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Daniel Mekonnen,1,2 Abaineh Munshea,2,3 Endalkachew Nibret,2,3 Bethlehem Adnew,4 Hailu Getachew,5 Amiro Kebede,5 Ananya Gebrewahid,5 Silvia Herrera-Leon,6 Aranzazu Amor Aramendia,7 Agustín Benito,8 Estefanía Abascal,6 Camille Jacqueline,6,9 Abraham Aseffa,4 Laura Herrera-Leon6,10 1Department of Medical Laboratory Sciences, School of Health Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 2Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia; 3Department of Biology, Bahir Dar University, Bahir Dar, Ethiopia; 4Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 5Amhara Public Health Institute, Bahir Dar, Ethiopia; 6National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; 7Fundación Mundo Sano, Madrid, Spain; 8National Center of Tropical Medicine, Institute of Health Carlos III, Centro de Investigación Biomédica En Red de Enfermedades Infecciosas, Madrid, Spain; 9European Public Health Microbiology Training Programme, European Centre for Disease Prevention and Control, Stockholm, Sweden; 10CIBER Epidemiologia y Salud Publica, Madrid, SpainCorrespondence: Daniel Mekonnen, Email nigusdaniel@gmail.comIntroduction: Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs).Methods: A facility-based cross-sectional study was conducted in 2020– 2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares.Results: Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance.Conclusion: The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.Keywords: Mycobacterium tuberculosis, L.4.2.2, SIT149, drug resistance, Ethiopia

The distribution of the spinetail devil ray Mobula mobular in the eastern tropical Atlantic remains poorly known compared to the Pacific and Indian Oceans. We used fishery-dependent data and generalized additive models to examine the environmental characteristics associated with the presence of M. mobular in the eastern Atlantic Ocean. Results revealed that the distribution of M. mobular is significantly associated with seasonal upwelling systems in coastal and pelagic areas. Our model predicted the presence of the species in areas where there is evidence of its occurrence, such as the Angolan upwelling system and the coast of Ghana. In addition, our model predicted new hotspot areas, including locations around the Mauritanian upwelling system, the Guinea coast, offshore Ghana and the south coast of Angola and Brazil, where sample sizes are limited. Those areas, as well as the environmental preferences depicted by the model, provide valuable information about the habitat and ecology of the spinetail devil ray. Future research lines derived from this study, as well as its limitations, are discussed. Furthermore, in light of our results we discuss the improvements that are needed to contribute to the conservation and management of this vulnerable species.

Bernardino Alcazar-Navarrete,1,2 Antonia Fuster,3 Patricia García Sidro,4 Juan Luis García Rivero,5 Beatriz Abascal-Bolado,6 Abel Pallarés-Sanmartín,7 Eduardo Márquez,2,8 Agustin Valido-Morales,9 Ana Boldova Loscertales,10 Francisco Javier Callejas-Gonzalez,11 Marta Palop,12 Juan Antonio Riesco,2,13 Rafael Golpe,14 Juan Jose Soler-Cataluña,2,15 Marc Miravitlles2,16 1AIG De Medicina. Hospital De Alta Resolución De Loja. Agencia Sanitaria Hospital De Poniente, Loja, Granada, Spain; 2CIBERES. Instituto De Salud Carlos III, Madrid, Spain; 3Servicio De Neumología. Hospital Universitario De Son Llatzer, Palma De Mallorca, Spain; 4Servicio De Neumología. Hospital De La Plana, Castellón, Spain; 5Servicio De Neumología. Hospital De Laredo, Laredo, Spain; 6Servicio De Neumología. Hospital Universitario Marqués De Valdecilla, Santander, Spain; 7Servicio De Neumología. Hospital Universitario Alvaro Cunqueiro, Vigo, Spain; 8Unidad Médico-Quirúrgica De Enfermedades Respiratorias. Hospital Virgen Del Rocío, Sevilla, Spain; 9UGC De Neumología. HU Virgen Macarena, Sevilla, Spain; 10Servicio De Neumología. Hospital Royo Villanova, Zaragoza, Spain; 11Servicio De Neumología. Complejo Hospitalario Universitario De Albacete, Albacete, Spain; 12Servicio De Neumología. Hospital De Sagunto, Sagunto, Spain; 13Servicio De Neumología. Hospital San Pedro De Alcántara, Cáceres, Spain; 14Servicio De Neumología. Hospital Universitario Lucus Augusti, Lugo, Spain; 15Servicio De Neumología. Hospital Arnau De Villanova- Lliria, Valencia, Spain; 16Servicio De Neumología. Hospital Universitari Vall De Hebron/Vall d’Hebron Institut De Recerca, Barcelona, SpainCorrespondence: Bernardino Alcazar-NavarreteHospital De Alta Resolución De Loja. Agencia Sanitaria Hospital De Poniente. Avda Tierno Galván s/n, Loja 18300, Granada, SpainEmail balcazar@telefonica.netBackground: The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control, reduced symptom severity and HRQoL has yet to be confirmed.Methods: This multicentre, prospective and observational study was carried out in 15 pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determined at V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS and HRQoL during follow-up was assessed with t-test.Results: A total of 126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV1 predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of − 4.6, − 5.6 and − 6.2 units at V0, V1 and V2, respectively, p< 0.005 for all comparisons) and to clinical criteria (mean differences of − 3.3, − 5-6 and − 4.99 units, respectively, p< 0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire (mean difference 0.13 and 0.10 at V2 by CAT or clinical criteria, respectively, p< 0.05).Conclusion: Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL.Keywords: control, symptoms, quality of life, impact, COPD

Beatriz Abascal-Bolado,1 Paul J Novotny,2 Jeff A Sloan,2 Craig Karpman,3 Megan M Dulohery,3 Roberto P Benzo31Pulmonary Division, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain; 2Department of Cancer Center Statistics, Health Science Research, 3Mindful Breathing Laboratory, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USAPurpose: Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care. There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care. The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use. Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD. Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization.Patients and methods: A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes. The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8±16.7, and modified Medical Research Council dyspnea scale score of 2±1.13.Results: Our analysis validated the original CRQ-SAS domains. Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization. We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD.Conclusion: We identified three themes – fear of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms – as important patient-reported outcomes to predict hospitalizations, and propose a short and easy algorithm to forecast hospitalizations in patients with COPD.Keywords: quality of life, COPD, exacerbation

ABSTRACT Purpose: To validate the Barcelona magnetic resonance imaging predictive model (BCN-MRI PM) in men with pre-biopsy multiparametric MRI (mpMRI) reported with the Prostate Imaging Reporting and Data System (PI-RADS) v2.1, followed by transrectal and transperineal prostate biopsies. Materials and Methods: Prospective analysis of 3,264 men with PSA >3.0 ng/mL and/or abnormal digital rectal examination who were referred to ten participant centers in the csPCa early detection program of Catalonia (Spain), between 2021 and 2023. MpMRI was reported with the PI-RADS v2.1, and 2- to 4-core MRI-transrectal ultrasound (TRUS) fusion-targeted biopsy of suspected lesions and/or 12-core systematic biopsy were conducted. 2,295 (70.3%) individuals were referred to six centers for transrectal prostate biopsies, while 969 (39.7%) were referred to four centers for transperineal prostate biopsies. CsPCa was classified whenever the International Society of Urologic Pathology grade group was 2 or higher. Results: CsPCa was detected in 41% of transrectal prostate biopsies and in 45.9% of transperineal prostate biopsies (p

Quality control of programs for detection of significant prostate cancer (sPCa) could be defined by the correlation between observed and reference 95% confidence intervals (CIs) for Prostate Imaging-Reporting and Data System (PI-RADS) categories. We used the area under the receiver operating characteristic curve (AUC) for the Barcelona magnetic resonance imaging (MRI) predictive model to screen the quality of ten participant centers in the sPCa opportunistic early detection program in Catalonia. We set an AUC of 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and two- to four-core targeted biopsies of PI-RADS ≥3 lesions and/or 12-core systematic biopsy, AUC values ranged from 0.527 to 0.914 and were

Introduction: Traumatic Brain Injury (TBI) is a significant public health concern that causes death, disability, and economic burden. Its repercussions affect physical, cognitive, emotional, and behavioral aspects of long-term care needs. Despite improvements in communication among multidisciplinary teams, the management of TBI remains fragmented. Objective: This study aimed to assess patients and caregivers’ experiences through sentiment analysis. Materials and methods: A qualitative cross-sectional study utilized structured topic modeling (STM) to analyze in-depth interview data. The study involved 29 patients with TBI and 27 caregivers in Madrid (Spain), using a survey design. The interviews were conducted, transcribed, and coded independently over 5 months. Sentiments such as anticipation, fear, and emotional concerns were analyzed using three dictionaries. The STM analysis identified four key concepts: desire for independence, potential improvement, need for injury information, and psychological consequences. STM diagnostic graphs were used to determine the number of topics relevant to the evaluation of patient and caregiver concerns. Furthermore, an analysis was conducted across four topics. Results: The average age of the patients was 44.2 ± 14.9 years (69 % males). Regarding TBI severity, 59 % of patients had severe TBI, whereas the remaining 41 % had experienced moderate TBI. Among the caregivers, the majority were parents (30 %), partners (24 %), or siblings (24 % each). Among the 51 participants, sentiments were analyzed using three dictionaries. While there were no significant age differences (Z = 0.24, p = 0.815), the STM model was adjusted for significant sex differences (p = 0.017) between patients and relatives. Anticipation and fear prevailed in both groups, highlighting the shared emotional patterns. Discussion: The analysis of diagnostic graphs indicated the optimal number of topics for evaluation, emphasizing key concerns across different phases of TBI. Patients' main worries shifted from physical symptoms to limitations in daily life and independence. Caregivers highlighted the importance of staff interactions, misinformation challenges, and the need for psychological care. Conclusion: Key patient concerns, including dependency on daily activities, limitations in autonomy, and caregiver burden, emphasize crucial areas for enhancement in multidisciplinary treatment. Moreover, the lack of long-term psychological support is a significant barrier to optimal patient and caregiver well-being.

BackgroundThe COVID-19 pandemic underscored the challenge of swiftly disseminating research findings to a global audience. Language barriers further exacerbated disparities in access to timely scientific information, particularly for non-English speaking communities. The majority of COVID-19 research was published in English, limiting accessibility for Spanish-speaking populations. ObjectiveThis paper aims to assess the reach and effectiveness of AccesoCovid.com, a platform designed to disseminate up-to-date COVID-19 research in both English and Spanish, addressing the language gap in scientific communication. MethodsAccesoCovid.com was developed through a partnership between the University of California, San Francisco (UCSF) and Universidad Nacional Autónoma de México (UNAM). The website’s performance and user engagement were evaluated using Google Analytics over a span of 2 years. Key metrics included user language preference, geographical distribution, and site traffic. The website summarized and translated 1032 articles on various COVID-19 topics, such as “Pharmaceutical Interventions and Vaccines.” ResultsFrom February 2021 to February 2023, the platform attracted 57,000 users. Of the 43,000 unique new visitors, 84.2% (n=36,219) hailed from Spanish-speaking regions. The majority accessed the site organically through search engines, with 88.4% (n=38,000) of users arriving this way, while 5000 (11.6%) users accessed the site directly. Most users (n=30,894, 72.1%) preferred the Spanish version of the site. The website’s most accessed category was “Pharmaceutical Interventions and Vaccines,” followed by “Clinical Presentation and Management” and “Mental Health.” Regarding language distribution, 72.1% (n=30,894) of users primarily used Spanish; 21.4% (n=9215) used English; and 6.7% (n=2891) spoke other languages, including Portuguese, Chinese, and German. Geographically, the website attracted visitors from 179 countries, with the highest visitor counts from Mexico (n=12,342, 28.7%), Spain (n=6405, 14.9%), the United States (n=4416, 10.3%), and Peru (n=3821, 8.9%). ConclusionsAccesoCovid.com successfully bridged a critical language gap in the dissemination of COVID-19 research. Its success underscores the pressing need for multilingual scientific resources. The platform demonstrated significant user engagement and reach, particularly in Spanish-speaking countries. This highlights the potential for similar platforms to ensure equitable access to scientific knowledge across diverse linguistic communities. Future efforts should focus on expanding to other languages and conducting formal evaluations to enhance user satisfaction and impact.

Purpose: To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)—small, median, and large—and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DREPVC and MRI-PV. Materials and Methods: A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. Results: The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19–37 mL) and 35 mL (23–30 mL), p=0.410; in median prostates they were 51 mL (38–58 mL) and 55 mL (48–63 mL) respectively, p

A distributed research infrastructure such as LifeWatch ERIC necessitates close cooperation among the various components that constitute the research infrastructure and contribute to the overall services, facilities and resources it offers to the user community. In-kind contributions are non-monetary contributions, consisting of labour, services, facilities and access to resources, typically provided by the distributed components of the research infrastructure. The financing for in-kind contributions is usually provided by the national funding agency on behalf of the LifeWatch member country or by the member directly, with a value being accredited towards the member's funding obligations to LifeWatch ERIC. The management and validation of in-kind contributions towards shared objectives are integral to the legal framework supporting LifeWatch ERIC. This involves a rigorous assessment process to verify each in-kind contribution. This short article outlines that process and explores the function of the In-Kind Contributions Committee (IKCC) at LifeWatch ERIC.

Abstract Several topics related to the oral cavity are briefly addressed in this article, from anatomical variations that, when recognized, avoid unnecessary investigations, to diseases that affect exclusively the mouth, mucocutaneous diseases, as well as oral manifestations of systemic diseases. A complete clinical examination comprises the examination of the mouth, and this approach facilitates clinical practice, shortening the path to diagnosis in the outpatient clinic as well as with in-hospital patients. The objective of this article is to encourage the examination of the oral cavity as a useful tool in medical practice, helping to recognize diseases in this location.

Abstract Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12,776 nucleotide variants. We identify 3432 functionally abnormal variants, in three distinct classes. We train a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performing in silico predictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants can account for almost all of the excess nonsynonymous DDX3X somatic mutations seen in DDX3X-driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.

Abstract Blepharoptosis is a recognized cause of reversible vision loss and a non-specific indicator of neurological issues, occasionally heralding life-threatening conditions. Currently, diagnosis relies on human expertise and eyelid examination, with most existing Artificial Intelligence algorithms focusing on eyelid positioning under specialized settings. This study introduces a deep learning model with convolutional neural networks to detect blepharoptosis in more realistic conditions. Our model was trained and tested using high quality periocular images from patients with blepharoptosis as well as those with other eyelid conditions. The model achieved an area under the receiver operating characteristic curve of 0.918. For validation, we compared the model's performance against nine medical experts—oculoplastic surgeons, general ophthalmologists, and general practitioners—with varied expertise. When tested on a new dataset with varied image quality, the model's performance remained statistically comparable to that of human graders. Our findings underscore the potential to enhance telemedicine services for blepharoptosis detection.

Background: The contraceptive preferences of obstetricians and gynecologists (OB/GYNs) are thought to influence the contraceptive counseling they provide. The purpose of this study was to assess contraceptive preferences of OB/GYNs and women in the general population (WGP) in the current Spanish contraceptive scenario. Materials and Methods: Anonymous online survey of 100 OB/GYNs and 1,217 WGP aged 23?49 years. Results: WGP were younger (35.3???7.3 vs. 37.9???6.2 years, respectively) and less likely to have stable partners (64.7% vs. 84.0%) and children (49.1% vs. 62.0%) (all p??0.05). Intrauterine devices (IUDs) were more frequently used by OB/GYNs (20% vs. 5%; p?0.05), especially the levonorgestrel-releasing intrauterine devices (LNG-IUDs) (18% vs. 2.6%; p?

Introduction Limited information is available regarding the clinical features, optimal treatment and prognosis of Paranoid Personality Disorder (PPD) and Delusional Disorder (DD). This is partly due to the low prevalence of cases and poor patient insight. The difference between DD and PPD has been questioned in the literature, as some studies have described them as a continuum, highlighting the role of specific personality traits in the transition to clinical delusions. Nonadherence to pharmacological treatment is one of the most challenging aspects. This further leads to relapses, increased use of emergency psychiatric services, psychiatric admissions, longer periods of hospitalization, and an increased cost of illness to healthcare systems. Objectives The primary goal of this study is to compare the differences between DD and PPD in terms of medication adherence, relapses, lost to follow-up, and costs. Other aims of this study are to analyze the differences in these variables between patients who are adequately adherent and patients who are not Methods An observational, retrospective, and multicenter descriptive epidemiological study was conducted. Patients were selected from four public departments of psychiatry in Madrid, providing an area of roughly one million people. All patients were older than 18 years-old, diagnosed with DD or PPD from 2005 to 2022. Data were extracted from electronic medical records and from electronic prescribing program used in the public health system.The study was approved by the Hospital Fundación Jiménez Díaz Ethics Committee. Results 1227 individuals diagnosed with DD (974 patients,79,3%) or PPD (253 patients, 20.61%). 23.81% (232 patients) of the DD-group did not take out the prescribed medication of the pharmacy, and 16.6% (42 patients) of the PPD-group were considered non-adherent. Adherent patients had greater follow-up (4.02 vs 2.89 years) and shorter hospital stays (5.15 vs 8.6 days, p

Introduction Suicide is one of the leading causes of unnatural death worldwide. There might be meaningful differences between those individuals that attempt suicide once in their lifespan and those who make multiple attempts in terms of sociodemographic and clinical characteristics. There are no previous meta-analysis addressing this topic in the adult population. Objectives We aimed to examine the factors that differentiate single and multiple suicide attempters in adult population. Methods We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to conduct this review and meta-analysis. The review protocol was registered in PROSPERO. We carried out a systematic literature search in three databases to identify original studies that explored the differences between single and multiple suicide attempters among adult population. A total of 75 studies were included in the review and 69 were included in the meta-analysis. Results Multiple attempters were more likely to present certain disorders such as mood and psychotic disorders, as well as personality or substance use disorders. Higher suicide ideation and suicide intent scores also characterized this group. Childhood trauma experiences, stressful life events, and higher rates of hopelessness were statistically significant in multiple attempters. Conclusions Identifying the factors predicting multiple suicide attempts helps to delineate a high-risk suicidal profile that should be taken into account in the clinical and suicide prevention scenario. Disclosure of Interest None Declared

Abstract Background Understanding the causes underlying heterogeneity of molecular evolutionary rates among lineages is a long-standing and central question in evolutionary biology. Although several earlier studies showed that modern frogs (Neobatrachia) experienced an acceleration of mitochondrial gene substitution rates compared to non-neobatrachian relatives, no further characterization of this phenomenon was attempted. To gain new insights on this topic, we sequenced the complete mitochondrial genomes and nine nuclear loci of one pelobatoid (Pelodytes punctatus) and five neobatrachians, Heleophryne regis (Heleophrynidae), Lechriodus melanopyga (Limnodynastidae), Calyptocephalella gayi (Calyptocephalellidae), Telmatobius bolivianus (Ceratophryidae), and Sooglossus thomasseti (Sooglossidae). These represent major clades not included in previous mitogenomic analyses, and most of them are remarkably species-poor compared to other neobatrachians. Results We reconstructed a fully resolved and robust phylogeny of extant frogs based on the new mitochondrial and nuclear sequence data, and dated major cladogenetic events. The reconstructed tree recovered Heleophryne as sister group to all other neobatrachians, the Australasian Lechriodus and the South American Calyptocephalella formed a clade that was the sister group to Nobleobatrachia, and the Seychellois Sooglossus was recovered as the sister group of Ranoides. We used relative-rate tests and direct comparison of branch lengths from mitochondrial and nuclear-based trees to demonstrate that both mitochondrial and nuclear evolutionary rates are significantly higher in all neobatrachians compared to their non-neobatrachian relatives, and that such rate acceleration started at the origin of Neobatrachia. Conclusions Through the analysis of the selection coefficient (ω) in different branches of the tree, we found compelling evidence of relaxation of purifying selection in neobatrachians, which could (at least in part) explain the observed higher mitochondrial and nuclear substitution rates in this clade. Our analyses allowed us to discard that changes in substitution rates could be correlated with increased mitochondrial genome rearrangement or diversification rates observed in different lineages of neobatrachians.

Entre 1990 y 2006 diversas excavaciones arqueológicas llevadas a cabo en la provincia de Alicante proporcionaron quince nuevas marcas de oficina sobre tégulas romanas. La mayor parte procede de la villa de El Moralet, en Benidorm, y el resto del área de la antigua colonia de Ilici y de su puerto, el Portus Ilicitanus (Santa Pola). En este trabajo se ofrece el catálogo de esos ejemplares.