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Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription. PVT1 undergoes developmentally regulated monoallelic expression, and the PVT1 promoter inhibits MYC expression only from the same chromosome via promoter competition. Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements.
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Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Genes myc , RNA Longo não Codificante/genética , Animais , Neoplasias da Mama/metabolismo , Sistemas CRISPR-Cas , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Cromatina , DNA de Neoplasias/genética , Elementos Facilitadores Genéticos , Feminino , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos NOD , Mutação , Transplante de Neoplasias , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , Transcrição GênicaRESUMO
Radial glia, the neural stem cells of the neocortex, are located in two niches: the ventricular zone and outer subventricular zone. Although outer subventricular zone radial glia may generate the majority of human cortical neurons, their molecular features remain elusive. By analyzing gene expression across single cells, we find that outer radial glia preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR. Using dynamic imaging, immunostaining, and clonal analysis, we relate these molecular features to distinctive behaviors of outer radial glia, demonstrate the necessity of STAT3 signaling for their cell cycle progression, and establish their extensive proliferative potential. These results suggest that outer radial glia directly support the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby enabling the developmental and evolutionary expansion of the human neocortex.
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Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Animais , Ciclo Celular , Humanos , Macaca , Camundongos , Neocórtex/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese , Neuroglia/citologia , Neuroglia/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Análise de Célula Única , Nicho de Células-TroncoRESUMO
BACKGROUND AND AIM: Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS: Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS: The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS: A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.
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Colonoscopia , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Fatores de Risco , Detecção Precoce de Câncer , AlucinaçõesRESUMO
The uncertain future due to the COVID-19 pandemic and the technological advancements may have altered young adults' experiences of romantic relationships. It is unclear whether individuals will continue to prefer traditional long-term romantic relationships (LTRR) or opt for short-term ones (STRR). This research describes how young adults in Malaysia perceive LTRR and STRR. Using the structured approach of the theory of social representations, data were collected from 512 participants; 238 (46.48%) male; Mage 21.75; majority were heterosexual and students, and analyzed using prototypical analysis to reveal high consensus elements. Five observations were made: (1) females prioritize "love" in both STRR and LTRR, while males prioritize "love" only in LTRR; (2) females prioritize "marriage" in LTRR, while males prioritize "trust," "comfort," and "stability." Males do not consider "marriage" as part of a LTRR; (3) both males and females view STRR positively, while LTRR are viewed more practically; (4) "sex" is a core element in STRR but is absent in LTRR; (5) males differentiate between STRR and LTRR with no overlapping elements. These findings provide insight into the social representations of romantic relationships among young adults in Malaysia and suggest future directions for research in the field.
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Relações Interpessoais , Pandemias , Feminino , Humanos , Masculino , Adulto Jovem , Adulto , MalásiaRESUMO
BACKGROUND: Does experiencing adversity engender kindness, and if so, for whom? Two studies tested the hypothesis that adversity predicts increased pro-social outcomes, and that this relationship is strongest for individuals who view others as good and trustworthy, or benevolent. METHOD: In Study 1, a cross-sectional survey design was utilized, and in Study 2 a longitudinal survey was conducted. RESULTS: In Study 1 (N = 359), the number of lifetime adverse life events was associated with increased volunteering, empathic concern, and self-reported altruism. The association of adversity and altruism was stronger for those with greater benevolence beliefs. In Study 2 (N = 1157), benevolence beliefs were assessed, and in subsequent years, adverse life events were reported. The number of past-year adverse life events predicted more volunteering and charitable involvement, but only among people with high benevolence beliefs. CONCLUSION: Exposure to adversity may be associated with increased pro-social behavior among those with higher benevolence beliefs. In part, this could be due to benevolence beliefs increasing the expectation that one's efforts will be appreciated and reciprocated.
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Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1-independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.
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Proliferação de Células/genética , Loci Gênicos , RNA Longo não Codificante/metabolismo , Apoptose/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA-SeqRESUMO
BACKGROUND: Discharge letters are a critical component in the continuity of care between specialists and primary care providers. However, these letters are time-consuming to write, underprioritized in comparison to direct clinical care, and are often tasked to junior doctors. Prior studies assessing the quality of discharge summaries written for inpatient hospital admissions show inadequacies in many domains. Large language models such as GPT have the ability to summarize large volumes of unstructured free text such as electronic medical records and have the potential to automate such tasks, providing time savings and consistency in quality. OBJECTIVE: The aim of this study was to assess the performance of GPT-4 in generating discharge letters written from urology specialist outpatient clinics to primary care providers and to compare their quality against letters written by junior clinicians. METHODS: Fictional electronic records were written by physicians simulating 5 common urology outpatient cases with long-term follow-up. Records comprised simulated consultation notes, referral letters and replies, and relevant discharge summaries from inpatient admissions. GPT-4 was tasked to write discharge letters for these cases with a specified target audience of primary care providers who would be continuing the patient's care. Prompts were written for safety, content, and style. Concurrently, junior clinicians were provided with the same case records and instructional prompts. GPT-4 output was assessed for instances of hallucination. A blinded panel of primary care physicians then evaluated the letters using a standardized questionnaire tool. RESULTS: GPT-4 outperformed human counterparts in information provision (mean 4.32, SD 0.95 vs 3.70, SD 1.27; P=.03) and had no instances of hallucination. There were no statistically significant differences in the mean clarity (4.16, SD 0.95 vs 3.68, SD 1.24; P=.12), collegiality (4.36, SD 1.00 vs 3.84, SD 1.22; P=.05), conciseness (3.60, SD 1.12 vs 3.64, SD 1.27; P=.71), follow-up recommendations (4.16, SD 1.03 vs 3.72, SD 1.13; P=.08), and overall satisfaction (3.96, SD 1.14 vs 3.62, SD 1.34; P=.36) between the letters generated by GPT-4 and humans, respectively. CONCLUSIONS: Discharge letters written by GPT-4 had equivalent quality to those written by junior clinicians, without any hallucinations. This study provides a proof of concept that large language models can be useful and safe tools in clinical documentation.
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Alta do Paciente , Humanos , Alta do Paciente/normas , Registros Eletrônicos de Saúde/normas , Método Simples-Cego , IdiomaRESUMO
The chromatin remodeler CHD8 represents a high-confidence risk factor in autism, a multistage progressive neurologic disorder, however the underlying stage-specific functions remain elusive. In this study, by analyzing Chd8 conditional knock-out mice (male and female), we find that CHD8 controls cortical neural stem/progenitor cell (NSC) proliferation and survival in a stage-dependent manner. Strikingly, inducible genetic deletion reveals that CHD8 is required for the production and fitness of transit-amplifying intermediate progenitors (IPCs) essential for upper-layer neuron expansion in the embryonic cortex. p53 loss of function partially rescues apoptosis and neurogenesis defects in the Chd8-deficient brain. Further, transcriptomic and epigenomic profiling indicates that CHD8 regulates the chromatin accessibility landscape to activate neurogenesis-promoting factors including TBR2, a key regulator of IPC neurogenesis, while repressing DNA damage- and p53-induced apoptotic programs. In the adult brain, CHD8 depletion impairs forebrain neurogenesis by impeding IPC differentiation from NSCs in both subventricular and subgranular zones; however, unlike in embryos, it does not affect NSC proliferation and survival. Treatment with an antidepressant approved by the Federal Drug Administration (FDA), fluoxetine, partially restores adult hippocampal neurogenesis in Chd8-ablated mice. Together, our multistage functional studies identify temporally specific roles for CHD8 in developmental and adult neurogenesis, pointing to a potential strategy to enhance neurogenesis in the CHD8-deficient brain.SIGNIFICANCE STATEMENT The role of the high-confidence autism gene CHD8 in neurogenesis remains incompletely understood. Here, we identify a stage-specific function of CHD8 in development of NSCs in developing and adult brains by conserved, yet spatiotemporally distinct, mechanisms. In embryonic cortex, CHD8 is critical for the proliferation, survival, and differentiation of both NSC and IPCs during cortical neurogenesis. In adult brain, CHD8 is required for IPC generation but not the proliferation and survival of adult NSCs. Treatment with FDA-approved antidepressant fluoxetine partially rescues the adult neurogenesis defects in CHD8 mutants. Thus, our findings help resolve CHD8 functions throughout life during embryonic and adult neurogenesis and point to a potential avenue to promote neurogenesis in CHD8 deficiency.
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Transtorno Autístico , Cromatina , Proteínas de Ligação a DNA , Neurogênese , Animais , Feminino , Masculino , Camundongos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fluoxetina , Hipocampo/metabolismo , Camundongos Knockout , Neurogênese/fisiologia , Proteína Supressora de Tumor p53 , ProsencéfaloRESUMO
Reduced glutathione (GSH) plays an essential role in relieving oxidative insult from the generation of free radicals via normal physiological processes. However, GSH can be exploited by bacteria as a signalling molecule for the regulation of virulence. We describe findings arising from a serendipitous observation that when GSH and Escherichia coli were incubated with 5'fluorodeoxyuridine (FUdR)-synchronised populations of Caenorhabditis elegans, the nematodes underwent rapid death. Death was mediated by the production of hydrogen sulphide mainly through the action of tnaA, a tryptophanase-encoding gene in E. coli. Other Enterobacteriaceae species possess similar cysteine desulfhydrases that can catabolise l-cysteine-containing compounds to hydrogen sulphide and mediate nematode killing when worms had been pre-treated with FUdR. When colonic epithelial cell lines were infected, hydrogen sulphide produced by these bacteria in the presence of GSH was also able to inhibit ATP synthesis in these cells particularly when cells had been treated with FUdR. Therefore, bacterial production of hydrogen sulphide could act in concert with a commonly used genotoxic cancer drug to exert host cell impairment. Hydrogen sulphide also increases bacterial adhesion to the intestinal cells. These findings could have implications for patients undergoing chemotherapy using FUdR analogues that could result in intestinal damage.
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Sulfeto de Hidrogênio , Animais , Bactérias/metabolismo , Caenorhabditis elegans/microbiologia , Enterobacteriaceae/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Floxuridina/metabolismo , Glutationa/metabolismo , Humanos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologiaRESUMO
COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.
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COVID-19 , Taxa Respiratória , Humanos , Cânula , COVID-19/terapia , Respiração , GasometriaRESUMO
OBJECTIVE: Understanding the social determinants of bystander cardiopulmonary resuscitation (CPR) receipt can inform the design of public health interventions to increase bystander CPR. The association of socioeconomic status with bystander CPR is generally poorly understood. We evaluated the relationship between socioeconomic status and bystander CPR in cases of out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study based on the Singapore cohort of the Pan-Asian Resuscitation Outcomes Study registry between 2010 and 2018. We categorized patients into low, medium, and high Singapore Housing Index (SHI) levels-a building-level index of socioeconomic status. The primary outcome was receipt of bystander CPR. The secondary outcomes were prehospital return of spontaneous circulation and survival to discharge. RESULTS: A total of 12,730 OHCA cases were included, the median age was 71 years, and 58.9% were male. The bystander CPR rate was 56.7%. Compared to patients in the low SHI category, those in the medium and high SHI categories were more likely to receive bystander CPR (medium SHI: adjusted odds ratio [aOR] 1.48, 95% CI 1.30-1.69; high SHI: aOR 1.93, 95% CI 1.67-2.24). High SHI patients had higher survival compared to low SHI patients on unadjusted analysis (OR 1.79, 95% CI 1.08-2.96), but not adjusted analysis (adjusted for age, sex, race, witness status, arrest time, past medical history of cancer, and first arrest rhythm). When comparing high with low SHI, females had larger increases in bystander CPR rates than males. CONCLUSIONS: Lower building-level socioeconomic status was independently associated with lower rate of bystander CPR, and females were more susceptible to the effect of low socioeconomic status on lower rate of bystander CPR.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Feminino , Humanos , Masculino , Idoso , Estudos Retrospectivos , Coleta de Dados , Classe Social , Parada Cardíaca Extra-Hospitalar/terapiaRESUMO
OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral. SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions. RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®. CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.
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Neoplasias Bucais , Telemedicina , Adulto , Humanos , Estudos Prospectivos , Neoplasias Bucais/diagnóstico , Sensibilidade e Especificidade , Encaminhamento e Consulta , Telemedicina/métodosRESUMO
BACKGROUND: Chronic stroke patients usually experience reduced hand functions, impeding their ability to perform activities of daily living (ADLs) independently. Additionally, improvements in hand functions by physical therapy beyond six months after the initial onset of stroke are much slower than in the earlier months. As such, chronic stroke patients could benefit from an assistive device to enhance their hand functions, allowing them to perform ADLs independently daily. In recent years, soft robotics has provided a novel approach to assistive devices for motor impaired individuals, offering more compliant and lightweight alternatives to traditional robotic devices. The scope of this study is to demonstrate the viability of a fabric-based soft robotic (SR) glove with bidirectional actuators in assisting chronic stroke study participants with hand impairments in performing ADLs. METHODS: Force and torque measurement tests were conducted to characterize the SR Glove, and hand functional tasks were given to eight chronic stroke patients to assess the efficacy of the SR Glove as an assistive device. The tasks involved object manipulation tasks that simulate ADLs, and the series of tasks was done by the participants once without assistance for baseline data, and once while using the SR Glove. A usability questionnaire was also given to each participant after the tasks were done to gain insight into how the SR Glove impacts their confidence and reliance on support while performing ADLs. RESULTS: The SR Glove improved the participants' manipulation of objects in ADL tasks. The difference in mean scores between the unassisted and assisted conditions was significant across all participants. Additionally, the usability questionnaire showed the participants felt more confident and less reliant on support while using the SR Glove to perform ADLs than without the SR Glove. CONCLUSIONS: The results from this study demonstrated that the SR Glove is a viable option to assist hand function in chronic stroke patients who suffer from hand motor impairments.
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Robótica , Acidente Vascular Cerebral , Humanos , Atividades Cotidianas , Mãos , Extremidade Superior , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382â IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751â IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.
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Vacina BNT162 , COVID-19 , Humanos , Idoso , SARS-CoV-2 , Formação de Anticorpos , Vacina de mRNA-1273 contra 2019-nCoV , Vacinação , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
OBJECTIVES: The purpose of this review was to appraise the quality of evidence of the existing publications on IR, and to perform a meta-analysis on the treatment outcomes of IR. METHODS: The specific PIO questions were as follows: Population: Patients with periapical periodontitis either before or after non-surgical endodontic therapy. INTERVENTION: IR performed with retrograde preparation and retrograde filling. OUTCOMES: the healing, treatment complications, and the factors influencing these outcomes after IR. Electronic and hand searches were performed in the Web of Science, PubMed, CINAHL, and Cochrane Library databases. Two authors independently screened the titles and abstracts for eligibility. The risk of bias was performed using the NIH Quality Assessment Tool, and each study was rated as "Good", "Fair" or "Poor". The analyses were performed on the treatment outcome (healing and complications), and the factors influencing the outcome of the procedure. RESULTS: Fourteen articles were included in the qualitative and quantitative syntheses. One was a prospective cohort study, and the other 13 were retrospective cohort studies. Overall, the evidence of this review was of poor-to-fair quality. The pooled healing rate was 80.2%, and there was a 21.7% of complication rate. Longer follow-up period, the presence of perio-endo disease, the use of non-bioceramic material as retrograde filling, longer extraoral time, and maxillary molar were found to be associated with lower healing rates. However, the differences between the subgroups were not statistically significant. CONCLUSIONS: The present review showed IR yielded a good overall healing rate with a low complication rate. Taking the quality of evidence into account, more high-quality studies are required to evaluate the validity of the factors that may influence the treatment outcome of IR.
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Periodontite Periapical , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Periodontite Periapical/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Socioeconomic status (SES) is an important determinant of health, and SES data is an important confounder to control for in epidemiology and health services research. Individual level SES measures are cumbersome to collect and susceptible to biases, while area level SES measures may have insufficient granularity. The 'Singapore Housing Index' (SHI) is a validated, building level SES measure that bridges individual and area level measures. However, determination of the SHI has previously required periodic data purchase and manual parsing. In this study, we describe a means of SHI determination for public housing buildings with open government data, and validate this against the previous SHI determination method. METHODS: Government open data sources (e.g. DATA: gov.sg, Singapore Land Authority OneMAP API, Urban Redevelopment Authority API) were queried using custom Python scripts. Data on residential public housing block address and composition from the HDB Property Information dataset (data.gov.sg) was matched to postal code and geographical coordinates via OneMAP API calls. The SHI was calculated from open data, and compared to the original SHI dataset that was curated from non-open data sources in 2018. RESULTS: Ten thousand seventy-seven unique residential buildings were identified from open data. OneMAP API calls generated valid geographical coordinates for all (100%) buildings, and valid postal code for 10,012 (99.36%) buildings. There was an overlap of 10,011 buildings between the open dataset and the original SHI dataset. Intraclass correlation coefficient was 0.999 for the two sources of SHI, indicating almost perfect agreement. A Bland-Altman plot analysis identified a small number of outliers, and this revealed 5 properties that had an incorrect SHI assigned by the original dataset. Information on recently transacted property prices was also obtained for 8599 (85.3%) of buildings. CONCLUSION: SHI, a useful tool for health services research, can be accurately reconstructed using open datasets at no cost. This method is a convenient means for future researchers to obtain updated building-level markers of socioeconomic status for policy and research.
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Habitação , Classe Social , Pesquisa sobre Serviços de Saúde , Humanos , SingapuraRESUMO
INTRODUCTION: During deep brain stimulation (DBS) surgery, computed tomography (CT) and magnetic resonance imaging (MRI) scans need to be co-registered or fused. Image fusion is associated with the error that can distort the location of anatomical structures. Co-registration in DBS surgery is usually performed automatically by proprietary software; the amount of error during this process is not well understood. Here, our goal is to quantify the error during automated image co-registration with FrameLink™, a commonly used software for DBS planning and clinical research. METHODS: This is a single-center retrospective study at a quaternary care referral center, comparing CT and MR imaging co-registration for a consecutive series of patients over a 12-month period. We collected CT images and MRI scans for 22 patients with Parkinson's disease requiring placement of DBS. Anatomical landmarks were located on CT images and MRI scans using a novel image analysis algorithm that included a method for capturing the potential error inherent in the image standardization step of the analysis. The distance between the anatomical landmarks was measured, and the error was found by averaging the distances across all patients. RESULTS: The average error during co-registration was 1.25 mm. This error was significantly larger than the error resulting from image standardization (0.19 mm) and was worse in the anterior-posterior direction. CONCLUSIONS: The image fusion errors found in this analysis were nontrivial. Although the estimated error may be inflated, it is sig-nificant enough that users must be aware of this potential inaccuracy, and developers of proprietary software should provide details about the magnitude and direction of co-registration errors.
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Estimulação Encefálica Profunda , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Software , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Preliminary evidence suggests dialectical behaviour therapy (DBT) may be beneficial for persons with intellectual disabilities. This pilot randomized controlled trial aimed to determine the feasibility of adapted DBT for adults with intellectual disabilities and co-morbid psychiatric disorders in the community. METHODS: An adapted DBT programme (aDBT-ID) was delivered to adults with mild-to-moderate intellectual disability (n = 20) and their caregivers (n = 20). A single-blind, mixed-methods design was employed with treatment (n = 10) and control (n = 10). In addition to feasibility, pre-post-measures of emotional regulation, anger and mental health were taken from clients and caregivers. RESULTS: Results suggest it was feasible and beneficial to deliver adapted DBT in the community. Qualitative findings found both participants and caregivers were satisfied with the treatment delivery. No differences between conditions were found. CONCLUSION: This pilot study highlights the feasibility of adapted DBT for individuals with intellectual disabilities and the practicalities of delivering community-based inclusive research.
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Terapia do Comportamento Dialético , Deficiência Intelectual , Adulto , Criança , Deficiências do Desenvolvimento , Estudos de Viabilidade , Humanos , Deficiência Intelectual/terapia , Projetos Piloto , Método Simples-Cego , Resultado do TratamentoRESUMO
Long non-coding RNAs (lncRNAs) have emerged as important regulators of cell biology. The mechanisms by which lncRNAs function are likely numerous, and most are poorly understood. Currently, the mechanisms of functional lncRNAs include those that directly involve the lncRNA transcript, the process of their own transcription and splicing, and even underlying transcriptional regulatory elements within the genomic DNA that encodes the lncRNA As our understanding of lncRNA biology evolves, so have the methods that are utilized to elucidate their functions. In this review, we survey a collection of different methods used to modulate lncRNA expression levels for the assessment of biological function. From RNA-targeted strategies, genetic deletions, to engineered gene regulatory systems, the advantages and caveats of each method will be discussed. Ultimately, the selection of tools will be guided by which potential lncRNA mechanisms are being investigated, and no single method alone will likely be sufficient to reveal the function of any particular lncRNA.
Assuntos
Regulação da Expressão Gênica , RNA Longo não Codificante/genética , Animais , Engenharia Genética , Genoma , Humanos , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Pectoral nerves (PECS II) block is a popular regional analgesia technique for breast surgery. PECS II block or local infiltration by surgeon may improve outcomes including quality of recovery (QoR). METHODS: In this multicenter randomized clinical trial, 104 female patients undergoing breast surgery received: (1) PECS II block with local anesthetic and surgical infiltration with 0.9% saline (PECS group) or (2) PECS II block with 0.9% saline and surgical infiltration with local anesthetic (infiltration group). Patients, anesthetists, surgeons, nursing staff, and research assistants were blinded to group allocation. Patients received standardized general anesthesia and multimodal analgesia. The primary outcome was the global score (maximum score, 150; good recovery, 118) of the multidimensional (pain, comfort, independence, psychological, emotional) QoR-15 questionnaire measured 24 hours postoperatively. Secondary outcomes were pain, and its functional interference measured 24 hours and 3 months postoperatively using the Brief Pain Inventory (BPI) short form (0, optimal; 120, worst possible). Randomly assigned groups were compared on outcomes using the Wilcoxon rank-sum test, and the results were reported as median difference with 95% confidence interval. RESULTS: One hundred eight patients were recruited from August 17, 2016 to June 8, 2018, and 4 patients were withdrawn. Twelve patients from 104 had mastectomy, with the remainder having less invasive surgery. Baseline QoR-15 global scores reported as median [quartiles] were 135 [129, 143] in the PECS group and 139 [127, 143] in the infiltration group. The 24-hour QoR-15 global score reported as median [quartiles] was 131 [116, 140] in the PECS group and 123 [117, 143] in the infiltration group (P = .60), with median difference (95% confidence interval) of -2 (-9 to 5). The median difference reported as infiltration minus PECS for QoR-15 domains was pain 0 (-2 to 1), physical comfort -1 (-3 to 2), physical independence 0 (-2 to 1), psychological support 0 (0-0), and emotions 0 (-1 to 2) (P > .28). The BPI pain subscale at 24 hours (0-40, lower score indicates less pain), reported as median [quartiles], was 7 [2, 13] in the PECS group and 10 [5, 17] in the infiltration group (P = .15). The BPI global score at 24 hours, reported as median [quartiles], was 20 [7, 36] in the PECS group and 23 [10, 43] in the infiltration group (P = .34) and at 3 months was 0 [0, 14] and 0 [0, 11] (P = .85). CONCLUSIONS: After mostly minor surgery for breast cancer, PECS II block was not superior to local infiltration by the surgeon.