Hasil untuk "Medicine (General)"

RenHui Wu, MengMeng Yang, TianChi Wu et al.

Background In recent years, skin health has garnered widespread attention, with hyperpigmentation disorders caused by excessive melanin deposition emerging as a particularly prominent concern. Tyrosinase, as the rate-limiting enzyme in the melanin synthesis process, has long been a major focus in the development of its inhibitors. However, only a limited number of tyrosinase inhibitors are currently available for clinical treatment of such disorders, and they are associated with certain toxicity concerns. Consequently, there is an urgent need to develop novel inhibitors that combine high efficacy with low toxicity. Recent studies have shown that deep learning technology exhibits strong capabilities in uncovering the intrinsic patterns of data and predicting the biological activities of compounds, providing a significant opportunity for the rapid screening of novel tyrosinase inhibitors. Methods Based on a dataset of tyrosinase-related compounds, this study constructed a deep learning model to predict compounds that inhibit tyrosinase activity. Using this model, we conducted activity predictions for 36,585 compound and selected the top 100 molecules with the highest prediction scores for screening and verification. Results Literature comparison revealed that 53 of these molecules had been reported to inhibit tyrosinase activity, providing initial support for the model’s reliability. After further screening based on specific criteria, 10 candidate molecules were ultimately selected for molecular docking studies. The docking results indicated that these molecules had good binding potential with the target protein, indirectly supporting the accuracy of the model’s prediction. The final experimental verification revealed that compounds 5 and 10 significantly inhibited tyrosinase activity and reduced melanin content.

F. J. D. Lange, Juliane C. Wilcke, Sabine Hoffmann et al.

Empirical substantive research, such as in the life or social sciences, is commonly categorized into the two modes exploratory and confirmatory, both of which are essential to scientific progress. The former is also referred to as hypothesis-generating or data-contingent research, while the latter is also called hypothesis-testing research. In the context of empirical methodological research in statistics, however, the exploratory-confirmatory distinction has received very little attention so far. Our paper aims to fill this gap. First, we revisit the concept of empirical methodological research through the lens of the exploratory-confirmatory distinction. Second, we examine current practice with respect to this distinction through a literature survey including 115 articles from the field of biostatistics. Third, we provide practical recommendations toward a more appropriate design, interpretation, and reporting of empirical methodological research in light of this distinction. In particular, we argue that both modes of research are crucial to methodological progress, but that most published studies -- even if sometimes disguised as confirmatory -- are essentially exploratory in nature. We emphasize that it may be adequate to consider empirical methodological research as a continuum between "pure" exploration and "strict" confirmation, recommend transparently reporting the mode of conducted research within the spectrum between exploratory and confirmatory, and stress the importance of study protocols written before conducting the study, especially in confirmatory methodological research.

Yannan Cao, Yixin Wang, Hang Liu et al.

With the development of artificial intelligence (AI), AI-related technologies are being applied in many fields of medicine. Anesthesia is now widely used in surgery, emergency resuscitation, pain treatment and other fields. However, different from some other common biomedical signals, such as the electrocardiogram (ECG), electroencephalogram (EEG), and some other medical imaging or biomarkers could be easily processed and analyzed by AI-related models, how to collect the relevant data in the anesthesia process is still a challenge, that has led to little current work on combining AI and anesthesia. However, it can be foreseen that the combination of AI and anesthesia will become increasingly important. This paper presents a comprehensive review of anesthesia with AI based methods which have been now used in the preoperative phase, intraoperative phase, and postoperative phase. We first overview some crucial concepts of artificial intelligence, then discuss the related applications of artificial intelligence used in different phases of the anesthesia period, finally, we look forward to the future development of intelligent anesthesia. We hope through this review, we can provide comprehensive and objective guidance in AI-related anesthesia process to help anesthesiologists use more advanced AI techniques to diagnose and treat patients during the anesthesia period.

Nils Wetzstein, Margo Diricks, Thomas B. Anton et al.

Abstract Background The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. Methods Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. Results Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04–0.28, p < 0.001 and OR 0.11 95% CI 0.02–0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). Conclusions This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.

Gembe M, Tariku T, Tesfaye T et al.

Maycas Gembe,1 Tizita Tariku,1 Temamen Tesfaye,2 Endalew Hailu Hailu2 1Department of Nursing, College of Health Science, Mattu University, Mattu, Ethiopia; 2School of Nursing, Faculty of Health Science, Jimma University, Jimma, EthiopiaCorrespondence: Maycas Gembe, Tel +251 936704900, Email MaycasDembelu27@gmail.comIntroduction: Palliative care is not yet widely available. Each year, approximately 58 million people worldwide require palliative care. In Africa, an estimated 9.7 million people require palliative care. In Ethiopia, the integration of palliative care into the country’s health system has taken several years. Previous studies conducted on palliative care have emphasized on the knowledge of nurses towards palliative care, and some studies have attempted to assess the practice of palliative care in specific areas of the country. However, we studied the practice of palliative care at a national level. So, the purpose of the study is to identify nurses’ palliative care practice level and factors associated with palliative care.Methods: We employed a facility-based cross-sectional study design to assess palliative care practices. We considered tertiary hospitals with functional cancer centers. To conduct this study, we included nurses from three hospitals; we recruited 255 nurses from these hospitals. The dependent variable of palliative care practice of nurses was first measured in continuous scale measurement and then converted to dichotomous outcome variable based on a 75% score cutoff value. Based on the multivariable logistic regression output, we considered variables with a p-value of < 0.05 as the factors significantly associated with good palliative care practice.Results: We collected data from 249 nurses, with a response rate of 98%. Based on our findings, 57% of nurses had good palliative care practices. We also identified that the type of healthcare facility, nurses’ knowledge of palliative care, nurses’ level of academic qualification, and nurses’ attitudes towards palliative care were factors associated with the level of palliative care practice.Conclusion: This score of palliative care practice level should be improved. The Federal Ministry of Health, along with healthcare facilities in general and tertiary hospitals in particular, should strengthen good palliative care practice by providing up-to-date training for nurses.Keywords: palliative care, nurses, tertiary hospital, Ethiopia

Kanankira A Nnko, Raphael T Pima, Calvin J Baraka et al.

Verrucous carcinoma is a well-recognized low-grade variant of squamous cell carcinoma. Cutaneous, oral, and anogenital forms exist. Exposure to persistent chronic irritation, inflammation, and repeated injury, as well as carcinogenic agents such as human papillomavirus infection, smoking, and alcohol use, are established risk factors. These neoplasms occur mostly in the oral cavity. The usual extraoral sites include the larynx, esophagus, genitals, and perineum. It is an extremely uncommon site of occurrence for the extraoral chin region. This unusual location makes the index case unique. Other uncommon sites reported include finger and foot. Case studies of verrucous carcinoma with huge tumor sizes are rare. Although it can be destructive locally, verrucous carcinoma typically does not spread to distant sites. Wide surgical excision with free margins is the most common treatment approach with a favorable prognosis. These tumors are likely to recur if they are incompletely excised, and recurred lesions tend to be more aggressive clinically as compared to their original counterparts. Herein, the authors describe a case of a huge oral verrucous carcinoma localized on the chin of a 43-year-old female patient. The clinical course, diagnostics, and proposed treatment have been discussed with the existing available literature.

Dimi Nyanga Y.I, Ondziel Opara S, Mouamba F et al.

ABSTRACT Le lichen plan (LP) est une maladie inflammatoire chronique cutanéomuqueuse dont les facteurs étiopathogéniques sont incertains. Il est rare dans la population générale et présente une multitude d’expressions cliniques ainsi qu’une diversité de localisations topographiques pouvant être isolées ou associées. La localisation unique et isolée du LP au niveau de la verge est rare, et son association avec l’infection à VIH n’est commune. Nous rapportons un cas de lichen plan hypertrophique de la verge chez un adulte de 66 ans séropositif au VIH qui a présenté une récidive de LP de la verge. Le LP se présentait comme une vaste lésion hypertrophique, hypochromique, siégeant au niveau de la face ventrale de la verge allant du gland jusqu’à la racine de la verge, enduite de plaques blanchâtres en sa périphérie. L’examen histologique a confirmé le diagnostic. La prise en charge en charge médico-chirurgicale a donné des résultats satisfaisants Cette observation souligne le fait que les lésions hypertrophiques de la verge doivent faire évoquer un LP, surtout chez le sujet immunodéficient. RÉSUMÉ Lichen planus (LP) is a chronic cutaneous-mucosal inflammatory disease whose etiopathogenic factors are uncertain. It is rare in the general population, and presents with a multitude of clinical expressions, as well as a diversity of topographical localizations that may be isolated or associated. Isolated, single localization of LP on the penis is rare, and its association with HIV infection is uncommon. We report a case of hypertrophic lichen planus of the penis in a 66-year-old HIV-positive adult who presented with a recurrence of LP of the penis. The LP presented as a large, hypertrophic, hypochromic lesion on the ventral surface of the penis, from the glans to the root of the penis, with whitish plaques around the periphery. Histological examination confirmed the diagnosis. This observation underlines the fact that hypertrophic lesions of the penis should raise the suspicion of LP, especially in immunodeficient subjects.

Merle Munko, Marc Ditzhaus, Dennis Dobler et al.

Several methods in survival analysis are based on the proportional hazards assumption. However, this assumption is very restrictive and often not justifiable in practice. Therefore, effect estimands that do not rely on the proportional hazards assumption are highly desirable in practical applications. One popular example for this is the restricted mean survival time (RMST). It is defined as the area under the survival curve up to a prespecified time point and, thus, summarizes the survival curve into a meaningful estimand. For two-sample comparisons based on the RMST, previous research found the inflation of the type I error of the asymptotic test for small samples and, therefore, a two-sample permutation test has already been developed. The first goal of the present paper is to further extend the permutation test for general factorial designs and general contrast hypotheses by considering a Wald-type test statistic and its asymptotic behavior. Additionally, a groupwise bootstrap approach is considered. Moreover, when a global test detects a significant difference by comparing the RMSTs of more than two groups, it is of interest which specific RMST differences cause the result. However, global tests do not provide this information. Therefore, multiple tests for the RMST are developed in a second step to infer several null hypotheses simultaneously. Hereby, the asymptotically exact dependence structure between the local test statistics is incorporated to gain more power. Finally, the small sample performance of the proposed global and multiple testing procedures is analyzed in simulations and illustrated in a real data example.

Santiago Hernández-Orozco, Abicumaran Uthamacumaran, Francisco Hernández-Quiroz et al.

For more than two decades, advances in personalised medicine and precision healthcare have largely been based on genomics and other omics data. These strategies aim to tailor interventions to individual patient profiles, promising greater treatment efficacy and more efficient allocation of healthcare resources. Here, we show that widely collected common haematologic markers can reliably predict and discriminate individual chronological age and health status from even noisy sources. Our analysis includes synthetic and real retrospective patient data, including medically relevant and extreme cases, and draws on more than 100\,000 complete blood count records over 13 years from the United States Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (CDC NHANES). We combine fully explainable risk assessment scores with machine and deep learning techniques to focus on clinically significant patterns and characteristics without functioning purely as a ''black-box model allowing interpretation and control. We validated the results with the UK Biobank, a larger cohort independent of the CDC NHANES and with very different collection techniques, the former a survey and the second a longitudinal study. Unlike current biological ageing indicators, this approach may offer rapid, and scalable implementations of personalised, precision and predictive approaches to healthcare and medicine without or before requiring other specialised, uncommon or costly tests.

Eva Steinke, Eva Steinke, Eva Steinke et al.

BackgroundLung disease as major cause for morbidity in patients with cystic fibrosis (CF) starts early in life. Its large phenotypic heterogeneity is partially explained by the genotype but other contributing factors are not well delineated. The close relationship between mucus, inflammation and infection, drives morpho-functional alterations already early in pediatric CF disease, The TRACK-CF cohort has been established to gain insight to disease onset and progression, assessed by lung function testing and imaging to capture morpho-functional changes and to associate these with risk and protective factors, which contribute to the variation of the CF lung disease progression.Methods and designTRACK-CF is a prospective, longitudinal, observational cohort study following patients with CF from newborn screening or clinical diagnosis throughout childhood. The study protocol includes monthly telephone interviews, quarterly visits with microbiological sampling and multiple-breath washout and as well as a yearly chest magnetic resonance imaging. A parallel biobank has been set up to enable the translation from the deeply phenotyped cohort to the validation of relevant biomarkers. The main goal is to determine influencing factors by the combined analysis of clinical information and biomaterials. Primary endpoints are the lung clearance index by multiple breath washout and semi-quantitative magnetic resonance imaging scores. The frequency of pulmonary exacerbations, infection with pro-inflammatory pathogens and anthropometric data are defined as secondary endpoints.DiscussionThis extensive cohort includes children after diagnosis with comprehensive monitoring throughout childhood. The unique composition and the use of validated, sensitive methods with the attached biobank bears the potential to decisively advance the understanding of early CF lung disease.Ethics and trial registrationThe study protocol was approved by the Ethics Committees of the University of Heidelberg (approval S-211/2011) and each participating site and is registered at clinicaltrials.gov (NCT02270476).

Johannes von Büren, Inga Hansen, Julian Kött et al.

Objective The use of direct-to-consumer (DTC) teledermatology platforms has increased, particularly for androgenetic alopecia (AGA). However, little is known about the efficacy and safety of these platforms. This study aimed to investigate the patient-reported treatment outcomes and safety of DTC teledermatology for the finasteride treatment of male AGA. Methods This retrospective, cross-sectional study used data from a German DTC platform for finasteride treatment between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided to the patients six weeks after the first prescription to assess treatment outcomes and safety. Results Data collection included 2269 patients. Of all patients who answered the follow-up questionnaire ( n  = 191), 79% (150 out of 191) self-reported positive changes in hair appearance, and 59% (113 out of 191) reported an improvement in self-esteem under treatment. Patients with self-reported positive changes in hair appearance were more likely to report improved self-esteem ( P  < 0.0001). Treatment-related adverse events occurred in 12% (22 out of 191) of the patients. Full treatment adherence was reported in 87% (167 out of 191) of patients. Conclusion From the patient's perspective, DTC teledermatology has the potential to improve hair appearance and self-esteem. Our results suggest that it may be an effective and safe treatment option for men with AGA, justifying low-threshold access. However, treatment-related adverse events should be closely monitored during follow-up. Further studies are required to evaluate the long-term effects of the DTC teledermatology treatment. By collecting real-world data, teledermatology platforms could be useful beyond their primary focus and could play an important role in the context of future research.

Mallana Gowdra Mallikarjuna, Manish Kumar Pandey, Rinku Sharma et al.

Raushan Buzyakova

We study topological groups of monotonic autohomeomorphisms on a generalized ordered space $L$. We find a condition that is necessary and sufficient for the set of all monotonic autohomeomorphisms on $L$ along with the function composition and the topology of point-wise convergence to be a topological group.

Cristina Garbacea, Qiaozhu Mei

Recent advances in deep neural language models combined with the capacity of large scale datasets have accelerated the development of natural language generation systems that produce fluent and coherent texts (to various degrees of success) in a multitude of tasks and application contexts. However, controlling the output of these models for desired user and task needs is still an open challenge. This is crucial not only to customizing the content and style of the generated language, but also to their safe and reliable deployment in the real world. We present an extensive survey on the emerging topic of constrained neural language generation in which we formally define and categorize the problems of natural language generation by distinguishing between conditions and constraints (the latter being testable conditions on the output text instead of the input), present constrained text generation tasks, and review existing methods and evaluation metrics for constrained text generation. Our aim is to highlight recent progress and trends in this emerging field, informing on the most promising directions and limitations towards advancing the state-of-the-art of constrained neural language generation research.

RT Pramod, Michael A Cohen, Joshua B Tenenbaum et al.

Successful engagement with the world requires the ability to predict what will happen next. Here, we investigate how the brain makes a fundamental prediction about the physical world: whether the situation in front of us is stable, and hence likely to stay the same, or unstable, and hence likely to change in the immediate future. Specifically, we ask if judgments of stability can be supported by the kinds of representations that have proven to be highly effective at visual object recognition in both machines and brains, or instead if the ability to determine the physical stability of natural scenes may require generative algorithms that simulate the physics of the world. To find out, we measured responses in both convolutional neural networks (CNNs) and the brain (using fMRI) to natural images of physically stable versus unstable scenarios. We find no evidence for generalizable representations of physical stability in either standard CNNs trained on visual object and scene classification (ImageNet), or in the human ventral visual pathway, which has long been implicated in the same process. However, in frontoparietal regions previously implicated in intuitive physical reasoning we find both scenario-invariant representations of physical stability, and higher univariate responses to unstable than stable scenes. These results demonstrate abstract representations of physical stability in the dorsal but not ventral pathway, consistent with the hypothesis that the computations underlying stability entail not just pattern classification but forward physical simulation.

S. Martin

Hector M Baillie

The words ‘Final Examination’ when applied to medical training seems inappropriate. Learning is lifelong, but there have to be milestones where judgement happens. In particular, an Oral Exam can invoke all sorts of excitement.