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1.
Microbes Infect ; : 105385, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950642

RESUMO

Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1-Vps34 complexes involved in autophagy and protein sorting. In T. cruzi epimastigotes, (a non-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that T. cruzi Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.

2.
J Pediatr (Rio J) ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38968956

RESUMO

OBJECTIVES: In the clinical routine of pediatricians, height is the most reliable indicator for assessing growth. However, there are situations where it is not possible to measure this parameter directly, making the estimation of height or length a useful alternative. The main goal of this study is to identify which segmental measure, including upper arm length (UAL), tibial length (TL), and knee-heel length (KHL), provides the stature estimate that most closely approximates directly measured height in the study participants. METHODS: Analytical cross-sectional study of the anthropometric and segmental measures of 248 participants, aged 0 to 14 years old, using Stevenson's and Kihara's equations to estimate indirectly measured height. RESULTS: The segmental measure that provided a measurement that deviated the least from the actual height was the KHL, followed by TL, both calculated using Stevenson's equations. CONCLUSION: The use of segmental measures to infer a child's stature is valuable in clinical practice, particularly in bedridden and incapacitated patients. Based on the present findings, the KHL and TL segments yielded more accurate results than the UAL.

3.
Environ Res ; 259: 119557, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969314

RESUMO

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 µg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

4.
Exp Cell Res ; 440(1): 114126, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857838

RESUMO

Microtubules are components of the cytoskeleton that perform essential functions in eukaryotes, such as those related to shape change, motility and cell division. In this context some characteristics of these filaments are essential, such as polarity and dynamic instability. In trypanosomatids, microtubules are integral to ultrastructure organization, intracellular transport and mitotic processes. Some species of trypanosomatids co-evolve with a symbiotic bacterium in a mutualistic association that is marked by extensive metabolic exchanges and a coordinated division of the symbiont with other cellular structures, such as the nucleus and the kinetoplast. It is already established that the bacterium division is microtubule-dependent, so in this work, it was investigated whether the dynamism and remodeling of these filaments is capable of affecting the prokaryote division. To this purpose, Angomonas deanei was treated with Trichostatin A (TSA), a deacetylase inhibitor, and mutant cells for histone deacetylase 6 (HDAC6) were obtained by CRISPR-Cas9. A decrease in proliferation, an enhancement in tubulin acetylation, as well as morphological and ultrastructural changes, were observed in TSA-treated protozoa and mutant cells. In both cases, symbiont filamentation occurred, indicating that prokaryote cell division is dependent on microtubule dynamism.


Assuntos
Divisão Celular , Microtúbulos , Simbiose , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Microtúbulos/efeitos dos fármacos , Trypanosomatina/genética , Trypanosomatina/metabolismo , Trypanosomatina/ultraestrutura , Trypanosomatina/fisiologia , Ácidos Hidroxâmicos/farmacologia , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Bactérias/metabolismo , Bactérias/genética , Acetilação , Inibidores de Histona Desacetilases/farmacologia , Desacetilase 6 de Histona/metabolismo , Desacetilase 6 de Histona/genética , Citoesqueleto/metabolismo , Citoesqueleto/ultraestrutura
5.
Cureus ; 16(5): e60199, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38868244

RESUMO

Non-traumatic bilateral acute subdural hematomas are a rare occurrence. Etiologies typically include, but are not limited to, cortical artery bleeding, vascular lesions, coagulopathies, and spontaneous intracranial hypotension. We report a case of a 45-year-old Korean male with no known co-morbid illnesses nor history of head or neck trauma, who came to the emergency department due to a 10-day history of dizziness and head heaviness, followed by disorientation and drowsiness. The patient was diagnosed with bilateral acute subdural hematoma; hence, a bilateral posterior parietal craniotomy with evacuation of hematoma was performed. Neurologic status initially improved remarkably; however, during rehabilitation, there was recurrence of acute bilateral subdural hematoma requiring repeat surgical evacuation. There was no clinical improvement after the repeat surgery, and his condition further deteriorated in the neurosciences critical care unit showing signs of rostrocaudal deterioration at the level of diencephalon. A plain cranial CT scan was performed, which showed central herniation and "brain sagging." A diagnosis of spontaneous intracranial hypotension was considered; thus, the patient was managed by positioning him in the Trendelenburg position alternating with flat position on the bed. A search for the cerebrospinal fluid leak was commenced by performing a whole spine MRI constructive interference in steady state (CISS) protocol, which showed a longitudinal spinal anterior epidural cerebrospinal fluid leak from spinal level C2 to T1. Radionuclide cisternography did not provide definitive scintigraphic evidence of a leak. The patient gradually improved and was eventually transferred out of the neurosciences critical care unit. After days of rehabilitation in the hospital, the patient was discharged ambulatory with minimal support.

7.
Abdom Radiol (NY) ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860996

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive. METHODS: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3). RESULTS: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct. CONCLUSION: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging. CLINICALTRIALS: gov number, NCT03318380.

8.
Immunol Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834764

RESUMO

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38922468

RESUMO

The growing anthropogenic contamination of natural water by microplastics (MPs) confirms the urgent need to preserve this precious resource. MPs are part of the group of contaminants of emerging concern, and the occurrence studies in surface water and water for human consumption (WHC) are mandatory for environmental and human health risk assessment. This study aims to optimize and validate a Fourier transform infrared spectroscopy method coupled with optical microscopy (micro-FTIR) in transmission mode to monitor MPs in WHC. Water sample (250 mL; without sample pre-treatment) was filtered through 5 µm silicon filters. The infrared spectra identification was performed by OMNIC mathematical correlation, using various spectra libraries for polymers (including the in-house IR spectra library), a background reading on a clean silicon filter, and an aperture of 100 µm × 100 µm. The validated method showed good accuracy, with an average recovery for representative polymers of 91%, a relative standard deviation of 13%, and a reporting limit (RL) of 44 MPs/L. Sixty WHC samples from the Lisbon water supply system showed MPs ranging from 0 (< RL) to 934 MPs/L, with an average value of 309 MPs/L. The most representative polymers were polyethylene (PE, 76.8%), polyethylene terephthalate (PET, 6.9%), polypropylene (PP, 6%), polystyrene (PS, 4%), and polyamide (PA,4%). In terms of size, the microplastic particles had an average length and width of 76 µm and 39 µm, respectively.

11.
Br J Dev Psychol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923552

RESUMO

Do children consider temporal distance in their reasoning about the world? Using a novel method that relied minimally on verbal ability, we asked N = 106 3- to 6-year-olds to judge which of two characters felt more 'happy'/'sad' right now: one engaging in a pleasant/unpleasant activity tomorrow or another engaging in this same activity when they are a year older. That is, we examined whether children understood that the closer in time a future event, the more intense the currently felt emotion. Starting at age 4, children correctly judged which child was more 'happy'/'sad' right now. However, 4- to 6-year-olds tended not to explain their judgements by referring to temporal distance, per se. Results suggest that children are sensitive to temporal distance early in development, but do not yet verbally express this understanding. Implications for theories about children's future thinking and future areas of research are discussed.

12.
Acad Radiol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908918

RESUMO

RATIONALE AND OBJECTIVE: Hepatocellular carcinoma (HCC) locoregional treatment response is commonly evaluated using the Modified Response Evaluation Criteria in Solid Tumors and the American College of Radiology (ACR) Liver Reporting and Data System (LI-RADS) Treatment Response Assessment (TRA) for MRI/CT. This study aims to evaluate the diagnostic performance of the new ACR contrast-enhanced ultrasound (CEUS) Nonradiation TRA LI-RADS v2024 in HCC treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective observational study included 87 patients treated with TACE from a previously reported cohort. At 15- and 30-days post-treatment, 68 and 72 HCC lesions were evaluated. Three blinded radiologists with different levels of CEUS experience interpreted the images independently. According to CEUS Nonradiation TRA LI-RADSv2024, both intralesional and perilesional tumor viability were evaluated and final TRA categories were as follows: TR-Nonviable, TR-Equivocal, and TR-Viable. The reference standard used was a composite of histology and imaging. RESULTS: 140 HCC lesions were analyzed. At 15 days post-treatment, the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy of TR-Viable classification ranged from 72.5-94.3%, 72.2-86.4%, 86.8-91.4%, 65.6-86.7%, 76.9-86.8%, respectively. At 30 days post-treatment, the SN, PPV, and NPV of TR-Viable classification decreased, ranging from 65.9-84.2%, 85.7-90.6%, and 59.5-73.9%, respectively, while the SP increased, ranging from 80.0-88.0%. Kappa values ranged from 0.557-0.730, indicating moderate to substantial agreement. CONCLUSION: CEUS Nonradiation TRA LI-RADS is a reliable tool for the detection of viable tumors in lesions treated with TACE and demonstrates reproducibility across readers.

13.
Antioxidants (Basel) ; 13(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38929187

RESUMO

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer's disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology.

14.
World Neurosurg ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777319

RESUMO

OBJECTIVE: Surgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently used after surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS. METHODS: We identified 32 patients from an institutional database with WHO grade 2 meningioma and residual/recurrent tumor treated with either SRS or fractionated RT. Patients were treated between 2007 and 2021 and had at least 1 year of follow-up. Kaplan-Meier estimators were used to determine gross tumor control (GTC) and intracranial control (IC). Univariate Cox proportional hazards models using biologically effective dose (BED) as a continuous parameter were used to assess for dose responses. RESULTS: With a median follow-up of 5.5 years, 13 patients (41%) received SRS to a recurrent or progressive nodule, 2 (6%) fractionated RT to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated RT following subtotal resection. Five-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, P = 0.03). Five-year IC was also better with fractionated RT versus SRS (82% vs. 11%, P < 0.001). On univariate analysis, increasing BED10 was significantly associated with better GTC (P = 0.039); increasing BED3 was not (P = 0.82). CONCLUSIONS: In this patient cohort, GTC and IC were significantly higher in patients treated with adjuvant fractionated RT compared with salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

16.
J Prosthodont ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715352

RESUMO

PURPOSE: To evaluate the fracture load of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) veneers fabricated with two conventional pre-crystallized and two fully crystallized lithium disilicate ceramic materials. MATERIALS AND METHODS: Seventy-five chairside CAD-CAM veneers (15 specimens/group) for maxillary right central incisors were fabricated with different lithium disilicate brands: (1) IPS e.max CAD; (2) Amber Mill; (3) Cerec Tessera; (4) n!ce Straumann; and (5) GC Initial LiSi Block. Restorations were cemented with resin luting cement (Variolink Esthetic, Ivoclar) to 3D-printed resin dies. Bonded restorations received 5000 thermal cycles and then were loaded until fracture. Statistical analysis included One-Way ANOVA. RESULTS: Conventional pre-crystallized e.max CAD displayed the highest fracture load value (640 N), followed by fully-crystallized n!ce Straumann (547 N), pre-crystallized Cerec Tessera (503 N), pre-crystallized Amber Mill (476 N), respectively; fully-crystallized GC Initial LiSi Block (431 N) displayed the lowest values. When comparing the fracture load of recent lithium disilicate ceramic material to the e.max group, which acted as the control, significant differences were noted. The LiSi Block GC group, in particular, had considerably higher mean difference values (208.867, p < 0.001, 95% CI [89.63, 328.10]), as did the Amber Mill group (164.200, p = 0.002, 95% CI [44.96, 283.44]) and CEREC Tessera group (137.533, p = 0.016, 95% CI [18.30, 256.77]). The e.max and n!ce Straumann groups had no statistically significant differences in mean scores (92.933, p = 0.198, 95% CI [-26.30, 212.17]). These findings imply that the clinical performance of recent lithium disilicate veneers varies when compared to the e.max CAD group. CONCLUSIONS: The fracture load of chairside CAD-CAM lithium disilicate veneers for maxillary central incisors varies according to the type of ceramic brands. Conventional pre-crystallized e.max CAD displayed higher fracture load than the recent pre- and fully-crystallized lithium disilicate materials, emphasizing the significance of choosing the right product based on the desired clinical outcome.

17.
BMC Vet Res ; 20(1): 176, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711127

RESUMO

BACKGROUND: This investigation assessed the effects of high dietary inclusion of Spirulina (Arthrospira platensis) on broiler chicken growth performance, meat quality and nutritional attributes. For this, 120 male broiler chicks were housed in 40 battery brooders (three birds per brooder). Initially, for 14 days, a standard corn and soybean meal diet was administered. Subsequently, from days 14 to 35, chicks were assigned to one of the four dietary treatments (n = 10 per treatment): (1) control diet (CTR); (2) diet with 15% Spirulina (SP); (3) diet with 15% extruded Spirulina (SPE); and (4) diet with 15% Spirulina plus a super-dosing enzymes supplement (0.20% pancreatin extract and 0.01% lysozyme) (SPM). RESULTS: Throughout the experimental period, both SP and SPM diets resulted in decreased final body weight and body weight gain compared to control (p < 0.001), with the SPE diet showing comparable results to CTR. The SPE diet prompted an increase in average daily feed intake (p = 0.026). However, all microalga treatments increased the feed conversion ratio compared to CTR. Dietary inclusion of Spirulina notably increased intestinal content viscosity (p < 0.010), which was mitigated by the SPM diet. Spirulina supplementation led to lower pH levels in breast meat 24 h post-mortem and heightened the b* colour value in both breast and thigh meats (p < 0.010). Furthermore, Spirulina contributed to an increased accumulation of total carotenoids, n-3 polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA), while diminishing n-6 PUFA, thus altering the n-6/n-3 and PUFA/SFA ratios favourably (p < 0.001). However, it also reduced zinc concentration in breast meat (p < 0.001). CONCLUSIONS: The findings indicate that high Spirulina levels in broiler diets impair growth due to increased intestinal viscosity, and that extrusion pre-treatment mitigates this effect. Despite reducing digesta viscosity, a super-dosing enzyme mix did not improve growth. Data also indicates that Spirulina enriches meat with antioxidants and n-3 PUFA but reduces α-tocopherol and increases saturated fats. Reduced zinc content in meat suggests the need for Spirulina biofortification to maintain its nutritional value.


Assuntos
Ração Animal , Galinhas , Dieta , Suplementos Nutricionais , Carne , Spirulina , Animais , Galinhas/crescimento & desenvolvimento , Ração Animal/análise , Spirulina/química , Dieta/veterinária , Masculino , Carne/análise , Carne/normas , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Muramidase/metabolismo
18.
JAMA Oncol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722664

RESUMO

Importance: Options for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe and active for newly diagnosed ALL. Objective: To assess the safety and clinical activity of DA-EPOCH and InO in adults with relapsed or refractory B-ALL. Design, Setting, and Participants: This single-center, single-arm, nonrandomized, phase 1 dose-escalation trial included adults with relapsed or refractory CD22+ B-ALL and was conducted between September 2019 and November 2022. At least 5% blood or marrow blasts or measurable extramedullary disease (EMD) was required for enrollment. Interventions: DA-EPOCH was given on days 1 to 5, while InO was given on day 8 and day 15 of a 28-day cycle. Three dose levels were studied using a bayesian optimal interval design. Main Outcomes and Measures: The primary outcome was the maximum tolerated dose of InO when combined with DA-EPOCH, defined as the highest dose level that produced a rate of dose-limiting toxicity below 33%. Secondary objectives included response rates, survival estimates, and descriptions of toxic effects. Results: A total of 24 participants were screened and enrolled (median age, 46 [range, 28-76] years; 15 [62%] male). The median number of lines of prior therapy was 3 (range, 1-12). Three of 11 participants (27%) treated at the highest dose level (InO, 0.6 mg/m2, on day 8 and day 15) experienced dose-limiting toxicity, making this the maximum tolerated dose. No deaths occurred during the study, and only 1 patient (4%; 95% CI, 0.1%-21%) developed sinusoidal obstructive syndrome after poststudy allograft. The morphologic complete response rate was 84% (95% CI, 60%-97%), 88% (95% CI, 62%-98%) of which was measurable residual disease negative by flow cytometry. Five of 6 participants with EMD experienced treatment response. The overall response rate was 83% (95% CI, 63%-95%). Median overall survival, duration of response, and event-free survival were 17.0 (95% CI, 8.4-not reached), 15.0 (95% CI, 6.7-not reached), and 9.6 (95% CI, 4.5-not reached) months, respectively. Conclusions: In this study, adding InO to DA-EPOCH in adults with relapsed or refractory B-ALL was feasible, with high response rates and sinusoidal obstructive syndrome occurring rarely in a heavily pretreated population. Many patients were able to proceed to poststudy consolidative allogeneic hematopoietic cell transplant and/or chimeric antigen receptor T-cell therapy. Further investigation of this combination is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03991884.

19.
Commun Biol ; 7(1): 612, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773256

RESUMO

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely "everted" telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.


Assuntos
Ciclídeos , Prosencéfalo , Telencéfalo , Animais , Telencéfalo/citologia , Prosencéfalo/citologia , Ciclídeos/genética , Transcriptoma , Vertebrados/genética , Evolução Biológica
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