Interpretable online network dictionary learning for inferring long-range chromatin interactions.

Dictionary learning (DL), implemented via matrix factorization (MF), is commonly used in computational biology to tackle ubiquitous clustering problems. The method is favored due to its conceptual simplicity and relatively low computational complexity. However, DL algorithms produce results that lack interpretability in terms of real biological data. Additionally, they are not optimized for graph-structured data and hence often fail to handle them in a scalable manner. In order to address these limitations, we propose a novel DL algorithm called online convex network dictionary learning (online cvxNDL). Unlike classical DL algorithms, online cvxNDL is implemented via MF and designed to handle extremely large datasets by virtue of its online nature. Importantly, it enables the interpretation of dictionary elements, which serve as cluster representatives, through convex combinations of real measurements. Moreover, the algorithm can be applied to data with a network structure by incorporating specialized subnetwork sampling techniques. To demonstrate the utility of our approach, we apply cvxNDL on 3D-genome RNAPII ChIA-Drop data with the goal of identifying important long-range interaction patterns (long-range dictionary elements). ChIA-Drop probes higher-order interactions, and produces data in the form of hypergraphs whose nodes represent genomic fragments. The hyperedges represent observed physical contacts. Our hypergraph model analysis has the objective of creating an interpretable dictionary of long-range interaction patterns that accurately represent global chromatin physical contact maps. Through the use of dictionary information, one can also associate the contact maps with RNA transcripts and infer cellular functions. To accomplish the task at hand, we focus on RNAPII-enriched ChIA-Drop data from Drosophila Melanogaster S2 cell lines. Our results offer two key insights. First, we demonstrate that online cvxNDL retains the accuracy of classical DL (MF) methods while simultaneously ensuring unique interpretability and scalability. Second, we identify distinct collections of proximal and distal interaction patterns involving chromatin elements shared by related processes across different chromosomes, as well as patterns unique to specific chromosomes. To associate the dictionary elements with biological properties of the corresponding chromatin regions, we employ Gene Ontology (GO) enrichment analysis and perform multiple RNA coexpression studies.

Semi-quantitative group testing for efficient and accurate qPCR screening of pathogens with a wide range of loads.

BACKGROUND: Pathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. RESULTS: To address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. Dynamic Ct threshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. CONCLUSION: In conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale.

Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoulder surgery.

BACKGROUND: Propionibacterium acnes infection is a significant problem after shoulder surgery. Residual P. acnes is found on the skin up to 29% of the time immediately after surgical skin preparation and in 70% of dermal biopsy specimens. These residual bacteria may be a source for infection. Identifying more ideal skin preparation may help reduce the risk of infection. The purpose of this study was to evaluate the effect that topical benzoyl peroxide (BPO), with chlorhexidine skin preparation, would have on the presence of P. acnes cultured at the time of shoulder surgery. We hypothesized that adding topical BPO to our skin preparation would reduce the number of positive P. acnes cultures identified during surgery. METHODS: Fifty patients undergoing first-time shoulder surgery were treated with topical 5% BPO cream 48 hours before surgery. After skin preparation, 13 samples per subject were obtained. Cultures were held for 14 days. RESULTS: Fifty patients underwent arthroscopic shoulder surgery; 650 culture specimens were obtained. The skin was positive at the initiation of surgery in 6% of cases. Tissue samples were positive in 6%. The skin was positive in 10% at the end of surgery. None of these rates of positive culture were different from the 4% rate observed with a control swab. CONCLUSION: Application of BPO is an effective way to reduce P. acnes on skin at the beginning and, importantly, at the end of a surgical procedure. This may result in a lower risk for postoperative infection.

Appraisal of extended cane length and fruit thinning strategies on the performance of growth yield and quality of kiwifruit.

The kiwifruit has been identified as an enormous fruit for mid-hill horticulture due to its wider adaptability and diversification. The size and quality of kiwifruit were affected by its market. As a result, appropriate canopy management and orchard techniques are key components in its production. Pruning and hand thinning, especially in kiwifruit, have been observed to improve the size and quality of the fruit. Traditional pruning maintained shorter canes with 6-12 nodes and 4 fruits/shoots. However, this study extended cane length and retained loads of 20 nodes/cane and 6 fruits/shoot. Considering the above, a study was conducted to determine the effects of extended cane length and fruit thinning on kiwifruit growth, yield, and fruiting performance. Five pruning levels have been employed: 8, 10, 12, 14, and 16 nodes/cane; 4, 6, and 8 fruits/fruiting shoot. The result revealed that the pruning of up to 12 nodes/cane coupled with thinning up to 6 fruits/fruiting shoot resulted in maximum cane diameter, leaf area, leaf: fruit ratio, advancement in flower initiation, bud break percentage (86.79 %), real fertility index, fruit yield and a proportion of grade "A" fruits. The highest leaf chlorophyll content (67.50), flowers per floral shoot, and productivity were recorded with pruning up to 16 nodes/cane coupled with thinning up to 6 fruits/fruiting shoot. The physico-chemical parameters such as fruit weight, diameter, volume, TSS, TSS: acid ratio, total sugars, and C: N ratio of the leaf and shoot were also found to be highest with pruning up to 12 nodes/cane coupled with thinning up to 6 fruits/fruiting shoot. This treatment also gave the maximum net return on a per-hectare basis, hence it was found to be the most profitable for the farmers.

Captivating actions of pomological crops waste as biosorbents for environmental remediation: a comprehensive review.

Water pollutants are an emerging environmental hurdle for crop production and human health risks. In recent decades, the removal of contaminants from water using a cutting-edge approach like biosorbents is a strategy that is both cost-efficient and sustainable. For instance, since biowaste from fruit crops implies the frequent occurrence of average annual waste, it is imperative to formulate strategic initiatives to mitigate this emerging problem while simultaneously recognizing the potential for reutilization and reintroduction of such waste into the industrial sector. Fruit crops such as peels, seeds, skins, branches and stalks can be altered into biosorbents for water treatment. Partially mitigating the adverse impacts of biowaste that estimate to incur costs of billions of dollars around the world would be achieved with this engineering application. This review provides a perspective on the existing literature and brings up-to-date information and findings in the field of pomological crop waste as biosorbents for environmental remediation. In this way, we review the detrimental impact of environmental contaminants on biological organisms and different types of fruit crop waste and their utilization for wastewater treatment, with special emphasis on the formulation of biowaste sorbents (removal efficiency is > 80%) and their application for capturing pollutants such as heavy metals, organic and inorganic dyes and oils. Besides, the newly invented techniques for the characterization of fruit-based biosorbents, the parametric evaluation of biosorbents and their comparison with other available biosorbents are discussed. This review will be helpful for remediating contaminants in wastewater and a panacea for practical engineering solutions.

Small-Sample Estimation of the Mutational Support and Distribution of SARS-CoV-2.

We consider the problem of determining the mutational support and distribution of the SARS-CoV-2 viral genome in the small-sample regime. The mutational support refers to the unknown number of sites that may eventually mutate in the SARS-CoV-2 genome while mutational distribution refers to the distribution of point mutations in the viral genome across a population. The mutational support may be used to assess the virulence of the virus and guide primer selection for real-time RT-PCR testing. Estimating the distribution of mutations in the genome of different subpopulations while accounting for the unseen may also aid in discovering new variants. To estimate the mutational support in the small-sample regime, we use GISAID sequencing data and our state-of-the-art polynomial estimation techniques based on new weighted and regularized Chebyshev approximation methods. For distribution estimation, we adapt the well-known Good-Turing estimator. Our analysis reveals several findings: First, the mutational supports exhibit significant differences in the ORF6 and ORF7a regions (older versus younger patients), ORF1b and ORF10 regions (females versus males) and in almost all ORFs (Asia/Europe/North America). Second, even though the N region of SARS-CoV-2 has a predicted 10% mutational support, mutations fall outside of the primer regions recommended by the CDC.

COVID-19 Mask Mandates in NY and Their Effect on the Incidence of Flu.

Objective: The goal of the study is to quantify the reduction in the cases of influenza and how this decrease in incidence correlates with the execution of masking requirements in public as well as social distancing. Methods: Influenza statistics were collected from Northwell Health, a 23-hospital system located throughout New York State. Positive influenza results were collected representing the 2018-2019 Flu season, 2019-2020 Flu season, and compared to the 2020-2021 Flu season, which corresponded to the mask mandates and social distancing measures implemented in NYS. Results: Our data showed a dramatic decrease in influenza rates during the 2020-2021 Flu season, which corresponded to NYS's strict social distancing and mask requirements during the pandemic. This shows a steep decline correlating with the implementation of public health mandates directed at decreasing the spread of aerosolized particles between members of the population. Conclusion: Our data show a significant decrease in the number of positive influenza tests during the same period of time when COVID-19 social distancing and mask-wearing requirements were in effect.

A Phase I/II Clinical Trial of Pembrolizumab and Cabozantinib in Metastatic Renal Cell Carcinoma.

Purpose: Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC. Experimental Design: Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0-1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9-78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5-99.9). Median DoR was 8.3 months (interquartile range, 4.6-15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25-14.63) and median OS was 30.81 months (95% CI, 24.2-not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib. Conclusions: Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations. Trial Registration: ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822. Significance: This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months.

Diagnosing and Managing Clinically Silent Lupus Nephritis and Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome: A Clinical Challange.

Lupus nephritis is typically associated with anti-nuclear antibodies and anti-double-stranded DNA antibodies resulting in the intrarenal immune complex deposition. Levels of anti-double-stranded DNA antibodies reflect disease activity in these patients. With negative anti-double-stranded DNA antibodies, establishing a diagnosis of lupus nephritis is difficult. Lupus nephritis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis is both a diagnostic and therapeutic dilemma. Herein, we describe a case of an asymptomatic 41-year-old female who had incidental findings of low hemoglobin and elevated serum creatinine. Making a clinical diagnosis of lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis in an asymptomatic patient can be challenging and must be made based on the interpretation of evolving serology, imaging studies, and histopathology. Based on extensive workup, the patient was diagnosed with concurrent lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis overlap syndrome warranting immediate immunosuppressive therapy.

Bebtelovimab-Induced Bradycardia Leading to Cardiac Arrest.

Bebtelovimab is a monoclonal antibody used to prevent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Complications of SARS-CoV-2 infection can include cardiac effects including sinus bradycardia. CASE SUMMARY: We describe the case of an 86-year-old male infected with SARS-CoV-2 who experienced bradycardia with cardiac arrest immediately following infusion of Bebtelovimab with return of spontaneous circulation obtained following 1 minute of chest compressions and administration of atropine. His bradycardia resolved, and he was extubated on hospital day 1, found to be neurologically intact, and discharged on hospital day 9. CONCLUSIONS: Due to the time course of the patient's symptomatology, we attribute the bradycardic arrest to the Bebtelovimab infusion. This case illustrates the need for further research into the etiology of bradycardia due to SARS-CoV-2 infection and to examine potential links to monoclonal antibody infusion. It also serves as important caution to maintain close cardiac monitoring while administering monoclonal antibodies for SARS-CoV-2.

Effect of Organic Manures on Growth, Yield, Leaf Nutrient Uptake and Soil Properties of Kiwifruit (Actinidia deliciosa Chev.) cv. Allison.

In recent decades, organic kiwifruit farming has come up as a feasible method for high-quality kiwi production without using chemical fertilizers. The primary objective of this research was to investigate how the sole application of organic and the combined application of organic manures affected the growth, yields, and quality of Allison kiwifruit, as well as the soil's physicochemical characteristics. The field trial was conducted on cv. Allison to determine the efficacy of organic manures (OM) on growth, nutrient absorption, production and soil health. The experiment involved eight treatments, viz.: T1: 100% Dairy manure (DM); T2: 100% Vermicompost (VC); T3: 100% chicken manure (CM); T4: 50% DM + 50% CM; T5: 50% DM + 50% VC; T6: 50% CM + 50% VC; T7: DM + CM + VC in equal proportions; and T8: Recommended nutrients inorganic NPK + 40 kg DM. A randomized complete block design comprising three replicas was used in this investigation. The use of inorganic fertilizers (NPK) in combination with DM enhanced Spad Values Chlorophyll, fruit production, leaf number, leaf area, and stem diameter while also improving the soil's chemical characteristics. The flower initiation was recorded with DM and Vermicompost (50:50). Furthermore, when compared to inorganic fertilizer treatment, OM treatment significantly improved fruit quality by improving fruit chemical composition in terms of soluble solids contents and leaf nutrient status, as well as improving soil's physical properties with DM and Vermicompost (50:50). The study's outcome revealed that OM had a significant impact on flowering time, fruit SSC, leaf nutritional status, and soil physical characteristics. In comparison to organic treatments, recommended fertilizer dosages (NPK + DM) improved plant growth, fruit yield, and soil chemical characteristics.

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia.

Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a "real-world" scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.

Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

Long-term radiotherapy outcomes for nasal cavity and septal cancers.

PURPOSE: Carcinoma of the nasal cavity and septum has historically been associated with a poor prognosis. This report updates the long-term outcomes for radiotherapy (RT) of this disease site at the University of Texas M.D. Anderson Cancer Center. METHODS AND MATERIALS: A retrospective analysis was performed on the data from 68 patients diagnosed with histologically proven carcinoma of the nasal cavity or septum treated with RT for curative intent between 1969 and 2000. The disease histologic type was as follows: 45 (66%) had squamous cell carcinoma, 12 (18%) had adenoid cystic carcinoma, 8 (12%) had adenocarcinoma, and 3 (4%) had poorly/undifferentiated carcinoma. Of the 68 patients, 32 (47%) had received definitive RT. Of these, 23 had received external beam RT and 9 brachytherapy. Of the remaining 36 patients, 3 (4%) underwent preoperative external beam RT and 33 (49%) postoperative external beam RT. Of the 68 patients, 13 (19%) received neck RT. The median dose for patients receiving definitive and postoperative RT was 65 and 58.2 Gy, respectively. The median follow-up for the entire cohort was 11 years (range, 2.4-30.1 years). RESULTS: Of the 68 patients, 19 (28%) developed a locoregional relapse, 14 (21%) locally and 5 (7%) regionally. The local control rate at 5 and 10 years was 86% and 76%, respectively. The disease-specific survival rate was 86% and 78%, and the overall survival rate was 82% and 62% at 5 and 10 years, respectively. CONCLUSION: This extended follow-up of our institutional experience has demonstrated that RT can provide durable long-term locoregional control and survival outcomes for patients with carcinoma of the nasal cavity and septum.

Clinical benefit of palliative radiation therapy in advanced gastric cancer.

BACKGROUND: Local progression of advanced gastric cancer often manifests as bleeding, dysphagia/obstruction, or pain. We evaluated the magnitude and durability of palliation with radiotherapy (RT). MATERIAL AND METHODS: From 1996 to 2004, 37 gastric cancer patients were treated with palliative RT (median dose 35 Gy in 14 fractions). Nearly two-thirds of all patients received concurrent chemoradiation therapy (CRT). Index pre-treatment symptoms were gastric bleeding, dysphagia/obstruction, and pain in 54%, 43%, and 19% of patients, respectively. RESULTS: The rates of control for bleeding, dysphagia/obstruction, and pain were 70% (14/20), 81% (13/16), and 86% (6/7), respectively. These symptoms were controlled without additional interventions for a median of 70%, 81%, and 49% of the patient's remaining life, respectively. Patients receiving CRT had a trend towards better median overall survival than those receiving RT alone (6.7 vs. 2.4 months, p=0.08). Lower (<41 Gy) biologically effective dose (BED, assuming an alpha/beta ratio of 10 for early responding tissues) predicted for poorer local control (6-month local control 70% vs. 100%, p=0.05) while T4 tumors had a trend towards inferior local control (6-month LC 56% vs. 100%, p=0.06). DISCUSSION: Palliative RT controls symptoms for most of the remaining life in the majority of gastric cancer patients. The role of a higher dose of RT (BED >or=41 Gy), especially in patients with T4 tumors, remains to be established. In order to accurately define the role for radiotherapy in palliation of these symptoms, prospective randomized studies need to be conducted.

Therapeutic options for patients with lymphoma and liver dysfunction or failure during mechlorethamine shortage.

Liver dysfunction in patients with lymphoma presents an important clinical dilemma because it limits the use of anthracyclines and vinca alkaloids for this potentially curable malignancy. Patients are typically treated with corticosteroids, rituximab and the nitrogen mustard mechlorethamine, and then transitioned to definitive therapy after improvement in liver function. Between 2010 and 2012 mechlorethamine was not available and other strategies were required. In this case series, we describe seven cases of patients with lymphoma and liver dysfunction successfully treated in this time period with ifosfamide/carboplatin or gemcitabine/cisplatin.

Comprehensive review of JAK inhibitors in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as 'BCR-ABL1-negative' MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in 'BCR-ABL1-negative' MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.

Prospective imaging assessment of mortality risk after head-and-neck radiotherapy.

PURPOSE: The optimal roles for imaging-based biomarkers in the management of head-and-neck cancer remain undefined. Unresolved questions include whether functional or anatomic imaging might improve mortality risk assessment for this disease. We addressed these issues in a prospective institutional trial. METHODS AND MATERIALS: Ninety-eight patients with locally advanced pharyngolaryngeal squamous cell cancer were enrolled. Each underwent pre- and post-chemoradiotherapy contrast-enhanced computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT imaging. Imaging parameters were correlated with survival outcomes. RESULTS: Low post-radiation primary tumor FDG avidity correlated with improved survival on multivariate analysis; so too did complete primary tumor response by CT alone. Although both imaging modalities lacked sensitivity, each had high specificity and negative predictive value for disease-specific mortality risk assessment. Kaplan-Meier estimates confirmed that both CT and FDG-PET/CT stratify patients into distinct high- and low-probability survivorship groups on the basis of primary tumor response to radiotherapy. Subset analyses demonstrated that the prognostic value for each imaging modality was primarily derived from patients at high risk for local treatment failure (human papillomavirus [HPV]-negative disease, nonoropharyngeal primary disease, or tobacco use). CONCLUSIONS: CT alone and FDG-PET/CT are potentially useful tools in head-and-neck cancer-specific mortality risk assessment after radiotherapy, particularly for selective use in cases of high-risk HPV-unrelated disease. Focus should be placed on corroboration and refinement of patient selection for imaging-based biomarkers in future studies.