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In 5G and beyond radios, the increased bandwidth, the fast-changing waveform scenarios, and the operation of large array multiple-input multiple-output (MIMO) transmitter architectures have challenged both the polynomial and the artificial neural network (ANN) MIMO adaptive digital predistortion (DPD) schemes. This article proposes training data selection methods and dimensionality reduction techniques that can be combined to enable relevant reductions of the DPD training time and the implementation complexity for MIMO transmitter architectures. In this work, the combination of an efficient uncorrelated equation selection (UES) mechanism together with orthogonal least squares (OLS) is proposed to reduce the training data length and the number of basis functions at every behavioral modeling matrix in the polynomial MIMO DPD scheme. For ANN MIMO DPD architectures, applying UES and principal component analysis (PCA) is proposed to reduce the input dataset length and features, respectively. The UES-OLS and the UES-PCA techniques are experimentally validated for a $2 \,\times \, 2$ MIMO test setup with strong power amplifier (PA) input and output crosstalk. [ABSTRACT FROM AUTHOR]

Objectives: To compare the outcomes of treosulfan‐based vs busulfan‐based conditioning regimens in allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Methods: Retrospective study of all consecutive patients (2012–2019) treated with allogenic HSCT and treosulfan‐ or busulfan‐based conditioning regimens at a single center. Results: A total of 101 HSCT were included: 66 HSCT with busulfan and 35 with treosulfan. In malignant diseases (n = 62), busulfan‐based conditioning was more commonly employed than treosulfan: 82.3% vs 17.7%. However, the use of treosulfan for malignant diseases increased over time: 6.5% of HSCT in 2012–2015 vs 29% of HSCT in 2015–2019 (p =.02). The cohort of treosulfan had more children under 1‐year of age than the busulfan cohort (31 vs 13%; p =.033). The percentage of patients who received serotherapy was 73 and 89% in the nonmalignant and malignant groups, respectively. The engraftment, time to neutrophil, and platelet engraftment were not significantly different between the busulfan and the treosulfan cohorts. Rate of grade II‐IV acute GvHD was significantly higher in the busulfan cohort than the treosulfan cohort (39% vs 15%; p =.016). No differences were observed in endothelial damage complications, chronic GvHD, relapse, overall survival, and transplant‐related mortality. Conclusions: Busulfan‐based conditioning regimens are used more frequently for children undergoing allogenic HSCT, but treosulfan‐based conditioning is gaining acceptance. Treosulfan‐based conditioning is associated with lower rates of acute GvHD, and no significant differences on overall survival were observed compared with busulfan. [ABSTRACT FROM AUTHOR]

La capacidad de las pandillas para ejercer control territorial en El Salvador está cambiando la dinámica social en las comunidades marginales, y las iglesias pentecostales son una de las pocas instituciones sociales que sobreviven en este contexto. En los últimos diez años, las pandillas han pasado de ser pequeñas bandas criminales locales a un fenómeno social influyente. La familiaridad y el acceso de los pentecostales a las pandillas tiene a muchos profesionales del desarrollo examinando si iniciativas de empoderamiento basadas en la fe pueden resolver amplios problemas sociales que influyen en la expansión de las pandillas. Al mismo tiempo, el embrollo de las pandillas plantea una clara amenaza para la seguridad y la estabilidad necesarias para lograr el desarrollo sostenible. Como practicante del desarrollo transformacional en El Salvador durante más de treinta años, recientemente he observado el creciente aislamiento que el control de las pandillas está teniendo en las comunidades marginales. Este artículo analiza más de cerca los efectos que el enredo de pandillas tiene en los enfoques de desarrollo transformacional sostenible en El Salvador, examinando específicamente tres programas en la comunidad de San Martín. El desafío es identificar políticas de desarrollo transformacionales, enfoques de promoción y recursos de apoyo que mejor se adapten a las comunidades controladas por pandillas. Para lograr esto, es fundamental una discusión más amplia sobre el desarrollo transformacional en comunidades enredadas por pandillas. [ABSTRACT FROM AUTHOR]

Background: Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high‐risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non‐acantholytic (naCSCC) or not. Methods: Retrospective case‐control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high‐risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. Results: The mean age was 86 years (SD 9.61). Sixty‐one patients were men. Thirty‐nine CSCCs were located in high‐risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor‐prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor‐prognosis events. Conclusion: The proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non‐acantholytic CSCC in our cohort. [ABSTRACT FROM AUTHOR]

Ruxolitinib, a selective Janus Kinase (JAK) 1/2 inhibitor, is a promising treatment for the steroid-refractory graft-vs-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT). Most studies have been performed in the adult population showing efficacy against GvHD. In this retrospective study, we evaluated the outcomes of 19 children who received ruxolitinib for refractory acute or chronic GvHD (cGvHD) after HSCT from two Pediatric Hemato-Oncology Departments in Spain between March 2017 and December 2018. Patients received a median number of 4 (IQR 2) previous lines of treatment before starting ruxolitinib. The overall response rate in acute GvHD (aGvHD) and cGvHD was 87% and 91%, respectively. Complete response (CR) was observed in 37% of aGvHD and 8.3% of cGvHD. Remarkably, 43% and 40% of patients with steroid-refractory gastrointestinal aGvHD and lung cGvHD achieved CR. During ruxolitinib treatment, there were 36%, 31%, and 10% infections caused by viruses, bacteria, and fungi, respectively. Overall, four patients interrupted ruxolitinib due to infectious complications, hematological, and liver toxicity. The 2-year overall survival was 71.9% (CI 95% 58.6–85.2). Our experience supports the use of ruxolitinib as an effective treatment for steroid-refractory acute and cGvHD in children with a moderate toxicity profile. [ABSTRACT FROM AUTHOR]

• Colombia continues to have a very high burden of invasive pneumococcal disease (IPD). • The introduction of pneumococcal conjugate vaccine-10 (PCV-10) in Colombian children reduced the incidence of IPD in children. • In Colombia, the introduction of PCV-10 in children did not reduce the burden of IPD in adults. Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007–2011 (before the introduction of PCV-10) and 2012–2017 (after the introduction of PCV-10). In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0–4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10. [ABSTRACT FROM AUTHOR]

The vertebrate brain is organized, from its embryonic origin and throughout adult life, around a dynamic and complex fluid, the cerebrospinal fluid (CSF). There is growing interest in the composition, dynamics and function of the CSF in brain development research. It has been demonstrated in higher vertebrates that CSF has key functions in delivering diffusible signals and nutrients to the developing brain, contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the patterning of the brain. It has also been shown that the composition and the homeostasis of CSF are tightly regulated following the closure of the anterior neuropore, just before the initiation of primary neurogenesis in the neural tissue surrounding brain cavities, before the formation of functional choroid plexus. In this review we draw together existing literature about the composition and formation of embryonic cerebrospinal fluid in birds and mammals, from the closure of the anterior neuropore to the formation of functional fetal choroid plexus, including mechanisms regulating its composition and homeostasis. The significance of CSF regulation within embryonic brain is also discussed from an evolutionary perspective. [ABSTRACT FROM AUTHOR]

This paper presents an estimation/adaptation method based on the adaptive principal component analysis (APCA) technique to guarantee the identification of the minimum necessary parameters of a digital predistorter. The proposed estimation/adaptation technique is suitable for online field-programmable gate array or system on chip implementation. By exploiting the orthogonality of the resulting transformed matrix obtained with the APCA technique, it is possible to reduce the number of coefficients to be estimated which, at the same time, has a beneficial regularization effect by preventing ill-conditioning or overfitting problems. Therefore, this identification/adaptation method enhances the robustness of the parameter estimation and simplifies the adaptation by reducing the number of estimated coefficients. Due to the orthogonality of the new basis, these parameters can be estimated independently, thus allowing for scalability. Experimental results will show that it is possible to determine the minimum number of parameters to be estimated in order to meet the targeted linearity levels while ensuring a robust well-conditioned identification. Moreover, the results will show how thanks to the orthogonality property of the new basis functions, the coefficients of the digital predistorter can be estimated independently. This allows to tradeoff the digital predistorter adaptation time versus performance and hardware complexity. [ABSTRACT FROM AUTHOR]

This paper presents a technique to estimate the coefficients of a multiple-look-up table (LUT) digital predistortion (DPD) architecture based on the partial least-squares (PLS) regression method. The proposed 3-D distributed memory LUT architecture is suitable for efficient FPGA implementation and compensates for the distortion arising in concurrent dual-band envelope tracking power amplifiers. On the one hand, a new variant of the orthogonal matching pursuit algorithm is proposed to properly select only the best LUTs of the DPD function in the forward path, and thus reduce the number of required coefficients. On the other hand, the PLS regression method is proposed to address both the regularization problem of the coefficient estimation and, at the same time, reducing the number of coefficients to be estimated in the DPD feedback identification path. Moreover, by exploiting the orthogonality of the PLS transformed matrix, the computational complexity of the parameters’ identification can be significantly simplified. Experimental results will prove how it is possible to reduce the DPD complexity (i.e., the number of coefficients) in both the forward and feedback paths while meeting the targeted linearity levels. [ABSTRACT FROM AUTHOR]

Tuberculosis of the chest wall represents less than 5% of cases of musculoskeletal tuberculosis. We present the case of a patient with a cold abscess in the pectoral region due to Mycobacterium tuberculosis. A 29-year-old male of Senegalese origin reported a progressive increase in size of the right hemi-thorax without trauma or previous effort. A liquid collection of 14 cm on the major axis, between the pectoralis major muscle and the costal wall, was demonstrated on magnetic resonance imaging. Surgical debridement revealed a marked granulomatous inflammatory reaction with focal necrosis; PCR was positive for M. tuberculosis complex and culture subsequently grew M. tuberculosis complex. Specific treatment for tuberculosis achieved a good clinical outcome. The diagnosis of tuberculosis of the chest wall is always difficult, being a clinical challenge. [ABSTRACT FROM AUTHOR]

Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, including behaviour. The central nervous system is one of the most intriguing systems in complex metazoans, as it controls all body and mind functions. Its failure is responsible for a number of severe and largely incurable diseases, including neurological and neurodegenerative ones. Moreover, the evolution of the nervous system is thought to be a critical step in the adaptive radiation of vertebrates. Brain formation is initiated early during development. Most embryological, genetic and evolutionary studies have focused on brain neurogenesis and regionalisation, including the formation and function of organising centres, and the comparison of homolog gene expression and function among model organisms from different taxa. The architecture of the vertebrate brain primordium also reveals the existence of connected internal cavities, the cephalic vesicles, which in fetuses and adults become the ventricular system of the brain. During embryonic and fetal development, brain cavities and ventricles are filled with a complex, protein-rich fluid called cerebrospinal fluid (CSF). However, CSF has not been widely analysed from either an embryological or evolutionary perspective. Recently, it has been demonstrated in higher vertebrates that embryonic cerebrospinal fluid has key functions in delivering diffusible signals and nutrients to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. Moreover, it has been shown that the composition and homeostasis of CSF are tightly controlled in a time-dependent manner from the closure of the anterior neuropore, just before the initiation of primary neurogenesis, up to the formation of functional choroid plexuses. In this review, we draw together existing literature about the formation, function and homeostatic regulation of embryonic cerebrospinal fluid, from the closure of the anterior neuropore to the formation of functional fetal choroid plexuses, from an evolutionary perspective. The relevance of these processes to the normal functions and diseases of adult brain will also be discussed. [ABSTRACT FROM AUTHOR]

The article presents literature review on formation and function of the temporary embryonic blood-cerebrospinal fluid (eCSF) barrier from anterior neuropore closure to the formation of functional fetal choroid plexuses, and role of eCSF in neural development. Topics discussed include traditional concept of blood-brain barrier during embryonic development and proteomic studies shows brain development by ion carriers osmotic pressure regulators and lipid metabolism regulators.

Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins. [Copyright &y& Elsevier]

Background: Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision‐making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT. Methods: We studied allogenic HSCTs performed on children with malignant disorders at a third‐level hospital between 1991 and 2021. Survival was analyzed using the Kaplan–Meier method, log‐rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1‐year survival after HSCT. Results: We analyzed 229 HSCTs in 201 patients with a median follow‐up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12–1.76, p =.003), oldest period of HSCT (HR 0.46, 95% CI 0.29–0.73, p <.001), and mismatched donor (HR 2.65, 95% CI 1.51–4.65, p =.001). Our prognostic index was associated with 3‐year overall survival (OS; p <.001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1‐year OS. Conclusions: Our index and random forest was effective in predicting 1‐year survival. However, further validation in diverse populations is necessary to establish their generalizability. [ABSTRACT FROM AUTHOR]

To provide information about which pneumococcal vaccine could have greater coverage in Colombia. This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18–64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines. [ABSTRACT FROM AUTHOR]

Introduction Lemierre's syndrome refers to the septic thrombophlebitis of the internal jugular vein, secondary to a pharyngeal infection. Although it mainly affects the internal jugular vein, isolated cases have been described of involvement of the external jugular vein. The main etiological agent is Fusobacterium necrophorum. Case report A 27-year-old male, previously healthy, presented with a 7-day history of sore throat and fever. He was diagnosed with Lemierre's syndrome, coinfection by Bacillus circulans, F. nucleatum and Staphylococcus aureus with an atypical presentation due to the involvement of the external jugular vein and the internal jugular vein. Conclusions As far as we are aware, we present the first case of Lemierre's syndrome with these characteristics. [ABSTRACT FROM AUTHOR]

This paper presents a new technique that dynamically estimates and updates the coefficients of a digital predistorter (DPD) for power amplifier (PA) linearization. The proposed technique is dynamic in the sense of estimating, at every iteration of the coefficient’s update, only the minimum necessary parameters according to a criterion based on the residual estimation error. At the first step, the original basis functions defining the DPD in the forward path are orthonormalized for DPD adaptation in the feedback path by means of a precalculated principal component analysis (PCA) transformation. The robustness and reliability of the precalculated PCA transformation (i.e., PCA transformation matrix obtained off line and only once) is tested and verified. Then, at the second step, a properly modified partial least squares (PLS) method, named dynamic partial least squares (DPLS), is applied to obtain the minimum and most relevant transformed components required for updating the coefficients of the DPD linearizer. The combination of the PCA transformation with the DPLS extraction of components is equivalent to a canonical correlation analysis (CCA) updating solution, which is optimum in the sense of generating components with maximum correlation (instead of maximum covariance as in the case of the DPLS extraction alone). The proposed dynamic extraction technique is evaluated and compared in terms of computational cost and performance with the commonly used QR decomposition approach for solving the least squares (LS) problem. Experimental results show that the proposed method (i.e., combining PCA with DPLS) drastically reduces the amount of DPD coefficients to be estimated while maintaining the same linearization performance. [ABSTRACT FROM AUTHOR]

Introduction Actinomycosis is an unusual chronic granulomatous infectious disease. They are commensals in various sites of the human body but with little pathogenicity. Actinomyces israelii is the most prevalent species but more than 30 species have been described. Infection of the lower respiratory tract is unusual, the involvement of mediastinum being even rarer. Case report A 63-year-old man, previously healthy and living in a rural area, presented with a 5-month history of hemoptysis, pleuritic pain, weight loss, and night sweats. Community-acquired pneumonia with a mediastinal mass was documented, for which he received antibiotic management. Thoracoscopy was carried out for diagnosis and resection of the mediastinal mass due to inconclusive findings in the percutaneous biopsy. Pathology reported the presence of filamentous Gram-positive bacteria visible in Grocott staining. Due to the pathology findings, and the fact that no other infectious agents were identified, a diagnosis of actinomycosis was established. Treatment with oral amoxicillin 1g TID for 6 months was initiated. Conclusions As far as we are aware, we present the sixth case of mediastinal actinomycosis. We present this case to bring attention to this rare but clinically relevant presentation to be considered as a differential diagnosis of mediastinal masses and to emphasize the need for specific anaerobic cultures to improve the diagnostic yield. [ABSTRACT FROM AUTHOR]

Abstract: In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). Most of the proteins contained within the E-CSF, which play crucial roles in CNS development, are transferred from the blood serum. Two important questions are how E-CSF is manufactured and how its homeostasis is controlled. In this respect, the timing of the blood–CSF barrier formation is controversial. Recently, the concept of a functional dynamic barrier has been introduced. This type of barrier is different from that found in adults and is adapted to the specific requirements and environment of the developing nervous system. In this study, we injected a number of proteins into the outflow of the heart and into the cephalic cavities and examined their transport rate between these two embryo compartments. The results indicated that a functional blood–CSF barrier dynamically controls E-CSF protein composition and homeostasis in chick embryos before the formation of functional choroid plexuses. We also showed that proteins are transferred through transcellular routes in a specific area of the brain stem, close to the ventral mesencephalic and prosencephalic neuroectoderm, lateral to the ventral midline, in particular blood vessels. This study contributes to our understanding of the mechanisms involved in CNS development, as this blood–CSF interface regulates the composition of E-CSF by regulating its specific composition. [Copyright &y& Elsevier]

Background: Naïve T-cell-depleted grafts have been employed as an ex vivo T-cell depletion (TCD) platform to prevent graft-versus-host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T-cell reconstitution after allogenic hematopoietic stem cell transplantation (allo-HSCT). CD45RA- memory T cells confer protection against viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)-6B encephalitis among pediatric allo-HSCT patients.Methods: We report the first 18 consecutive allo-HSCT, 16 haplo-HSCT, and two human leukocyte antigen-matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV-6B encephalitis.Results: Engraftment was achieved in 94.5% of cases; 2-year overall survival, event-free survival, and GvHD/relapse-free survival were 87.2% (95% CI 78.6-95.8), 67.3% (95% CI 53.1-81.5), and 64% (95% CI 50.5-78.1), respectively. HHV-6B reactivation occurred in 7 of the haplo-HSCT patients, six of who received a cell infusion with an NK/CD4 ratio <2. None of the patients developed encephalitis.Conclusions: In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo-HSCT graft is safe and can prevent HHV-6B encephalitis. We recommend infusing adoptive NK cells after allo-HSCT using CD45RA+ TCD grafts. [ABSTRACT FROM AUTHOR]

Purpose: Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. Methods: We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. Results: Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17–52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10–99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54–1687)]. Conclusions: In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT. [ABSTRACT FROM AUTHOR]

Objective: Describe the GETH haploidentical stem cell transplantation (haplo‐HSCT) activity in non‐malignant disease (NMDs). Methods: We retrospectively analyzed data from children with NMDs who underwent haplo‐HSCT. Results: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo‐HSCT through ex vivo T cell‐depleted (TCD) graft platforms or post‐transplantation cyclophosphamide (PT‐Cy) at 7 Spanish centers. Five cases employed unmanipulated PT‐Cy haplo‐HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+CD19+ depletion, TCRαβ+CD19+ selection or naive CD45RA+ T‐cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo‐HSCT, and bone marrow was the source for one PT‐Cy haplo‐HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1‐year cumulative incidence of graft failure was 27.4%. The 1‐year III‐IV acute graft‐versus‐host disease (GvHD) and 1‐year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2‐year overall survival was 44.9% for PIDs, and the 2‐year graft‐versus‐host disease‐free and relapse‐free survival rate was 37.6% for the other NMDs. The transplantation‐related mortality at day 100 was 30.8%. Conclusion: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise. [ABSTRACT FROM AUTHOR]

The central nervous system develops around a fluid filled space which persists in the adult within the ventricles, spinal canal and around the outside of the brain and spinal cord. Ventricular fluid is known to act as a growth medium and stimulator of proliferation and differentiation to neural stem cells but the role of CSF in the subarachnoid space has not been fully investigated except for its role in the recently described "glymphatic" system. Fundamental changes occur in the control and coordination of CNS development upon completion of brain stem and spinal cord development and initiation of cortical development. These include changes in gene expression, changes in fluid and fluid source from neural tube fluid to cerebrospinal fluid (CSF), changes in fluid volume, composition and fluid flow pathway, with exit of high volume CSF into the subarachnoid space and the critical need for fluid drainage. We used a number of experimental approaches to test a predicted critical role for CSF in development of the cerebral cortex in rodents and humans. Data from fetuses affected by spina bifida and/or hydrocephalus are correlated with experimental evidence on proliferation and migration of cortical cells from the germinal epithelium in rodent neural tube defects, as well as embryonic brain slice experiments demonstrating a requirement for CSF to contact both ventricular and pial surfaces of the developing cortex for normal proliferation and migration. We discuss the possibility that complications with the fluid system are likely to underlie developmental disorders affecting the cerebral cortex as well as function and integrity of the cortex throughout life. [ABSTRACT FROM AUTHOR]

Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients. [ABSTRACT FROM AUTHOR]

Highlights • CD45RA+ TCD allows the retention of high amounts of donor memory T cells. • HHV-6 can reactivate from donor CD4+ T lymphocytes. • Inflammation of engraftment could facilitate HHV-6 encephalitis. Abstract The CD45RA T cell depletion (TCD) method has been used to deplete naive T cells, preventing graft-versus-host disease (GVHD) but preserving memory cells, providing immediate functional T cells with anti-infection, antileukemia, and antirejection effects. We describe a series of 25 consecutive high-risk patients with leukemia who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with CD45RA TCD. Each patient received 2 cell products: 1 created by CD34 positive selection and the other through CD45RA depletion from the CD34 negative fraction by a CliniMACS device. CD45RA-depleted haplo-HSCT was well tolerated, with rapid engraftment and low risk of severe acute GVHD and chronic GVHD. Although this treatment achieved a good control of viral reactivations, such as cytomegalovirus and adenovirus, we observed an unexpectedly high rate of limbic encephalitis due to human herpesvirus-6 (HHV-6; 8 cases). Characteristically, the infection appeared early in almost all patients, just after the engraftment. Although no patient died from encephalitis, 1 patient showed neuropsychological sequelae, and another experienced secondary graft failure just after the HHV-6 reactivation. [ABSTRACT FROM AUTHOR]

Background: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use.Study Design and Methods: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line. We analyzed the NK cell recovery and expansion, T cell depletion, phenotype, cytotoxicity, safety, and genomic stability of two good manufacturing practices (GMP)-grade IL-15-activated NK cell products.Results: The number of NK cells obtained from NKIL15 cell and NKAE cell products was similar; however, there were significantly fewer T cells in the NKIL15 cell product. The haploidentical NKAE cell product contained more T cells than the autologous NKAE cell product. The surface expression of the activating receptors CD69, CD25, natural killer group-2 member D receptor, NKp44, NKp46, NKp30, and DNA accessory molecule 1 was up regulated in both NK cell products. NKIL15 cell and NKAE cell products had significantly higher lytic activity than unstimulated NK cells and showed no lytic activity against PBMNCs from healthy donors. No genetic alterations or potential oncogenic effects were found.Conclusion: Different GMP-grade procedures can be used to obtain large numbers of highly IL-15-activated NK cells with extremely low T cell content for clinical use. [ABSTRACT FROM AUTHOR]

An abstract of the article "Rollover Protective Structure (ROPS) Retrofitting on Agricultural Tractors: Goals and Approaches in Different Countries" by Eugenio Cavallo, Thierry Langle and David Bueno is presented.

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting from variants in theWASgene, characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the fact that WAS is traditionally differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets, in practice, microthrombocytopenia may occasionally not be present, and in certain cases, WAS patients exhibit some parallelism to ITP patients. We characterized one patient presenting with the classic form of the disease but increased mean platelet volume. Molecular studies revealed a novel hemizygous 1-bp deletion inWASgene, c.802delC, leading to a frameshift and stop codon at amino acid 308 (p.Arg268Glyfs*40). Next-generation sequencing of a total of 70 additional genes known to harbor variants implicated in inherited platelet disorders did not identify additional defects. The pathogenesis of macrothrombocytopenia in this case is not known, but probably the coexistence of a still unidentified additional genetic variant might be involved. [ABSTRACT FROM PUBLISHER]