Determination of the frequency of individuals with broadly cross-reactive neutralizing antibodies against PRRSV in the sow population under field conditions.

BACKGROUND: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant swine pathogen, yet the immune response components contributing to protection remain incompletely understood. Broadly reactive neutralizing antibodies (bNAs) may play a crucial role in preventing reinfections by heterologous viruses, although their occurrence is considered low under both field and experimental conditions. This study aimed to assess the frequency of sows exhibiting bNAs against PRRSV under field conditions and to analyze the epidemiological factors influencing the occurrence of these elite neutralizers. Blood samples were collected from breeding sows across eleven unrelated pig farms, with samples categorized by parity. Serum obtained was utilized in virus neutralization assays (VNs) against six PRRSV field isolates and two MLV strains. RESULTS: Approximately 7% of the sows exhibited neutralization activity against all viruses in the panel, with a geometric mean of the titer (GMT) of NAs at or exceeding 4 log2. Exclusion of the PRRSV-2 isolate from the panel increased the proportion of elite neutralizers to around 15%. Farm-specific analysis revealed significant variations in both GMT of NAs and proportion of elite neutralizers. PRRSV unstable farms and those with a PRRS outbreak in the last 12 months displayed higher GMT of NAs compared to stable farms without recent outbreaks. The GMT of NAs showed a gradual, albeit moderate, increase with the parity of the sows. Parity's impact on bNA response was consistently observed in stable farms but not necessarily in unstable farms or those with recent outbreaks. Finally, the results indicated that vaccinated animals had higher NA titers against the vaccine virus used in the farm than against field viruses. CONCLUSION: bNAs against heterologous isolates induced by PRRSV infection under field conditions are generally low, often falling below titers necessary for protection against reproductive failure. However, a subset of sows (approximately 15%) can be considered elite neutralizers, efficiently recognizing various PRRSV strains. Repeated exposures to PRRSV play a crucial role in eliciting these bNAs, with a higher frequency observed in unstable farms and those with recent outbreaks. In stable farms, parity only marginally influences bNA titers, highlighting its limited role compared to the impact of PRRSV exposure history.

Real-life clinical practice in Spain in the setting of new drug availability for ITP treatment. A Delphi-based Spanish expert panel consensus.

Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.

What is the context? Immune thrombocytopenia (ITP) is a hematologic autoimmune disease characterized by accelerated destruction and inadequate production of platelets mediated by autoantibodies (platelet count <100 × 10⁹ /L).Despite being a common condition, its heterogeneous clinical course makes its diagnosis and management still a challenge.In recent years, new molecules with different mechanisms of action have emerged for the treatment of ITP.Due to the increasing information about the pathology and its therapies, several international guidelines have recently been established to provide recommendations for the management and treatment of ITP.There are still many patient scenarios and disease aspects which are not addressed in the guidelines.What is new? Our Spanish ITP Expert Group has developed a Delphi consensus study to provide recommendations and promote standardization of the management of adult patients with ITP in Spain.The scientific committee defined 127 statements for consensus, corresponding to 13 chapters: (i) Diagnosis of ITP, (ii) First-line treatment, (iii) Second-line treatment, (iv) Treatment of refractory patients, (v) Follow-up, (vi) Emergency and surgery, (vii) ITP in the elderly, (viii) ITP in pregnancy, (ix) Anticoagulation and antiplatelet, (x) Secondary ITP, (xi) Quality of life, (xii) Discontinuation of TPO-RA, and (xiii) ITP and Covid.The total number of agreed statements achieved was 103, giving a final percentage of consensus in the Delphi questionnaire of 81%.What is the impact? This Delphi consensus provides recommendations based on real clinical practice data, regarding the diagnosis, treatment, and management of patients and scenarios in ITP to assist clinicians in addressing this disease and achieving optimal outcomes for the patient.

Artificial neural networks reconstruct missing perikymata in worn teeth.

Dental evolutionary studies in hominins are key to understanding how our ancestors and close fossil relatives grew from the early stages of embryogenesis into adults. In a sense, teeth are like an airplane's 'black box' as they record important variables for assessing developmental timing, enabling comparisons within and between populations, species, and genera. The ability to discern this type of nuanced information is embedded in the nature of how tooth enamel and dentin form: incrementally and over years. This incremental growth leaves chronological indicators in the histological structure of enamel, visible on the crown surface as perikymata. These structures are used in the process of reconstructing the rate and timing of tooth formation. Unfortunately, the developmentally earliest growth lines in lateral enamel are quickly lost to wear once the tooth crown erupts. We developed a method to reconstruct these earliest, missing perilymata from worn teeth through knowledge of the later-developed, visible perikymata for all tooth types (incisors, canines, premolars, and molars) using a modern human dataset. Building on our previous research using polynomial regressions, here we describe an artificial neural networks (ANN) method. This new ANN method mostly predicts within 2 counts the number of perikymata present in each of the first three deciles of the crown height for all tooth types. Our ANN method for estimating perikymata lost through wear has two immediate benefits: more accurate values can be produced and worn teeth can be included in dental research. This tool is available on the open-source platform R within the package teethR released under GPL v3.0 license, enabling other researchers the opportunity to expand their datasets for studies of periodicity in histological growth, dental development, and evolution.

Sexual dimorphism in the enamel-dentine junction (EDJ) of permanent canines of European modern humans.

OBJECTIVES: Dental anthropological investigations into sexual dimorphism have conventionally concentrated on evaluating the dimensions and configuration of the enamel cap of canines. However, the morphology of the crown dentine surface can be closely linked to that of the enamel surface. This link can facilitate examination of crown morphology even when the enamel surface is slightly worn. Here, we determine if the morphology of the enamel-dentine junction (EDJ) differs within (maxillary vs. mandibular) and between a sample of male (n = 26) and female (n = 21) contemporary human permanent canines from Europe. METHODS: The morphological data of the EDJ were gathered employing a template comprising 96 landmarks and sliding semilandmarks. Subsequently, the data underwent analysis through form space principal component analysis following Procrustes registration, utilizing standard 3D geometric morphometric techniques. RESULTS: Significant differences in the morphology of the EDJ were observed between the sexes, particularly concerning the overall shape of the crown, the symmetry of the mesial and distal edges, and the development of the distal accessory ridge. CONCLUSIONS: Sex differences in the morphology of the EDJ could relate in part to retention of the canine-premolar honing complex in males. Our results indicate that analyses of the permanent canine EDJ may potentially provide a novel method for estimating the sex of adult and nonadult skeletons.

Ultrafast 30-min infusion of a rituximab biosimilar (Truxima).

In this clinical trial, we demonstrate that ultrarapid fast infusion of rituximab (Truxima) in 30 min with oral premedication is feasible and secure for patients, and reduce the day-care hospital stays.

Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI).

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.

Morphological and morphometric analyses of a late Middle Pleistocene hominin mandible from Hualongdong, China.

Excavations in Hualongdong (HLD), East China, have yielded abundant hominin fossils dated to 300 ka. There is a nearly complete mandible that fits well with a partial cranium, and together they compose the skull labeled as HLD 6. Thus far, detailed morphological description and comparisons of the mandible have not been conducted. Here we present a comprehensive morphological, metric, and geometric morphometric assessment of this mandible and compare it with both adult and immature specimens of Pleistocene hominins and recent modern humans. Results indicate that the HLD 6 mandible exhibits a mosaic morphological pattern characterized by a robust corpus and relatively gracile symphysis and ramus. The moderately developed mental trigone and a clear anterior mandibular incurvation of the HLD 6 mandible are reminiscent of Late Pleistocene hominin and recent modern human morphology. However, the weak expression of all these features indicates that this mandible does not possess a true chin. Moreover, a suite of archaic features that resemble those of Middle Pleistocene hominins includes pronounced alveolar planum, superior transverse torus, thick corpus, a pronounced endocondyloid crest, and a well-developed medial pterygoid tubercle. The geometric morphometric analysis further confirms the mosaic pattern of the HLD 6 mandible. The combination of both archaic and modern human features identified in the HLD 6 mandible is unexpected, given its late Middle Pleistocene age and differs from approximately contemporaneous Homo members such as Xujiayao, Penghu, and Xiahe. This mosaic pattern has never been recorded in late Middle Pleistocene hominin fossil assemblages in East Asia. The HLD 6 mandible provides further support for the high morphological diversity during late Middle Pleistocene hominin evolution. With these findings, it is possible that modern human morphologies are present as early as 300 ka and earlier than the emergence of modern humans in East Asia.

Recommendations on the Management of Patients with Immune Thrombocytopenia (ITP) in the Context of SARS-CoV-2 Infection and Vaccination: Consensus Guidelines from a Spanish ITP Expert Group.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with highly variable presentation, characteristics, and clinical course. Thrombocytopenia is a common complication of many viral infections, including SARS-CoV-2. In addition, both de novo ITP and exacerbation of ITP after vaccination against SARS-CoV-2 have been reported. Patients infected with SARS-CoV-2 develop a prothrombotic coagulopathy called COVID-19-associated coagulopathy (CAC). In addition, autoimmune hematological disorders secondary to SARS-CoV-2 infection, mainly ITP and autoimmune hemolytic anemia (AIHA), have been described. Furthermore, SARS-CoV-2 infection has been associated with exacerbation of autoimmune processes, including ITP. In fact, there is evidence of a high relapse rate in patients with preexisting ITP and COVID-19. As for vaccination against SARS-CoV-2, hematological adverse events (HAE) are practically anecdotal. The most common HAE is thrombocytopenia-associated thrombosis syndrome (TTS) linked to vectored virus vaccines. Other HAEs are very rare, but should be considered in patients with previous complement activation disease or autoimmunity. In patients with ITP who are vaccinated against SARS-CoV-2, the main complication is exacerbation of ITP and the bleeding that may result. In fact, this complication occurs in 12% of patients, with splenectomized and refractory patients with more than five lines of previous treatment and platelet counts below 50 × 109/L being the most vulnerable. We conclude that, in general, there is no greater risk of severe SARS-CoV-2 infection in ITP patients than in the general population. Furthermore, no changes are advised in patients with stable ITP, the use of immunosuppressants is discouraged unless there is no other therapeutic option, and patients with ITP are not contraindicated for vaccination against COVID-19.

Frontal sinuses and human evolution.

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species' holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species.

Comparing the Boxgrove and Atapuerca (Sima de los Huesos) human fossils: Do they represent distinct paleodemes?

The early Middle Pleistocene human material from Boxgrove (West Sussex, UK) consists of a partial left tibia and two lower incisors from a separate adult individual. These remains derive from deposits assigned to the MIS 13 interglacial at about 480 ka and have been referred to as Homo cf. heidelbergensis. The much larger skeletal sample from the Sima de los Huesos (Atapuerca, Spain) is dated to the succeeding MIS 12, at about 430 ka. This fossil material has previously been assigned to Homo heidelbergensis but is now placed within the Neanderthal clade. Because of the scarcity of human remains from the Middle Pleistocene and their morphological variability, this study assessed whether the Boxgrove specimens fit within the morphological variability of the homogeneous Sima de los Huesos population. Based on morphometric analyses performed against 22 lower incisors from Sima de los Huesos and published material, the data from the Boxgrove incisors place them comfortably within the range of Sima de los Huesos. Both assemblages present robust incisors distinct from the overall small recent Homo sapiens incisors, and Boxgrove also aligns closely with Homo neanderthalensis and some other European Middle Pleistocene hominins. Following morphological and cross-sectional analyses of the Boxgrove tibia compared to seven adult Sima de los Huesos specimens and a set of comparative tibiae, Boxgrove is shown to be similar to Sima de los Huesos and Neanderthals in having thick cortices and bone walls, but in contrast resembles modern humans in having a straight anterior tibial crest and a suggestion of a lateral concavity. Based on the patterns observed, there is no justification for assigning the Boxgrove and Sima de los Huesos incisors to distinct paleodemes, but the tibial data show greater contrasts and suggest that all three of these samples are unlikely to represent the same paleodeme.

Early Pleistocene hominin teeth from Gongwangling of Lantian, Central China.

The fossil hominin individual from Gongwangling of Lantian, Central China, represents one of the earliest members attributed to Homo erectus in East Asia. Recent paleomagnetic analyses have yielded an age of 1.63 Ma for the Gongwangling hominin. The fossils from this site are critical to characterize the morphological features of early hominins in East Asia and to understand their relationships with other earlier and later members of the genus Homo. However, most morphological details of the Gongwangling cranium were obliterated due to postmortem erosion and deformation. Here we used high-resolution microcomputed tomography and three-dimensional virtual imaging techniques to extract the teeth and reconstruct the worn/damaged areas, describe the external morphology, measure crown diameters, record nonmetric traits of the crown and root, and investigate the shape of the enamel-dentine junction using geometric morphometrics. We compared the data obtained from the six teeth of the Gongwangling hominin with African early Homo, African and Georgian Homo erectus s.l., Asian Homo erectus, Homo antecessor, pre-Neanderthals, Neanderthals, and modern humans. Our results show that the Gongwangling specimens display affinities with other specimens attributed to H. erectus s.l. The highly divergent and noncoalesced three-root system in the Gongwangling specimens is comparable to that in the Early Pleistocene members of H. erectus s.l., and differs from Middle Pleistocene representatives of the species. The enamel-dentine junction shape of the Gongwangling molars prefigures the Asian H. erectus pattern later found in East Asian Middle Pleistocene H. erectus. The morphological comparisons between East Asian Early Pleistocene (e.g., Gongwangling, Meipu, and Quyuan River Mouth) and Middle Pleistocene H. erectus (e.g., Zhoukoudian, Hexian, and Yiyuan) suggest a potential temporal trend within this species in East Asia.

The protoconid: a key cusp in lower molars. Evidence from a recent modern human population.

BACKGROUND: The molar (M) size sequence in the genus Homo is decreasing and the general pattern in Homo sapiens is M1> M2 > M3. AIM: To gain a better understanding of the reduction patterns of M components (cusps), we aim to assess the area of the protoconid (Prd), the phylogenetically oldest cusp of the lower Ms. SUBJECT AND METHODS: We measured the Prd and the total crown area in the scaled photographs of a recent modern human sample of lower Ms (76 males and 39 females). The values were statistically analysed. RESULTS: The absolute size of the Prd increases significantly between M1 and M2/M3, whereas the relative size of this cusp increases significantly from M1 to M3. In the latter, reduction or disappearance of the cusps of the talonid is common. CONCLUSIONS: The results can be explained in the framework of the patterning cascade model. As the first cusp to appear developmentally, the Prd forms in response to signals from the primary enamel knot, likely contributing to its stability. Inhibitory signals emitted during the Prd formation may lead to the reduction or disappearance of the talonid cusps, if these do not have enough time to form before the end of the M morphogenetic process.

Similarities and differences in the dental tissue proportions of the deciduous and permanent canines of Early and Middle Pleistocene human populations.

The two- and three-dimensional assessment of dental tissues has become routine in human taxonomic studies throughout the years. Nonetheless, most of our knowledge of the variability of the enamel and dentine dimensions of the human evolutionary lineage comes from the study of permanent dentition, and particularly from molars. This leads to a biased view of the variability of these features. Due to their early formation and rapid development, the deciduous teeth allow more simplified inferences regarding the processes involved in the dental tissue development of each group. Therefore, their study could be very valuable in dental palaeohistology. In this research, we have explored the dental tissue proportions of the deciduous canines belonging to some human samples of the Early and Middle Pleistocene. The purpose of this was to discuss the meaning of the similarities and differences observed in their histological pattern, as well as to evaluate the degree of covariance with that observed in the permanent dentition of these populations. Our results show that, although there are some similarities in the dental tissue proportions between the deciduous and permanent canines of the study samples, the two dental classes do not provide a similar or comparable pictures of the dental tissue pattern present in the dentition of fossil hominins. Future works on the dental tissue patterns of the anterior and posterior dentition, including deciduous teeth, of fossil samples, may help to shed light on this hypothesis.

Dental remains of the Middle Pleistocene hominins from the Sima de los Huesos site (Sierra de Atapuerca, Spain): Mandibular dentition.

The Middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, northern Spain) has yielded a considerable number of human fossils during the period 1984-2020. Among them, up to 314 mandibular teeth have been identified. In this second paper dedicated to the dentition we present the description of the eight dental classes of the mandible following the Arizona State University Dental Anthropology System (ASUDAS) classification. In addition, we show the mean mesiodistal and buccolingual diameters obtained in these teeth compared to those of Neanderthals and a modern human sample. The morphology of both the anterior and posterior teeth suggests a close relationship of the Sima de los Huesos hominins with the populations of the second half of the Middle Pleistocene of Europe and the Near East, as well as with the so-called classic Neanderthals of Europe. The combination of dental traits in these populations is characteristic and diagnostic and suggests grouping the Sima de los Huesos hominins with the other paleodemes in a Neanderthal clade. The dental evidence of the Sima de los Huesos hominins is key to propose a complex model for the settlement of Europe during the Middle Pleistocene. In this period, different migrations of human groups probably coming from Southwest Asia, replacements, prolonged isolations, as well as hybridization and introgression processes would have contributed to the diversity of hominins in Europe.

Response to Comment on "A Middle Pleistocene Homo from Nesher Ramla, Israel".

Marom and Rak claim, on the basis of a few mandibular features, that the Nesher Ramla (NR) Homo is a Neanderthal. Their comments lack substance and contribute little to the debate surrounding the evolution of Middle Pleistocene Homo. Limitations and preconceptions in their study prevented them from achieving resolution beyond a dichotomous interpretation of the NR as either a Neanderthal or a modern human.