Clusters of medical specialties around patients with multimorbidity - employing fuzzy c-means clustering to explore multidisciplinary collaboration.

BACKGROUND: Hospital care organization, structured around medical specialties and focused on the separate treatment of individual organ systems, is challenged by the increasing prevalence of multimorbidity. To support the hospitals' realization of multidisciplinary care, we hypothesized that using machine learning on clinical data helps to identify groups of medical specialties who are simultaneously involved in hospital care for patients with multimorbidity. METHODS: We conducted a cross-sectional study of patients in a Dutch general hospital and used a fuzzy c-means clustering algorithm for the analysis. We explored the patients' membership degrees in each cluster to identify subgroups of medical specialties that provide care to the same patients with multimorbidity. We used retrospectively collected electronic health record data from 2017. We extracted data from 22,133 patients aged ≥18 years who had received outpatient clinical care for two or more chronic and/ or oncological diagnoses. RESULTS: We found six clusters of medical specialties and identified 22 subgroups. The clusters were labeled based on the specialties that most characterized them: 1. dermatology/ plastic surgery, 2. six specialties (gynecology/ rheumatology/ orthopedic surgery/ urology/ gastroenterology/ otorhinolaryngology), 3. pulmonology, 4. internal medicine/ cardiology/ geriatrics, 5. neurology/ physiatry (rehabilitation)/ anesthesiology, and 6. internal medicine. Most patients had a full or dominant membership to one of these clusters of medical specialties (11 subgroups), whereas fewer patients had a membership to two clusters. The prevalence of specific diagnosis groups, patient characteristics, and healthcare utilization differed between subgroups. CONCLUSION: Our study shows that clusters and subgroups of medical specialties simultaneously involved in hospital care for patients with multimorbidity can be identified with fuzzy c-means cluster analysis using clinical data. Clusters and subgroups differed regarding the involved medical specialties, diagnoses, patient characteristics, and healthcare utilization. With this strategy, hospitals and medical specialists can further analyze which subgroups are target populations that might benefit from improved multidisciplinary collaboration.

User QoS-Based Optimized Handover Algorithm for Wireless Networks.

Due to the development of wireless network technology, various applications relying on good network quality are widely used on mobile devices. Taking the commonly used video streaming service as an example, a network with high throughput and low packet loss rate can meet the service requirements. When the moving distance of the mobile device is greater than the signal coverage of the AP, it will trigger the handover process to connect to another AP, and cause the network to disconnect and reconnect instantaneously. However, frequently triggering the handover procedure will cause a significant drop in network performance and affect the operation of application services. In order to solve this problem, this paper proposes the OHA and OHAQR. The OHA considers whether the signal quality is good or bad, and uses the corresponding HM method to solve the problem of frequent handover procedures. The OHAQR integrates the QoS requirements of the throughput and packet loss rate into the OHA with the Q-handover score, to provide high-performance handover services with QoS. Our experimental results show that the OHA and OHAQR have 13 and 15 handovers in a high-density scenario, respectively, and are better than the other two methods. The actual throughput and packet loss rate of the OHAQR are 123 Mbps and 5%, respectively, and the network performance is better than that of other methods. The proposed method shows excellent performance in ensuring the network QoS requirements and reducing the number of handover procedures.

A CNN Sound Classification Mechanism Using Data Augmentation.

Sound classification has been widely used in many fields. Unlike traditional signal-processing methods, using deep learning technology for sound classification is one of the most feasible and effective methods. However, limited by the quality of the training dataset, such as cost and resource constraints, data imbalance, and data annotation issues, the classification performance is affected. Therefore, we propose a sound classification mechanism based on convolutional neural networks and use the sound feature extraction method of Mel-Frequency Cepstral Coefficients (MFCCs) to convert sound signals into spectrograms. Spectrograms are suitable as input for CNN models. To provide the function of data augmentation, we can increase the number of spectrograms by setting the number of triangular bandpass filters. The experimental results show that there are 50 semantic categories in the ESC-50 dataset, the types are complex, and the amount of data is insufficient, resulting in a classification accuracy of only 63%. When using the proposed data augmentation method (K = 5), the accuracy is effectively increased to 97%. Furthermore, in the UrbanSound8K dataset, the amount of data is sufficient, so the classification accuracy can reach 90%, and the classification accuracy can be slightly increased to 92% via data augmentation. However, when only 50% of the training dataset is used, along with data augmentation, the establishment of the training model can be accelerated, and the classification accuracy can reach 91%.

Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells.

BACKGROUND: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit p53 expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates p53 and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. METHODS: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3',5,5'-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. RESULTS: Heteronemin inhibited not only expression of proliferative genes and Homo Sapiens Thrombospondin 1 (THBS-1) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-ß1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. CONCLUSIONS: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited THBS-1 expression. Moreover, tetrac suppressed TGF-ß expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.

Antimicrobial Peptides with Enhanced Salt Resistance and Antiendotoxin Properties.

A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.

Phytochemical Investigation and Anti-Inflammatory Activity of the Leaves of Machilus japonica var. kusanoi.

In a series of anti-inflammatory screenings of lauraceous plants, the methanolic extract of the leaves of Machilus japonica var. kusanoi (Hayata) J.C. Liao showed potent inhibition on both superoxide anion generation and elastase release in human neutrophils. Bioassay-guided fractionation of the leaves of M. japonica var. kusanoi led to the isolation of twenty compounds, including six new butanolides, machinolides A-F (1-6), and fourteen known compounds (7-20). Their structures were characterized by 1D and 2D NMR, UV, IR, CD, and MS data. The absolute configuration of the new compounds were unambiguously confirmed by single-crystal X-ray diffraction analyses (1, 2, and 3) and Mosher's method (4, 5, and 6). In addition, lignans, (+)-eudesmin (11), (+)-methylpiperitol (12), (+)-pinoresinol (13), and (+)-galbelgin (16) exhibited inhibitory effects on N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation in human neutrophils with IC50 values of 8.71 ± 0.74 µM, 2.23 ± 0.92 µM, 6.81 ± 1.07 µM, and 7.15 ± 2.26 µM, respectively. The results revealed the anti-inflammatory potentials of Formosan Machilus japonica var. kusanoi.

Chemical Constituent of ß-Glucuronidase Inhibitors from the Root of Neolitsea acuminatissima.

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4-15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial ß-Glucuronidase (ßG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-ßG inhibitors with no effect on human ßG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-ßG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial ßG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial ßG but not human ßG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action.

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve.

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 µg/mL, 16 µg/mL, and 500 µg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

Secondary Metabolites of the Endophytic Fungus Lachnum abnorme from Ardisia cornudentata.

Fractionation of an EtOAc-soluble fraction of the solid fermentate of an endophytic fungus, Lachnum abnorme Mont. BCRC 09F0006, derived from the endemic plant, Ardisia cornudentata Mez. (Myrsinaceae), resulted in the isolation of three new chromones, lachnochromonins D-F (1-3), one novel compound, lachabnormic acid (4), along with nine known compounds (5-13). Their structures were elucidated by spectroscopic analyses. Alternariol-3,9-dimethyl ether (6) was given the correct data as well as 2D spectral analyses for the first time. This is the first report of the isolation of one unprecedented compound 4 from Lachnum genus, while all known compounds were also found for the first time from Lachnum. The effects of some isolates (3, 4, 7-9, 10, and 13) on the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages were also evaluated. Several compounds exhibited weak inhibitory activity on lipopolysaccharide (LPS)-stimulated NO production in RAW 264.7 macrophages.

Ultrashort Antimicrobial Peptides with Antiendotoxin Properties.

Release of lipopolysaccharide (LPS) (endotoxin) from bacteria into the bloodstream may cause serious unwanted stimulation of the host immune system. Some but not all antimicrobial peptides can neutralize LPS-stimulated proinflammatory responses. Salt resistance and serum stability of short antimicrobial peptides can be boosted by adding ß-naphthylalanine to their termini. Herein, significant antiendotoxin effects were observed in vitro and in vivo with the ß-naphthylalanine end-tagged variants of the short antimicrobial peptides S1 and KWWK.

Biological evaluation of secondary metabolites from the root of Machilus obovatifolia.

Bioassay-guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B (1), threo-(7'R,8'R) and threo-(7'S,8'S)-methylmachilusol D (2 and 3), and isofragransol A (4), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2/3 and 4/20, resp.). The structures were elucidated by spectral analyses. Among the isolates, 1, licarin A (12), guaiacin (14), (±)-syringaresinol (21), and (-)-epicatechin (23) showed ABTS (=2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical-scavenging activity, with SC50 values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 µM in 20 min, respectively. In addition, kachirachirol B (17) showed cytotoxicity against the NCI-H460 cell line with an IC50 value of 3.1 µg/ml.

Light-addressable measurement of in vivo tissue oxygenation in an unanesthetized zebrafish embryo via phase-based phosphorescence lifetime detection.

We have developed a digital light modulation system that utilizes a modified commercial projector equipped with a laser diode as a light source for quantitative measurements of in vivo tissue oxygenation in an unanesthetized zebrafish embryo via phase-based phosphorescence lifetime detection. The oxygen-sensitive phosphorescent probe (Oxyphor G4) was first inoculated into the bloodstream of 48 h post-fertilization (48 hpf) zebrafish embryos via the circulation valley to rapidly disperse probes throughout the embryo. The unanesthetized zebrafish embryo was introduced into the microfluidic device and immobilized on its lateral side by using a pneumatically actuated membrane. By controlling the illumination pattern on the digital micromirror device in the projector, the modulated excitation light can be spatially projected to illuminate arbitrarily-shaped regions of tissue of interest for in vivo oxygen measurements. We have successfully measured in vivo oxygen changes in the cardiac region and cardinal vein of a 48 hpf zebrafish embryo that experience hypoxia and subsequent normoxic conditions. Our proposed platform provides the potential for the real-time investigation of oxygen distribution in tissue microvasculature that relates to physiological stimulation and diseases in a developing organism.

Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells.

Metastatic disease is the leading cause of cancer mortality. Identifying biomarkers and regulatory mechanisms is important toward developing diagnostic and therapeutic tools against metastatic cancer. In this study, we demonstrated that podocalyxin-like 1 (PODXL) is overexpressed in breast tumor cells and increased in lymph node metastatic cancer. Mechanistically, we found that the expression of PODXL was associated with cell motility and invasiveness. Suppression of PODXL in MDA-MB-231 cells reduced lamellipodia formation and focal adhesion kinase (FAK) and paxillin phosphorylation. PODXL knockdown reduced the formation of invadopodia, such as inhibiting the colocalization of F-actin with cortactin and suppressing phosphorylation of cortactin and neural Wiskott-Aldrich syndrome protein. Conversely, overexpression of PODXL in MCF7 cells induced F-actin/cortactin colocalization and enhanced invadopodia formation and activation. Invadopodia activity and tumor invasion in PODXL-knockdown cells are similar to that in cortactin-knockdown cells. We further found that the DTHL motif in PODXL is crucial for regulating cortactin phosphorylation and Rac1/Cdc42 activation. Inhibition of Rac1/Cdc42 impeded PODXL-mediated cortactin activation and FAK and paxillin phosphorylation. Moreover, inhibition of PODXL in MDA-MB-231 cells significantly suppressed tumor colonization in the lungs and distant metastases, similar to those in cortactin-knockdown cells. These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network.

Correlations between membrane immersion depth, orientation, and salt-resistance of tryptophan-rich antimicrobial peptides.

The efficacies of many antimicrobial peptides are greatly reduced in the presence of high salt concentrations therefore limiting their development as pharmaceutical compounds. PEM-2-W5K/A9W, a short Trp-rich antimicrobial peptide developed based on the structural studies of PEM-2, has been shown to be highly active against various bacterial strains with less hemolytic activity. Here, correlations between membrane immersion depth, orientation, and salt-resistance of PEM-2 and PEM-2-W5K/A9W have been investigated via solution structure and paramagnetic resonance enhancement studies. The antimicrobial activities of PEM-2-W5K/A9W and PEM-2 against various bacterial and fungal strains including multidrug-resistant and clinical isolates under high salt conditions were tested. The activities of the salt-sensitive peptide PEM-2 were reduced and diminished at high salt concentrations, whereas the activities of PEM-2-W5K/A9W were less affected. The results indicated that the strong salt-resistance of PEM-2-W5K/A9W may arise from the peptide positioning itself deeply into microbial cell membranes and thus able to disrupt the membranes more efficiently.

Effect of Two-step Time-restricted Feeding on the Fattening Traits in Geese.

The present study was conducted to determine whether the two-step time-restricted feeding improves the fattening traits of one-step time-restricted feeding in geese. Thirty-six 8-wk-old geese were allotted into one of three groups. Group R1 (the 1-step restricted feeding group) was allowed access to feed for 2 h in the morning from 8 wk to 14 wk of age. Group R2 (the 2-step restricted feeding group) was treated as Group R1, but was additionally fed for 2 h in the afternoon from 12 wk to 14 wk of age. Group C (the control group) was fed ad libitum from 8 wk to 14 wk of age. Feed intake and body weight (BW) were recorded daily and weekly, respectively. At 14 wk of age, the blood samples were collected to determine the fasting plasma levels of glucose, triacylglycerols and uric acid before sacrifice. The results showed that daily feed intake (DFI) was lower, feed efficiency (FE) was higher in both Groups R1 and R2 than in Group C, and daily gain (DG) in Group R2 was higher than in Group R1 during the whole experimental period (p<0.05). Group R1 exhibited lower abdominal and visceral fat weights in carcass than did Group C (p<0.05), and Group R2 was in intermediate. The fasting plasma glucose levels in Group C were higher, and triacylglycerol levels in Group R1 were higher, compared with the other groups (p<0.05). It is concluded that time-restricted feeding in the fattening period not only increases FE but reduces DFI, and the additional meal during the late fattening period improves the DG without the expense of FE in geese.

The role of vestibular function tests in nontuberculous mycobacterial otomastoiditis: A case report.

BACKGROUND: Nontuberculous mycobacteria (NTM), an extremely rare pathogen causing cervicofacial infections, may result in permanent hearing impairment or intracranial complications. Due to the lack of specific manifestations during the initial onset of NTM otomastoiditis, physicians may misdiagnose it as cholesteatoma or other common bacterial infections. PATIENT CONCERNS: A 44-year-old male who complained of left-sided aural fullness, otalgia, and dizziness for 2 months. DIAGNOSIS: The initial diagnosis was hypothesized to be cholesteatoma based on a whitish mass with mucoid discharge filling the entire outer ear canal on otoscopy and left-sided mixed hearing loss. However, NTM was identified by microbial culture at the 2-month follow-up after surgery. INTERVENTIONS: The patient underwent a left-sided exploratory tympanotomy. Because NTM otomastoiditis was diagnosed, 3 weeks of starting therapies were administered with azithromycin (500 mg/day, oral administration), cefoxitin (3 g/day, intravenous drip), and amikacin (750 mg/day, intravenous drip). The maintenance therapies were azithromycin (500 mg/day, oral administration) and doxycycline (200 mg/day, oral administration) for 7 months. OUTCOMES: The patient's clinical condition improved initially after surgery, but the otomastoiditis gradually worsened, combined with subtle meningitis, 2 months after surgery. The external auditory canal became swollen and obstructed, making it difficult to monitor the treatment efficacy through otoscopy. Thus, we used regular vestibular function tests, including static posturography, cervical vestibular evoked myogenic potentials, and video Head Impulse Test, to assess recovery outcomes. After antibiotic treatment, the infectious symptoms subsided significantly, and there was no evidence of infection recurrence 7 months after treatment. Improvements in static posturography and cervical vestibular evoked myogenic potentials were compatible with the clinical manifestations, but video Head Impulse Test showed an unremarkable correlation. LESSONS: The clinical condition of NTM otomastoiditis may be evaluated using vestibular tests if patients have symptoms of dizziness.

3D deep learning Normal Tissue Complication Probability model to predict late xerostomia in head and neck cancer patients.

BACKGROUND AND PURPOSE: Conventional normal tissue complication probability (NTCP) models for head and neck cancer (HNC) patients are typically based on single-value variables, which for radiation-induced xerostomia are baseline xerostomia and mean salivary gland doses. This study aims to improve the prediction of late xerostomia by utilizing 3D information from radiation dose distributions, CT imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL). MATERIALS AND METHODS: An international cohort of 1208 HNC patients from two institutes was used to train and twice validate DL models (DCNN, EfficientNet-v2, and ResNet) with 3D dose distribution, CT scan, organ-at-risk segmentations, baseline xerostomia score, sex, and age as input. The NTCP endpoint was moderate-to-severe xerostomia 12 months post-radiotherapy. The DL models' prediction performance was compared to a reference model: a recently published xerostomia NTCP model that used baseline xerostomia score and mean salivary gland doses as input. Attention maps were created to visualize the focus regions of the DL predictions. Transfer learning was conducted to improve the DL model performance on the external validation set. RESULTS: All DL-based NTCP models showed better performance (AUCtest=0.78 - 0.79) than the reference NTCP model (AUCtest=0.74) in the independent test. Attention maps showed that the DL model focused on the major salivary glands, particularly the stem cell-rich region of the parotid glands. DL models obtained lower external validation performance (AUCexternal=0.63) than the reference model (AUCexternal=0.66). After transfer learning on a small external subset, the DL model (AUCtl, external=0.66) performed better than the reference model (AUCtl, external=0.64). CONCLUSION: DL-based NTCP models performed better than the reference model when validated in data from the same institute. Improved performance in the external dataset was achieved with transfer learning, demonstrating the need for multicenter training data to realize generalizable DL-based NTCP models.

Clinical Outcomes of Non-Stent Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry.

BACKGROUND: For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent (balloon angioplasty or PTA and adjunctive treatment) with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. METHODS: 1060 patients from the multicenter XLPAD Registry between 2006-2021 with non-stent based BTK PAD intervention are included. PRIMARY OUTCOME: 1-year incidence of major adverse limb events (MALE), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. RESULTS: 566 patients underwent BTK and 494 BTK + FP interventions; 72% men, with mean age 68.4 ± 10.9 years. Diabetes mellitus is more prevalent in BTK only group (76.5% vs. 69%, p=0.006). Mean Rutherford class 4.2 ± 1.18; chronic limb threatening ischemia is more frequent in the BTK group (55.3% vs. 49%, p=0.040). Moderate to severe calcification is higher in BTK + FP (21.2% vs. 27.1%, p=0.024), so is lesion length (110.6 ± 77.3 vs. 135.4 ± 86.3 mm; p<0.001). Nearly, 81% lesions are treated with PTA. DCB (1.6% vs 14%, p<0.001) and atherectomy (38% vs. 58.5%; p<0.001) use is greater in BTK + FP. Procedural success is higher in BTK + FP group (86% vs. 91%, p=0.009), with amputation being the most common complication at 3.3% ≤30 days. One-year MALE (21.2% vs. 22.3%, p=0.675) and mortality (4.6% vs. 3.4%; p=0.3) are similar across BTK and BTK + FP groups. CONCLUSION: Non-stent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. CONDENSED ABSTRACT: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal (FP) PAD in patients undergoing BTK interventions can affect the outcome of the procedure. This report explores the immediate procedural success and major adverse limb events at 1 year following balloon angioplasty treatment for isolated BTK and in those undergoing an additional FP PAD intervention.

Arginine methylation of DDX3 by PRMT1 mediates mitochondrial homeostasis to promote breast cancer metastasis.

Dysregulated mitochondrial dynamics and metabolism play important roles in tumorigenesis. Metastasizing tumor cells predominantly utilize mitochondrial metabolism, and regulators of metabolic reprogramming may provide reliable biomarkers for diagnosing cancer metastasis. Here, we identified a PRMT1-DDX3 axis that promotes breast cancer metastasis by coordinating mitochondrial biogenesis and mitophagy to ensure mitochondrial quality control. Mechanistically, PRMT1 induces arginine methylation of DDX3, which enhances its protein stability and prevents proteasomal degradation. DDX3 mediates mitochondrial homeostasis by translocating to mitochondria where it facilitates PINK1 translation in response to mitochondrial stress. Inhibition of DDX3 suppresses mitochondrial biogenesis and mitophagy, resulting in diminished cancer stemness and metastatic properties. Overall, this study uncovers a mechanism by which the PRMT1-DDX3 axis regulates mitochondrial homeostasis to support breast cancer metastasis, suggesting strategies for targeting metabolic vulnerabilities to treat metastatic breast cancer.

Boosting salt resistance of short antimicrobial peptides.

The efficacies of many antimicrobial peptides are greatly reduced under high salt concentrations, therefore limiting their use as pharmaceutical agents. Here, we describe a strategy to boost salt resistance and serum stability of short antimicrobial peptides by adding the nonnatural bulky amino acid ß-naphthylalanine to their termini. The activities of the short salt-sensitive tryptophan-rich peptide S1 were diminished at high salt concentrations, whereas the activities of its ß-naphthylalanine end-tagged variants were less affected.