Evidence of thickness-dependent surface-induced ferroelectricity in few-layer germanium sulfide obtained via scanning tunneling spectroscopy.

The discovery of ferroelectricity in two-dimensional van der Waals materials has sparked enormous interest from the scientific community, due to its possible applications in next-generation nanoelectronic devices, such as random-access memory devices, digital signal processors, and solar cells, among others. In the present study, we used vapor phase deposition to synthesize ultrathin germanium sulfide nano-flakes on a highly oriented pyrolytic graphite substrate. Nanostructures of variable thicknesses were characterized using scanning tunneling microscopy and spectroscopy. Tunneling currents under forward and backward biases were measured as a function of nano-flake thickness. Remarkably, we clearly observed a hysteresis pattern, which we attributed to surface ferroelectric behavior, consistent with the screening conditions of polarization charges. The effect increases as the number of layers is reduced. This experimental result may be directly applicable to miniaturized memory devices, given the two-dimensional nature of this effect.

Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification.

Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.

Scanning Tunneling Spectroscopy Method for the Prediction of Semiconductor Heterojunction Performance as a Prequel for Device Development.

The prediction of semiconductor device performance is a persistent challenge in materials science, and the ability to anticipate useful specifications prior to construction is crucial for enhancing the overall efficiency. In this study, we investigate the constituents of a solar cell by employing scanning tunneling microscopy (STM) and spectroscopy (STS). Through our observations, we identify a spatial distribution of the dopant type in thin films of materials that were designed to present major p-doping for germanium sulfide (GeS) and dominant n-doping for tin disulfide (SnS2). By generating separate STS maps for each semiconductor film and conducting a statistical analysis of the gap and doping distribution, we determine intrinsic limitations for the solar cell efficiency that must be understood prior to processing. Subsequently, we fabricate a solar cell utilizing these materials (GeS and SnS2) via vapor phase deposition and carry out a characterization using standard J-V curves under both dark/illuminated irradiance conditions. Our devices corroborate the expected reduced efficiency due to doping fluctuation but exhibit stable photocurrent responses. As originally planned, quantum efficiency measurements reveal that the peak efficiency of our solar cell coincides with the range where the standard silicon solar cells sharply decline. Our STS method is suggested as a prequel to device development in novel material junctions or deposition processes where fluctuations of doping levels are retrieved due to intrinsic material characteristics such as the occurrence of defects, roughness, local chemical segregation, and faceting or step bunching.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

Machine Learning Improves Risk Stratification in Myelodysplastic Neoplasms: An Analysis of the Spanish Group of Myelodysplastic Syndromes.

Myelodysplastic neoplasms (MDS) are a heterogeneous group of hematological stem cell disorders characterized by dysplasia, cytopenias, and increased risk of acute leukemia. As prognosis differs widely between patients, and treatment options vary from observation to allogeneic stem cell transplantation, accurate and precise disease risk prognostication is critical for decision making. With this aim, we retrieved registry data from MDS patients from 90 Spanish institutions. A total of 7202 patients were included, which were divided into a training (80%) and a test (20%) set. A machine learning technique (random survival forests) was used to model overall survival (OS) and leukemia-free survival (LFS). The optimal model was based on 8 variables (age, gender, hemoglobin, leukocyte count, platelet count, neutrophil percentage, bone marrow blast, and cytogenetic risk group). This model achieved high accuracy in predicting OS (c-indexes; 0.759 and 0.776) and LFS (c-indexes; 0.812 and 0.845). Importantly, the model was superior to the revised International Prognostic Scoring System (IPSS-R) and the age-adjusted IPSS-R. This difference persisted in different age ranges and in all evaluated disease subgroups. Finally, we validated our results in an external cohort, confirming the superiority of the Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS) over the IPSS-R, and achieving a similar performance as the molecular IPSS. In conclusion, the AIPSS-MDS score is a new prognostic model based exclusively on traditional clinical, hematological, and cytogenetic variables. AIPSS-MDS has a high prognostic accuracy in predicting survival in MDS patients, outperforming other well-established risk-scoring systems.

Manejo clínico de las complicaciones agudas de la anemia falciforme: 11 años de experiencia en un hospital terciario / Clinical management of the acute complications of sickle cell anemia: 11 years of experience in a tertiary hospital

Introducción: La drepanocitosis es una anemia emergente en Europa que condiciona una elevada morbilidad con complicaciones agudas y crónicas. El manejo de estos pacientes es complejo y requiere atención interdisciplinar. El objetivo del estudio es analizar las características y el manejo de los pacientes con drepanocitosis que ingresan por complicaciones agudas.Métodos: Estudio descriptivo retrospectivo de los ingresos por complicaciones agudas de pacientes con drepanocitosis menores de 16 años en un hospital terciario entre 2010 y 2020. Se revisaron los datos clínicos, analíticos y radiológicos.Resultados: Se incluyeron 71 ingresos correspondientes a 25 pacientes, el 40% diagnosticados por cribado neonatal. Los ingresos se incrementaron de forma progresiva durante este periodo. Los diagnósticos más frecuentes fueron la crisis vasooclusiva (35,2%), el síndrome febril (33,8%) y el síndrome torácico agudo (32,3%). Nueve pacientes precisaron ingreso en cuidados intensivos. En 20 ingresos se obtuvo documentación microbiológica, 60% bacterias. En el 86% se administró antibioterapia y 28% precisaron analgesia con opioides. El 89% cumplían la pauta de vacunación adecuada y el 41% recibían hidroxiurea previo al ingreso.Conclusiones: Las complicaciones agudas que precisan ingreso hospitalario son frecuentes en los pacientes con drepanocitosis, siendo las más habituales la crisis vasooclusiva y el síndrome febril. Esto conlleva un uso elevado de antibioterapia y opioides. El diagnóstico precoz facilita el reconocimiento de complicaciones de riesgo vital como el síndrome torácico agudo y el secuestro esplénico. A pesar de las medidas preventivas y los tratamientos indicados en la actualidad, estas complicaciones agudas precisan manejo hospitalario. (AU)

Introduction: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications.Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed.Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%.Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management. (AU)

Clinical management of the acute complications of sickle cell anemia: 11 years of experience in a tertiary hospital.

INTRODUCTION: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. METHODS: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. RESULTS: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. CONCLUSIONS: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.

Real-world analysis of main clinical outcomes in patients with polycythemia vera treated with ruxolitinib or best available therapy after developing resistance/intolerance to hydroxyurea.

BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.

Na improves the growth of K-deficient but not K-sufficient kale.

The decrease in the use of K fertilizers may be relevant for developing countries that depend on imports, as well as for specific groups such as patients with chronic kidney disease, who have restricted K in their diets. However, the decrease in the use of K affects plant yield, requiring the study of alternatives to mitigate nutritional stress. Sodium is a beneficial element that can mitigate K deficiency, but studies on kale plants are lacking. We investigated the role of Na in kale grown with and without K in nutrient feed solution. Four treatments were used: abundant K, abundant K plus Na, deficient K, and deficient K plus Na. Low Na (2 mmol L-1) attenuated the symptoms of K deficiency in kale by minimizing leaf water loss and increasing pigment content, leaf area, and plant dry mass. The synergism between K and Na negatively affected the growth of kale plants.

Are the interaction effects of warming and drought on nutritional status and biomass production in a tropical forage legume greater than their individual effects?

MAIN CONCLUSION: Drought alone and drought plus warming will change the nutrient requirements and biomass distributions of Stylosanthes capitata, while warming will be advantageous only under well-watered condition for the next decades. Climate change effects on natural and managed ecosystems are difficult to predict due to its multi-factor nature. However, most studies that investigate the impacts of climate change factors on plants, such as warming or drought, were conducted under one single stress and controlled environments. In this study, we evaluated the effects of elevated temperature (+ 2 °C) (T) under different conditions of soil water availability (W) to understand the interactive effects of both factors on leaf, stem, and inflorescence macro and micronutrients concentration and biomass allocation of a tropical forage species, Stylosanthes capitata Vogel under field conditions. Temperature control was performed by a temperature free-air controlled enhancement (T-FACE) system. We observed that warming changed nutrient concentrations and plant growth depending on soil moisture levels, but the responses were specific for each plant organ. In general, we found that warming under well-watered conditions greatly improved nutrient concentration and biomass production, whilst the opposite effect was observed under non-irrigated and non-warmed conditions. However, under warmed and non-irrigated conditions, leaf biomass and leaf nutrient concentration were greatly reduced when compared to non-warmed and irrigated plants. Our findings suggest that warming (2 °C above ambient temperature) and drought, as well as both combined stresses, will change the nutrient requirements and biomass distributions between plant aerial organs of S. capitata in tropical ecosystems, which may impact animal feeding in the future.

Metabolic Biomarkers for the Early Detection of Cancer Cachexia.

Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia. Methods: Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n = 5) were sacrificed every other day over the 14-day time course and control mice (n = 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia. Results: Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss. Conclusion: The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions.

Pre-selection of banana somaclones resistant to Fusarium oxysporum f. sp. cubense, subtropical race 4.

- Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most destructive diseases affecting banana crops worldwide. Therefore, the development of resistant cultivars is a promising alternative to mitigate the effects of the disease on banana plantations. The objectives of this study were to induce somaclonal variation in banana cultivars of the Silk and Cavendish types and to select somaclones resistant to subtropical race 4, thereby enabling the production of fruit in areas where this race is present. Shoot clump apexes of the Grand Naine and Maçã (Silk) cultivars were grown in MS medium. The cultures were subcultured four times. They were then challenged with fusaric acid (FA) in an experiment consisting of four treatments with different concentrations (0.1, 0.2, 0.3, and 0.4 mM) and five repetitions, each consisting of a Petri dish containing seven multiple shoot clumps in MS culture medium supplemented with 2.5 mg/L benzylamine purine. Multiple shoot clumps without the addition of FA were also used in the experiment, and were subcultured three times and maintained in a dark room. The multiple shoot clumps that survived the treatment with FA were transferred to MS medium and maintained in the growth chamber in the presence of light. The regenerated plants were later planted in tanks containing soil infested with an isolate classified as Foc subtropical race 4 (Foc STR4), and were evaluated for resistance to the pathogen at 90 days after inoculation (d.a.i.). Pathogen structures were confirmed by root clarification and root staining technique. All somaclones of the Maçã (Silk) cultivar were susceptible to Fusarium wilt and two somaclones of the Grand Naine cultivar were selected as resistant. The addition of FA as a selective agent was effective in the selection of somaclones among plants of the Grand Naine cultivar, as shown by the selection of two somaclones resistant to Foc STR4. The next step will consist of the agronomic and market potential validation of the selected somaclones, aiming to confirm their potential use by producers.

The invisibility of the LGBTQIA+ people in the databases: new possibilities in the 2019 National Health Research? / A invisibilidade das pessoas LGBTQIA+ nas bases de dados: novas possibilidades na Pesquisa Nacional de Saúde 2019?

The availability of information about population minorities, in this case, the LGBTQIA+ population (Lesbians, Gays, Bisexual, Transvestite/Transsexual, Queer, Intersex, and Asexual), and the possible intersections with other variables on population bases is essential for understanding the similarities and specificities of the reality experienced by these groups, and the establishment of focused public policies. In this sense, this paper aims to reflect on the problems related to research about the sex and gender orientations/performances and, consequently, the lack of information on this topic available in population databases. From the inclusion of the question about sexual orientation in the 2019 National Health Survey database, despite the limitations, this paper presents possible opportunities for investigations on the topic from different perspectives.

A disponibilidade de informações a respeito das minorias populacionais, nesse caso, da população LGBTQIA+ (Lésbicas, Gays, Bissexuais, Travestis e Transexuais, Queers, Intersexuais e Assexuais) e a possibilidade de cruzamentos com demais variáveis em bases populacionais é imprescindível para a compreensão das similaridades e especificidades da realidade vivenciada por estes grupos, bem como para a criação de políticas públicas focalizadas. Nesse sentido, buscamos refletir nesse artigo sobre os problemas relativos à investigação sobre as orientações/performances de sexo e gênero e, por consequência, a falta de informação sobre tal temática disponível nas bases de dados populacionais. A partir da inclusão da pergunta sobre orientação sexual na base de dados da Pesquisa Nacional de Saúde (PNS), de 2019, apesar das limitações, apresentamos algumas das possíveis oportunidades de investigações sobre o tema a partir de diferentes óticas.

A invisibilidade das pessoas LGBTQIA+ nas bases de dados: novas possibilidades na Pesquisa Nacional de Saúde 2019? / The invisibility of the LGBTQIA+ people in the databases: new possibilities in the 2019 National Health Research?

Resumo A disponibilidade de informações a respeito das minorias populacionais, nesse caso, da população LGBTQIA+ (Lésbicas, Gays, Bissexuais, Travestis e Transexuais, Queers, Intersexuais e Assexuais) e a possibilidade de cruzamentos com demais variáveis em bases populacionais é imprescindível para a compreensão das similaridades e especificidades da realidade vivenciada por estes grupos, bem como para a criação de políticas públicas focalizadas. Nesse sentido, buscamos refletir nesse artigo sobre os problemas relativos à investigação sobre as orientações/performances de sexo e gênero e, por consequência, a falta de informação sobre tal temática disponível nas bases de dados populacionais. A partir da inclusão da pergunta sobre orientação sexual na base de dados da Pesquisa Nacional de Saúde (PNS), de 2019, apesar das limitações, apresentamos algumas das possíveis oportunidades de investigações sobre o tema a partir de diferentes óticas.

Abstract The availability of information about population minorities, in this case, the LGBTQIA+ population (Lesbians, Gays, Bisexual, Transvestite/Transsexual, Queer, Intersex, and Asexual), and the possible intersections with other variables on population bases is essential for understanding the similarities and specificities of the reality experienced by these groups, and the establishment of focused public policies. In this sense, this paper aims to reflect on the problems related to research about the sex and gender orientations/performances and, consequently, the lack of information on this topic available in population databases. From the inclusion of the question about sexual orientation in the 2019 National Health Survey database, despite the limitations, this paper presents possible opportunities for investigations on the topic from different perspectives.

Documento de consenso para el diagnóstico y tratamiento del déficit de piruvato quinasa / Consensus document for the diagnosis and treatment of pyruvate kinase deficiency

El déficit de piruvato quinasa es la segunda enzimopatía más frecuente y la principal causa de anemia hemolítica congénita crónica no esferocítica. Su prevalencia está infraestimada por la baja sospecha clínica de los casos leves, las dificultades del correcto diagnóstico enzimático y la gran variedad de diagnósticos diferenciales. Los avances en las técnicas moleculares están permitiendo mejorar notablemente el diagnóstico. El tratamiento continúa basado en soporte transfusional y esplenectomía, siendo necesarios la vigilancia y el tratamiento de la sobrecarga férrica en todos los pacientes, transfundidos o no. Actualmente el único tratamiento curativo es el trasplante alogénico de progenitores hematopoyéticos, indicado en los casos graves con donante idéntico. Las nuevas terapias farmacológicas y génicas parecen prometedoras. En este artículo, el Grupo Español de Eritropatología realiza una actualización de la situación actual de esta enfermedad, con especial atención a los métodos diagnósticos y a los tratamientos actuales y futuros. (AU)

Pyruvate kinase (PK) deficiency is the second most frequent enzymopathy and the most common cause of chronic hereditary non-spherocytic haemolytic anaemia. Its global prevalence is underestimated due to low clinical suspicion of mild cases, associated with difficulties in the performance and interpretation of PK enzymatic activity assays. With the advent of next generation sequencing techniques, a better diagnostic approach is achieved. Treatment remains based on red blood cell transfusions and splenectomy, with special attention to iron overload, not only in transfusion-dependent patients. Nowadays, allogeneic hematopoietic stem cell transplantation is the only curative treatment, recommended only in selected cases of severely affected patients with an HLA-identical donor. Novel pharmacological and gene therapies are in clinical trials, with promising results. In this article, the Spanish Erythropathology Group reviews the current situation of PK deficiency, paying special attention to the usefulness of different diagnostic techniques and to actual and emerging treatments. (AU)

Cryptochrome 1a depends on blue light fluence rate to mediate osmotic stress responses in tomato.

The participation of plant cryptochromes in water deficit response mechanisms has been highlighted in several reports. However, the role of tomato (Solanum lycopersicum L.) cryptochrome 1a (cry1a) in the blue light fluence-dependent modulation of the water deficit response remains largely elusive. The tomato cry1a mutant and its wild-type counterpart were grown in water (no stress) or PEG6000 (osmotic stress) treatments under white light (60 µmol m-2 s-1) or from low to high blue light fluence (1, 5, 10, 15 and 25 µmol m-2 s-1). We first demonstrate that under nonstress conditions cry1a regulates seedling growth by mechanisms that involve pigmentation, lipid peroxidation and osmoprotectant accumulation in a blue light-dependent manner. In addition, we further highlighted under osmotic stress conditions that cry1a increased tomato growth by reduced malondialdehyde (MDA) and proline accumulation. Although blue light is an environmental signal that influences osmotic stress responses mediated by tomato cry1a, specific blue light fluence rates are required during these responses. Here, we show that CRY1a manipulation may be a potential biotechnological target to develop a drought-tolerant tomato variety. Nevertheless, the complete understanding of this phenomenon requires further investigation.

[Consensus document for the diagnosis and treatment of pyruvate kinase deficiency]. / Documento de consenso para el diagnóstico y tratamiento del déficit de piruvato quinasa.

Pyruvate kinase (PK) deficiency is the second most frequent enzymopathy and the most common cause of chronic hereditary non-spherocytic haemolytic anaemia. Its global prevalence is underestimated due to low clinical suspicion of mild cases, associated with difficulties in the performance and interpretation of PK enzymatic activity assays. With the advent of next generation sequencing techniques, a better diagnostic approach is achieved. Treatment remains based on red blood cell transfusions and splenectomy, with special attention to iron overload, not only in transfusion-dependent patients. Nowadays, allogeneic hematopoietic stem cell transplantation is the only curative treatment, recommended only in selected cases of severely affected patients with an HLA-identical donor. Novel pharmacological and gene therapies are in clinical trials, with promising results. In this article, the Spanish Erythropathology Group reviews the current situation of PK deficiency, paying special attention to the usefulness of different diagnostic techniques and to actual and emerging treatments.