•Despite major efforts in the management of PeCa aimed at improving staging and consequently providing more solid indications for OSS, there hasn't been a notable shift towards more conservative ...treatments.•Surgeries for advanced-stage tumors are still marked by high rates of complications potentially affect the sexual and psychosocial health of patients.•Mutations in SWI-SNF complex and inactivated JAK-STAT signaling enriched at relapse.•These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation of the disease as well as its treatment.
Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors.
Primary aim of our study is to evaluate the incidence and risk factors of PeCa and to outline the adopted diagnostic and therapeutic approaches. Secondary aim is to investigate risk factors associated with aggressive disease and to identify the complications arising from its surgical treatment.
We conducted a retrospective analysis using the PearlDiver™ Mariner database, from January 1, 2011, to December 31, 2021, identifying all patients diagnosed with PeCa and PeIN, evaluating comorbidities, risk factors, and social and economic conditions. We evaluated the imaging modalities employed for staging as well as the treatment strategies. Finally, we evaluated the most frequent complications associated with inguinal lymphadenectomy (ILND).
During the study period, 17,494 patients were diagnosed with PeCa and 5,965 with penile intraepithelial neoplasia (PeIN). US was the most frequently utilized imaging modality, followed by PET and PET/CT. Use of CT and MRI was around 5%. Surgical treatment was the predominant strategy, utilized in 31.3% of PeCa and 22.9% of PeIN. Wide Local Excision/Glansectomy emerged as the most common surgical procedures. MLR analysis identified smoking as a risk factor for metastatic PeCa (OR; 95% CI = 1.49; 1.379–1.609), HPV infections were associated with a 35% decrease in risk (OR; 95% CI = 0.65; 0.562–0.744) (all P < 0.001). Lichen sclerosus and phimosis were associated with a doubled risk of demolitive surgery. Approximately 40% of patients experienced complications associated with ILND.
Despite advances in PeCa management, there's no significant move toward more conservative treatments. Surgical treatments are still marked by high rates of complications, potentially affect the sexual and psychosocial health of patients. These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation and treatment.
Near-real-time precipitation estimates based on geostationary meteorological satellites are of great importance for monitoring hydrology-related disasters. Currently, the contributions of ...multispectral infrared observations to precipitation estimation have not been fully understood thus far. Motivated by estimating precipitation based on real-time data from geostationary satellites, this study proposes the Precipitation Estimation using Chromatographic Analysis (PECA) methodology based on full-disc observations from Advanced Geosynchronous Radiation Imager (AGRI) of FengYun-4A (FY-4A). Compared with PERSIANN-CCS and FY4AQPE-Official, the results of PECA (PECA-FY4A) are comprehensively evaluated against the GSOD (global gauge data), CMS (Chinese gauge data) and IMERG-LR (micro-wave precipitation products) for the period from January, 2019 to November, 2021. The findings and conclusions mainly include but are not limited to the following: (1) PECA clearly reveals that T12, ∆T10−14, ∆T7−14, and ∆T7−8 are effective for estimating precipitation volumes, with strong correlation to precipitation volumes but significantly less redundant information. (2) IR band differences are still sensitive to heavy precipitation although the abilities of single IR bands have become insufficient. For example, ∆T7−8 are sensitive to heavy precipitation in the eye walls of the typhoons. (3) The evaluation results show that PERSIANN-CCS generally outperforms FY4AQPE-Official, while PECA-FY4A features significant improvements over PERSIANN-CCS (the international benchmark of IR precipitation products) in terms of CC (∼10%, ∼100%, and ∼ 21%), RMSE (∼20%, ∼36%, and ∼ 11%), and CSI (∼25%, ∼100%, and ∼ 12%) against IMERG-LR, CMS and GSOD, respectively. The findings are expected to considerably contribute towards extending the current three-geostationary-satellite-series network (GOES, Meteosat, and Himawari) in PERSIANN-CCS to a four-geostationary-satellite-series network (by adding FY-4A and FY-4B) using PECA with higher quality, especially over the Asia-Pacific areas.
•Full disk multispectral observations of FY-4A are comprehensively considered.•The relationships between precipitation and multiple IR bands are quantified.•The mathematical mechanism of PECA is explainable.•The parameters in PECA are adaptive to the seasonal variances.
Theoretical simulations of dispersed solid particle behaviour inside a scrubbing pool within the bubble rise region are presented. The goal is to evaluate the decontamination factor of the particles ...during the pool scrubbing process. The basic phenomena of pool scrubbing are described. The setup used for the simulation validation is presented. Then, the boundary and initial conditions of the PECA experiments, which were performed at CIEMAT (Madrid, Spain) and were used for simulations, are presented. The subgrid model for decontamination through transfer of particles from gas bubbles to the surrounding liquid is described. The calculation results are evaluated and compared with the part of the PECA experimental results to which the proposed modelling is applicable.
The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in ...mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse‐like pattern and returned to values close to pre‐treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes.
Synopsis
The contribution of mRNA and protein level regulation in the mammalian endoplasmic reticulum stress response is deconvoluted by analyzing time‐series protein and matching mRNA concentrations with a new statistical tool.
Protein and mRNA concentrations are quantified at different time points, generating a high‐confidence dataset of 1,237 genes/mRNAs.
A new statistical tool quantifies the contribution of regulatory processes and shows that mRNA and protein level regulation play similarly important roles.
mRNA and protein level regulation have different dynamics: mRNA concentrations spike in their change and return to pre‐perturbation levels, while protein concentrations switch in their behavior and reach a new steady‐state.
Hypotheses on modes of regulation for several groups of genes are presented.
The contribution of mRNA and protein level regulation in the mammalian endoplasmic reticulum stress response is deconvoluted by analyzing time‐series protein and matching mRNA concentrations with a new statistical tool.
Background:
Patients with severe hallux valgus deformity present technical and operative challenges with high rates of recurrence and residual deformity. The clinical and radiologic outcomes of ...percutaneous surgery for severe hallux valgus are not known.
Methods:
A retrospective review of consecutive patients with a hallux valgus angle (HVA) >40 degrees or intermetatarsal angle (IMA) >20 degrees who underwent third-generation percutaneous chevron and Akin osteotomy (PECA) for hallux valgus deformity correction.
Results:
Between December 2012 and August 2019, 59 feet in 50 patients underwent PECA. Preoperative and follow-up radiographic data were available for 53 feet (89.8%). Postoperative clinical patient-reported outcome measures and satisfaction results were available for 51 feet (86.4%). The mean clinical and radiographic follow-up was 3.1 years and the mean postoperative Manchester-Oxford Foot Questionnaire Index score was 15.1. There was a statistically significant improvement (P < .001) in both IMA and HVA following surgery (IMA 17.5-5.1 degrees; HVA 44.1-11.5 degrees). All patients reported they were satisfied with their outcome, with 76.8% reporting they were highly satisfied. The hallux valgus recurrence rate was 7.5%.
Conclusion:
Percutaneous surgery for severe hallux valgus deformity can achieve a large deformity correction, patient satisfaction, and quality of life, with reasonable rates of residual deformity and low rates of recurrence.
Level of Evidence:
Level IV, case series.
iPSC reprogramming involves dynamic changes in chromatin accessibility necessary for the conversion of somatic cells into induced pluripotent stem cells (iPSCs). IPSCs can be used to generate a wide ...range of cells to potentially replace damaged cells in a patient without the threat of immune rejection; however, efficiently reprogramming cells for medical applications remains a challenge, particularly in human cells. Here, we conducted a cross-species meta-analysis to identify conserved and species-specific differences in regulatory patterns during reprogramming. Chromatin accessibility and transcriptional data as fibroblasts transitioned to iPSCs were obtained from the publicly available Gene Expression Omnibus (GEO) database and integrated to generate time-resolved regulatory networks during cellular reprogramming. We observed consistent and conserved trends between the species in the chromatin accessibility signatures as cells transitioned from fibroblasts into iPSCs, indicating distal control of genes associated with pluripotency by master reprogramming regulators. Multi-omic integration showed key network changes across reprogramming states, revealing regulatory relationships between chromatin regulators, enhancers, transcription factors, and target genes that result in the silencing of the somatic transcription program and activation of the pluripotency gene regulatory network. This integrative analysis revealed distinct network changes between timepoints and leveraged multi-omics to gain novel insights into the regulatory mechanisms underlying reprogramming.
Theoretical simulations of dispersed solid particle behaviour inside a scrubbing pool within the bubble rise region are presented. The goal is to evaluate the decontamination factor of the particles ...during the pool scrubbing process. The basic phenomena of pool scrubbing are described. The setup used for the simulation validation is presented. Then, the boundary and initial conditions of the PECA experiments, which were performed at CIEMAT (Madrid, Spain) and were used for simulations, are presented. The subgrid model for decontamination through transfer of particles from gas bubbles to the surrounding liquid is described. The calculation results are evaluated and compared with the part of the PECA experimental results to which the proposed modelling is applicable.
Background:
Fourth-generation minimally invasive surgery (MIS) includes the multiplanar rotational deformity correction achieved through manipulation of an extra-articular distal first metatarsal ...osteotomy that is held with rigid fixation using 2 fully threaded screws, of which one must be bicortical to provide rotational and biomechanical stability. The aim of this study is to report the clinical and radiologic outcomes of an evolved fourth-generation MIS hallux valgus technique.
Methods:
A prospective single-surgeon series of consecutive patients undergoing fourth-generation MIS was performed using a distal transverse osteotomy with a minimum 12-month follow-up. The primary outcome was the Manchester-Oxford Foot Questionnaire (MOXFQ), a validated clinical patient-reported outcome measure (PROM). Secondary outcomes included radiographic deformity correction, clinical assessment, and EuroQol-5D-5L PROMs.
Results:
Between September 2019 and June 2021, 50 feet underwent fourth-generation MIS. The mean age was 55.8±15.3 years with a mean follow-up of 1.4 years. Preoperative and minimum 12-month primary outcome data were available for 100% of feet. There was a significant improvement in all MOXFQ domain scores, with the index domain improving from 53.4 to 13.1 (P < .001). There was a significant improvement (P < .001) in hallux valgus angle (32.7 to 7.9 degrees), intermetatarsal angle (14.0 to 4.2 degrees) and distal metatarsal articular angle (18.5 to 5.6 degrees). There was a significant improvement in general health-related quality of life EQ-5D-5L index and EQ-VAS scores (P < .05).
Conclusion:
The fourth-generation MIS technique is a safe and effective approach to hallux valgus deformity correction with significant improvement in clinical and radiographic outcomes.
Level of Evidence:
Level IV, prospective case series.
The learning curve to reach technical proficiency for third-generation percutaneous or minimally invasive chevron and Akin osteotomies (PECA/MICA) is recognized to be steep however it is poorly ...defined in the literature. This study is a retrospective review of the first 58 consecutive PECA cases of a single surgeon. The primary outcome was the number of cases required to reach technical proficiency as defined by the operation time. Secondary outcomes included radiation exposure, radiographic deformity correction, and complication rates. Between November 2017 and March 2019, 61 consecutive PECA cases were performed with outcome data available for 58 of these (95%). Technical proficiency was reached after 38 cases. Operation time and radiation exposure significantly decreased after this transition point (p < .05). There was no difference in complication rate or radiographic deformity correction regardless of position along the learning curve (p > .05). In conclusion, the mean number of cases required to reach technical proficiency in third-generation PECA is 38 cases. The complication rate does not correlate to the number of cases performed, therefore surgeons interested in learning minimally invasive surgery can be reassured that there is unlikely to be an additional risk of harm to a patient during the learning curve.
Background:
Recent large studies of third-generation minimally invasive hallux valgus surgery (MIS) have demonstrated significant improvement in clinical and radiologic outcomes. It remains unknown ...whether these clinical and radiologic outcomes are maintained in the medium to long term. The aim of this study was to investigate the minimum 5-year clinical and radiologic outcomes following third-generation MIS hallux valgus surgery in the hands of a high-volume MIS surgeon.
Methods:
A retrospective observational single highly experienced MIS surgeon case series of consecutive patients undergoing primary isolated third-generation percutaneous chevron and Akin osteotomies (PECA) for hallux valgus with a minimum 60-month clinical and radiographic follow-up. Primary outcome was radiographic assessment of the hallux valgus angle (HVA) and intermetatarsal angle (IMA) preoperatively, 6 months, and ≥60 months following PECA. Secondary outcomes included the Manchester-Oxford Foot Questionnaire, patient satisfaction, EuroQol-5D visual analog scale and the visual analog scale for pain.
Results:
Between 2012 and 2014, 126 consecutive feet underwent isolated third-generation PECA, with complete data available for 78 (61.9%) feet. The median follow-up was 65.0 (IQR 64-69; range 60-88) months. There was a significant improvement in radiographic deformity correction; the median IMA improved from 12.0 degrees (interquartile range IQR: 10.8-14.2) to 6.0 degrees (IQR: 4.2-7.3) (P < .001), and the median HVA improved from 27.2 degrees (IQR: 20.6-34.4) to 7.2 degrees (IQR: 3.4-11.6). Median MOXFQ Index score at ≥60-month follow-up was 2.3 (IQR: 0.0-7.8). The radiographic recurrence rate (defined as HVA >15 degrees) was 7.7% at final follow-up. The complication rate was 4.8%.
Conclusion:
Radiologic deformity correction for the 78 feet we were able to follow that had third-generation PECA performed by a single highly experienced MIS surgeon was found to be maintained at a mean follow-up of average 66.8 months, with a radiographic recurrence rate of 7.7%. Clinical PROMs and patient satisfaction levels were high and comparable to other third-generation studies with shorter duration of follow-up.
Level of Evidence:
Level IV, retrospective cohort study.
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