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Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However, there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) and the greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences, particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.
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Quirópteros , Células-Tronco Pluripotentes , Viroses , Vírus , Animais , Vírus/genética , Transcriptoma , FilogeniaRESUMO
Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Changes in glycocalyx thickness of approximately 10 nm can alter the susceptibility to immune cell attack. Enhanced stimulation of natural killer and T cells through equipment with chimeric antigen receptors can improve the cytotoxicity against mucin-bearing target cells. Alternatively, cytotoxicity can be enhanced through engineering effector cells to display glycocalyx-editing enzymes, including mucinases and sialidases. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells.
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Antineoplásicos , Neoplasias , Humanos , Glicocálix/metabolismo , Mucinas/metabolismo , Antineoplásicos/metabolismo , Neoplasias/terapiaRESUMO
Currently, the construction of anti-ambipolar transistors (AATs) is primarily based on asymmetric heterostructures, which are challenging to fabricate. AATs used for photodetection are accompanied by dark currents that prove difficult to suppress, resulting in reduced sensitivity. This work presents light-triggered AATs based on an in-plane lateral WSe2 homojunction without van der Waals heterostructures. In this device, the WSe2 channel is partially electrically controlled by the back gate due to the screening effect of the bottom electrode, resulting in a homojunction that is dynamically modulated with gate voltage, exhibiting electrostatically reconfigurable and light-triggered anti-ambipolar behaviors. It exhibits high responsivity (188 A/W) and detectivity (8.94 × 1014 Jones) under 635 nm illumination with a low power density of 0.23 µW/cm2, promising a new approach to low-power, high-performance photodetectors. Moreover, the device demonstrates efficient self-driven photodetection. Furthermore, ternary inverters are realized using monolithic WSe2, simplifying the manufacturing of multivalued logic devices.
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BACKGROUND: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy. METHODS: We searched the University of California, Los Angeles (UCLA) sarcoma program database for patients with a diagnosis of sarcoma and LS from 2016 to 2023. Three such patients were identified and all three were treated with PD1 blockade. RESULTS: We present three cases of LS-associated sarcomas (two soft tissue sarcoma and one osteosarcoma) with increased tumor mutational burdens. These patients were each treated with an anti-PD1 antibody and experienced a response far superior to that reported for non-LS-associated sarcomas. CONCLUSIONS: Increased mutational burden and immune infiltrate are observed for sarcomas associated with LS. Although unselected patients with sarcoma have demonstrated poor response rates to immunotherapy, our findings suggest that patients with Lynch-associated sarcomas are more likely to respond to treatment with anti-PD1. These patients should be given consideration for immunotherapy.
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Neoplasias Colorretais Hereditárias sem Polipose , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patologia , Biomarcadores Tumorais/genética , Imunoterapia , Reparo de Erro de Pareamento de DNARESUMO
In recent years, extensive research endeavors are being undertaken for synthesis of an efficient, economic and eco-friendly cerium oxide nanoparticles (CeO2 NPs) using plant extract mediated greener approach. A number of medicinal plants and their specific parts (flowers, bark, seeds, fruits, seeds and leaves) have been found to be capable of synthesizing CeO2 NPs. The specific key phytochemical constituents of plants such as alkaloids, terpenoids, phenolic acids, flavones and tannins can play significant role as a reducing, stabilizing and capping agents in the synthesis of CeO2 NPs from their respective precursor solution of metal ions. The CeO2 NPs are frequently using in diverse fields of science and technology including photocatalytic degradation of dyes, antibiotics as well as antimicrobial applications. In this review, the mechanism behind the green synthesis CeO2 NPs using plant entities are summarized along with discussion of analytical results from characterization techniques. An overview of CeO2 NPs for water remediation application via photocatalytic degradation of dyes and antibiotics are discussed. In addition, the mechanisms of antimicrobial efficacy of CeO2 NPs and current challenges for their sustainable application at large scale in real environmental conditions are discussed.
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Anti-Infecciosos , Cério , Nanopartículas Metálicas , Nanopartículas , Antibacterianos/química , Corantes , Nanopartículas/química , Cério/química , Plantas , Nanopartículas Metálicas/químicaRESUMO
The field of image processing is experiencing significant advancements to support professionals in analyzing histological images obtained from biopsies. The primary objective is to enhance the process of diagnosis and prognostic evaluations. Various forms of cancer can be diagnosed by employing different segmentation techniques followed by postprocessing approaches that can identify distinct neoplastic areas. Using computer approaches facilitates a more objective and efficient study of experts. The progressive advancement of histological image analysis holds significant importance in modern medicine. This paper provides an overview of the current advances in segmentation and classification approaches for images of follicular lymphoma. This research analyzes the primary image processing techniques utilized in the various stages of preprocessing, segmentation of the region of interest, classification, and postprocessing as described in the existing literature. The study also examines the strengths and weaknesses associated with these approaches. Additionally, this study encompasses an examination of validation procedures and an exploration of prospective future research roads in the segmentation of neoplasias.
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Diagnóstico por Computador , Processamento de Imagem Assistida por Computador , Linfoma Folicular , Linfoma Folicular/diagnóstico , Linfoma Folicular/patologia , HumanosRESUMO
This study delves into the critical role of microbial ecosystems in landfills, which are pivotal for handling municipal solid waste (MSW). Within these landfills, a complex interplay of several microorganisms (aerobic/anaerobic bacteria, archaea or methanotrophs), drives the conversion of complex substrates into simplified compounds and complete mineralization into the water, inorganic salts, and gases, including biofuel methane gas. These landfills have dominant biotic and abiotic environments where various bacterial, archaeal, and fungal groups evolve and interact to decompose substrate by enabling hydrolytic, fermentative, and methanogenic processes. Each landfill consists of diverse bio-geochemical environments with complex microbial populations, ranging from deeply underground anaerobic methanogenic systems to near-surface aerobic systems. These kinds of landfill generate leachates which in turn emerged as a significant risk to the surrounding because generated leachates are rich in toxic organic/inorganic components, heavy metals, minerals, ammonia and xenobiotics. In addition to this, microbial communities in a landfill ecosystem could not be accurately identified using lab microbial-culturing methods alone because most of the landfill's microorganisms cannot grow on a culture medium. Due to these reasons, research on landfills microbiome has flourished which has been characterized by a change from a culture-dependent approach to a more sophisticated use of molecular techniques like Sanger Sequencing and Next-Generation Sequencing (NGS). These sequencing techniques have completely revolutionized the identification and analysis of these diverse microbial communities. This review underscores the significance of microbial functions in waste decomposition, gas management, and heat control in landfills. It further explores how modern sequencing technologies have transformed our approach to studying these complex ecosystems, offering deeper insights into their taxonomic composition and functionality.
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Bacteriologia , Eliminação de Resíduos , Temperatura Alta , Ecossistema , Resíduos Sólidos/análise , Instalações de Eliminação de Resíduos , Gases/análiseRESUMO
BACKGROUND: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) after surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined because the natural history of RP-LPS after treatment is poorly understood. This study evaluated the long-term risk of recurrence and disease-specific survival (DSS) for a cohort of patients with at least 10 years of progression-free survival (10yr-PFS) from their primary resection. METHODS: The prospective University of California, Los Angeles (UCLA) Sarcoma Database identified RP-LPS patients with 10yr-PFS after initial resection. The patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. The time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. RESULTS: From 1972 to 2010, 76 patients with RP-LPS had at least 10 years of follow-up evaluation. Of these 76 patients, 39 (51%) demonstrated 10yr-PFS. The median follow-up period was 15 years (range 10-33 years). Among the 10yr-PFS patients, 49% (19/39) experienced a recurrence at least 10 years after surgery. Of those who experienced recurrence, 42% (8/19) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or perioperative treatment with radiation or chemotherapy. CONCLUSION: Patients who have primary RP-LPS treated with surgical resection ± multimodality therapy face a long-term risk of recurrence and disease-specific death unacknowledged by current surveillance imaging guidelines. Among the patients with 10yr-PFS, 49% experienced a recurrence, and 42% of those died of disease. These findings suggest a need for lifelong surveillance imaging for patients with RP-LPS.
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Lipossarcoma , Neoplasias Retroperitoneais , Humanos , Estudos Prospectivos , Lipopolissacarídeos , Estudos Retrospectivos , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Cognitive dysfunction is a major feature of Parkinson's disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that mid-frontal delta/theta rhythms predict cognitive dysfunction in PD. METHOD: We recruited 100 patients with PD and 49 demographically similar control participants who completed a series of cognitive control tasks, including the Simon, oddball and interval-timing tasks. We focused on cue-evoked delta (1-4 Hz) and theta (4-7 Hz) rhythms from a single mid-frontal EEG electrode (cranial vertex (Cz)) in patients with PD who were either cognitively normal, with mild-cognitive impairments (Parkinson's disease with mild-cognitive impairment) or had dementia (Parkinson's disease dementia). RESULTS: We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased mid-frontal delta power across all tasks. Within patients with PD, the first principal component of evoked electroencephalography features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment score (r=0.34) and with National Institutes of Health Toolbox Executive Function score (r=0.46). CONCLUSIONS: These data demonstrate that cue-evoked mid-frontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.
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Disfunção Cognitiva , Demência , Doença de Parkinson , Humanos , Demência/complicações , Disfunção Cognitiva/complicações , Eletroencefalografia/métodos , Ritmo Teta/fisiologiaRESUMO
Novelty detection is a primitive subcomponent of cognitive control that can be deficient in Parkinson's disease (PD) patients. Here, we studied the corticostriatal mechanisms underlying novelty-response deficits. In participants with PD, we recorded from cortical circuits with scalp-based electroencephalography (EEG) and from subcortical circuits using intraoperative neurophysiology during surgeries for implantation of deep brain stimulation (DBS) electrodes. We report three major results. First, novel auditory stimuli triggered midfrontal low-frequency rhythms; of these, 1-4 Hz "delta" rhythms were linked to novelty-associated slowing, whereas 4-7 Hz "theta" rhythms were specifically attenuated in PD. Second, 32% of subthalamic nucleus (STN) neurons were response-modulated; nearly all (94%) of these were also modulated by novel stimuli. Third, response-modulated STN neurons were coherent with midfrontal 1-4 Hz activity. These findings link scalp-based measurements of neural activity with neuronal activity in the STN. Our results provide insight into midfrontal cognitive control mechanisms and how purported hyperdirect frontobasal ganglia circuits evaluate new information.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Núcleo Subtalâmico/fisiologia , Doença de Parkinson/terapia , Estimulação Encefálica Profunda/métodos , Eletroencefalografia , Neurônios/fisiologiaRESUMO
To compare whether alternate rotation of nasal mask with nasal prongs every 8 h as compared to continuous use of either interface alone decreases the incidence of nasal injury in preterm infants receiving nasal Continuous Positive Airway Pressure (nCPAP). This was an open-label, three-arm, stratified randomized controlled trial where infants < 35 weeks receiving nCPAP were randomized into three groups using two different nasal interfaces (continuous prongs group, continuous mask group, and rotation group). All infants were assessed for nasal injury six hours post-removal of nCPAP using grading suggested by Fischer et al. The nursing care was uniform across all three groups. Intention-to-treat analysis was done. Fifty-seven infants were enrolled, with nineteen in each group. The incidence of nasal injury was 42.1% vs. 47.4% vs. 68.4% in the rotation group, continuous mask, and continuous prongs groups, respectively (P = 0.228). On adjusted analysis (gestational age, birth weight, and duration of nCPAP therapy), the incidence of nasal injury was significantly less in the rotation group as compared to continuous prongs group (Adjusted Odds Ratio [AOR], 95% confidence interval [CI]; 0.10 [0.01-0.69], P = 0.02) and a trend towards lesser nasal injury as compared to continuous mask group (AOR, 95% CI; 0.15 [0.02-1.08], P = 0.06). However, there was no significant difference in incidence of nasal injuries between continuous prongs versus continuous mask group (P = 0.60). The need for surfactant, nCPAP failure rate, duration of nCPAP, and common neonatal co-morbidities were similar across all three groups. Conclusion: Systematic rotation of nasal mask with nasal prongs significantly reduced nasal injury among preterm infants on nCPAP as compared to continuous use of nasal prongs alone without affecting nCPAP failure rate. Trial registration: CTRI/2019/01/017320, registered on 31/01/2019. What is Known: ⢠Use of nasal mask as an interface for nasal Continuous Positive Airway Pressure decreases nasal injury as compared to nasal prongs. What is New: ⢠Rotation of nasal prongs and nasal mask interfaces alternately every 8 h may reduce the nasal injury even further as compared to either interface alone.
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Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Rotação , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Idade GestacionalRESUMO
Breast cancer is the most common cancer among women globally and presents a significant challenge due to its rising incidence and fatality rates. Factors such as cultural, socioeconomic, and educational barriers contribute to inadequate awareness and access to healthcare services, often leading to delayed diagnoses and poor patient outcomes. Furthermore, fostering a collaborative approach among healthcare providers, policymakers, and community leaders is crucial in addressing this critical women's health issue, reducing mortality rates, alleviating, and the overall burden of breast cancer. The main goal of this review is to explore various techniques of machine learning algorithms to examine high accuracy and early detection of breast cancer for the safe health of women.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Algoritmos , Aprendizado de MáquinaRESUMO
PURPOSE: To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients with radiation retinopathy-related cystoid macular edema. METHODS: A retrospective review of seven patients treated for uveal melanoma who developed radiation retinopathy-related cystoid macular edema. They were initially treated with intravitreal anti-vascular endothelial growth factor and/or steroid injections and then transitioned to intravitreal FA implant. Primary outcomes include best-corrected visual acuity, central subfield thickness, and number of additional injections. RESULTS: After FA implant insertion, best-corrected visual acuity and central subfield thickness remained stable in all patients. The variance in best-corrected visual acuity decreased from 75.5 ETDRS letters (range 0-199 letters) to 29.8 (range 1.2-134) after FA implant insertion. Mean central subfield thickness was 384 µ m (range 165-641) and 354 µ m (range 282-493) before and after FA implant insertion, resulting in a 30- µ m mean reduction. The number of intravitreal injections (average 4.9, range 2-10) decreased after intravitreal FA implant insertion with only two patients requiring one additional FA implant (average 0.29, range 0-1) over a mean of 12.1 months (range 0.9-18.5) follow-up. CONCLUSION: Intravitreal FA implant is an effective treatment for cystoid macular edema radiation retinopathy. The slow release of steroid allows for sustained control of macular edema, which correlated with stable visual acuity and decreased injection burden for patients.
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Retinopatia Diabética , Edema Macular , Humanos , Glucocorticoides , Edema Macular/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento , Fluocinolona Acetonida , Estudos Retrospectivos , Injeções IntravítreasRESUMO
Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated as potential sources of the ailment. However, no conclusive etiology for AES has been identified in the affected children. During recent rounds of the outbreak, metabolic abnormalities have been documented in these children, and a direct correlation was observed between higher environmental temperature during the peak-summer month and AES caseload. The clinical and metabolic profiles of these children suggested the possible involvement of mitochondrial dysfunction during heat stress as one of the several contributory factors leading to multisystem metabolic derangement. The present study observed that mitochondrial function parameters such as cell death, mitochondrial membrane potential, oxidative stress, and mitochondrial pathway-related gene expression in peripheral blood mononuclear cells (PBMCs) isolated from children were affected in peak-summer when compared to post-summer months. Similar observations of mitochondrial function parameters along with impaired bioenergetic parameters were demonstrated in the heat-exposed model of PBMCs isolated from healthy adult individuals. In conclusion, the results suggested that there is an association of transient mitochondrial dysfunction when exposed to sustained heat during the summer months. One may consider mitochondrial dysfunction as one of the important factors leading to an outbreak of AES among the children from affected regions though this needs to be substantiated with further studies.
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Encefalopatia Aguda Febril , Leucócitos Mononucleares , Adulto , Humanos , Criança , Pré-Escolar , Índia/epidemiologia , Surtos de Doenças , Metabolismo Energético , Encefalopatia Aguda Febril/epidemiologia , Encefalopatia Aguda Febril/etiologia , MitocôndriasRESUMO
Many hand surgeons treat benign bone tumors without referral to orthopedic oncologists. However, there have been considerable advances in medical therapy for some of these tumors, with which hand surgeons may not be as familiar. This review focuses on the mechanism and uses of denosumab in the treatment of benign tumors of bone. Although the hand surgeon may not be directly prescribing this therapy, they are often the only physician treating the patient for these conditions. As such, awareness regarding the use of this therapy in reducing pain, decreasing tumor volume, and treatment of potential lung metastases is critical to those taking on these cases without the support of an orthopedic oncologist. This article aims to familiarize hand surgeons with denosumab to help promote knowledge of this therapeutic option and the potential role of this medication in the treatment of primary bone tumors in the hand.
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Conservadores da Densidade Óssea , Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Denosumab/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Tumor de Células Gigantes do Osso/cirurgia , Osso e Ossos , Neoplasias Ósseas/patologiaRESUMO
BACKGROUND: Stereotactic brain biopsy for eloquent area brain tumours is associated with complications like hemorrhage due to multiple sampling and increased operative time due to dependence on neuropathologist for frozen section assessment. In order to curb these limitations, we investigated the use of Fluorescein sodium fluorescence in confirming pathological tissue samples in stereotactic brain biopsy of gadolinium-enhancing tumours. METHODS: This prospective observational study included 23 consecutive patients who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. 93 specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Later the nature of the samples was confirmed on histopathology. The sensitivity and specificity of flourescein sodium fluorescence were calculated based on histopathological confirmation. RESULTS: 58 (62.3%) fluorescent and 35 (37.6%) nonfluorescent samples were obtained. All fluorescent specimens contained diagnostic tissue appropriate for tumor grading. Of 35 nonfluorescent specimens, 12 (34.3%) did not contain tumor, 11 (31.4%) contained minor hypercellularity or gliosis, and 12 (34.3%) contained tumor with a high proportion of necrosis. The sensitivity and specificity for fluorescein fluorescence were 83% and 100%, respectively. CONCLUSIONS: Fluorescein fluorescence is a handy tool to detect the pathological tissue in stereotactic brain biopsy and may improve its diagnostic accuracy and expedite the procedure.
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Neoplasias Encefálicas , Gadolínio , Humanos , Fluoresceína , Biópsia/métodos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Técnicas EstereotáxicasRESUMO
Hybrid rice technology offers great promise to further enhance rice production and productivity for global food security. Improving hybrid rice parental lines is the first step in developing heterotic rice hybrids. To improve resistance against blast disease, a maintainer line DRR 9B was fortified with a major broad-spectrum blast resistance gene Pi2 through marker-assisted selection. The rice blast caused by Magnaporthe oryzae is a major disease and can cause severe yield losses upto 100%. The NILs of Samba Mahsuri namely BA-23-11-89-12-168 possessing Pi2 was utilized as a donor parent. The PCR-based molecular marker tightly linked to Pi2 gene was used for the foreground selection at BC1F1 generation. The molecular marker tightly linked to the major fertility restorer gene Rf4 was used for negative selection (i.e., selection of plants possessing non fertility restoring alleles) at BC1F1 generation to identify maintainer lines. The positive plants with Rf4 gene were added to the restorer pool for restorer line development. At each stage, MAS for Pi2 coupled with stringent phenotypic selection for agro-morphological and grain quality traits were exercised. At BC1F3 generation, one hundred families were screened against blast disease at uniform blast nursery (UBN) and selected resistant lines were advanced to next generations. In the BC1F5 generation plants were subjected to agro-morphological evaluation for yield and yield-contributing traits. The selected plants at BC1F5 generation were crossed with DRR 9A to assess the maintainer ability of blast resistance lines and for further CMS line conversion for hybrid rice breeding for developing blast resistance rice hybrids.
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Background: The unprecedented demands on health-care systems due to the COVID-19 pandemic made countries including India to switch toward alternative modes of health-care delivery. Objectives: The aim of this study was to describe the various COVID-related services delivered through 104 health information helpline (HIHL), located in Jharkhand during the pandemic. Methods: The de-identified secondary data from February 2020 to December 2021 related to COVID services delivered through HIHL were analyzed. Results: There was a significant increase in the COVID call volume during the first as well as the second wave. The HIHL has been able to guide the callers on testing, home isolation and follow-up, home-based teleconsultation, vaccination, timely referral, and support with logistic-related information. Conclusion: The 104 HIHL has played a critical role in sustaining health-care delivery during the pandemic, combating the "infodemic" and guiding the general public by providing authentic information.
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COVID-19 , Humanos , Pandemias , Índia/epidemiologia , Atenção à Saúde , Encaminhamento e ConsultaRESUMO
BACKGROUND: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. METHODS: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. RESULTS: Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M - PP3M) in the percentages of patients who remained relapse free was -2.9% (-6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of -10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. CONCLUSIONS: The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT03345342.
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Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Humanos , Palmitato de Paliperidona/efeitos adversos , Recidiva , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológicoRESUMO
Recent anatomical studies have shown connections between the basal ganglia and the cerebellum. The basal ganglia and cerebellum are major subcortical structures that influence motor and cognitive functions. Recent neuroimaging and animal studies have suggested the role of the cerebellum in the pathophysiology of Parkinson's disease. However, the role of cerebellar oscillations in PD has not been studied. Here, we recruited 75 PD and 39 healthy control subjects to collect cerebellar EEG during a resting-state condition. We followed the recently published protocols to collect cerebellar oscillations. Relative spectral power was computed in the delta, theta, beta, and gamma frequency bands. Further, we performed classifier methods to differentiate PD subjects from controls. We observed significantly increased theta-band (4-7 Hz) relative power in the cerebellar electrodes in PD subjects compared to controls. We also found differences in different frequency bands between mid-cerebellar and nearby mid-occipital EEG signals. Classification analysis using mid-cerebellar theta relative power showed differentiation between PD and control groups. Our results demonstrate that in addition to established cortical and basal ganglia oscillations, abnormal cerebellar oscillations in the theta-band may also participate in the underlying pathophysiology of PD. We suggest that low-frequency cerebellar oscillations may be a potential target for non-invasive neuromodulation to improve PD symptoms.