Computational identification of key residues regulating fluorescence emission in a red/green cyanobacteriochrome.

Cyanobacteriochromes (CBCRs) are linear tetrapyrrole bilin-binding photoreceptors of cyanobacteria that exhibit high spectral diversity, gaining attention in optogenetics and bioimaging applications. Several engineering studies on CBCRs were attempted, especially for designing near-infrared (NIR) fluorescent proteins with longer fluorescence wavelengths. However, despite continuous efforts, a key component regulating fluorescence emission property in CBCRs is still poorly understood. As a model system, we focused on red/green CBCR Slr1393g3, from the unicellular cyanobacterium Synechocystis sp. PCC 6803 to engineer Pr to get far-red light-emitting property. Energy profiling and pairwise structural comparison of Slr1393g3 variants effectively reveal the mutations that are critical to the fluorescence changes. H497 seems to play a key role in stabilizing the chromophore environment, especially the α3 helix, while H495, T499, and Q502 are potential key residues determining fluorescence emission peak wavelength. We also found that mutations of α2 and α4 helical regions are closely related to the chromophore binding stability and likely affect fluorescence properties. Taken together, our computational analysis suggests that the fluorescence of Slr1393g3 is mainly controlled by the stabilization of the chromophore binding pocket. The predicted key residues potentially regulating the fluorescence emission property of a red/green CBCR will be advantageous for designing improved NIR fluorescent protein when combined with in vitro molecular evolution approaches.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

SUnSeT: spectral unmixing of hyperspectral images for phenotyping soybean seed traits.

KEY MESSAGE: Hyperspectral features enable accurate classification of soybean seeds using linear discriminant analysis and GWAS for novel seed trait genes. Evaluating crop seed traits such as size, shape, and color is crucial for assessing seed quality and improving agricultural productivity. The introduction of the SUnSet toolbox, which employs hyperspectral sensor-derived image analysis, addresses this necessity. In a validation test involving 420 seed accessions from the Korean Soybean Core Collections, the pixel purity index algorithm identified seed- specific hyperspectral endmembers to facilitate segmentation. Various metrics extracted from ventral and lateral side images facilitated the categorization of seeds into three size groups and four shape groups. Additionally, quantitative RGB triplets representing seven seed coat colors, averaged reflectance spectra, and pigment indices were acquired. Machine learning models, trained on a dataset comprising 420 accession seeds and 199 predictors encompassing seed size, shape, and reflectance spectra, achieved accuracy rates of 95.8% for linear discriminant analysis model. Furthermore, a genome-wide association study utilizing hyperspectral features uncovered associations between seed traits and genes governing seed pigmentation and shapes. This comprehensive approach underscores the effectiveness of SUnSet in advancing precision agriculture through meticulous seed trait analysis.

Mean 23-Year Outcomes of Total Hip Arthroplasty Using a Modular Femoral Stem With Metaphyseal Fixation Sleeve.

BACKGROUND: Although the modular sleeve concept for femoral implants has several advantages, studies reporting on greater than 20-year outcomes are limited. This study aimed to report the mean 23-year results of total hip arthroplasty (THA) using a modular stem with metaphyseal fixation sleeve. METHODS: This study reviewed primary THAs performed using a modular stem between October 1994 and April 1998. Of the 272 hips (221 patients) identified, 220 hips (177 patients) satisfying the minimum 20-year follow-up were included. The Harris Hip Score was used for clinical evaluation. Final hip radiographs were analyzed to evaluate the implant stability and the extent of femoral osteolysis. The mean follow-up duration was 23 years (range, 20 to 28). RESULTS: The mean Harris Hip Score improved from 38 points (range, 26 to 67) preoperatively to 90 points (range, 71 to 100) at the final follow-up (P < .001). Femoral osteolysis was observed in 146 hips (67.1%), but 145 were located proximal to the osseo-integrated sleeve. Overall, 4 femoral revisions were performed; 2 for chronic infection, one for aseptic loosening, and one for periprosthetic femoral fracture. Of the 19 (8.6%) periprosthetic femoral fractures, the most common type was Vancouver AG (13 hips). One (0.5%) asymptomatic distal stem fracture occurred, while no complications were identified at the stem-sleeve junction. Implant survivorship free of any femoral revision was 98.3% at 23 years. CONCLUSIONS: A THA using a modular stem with metaphyseal fixation sleeve demonstrated 98.3% stem survivorship with excellent clinical outcomes at a mean follow-up of 23 years in non-obese patients.

Bearing-Related Complications of Total Hip Arthroplasty Using Fourth-Generation Ceramic-On-Ceramic Articulations: Does Articular Noise Increase Over Time?

BACKGROUND: We previously reported the mean 6-year outcomes of total hip arthroplasty (THA) using fourth-generation ceramic-on-ceramic (CoC) articulations. With extended observations, this study aimed to report the mean 12-year outcomes focusing on bearing-related complications of CoC THA. METHODS: We reviewed primary CoC THAs performed between May 2009 and April 2012 at a single institution. Of the 831 hips (739 patients), 716 hips (635 patients) that satisfied a minimum 10-year follow-up were included. The mean age at operation was 54 years (range, 16 to 83). The occurrence of bearing-specific complications, including ceramic fractures and noise generation, was evaluated. The mean follow-up duration was 12 years (range, 10 to 14). RESULTS: A total of 2 (0.3%) ceramic liner fractures occurred, as previously reported. No additional ceramic fractures were observed during the extended follow-up period. However, the cumulative incidence of audible noise increased from 6.4 (48 of 749) to 8.2% (59 of 716). Of the 59 hips with noise, 26 (44.1%) developed noise within 1 year, whereas 13 (22.0%) presented with noise more than 5 years after THA. The noise was described as clicking in 35 hips (4.9%) and as squeaking in 24 hips (3.4%). No revision surgeries were performed for noise, except in 2 cases of concomitant liner fractures. The implant survivorship free of any revision was 98.1% at 12 years. CONCLUSIONS: No additional ceramic fractures were identified in this extension study at a minimum follow-up of 10 years. However, the prevalence of articular noise has increased from 6.4 to 8.2% since the previous report. Possible late-onset noise should be considered when performing CoC THA in younger patients.

A Hybrid Approach for Energy Consumption and Improvement in Sensor Network Lifespan in Wireless Sensor Networks.

In this paper, we propose an improved clustering algorithm for wireless sensor networks (WSNs) that aims to increase network lifetime and efficiency. We introduce an enhanced fuzzy spider monkey optimization technique and a hidden Markov model-based clustering algorithm for selecting cluster heads. Our approach considers factors such as network cluster head energy, cluster head density, and cluster head position. We also enhance the energy-efficient routing strategy for connecting cluster heads to the base station. Additionally, we introduce a polling control method to improve network performance while maintaining energy efficiency during steady transmission periods. Simulation results demonstrate a 1.2% improvement in network performance using our proposed model.

Incidence and Risk Factors of Iliopsoas Tendinopathy After Total Hip Arthroplasty: A Radiographic Analysis of 1,602 Hips.

BACKGROUND: Iliopsoas tendinopathy (IPT) can cause persistent groin pain and lead to dissatisfaction after total hip arthroplasty (THA). This study aimed to report the characteristics, incidences, risk factors, and treatment outcomes of IPT after THA. METHODS: We reviewed primary THAs performed at a single institution between January 2012 and May 2018. Clinical and radiographic analyses were performed on 1,602 THAs (1,370 patients). Patient characteristics, component sizes, inclination and anteversion angles, and antero-inferior cup prominence (≥8 millimeters (mm)), were compared between the groups with and without IPT. Changes in teardrop to lesser trochanter distance were measured to estimate changes in leg length and horizontal offset caused by THA. Logistic regression models were used to identify the risk factors for IPT. IPT was identified in 53 hips (3.3%). RESULTS: Patients with IPT had greater leg lengthening (12.3 versus 9.3 mm; P = .001) and higher prevalence of antero-inferior cup prominence (5.7 versus 0.4%; P = .002). There was no significant difference in inclination, anteversion, and horizontal offset change between the two groups. In multivariate analyses, greater leg lengthening, prominent acetabular cup, women, and higher body mass index were associated with IPT. All patients reported improvement in groin pain after arthroscopic tenotomy, while 35.7% with nonoperative management reported improvement (P < .001). CONCLUSIONS: Symptomatic IPT occurred in 53 (3.3%) of the 1,602 primary THAs. Our findings suggest that leg lengthening as well as prominent acetabular cup in THAs can be associated with the development of IPT. Arthroscopic tenotomy was effective in relieving groin pain caused by IPT.

Long-Term Outcomes of Cementing Highly Cross-Linked Polyethylene Liners Into Well-Fixed Acetabular Shells in Revision Total Hip Arthroplasty.

BACKGROUND: Cementing a new liner into a secure, well-positioned metallic shell can be a less-invasive strategy in revision total hip arthroplasty (THA). This study aimed to report the mean 14-year outcomes of cementing highly cross-linked polyethylene (XLPE) liners into well-fixed acetabular shells in revision THAs. METHODS: This study reviewed a single-surgeon series of cementing XLPE liners into well-fixed acetabular components. Of the 52 hips (51 patients) evaluated, 48 hips (47 patients) that satisfied a minimum follow-up of 10 years were included. The Harris Hip score was used for clinical evaluation. Final hip radiographs were used to determine the extent of acetabular osteolysis and stability of the components. The mean age at index operation was 53 years (range, 32 to 72). The mean follow-up duration was 14 years (range, 10 to 18). RESULTS: The mean Harris Hip score improved from 58 points (range, 23-81) preoperatively to 91 points (range, 45-100) at the final evaluation (P < .001). A total of 3 acetabular rerevisions were performed, all for aseptic loosening of the outer shell. One postoperative dislocation occurred, but it was successfully treated with a closed reduction. Final radiographs showed a significant reduction in acetabular osteolysis (P < .001). Implant survivorship free from any rerevision was 93.3% (95% confidence interval, 85.9-100%) at 14 years. CONCLUSION: Cementing an XLPE liner into a well-fixed acetabular shell in revision THA demonstrated excellent clinical and radiographic outcomes at a mean of 14 years postoperatively. This technique could be a safe and durable option in the absence of XLPE liners compatible with preimplanted shells.

Rectangular Taper Stem Designs Are Associated With a Higher Risk for Periprosthstic Femoral Fractures After Cementless Total Hip Arthroplasty.

BACKGROUND: Periprosthetic femoral fractures (PFFs) remain a major concern following cementless total hip arthroplasty (THA). This study aimed to evaluate the association between different types of cementless tapered stems and the risk of postoperative PFF. METHODS: A retrospective review of primary THAs performed at a single center from January 2011 to December 2018 included 3,315 hips (2,326 patients). Cementless stems were classified according to their design. The incidence of PFF was compared between flat taper porous-coated stems (type A), rectangular taper grit-blasted stems (type B1), and quadrangular taper hydroxyapatite-coated stems (type B2). Multivariate regression analyses were performed to identify independent factors related to PFF. The mean follow-up duration was 61 months (range, 12 to 139). Overall, 45 (1.4%) postoperative PFFs occurred. RESULTS: The incidence of PFF was significantly higher in type B1 stems than in type A and type B2 stems (1.8 versus 0.7 versus 0.7%; P = .022). Additionally, more surgical treatments (1.7 versus 0.5 versus 0.7%; P = .013) and femoral revisions (1.2 versus 0.2 versus 0%; P = .004) were required for PFF in type B1 stems. After controlling for confounding variables, older age, diagnosis of hip fracture, and use of type B1 stems were significant factors associated with PFF. CONCLUSION: Type B1 rectangular taper stems were found to have higher risks for postoperative PFF and PFF requiring surgical management than type A and type B2 stems in THA. Femoral stem geometry should be considered when planning for cementless THA in elderly patients who have compromised bone quality.

ORESARA 15, a PLATZ transcription factor, controls root meristem size through auxin and cytokinin signalling-related pathways.

An optimal size of post-embryonic root apical meristem (RAM) is achieved by a balance between cell division and differentiation. Despite extensive research, molecular mechanisms underlying the coordination of cell division and differentiation are still fragmentary. Here, we report that ORESARA 15 (ORE15), an Arabidopsis PLANT A/T-RICH SEQUENCE-AND ZINC-BINDING PROTEIN (PLATZ) transcription factor preferentially expressed in the RAM, determines RAM size. Primary root length, RAM size, cell division rate, and stem cell niche activity were reduced in an ore15 loss-of-function mutant but enhanced in an activation-tagged line overexpressing ORE15, compared with wild type. ORE15 forms mutually positive and negative feedback loops with auxin and cytokinin signalling, respectively. Collectively, our findings imply that ORE15 controls RAM size by mediating the antagonistic interaction between auxin and cytokinin signalling-related pathways.

Short-Term Impact of Temporary Shutdown of a University-Affiliated Hospital on Patients With Colorectal Cancer During the Coronavirus Disease 2019 Pandemic.

Owing to in-hospital transmission of coronavirus disease 2019 (COVID-19), Uijeongbu St. Mary's Hospital, a university-affiliated hospital in South Korea, was temporarily closed for disinfection in March 2020. This study aimed to investigate the impact of both the hospital shutdown and the prolonged COVID-19 pandemic on short-term outcomes of colorectal cancer (CRC) patients. We retrospectively reviewed the clinicopathologic data of 607 patients who were surgically treated for CRC from May 2018 to September 2021. Nodal upstaging, higher lymphatic invasion and abdominoperineal resection rates for 3 months after the hospital resumed surgery following the shutdown in the first wave of the COVID-19 pandemic were detected, without worse short-term morbidity or mortality. The incidence of adverse pathologic features of CRC such as lymphatic, venous, and perineural invasion was higher throughout the COVID-19 pandemic era. Further follow-up of CRC patients treated in the pandemic era for long-term oncologic outcomes is needed.

Effects of nurse-led nonpharmacological pain interventions for patients with cancer: A systematic review and meta-analysis.

PURPOSE: The purposes of this study were to review the types of nurse-led nonpharmacological pain interventions (NPI) offered to cancer patients and/or family caregivers, and to determine a comprehensive and robust estimate of the effect size of nurse-led NPI for cancer patients on various pain-related outcomes. DESIGN: Systematic review and meta-analysis. Studies assessing nurse-led NPIs targeting cancer patients and published between January 2008 and December 2020 were identified by searching multiple literature databases, including MEDLINE® , EMBASE, Google Scholar, Cochrane Library, ProQuest Medical Library, and CINAHL® . METHODS: This review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-analyses guidelines. The selected randomized clinical trials were independently assessed for methodological quality. The effect sizes (ESs) of treatment were presented as standardized mean differences (Hedges' g) and 95% confidence intervals (CIs). FINDINGS: A meta-analysis was performed to analyze data from 22 randomized clinical trials. Three types of nurse-led NPI were offered, mainly to cancer patients but also to some caregivers: music, physical, and psycho-educational interventions. The dose and duration of nonpharmacological interventions varied widely. The study participants ranged in age from 44.1 to 67.3 years. Meta-analysis indicated that, although these interventions had small effects in long-term (g = 0.24, 95% CI: 0.06-0.43, p = 0.011) to medium effects in short-term (g = 0.43, 95% CI: 0.32-0.53, p < 0.001), they significantly reduced patients' pain, increased their knowledge of pain management, reduced barriers to pain management and pain coping, and improved other physical and emotional symptoms. The significance of the ES differed according to the type of intervention, with psycho-educational and physical NPIs having a significant but medium short-term ES, whereas music NPI had a significant but large short-term ES. Only psycho-educational NPIs had significant long-term effects. CONCLUSION: The combined ES showed that these nurse-led NPIs were significantly effective in both the short and long-term. Types of intervention as a potential moderator were associated with short-term and long-term effects of nonpharmacological interventions on patient outcomes. CLINICAL RELEVANCE: Research-tested interventions should be provided to help patients cope effectively with pain.

Long-Term Outcomes of Revision Total Hip Arthroplasty Using a Tapered and Fluted Modular Stem: A Mean Follow-Up of 16 Years.

BACKGROUND: Tapered modular stems are increasingly used in revision total hip arthroplasty (THA) with deficient femoral bone stock. This study aimed to report the long-term outcomes of revision THA using a tapered and fluted modular stem. METHODS: Between December 1998 and February 2006, 113 revision THAs (110 patients) were performed with a tapered and fluted modular stem at a single institution. Hip radiographs were used to identify stem subsidence, stability, and femoral radiolucency. Final outcomes were assessed in 72 hips (70 patients), with a minimum follow-up of 10 years. RESULTS: The mean follow-up duration was 16 years (range, 10-23). At the final evaluation, the Harris Hip Score improved from a mean of 41 points (range, 10-72) preoperatively to 83 points (range, 56-100) (P < .001). Six femoral re-revisions were performed for the following reasons: 1 aseptic loosening, 2 stem fractures, and 3 infections. One stem fracture occurred at the modular junction after 14 years, and the other at a more distal location after 15 years. Stem subsidence was >5 mm in 6 hips (9.1%), but secondary stability was achieved in all stems. Osseointegration was observed in 63 (95.5%) hips. Stem survivorship was 91.1% with an end point of any re-revision and 94.6% for aseptic re-revision. CONCLUSION: A tapered and fluted modular stem demonstrated excellent implant survivorship with reliable bony fixation at a mean follow-up of 16 years. This type of stem can be a durable option for revision THA in patients who have femoral defects.

Outcomes of revision total hip arthroplasty using the modular dual mobility acetabular system to treat recurrent dislocation.

BACKGROUND: Recurrent dislocation is a difficult complication after total hip arthroplasty (THA). This study aimed to report the clinical and radiographic outcomes of revision THA using the modular dual mobility (MDM) acetabular system to treat recurrent dislocation. METHODS: Between March 2015 and February 2019, 34 revision THAs were performed using the MDM system for treating recurrent dislocation in a single institution. Of these, 32 revision THAs (32 patients) that satisfied a minimum follow-up of one year (mean, 4 years) were included in this study. Patient-reported outcomes, complication rates, and radiographic results were evaluated. RESULTS: Seventeen patients (53.1%) had lumbar degenerative kyphosis, and six (18.8%) had surgically fused lumbar spines during the index operation. All acetabular components were revised, whereas femoral stems were retained in 29 patients (90.6%). No redislocation or intraprosthetic dislocation was noted after revision. One additional revision was required for acetabular loosening with periprosthetic joint infection. No additional revision was performed for aseptic loosening. A partial radiolucent line was found in two hips (6.3%) confined to one acetabular zone. CONCLUSIONS: Revision THA using the MDM system was effective in treating recurrent dislocation in a group of patients with a high prevalence of lumbar spinal pathology. During a mean follow-up of 4 years, one additional revision THA was performed for septic loosening and none for aseptic loosening.

Spectral and photochemical diversity of tandem cysteine cyanobacterial phytochromes.

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue-absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical "second" cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.

The NanDeSyn database for Nannochloropsis systems and synthetic biology.

Nannochloropsis species, unicellular industrial oleaginous microalgae, are model organisms for microalgal systems and synthetic biology. To facilitate community-based annotation and mining of the rapidly accumulating functional genomics resources, we have initiated an international consortium and present a comprehensive multi-omics resource database named Nannochloropsis Design and Synthesis (NanDeSyn; http://nandesyn.single-cell.cn). Via the Tripal toolkit, it features user-friendly interfaces hosting genomic resources with gene annotations and transcriptomic and proteomic data for six Nannochloropsis species, including two updated genomes of Nannochloropsis oceanica IMET1 and Nannochloropsis salina CCMP1776. Toolboxes for search, Blast, synteny view, enrichment analysis, metabolic pathway analysis, a genome browser, etc. are also included. In addition, functional validation of genes is indicated based on phenotypes of mutants and relevant bibliography. Furthermore, epigenomic resources are also incorporated, especially for sequencing of small RNAs including microRNAs and circular RNAs. Such comprehensive and integrated landscapes of Nannochloropsis genomics and epigenomics will promote and accelerate community efforts in systems and synthetic biology of these industrially important microalgae.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

BACKGROUND: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODS: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTS: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONS: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).

Routine colonoscopy may be needed for uncomplicated acute right colonic diverticulitis.

BACKGROUND: Routine colonoscopy is recommended to determine the coexistence of colon cancer after medical treatment for colon diverticulitis. However, in the case of uncomplicated diverticulitis diagnosed by computed tomography, the clinical relevance of routine follow-up colonoscopy has recently been debated. Yet, the role of follow-up colonoscopy for right colon diverticulitis, which tends to develop at a younger age than left colon diverticulitis, has not been specifically evaluated. Therefore, we aimed to evaluate the incidence of right colon cancer or colonic adenomatous polyps, detected by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis. METHODS: Patients with uncomplicated right colon diverticulitis (modified Hinchey stage Ia) diagnosed by computed tomography imaging, between 2011 and 2017, and who underwent follow-up colonoscopy surveillance after treatment were included. The primary outcome was the incidence of colon cancer, with the detection rate of adenoma being the secondary outcome. Information for analysis was retrieved retrospectively from patients' medical records. RESULTS: The study group included 330 consecutive patients, with a mean age of 41.9 years, and 51.9% being men. For the primary outcome, the rate of colon cancer on follow-up colonoscopy was 0.3% (1/330 cases). The rate of adenoma detection was 20.9% (69/330 cases) and advanced adenoma (> 10 mm in diameter; or exhibiting a > 25% villous component or severe dysplasia), including colon cancer, was observed in 9 patients (2.7%). CONCLUSIONS: In patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because although the colon cancer detection rate is low, it is possible to detect advanced colon adenoma.

The continuous development of a complete and objective automatic grading system of facial signs from selfie pictures: Asian validation study and application to women of three ethnic origins, differently aged.

OBJECTIVE: To evaluate the capacity of the automatic detection system to accurately grade, from smartphones' selfie pictures, the severity of seven new facial signs added to the nine previously integrated. METHODS: A two-step approach was conducted: first, to check on 112 Korean women, how the AI-based automatic grading system may correlate with dermatological assessments, taken as reference; second, to confirm on 1140 women of three ancestries (African, Asian, and Caucasian) the relevance of the newly input facial signs. RESULTS: The sixteen specific Asian facial signs, detected automatically, were found significantly (P < .0001) highly correlated with the clinical evaluations made by two Korean dermatologists (wrinkles: r = .90; sagging: r = .75-.95; vascular: r = .85; pores: r = .60; pigmentation: r = .50-.80). When applied at a larger scale on women of different ethnicities, new signs were found of good accuracy and reproducibility, albeit depending on ethnicity. Due to contrast with the innate skin complexion, the facial signs dealing with skin pigmentation were found of a much higher relevance among Asian women than African or Caucasian women. The automatic gradings were even found of a slightly higher accuracy than the clinical gradings. CONCLUSION: The previously used automatic grading system is now completed by adding new facial signs apt at being detected. The continuous development is now integrating some limitations with regard to the constitutive skin complexion of the self-pictured subjects. Presenting reproducible assessments, highly correlated with medical grading, this system could change tremendously clinical researches, like in epidemiological studies, where it offers an easy, fast, affordable, and confidential approach in the objective quantification of facial signs.

Peptide transporter2 (PTR2) enhances water uptake during early seed germination in Arabidopsis thaliana.

KEY MESSAGE: PTR2 in Arabidopsis thaliana is negatively regulated by ABI4 and plays a key role in water uptake by seeds, ensuring that imbibed seeds proceed to germination. Peptide transporters (PTRs) transport nitrogen-containing substrates in a proton-dependent manner. Among the six PTRs in Arabidopsis thaliana, the physiological role of the tonoplast-localized, seed embryo abundant PTR2 is unknown. In the present study, a molecular physiological analysis of PTR2 was conducted using ptr2 mutants and PTR2CO complementation lines. Compared with the wild type, the ptr2 mutant showed ca. 6 h delay in testa rupture and consequently endosperm rupture because of 17% lower water content and 10% higher free abscisic acid (ABA) content. Constitutive overexpression of the PTR2 gene under the control of the Cauliflower mosaic virus (CaMV) 35S promoter in ptr2 mutants rescued the mutant phenotypes. After cold stratification, a transient increase in ABA INSENSITIVE4 (ABI4) transcript levels during induction of testa rupture was followed by a similar increase in PTR2 transcript levels, which peaked prior to endosperm rupture. The PTR2 promoter region containing multiple CCAC motifs was recognized by ABI4 in electrophoretic mobility shift assays, and PTR2 expression was repressed by 67% in ABI4 overexpression lines compared with the wild type, suggesting that PTR2 is an immediate downstream target of ABI4. Taken together, the results suggest that ABI4-dependent temporal regulation of PTR2 expression may influence water status during seed germination to promote the post-germinative growth of imbibed seeds.