suitable for the low load HEV milk with no further dilutions.
Expressão tecidual e reconhecimento imune da paramiosina do carrapato Rhipicephalus (Boophilus) microplus

Rhipicephalus microplus e um carrapato que parasita bovinos, prejudicando a producao de leite e carne, alem de ser um vetor para agentes de diversas doencas. O R. microplus causa serios prejuizos em paises que dependem da pecuaria, e os metodos de controle utilizados sao baseados no uso de acaricidas, os quais apresentam alto custo e contaminam o leite e a carne, alem de causarem impactos ao meio ambiente. Desta forma, novos metodos de controle, como o desenvolvimento de vacinas, tem sido sugeridos. Antigenos protetores ao gado tem sido divididos em dois grupos: expostos, que interagem com o sistema imune do hospedeiro, e ocultos, que nao interagem com o sistema imune do hospedeiro. A paramiosina (PRM) e uma proteina presente em invertebrados primariamente caracterizada pela sua funcao muscular, porem em diversos parasitos tem sido localizada em regioes nao musculares, sugerindo que a mesma tambem possa apresentar funcoes envolvidas com a evasao do sistema imune do hospedeiro. A PRM de Taenia solium inibe in vitro a via classica do sistema complemento, por meio do bloqueio da funcao de C1, e a de R. microplus liga a porcao Fc de imunoglobulinas. Este estudo teve por objetivo avaliar o reconhecimento da paramiosina de R. microplus (RmPRM) por bovinos infectados com o carrapato e determinar os niveis de expressao do gene da paramiosina em tecidos e diferentes estagios de desenvolvimento do carrapato, tendo sido tambem avaliada a atividade anti-complemento da proteina recombinante. Os resultados mostraram que o soro de bovinos Bos indicus e B. taurus naturalmente infectados foram capazes de reconhecer paramiosina recombinante. Os niveis de anticorpos encontrados entre os bovinos apresentaram variacoes consideraveis, porem com os maiores titulos predominando entre individuos B. indicus. A transcricao do gene da RmPRM foi constatada na maioria dos tecidos, orgaos, ovos e larvas testados, com maior nivel de expressao encontrado no corpo gorduroso, um orgao sem predominância de tecido muscular. Alem disso, este trabalho mostra que a RmPRM e capaz de inibir o sistema complemento, indicando que esta proteina deve ser um importante componente para a sobrevivencia do parasito, possivelmente envolvida na modulacao do sistema imune do hospedeiro. Corroborando com outros trabalhos em parasitos, estes resultados sugerem que a RmPRM desempenha outras funcoes alem das classicamente descritas na musculatura.
Learning Adaptive Embedding Considering Incremental Class

Class-Incremental Learning (CIL) aims to train a reliable model with the streaming data, which emerges unknown classes sequentially. Different from traditional closed set learning, CIL has two main challenges: (1) Novel class detection. The initial training data only contains incomplete classes, and streaming test data will accept unknown classes. Therefore, the model needs to not only accurately classify known classes, but also effectively detect unknown classes; (2) Model expansion. After the novel classes are detected, the model needs to be updated without re-training using the entire previous data. However, traditional CIL methods have not fully considered these two challenges. First, they are always restricted to single novel class detection within each phase and embedding confusion caused by unknown classes. Besides, they ignore the catastrophic forgetting of known categories in model update. To this end, we propose a semi-supervised style Class-Incremental Learning without Forgetting (CILF) method, which aims to learn adaptive embedding for processing novel class detection and model update in a unified framework. In detail, CILF designs to regularize classification with decoupled prototype based loss, which can improve the intra-class and inter-class structure significantly, and acquires a compact embedding representation for novel class detection in result. Then, CILF employs a learnable curriculum clustering operator to estimate the number of semantic clusters via fine-tuning the learned network, in which curriculum operator can adaptively learn the embedding in self-taught form. Therefore, CILF can detect multiple novel classes and mitigate the embedding confusion problem. Last, with the labeled streaming test data, CILF can update the network with robust regularization to mitigate the catastrophic forgetting. Consequently, CILF is able to iteratively perform novel class detection and model update. We verify the effectiveness of our model on four streaming classification tasks, and empirical studies show the superior performance of the proposed method.
The use of enzyme supplementation for wheat-barley diets in poultry as a means of improving productive performance.

The objective of the study was to evaluate the effect of an exogenous multi-blend enzyme (βglucanase and xylanase) on the performance of the broiler chickens and laying hens fed diets based on wheat and barley. Experiments were conducted on a flock of broilers and two flocks of laying hens. In both cases feed and water were provided ad libitum. The enzyme effect of enzyme addition on the broiler performance involved 2080 day-old male and female chicks in 48 pens, allocated one of four dietary treatments (0, 50, 100 or 200 g/ton enzyme supplementation), to 35 days of age. On day 35, ten birds from each treatment were sacrificed for the analysis of the digestive organs weight (gizzards and livers). The trial was divided into two phases: a starter (1 to 21 d) and grower (22 to 35 d). Feed consumption was measured weekly and birds were also weighed weekly. The investigation of enzyme effect in laying hen diets involved 896 birds for each specific period. Each replicate consisted of four cages (four birds per cage) with a common feeder; 16 hens/pen of 56 pens. Eggs were weighed three times a week, feed consumption weekly and birds every weeks The addition of a multi-blend enzyme significantly improve body weight, body weight gain, food intake, and feed conversion ratio for both sexes (P<0.05) in broiler chickens. There was a significant improvement in egg production in laying hens (P<0.05). Egg weight and egg mass were not significantly improved. Wheat and barley have cell wall components (arabinoxylans and β-glucans respectively) which have a negative effect on the nutritive value of these feeds and therefore performance in poultry fed diets based on these ingredients. Addition of an exogenous multi-blend enzyme (β-glucanase and xylanase) could help reduce these effects and improve performance and digestibility values in poultry. The null hypothesis was there will be no difference between supplemented and un-supplemented diets based on wheat and barley in performance of poultry. The results of this study suggest that the inclusion of 50 g/ton enzyme helps improve poultry performance, especially in young birds.
Effects of re‐oligotrophication and climate change on lake thermal structure

Summary During recent decades, climate change and re-oligotrophication have been affecting many lakes. Most long-term research focuses on large North American and northern European lakes, but climate forcing south of the Alps seems to be different. Furthermore, lake restoration frequently involves smaller lakes (<10 km2) that are often overlooked in long-term limnological studies despite their importance for local stakeholders. We investigated the effects of climate change and re-oligotrophication on the thermal structure of Lake Caldonazzo (Italy – southern Alps; area = 5.6 km2; maximum depth = 49 m) for the years 1973–2014. The lake received untreated wastewaters from its catchment until the mid-1970s, leading to algal blooms, severe hypolimnetic anoxia and fish kills. Afterwards, local government initiated sewage removal that was completed in 1989. We used transparency, phosphorus and chlorophyll concentrations as trophic indicators, air temperature and global circulation indices as climatic indicators and epilimnion depth and temperature, hypolimnion temperature, thermocline depth and Schmidt stability as indicators of thermal structure. For these time series, we determined trend patterns and timing of change points. Epilimnetic temperatures showed an upward shift in 1985. Here, we present an alternative explanation for this observed change that generally has been attributed to global circulation indices. Epilimnetic depth continually increased until 1989, but less markedly afterwards. We suggest that until restoration continued, the increasingly deeper epilimnion absorbed the incoming heat of climate change without increasing epilimnetic temperature. After sewage removal, however, the epilimnion did not deepen enough to prevent an upward shift in epilimnetic temperature. We linked the deepening of the epilimnion to increased water transparency. Hypolimnetic temperatures showed a downward shift in 1998. Hypolimnetic cooling has been seldom observed and was in our case related to specific interactions between re-oligotrophication, climate and lake depth. Penetration of incident solar radiation was insufficient to heat the hypolimnion (>50% of lake volume), while deeper mixing released accumulated heat from the previous season and earlier stratification trapped colder water in the hypolimnion. We suggest that these combined effects resulted in a decrease in hypolimnetic temperature. Our study indicated that re-oligotrophication mitigated the effects of climate change, but when re-oligotrophication was no longer progressing, the effects of climate on thermal structure were perceivable. These changes were site specific and not tied to atmospheric circulation indices. Epilimnetic warming in particular will have repercussions on plankton dynamics. Management of non-point sources of nutrients will become increasingly important to limit the eutrophication-like effects of climate change, especially in the case of a warming epilimnion.
Who gets to imagine transformative change? Participation and representation in biodiversity assessments

The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) has been mandated to assess transformative change in order to identify pathways for achieving the 2050 Vision for Biodiversity. Yet, the topic of transformative change raises significant new challenges for biodiversity assessments because it combines scientifically plausible projections about the drivers and trends of biodiversity loss with normative and collective visions of a sustainable world for nature and people. In this commentary, we argue that assessments of visions of a sustainable world should also ask ‘whose values and visions count? ’ because different values and visions influence which voices and perspectives are considered relevant for generating scientific knowledge for transformative change. In particular, we argue that this situation requires rethinking modes of participation and co-production in assessments of transformative change: from consulting different groups as potential ‘users’ of assessments to seeing how visions of a sustainable world are represented through the selection of evidence and actors. In other words, assessments need to be less concerned about the inclusion and exclusion of actors, and more concerned about how these actors bring the perspectives of others with them.
Theoretical basis for evaluating the deformability of rock blocks

A theoretical basis for evaluating the deformability of rock blocks is presented in this study and is used to derive an equation that governs the relationship between the normal force applied and the displacement produced. This relationship depends on the distribution of forces in the contact; therefore, it depends on the load process acting at the asperities of the rock block. Most previous studies do not take into account the crushing effect of the contact points and do not address large pressures. However, this effect is more crucial when the material is thicker. The interpretation of the deformability tests with coarse granular materials is difficult because the stresses within the material are not known but are estimated from boundary conditions. The load is distributed in a general situation between asperities in an elastic state, asperities in a plastic state and the body of the block. A mathematical model based on a suitable geometrical characterization of the roughness of the surface of the rock block, height and radius, and well‐known mechanical principles is developed. This model makes it possible to evaluate partially the force‐displacement relationship of particle breakage tests. The main objective is to obtain the stress‐strain relationship of rock blocks considering the influence of roughness on its surface. The described theoretical formulation is applied to the rockfill of the dock of the Minerales harbor (Huelva). Their strength characteristics and deformation modulus are known, and the distribution of roughness on its surface is obtained using a specialized scanner on one of the block samples. From these results, the arrangement of the irregularities and the parameters of this developed mathematical model are applied to obtain adequate predictions and behavior patterns of particle breakage tests. The developed model adequately reproduces the different behaviors of the force‐displacement relationship depending on the fragility index (FI). Realistic values of this index make it possible to obtain adequate predictions.