Aggregation-induced emission: Application in diagnosis and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.

A rare case report of Prevotella lung abscess diagnosed using third-generation metagenomic sequencing.

The Prevotella genus consists of obligate anaerobic Gram-negative bacteria that are symbiotic with the oral, intestinal, and vaginal mucosa. While several species of Prevotella have been implicated in pulmonary infections, identification of Prevotella as the causative agent of lung abscess is uncommon because of the requirement for stringent anaerobic culture conditions. In this report, we highlight a case of lung abscess caused by Prevotella salivae and Prevotella veroralis, underscoring the importance of third-generation metagenomic sequencing using devices from Oxford Nanopore Technologies for the precise diagnosis of specific pathogens.

Adult Jejunojejunal Intussusception Caused by Small Bowel Leiomyoma.

This article reports a case of a patient with intestinal obstruction admitted to the hospital whose presumed diagnosis by CT was jejunojejunal intussusception. The patient underwent exploratory laparotomy with an enterectomy of the invaginated segment. The histopathological and immunohistochemical results of the surgical specimen confirmed the presence of a small bowel leiomyoma. This case highlights the importance of a detailed clinical evaluation of patients with an intestinal obstruction who seek emergency care. The cause of intestinal obstruction is a diagnostic challenge due to the numerous pathologies that can lead to the development of the condition. Guided anamnesis, detailed physical examinations, and accurate subsidiary exams that do not delay diagnosis are the cornerstones of emergency room care. Knowing the ideal time to refer the patient to the operating room requires knowledge and practice. The patient reported in this article with jejunal leiomyoma as a cause of intestinal intussusception is surprising for its rarity and illustrates the range of pathologies that can lead to intestinal obstruction.

[Research Progress of Artificial Intelligence in Prostate Cancer Diagnosis Application].

With the continuous advancement of artificial intelligence in the field of prostate cancer research, numerous studies have shown that AI performance can rival that of physicians. This review examines the recent applications and developments of AI in the early, accurate, and non-invasive diagnosis of prostate cancer, subsequently elucidating its importance, benefits, and limitations. The review emphasizes the exploration of the potential integration of AI with multi-omics and other cutting-edge technologies. Considering the current status of AI in prostate cancer diagnosis, the review summarizes the challenges faced in the clinical adoption of AI technologies and looks forward to improved and enhanced AI-based prostate cancer diagnostic techniques. The goal is to offer a reference for the integration of artificial intelligence into clinical practice.

Simultaneous noninvasive ultrasensitive detection of prostate specific antigen and lncRNA PCA3 using multiplexed dual optical microfibers with strong plasmonic nanointerfaces.

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10-15 mol/L and 1.56 × 10-14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals.

Dual-reporter fluorescent probe for precise identification of liver cancer by sequentially responding to carboxylesterase and polarity.

Early treatment significantly improves the survival rate of liver cancer patients, so the development of early diagnostic methods for liver cancer is urgent. Liver cancer can develop from viral hepatitis, alcoholic liver, and fatty liver, thus making the above diseases share common features such as elevated viscosity, reactive oxygen species, and reactive nitrogen species. Therefore, accurate differentiation between other liver diseases and liver cancer is both a paramount practical need and challenging. Numerous fluorescent probes have been reported for the diagnosis of liver cancer by detecting a single biomarker, but these probes lack specificity for liver cancer in complex biological systems. Obviously, using multiple liver cancer biomarkers as the basis for judgment can dramatically improve diagnostic accuracy. Herein, we report the first fluorescent probe, LD-TCE, that sequentially detects carboxylesterase (CE) and lipid droplet polarity in liver cancer cells with high sensitivity and selectivity, with linear detection of CE in the range of 0-6 U/mL and a 65-fold fluorescence enhancement in response to polarity. The probe first reacts with CE and releases weak fluorescence, which is then dramatically enhanced due to the decrease in lipid droplet polarity in liver cancer cells. This approach allows the probe to enable specific imaging of liver cancer with higher contrast and accuracy. The probe successfully achieved the screening of liver cancer cells and the precise identification of liver cancer in mice. More importantly, it is not disturbed by liver fibrosis, which is a common pathological feature of many liver diseases. We believe that the LD-TCE is expected to be a powerful tool for early diagnosis of liver cancer.

Accuracy of Telehealth Visits for Acute Care Needs in Family Medicine.

Introduction As primary care practices transition to a post-pandemic system of healthcare, it is important to recognize the benefits of offering telehealth services. Little research is available on the effectiveness of telehealth visits for managing acute illnesses or conditions in primary care practice. Methods Using the reporting functionality in the Epic™ electronic health record (EHR) (Epic Systems Corporation, Verona), a report was generated to identify all telehealth visit encounters that were completed in a family medicine clinic from March 1, 2020, to June 30, 2020. The report identified patients who had an acute complaint and required an in-office visit within 60 days of the telehealth encounter. If the patient required a face-to-face visit, that was not directed by the provider, the chart was reviewed to determine whether the diagnosis changed. The primary outcome was returning for a face-to-face visit within 30 days of the telehealth visit for the same acute need. Results The cohort included 349 telehealth visits for 303 patients. For patients who had more than one telehealth visit, only the first one was included in the analysis. Among the 303 patients, 50 (16.5%) returned for a face-to-face visit within 30 days of the telehealth visit (95% confidence interval: 12.5%-21.2%), and 71 (23.6%) returned for a telehealth visit within 60 days (95% confidence interval: 18.9%-28.8%). Furthermore, 19 of the 50 patients (38%) that returned for a face-to-face visit did not have a change in diagnosis, and, in some instances, the diagnosis made on the telehealth visit was only slightly different from the face-to-face visit. Discussion and conclusion Telehealth, specifically two-way, synchronous, interactive patient-provider communication through audio and video equipment, for acute care needs in a primary care practice helps reduce the need for in-person visits and can address patient complaints without the need for in-person follow-up.

Essentials for early diagnosis of primary intramedullary spinal cord lymphoma. How to suspect primary intramedullary spinal cord lymphoma early and proceed to invasive biopsy? A case report and literature review.

Background: Primary intramedullary spinal cord lymphoma (PISCL) is an extremely rare condition. Early diagnosis is very difficult due to the nonspecific clinical and imaging findings. A biopsy is essential for a definitive diagnosis, but courage is required to perform the surgery. Here, we present a case of PISCL and suggest useful indicators for accurate diagnosis of this pathological entity. Case Description: A 70-year-old woman presented with subacute bilateral lower-limb paralysis, disturbance of warm and pain sensations, and vesicorectal disturbance. Magnetic resonance imaging showed a contrast-enhanced mass from C7 to Th2 and large, edematous lesions from the upper cervical to lower thoracic spinal cord. Elevated uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) was identified in the enhanced regions on FDG-positron emission tomography (PET). Cerebrospinal fluid (CSF) analysis revealed highly elevated levels of ß2-microglobulin (ß2-MG). Steroid pulse therapy and therapeutic plasma exchange were performed for suspected myelitis, but symptoms did not improve. Spinal cord biopsy was, therefore, performed for treatment-resistant myelopathy. Histopathological examination revealed diffuse large B-cell lymphoma, which was diagnosed as PISCL because systemic examination showed no other findings suggestive of malignant lymphoma. Conclusion: In cases with poor response to treatment and a progressive course, PISCL should be considered, and spinal cord biopsy should be performed if PET shows increased 18F-FDG uptake and ß2-MG is elevated in CSF.

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

Rational Design of NIR-II Ratiometric Fluorescence Probes for Accurate Bioimaging and Biosensing In Vivo.

Intravital fluorescence imaging in the second near-infrared window (NIR-II, 900-1700 nm) has emerged as a promising method for non-invasive diagnostics in complex biological systems due to its advantages of less background interference, high tissue penetration depth, high imaging contrast, and sensitivity. However, traditional NIR-II fluorescence imaging, which is characterized by the "always on" or "turn on" mode, lacks the ability of quantitative detection, leading to low reproducibility and reliability during bio-detection. In contrast, NIR-II ratiometric fluorescence imaging can realize quantitative and reliable analysis and detection in vivo by providing reference signals for fluorescence correction, generating new opportunities and prospects during in vivo bioimaging and biosensing. In this review, the current design strategies and sensing mechanisms of NIR-II ratiometric fluorescence probes for bioimaging and biosensing applications are systematically summarized. Further, current challenges, future perspectives and opportunities for designing NIR-II ratiometric fluorescence probes are also discussed. It is hoped that this review can provide effective guidance for the design of NIR-II ratiometric fluorescence probes and promote its adoption in reliable biological imaging and sensing in vivo.

The grading diagnostic strategy of molecular autopsy combined with pathological autopsy in the forensic diagnosis of cardiomyopathy.

The diagnosis of cardiomyopathy often relies on the subjective judgment of pathologists due to the variety of morphologic changes in the condition and its low specificity. This uncertainty can contribute to unexplained sudden cardiac deaths (USCD). To enhance the accuracy of hereditary cardiomyopathy diagnosis in forensic medicine, we proposed a combination of molecular autopsy and pathologic autopsy. By analyzing 16 deceased patients suspected of cardiomyopathy, using whole exome sequencing (WES) in molecular autopsy, and applying a combined diagnostic strategy, the study found pathogenic or likely pathogenic variants in 6 cases. Out of the 16 cases, cardiomyopathy was confirmed in 3, while 3 exhibited conditions consistent with it. Data for 4 cases was inconclusive, and cardiomyopathy was ruled out in 6. Notably, a novel variant of the TTN gene was identified. This research suggests that a grading diagnostic strategy, combining molecular and pathological evidence, can improve the accuracy of forensic cardiomyopathy diagnosis. This approach provides a practical model and strategy for precise forensic cause-of-death determination, addressing the limitations of relying solely on morphologic assessments in cardiomyopathy cases, and integrating genetic information for a more comprehensive diagnosis.

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors.

Introduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy. Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO). Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells. Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

Comorbidity of bathing suit ichthyosis and limb-girdle muscular dystrophy type 2 A in a Tunisian patient revealed by Whole Exome Sequencing.

Elevated rates of consanguinity and inbreeding are responsible for the high prevalence of recessively inherited diseases among inbred populations including Tunisia. In addition, the co-occurrence of two of these conditions, called also comorbidity, within the same individual or in members of the same family are often described in Tunisia which is challenging for diagnosis. The high throughput sequencing has improved the diagnosis of inherited diseases. We report here on a 32-year-old woman born to consanguineous parents. She presented with congenital ichthyosis and muscular dystrophy. She was primarily suspected as suffering from Chanarin-Dorfman syndrome (CDS) with unusual form. Screening of founder mutations allowed only the elucidation of the molecular etiology of Ichthyosis. As the result was inconclusive, Whole Exome Sequencing (WES) was conducted. WES data analysis led to the identification of a mutation in the CAPN3 gene underlying limb-girdle muscular dystrophy type 2A (LGMD2A). Sanger sequencing confirmed the familial segregation of mutations. This work presents the first case worldwide of individual comorbidity of bathing suit ichthyosis and LGMD2A. The co-occurrence of two diseases should be systematically considered when establishing a diagnosis especially in consanguineous populations. WES is a powerful tool for molecular diagnosis in particular for revealing comorbidities and rectifying the diagnosis.

Portable and Rapid Dual-Biomarker Detection Using Solution-Gated Graphene Field Transistors in the Accurate Diagnosis of Prostate Cancer.

Prostate-specific antigen (PSA) is the common serum-relevant biomarker for early prostate cancer (PCa) detection in clinical diagnosis. However, it is difficult to accurately diagnose PCa in the early stage due to the low specificity of PSA. Herein, a new solution-gated graphene field transistor (SGGT) biosensor with dual-gate for dual-biomarker detection is designed. The sensing mechanism is that the designed aptamers immobilized on the surface of the gate electrodes can capture PSA and sarcosine (SAR) biomolecules and induce the capacitance changes of the electric double layers of SGGT. The limit of detections of PSA and SAR biomarkers can reach 0.01 fg mL-1 , which is three-to-four orders of magnitude lower than previously reported assays. The detection time of PSA and SAR is ≈4.5 and ≈13 min, which is significantly faster than the detection time (1-2 h) of conventional methods. The clinical serum samples testing demonstrates that the biosensor can distinguish the PCa patients from the control group and the diagnosis accuracy can reach 100%. The SGGT biosensor can be integrated into the portable platform and the diagnostic results can directly display on the smartphone/Pad. Therefore, the integrated portable platform of the biosensor can distinguish cancer types through the dual-biomarker detection.

Association of arbitrary prescribing behavior to costly drug expenditures: a pharmacoeconomic study in primary care.

BACKGROUND: We aimed to examine the cost-related prescribing performance of primary care physicians who had a higher versus lower tendency of arbitrary prescribing. METHODS: In this cross-sectional study, we evaluated the prescriptions of primary care physicians in Istanbul, collected with 3:1 systematic sampling. We determined higher versus lower arbitrary prescribing by the physician's degree of writing the solo diagnosis of "Z00- General examination without diagnosis/complaint": those for whom such prescriptions constituted >5% were classified as Group A and those with them at <0.5% as Group B. We compared these two groups by the total and disease-specific drug costs per prescription they produced for 10 frequently encountered indications. RESULTS: The median cost of disease-specific medication for all diagnoses in Group A and Group B, except anemia, was equal. In upper respiratory tract infections (URTIs), hypertension, anemia, diabetes, and conjunctivitis, the mean prescription costs of Group A were significantly higher than those of Group B (P < .001, P < .001, P = .009, P = .007, and P < .001, respectively), whereas disease-specific drug costs per prescription were similar (P > .05 in all diagnoses). In myalgia, Group A had lower cost per prescription (P < .001) and higher analgesic costs per prescription (P < .001) compared to those in Group B. We found significantly higher disease-specific drug cost share in Group B for URTIs (antibiotic), gastroesophageal reflux disease (gastric acid-suppressant), hypertension (antihypertensive), anemia (iron preparations), diabetes (antidiabetic), depression (antidepressant), and conjunctivitis (corticosteroid) than those in Group A (P < .001 for each). CONCLUSIONS: Our study showed that physicians who had a higher tendency of prescribing for no clear indication are also more likely to produce costly prescriptions.

NIR-propelled Janus nanomotors for active photoacoustic imaging and synergistic photothermal/chemodynamic therapy.

Synthetic nanomotors have great application potential in deep tissue imaging and tumor treatment due to their active movement ability. Herein, a novel near infrared (NIR) light-driven Janus nanomotor is reported for active photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT). Au nanoparticles (Au NPs) are sputtered on the half-sphere surface of copper-doped hollow cerium oxide nanoparticles after bovine serum albumin (BSA) modification. Such Janus nanomotors exhibit a rapid autonomous motion with a maximum speed of 110.6 ± 0.2 µm/s under 808 nm laser irradiation with a density of 3.0 W/cm2. With the assistance of light-powered motion, the Au/Cu-CeO2@BSA nanomotors (ACCB Janus NMs) can effectively adhere to and mechanically perforate tumor cells, thereby causing the higher cellular uptake and significantly enhancing the tumor tissue permeability in the tumor microenvironment (TME). ACCB Janus NMs also exhibit high nanozyme activity that can catalyze the production of reactive oxygen species (ROS) to reduce the TME oxidative stress response. Meanwhile, the potential PA imaging capability of ACCB Janus NMs offer promise for early diagnosis of tumors due to the photothermal conversion efficiency of Au NPs. Therefore, the nanotherapeutic platform provides a new tool for effectively imaging of deep tumors site in vivo to achieve synergistic PTT/CDT and accurate diagnosis.

Clinical manifestations, diagnosis, treatment, and outcome of pyogenic liver abscess: a retrospective study.

OBJECTIVE: The incidence of pyogenic liver abscess (PLA) continues to rise, yet atypical clinical symptoms result in considerable incidence of misdiagnosis. This study was conducted to identify potential warning indicators and summarize efficacious diagnostic and therapeutic approaches for potential clinical guidelines. METHODS: Hospitalized patients aged ≥18 years and diagnosed with PLA were included in this retrospective study. Data were collected from participant's clinical records. Patients were grouped according to type 2 diabetes mellitus status and ultrasound-guided percutaneous drainage (USPD). Between-group differences were analysed with Student's t-test. RESULTS: A total of 104 hospitalized patients were included, 33 of whom (31.73%) had type 2 diabetes. Procalcitonin levels were raised in all patients, suggesting potential effectiveness and sensitivity as a warning marker for PLA. Contrast-enhanced computed tomography was the most frequently used method (63.46% of cases) for diagnosing PLA. Klebsiella pneumoniae was the main pathogen found in patients with PLA in southeast China (isolated in 92.86% [26/28] of positive blood cultures and 90.70% [39/43] of positive abscess fluid cultures). Duration of hospital stay was shorter in patients who received USPD versus those who did not (17.91 ± 6.84 days versus 21.47 ± 9.82 days). CONCLUSION: Types of PLA-susceptible patients, infection markers, highly sensitive imaging techniques and clinical treatment options were identified. These results may help with early accurate diagnosis of patients with PLA, avoiding treatment delay.

Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms.

Objective: To retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China. Methods: A retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis. Results: In total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common. Conclusion: The accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

Machine learning method for the cellular phenotyping of nasal polyps from multicentre tissue scans.

BACKGROUND: This study aimed to establish a convenient and accurate chronic rhinosinusitis evaluation platform CRSAI 1.0 according to four phenotypes of nasal polyps. RESEARCH DESIGN AND METHODS: Tissue sections of a training (n = 54) and test cohort (n = 13) were sourced from the Tongren Hospital, and those for a validation cohort (n = 55) from external hospitals. Redundant tissues were automatically removed by the semantic segmentation algorithm of Unet++ with Efficientnet-B4 as backbone. After independent analysis by two pathologists, four types of inflammatory cells were detected and used to train the CRSAI 1.0. Dataset from Tongren Hospital were used for training and testing, and validation tests used the multicentre dataset. RESULTS: The mean average precision (mAP) in the training and test cohorts for tissue eosinophil%, neutrophil%, lymphocyte%, and plasma cell% was 0.924, 0.743, 0.854, 0.911 and 0.94, 0.74, 0.839, and 0.881, respectively. The mAP in the validation dataset was consistent with that of the test cohort. The four phenotypes of nasal polyps varied significantly according to the occurrence of asthma or recurrence. CONCLUSIONS: CRSAI 1.0 can accurately identify various types of inflammatory cells in CRSwNP from multicentre data, which could enable rapid diagnosis and personalized treatment.