Search

Barber–Say syndrome (BSS) is a rare congenital ectodermal dysplasia with few cases reported in the literature. We describe a 9‐year‐old boy with congenital generalized hypertrichosis and multiple rhabdomyomatous mesenchymal hamartomas (RMHs) on his nose and periocular region. Next‐generation sequencing, performed in DNA from a blood sample, and RMH tissue, revealed a pathogenic variant in the TWIST2 gene, which was not detected in a salivary sample of the patient, nor in his parents. Therefore, we consider this variant as de novo mosaicism. To our knowledge, this is the first case of multiple RMHs associated with BSS. [ABSTRACT FROM AUTHOR]

Summary: Diffuse large B‐cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R‐ESHAP (LR‐ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1–14 of every 21‐day cycle, in combination with R‐ESHAP at standard doses. Responding patients underwent autologous stem‐cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell‐of‐origin (COO) classification was performed. Forty‐six patients were included. The ORR after LR‐ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non‐refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty‐eight patients (61%) underwent ASCT. At a median follow‐up of 41 months, the estimated 3‐year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment‐related deaths during LR‐ESHAP cycles. In conclusion, LR‐ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL. [ABSTRACT FROM AUTHOR]

Variation in offspring sex ratio, particularly in birds, has been frequently studied over the last century, although seldom using long‐term monitoring data. In raptors, the cost of raising males and females is not equal, and several variables have been found to have significant effects on sex ratio, including food availability, parental age, and hatching order. Sex ratio differences between island populations and their mainland counterparts have been poorly documented, despite broad scientific literature on the island syndrome reporting substantial differences in population demography and ecology. Here, we assessed individual and environmental factors potentially affecting the secondary sex ratio of the long‐lived Egyptian vulture Neophron percnopterus. We used data collected from Spanish mainland and island populations over a ca. 30‐year period (1995–2021) to assess the effects of insularity, parental age, breeding phenology, brood size, hatching order, type of breeding unit (pairs vs. trios), and spatial and temporal variability on offspring sex ratio. No sex bias was found at the population level, but two opposite trends were observed between mainland and island populations consistent with the island syndrome. Offspring sex ratio was nonsignificantly female‐biased in mainland Spain (0.47, n = 1112) but significantly male‐biased in the Canary Islands (0.55, n = 499), where a male‐biased mortality among immatures could be compensating for offspring biases and maintaining a paired adult sex ratio. Temporal and spatial variation in food availability might also have some influence on sex ratio, although the difficulties in quantifying them preclude us from determining the magnitude of such influence. This study shows that insularity influences the offspring sex ratio of the Egyptian vulture through several processes that can affect island and mainland populations differentially. Our research contributes to improving our understanding of sex allocation theory by investigating whether sex ratio deviations from parity are possible as a response to changing environments comprised by multiple and complexly interrelated factors. [ABSTRACT FROM AUTHOR]

Elemental selenium (Se0) nanomaterials undergo allotropic transition from thermodynamically‐unstable to more stable phases. This process is significantly different when Se0 nanoparticles (NPs) are produced via physico‐chemical and biological pathways. While the allotropic transition of physico‐chemically synthesized Se0 is fast (minutes to hours), the biogenic Se0 takes months to complete. The biopolymer layer covering biogenic Se0 NPs might be the main factor controlling this retardation, but this still remains an open question. Phylogenetically‐diverse bacteria reduce selenium oxyanions to red amorphous Se0 allotrope, which has low market value. Then, red Se0 undergoes allotropic transition to trigonal (metallic grey) allotrope, the end product having important industrial applications (e.g. semiconductors, alloys). Is it not yet clear whether biogenic Se0 presents any biological function, or it is mainly a detoxification and respiratory by‐product. The better understanding of this transition would benefit the recovery of Se0 NPs from secondary resources and its targeted utilization with respect to each allotropic stage. This review article presents and critically discusses the main physico‐chemical methods and biosynthetic pathways of Se0 (bio)mineralization. In addition, the article proposes a conceptual model for the resource recovery potential of trigonal selenium nanomaterials in the context of circular economy. [ABSTRACT FROM AUTHOR]

Summary: Although follicular lymphoma (FL) patients relapsing within 24 months after first‐line treatment (POD24) have a poor prognosis, some cases show notable survival after first relapse (SF1R). We aimed to characterize the POD24 FL population and to identify the main prognostic factors at progression. We selected 162 POD24 patients (80F; median age at first relapse 59 years) from a cohort of 1067 grades 1‐3a FL‐treated patients. The remaining 905 patients treated with first‐line immunochemotherapy and diagnosed during the same period were used to compare outcomes in terms of survival. After a median follow‐up of 11.0 years, 96 patients died (10y‐SF1R of 40%). Age over 60 years (p < 0.001), high lactate dehydrogenase (LDH) (p < 0.001), haemoglobin (Hb) less than 120 g/L (p < 0.001), advanced stage (p < 0.001), high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) (p < 0.001), histological transformation (HT) (p < 0.001) and reaching less than complete response (CR) after salvage therapy (p < 0.001), predicted poor SF1R at relapse. In multivariate analysis only high‐risk FLIPI and HT maintained prognostic significance for SF1R. POD24 patients not transformed and with low/intermediate FLIPI at relapse behaved better than the remaining cases. POD24 patients showed an excess mortality of 38% compared to the general population. Although outcome of POD24 FL patients is poor, a considerable group of them (low/intermediate FLIPI and not transformed at first relapse) behave better. [ABSTRACT FROM AUTHOR]

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti‐CD38 antibody) in combination with cemiplimab (Cemi, anti‐programmed death‐1 [PD‐1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), and peripheral T‐cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de‐escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti‐PD‐1/programmed death‐ligand 1 [PD‐L1] naïve), and objective response rate in Cohorts A2 (cHL anti‐PD‐1/PD‐L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose‐limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti‐PD‐1/PD‐L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations. [ABSTRACT FROM AUTHOR]

Serum soluble CD23 (sCD23) levels have been acknowledged as a prognostic factor in patients with chronic lymphocytic leukemia (CLL), but their potential relevance has not been analyzed in recent times. We retrospectively studied 338 CLL, small lymphocytic lymphoma, or CLL‐type monoclonal B‐cell lymphocytosis patients from a single institution, with available sCD23 levels at diagnosis. Baseline features and outcomes were compared between patients with sCD23 ≤/>1000 UI/L. The 140 patients (41%) who had sCD23 > 1000 UI/L showed adverse‐risk clinical and biological characteristics. High sCD23 levels were predictive of a shorter time to first treatment (5‐year probability of requiring treatment: 60 vs. 20%, p < 0.0001; hazard ratio (HR) = 1.72, p = 0.003 in a multivariable model also including the CLL International Prognostic Index and the absolute lymphocyte count), and a poorer 5‐year overall survival (70 vs. 82%, p = 0.0009). These data suggest the potential of sCD23 to predict treatment‐free survival and to shed light on mechanisms of activity and resistance to CD23‐directed therapies. [ABSTRACT FROM AUTHOR]

B Introduction: b The TRANSFORM primary analysis (PA; NCT03575351) confirmed the superior efficacy of liso-cel versus SOC as second-line (2L) therapy in patients (pts) with primary refractory (refr) or early relapsed (rel) large B-cell lymphoma (LBCL) (Abramson et al. I Blood i , 2022). LISOCABTAGENE MARALEUCEL (LISO-CEL) VERSUS STANDARD OF CARE (SOC) AS SECOND-LINE THERAPY IN LARGE B-CELL LYMPHOMA (TRANSFORM STUDY): SUBGROUP ANALYSES BY PRIOR THERAPY RESPONSE Baseline characteristics in the refr and rel subgroups, respectively, were generally balanced: median LDH (U/L; liso-cel, 228.5 and 225; SOC, 259 and 259); median SPD (cm SP 2 sp ; liso-cel, 11 and 12; SOC, 15.5 and 18); high-grade B-cell lymphoma (liso-cel, 27% and 16%; SOC, 27% and 9%); diffuse LBCL not otherwise specified (liso-cel, 58% and 56%; SOC, 49% and 73%). [Extracted from the article]

The FLIPI‐L has recently been proposed as a novel prognostic index in follicular lymphoma (FL), combining FLIPI and the presence of lymphopenia. In our single‐center validation in 381 FL patients, lymphopenia was less frequent than in the original publication and thus the distribution of risk categories was different. Although it was not able to properly predict time to first treatment, FLIPI‐L performed slightly better than FLIPI alone in the prediction of response, early relapse, progression‐free and overall survival, and histological transformation. This new tool or others encompassing parameters from the microenvironment might improve upon the prognostic ability of classical scores. [ABSTRACT FROM AUTHOR]

ZrO2 and ZrO2:Sm3+ nanopowders are synthesized by means of polyol method, from [Zr(NO3)2.xH2O] and (SmCl3·6H2O) precursors dissolved in a diethylene glycol medium. X‐ray diffraction (XRD) results show polymorphic powders because monoclinic structure and tetragonal are exhibited. The crystal size is estimated by Scherrer formula; an averaged crystallite size of 9 nm is obtained. Surface morphology study, by means of SEM, evidences multiform particles, some with straight edges associated with monoclinic or tetragonal structure. The chemical composition microanalysis results indicate agreement with ideal stoichiometry for ZrO2 and ZrO2:Sm3+ powders. The photoluminescence emission spectra show that maximum intensity is reached at λ = 614 nm due to transition 4G5/2→6H7/2, exciting with λex = 240 nm, which corresponds to sample ZrO2:Sm3+ (0.75 at%); this sample is labeled as M3. Very similar results are obtained by cathodoluminescence studies. On the contrary, exciting with λex = 380 nm (monitoring emission band peaked at 614 nm), emission bands of host lattice and ZrO2:Sm3+ are favored simultaneously. The luminescent quenching phenomenon occurs when doping concentration (Sm3+ ions) is >=0.75 at%. The photoluminescent emission exhibits a reddish orange color, characteristic of Sm3+ ions, and yellowish‐orange for cathodoluminescence emission. [ABSTRACT FROM AUTHOR]

With the intention of identifying follicular lymphoma (FL) patients at higher risk of progression, early relapse (POD24), histological transformation (HT) or death, multiple risk scores (RS) have been proposed. However, it has not yet been established whether any of them globally outperforms the others. We evaluated the clinical utility and statistical performance of the five most widely used clinical scores (IPI, ILI, FLIPI, FLIPI2, PRIMA‐PI) in a single‐center series of 414 grade 1‐3A FL patients diagnosed in the rituximab era. Overall concordance (proportion of patients allocated to the same risk category by all five RS) was 24%. FLIPI and FLIPI2 were predictive of time to first treatment. All five scores were predictive of response, POD24, progression‐free, and OS, while only FLIPI predicted HT. IPI identified a small subset (7%) of truly high‐risk patients (10‐year OS of 16%). In subgroup analyses, we showed that ILI is useful in the prognostication of limited‐disease patients, and PRIMA‐PI is an age‐independent score that can identify a high‐risk subset of older patients. Performance metrics were slightly better for IPI in terms of calibration (Harrell's c‐index 0.73), without major differences among RS regarding other parameters. Although the incorporation of molecular and imaging data will continue to refine the stratification of FL patients, FLIPI remains the most powerful clinical prognostic index in the rituximab era, predicting the greatest number of endpoints. [ABSTRACT FROM AUTHOR]

Summary: The presence of a serum monoclonal component has been associated with poor outcomes in some lymphomas. However, data in follicular lymphoma (FL) are scarce. We studied 311 FL patients diagnosed at a single institution, for whom information on serum immunofixation electrophoresis (sIFE) at diagnosis was available. Baseline characteristics and outcomes were compared between patients with a positive (+sIFE) and a negative sIFE (−sIFE). sIFE was positive in 82 patients (26%). Baseline features were comparable between both groups, except for an older age and higher proportion of elevated β2‐microglobulin levels in the +sIFE group. With a median follow‐up of 4.6 years, a +sIFE was associated with a higher risk of early relapse (POD24, 27% vs. 15%, P = 0·02), shorter progression‐free survival (PFS; 42% vs. 52% at 5 years, P = 0·008), and shorter overall survival (OS; 59% vs. 77% at 10 years, P = 0·046). In patients >60 years, a +sIFE was an independent predictor of OS [hazard ratio (HR) = 2·4, 95% confidence interval (CI): 1·2–5·0; P = 0·02]. Approximately one quarter of patients with FL has a +sIFE at diagnosis, which is a predictor of poor outcome. These findings encourage further investigation of its relationship with B‐cell biology and the tumour microenvironment. [ABSTRACT FROM AUTHOR]

This is the first study analyzing the interval between frontline treatment and the second relapse (PFS2) in follicular lymphoma. The PFS2 was <2 years in 41 patients (46%), 2-5 years in 29 patients (33%), and >5 years in 19 patients (21%). Although not statistically significant, the CR rate after frontline and second-line treatments was higher for patients with a PFS2 > 5 years (95 and 84% for first- and second-line treatment), compared with those with a PFS2 2-5 years and <2 years. [Extracted from the article]

In addition, FL patients had a significantly lower percentage of naïve T lymphocytes, a higher percentage of effector memory and effector lymphocytes, both CD4 SP + sp and CD8 SP + sp . Of note, regulatory T lymphocytes (Treg) and Th1 cells were increased in FL patients, while NK-cells were diminished. The aim of this study was to characterise the PB immune profile of FL patients at diagnosis, first relapse (R1) and subsequent relapses (> I R i SP 2 sp ) and compare them with healthy controls. [Extracted from the article]

Summary: The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression‐free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age‐matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10‐year period who needed therapy and were treated with rituximab‐containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10‐year overall survival (OS) of 53% and 87% for non‐CR30 and CR30 patients, respectively. Ten‐year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex‐ and age‐matched Spanish general population. [ABSTRACT FROM AUTHOR]

The article presents a study which explored the possible role of Transcribed Ultraconserved Region (T-UCR) in the pathogenesis of CLL. Topics include potential clinical value of the significantly modulated T-UCRs in two independent cohorts of chronic lymphocytic leukemia (CLL) patients, expression levels of uc.70 and uc.414 in the same cases studied by microarrays and in an independent series of CLL cases, and expression of uc.70-related transcripts using RNAseq data of CLL cases.

Summary: Follicular lymphoma (FL) is an indolent disease characterized by long survival but frequent relapses. Before the introduction of rituximab, the clinical course of these patients showed a shorter response duration (RD) after each relapse. In this study, we analysed if this pattern of shortened responses remains in patients treated in the rituximab era. We selected 348 patients newly diagnosed with FL in two institutions between 2001 and 2014 that received chemoimmunotherapy. After a median follow‐up of 6·3 years, 10‐year progression‐free and overall survivals were 53% and 72%, respectively. All patients received first‐line, 111 second‐line and 41 third‐line treatments, with a 5‐year RD of 62%, 39% and 24%, respectively (P < 0·0001). Variables predicting longer RD after first‐line treatment were normal β2microglobulin, complete remission achievement and maintenance with rituximab. Patients with longer RD after first‐line showed significantly longer RD after second‐line therapy. Autologous stem‐cell transplantation after second‐line therapy did not significantly impact RD. Median survival after first, second and third therapies was not reached, 7·6 and 4·8 years, respectively, whereas relative survival with respect to a sex‐ and age‐matched Spanish population, the decrease in the life expectancy at 10 years was 17%, 45% and 79%, respectively. Thus, RD still shortens after each relapse in patients with FL treated in first line with rituximab combinations. [ABSTRACT FROM AUTHOR]

Summary: Long non‐coding RNAs (lncRNAs) comprise a family of non‐coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL) we performed RNA‐sequencing at high depth sequencing in primary FL samples ranging from grade 1‐3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNAs (dif‐lncRNAs) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif‐lncRNAs were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL. RP4‐694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP4‐694A7.2 silencing in the WSU‐FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP4‐694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki‐67 proliferation index. In summary, lncRNAs are differentially expressed across the clinico‐biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours. [ABSTRACT FROM AUTHOR]

Permanent epicardial pacing wires are sometimes left in place and can lead to long‐term complications. We report on a case of a granulomatous reaction with a cutaneous fistula secondary to the retained epicardial pacing wires in a child and highlight the relevance of sonography as an additional tool in the diagnosis and management of dermatologic conditions. [ABSTRACT FROM AUTHOR]

Summary: The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO‐IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated with immunochaemotherapy: low (LR), low‐intermediate (LIR), high‐intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO‐IPI in the DLBCL subtypes defined by the immunohistochaemistry‐based Hans algorithm, Germinal Centre B (GCB) and non‐GCB. A multivariate Cox regression model including GELTAMO‐IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non‐GCB) and both the GELTAMO‐IPI and the COO subtype in 780 (353 GCB; 427 non‐GCB). There were no differences in 5‐year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO‐IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO‐IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5‐year OS of 100%, 75% and 52%, respectively. In the non‐GCB subtype, LR, the combined LIR+HIR and HR had a 5‐year OS of, 97%, 82% and 35% respectively. GELTAMO‐IPI identifies a genuine poor outcome group of patients in the DLBCL non‐GCB subtype. [ABSTRACT FROM AUTHOR]

These patients were further stratified by ctDNA levels and GS, and those unfavorable GS or ctDNA concentration >4 log hGE/ml presented worse PFS and OS than without risk factors a 3-year PFS of 34.6% and 90.9%, respectively (Figure 1B). Circulating tumour DNA concentration and genetic classification improve risk stratification in newly diagnosed patients with Diffuse Large B-Cell Lymphoma B Introduction: b Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with poor outcomes for the 40% of patients who relapse or are refractory to upfront therapy, and current prognostic tools are unable to identify many of those patients. [Extracted from the article]

The article offers information on the hairy-cell leukaemia (HCL) which is a B-cell lymphoproliferative disorder with the morphological, molecular and immunophenotypic profile. It mentions that markers are determined by flow cytometry (FC), that allows an accurate diagnosis and minimal residual disease (MRD) monitoring.

The differential diagnosis in children with TA may include alopecia areata (AA) and trichotillomania, two conditions that do not display PHC on dermoscopy.1,3 Frequent trichoscopic findings in AA are yellow and black dots, short vellus hairs, broken hairs, exclamation point hairs, pigtail hairs, and Pohl-Pinkus constrictions.6 On the other hand, in trichotillomania, it is common to see broken hairs, short vellus hairs, black dots, trichoptilosis, V hairs, hair powder, yellow dots, mace hairs, coiled hairs, exclamation point hairs, blood spots, branched hairs, angulated hairs, concentric hairs, flame hairs, and tulip hairs.7 Dermoscopy is a useful instrument, although there is no pathognomonic trichoscopic sign to differentiate the alopecias. A 9-year-old girl presented with apparent decrease in frontotemporal hair density over the previous year (Figure 1A,B). Peripilar hair casts are usually located at the periphery of the patch of alopecia and are present in more than 80% of patients with TA. [Extracted from the article]

In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such a process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi-step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. In addition, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca2+ ions. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma ( DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose ( MTD) of lenalidomide in combination with R- ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) ( LR- ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15 mg) given on days 1-14 of every 21-day cycle, in combination with R- ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10 mg/d was identified as the MTD because, in the 15 mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15 mg cohorts, respectively) were evaluable. All toxicities occurring during LR- ESHAP cycles resolved appropriately and no grade 4-5 non-haematological toxicities were observed. The complete remission and overall response rates were 47·4% and 78·9%, respectively. With a median follow-up of 24·6 (17·4-38·2) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR- ESHAP regimen is feasible and yields encouraging outcomes. [ABSTRACT FROM AUTHOR]

Background: Neural crest formation is one of the fundamental processes in the early stages of embryonic development in vertebrates. This transient and multipotent embryonic cell population is able to generate a variety of tissues and cell types in the adult body. hairy genes are transcription factors that contain a basic helix-loop-helix domain which binds to DNA. In Xenopus three hairy genes are known: hairy1, hairy2a, and hairy2b. The requirement of hairy genes was explored in early neural crest development although the late requirements of these genes during neural crest maintenance, migration and derivatives formation are still unknown. Results: In this work, we extended the analysis of Xenopus hairy genes expression patterns and described new domains of expression. Functional analysis showed that hairy genes are required for the induction and migration of the neural crest and for the control of apoptosis. Moreover, we showed that hairy genes function as transcriptional repressors and that they are down-regulated by bone morphogenetic protein-Smad signaling and positively regulated by the Notch/Delta-Su(h) pathway. Conclusions: Our results indicate that hairy genes have a functional equivalence between them and that they are required for multiple processes during neural crest development. Developmental Dynamics 244:988-1013, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Although the content of Mg2+ in hard tissues is very low (typically ≤1.5 wt %), its incorporation into synthetic hydroxyapatite (HAp) particles and its role in the mineral's properties are still subject of intensive debate. A combined experimental-computational approach is used to answer many of the open questions. Mg2+-enriched HAp particles are prepared using different synthetic approaches and considering different concentrations of Mg2+ in the reaction medium. The composition, morphology and structure of the resulting particles are investigated using X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, scanning and transmission electron microscopies, FTIR, and wide-angle X-ray diffraction. After this scrutiny, the role of the Mg2+ in the first nucleation stages, before HAp formation, is investigated using atomistic molecular dynamics simulations. Saturated solutions are simulated with and without the presence of DNA, which has been recently used as a soft template in the biomineralization process. This synergistic investigation provides a complete picture of how Mg2+ ions affect the mineralization from the first stages onwards. [ABSTRACT FROM AUTHOR]

New fossil mammals found at the base of Acantilados II Allomember of the La Meseta Formation, from the early Eocene ( Ypresian) of Seymour Island, represent the oldest evidence of this group in Antarctica. Two specimens are here described; the first belongs to a talonid portion of a lower right molar assigned to the sparnotheriodontid litoptern Notiolofos sp. cf. N. arquinotiensis. Sparnotheriodontid were medium- to large-sized ungulates, with a wide distribution in the Eocene of South America and Antarctica. The second specimen is an intermediate phalanx referred to an indeterminate Eutheria, probably a South American native ungulate. These Antarctic findings in sediments of 55.3 Ma query the minimum age needed for terrestrial mammals to spread from South America to Antarctica, which should have occurred before the final break-up of Gondwana. This event involves the disappearance of the land bridge formed by the Weddellian Isthmus, which connected West Antarctica and southern South America from the Late Cretaceous until sometime in the earliest Palaeogene. [ABSTRACT FROM AUTHOR]

Follicular lymphoma ( FL) is one of the most common malignant lymphomas. The t(14;18)(q32;q21) translocation is found in about 80% of cases and plays an important role in lymphomagenesis. However, the molecular mechanisms involved in the development and transformation of this lymphoma are not fully understood. Gain-of-function mutations of NOTCH1 or NOTCH2 have recently been reported in several B cell lymphoid neoplasms but the role of these mutations in FL is not known. In this study we investigated the mutational status of these genes in 112 FLs. NOTCH1 and NOTCH2 mutations were identified in five and two cases, respectively (total 7/112, 6.3%). All mutations predicted for truncated protein in the PEST domain and were identical to those identified in other B cell lymphoid neoplasms. NOTCH-mutated FL cases were characterized by lower frequency of t(14;18) (14% versus 69%, p = 0.01), higher incidence of splenic involvement (71% versus 25%, p = 0.02) and female predominance (100% versus 55%, p = 0.04). A diffuse large B cell lymphoma ( DLBCL) component was more frequently identified in NOTCH-mutated FL than in wild-type cases (57% versus 18%, p = 0.03). These results indicate that NOTCH mutations are uncommon in FL but may occur in a subset of cases with distinctive, characteristic, clinicopathological features. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The manifold applications of ionene-based materials such as hydrogels in daily life, biomedical sciences, and industrial processes are a consequence of their unique physical and chemical properties, which are governed by a judicious balance between multiple non-covalent interactions. However, one of the most critical aspects identified for a broader use of different polyelectrolytes is the need of raising their gelation efficiency. This work focuses on surfactant-free ionene polymers 1− 3 containing DABCO and N, N′-( x-phenylene)dibenzamide ( x = ortho-/ meta-/ para-) linkages as model systems to develop a combined computational-experimental approach to improve the hydrogelation through a better understanding of the gelation mechanism. Molecular dynamics simulations of isomeric ionenes 1-3 with explicit water molecules point out remarkable differences in the assembly of the polymeric chains in each case. Interchain regions with high degree of hydration (i.e., polymer···water interactions) and zones dominated by polymer···polymer interactions are evident in the case of ortho- ( 1) and meta- ( 2) isomeric ionenes, whereas domains controlled by polymer···polymer interactions are practically inexistent in 3. In excellent agreement, ortho-ionene 1 provides experimentally the best hydrogels with unique features such as thixotropic behavior and dispersion ability for single-walles carbon nanotubes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: The neural crest is a transient multipotent migratory cell population unique to vertebrates. These cells undergo an epithelial-to-mesenchymal transition and migrate extensively through the embryo. They differentiate into numerous diverse derivatives including the peripheral nervous system, melanocytes,and craniofacial cartilages. The development of the neural crest is mediated by complex interactions of multiple signals and transcription factors. The kinesin Eg5 is a plus end-directed microtubule-based motor protein that is essential for bipolar spindle formation during mitosis and meiosis, axon growth, and mammal embryonic development. Results: We analyzed in detail the expression pattern of eg5 and established that it is expressed at the prospective neural fold, in the premigratory and migratory neural crest. Functional analysis revealed that in Xenopus, early embryogenesis eg5 function is required during neural crest induction, specification, and maintenance. eg5 is also required during neural crest migration and for derivatives formation. Moreover, we demonstrated a hierarchical relationship with the Indian Hedgehog signaling pathway. Conclusions: Our results show that eg5 is essential for the specification and maintenance of neural crest progenitors during Xenopus early embryogenesis rather than cell proliferation and survival. Developmental Dynamics 243:527-540, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The author discusses the ongoing conservation efforts for the Iberian lynx, which was declared critically endangered by the International Union for the Conservation of Nature (IUCN) in 2002. It mentions the study conducted by Palomares and colleagues in 2011 which criticized conservation efforts for lacking continuity and being applied over a very small area. Information on the European Union's LIFE project for the conservation of Iberian lynx in Andalusia (ILLP) in Spain is presented.

Follicular lymphoma (FL), a typically nodal disease, can arise in extranodal sites in about 10% of cases. The present study aimed to analyse the main differential features of patients with primary extranodal FL. Thirty-nine patients with primary extranodal FL were identified from a series of 354 patients with FL diagnosed at a single institution and their main clinicobiological features were analysed. Twenty patients (5·6%) had a primary extranodal non-cutaneous FL, and 19 (5·4%) a cutaneous FL. BCL2 and CD10 expression and BCL2/ IGHJ@ rearrangement were less frequently observed in cutaneous FL. Absence of 'B'-symptoms, early stage, absence of bone marrow involvement and low-risk Follicular Lymphoma International Prognostic Index (FLIPI) were more frequent in extranodal FL. Five-year overall survival (OS) was 100%, 83% and 78% for cutaneous, non-cutaneous and nodal FL, respectively. When stage I patients were analysed separately, no differences were seen in terms of OS. In multivariate analysis, FLIPI was the most important variable to predict outcome. In conclusion, extranodal FLs, particularly cutaneous, have particular clinico-biological features, which differentiate them from nodal cases. Nevertheless, primary site of the disease is not the main issue to predict outcome. [ABSTRACT FROM AUTHOR]

The article presents a study which determines the effects of exotic species in an island environment. The study introduces goats as an exotic specie and identifies its effects on the native bird Lesser Short-toed Lark inhabiting the island of Fuerteventura, Canary Islands. The study revealed that the prevalence of poxvirus lesions are high in larks from Fuerteventura compared with other bird populations worldwide. The study stresses that the well-being and dynamics of animal populations are determined by nutrition and infectious diseases. It also concludes the importance of health research when conducting design monitoring programs and conservation strategies.

Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 ( n = 26), 2 ( n = 19), 3 ( n = 20) and 4 or 5 ( n = 16), and median CD4 lymphocyte count of 0·158 × 109/l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART. [ABSTRACT FROM AUTHOR]

The article focuses on a study that analyzed the prevalence and the biologic and clinical significance of leukemic involvement in patients with mantle cell lymphoma (MCL). The researchers applied conventional morphology and flow cytometry (FC) to assess leukemic expression. CONCLUSIONS. The results indicate that leukemic expression at diagnosis detected by FC was highly frequent in the MCL patients.

The possible role of minimal residual disease (MRD) in the management of patients with follicular lymphoma (FL) has been a recurrent topic in this field for at least two decades. In this issue of the journal, Pulsoni I et al i ([9]) report a study using MRD, determined in bone marrow (BM) and/or peripheral blood (PB), in patients with early stage FL treated with involved-field radiotherapy (IF-RT). More recently, interest has been raised regarding the application of more modern techniques to detect MRD, including next generation sequencing (NGS), in the search for biomarkers that may help in adapting therapy to the disease risk. [Extracted from the article]