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The paper industry faces two critical challenges: the scarcity of raw materials and the environmental impact of chemical waste pollution. Addressing the first challenge involves harnessing alternative, sustainable raw materials, while the second challenge can be mitigated through the adoption of bio-bleaching processes, which significantly reduce chemical consumption while enhancing paper brightness and quality. This study proposes a solution to both challenges by using non-woody Calotropis procera (Ankara) and a xylanase-producing microbial consortium for sustainable handmade paper production, a combination not extensively explored in prior research. To evaluate this approach, the process was divided into three stages. In stage I, Ankara fibre was pulped through open hot digestion. In stage II, the pulp was subjected to bio-bleaching in two experimental setups: Set I (without sucrose) and Set II (with sucrose) for 5 days. In stage III, chemical bleaching was used to improve the final brightness of the treated pulps. A novel comparison was made between the bio-bleaching efficiency of an individual isolate g5 (BI) and a bacterial consortium (BC). This research highlighted that bio-bleaching with the consortium effectively removed lignin (140±60 mg/l) and colour (1830±50 PCU), especially in the presence of sucrose, compared to using a single xylanase isolate. Pulp residue/filtrate collected at each stage was estimated based on parameters such as colour and lignin content. After stage III (chemical bleaching), the release of colour and lignin in pulp filtrate was higher in BI compared to BC, indicating the consortium's effectiveness during bio-bleaching, which leaves fewer degradable lignin structures for the chemical bleaching stage. Papers crafted from consortium-treated pulp also exhibited higher brightness than those treated with the isolate. This study reveals the synergistic effect of microbial consortia, leading to more efficient lignin degradation and enhanced bio-bleaching capabilities, supporting the development of greener industrial processes. Ultimately, this study demonstrates a unique and eco-friendly approach to papermaking, combining C. procera and enzymatic bio-bleaching to reduce dependency on hazardous chemicals and support sustainable industry practices.
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Due to the excessive growth of PM 2.5 in aerosol, the cases of lung cancer are increasing rapidly and are most severe among other types as the highest mortality rate. In most of the cases, lung cancer is detected with least symptoms at its later stage. Hence, clinical records may play a vital role to diagnose this disease at the correct stage for suitable medication to cure it. To detect lung cancer an accurate prediction method is needed which is significantly reliable. In the digital clinical record era with advancement in computing algorithms including machine learning techniques opens an opportunity to ease the process. Various machine learning algorithms may be applied over realistic clinical data but the predictive power is yet to be comprehended for accurate results. This paper envisages to compare twelve potential machine learning algorithms over clinical data with eleven symptoms of lung cancer along with two major habits of patients to predict a positive case accurately. The result has been found based on classification and heat map correlation. K-Nearest Neighbor Model and Bernoulli Naive Bayes Model are found most significant methods for early lung cancer prediction.
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Algoritmos , Neoplasias Pulmonares , Aprendizaje Automático , Humanos , Neoplasias Pulmonares/diagnóstico , Teorema de Bayes , Masculino , FemeninoRESUMEN
Hallux amputations have long been performed for the definitive treatment of hallux osteomyelitis resulting from ulcerations. These amputations have been performed at various levels of the hallux. The aim of this study is to assess the long-term outcomes in patients with hallux amputations performed at these various levels and to determine whether there is an ideal anatomic level that would limit post-operative complications and need for revisional surgery. An Institutional Review Board (IRB)-approved retrospective chart review of 148 feet with hallux amputations performed at various levels from July 1, 2013 to July 16, 2020 at an academic medical center was conducted. A 2-year minimum follow up was required for inclusion in the study. Incidence of re-ulceration, need for further amputation, healing of index procedure, and revascularization status were evaluated. Statistical analysis utilizing chi square analysis was performed to calculate p-values where <.05 was statistically significant. In this retrospective study with a minimum of 2-year follow-up, there was a tendency for amputations performed at the level of the head of the proximal phalanx (21%) to have a lower rate of reulceration (24%) followed by amputations performed at the level of the metatarsophalangeal joint and interphalangeal joints (36%). However, neither proved to be statistically significant.
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Understanding the spatial distribution of plant available soil nutrients and influencing soil properties and delineation soil nutrient management zones (MZs) are important for implementing precision nutrient management options (PNMO) in an area to achieve maintainable crop production. We assessed spatial distribution pattern of plant available sulphur (S) (PAS), boron (B) (PAB), zinc (PAZn), manganese (PAMn), iron (PAFe), and copper (PACu), and soil organic carbon (SOC), pH, and electrical conductivity (EC) to delineate soil nutrients MZs in northeastern region of India. A total of 17,471 representative surface (0-15 cm depth) soil samples were collected from the region, processed, and analysed for above-mentioned soil parameters. The values of PAS (0.22-99.2 mg kg-1), PAB (0.01-6.45 mg kg-1), PAZn (0.05-13.9 mg kg-1), PAMn (0.08-158 mg kg-1), PAFe (0.50-472 mg kg-1), PACu (0.01-19.2 mg kg-1), SOC (0.01-5.80%), pH (3.19-7.56) and EC (0.01-1.66 dS m-1) varied widely with coefficient of variation of 15.5-108%. The semivariogram analysis highlighted exponential, Gaussian and stable best fitted models for soil parameters with weak (PACu), moderate (PAB, PAZn, PAFe, SOC, pH, and EC) and strong (PAS, and PAMn) spatial dependence. The ordinary kriging interpolation revealed different distribution patterns of soil parameters. About 14.8, 27.5, and 3.40% area of the region had PAS of ≤15.0 mg kg-1, PAB of ≤0.50 mg kg-1, and PAZn of had ≤0.90 mg kg-1, respectively. About 67.5, and 32.5% area had SOC content >1.00 and < 1.00%, respectively. Soil pH was ≤5.50, and >5.50 to ≤6.50 in 41.7 and 40.3% area of the region, respectively. The techniques of principal component analysis and fuzzy c-mean algorithm clustering produced 6 MZs of the region with different areas and values of soil parameters. The MZs had different levels of deficiency pertaining to PAS, PAB, and PAZn. The produced MZ maps could be used for managing PAS, PAB, PAZn, SOC and soil pH in order to implement PNMO. The study highlighted the usefulness of MZ delineation technique for implementation of PNMO in different cultivated areas for sustainable crop production.
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Suelo , Suelo/química , India , Zinc/análisis , Nutrientes/análisis , Hierro/análisis , Boro/análisis , Análisis de Componente Principal , Análisis por Conglomerados , Lógica Difusa , Manganeso/análisisRESUMEN
BACKGROUND: Widespread misinformation in web resources can lead to serious implications for individuals seeking health advice. Despite that, information retrieval models are often focused only on the query-document relevance dimension to rank results. OBJECTIVE: We investigate a multidimensional information quality retrieval model based on deep learning to enhance the effectiveness of online health care information search results. METHODS: In this study, we simulated online health information search scenarios with a topic set of 32 different health-related inquiries and a corpus containing 1 billion web documents from the April 2019 snapshot of Common Crawl. Using state-of-the-art pretrained language models, we assessed the quality of the retrieved documents according to their usefulness, supportiveness, and credibility dimensions for a given search query on 6030 human-annotated, query-document pairs. We evaluated this approach using transfer learning and more specific domain adaptation techniques. RESULTS: In the transfer learning setting, the usefulness model provided the largest distinction between help- and harm-compatible documents, with a difference of +5.6%, leading to a majority of helpful documents in the top 10 retrieved. The supportiveness model achieved the best harm compatibility (+2.4%), while the combination of usefulness, supportiveness, and credibility models achieved the largest distinction between help- and harm-compatibility on helpful topics (+16.9%). In the domain adaptation setting, the linear combination of different models showed robust performance, with help-harm compatibility above +4.4% for all dimensions and going as high as +6.8%. CONCLUSIONS: These results suggest that integrating automatic ranking models created for specific information quality dimensions can increase the effectiveness of health-related information retrieval. Thus, our approach could be used to enhance searches made by individuals seeking online health information.
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AIM: This article investigates the oral health preferences of parents residing in rural areas for their children, including dental maintenance and treatment. MATERIALS AND METHODS: Data were collected through a cross-sectional survey of 500 parents who sought dental consultation for their children between two and seven years old, excluding those with systemic or neurological disorders. Demographic characteristics, including child and parent age and gender, family structure, and parental education levels, were collected using self-administered questionnaires. RESULTS: The study on oral health preferences of rural parents reveals the following key trends: peak dental treatment interest at six years old (104 children), slight gender disparity favoring males (54.8%), prevalent joint family structures (58%), and families with two children (48%). Most mothers marry before age 21 (62.8%), with varied education levels. Toothpaste and toothbrushes are preferred by the majority (65.2%) for oral hygiene. Common treatments include oral prophylaxis (164), pulpectomy/pulpotomy (114), and extractions (86). However, significant gaps exist: 62.8% do not grasp the importance of primary teeth, and 72% lack knowledge about specific treatments and drug-induced tooth problems, urging targeted educational strategies. CONCLUSION: The study's outcome focuses on parental preferences for oral hygiene maintenance and their choices for dental treatment in primary dentition. The results highlight the influence of various factors on parental preferences and underscore the importance of improving parental knowledge for better oral health outcomes in rural populations.
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The developed asymmetric monovalent bispecific IgG1 or Duet monoclonal antibody (Duet mAb) has two distinct fragment antigen-binding region (Fab) subunits that target two different epitope specificities sequentially or simultaneously. The design features include unique engineered disulfide bridges, knob-into-hole mutations, and kappa and lambda chains to produce Duet mAbs. These make it structurally and functionally complex, so one expects challenging developability linked to instability, degradation of products and pathways, and limited reports available. Here, we have treated the product with different sources of extreme stress over a lengthy period, including varying heat, pH, photo stress, chemical oxidative stress, accelerated stress in physiological conditions, and forced glycation conditions. The effects of different stress conditions on the product were assessed using various analytical characterization tools to measure product-related substances, post-translational modifications (PTMs), structural integrity, higher-order disulfide linkages, and biological activity. The results revealed degradation products and pathways of Duet mAb. A moderate increase in size, charge, and hydrophobic variants, PTMs, including deamidation, oxidation, isomerization, and glycation were observed, with most conditions exhibiting biological activity. In addition, the characterization of fractionated charge variants, including deamidated species, showed satisfactory biological activity. This study demonstrated the prominent stability of the Duet mAb format comparable to most marketed mAbs.
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T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in CML. It is difficult to differentiate between de novo Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML. We present a case of adult Ph+ T-ALL/LBL with a likely history of antecedent CML. Initially thought to be a case of chronic-phase CML, a diagnostic quandary led to the pursuit of a lymph node biopsy that established the diagnosis of Ph+ T-LBL or T lymphoblastic blast crisis of CML, a clinical presentation extremely rare and only the second of its kind from our review of the literature. The patient was treated with an intensive chemotherapy regimen for over a year due to persistent minimal residual disease (MRD) positivity indicating aggressive disease.
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Background: Cardiac implantable electronic devices (CIEDs), such as permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, alleviate morbidity and mortality in various diseases. There is a paucity of real-world data on CIED complications and trends. Objectives: We sought to describe trends in noninfectious CIED complications over the past 3 decades in Olmsted County. Methods: The Rochester Epidemiology Project is a medical records linkage system comprising records of over 500,000 residents of Olmsted County from 1966 to present. CIED implantations between 1988 and 2018 were determined. Trends in noninfectious complications within 30 days of implantation were analyzed. Results: A total of 157 (6.2%) of 2536 patients who received CIED experienced device complications. A total of 2.7% of the implants had major complications requiring intervention. Lead dislodgement was the most common (2.8%), followed by hematoma (1.7%). Complications went up from 1988 to 2005, and then showed a downtrend until 2018, driven by a decline in hematomas in the last decade (P < .01). Those with complications were more likely to have prosthetic valves. Obesity appeared to have a protective effect in a multivariate regression model. The mean Charlson comorbidity index has trended up over the 30 years. Conclusion: Our study describes a real-world trend of CIED complications over 3 decades. Lead dislodgements and hematomas were the most common complications. Complications have declined over the last decade due to safer practices and a better understanding of anticoagulant management.
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BACKGROUND: Temporomandibular disorder (TMD) encompasses a range of conditions affecting the temporomandibular joint (TMJ) and associated structures, with TMJ pain being a prevalent symptom. Conventional management strategies have limitations, which require the exploration of innovative interventions. Platelet-rich plasma (PRP), known for its regenerative properties, presents a potential therapeutic avenue. This study aims to investigate the effectiveness of PRP in reducing the pain associated with mild TMJ in young adults. METHODOLOGY: Participants (n = 128) aged 18 to 35 years with mild TMD were evenly randomized into PRP treatment and placebo control groups. PRP was prepared using a standardized protocol, and intra-articular injections were administered. Placebo injections mimic PRP. Follow-up evaluations were carried out at four and eight weeks after the intervention. RESULTS: The study successfully randomized comparable groups, and the PRP treatment group experienced a significant reduction in TMJ pain (visual analog scale [VAS] score: 6.8 ± 1.2 to 2.1 ± 1.0 at eight weeks, P < 0.001). The PRP treatment also increased the largest opening of the mouth (from 38.2 ± 2.5 to 43.5 ± 3.1, P < 0.001) and the number of lateral movements (12.3 ± 1.5 to 14.9 ± 2.0, P < 0.001), while the placebo group had very few changes. Positive patient-reported outcomes on daily activities were observed, with no serious complications reported in either group. CONCLUSIONS: This study provides evidence supporting the efficacy of PRP in reducing TMJ pain, improving jaw function, and improving quality of life in young adults with mild TMD. The results underscore the potential of PRP as a minimally invasive intervention for TMJ disorders.
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Context: The link between oral infections and systemic disease is a well-proven hypothesis in the current literature. This relationship is the result of interaction between periodontal microbe that triggers inflammatory processes leading to the secretion of cytokines and other mediators of inflammation resulting in the systemic effects of pathogenesis. Materials and Methods: In this study, erythrocyte sedimentation rate (ESR), probing pocket depth, plaque index, gingival index, and the parameters were assessed initially and 1 month after scaling and root planing (SRP). Statistical Analysis Used: The paired t-test and the Pearson correlation were needed to examine and compare measured data. Results: The data from the study reveal that all the clinical parameters like the plaque index, the gingival index, and the probing pocket depth were statistically significantly reduced after 1 month of SRP with respect to baseline. While ESR mean value was also reduced, that is, 3.27 ± 1.24 mm/hr which was also considered statistically significant. Conclusions: The findings from the study showed a positive correlation between periodontal inflammation and ESR.
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SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, it enters the host cell by activating the ACE2 receptor with the help of two proteasesi.e., Furin and TMPRSS2. Therefore, variations in these genes may account for differential susceptibility and severity between populations. Previous studies have shown that the role of ACE2 and TMPRSS2 gene variants in understanding COVID-19 susceptibility among Indian populations. Nevertheless, a knowledge gap exists concerning the COVID-19 susceptibility of Furin gene variants among diverse South Asian ethnic groups. Investigating the role of Furin gene variants and their global phylogeographic structure is essential to comprehensively understanding COVID-19 susceptibility in these populations. We have used 450 samples from diverse Indian states and performed linear regression to analyse the Furin gene variant's with COVID-19 Case Fatality Rate (CFR) that could be epidemiologically associated with disease severity outcomes. Associated genetic variants were further evaluated for their expression and regulatory potential through various Insilco analyses. Additionally, we examined the Furin gene using next-generation sequencing (NGS) data from 393 diverse global samples, with a particular emphasis on South Asia, to investigate its Phylogeographic structure among diverse world populations. We found a significant positive association for the SNP rs1981458 with COVID-19 CFR (p < 0.05) among diverse Indian populations at different timelines of the first and second waves. Further, QTL and other regulatory analyses showed various significant associations for positive regulatory roles of rs1981458 and Furin gene, mainly in Immune cells and virus infection process, highlighting their role in host immunity and viral assembly and processing. The Furin protein-protein interaction suggested that COVID-19 may contribute to Pulmonary arterial hypertension via a typical inflammation mechanism. The phylogeographic architecture of the Furin gene demonstrated a closer genetic affinity of South Asia with West Eurasian populations. Therefore, it is worth proposing that for the Furin gene, the COVID-19 susceptibility of South Asians will be more similar to the West Eurasian population. Our previous studies on the ACE2 and TMPRSS2 genes showed genetic affinity of South Asian with East Eurasians and West Eurasians, respectively. Therefore, with the collective information from these three important genes (ACE2, TMPRSS2 and Furin) we modelled COVID-19 susceptibilityof South Asia in between these two major ancestries with an inclination towards West Eurasia. In conclusion, this study, for the first time, concluded the role of rs1981458 in COVID-19 severity among the Indian population and outlined its regulatory potential.This study also highlights that the genetic structure for COVID-19 susceptibilityof South Asia is distinct, however, inclined to the West Eurasian population. We believe this insight may be utilised as a genetic biomarker to identify vulnerable populations, which might be directly relevant for developing policies and allocating resources more effectively during an epidemic.
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COVID-19 , Humanos , Enzima Convertidora de Angiotensina 2/genética , COVID-19/epidemiología , COVID-19/genética , Furina/genética , Pandemias , Polimorfismo GenéticoRESUMEN
Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants. Here, we report a highly sensitive reverse-phase polyphenyl ultra-high-performance liquid chromatography (RP-UHPLC) method to accurately measure mispaired species of Duet mAb format, an asymmetric IgG1 bispecific mAb, for both process development and quality control analytical tests. Coupled with electrospray ionization mass spectrometry (ESI-MS), it enabled direct online characterization of mispaired species. This single direct assay detected diverse mispaired IgG-like species and LMWS. The method resolved eight disulfide bonds dissociated LMWS and three mispaired LMWS. It also resolved three different types of IgG-like mispaired species, including two homodimers and one heterodimer. The characterization and quantification simultaneously enabled the cell line selection that produces a lesser heterogeneity and lower levels of mispaired species with the desired correctly paired product. The biological activity assessment of samples with increased levels of these species quantified by the method exhibited a linear decline in potency with increasing levels of mispaired species in the desired product. We also demonstrated the utility of the technique for testing in-process intermediate materials to determine and assess downstream purification process capability in removing diverse mispaired IgG-like species and LMWS to a certain level during the downstream purification process. Our investigation demonstrates that adopting this method was vital in developing asymmetric bispecific mAb from the initial stage of cell line development to manufacturing process development. Therefore, this tool could be used in the control strategy to monitor and control mispaired species during manufacturing, thus improving the quality control of the final product.
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Anticuerpos Biespecíficos , Espectrometría de Masa por Ionización de Electrospray , Inmunoglobulina G/química , Cromatografía de Fase Inversa , Dominios Proteicos , Anticuerpos Biespecíficos/química , Anticuerpos Monoclonales/químicaRESUMEN
The remarkable spin-charge interconversion ability of transition metal dichalcogenides (TMDs) makes them promising candidates for spintronic applications. Nevertheless, their potential as spintronic terahertz (THz) emitters (STEs) remains constrained mainly due to their sizable resistivity and low spin Hall conductivity (SHC), which consequently result in modest THz emission. In this work, the TMD PtTe2, a type-II Dirac semimetal is effectively utilized to develop efficient STEs. This high efficiency primarily results from the large SHC of PtTe2, stemming from its low resistivity and significant spin-to-charge conversion efficiency, attributed to surface states and the local Rashba effect in addition to the inverse spin Hall effect. Remarkably, the peak THz emission from PtTe2/Co-STE exceeds that of Pt/Co-STE by â¼15% and is nearly double that of a similarly thick Pt/Co-STE. The efficient THz emission in the PtTe2/Co heterostructure opens new possibilities for utilizing the semimetal TMDs for developing THz emitters.
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The outbreak of COVID-19 has shocked the entire world with its fairly rapid spread, and has challenged different sectors. One of the most effective ways to limit its spread is the early and accurate diagnosing of infected patients. Medical imaging, such as X-ray and computed tomography (CT), combined with the potential of artificial intelligence (AI), plays an essential role in supporting medical personnel in the diagnosis process. Thus, in this article, five different deep learning models (ResNet18, ResNet34, InceptionV3, InceptionResNetV2, and DenseNet161) and their ensemble, using majority voting, have been used to classify COVID-19, pneumoniæ and healthy subjects using chest X-ray images. Multilabel classification was performed to predict multiple pathologies for each patient, if present. Firstly, the interpretability of each of the networks was thoroughly studied using local interpretability methods-occlusion, saliency, input X gradient, guided backpropagation, integrated gradients, and DeepLIFT-and using a global technique-neuron activation profiles. The mean micro F1 score of the models for COVID-19 classifications ranged from 0.66 to 0.875, and was 0.89 for the ensemble of the network models. The qualitative results showed that the ResNets were the most interpretable models. This research demonstrates the importance of using interpretability methods to compare different models before making a decision regarding the best performing model.
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A group of fluorinated organic molecules known as per- and poly-fluoroalkyl substances (PFAS) have been commonly produced and circulated in the environment. PFAS, owing to multiple strong CF bonds, exhibit exceptional stability and possess a high level of resistance against biological or chemical degradation. Recently, PFAS have been identified to cause numerous hazardous effects on the biotic ecosystem. As a result, extensive efforts have been made in recent years to develop effective methods to remove PFAS. Adsorption, filtration, heat treatment, chemical oxidation/reduction, and soil washing are a few of the physicochemical techniques that have shown their ability to remove PFAS from contaminated matrixes. However these methods also carry significant drawbacks, including the fact that they are expensive, energy-intensive, unsuitable for in-situ treatment, and requirement to be carried under dormant conditions. The metabolic products released upon PFAS degradation are largely unknown, despite the fact that thermal disintegration methods are widely used. In contrast to physical and chemical methods, biological degradation of PFAS has been regarded as efficient method. However, PFAS are difficult to instantly and completely metabolize through biological methods due to the limitations of biocatalytic mechanisms. Nevertheless, cost, easy-to-operate and environmentally safe are some of the advantages over its counterpart. The present review comprehensively discusses the occurrence of PFAS, the state-of-the science of remediation technologies and approaches applied, and the remediation challenges. The article also focuses on the future research directions toward the development of effective methods for PFAS-contaminated site in-situ treatment.
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Fluorocarburos , Contaminantes Químicos del Agua , Ecosistema , Adsorción , Biocatálisis , FiltraciónRESUMEN
BACKGROUND: Diarrhea and rectal urgency are risk factors for fecal incontinence (FI). The effectiveness of bowel modifiers for improving FI is unclear. METHODS: In this double-blind, parallel-group, randomized trial, women with urge FI were randomly assigned in a 1:1 ratio to a combination of oral clonidine (0.1 mg twice daily) with colesevelam (1875 mg twice daily) or two inert tablets for 4 weeks. The primary outcome was a ≥50% decrease in number of weekly FI episodes. KEY RESULTS: Fifty-six participants were randomly assigned to clonidine-colesevelam (n = 24) or placebo (n = 32); 51 (91%) completed 4 weeks of treatment. At baseline, participants had a mean (SD) of 7.5 (8.2) FI episodes weekly. The primary outcome was met for 13 of 24 participants (54%) treated with clonidine-colesevelam versus 17 of 32 (53%) treated with placebo (p = 0.85). The Bristol stool form score decreased significantly, reflecting more formed stools with clonidine-colesevelam treatment (mean [SD], 4.5 [1.5] to 3.2 [1.5]; p = 0.02) but not with placebo (4.2 [1.9] to 4.1 [1.9]; p = 0.47). The proportion of FI episodes for semiformed stools decreased significantly from a mean (SD) of 76% (8%) to 61% (10%) in the clonidine-colesevelam group (p = 0.007) but not the placebo group (61% [8%] to 67% [8%]; p = 0.76). However, these treatment effects did not differ significantly between groups. Overall, clonidine-colesevelam was well tolerated. CONCLUSIONS AND INFERENCES: Compared with placebo, clonidine-colesevelam did not significantly improve FI despite being associated with more formed stools and fewer FI episodes for semiformed stools.
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Clonidina , Incontinencia Fecal , Humanos , Femenino , Clonidina/uso terapéutico , Incontinencia Fecal/tratamiento farmacológico , Incontinencia Fecal/complicaciones , Clorhidrato de Colesevelam/uso terapéutico , Diarrea/etiología , Intestinos , Método Doble CiegoRESUMEN
Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéuticoRESUMEN
Concept extraction from prescriptions is a very important task that provides a foundation for many of the downstream healthcare applications in decision making across the areas of pharmacovigilance, medication adherence, inventory management, and other matters of value-based care. Although short, these directions can sometimes be complex. With the increase in complexity of direction, it becomes harder to extract various concepts by only rule based expert system. It identifies major concepts like frequency, dosage, duration, etc. from the natural text direction using a combination of rules and deep learning (DL) based methods on a large real world data of a pharmacy chain. The DL module includes a fine-tuned BERT transformer and Gram CNN (Convolutional Neural Network) based NER (Named Entity Recognition) architecture. The proposed method utilizes the domain heuristics along with intelligent labelling and bootstrapping to help DL models extract concepts with high evaluation scores and thus provides a way for carrying out concept extraction using targeted methods instead of one single method. To the best of our knowledge, this is the best performance reported in the literature for concept extraction from doctor's prescription.