pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties.

The development of new, effective, and safe drugs to treat cancer remains a challenging and time-consuming task due to limited hit rates, restraining subsequent development efforts. Despite the impressive progress of quantitative structure-activity relationship and machine learning-based models that have been developed to predict molecule pharmacodynamics and bioactivity, they have had mixed success at identifying compounds with anticancer properties against multiple cell lines. Here, we have developed a novel predictive tool, pdCSM-cancer, which uses a graph-based signature representation of the chemical structure of a small molecule in order to accurately predict molecules likely to be active against one or multiple cancer cell lines. pdCSM-cancer represents the most comprehensive anticancer bioactivity prediction platform developed till date, comprising trained and validated models on experimental data of the growth inhibition concentration (GI50%) effects, including over 18,000 compounds, on 9 tumor types and 74 distinct cancer cell lines. Across 10-fold cross-validation, it achieved Pearson's correlation coefficients of up to 0.74 and comparable performance of up to 0.67 across independent, non-redundant blind tests. Leveraging the insights from these cell line-specific models, we developed a generic predictive model to identify molecules active in at least 60 cell lines. Our final model achieved an area under the receiver operating characteristic curve (AUC) of up to 0.94 on 10-fold cross-validation and up to 0.94 on independent non-redundant blind tests, outperforming alternative approaches. We believe that our predictive tool will provide a valuable resource to optimizing and enriching screening libraries for the identification of effective and safe anticancer molecules. To provide a simple and integrated platform to rapidly screen for potential biologically active molecules with favorable anticancer properties, we made pdCSM-cancer freely available online at http://biosig.unimelb.edu.au/pdcsm_cancer

The role of collaboration in reducing quality variability in Brazilian breweries

This paper aims to analyse how small-scale breweries undertake vertical and horizontal collaborations to manage their quality performance (when measured by reducing quality variabilities). While vertical collaborations are overemphasised, horizontal and simultaneous collaboration efforts have been understudied. Our contribution lies in proposing an interplay of vertical and horizontal collaborations through information sharing, joint decision-making, and knowledge exchange with intra- and inter-supply chain partners to address quality variability issues. We draw attention to supply chain relationships being predominantly informal, which contribute strongly towards accessing external sources of knowledge. Additionally, such collaborative efforts have led companies to achieve mutual gains in their relationships. Finally, a framework is presented that consolidates the supply chain actors, collaboration types, socialisation mechanisms, and relationship types

Species boundaries and biogeography of East African torrent frogs of the genus Petropedetes (Amphibia: Anura: Petropeditidae)

Based on morphology there are currently three described East African species of torrent frogs belonging to the tropical African genus Petropedetes (P. dutoiti, P. martiennseni and P. yakusini). Taxonomic uncertainties are evident within this group: a putative new species reported from the Nguru Mountains and the species P. yakusini have a fragmented distribution across the Southern Tanzanian highlands. We conducted a molecular systematic study, sampling populations of East African petropedetids occurring in the mountains of Tanzania (P. martiennseni and P. yakusini), to investigate species boundaries and biogeography. Data provide evidence for the recognition of well-defined genetically distinct populations occurring in each mountain fragment (for P. yakusini), and further support for a new undescribed species from the Nguru Mountains. We examine phylogenetic patterns in relation to the biogeographic history of the region

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.info:eu-repo/semantics/publishedVersio

Is The Amphibian Tree of Life really fatally flawed?

Wiens (2007, Q. Rev. Biol. 82, 55–56) recently published a severe critique of Frost et al.\u27s (2006, Bull. Am. Mus. Nat. Hist. 297, 1–370) monographic study of amphibian systematics, concluding that it is “a disaster” and recommending that readers “simply ignore this study”. Beyond the hyperbole, Wiens raised four general objections that he regarded as “fatal flaws”: (1) the sampling design was insufficient for the generic changes made and taxonomic changes were made without including all type species; (2) the nuclear gene most commonly used in amphibian phylogenetics, RAG-1, was not included, nor were the morphological characters that had justified the older taxonomy; (3) the analytical method employed is questionable because equally weighted parsimony “assumes that all characters are evolving at equal rates”; and (4) the results were at times “clearly erroneous”, as evidenced by the inferred non-monophyly of marsupial frogs. In this paper we respond to these criticisms. In brief: (1) the study of Frost et al. did not exist in a vacuum and we discussed our evidence and evidence previously obtained by others that documented the non-monophyletic taxa that we corrected. Beyond that, we agree that all type species should ideally be included, but inclusion of all potentially relevant type species is not feasible in a study of the magnitude of Frost et al. and we contend that this should not prevent progress in the formulation of phylogenetic hypotheses or their application outside of systematics. (2) Rhodopsin, a gene included by Frost et al. is the nuclear gene that is most commonly used in amphibian systematics, not RAG-1. Regardless, ignoring a study because of the absence of a single locus strikes us as unsound practice. With respect to previously hypothesized morphological synapomorphies, Frost et al. provided a lengthy review of the published evidence for all groups, and this was used to inform taxonomic decisions. We noted that confirming and reconciling all morphological transformation series published among previous studies needed to be done, and we included evidence from the only published data set at that time to explicitly code morphological characters (including a number of traditionally applied synapomorphies from adult morphology) across the bulk of the diversity of amphibians (Haas, 2003, Cladistics 19, 23–90). Moreover, the phylogenetic results of the Frost et al. study were largely consistent with previous morphological and molecular studies and where they differed, this was discussed with reference to the weight of evidence. (3) The claim that equally weighted parsimony assumes that all characters are evolving at equal rates has been shown to be false in both analytical and simulation studies. (4) The claimed “strong support” for marsupial frog monophyly is questionable. Several studies have also found marsupial frogs to be non-monophyletic. Wiens et al. (2005, Syst. Biol. 54, 719–748) recovered marsupial frogs as monophyletic, but that result was strongly supported only by Bayesian clade confidence values (which are known to overestimate support) and bootstrap support in his parsimony analysis was \u3c 50%. Further, in a more recent parsimony analysis of an expanded data set that included RAG-1 and the three traditional morphological synapomorphies of marsupial frogs, Wiens et al. (2006, Am. Nat. 168, 579–596) also found them to be non-monophyletic. Although we attempted to apply the rule of monophyly to the naming of taxonomic groups, our phylogenetic results are largely consistent with conventional views even if not with the taxonomy current at the time of our writing. Most of our taxonomic changes addressed examples of non-monophyly that had previously been known or suspected (e.g., the non-monophyly of traditional Hyperoliidae, Microhylidae, Hemiphractinae, Leptodactylidae, Phrynobatrachus, Ranidae, Rana, Bufo; and the placement of Brachycephalus within “Eleutherodactylus”, and Lineatriton within “Pseudoeurycea”), and it is troubling that Wiens and others, as evidenced by recent publications, continue to perpetuate recognition of non-monophyletic taxonomic groups that so profoundly misrepresent what is known about amphibian phylogeny

Pushing Taxonomy to Extiction?

Can we describe all species on Earth before they disappear? We argue that this is possible only by endowing taxonomy with professional manpower and appropriate material resources as required by big science. Contrary to Costello et al.’s (CMS) (1) statements, taxonomy is not an easy discipline accessible to all through a smartphone. It requires exhaustive training and long familiarity with field, specimens and literature (2). CMS’s argument is framed in terms of species numbers, but different, non-overlapping species concepts apply to bacteria, brambles and birds (3,4,5): “the species” as common unit of biodiversity does not exist (6). Even ignoring this conceptual and semantic issue, CMS’s estimates of undescribed biodiversity and extinction rates are based on insufficient evidence and poorly supported models. Biodiversity hotspots steadily emerge in geographic areas where diversity was long assumed to be largely described (7,8). The number of species, whatever species are, cannot be easily estimated because of the historical, rather than deterministic or teleological, nature of biological evolution (9,10). Extinction rates are highly context-sensitive (11), lineage- and region-dependant, thus generally difficult to ascertain (12) without thorough analyses of data such as IUCN’s estimates of threats and extinctions (13). However, evidence being mainly restricted to vertebrates, the extinction risks in most other groups remain terra incognita. Furthermore, recent surveys (14,15) do not support CMS’s optimistic predictions regarding extinction rates. CMS’s agenda emphasizes technology, voluntary work and recognition of subjective “morphospecies” (16). However, improvement of data storage and retrieval cannot substitute for the production of sound data. Serious taxonomists cannot describe two new species per week, as suggested by CMS’s calculations. Describing new species, even with the help of molecular data and especially in best-investigated groups, is increasingly demanding, following the “law of diminishing returns” (17). More than anything else, taxonomy requires professional manpower, unrestricted fieldwork and permanent collections

Long-term data for endemic frog genera reveal potential conservation crisis in the Bale Mountains, Ethiopia

Populations of many frogs have declined alarmingly in recent years, placing nearly one third of the \u3e 6,000 species under threat of extinction. Declines have been attributed largely to habitat loss, environmental degradation and/or infectious diseases such as chytridiomycosis. Many frogs undergo dramatic natural population fluctuations such that long-term data are required to determine population trends without undue influence of stochastic factors. We present long-term quantitative data (individuals encountered per person hour of searching) for four monotypic frog genera endemic to an Afromontane region of exceptional importance but growing conservation concern: one endemic to the Ethiopian highlands (Spinophrynoides osgoodi) and three endemic to the Bale Mountains (Altiphrynoides malcolmi, Balebreviceps hillmani, Ericabatrachus baleensis), collected during 15 field trips to the Bale Mountains between 1971 and 2009. Only a single confirmed sighting of S. osgoodi has been made since 1995. The other three species have also declined, at least locally. E. baleensis appears to have been extirpated at its type locality and at the same site B. hillmani has declined. These declines are in association with substantial habitat degradation caused by a growing human population. Chytrid fungus has been found on several frog species in Bale, although no dead or moribund frogs have been encountered. These results expose an urgent need for more amphibian surveys in the Bale Mountains. Additionally, we argue that detrimental human exploitation must be halted immediately in at least some parts of the Harenna Forest if a conservation crisis is to be averted

Enhanced photoelectrochemical performance of atomic layer deposited Hf-doped ZnO

Generation of hydrogen using photoelectrochemical (PEC) water splitting has attracted researchers for the last two decades. Several materials have been utilized as a photoanode in a water splitting cell, including ZnO due to its abundance, low production cost and suitable electronic structure. Most research attempts focused on doping ZnO to tailor its properties for a specific application. In this work, atomic layer deposition (ALD) was used to precisely dope ZnO with hafnium (Hf) in order to enhance its PEC performance. The resultant doped materials showed a significant improvement in PEC efficiency compared to pristine ZnO, which is linked directly to Hf introduction revealed by detailed optical, structural and electrical analyses. The photocurrent obtained in the best performing Hf-doped sample (0.75 wt% Hf) was roughly threefold higher compared to the undoped ZnO. Electrochemical impedance spectroscopy (EIS) and open-circuit potential-decay (OCPD) measurements confirmed suppression in photocarriers' surface recombination in the doped films, which led to a more efficient PEC water oxidation. The enhanced PEC performance of Hf-doped ZnO and effectiveness of the used metal dopant are credited to the synergistic optimization of chemical composition, which enhanced the electrical, structural including morphological, and optical properties of the final material, making Hf-doping an attractive candidate for novel PEC electrodes

Taxonomic Review of South American Butter Frogs: Phylogeny, Geographic Patterns, and Species Delimitation in the Leptodactylus latrans Species Group (Anura: Leptodactylidae)

The Leptodactylus latrans species group currently comprises eight medium- to large-sized frog species with a convoluted taxonomic history, particularly related to the specific limits of the L. latrans complex, and the species pair Leptodactylus chaquensis–Leptodactylus macrosternum. Their homogeneous external morphology and continental geographic distribution in South America have posed severe limitations to a comprehensive review, such that taxonomic consensus and species limits remain uncertain. This is further worsened by the presence of chromatic polymorphism among coexisting species that can hardly be distinguished by external morphology. Based on a large-scale geographic sampling including multilocus DNA analyses, and acoustic and morphological data, we provide a comprehensive evaluation of the taxonomic status and species limits of the L. latrans group, focusing on the resolution of the L. latranscomplex and the species pair L. chaquensis–L. macrosternum. We gathered 728 mitochondrial sequences from 429 localities, encompassing the entire geographic distribution of the group. Both generalized mixed Yule coalescent and automatic barcode gap discovery species delimitation methods recovered four major mitochondrial evolutionary lineages within the L. latrans complex, also supported by distribution patterns, multilocus molecular, morphological and/or bioacoustic data. One lineage is linked to nominal L. latrans,one revalidated as Leptodactylus luctator, and the other two are formally named and described. Another lineage encompasses all specimens previously assigned to the species pair L. chaquensis–L. macrosternum, clustered as a single evolutionary entity and is now regarded as L. macrosternum. We provide a revised diagnosis for these species based on acoustic data, morphological/chromatic variation, and phylogenetic relationships of all species currently included in the L. latrans group. Our findings reinforce the view that Neotropical diversity is highly underestimated and stress that appropriate geographic sampling in an integrative framework is crucial for the establishment of specific limits among broadly distributed and morphologically cryptic Neotropical frogs

Cardiopulmonary Response in Post-COVID-19 Individuals: A Cross-Sectional Study Comparing the Londrina Activities of Daily Living Protocol, 6-Minute Walk Test, and Glittre Activities of Daily Living Test

This study addresses the imperative need for reliable assessment protocols in guiding rehabilitation interventions for individuals post-COVID-19, considering the enduring physiological effects of the virus. A cohort of 40 post-COVID-19 individuals underwent assessments using the Londrina ADL protocol, Glittre ADL test, and the 6-minute walk test (6MWT). Physiological parameters were recorded during and after each test, including heart rate, respiratory rate, and oxygen saturation. The post hoc comparisons between the pre-test and post-test cardiopulmonary response of the three tests showed significant differences, except diastolic blood pressure (6MWT vs. Londrina ADL protocol), heart rate (6MWT vs. Londrina ADL protocol), respiratory rate (6MWT vs. Londrina ADL protocol), blood oxygen level (SpO2) (6MWT vs. Londrina ADL protocol), dyspnea (Londrina ADL protocol vs. Glittre ADL test), and fatigue (Londrina ADL protocol vs. Glittre ADL test). The Londrina ADL protocol demonstrated cardio-pulmonary responses comparable to the Glittre ADL test, as well as the 6MWT, emphasizing its effectiveness in evaluating walking-related outcomes. The study concludes that the Londrina ADL protocol is a robust and practical tool for the routine clinical testing of daily living activities in post-COVID-19 individuals. While the 6MWT remains valuable for assessing walking-related outcomes, a combined approach employing the Londrina ADL protocol and 6MWT offers a comprehensive strategy for evaluating multifaceted functional capacities in this population.</jats:p