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Plants and their associated microbes live in complicated, changeable, and unpredictable environments. They usually interact with each other in many ways through multidimensional, multiscale, and multilevel coupling manners, leading to challenges in the coexistence of randomness and determinism or continuity and discreteness. Gaining a deeper understanding of these diverse interaction mechanisms can facilitate the development of data-mining theories and methods for complex systems, coupled modeling for systems with different spatiotemporal scales and functional properties, or even a universal theory of information and information interactions. In this study, we use a "closed-loop" model to present a plant-microbe interaction system and describe the probable functions of microbial natural products. Specifically, we report a rhizosphere species, Streptomyces ginsengnesis G7, which produces polyketide lydicamycins and other active metabolites. Interestingly, these distinct molecules have the potential to function both as antibiotics and as herbicides for crop protection. Detailed laboratory experiments conducted in Arabidopsis (Arabidopsis thaliana), combined with a comprehensive bioinformatics analysis, allow us to rationalize a model for this specific plant-microbe interaction process. Our work reveals the benefits of exploring otherwise neglected resources for the identification of potential functional molecules and provides a reference to better understand the system biology of complex ecosystems.
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Arabidopsis , Microbiota , Panax , Streptomyces , Rizosfera , Plantas/metabolismo , Microbiologia do SoloRESUMO
The association between the B and T lymphocyte attenuator (BTLA) gene rs1982809 polymorphism and cancer susceptibility has been reported, but these findings are inconsistent. In addition to clarifying the relationship between the rs1982809 polymorphism and cancer susceptibility, the current study also explored the clinical significance of BTLA gene expression. The GSCA tool and Stata software were used to explore the association between BTLA gene expression and tumor stage, immune infiltration, survival prognosis, and drug sensitivity for pan-cancer, and the association of BTLA gene rs1982809 polymorphism with cancer susceptibility, respectively. BTLA gene expression was associated not only with the pathologic stages of thyroid carcinoma, skin cutaneous melanoma, and kidney renal clear cell carcinoma, but also with immune infiltration in 33 types of cancers. In addition, BTLA gene expression was linked to survival prognosis in 8 types of cancers and the sensitivity of 255 drugs such as 5-Fluorouracil, docetaxel, and methotrexate. A meta-analysis of 7 relevant studies with 4002 cancer patients and 5278 healthy controls showed that the BTLA gene rs1982809 polymorphism was unrelated to cancer susceptibility under all genetic models. However, a country-based stratification analysis suggested that the rs1982809 polymorphism could reduce cancer susceptibility in Polish and Tunisian populations. In conclusion, BTLA is expected to serve as a prognostic marker and therapeutic target for certain cancers, and the rs1982809 polymorphism is expected to serve as a cancer susceptibility marker in Polish and Tunisian populations.
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The amine-catalyzed [3 + 3] annulations of ß'-acetoxy allenoates with 1C,3N-bisnucleophiles have been established. Under the optimal reaction conditions, this operationally simple synthetic process works well with a wide substrate scope, delivering novel 1,2-fused benzimidazole derivatives in moderate to good yields. In addition, preliminary attempts on the asymmetric version of this reaction have been explored by using cinchona alkaloid-based tertiary amines.
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Aminas , Alcaloides de Cinchona , Benzimidazóis , CatáliseRESUMO
Inkjet printing, capable of rapid and template-free fabrication with high resolution and low material waste, is a promising method to construct electrochemical biosensor devices. However, the construction of fully inkjet-printed electrochemical biosensor remains a challenge owing to the lack of appropriate inks, especially the sensing inks of bioactive materials. Herein, we demonstrate a fully inkjet-printed, integrated and multiplexed electrochemical biosensor by combining rationally designed nanoparticle Inks. The stable gold (Au) nanoparticles ink with lower sintering temperature is prepared by using L-cysteine as stabilizer, and it is used to print the interconnects, the counter electrodes, and the working electrodes. The SU-8 ink is used to serve as dielectric layer for the biosensor, whereas the silver electrode is printed on the Au electrode by using commercially silver nanoparticles ink before it is chlorinated to prepare Ag/AgCl reference electrode. Moreover, we synthesize an inkjet-printable and electroactive ink, by the 'one-pot method', which is composed of conductive poly 6-aminoindole (PIn-6-NH2) and gold-palladium (Au-Pd) alloy nanoparticle (Au-Pd@PIn-6-NH2) to enhance the sensing performance of gold electrode towards hydrogen peroxide (H2O2). Especially, the amino groups in PIn-6-NH2can be further used to immobilizing glucose oxidase (GOx) and lactic acid oxidase (LOx) by glutaraldehyde to prepare printable sensing ink for the detection of glucose and lactate. The fully inkjet-printed electrochemical biosensor enabled by advanced inks can simultaneously detect glucose and lactate with good sensitivity and selectivity, as well as facile and scalable fabrication, showing great promise for metabolic monitoring.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Tinta , Prata , Peróxido de Hidrogênio , Técnicas Biossensoriais/métodos , Glucose , Ouro , LactatosRESUMO
OBJECTIVE: To explore the feasibility of using random forest (RF) machine learning algorithm in assessing normal and malignant peripheral pulmonary nodules based on in vivo endobronchial optical coherence tomography (EB-OCT). METHODS: A total of 31 patients with pulmonary nodules were admitted to Department of Respiratory Medicine, Zhongda Hospital, Southeast University, and underwent chest CT, EB-OCT and biopsy. Attenuation coefficient and up to 56 different image features were extracted from A-line and B-scan of 1703 EB-OCT images. Attenuation coefficient and 29 image features with significant p-values were used to analyze the differences between normal and malignant samples. A RF classifier was trained using 70% images as training set, while 30% images were included in the testing set. The accuracy of the automated classification was validated by clinically proven pathological results. RESULTS: Attenuation coefficient and 29 image features were found to present different properties with significant p-values between normal and malignant EB-OCT images. The RF algorithm successfully classified the malignant pulmonary nodules with sensitivity, specificity, and accuracy of 90.41%, 77.87% and 83.51% respectively. CONCLUSION: It is clinically practical to distinguish the nature of pulmonary nodules by integrating EB-OCT imaging with automated machine learning algorithm. Diagnosis of malignant pulmonary nodules by analyzing quantitative features from EB-OCT images could be a potentially powerful way for early detection of lung cancer.
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Algoritmos , Aprendizado de Máquina , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Tomografia Computadorizada por Raios XRESUMO
Infection with the avian leukosis virus subgroup J (ALV-J) impairs host genes and facilitates the establishment of chronic infection and the viral life cycle. However, the involvement of long noncoding RNAs (lncRNAs) in ALV-J infection remains largely unknown. In this study, we identified a novel chicken lncRNA derived from LTR5B of the ERV-L family (namely lnc-LTR5B), which is significantly downregulated in ALV-J infected cells. lnc-LTR5B was localized in the cytoplasm and was relatively high expressed in the chicken lung and liver. Notably, the replication of ALV-J was inhibited by the overexpression of lnc-LTR5B but enhanced when lnc-LTR5B expression was knocked down. We further confirmed that lnc-LTR5B could bind to the binding immunoglobulin protein (BiP), a master regulator of endoplasmic reticulum (ER) function. Mechanistically, lnc-LTR5B serves as a competing endogenous RNA for BiP, restricting its physical availability. Upon ALV-J infection, the reduction of lnc-LTR5B released BiP, which facilitated its translocation to the cell surface. This is crucial for ALV-J entry as well as pro-survival signaling. In conclusion, we identified an endogenous retroviral LTR-activated lnc-LTR5B that is involved in regulating the cell surface translocation of BiP, and such regulatory machinery can be exploited by ALV-J to complete its life cycle and propagate.
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BACKGROUND The aim of the present study was to assess the relationship between inflammatory bowel disease (IBD) and quality of sleep, quality of life (QoL), mental health, and dietary intake to identify potential risk factors for IBD. MATERIAL AND METHODS This was a retrospective analysis from September 2019 to August 2020. We enrolled 71 patients with IBD aged 14 to 69 years who completed the IBD-Life Habits Questionnaire, which included data on demographics, environmental factors, and dietary habits; the Pittsburgh Sleep Quality Index (PSQI); Patient Health Questionnaire (PHQ-9); Generalized Anxiety Disorder-7 (GAD-7); and the Inflammatory Bowel Disease Questionnaire (IBDQ). Of the patients, 46 had IBD that was in remission and in 25 the disease was active, based on scores used to assess clinical symptoms. The Crohn's Disease Activity Index (CDAI) and the Partial Mayo Score were used for Crohn disease (CD) and ulcerative colitis (UC), respectively. The patients were divided into 2 groups, based on disease status: remission (CDAI <150 or Mayo Score=0) and active (CDAI ≥150 or Mayo Score >0). Because sleep and dietary habits in the patients with UC and CD were not significantly different, the 2 groups of patients were eventually combined into a single IBD group. The IBD-Life Habits Questionnaire, except for IBDQ, was completed by 68 age- and sex-matched healthy controls. RESULTS Scores for PSQI (P=.001), PHQ-9 (P=.003), GAD-7 (P=.007), and IBDQ (P=.001) were significantly higher in the patients with active IBD. An IBDQ score >168.0 (PSQI score >7.5) indicates a clinically active state of IBD with a sensitivity of 84.8% (72.0%) and a specificity of 88.0% (82.6%). Diet composition was not related to disease activity. An analysis of patients and controls showed that lack of siblings could be a protective factor for onset of IBD (OR 0.300, 95% CI 0.119-0.785), while not being breastfed (OR 2.753, 95% CI 1.025-7.396) and consuming spicy foods could be risk factors for onset of IBD (OR 2.186, 95% CI 1.370-3.488). CONCLUSIONS In patients with IBD, poor sleep quality, poor QoL, depression, and anxiety were related to having active disease, whereas diet was not. Attempting to control dietary composition in patients with IBD may not be effective in preventing disease flare, but attention should be paid to intake of spicy foods.
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Ansiedade/epidemiologia , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Depressão/epidemiologia , Qualidade do Sono , Adolescente , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Doença de Crohn/fisiopatologia , Doença de Crohn/psicologia , Depressão/diagnóstico , Depressão/psicologia , Inquéritos sobre Dietas/estatística & dados numéricos , Comportamento Alimentar/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Autorrelato/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal disease. Our previous work showed that long non-coding RNA (LncRNA) nuclear enriched abundant transcript 1 (NEAT1) plays an important role in IBD. In the current study, we aimed to explore the underlying mechanism by which NEAT1 participates in the development of the disease. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of NEAT1 and tumor necrosis factor superfamily member 1B (TNFRSF1B) in clinical specimens and dextran sulfate sodium (DSS) colitis mice. Inflammatory cell models were established by stimulating human normal intestinal epithelial cell line NCM460 and human colon cancer cell line HT-29 with tumor necrosis factor alpha (TNF-α). Expressions of inflammatory cytokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) or RT-qPCR, TNFRSF1B, NF-κB p65 and p-NF-κB p65 followed by the knockdown or overexpression of NEAT1 and TNFRSF1B were analyzed by western blotting, and the regulatory effects of NEAT1 on TNFRSF1B were detected by RNA pull-down experiments and RNA-decay assay. The translocation of NF-κB p65 to the nucleus was detected by immunofluorescence. RESULTS: In patients' specimens and DSS colitis mouse models, NEAT1 and TNFRSF1B expression were up-regulated compared with the control group. TNF-α stimulation increased NEAT1 and TNFRSF1B expression and activated NF-κB signaling pathway by increasing the translocation of NF-κB p65 to the nucleus. In the presence of TNF-α stimulation, NEAT1 knockdown reduces the expression of TNFRSF1B and the translocation of NF-κB p65, thereby relieves cell inflammation. These effects can be reversed by the overexpression of TNFRSF1B.In addition, NEAT1 is involved in inflammatory response by up-regulating the mRNA levels of TNFRSF1B, and knocking down NEAT1 can alleviate inflammation by down-regulating TNFRSF1B. Moreover, NEAT1 co-precipitates TNFRSF1B mRNA in RNA-pulldown assay, and the presence of NEAT1 stabilizes the mRNA of TNFRSF1B. CONCLUSIONS: Our results showed that LncRNA NEAT1 promotes NF-κB p65 translocation and mediates intestinal inflammation by regulating TNFRSF1B.
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OBJECTIVE: To evaluate the quantitative changes of respiratory functions for critically ill COVID-19 patients with mechanical ventilation, computational fluid dynamics (CFD) analysis was performed based on patient-specific three-dimensional airway geometry. METHODS: 37 cases of critically ill patients with COVID-19 admitted to the ICU of Huangshi Traditional Chinese Medicine Hospital from February 1st to March 20th, 2020 were retrospectively analyzed. 5 patients whose clinical data met the specific criteria were finally cataloged into death group (2 patients) and survival group (3 patients). The patient-specific three-dimensional airways were reconstructed from the central airways down to the 4th-5th bifurcation of the tracheobronchial tree. The volume changes of bronchi were calculated during the disease progression according to the comparison of two CT scans. Additionally, the changes of air flow resistance were analyzed using numerical simulation of CFD. RESULTS: Pearson correlation analysis demonstrated that there was negative correlation between the change of volume (ΔV) and the change of resistance (ΔR) for all COVID-19 patients (r=-0.7025). For total airway volume, an average decrease of -11.41±15.71% was observed in death group compared to an average increase of 1.86±10.80% in survival group (p=0.0232). For air flow through airways in lower lobe, the resistance increases for death group by 10.97±77.66% and decreases for survival group by -45.49±42.04% (p=0.0246). CONCLUSION: The variation of flow resistance in the airway could be used as a non-invasive functional evaluation for the prognosis and outcome of critically ill patients with COVID-19. The 'virtual' pulmonary function test by integrating follow-up CT scans with patient-derived CFD analysis could be a potentially powerful way in improving the efficiency of treatment for critically ill patients with COVID-19.
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Resistência das Vias Respiratórias , COVID-19 , Estado Terminal , Humanos , Hidrodinâmica , Pulmão , Prognóstico , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVES: To investigate the differences in the temporomandibular joints (TMJs) between patients with anterior disc displacement with reduction (ADDwR) and asymptomatic subjects by using 3D morphometric measurements. METHODS: A total of 15 patients with ADDwR and 10 asymptomatic subjects were enrolled. Then, 3D models of the maxilla and mandible were reconstructed using MIMICS 20.0. Nine morphologic parameters of TMJs on both sides were measured on the 3D solid model. The differences in the parameters were analyzed between the patients and the asymptomatic subjects and between the left and right sides of each group. RESULTS: The horizontal and coronal condylar angles on the ipsilateral side of the patients were significantly greater than those of the asymptomatic subjects (P<0.01). Meanwhile, the sagittal ramus angle (SRA), medial joint space, lateral joint space, superior joint space, anterior joint space, and posterior joint space in the patients were significantly lower than those in the asymptomatic subjects (P<0.01). CONCLUSIONS: ADDwR will increase the condylar angles to be significantly greater than the normal level and decrease SRA and articular spaces to be significantly smaller than the normal level. The condyles will be displaced upward, closer to the fossa.
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Luxações Articulares , Transtornos da Articulação Temporomandibular , Dente , Humanos , Imageamento por Ressonância Magnética , Mandíbula , Côndilo Mandibular , Maxila , Articulação TemporomandibularRESUMO
BACKGROUND AND AIM: Although endoscopic ultrasound-guided fine-needle biopsy is widely applied, there is no clear consensus on the optimal biopsy technique. We described a modified wet suction technique (MWEST) with the aim to compare the efficacy and safety between MWEST and the dry suction technique (DST). METHODS: In this prospective, randomized, crossover, single-blinded study, patients with suspected pancreatic malignancy were randomized to the DST (group A) or MWEST (group B) for the first pass, and the two techniques were performed alternately. The primary outcome was the comparison of specimen adequacy and diagnostic yield between the techniques. Secondary outcomes included the macroscopic visible core length, blood contamination of specimens, and adverse events of both techniques. RESULTS: From January 2019 to September 2019, 216 passes were performed in 50 patients. The specimen adequacy was significantly higher in "per-lesion" (P = 0.026), "per-pass" (cytology: P = 0.034; histology: P = 0.042), and first-pass analysis (P = 0.034) for MWEST than for DST. In diagnostic yield, MWEST showed significantly superior histological yield (P = 0.014) and first-pass analysis (κ: MWEST: 0.743 and DST: 0.519) compared with DST. The median macroscopic visible core lengths were 8 mm (interquartile range: 3.25-15 mm) and 10 mm (interquartile range: 5.25-15 mm) for DST and MWEST, respectively (P = 0.036). Blood contamination was significantly more serious in DST than in MWEST (cytology: P = 0.021; histology: P = 0.042). CONCLUSIONS: Endoscopic ultrasound-guided fine-needle biopsy with MWEST resulted in significantly better quality of specimen, histological, and first-pass diagnostic yields and comparable safety compared with the DST. MWEST is preferred for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Manejo de Espécimes/métodos , Sucção/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Estudos Prospectivos , Método Simples-CegoRESUMO
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is a chronic, relapsing condition associated with the disorder of gut microbial communities. A previous study reported that levels of Roseburia intestinalis (R.I), a butyrateproducing bacterium, are significantly decreased in patients with IBD and exert an antiinflammatory function in dextran sulfate sodium (DSS)induced colitis. However, the role of R.I flagellin in UC and its underlying molecular mechanism are not yet fully understood. Therefore, a DSSinduced colitis model in C57Bl/6 mice and the LPS/ATPinduced THP1 macrophages were treated with R.I flagellin, which were used to investigate the antiinflammatory effects of R.I flagellin. The results demonstrated that R.I flagellin decreased colitisassociated disease activity index, colonic shortening and the pathological damage of the colon tissues in murine colitis models. Furthermore, R.I flagellin decreased the serum levels of proinflammatory cytokines and inhibited activation of the nucleotidebinding oligomerization segmentlike receptor family 3 (NLRP3) inflammasome in murine colitis. R.I flagellin was also demonstrated to decrease the Gasdermin D to yield the Nterminal fragment membrane pore and inhibit inflammasometriggered pyroptosis. In vitro analysis indicated that microRNA (miR)2233p was involved in the regulation of R.I flagellin on NLRP3 inflammasome activation. Taken together, the results of the present study demonstrated that R.I flagellin inhibited activation of the NLRP3 inflammasome and pyroptosis via miR2233p/NLRP3 signaling in macrophages, suggesting that R.I flagellin may be used as a novel probiotic product for the treatment of UC.
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Anti-Inflamatórios/farmacologia , Clostridiales/química , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Flagelina/farmacologia , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Trifosfato de Adenosina/toxicidade , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/toxicidade , Humanos , Inflamassomos/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Células THP-1 , Receptores Toll-Like/metabolismoRESUMO
Endophytes are considered to be excellent biocontrol agents and biofertilizers, and are associated with plant growth promotion and health. In particular, seed-endophytic bacteria benefit the host plant's progeny via vertical transmission, and can play a role in plant growth and defense. However, seed-associated endophytic bacteria have not been fully explored, with very little known about how they interact with peanut (Arachis hypogaea), for example. Here, 10 genera of endophytic bacteria were isolated from the root tips of peanut seedlings grown either aseptically or in soil. Forty-two bacterial colonies were obtained from peanut seedlings grown in soil, mostly from the genus Bacillus. Eight colonies were obtained from aseptic seedling root tips, including Bacillus sp., Paenibacillus sp., and Pantoea dispersa. Four Bacillus peanut strains GL1-GL4 (B.p.GL1-GL4) produced bio-films, while B.p.GL2 and Paenibacillus glycanilyticus YMR3 (P.g.YMR3) showed strong amylolytic capability, enhanced peanut biomass, and increased numbers of root nodules. Conversely, P. dispersa YMR1 (P.d.YMR1) caused peanut plants to wilt. P.g.YMR3 was distributed mainly around or inside vacuoles and was transmitted to the next generation through gynophores and ovules. Hexanoate, succinate, and jasmonic acid (JA) accumulated in peanut root tips after incubation with P.g.YMR3, but linolenate content decreased dramatically. This suggests that strain P.g.YMR3 increases JA content (14.93-fold change) and modulates the metabolism of peanut to facilitate nodule formation and growth. These findings provide new insight into plant-seed endophytic bacterial interactions in peanut.
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BACKGROUND: Until recently, treatment options were limited for patients with acute myeloid leukemia and myelodysplastic syndrome (AML and MDS) who are ineligible for intensive chemotherapy. Owing to the condition's rapid progression, it is difficult to identify what is most important to patients when making treatment decisions. Patients' needs can be better addressed by gaining a deeper understanding of their perspectives, which is valuable in the decision-making process. The Food and Drug Administration recently encouraged the use of social media as a tool to gain insight on patients' perspectives regarding symptoms experienced and the impacts of their disease. OBJECTIVE: This study aimed to use disease-specific social media posts by patients with AML or MDS who are ineligible for intensive chemotherapy and their caregivers to capture factors they feel are most important, and to provide current evidence to inform and characterize these perspectives. METHODS: Posts by patients with AML or MDS and their caregivers were extracted from publicly available discussions on 3 large AML- or MDS-specific sites. These posts were manually reviewed to only include patients who are ineligible for intensive chemotherapy. A total of 1443 posts from 220 AML patients/caregivers and 2733 posts from 127 MDS patients/caregivers met the study inclusion criteria. A qualitative data analysis (QDA) of a sample of 85 patients'/caregivers' posts was conducted to identify themes, and a targeted QDA of posts from 79 users focused on treatment decision discussions. Posts were manually reviewed, and relevant text segments were coded and grouped into categories and overall themes. RESULTS: Eighty-six percent (73/85) of users in the overall QDA had relevant information about the key objectives. The most commonly discussed treatment experience theme was the humanistic burden of AML or MDS in terms of emotional/physical impact and impact on family (86%, 63/73 of users), followed by treatment decisions (56%, 41/73) and unmet needs (50%, 37/73). In the QDA of treatment decisions, 60 posts from 45 users contained relevant information. Patients commonly reported the desire to reach specific milestones, including birthdays and weddings. They wished for a better quality of life over quantity of life, did not want the risk of suffering from side effects, and expressed a clear preference to be at home rather than in a hospital or care home. CONCLUSIONS: This study was a novel application of disease-specific social media. It highlighted experiences in the current treatment of AML and MDS, including information gaps, patient/caregiver uncertainty, and the importance of understanding patients'/caregivers' goals and opinions. A clear finding from this research was the importance of reaching certain personal life goals and being at home with family and friends. The analysis showed that patients/caregivers face additional challenges, including humanistic impacts and a lack of information regarding treatment options.