Prognostic and Predictive Significance of Ki67 in Primary Non-metastatic or Recurrent Acral Melanoma: Evidence from a Multicenter Retrospective Study.

BACKGROUND: The purpose of this work was to investigate the prognostic significance of Ki67 in acral melanoma (AM). PATIENTS AND METHODS: Ki67 values in primary lesions (pKi67) of 481 patients with primary non-metastatic AM (primary cohort) from three tertiary hospitals and in recurrent lesions (rKi67) of 97 patients (recurrent cohort) were recorded. The associations of p/rKi67 with clinicopathological features and prognosis were analyzed. RESULTS: In the primary cohort, high pKi67 group tended to have more ulceration, pT4, lymph node metastasis (LNM), nodal macrometastases, and recurrence (all P < 0.05). Logistic regression analysis revealed that pKi67 was significantly associated with pT4 and LNM (P = 0.004 and 0.027, respectively). Furthermore, both 5-year overall survival (OS) and recurrence-free survival (RFS) rates in high pKi67 group were significantly worse than those in moderate and low pKi67 groups (OS 47.8% versus 55.7 versus 76.8%, P = 0.002; RFS: 27.1 versus 42.8 versus 61.8%, P < 0.001). Similarly, in the recurrent cohort, the 5-year survival after recurrence (SAR) rates in high rKi67 group was significantly worse than those in moderate and low rKi67 groups (31.7 versus 47.4 versus 75%; P = 0.026). Stratified analysis also indicated a significant survival difference among pKi67 groups within various subgroups. Most importantly, multivariate Cox analysis demonstrated that pKi67 could be independently associated with OS and RFS, as well as rKi67 for SAR (all P < 0.05). CONCLUSIONS: A high Ki67 value was significantly associated with adverse pathological and prognostic features in both primary and recurrent AM cohorts. Ki67 should be routinely evaluated to guide risk stratification and prognostic prediction.

Immune characteristics and clinical significance of peripheral blood lymphocytes in breast cancer.

BACKGROUND: In the context of breast cancer (BC), the correlation between lymphocytes and clinical outcomes, along with treatment response, has garnered attention. Despite this, few investigations have delved into the interplay among distinct peripheral blood lymphocyte (PBL) types, immune attributes, and their clinical implications within the BC landscape. METHODS: The primary objective of this study was to scrutinize the baseline status of PBL subsets in patients with primary BC, track their dynamic changes throughout treatment, and ascertain their interrelation with prognosis. Flow cytometry was employed to analyse PBLs from a cohort of 74 BC patients. RESULTS: Our analysis revealed that baseline levels of Treg and PD-L1 + T cells were lower in BC patients compared to the reference values. Notably, a disparity in baseline PD-L1 + T cell levels surfaced between patients who underwent adjuvant therapy and those subjected to neoadjuvant therapy (NAT). Furthermore, a meticulous evaluation of PBL subsets before and after treatment underscored discernible alterations in 324 + T cells and CD19 + CD32 + B cells over the course of therapy. Strikingly, heightened CD4 + T cell levels at baseline were linked to enhanced event-free survival (EFS) (p = 0.02) and a robust response to chemotherapy. CONCLUSIONS: These results indicate that PBLs may serve as a significant marker to assess the immune status of BC patients, and therapy has the potential to modify patient immune profiles. In addition, peripheral blood CD4 + T cell levels may serve as promising biomarkers for diagnosis and prognosis in future studies of BC.

Delay in Time to Adjuvant Chemotherapy and its Impact on Oncological Outcomes in Patients Undergoing Optimal Cytoreductive Surgery for Advanced Ovarian Cancer: Analysis of 1480 Cases From the Indian HIPEC Registry.

BACKGROUND AND OBJECTIVES: The impact of delay in initiation of adjuvant chemotherapy following optimal CRS in different settings of treatment for advanced ovarian cancer needs to be studied with special reference to CRS HIPEC. METHODS: The 1480 advanced EOC patients underwent optimal CRS, followed by adjuvant chemotheraphy, with or without intraperitoneal (IP) chemotherapy in Normothermic or Hyperthermic form. Interval between the day of surgery and start of adjuvant chemotherapy and its impact on outcome was analyzed. RESULTS: CRS, CRS with IP or HIPEC was done in 400, 480, and 600 patients respectively. Median interval of starting adjuvant chemotherapy was 32 days CRS group, 34 days CRS + IP group and 41 days CRS + HIPEC group. Delay in chemotherapy impacted on recurrence free survival (RFS) in CRS + IV group (36 vs. 17 months: p = 0.02) and some impact in CRS + IP group (38 vs. 28 months; P 0.78) and no impact on CRS + HIPEC group (35 vs. 32 months; p = 0.17). CONCLUSIONS: Delay in starting adjuvant chemotherapy adversely affects RFS in patients undergoing optimal CRS alone. However, the delay didn't have an impact in the CRS + HIPEC group. Well-designed clinical studies are required to evaluate the impact of single dose of HIPEC.

Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

Comparative assessment of disease recurrence after transurethral resection of non-muscle-invasive bladder cancer with and without a photodynamic diagnosis using 5-aminolevulinic acid: a propensity score-matching analysis.

BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.

Prognostic Value of HHLA2 in Patients with Solid Tumors: A Meta-Analysis.

HHLA2 is a checkpoint from the B7 family that can play a co-stimulatory or co-inhibitory role in cancer, depending on the binding receptor. The aim of this meta-analysis was to assess the relationship between HHLA2 levels and its impact on the prognosis of patients with solid cancers. The study used data from PubMed, Embase, Web of Science (WOS), Cochrane and SCOPUS databases. The R studio software was used for the data analysis. The study assessed overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) by pooling appropriate hazard ratios (HR). Eighteen studies (2880 patients' data) were included. High expression of HHLA2 was associated with worse OS (HR = 1.58, 95% CI: 1.23-2.03), shorter RFS (HR = 1.95, 95% CI: 1.38-2.77) and worse DFS (HR = 1.45, 95% CI: 1.01-2.09) in patients with solid cancers. The current study suggests that high expression of HHLA2 is associated with poorer prognosis in patients with solid cancers.

SPR9 encodes a 60 S ribosomal protein that modulates panicle spreading and affects resistance to false smut in rice (Oryza sativa. L).

BACKGROUND: The architecture of inflorescence in crops is a key agronomic feature determining grain yield and thus has been a major target trait of cereal domestication. RESULTS: In this study, we show that a simple spreading panicle change in rice panicle shape, controlled by the Spreading Panicle 9 (SPR9) locus, also has a significant impact on the resistance to rice false smut (RFS). Meanwhile, we mapped a novel spr9 mutant gene between markers Indel5-18 and Indel5-22 encompassing a genomic region of 43-kb with six candidate genes. Through gene prediction and cDNA sequencing, we confirmed that LOC_Os05g38520 is the target gene in the spr9 mutant, which encodes 60 S ribosomal protein L36-2. Further analysis showed that the spr9 mutant is caused by a 1 bp deletion in the first exon that resulted in premature termination. Knockout experiments showed that the SPR9 gene is responsible for the spreading panicle phenotype of the spr9 mutant. Interestingly, the spr9 mutant was found to improve resistance to RFS without affecting major agronomic traits. Taken together, our results revealed that the spr9 allele has good application prospects in rice breeding for disease resistance and panicle improvement. CONCLUSIONS: We report the map-based cloning and functional characterization of SPR9, which encodes a 60 S ribosomal protein that regulates spreading panicles and affects the resistance to false smut in rice.

CT radiomic predictors of local relapse after SBRT for lung oligometastases from colorectal cancer: a single institute pilot study.

OBJECTIVES: To assess the potential of radiomic features (RFs) extracted from simulation computed tomography (CT) images in discriminating local progression (LP) after stereotactic body radiotherapy (SBRT) in the management of lung oligometastases (LOM) from colorectal cancer (CRC). MATERIALS AND METHODS: Thirty-eight patients with 70 LOM treated with SBRT were analyzed. The largest LOM was considered as most representative for each patient and was manually delineated by two blinded radiation oncologists. In all, 141 RFs were extracted from both contours according to IBSI (International Biomarker Standardization Initiative) recommendations. Based on the agreement between the two observers, 134/141 RFs were found to be robust against delineation (intraclass correlation coefficient [ICC] > 0.80); independent RFs were then assessed by Spearman correlation coefficients. The association between RFs and LP was assessed with Mann-Whitney test and univariate logistic regression (ULR): the discriminative power of the most informative RF was quantified by receiver-operating characteristics (ROC) analysis through area under curve (AUC). RESULTS: In all, 15/38 patients presented LP. Median time to progression was 14.6 months (range 2.4-66 months); 5/141 RFs were significantly associated to LP at ULR analysis (p < 0.05); among them, 4 RFs were selected as robust and independent: Statistical_Variance (AUC = 0.75, p = 0.002), Statistical_Range (AUC = 0.72, p = 0.013), Grey Level Size Zone Matrix (GLSZM) _zoneSizeNonUniformity (AUC = 0.70, p = 0.022), Grey Level Dependence Zone Matrix (GLDZM) _zoneDistanceEntropy (AUC = 0.70, p = 0.026). Importantly, the RF with the best performance (Statisical_Variance) is simply representative of density heterogeneity within LOM. CONCLUSION: Four RFs extracted from planning CT were significantly associated with LP of LOM from CRC treated with SBRT. Results encourage further research on a larger population aiming to define a usable radiomic score combining the most predictive RFs and, possibly, additional clinical features.

Comparison of acute myeloid leukemia and myelodysplastic syndromes with TP53 aberrations.

TP53 aberrations are found in approximately 10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and are considered early driver events affecting leukemia stem cells. In this study, we compared features of a total of 84 patients with these disorders seen at a tertiary cancer center. Clinical and cytogenetic characteristics as well as immunophenotypes of immature blast cells were similar between AML and MDS patients. Median overall survival (OS) was 226 days (95% confidence interval [CI], 131-300) for the entire cohort with an estimated 3-year OS rate of 11% (95% CI, 6-22). OS showed a significant difference between MDS (median, 345 days; 95% CI, 235-590) and AML patients (median, 91 days; 95% CI, 64-226) which is likely due to a different co-mutational pattern as revealed by next-generation sequencing. Transformation of TP53 aberrant MDS occurred in 60.5% of cases and substantially reduced their survival probability. Cox regression analysis revealed treatment class and TP53 variant allele frequency as prognostically relevant parameters but not the TP53-specific prognostic scores EAp53 and RFS. These data emphasize similarities between TP53 aberrant AML and MDS and support previous notions that they should be classified and treated as a distinct disorder.

Factors associated with disease-free and abdominal recurrence-free survival in abdominopelvic and retroperitoneal sarcomas.

BACKGROUND AND OBJECTIVES: Retroperitoneal and abdominopelvic sarcomas are rare heterogeneous malignancies. The only therapy proven to improve disease-free survival (DFS) is R0/R1 surgical resection. We sought to analyze whether additional factors such as radiation and systemic therapy were associated with DFS and abdominal recurrence-free survival (RFS). METHODS: Retrospective review of adults (≥18) with resectable abdominopelvic and retroperitoneal sarcomas who underwent intent-to-cure surgery at a high-volume tertiary referral center between 1998 and 2015. The main outcome measures were DFS and abdominal RFS. RESULTS: Overall, 159 patients met the criteria for inclusion. Median follow-up was 4.8 years (range 0.1-18.9 years). The most common histology was liposarcoma (49%). Systemic therapy was administered to 48% of patients and was not associated with improved outcomes. The neoadjuvant radiotherapy group (11%) had improved adjusted DFS (5.46 years, 95% CI [3.68, 7.24] vs. 3.1 years, 95% CI [2.48, 3.73]) and abdominal RFS (6.14 years, 95% CI [4.38, 7.89] vs. 3.22 years, 95% CI [2.61, 3.84]). The adjuvant radiotherapy group (19%) had no improvement. CONCLUSIONS: In a cohort of patients undergoing resection for retroperitoneal or abdominopelvic sarcoma, neoadjuvant radiation improved DFS and abdominal RFS. A follow-up of over three years was needed to appreciate a difference in outcomes.

The association between recommended and non-recommended food scores on cardiovascular risk factors in obese and overweight adult women: a cross-sectional study.

OBJECTIVE: Obesity is a highly prevalent, non-communicable, disease associated with numerous comorbid complications, such as cardiovascular disease. Following a healthy diet is known to help reduce the risk of both obesity and cardiovascular disease. This study was conducted to evaluate the association of recommended food score (RFS) and none recommended food score (NRFS) with cardiovascular risk factors in overweight and obese women. METHODS: This cross-sectional study was performed on 379 overweight and obese (BMI ≥25 kg/m2) women aged 18-48 years. Anthropometric measurements and body composition analysis were assessed in all participants. Dietary intake was assessed by a valid and reliable food frequency questionnaire (FFQ) containing 147 items, and RFS and NRFS was calculated. Biochemical assessments including TC, HDL, LDL, TG, FBS, insulin, HOMA-IR, and hs-CRP were quantified by ELISA. RESULTS: The mean age and BMI of participants were 36.73 ± 9.21 (y) and 31.17 ± 4.22 (kg/m2), respectively. Binary logistic regression showed that participants in the highest tertile of the RFS compared to the lowest tertile had 57% lower odds for hypertriglyceridemia [OR = 0.43, 95%CI = 0.20-0.92, P = 0.03]. Subjects with high adherence to the NRFS had lower HDL [OR = 2.11, 95%CI = 1.08-4.12, P = 0.02] and higher odds for hypertriglyceridemia [OR = 2.95, 95%CI = 1.47-5.94, P = 0.002] compared to low adherence. CONCLUSIONS: There was an inverse significant association between adherence to RFS and odds of hypertriglyceridemia. There was a significant association between NRFS and hypertriglyceridemia, in addition to an inverse association between NRFS and HDL. We recommend that people increase their consumption of fruits, vegetables, whole grains, lean meats or meat alternates, and low-fat dairy and avoid red meat, processed meat, chips, high-fat dairy, solid oil, refined grains, and variety of sweetened foods to prevent cardiovascular disease.

The diagnostic value of pepsin concentration in saliva for laryngopharyngeal reflux disease.

OBJECTIVE: To explore the diagnostic efficacy of pepsin concentration in saliva for laryngopharyngeal reflux (LPR) disease. METHODS: In this study, we recruited 40 participants with abnormal sensation of throat into the study who visited our hospital from March 2020 to December 2020. The 24 h multichannel intraluminal impedance and pH monitoring (24 h MII-pH), reflux symptom index (RSI) and reflux finding score (RFS), pepsin concentration in saliva were collected. The Cohen's kappa test and receiver-operating characteristic (ROC) curves were performed to determine and compare the sensitivity and specificity of five diagnostic methods: RSI; RFS, pepsin concentration, RSI + RFS, RSI + RFS + pepsin concentration. RESULTS: The area under the curve (AUC) of RSI, RFS, pepsin concentration, RSI + RFS, RSI + RFS + pepsin concentration were 0.767, 0.733, 0.870, 0.750,0.867, respectively. That is, the pepsin concentration has maximum AUC (the cutoff point is 219.47 (ng/mL); the sensitivity and 1-specificity is 0.300, 0.933, respectively.). The positive predictive value was 90.3% (28/31), and the negative predictive value was 77.8% (7/9). The Cohen's kappa coefficients of the five diagnostic subgroups were: RSI 0.486 (95% CI 0.207-0.764, P = 0.001); RFS 0.333 (95% CI 0.021-0.644, P = 0.032); RSI + RFS: 0.517 (95% CI 0.205-0.829, P = 0.001); pepsin concentration: 0.699 (95% CI 0.379-0.931, P = 0.001); RSI + RFS + pepsin concentration: 0.500 (95% CI 0.181-0.819, P < 0.001). CONCLUSION: The pepsin concentration has the maximum AUC area and highest consistency with the 24 h MII-pH. Therefore, it has certain value in the screening and diagnosis of diseases related to LPR disease.

A Two-Stage Feature Point Detection and Marking Approach Based on the Labeled Multi-Bernoulli Filter.

In recent years, various algorithms using random finite sets (RFS) to solve the issue of simultaneous localization and mapping (SLAM) have been proposed. Compared with the traditional method, the advantage of the RFS method is that it can avoid data association, landmark appearance and disappearance, missed detections, and false alarms in Bayesian recursion. There are many problems in the existing robot SLAM methods, such as low estimation accuracy, poor back-end optimization, etc. On the basis of previous studies, this paper presents a labeled random finite set (L-RFS) SLAM method. We describe a scene where the sensor moves along a given path and avoids obstacles based on the L-RFS framework. Then, we use the labeled multi-Bernoulli filter (LMB) to estimate the state of the sensor and feature points. At the same time, the B-spline curve is used to smooth the obstacle avoidance path of the sensor. The effectiveness of the algorithm is verified in the final simulation.

Multi-Feature Matching GM-PHD Filter for Radar Multi-Target Tracking.

Multi-target tracking (MTT) is one of the most important functions of radar systems. Traditional multi-target tracking methods based on data association convert multi-target tracking problems into single-target tracking problems. When the number of targets is large, the amount of computation increases exponentially. The Gaussian mixture probability hypothesis density (GM-PHD) filtering based on a random finite set (RFS) provides an effective method to solve multi-target tracking problems without the requirement of explicit data association. However, it is difficult to track targets accurately in real-time with dense clutter and low detection probability. To solve this problem, this paper proposes a multi-feature matching GM-PHD (MFGM-PHD) filter for radar multi-target tracking. Using Doppler and amplitude information contained in radar echo to modify the weights of Gaussian components, the weight of the clutter can be greatly reduced and the target can be distinguished from clutter. Simulations show that the proposed MFGM-PHD filter can improve the accuracy of multi-target tracking as well as the real-time performance with high clutter density and low detection probability.

Association of De Ritis ratio with oncological outcomes in patients with non-muscle invasive bladder cancer (NMIBC).

PURPOSE: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut-off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut-off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). RESULTS: Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02-1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65-1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00-1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. CONCLUSION: Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.

Effect of perioperative flurbiprofen axetil on long-term survival of patients with esophageal carcinoma who underwent thoracoscopic esophagectomy: A retrospective study.

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) have an anti-inflammatory response, but it remains unclear whether the perioperative use of flurbiprofen axetil can influence postoperative tumor recurrence and survival in esophageal carcinoma. We aimed to explore the effect of perioperative intravenous flurbiprofen axetil on recurrence-free survival (RFS) and overall survival (OS) in patients with esophageal carcinoma who underwent thoracoscopic esophagectomy. METHODS: This retrospective study included patients who underwent surgery for esophageal carcinoma between December 2009 and May 2015 at the Department of Thoracic Surgery, Anhui Provincial Hospital. Patients were categorized into a non-NSAIDs group (did not receive flurbiprofen axetil), single-dose NSAIDs group (received a single dose of flurbiprofen axetil intravenously), and multiple-dose NSAIDs group (received multiple doses of flurbiprofen). RESULTS: A total of 847 eligible patients were enrolled. Univariable and multivariable analyses revealed that the intraoperative use of flurbiprofen was associated with long-term RFS (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.42-0.76, p = .001) and prolonged OS (HR: 0.49, 95% CI: 0.38-0.63, p = .001). CONCLUSIONS: Perioperative flurbiprofen axetil therapy may be associated with prolonged RFS and OS in patients with esophageal carcinoma undergoing thoracoscopic esophagectomy.

Restriction Factors expression decreases in HIV-1 patients after cART.

Activation of interferon (IFN) mediated responses and the consequent expression of restriction factors (RFs) represent an early line of defense against HIV-1 infection. The levels of viral replication and the antiviral are among the determinants influencing RFs' expression pattern. A deeper understanding of the molecular mechanisms regulating RFs activity and their relationship with viral replication factors might lead to new therapeutic strategies based on the enhancement of immune response against the virus. The aim of this study is to perform a longitudinal evaluation of the variations in the levels of a group of selected RFs (APOBEC3G, BST2, TRIM5α, MX2, SAMHD1, SERINC3/5, IFI16 and STING) to determine the impact of cART on their expression in HIV-1 positive patients. Together with RFs expression, immunological and virological parameters (plasma HIV1-RNA load and total HIV1-DNA) were longitudinally evaluated in a cohorts fourteen HIV-1 cART na ve patients, who were evaluated at diagnosis (T0) and followed at 4 (T1) and 8 (T2) months after starting cART. Fourteen long-term treated patients who achieved sustained undetectable viremia for at least 2 years were also included in the study as a reference group. We observed a restoration of immunological conditions during cART, together with a progressive decrease of HIV1-RNA load, which became undetectable at 8 months after starting treatment. On the other hand, despite showing a trend towards decrease, total HIV1-DNA remained detectable after reaching viral suppression, similarly to what observed in long term treated patients. The expression of APOBEC3G, SAMHD1, BST2, IFI16, SERINC3, and SERINC5 was higher at the time of diagnosis and decreased significantly during therapy, reaching levels similar to the ones observed in virally suppressed patients. On the other hand, MX2 and TRIM5a high expression values up to T0, reaching lower levels immediately after the initiation of cART treatment. Correlation analysis showed a positive association between the expression levels of APOBEC3G, IFI16, MX2, SAMHD1, SERINC3 and TRIM5α with the HIV-1 viral load. On the contrary, no significant association was observed for BST2, SERINC5 and STING, even BST2 expression showed a tendency to correlate with viral load. We observed a tendency for a positive association of MX2, SAMHD1 and SERINC5 with the size of viral reservoir and a trend for a negative association for STING. STING appeared also as the only one factor whose expression correlates with the CD4 count and the CD4/CD8 ratio. Our data confirm the correlation between viral replication and expression of RFs, with, the levels of cellular defense proteins decreasing in parallel to the reduction of viral replication.

Label GM-PHD Filter Based on Threshold Separation Clustering.

Gaussian mixture probability hypothesis density (GM-PHD) filtering based on random finite set (RFS) is an effective method to deal with multi-target tracking (MTT). However, the traditional GM-PHD filter cannot form a continuous track in the tracking process, and it is easy to produce a large number of redundant invalid likelihood functions in a dense clutter environment, which reduces the computational efficiency and affects the update result of target probability hypothesis density, resulting in excessive tracking error. Therefore, based on the GM-PHD filter framework, the target state space is extended to a higher dimension. By adding a label set, each Gaussian component is assigned a label, and the label is merged in the pruning and merging step to increase the merging threshold to reduce the Gaussian component generated by dense clutter update, which reduces the computation in the next prediction and update. After pruning and merging, the Gaussian components are further clustered and optimized by threshold separation clustering, thus as to improve the tracking performance of the filter and finally realizing the accurate formation of multi-target tracks in a dense clutter environment. Simulation results show that the proposed algorithm can form a continuous and reliable track in dense clutter environment and has good tracking performance and computational efficiency.

The Rice CHD3/Mi-2 Chromatin Remodeling Factor Rolled Fine Striped Promotes Flowering Independent of Photoperiod.

Genetic studies have revealed that chromatin modifications affect flowering time, but the underlying mechanisms by which chromatin remodeling factors alter flowering remain largely unknown in rice (Oryza sativa). Here, we show that Rolled Fine Striped (RFS), a chromodomain helicase DNA-binding 3 (CHD3)/Mi-2 subfamily ATP-dependent chromatin remodeling factor, promotes flowering in rice. Diurnal expression of RFS peaked at night under short-day (SD) conditions and at dawn under long-day (LD) conditions. The rfs-1 and rfs-2 mutants (derived from different genetic backgrounds) displayed a late-flowering phenotype under SD and LD conditions. Reverse transcription-quantitative PCR analysis revealed that among the flowering time-related genes, the expression of the major floral repressor Grain number and heading date 7 (Ghd7) was mainly upregulated in rfs mutants, resulting in downregulation of its downstream floral inducers, including Early heading date 1 (Ehd1), Heading date 3a (Hd3a), and Rice FLOWERING LOCUS T 1 (RFT1). The rfs mutation had pleiotropic negative effects on rice grain yield and yield components, such as plant height and fertility. Taking these observations together, we propose that RFS participates in multiple aspects of rice development, including the promotion of flowering independent of photoperiod.

Expanding Ethanol Production in the United States: The Roles of Policy, Price, and Demand.

Assessments of the impact of the U.S. renewable fuel standard (RFS) should inform consideration of future biofuels policy. Conventional wisdom suggests the RFS played a major role in stimulating the ten-fold expansion in ethanol production and consumption in the United States from 2002 to 2019, but evidence increasingly suggests the RFS might have had a smaller effect than previously assumed. Price competitiveness, federal and state policies such as reformulated gasoline requirements, and octane content in ethanol also affect ethanol market attractiveness. This study explores the roles of policy and economic factors by comparing historical data with results from scenarios simulated in a system dynamics model. Results suggest price competitiveness explains much of the growth in the ethanol industry from 2002 to 2019. The Volumetric Ethanol Excise Tax Credit and phaseout of the oxygenate methyl tert-butyl ether contributed to earlier growth relative to expected timing of growth based on fuel price alone. The RFS (modeled through observed Renewable Identification Numbers [RINs]) contributed to increased ethanol production in later years and may have increased production in the earlier years if risk of investment was decreased.