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Abstract The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy.Main bodyA 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient’s condition.ConclusionThe combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

Abstract Accurate target detection in complex orchard environments is the basis for automatic picking and pollination. The characteristics of small, clustered and complex interference greatly increase the difficulty of detection. Toward this end, we explore a detector in the orchard and improve the detection ability of complex targets. Our model includes two core designs to make it suitable for reducing the risk of error detection due to small and camouflaged object features. Multi-scale texture enhancement design focuses on extracting and enhancing more distinguishable features for each level with multiple parallel branches. Our adaptive region-aware feature fusion module extracts the dependencies between locations and channels, potential cross-relations among different levels and multi-types information to build distinctive representations. By combining enhancement and fusion, experiments on various real-world datasets show that the proposed network can outperform previous state-of-the-art methods, especially for detection in complex conditions.

Abstract Background Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short‐ and long‐term outcomes of RTG and laparoscopic total gastrectomy (LTG). Methods A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short‐ and long‐term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared. Results After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p

The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae. The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.

We obtain a characterization of bijective maps preserving the trace of products on the set of tensor products of rank-1 idempotents, which may be considered as a generalization of Molnár’s Wigner-type theorem in multipartite systems. The proof is based on the studies in linear preserver problems on tensor products. Moreover, a corresponding result on the finite-dimensional case is presented.

Objective To investigate the association of fat and lean mass in specific regions with all-cause and cardiovascular-related mortality.Design Population based cohort study.Setting US National Health and Nutrition Examination Survey (2003–2006 and 2011–2018).Participants 22 652 US adults aged 20 years or older.Exposures Fat and lean mass in specific regions obtained from the whole-body dual-energy X-ray absorptiometry.Main outcome measures All-cause and cardiovascular-related mortality.Results During a median of 83 months of follow-up, 1432 deaths were identified. Associations between body composition metrics and mortality risks were evident above specific thresholds. For all-cause mortality, Android fat mass showed elevated HRs above 2.46 kg (HR: 1.17, 95% CI 1.02 to 1.34), while Android lean mass (ALM) had similar trends above 2.75 kg (HR: 1.17, 95% CI 1.03 to 1.33), and Android total mass above 5.75 kg (HR: 1.08, 95% CI 1.01 to 1.16). Conversely, lower HRs were observed below certain thresholds: Gynoid fat mass (GFM) below 3.71 kg (HR: 0.72, 95% CI 0.56 to 0.93), Gynoid lean mass below 6.44 kg (HR: 0.77, 95% CI 0.64 to 0.92), and Gynoid total mass below 11.78 kg (HR: 0.76, 95% CI 0.70 to 0.84). Notably, below 0.722 kg, the HR of visceral adipose tissue mass (VATM) was 1.25 (95% CI 1.04 to 1.48) for all-cause mortality, and above 3.18 kg, the HR of total abdominal fat mass was 2.41 (95% CI 1.15 to 5.05). Cardiovascular-related mortality exhibited associations as well, particularly for Android fat mass (AFM) above 1.78 kg (HR: 1.22, 95% CI 1.01 to 1.47) and below 7.16 kg (HR: 0.50, 95% CI 0.36 to 0.69). HRs varied for Gynoid total mass below and above 10.98 kg (HRs: 0.70, 95% CI 0.54 to 0.93, and 1.12, 95% CI 1.02 to 1.23). Android per cent fat, subcutaneous fat mass (SFM), AFM/GFM, and VATM/SFM were not statistically associated with all-cause mortality. Android per cent fat, Gynoid per cent fat, AFM/GFM, and VATM/SFM were not statistically associated with cardiovascular-related mortality. Conicity index showed that the ALM/GLM had the highest performance for all-cause and cardiovascular-related mortality with AUCs of 0.785, and 0.746, respectively.Conclusions The relationship between fat or lean mass and all-cause mortality varies by region. Fat mass was positively correlated with cardiovascular mortality, regardless of the region in which they located. ALM/GLM might be a better predictor of all-cause and cardiovascular-related mortality than other body components or body mass index.

Abstract Objective To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. Methods The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell’s concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. Results In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C‐index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. Conclusion The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

Introduction Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC.Methods and analysis The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients’ quality of life.Ethics and dissemination All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals.Trial registration number NCT05352802.

Abstract Background Neuro-oncological ventral antigen 1 (NOVA1) is a neuron-specific RNA-binding protein which regulates alternative splicing in the developing nervous system. Recent research has found that NOVA1 plays a significant role in carcinogenesis. In this paper, we examine the role of NOVA1 in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms. Methods The expression of NOVA1 in NSCLC was detected by immunohistochemistry and correlations between NOVA1 expression and clinicopathological factors were analyzed by chi–square tests. Kaplan–Meier survival analysis and the Cox regression model were used to evaluate the predictive effect of prognostic factors. Western blotting, Cell Counting Kit-8, colony formation, apoptosis, migration and invasion assays were used to detect the effects of silencing (si)NOVA1 RNA on Wnt/β-catenin signaling and biological behavior in NSCLC cell lines. Results Our study showed that expression of NOVA1 was up-regulated and significantly correlated with poor differentiation (p = 0.020), advanced TNM stage (P = 0.001), T stage (P = 0.001) and lymph node metastasis (P = 0.000) as well as the expression of β-catenin (P = 0.012) in NSCLC. The down-regulation of NSCLC by siRNA significantly inhibited proliferation, migration and invasion and promoted apoptosis in NSCLC cells. Expression of Wnt signaling molecules, including β-catenin, activated β-catenin, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-7, was also significantly reduced by siNOVA1. The inhibition of Wnt/β-catenin signaling in A549 and H1299 cells by siNOVA1 was reversed after treatment with a β-catenin expression plasmid. Conclusion The present study suggests that NOVA1 may serve as a potential prognosis biomarker in NSCLC. High NOVA1 expression was associated with poor survival rate. Finally, in vitro experiments verified that NOVA1 promotes NSCLC cell proliferation and invasion by regulating Wnt/β-catenin signaling.

Abstract Background Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes. Method The GISSG 20–01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS. Discussion It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy. Trial registration ClinicalTrials.gov , NCT04636099. Registered November 19, 2020

The preferred treatment for lung cancer is surgical resection, but a large number of patients are not suitable for surgical resection in clinic. CT-guided cryoablation and immunotherapy can play an important role in patients with advanced lung cancer who are ineligible for surgery. CT-guided cryoablation has been widely used in the clinical treatment of lung tumors due to its advantages of less trauma, fewer complications, significant efficacy and rapid recovery. Cryoablation can not only cause tumor necrosis and apoptosis, but also promote the release of tumor-derived autoantigens into the blood circulation, and stimulate the host immune system to produce a good anti-tumor immune effect against primary and metastatic tumors. Since the study of immune checkpoint inhibitors has proved that lung cancer can be an immunotherapeutic response disease, the relationship between cryoablation and immunotherapy of lung cancer has been paid more attention. Therefore, we reviewed the literature on cryoablation for lung cancer, as well as the research progress of cryoablation combined with immunotherapy.

Abstract Background The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer. Methods/design This study is a prospective, multicentre RCT. This experiment will consist of two groups – an experimental group and a control group – randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups. Discussion The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer. Trial registration Chinese Clinical Trial Registry, CHiCTR1900022438 . Registered on 11 April 2019.

IntroductionPancreatic neuroendocrine neoplasms (PNENs) are rare pancreatic tumors originating from pancreatic neuroendocrine cells. There is no consensus on the treatment for PNENs with unresectable liver metastases. Transcatheter arterial chemoembolization (TACE) is the preferred treatment for unresectable primary liver cancer. But the efficacy of TACE and anticoagulation in PNENs with unresectable liver metastases and portal vein thrombosis has never been reported.Methods and ResultsWe present the case of a 50-year-old male patient with hepatitis C who was found to have a single liver mass during a regular physical examination in 2016. The liver mass was surgically removed. Postoperative pathology suggested a neuroendocrine tumor of the liver, and it was suggested to look for the primary tumor. The patient was followed up until 2020, and the primary pancreatic tumor was found, along with multiple liver metastases and portal vein thrombosis. After transcatheter arterial embolization, anticoagulation, and endocrine therapy, the patient’s tumor load was relieved, and the portal vein was recanalized.ConclusionThe article reports the disease course in a case of a functional pancreatic neuroendocrine tumor with liver metastasis and portal vein thrombosis and reviews previous literature. To our knowledge, we reported for the first time the efficacy of TACE and anticoagulation in PNENs with unresectable liver metastases and portal vein thrombosis.

Discovering novel biomarkers that easily accessed is a key step towards the personalized medicine approach for gastric cancer patients. Integrin-β6 (ITGB6) is a subtype of integrin that is exclusively expressed on the surface of epithelial cells and is up-regulated in various tumors. In the present study, a retrospective cohort with 135 gastric cancer patients and a prospective cohort with 34 gastric cancer patients were constructed, ITGB6 expression were detected in both the serum specimens and the tissue specimens. Detailed clinicopathological parameters as well as patients’ survival were recorded. A nomogram including ITGB6 expression was also constructed and validated to predict the prognosis of gastric cancer patients. Results showed that serum ITGB6 expression was obviously increased and associated with tumor stage in gastric cancer patients, serum ITGB6 expression was relatively high in patients with liver metastasis. High ITGB6 expression indicated a poor prognosis, and nomogram including serum ITGB6 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. Furthermore, combined serum ITGB6 and CEA levels contributed to the risk stratification and prognostic prediction for gastric cancer patients. In addition, the serum expression of ITGB6 decreased significantly after radical surgery, and a new rise in serum ITGB6 expression indicated tumor recurrence or progression. The present study identified a novel serum biomarker for the risk stratification, prognostic prediction and surveillance of gastric cancer patients.

A 55-year-old man developed deep venous thrombosis and inferior vena cava (IVC) thrombosis 7 years earlier and was treated by placement of a permanent IVC filter. One week ago, he was admitted with bilateral lower limb swelling and pain. Digital subtraction angiography showed a filling defect above the original filter. A retrievable Tulip filter was placed and catheter-directed thrombolysis was performed. Six days later, the patient experienced sudden, persistent upper right abdominal pain, and a computed tomography scan revealed the formation of retroperitoneal hematoma. Symptomatic treatments were administered, and the hematoma gradually resolved during follow-up.

Chitosan (CTS) is a deacetylated derivative of chitin that is involved in adaptive response to abiotic stresses. However, the regulatory role of CTS in heat tolerance is still not fully understood in plants, especially in grass species. The aim of this study was to investigate whether the CTS could reduce heat-induced senescence and damage to creeping bentgrass associated with alterations in antioxidant defense, chlorophyll (Chl) metabolism, and the heat shock pathway. Plants were pretreated exogenously with or without CTS (0.1 g L−1) before being exposed to normal (23/18 °C) or high-temperature (38/33 °C) conditions for 15 days. Heat stress induced detrimental effects, including declines in leaf relative water content and photochemical efficiency, but significantly increased reactive oxygen species (ROS) accumulation, membrane lipid peroxidation, and Chl loss in leaves. The exogenous application of CTS significantly alleviated heat-induced damage in creeping bentgrass leaves by ameliorating water balance, ROS scavenging, the maintenance of Chl metabolism, and photosynthesis. Compared to untreated plants under heat stress, CTS-treated creeping bentgrass exhibited a significantly higher transcription level of genes involved in Chl biosynthesis (AsPBGD and AsCHLH), as well as a lower expression level of Chl degradation-related gene (AsPPH) and senescence-associated genes (AsSAG12, AsSAG39, Asl20, and Ash36), thus reducing leaf senescence and enhancing photosynthetic performance under heat stress. In addition, the foliar application of CTS significantly improved antioxidant enzyme activities (SOD, CAT, POD, and APX), thereby effectively reducing heat-induced oxidative damage. Furthermore, heat tolerance regulated by the CTS in creeping bentgrass was also associated with the heat shock pathway, since AsHSFA-6a and AsHSP82 were significantly up-regulated by the CTS during heat stress. The potential mechanisms of CTS-regulated thermotolerance associated with other metabolic pathways still need to be further studied in grass species.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a standard treatment option for the management of portal hypertension in liver cirrhosis. Since the introduction of covered stents, shunt patency has been greatly improved. However, it remains uncertain about whether covered stents could improve survival. A meta-analysis of randomized controlled trials has been performed to compare the outcomes of covered versus bare stents for TIPS. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to identify the relevant randomized controlled trials. Overall survival, shunt patency, and hepatic encephalopathy were the major endpoints. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was calculated. Cochrane risk of bias tool was employed. Results: Overall, 119 papers were identified. Among them, four randomized controlled trials were eligible. Viatorr covered stents alone, Fluency covered stents alone, and Viatorr plus Fluency covered stents were employed in one, two, and one randomized controlled trials, respectively. Risk of bias was relatively low. Meta-analyses demonstrated that the covered-stents group had significantly higher probabilities of overall survival (HR = 0.67, 95% CI = 0.50–0.90, p = 0.008) and shunt patency (HR = 0.42, 95% CI = 0.29–0.62, p

Purpose: Accurate preoperative diagnosis of parotid tumor is essential for the formulation of optimal individualized surgical plans. The study aims to investigate the diagnostic performance of radiomics nomogram based on contrast-enhanced computed tomography (CT) images in the differentiation of the two most common benign parotid gland tumors. Methods: One hundred and ten patients with parotid gland tumors including 76 with pleomorphic adenoma (PA) and 34 with adenolymphoma (AL) confirmed by histopathology were included in this study. Radiomics features were extracted from contrast-enhanced CT images of venous phase. A radiomics model was established and a radiomics score (Rad-score) was calculated. Clinical factors including clinical data and CT features were assessed to build a clinical factor model. Finally, a nomogram incorporating the Rad-score and independent clinical factors was constructed. Receiver operator characteristics (ROC) curve was generated and the area under the ROC curve (AUC) was calculated to quantify the discriminative performance of each model on both the training and validation cohorts. Decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of each model. Results: The radiomicsmodel showed good discrimination in the training cohort [AUC,0.89;95% confidence interval (CI),0.80-0.98] and validation cohort (AUC, 0.89; 95% CI, 0.77-1.00). The radiomics nomogram showed excellent discrimination in the training cohort (AUC, 0.98; 95% CI, 0.96-1.00) and validation cohort (AUC, 0.95; 95% CI, 0.88-1.00) and displayed better discrimination efficacy compared with the clinical factor model (AUC, 0.93; 95% CI, 0.88-0.99) in the training cohort (p < 0.05). The DCA demonstrated that the combined radiomics nomogram provided superior clinical usefulness than clinical factor model and radiomics model. Conclusions: The CT-based radiomics nomogram combining Rad-score and clinical factors exhibits excellent predictive capability for differentiating parotid PA from AL, which might hold promise in assisting radiologists and clinicians in the exact differential diagnosis and formulation of appropriate treatment strategy. [ABSTRACT FROM AUTHOR]