Identification of memory mechanism in tissue-resident stem cells via ANGPTL4 beyond immune cells upon viral antigen exposure.

Although memory functions of immune cells characterized by increased resistance to subsequent infections after initial pathogen exposure are well-established, it remains unclear whether non-immune cells, especially tissue-resident stem cells, exhibit similar memory mechanisms. The present study revealed that detrimental effects of initial viral antigen exposure (human papillomavirus [HPV]) on diverse stem cell functions were significantly exacerbated upon subsequent secondary exposure both in vitro and in vivo. Importantly, endometrial stem cells exhibited robust memory functions following consecutive HPV antigen exposures, whereas fully differentiated cells such as fibroblasts and vesicular cells did not show corresponding changes in response to the same antigen exposures. Deficiency of angiopoietin-like 4 (ANGPTL4) achieved through small hairpin RNA knockdown in vitro and knockout (KO) mice in vivo highlighted the critical role of ANGPTL4 in governing memory functions associated with various stem cell processes. This regulation occurred through histone H3 methylation alterations and PI3K/Akt signaling pathways in response to successive HPV antigen exposures. Furthermore, memory functions associated with various stem cell functions that were evident in wild-type mice following consecutive exposures to HPV antigen were not observed in ANGPTL4 KO mice. In summary, our findings strongly support the presence of memory mechanism in non-immune cells, particularly tissue-resident stem cells.

Protein S-palmitoylation enhances profibrotic signaling in response to cadmium.

Cadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-ß1 and ß3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFß1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFß1-dependent proteins.

Engineering Escherichia coli for constitutive production of monophosphoryl lipid A vaccine adjuvant.

During the COVID-19 pandemic, expedient vaccine production has been slowed by the shortage of safe and effective raw materials, such as adjuvants, essential components to enhance the efficacy of vaccines. Monophosphoryl lipid A (MPLA) is a potent and safe adjuvant used in human vaccines, including the Shingles vaccine, Shingrix. 3-O-desacyl-4'-monophosphoryl lipid A (MPL), a representative MPLA adjuvant commercialized by GSK, was prepared via chemical conversion of precursors isolated from Salmonella typhimurium R595. However, the high price of these materials limits their use in premium vaccines. To combat the scarcity and high cost of safe raw materials for vaccines, we need to develop a feasible MPLA production method that is easily scaled up to meet industrial requirements. In this study, we engineered peptidoglycan and outer membrane biosynthetic pathways in Escherichia coli and developed a Escherichia coli strain, KHSC0055, that constitutively produces EcML (E. coli-produced monophosphoryl lipid A) without additives such as antibiotics or overexpression inducers. EcML production was optimized on an industrial scale via high-density fed-batch fermentation, and obtained 2.7 g of EcML (about 135,000 doses of vaccine) from a 30-L-scale fermentation. Using KHSC0055, we simplified the production process and decreased the production costs of MPLA. Then, we applied EcML purified from KHSC0055 as an adjuvant for a COVID-19 vaccine candidate (EuCorVac-19) currently in clinical trial stage III in the Philippines. By probing the efficacy and safety of EcML in humans, we established KHSC0055 as an efficient cell factory for MPLA adjuvant production.

Evaluation of selected tropical marine microalgal cultures for use in biophotovoltaic platforms.

In this study, the bioelectrical power generation potential of four tropical marine microalgal strains native to Malaysia was investigated using BPV platforms. Chlorella UMACC 258 produced the highest power density (0.108 mW m-2), followed by Halamphora subtropica UMACC 370 (0.090 mW m-2), Synechococcus UMACC 371 (0.065 mW m-2) and Parachlorella UMACC 245 (0.017 mW m-2). The chlorophyll-a (chl-a) content was examined to have a linear positive relationship with the power density (p < 0.05). The photosynthetic performance of strains was studied using the pulse-amplitude modulation (PAM) fluorometer; parameters measured include the following: maximum quantum efficiency (Fv/Fm), alpha (α), maximum relative electron transport rate (rETRmax), photo-adaptive index (Ek) and non-photochemical quenching (NPQ). The Fv/Fm values of all strains, except Synechococcus UMACC 371, ranged between 0.37 and 0.50 during exponential and stationary growth phases, suggesting their general health during those periods. The low Fv/Fm value of Synechococcus UMACC 371 was possibly caused by the presence of background fluorescence from phycobilisomes or phycobiliproteins. Electrochemical studies via cyclic voltammetry (CV) suggest the presence of electrochemically active proteins on the cellular surface of strains on the carbon anode of the BPV platform, while morphological studies via field emission scanning electron microscope (FESEM) imaging verify the biocompatibility of the biofilms on the carbon anode. KEY POINTS: • Maximum power output of 0.108 mW m-2 is recorded by Chlorella UMACC 258 • There is a positive correlation between chl-a content and power output • Proven biocompatibility between biofilms and carbon anode sans exogenous mediators.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Can We Control Lateral Shoulder Balance Through Proximal Thoracic Curve Correction in Lenke Type 2 Adolescent Idiopathic Scoliosis?

BACKGROUND: Proximal thoracic curve (PTC) correction has been considered to prevent lateral shoulder imbalance in Lenke Type 2 adolescent idiopathic scoliosis (AIS) patients; however, postoperative shoulder imbalance (PSI) commonly occurs despite these strategies with PTC correction. We investigated the hypothesis that PTC correction would not directly affect PSI in the majority of Lenke type 2 AIS cases. Furthermore, we investigated the risk factors for lateral PSI after corrective surgery. METHODS: This study examined the records for AIS patients with Lenke type 2 who underwent corrective surgery and followed up for >2 years. Patients were categorized into PSI (-); radiologic shoulder height (RSH)<15 mm, and PSI (+); RSH≥15 mm. Repeated measures analysis of variance was performed at preoperatively, postoperatively, 1 month, and final follow-up. Postoperative lateral shoulder imbalance was predicted by the identification of univariate analysis and multivariate analysis. RESULTS: Among the 151 patients reviewed, 29 (19.2%) showed PSI at final follow-up. Lateral shoulder balance parameters showed different directionalities between PSI (-) and (+) groups at postoperatively, 1 month, and final follow-up ( P <0.01 each). Preoperative PTC, middle thoracic curve (MTC) curve and MTC correction showed strong correlations with the RSH ( P =0.01, 0.03, and 0.04, respectively). However, PTC correction did not show a significant correlation with the RSH. Moreover, only a smaller MTC curve and larger MTC correction rate were related to lateral PSI in multivariate analysis. CONCLUSIONS: In Lenke type 2 AIS curves, the MTC curve and its correction predominantly influence lateral shoulder imbalance after corrective surgery, irrespective of the PTC correction extent. Consequently, overemphasizing the correction of the PTC curve may not necessarily lead to an improved lateral shoulder balance. When MTC curve is smaller, surgeons should be more careful for MCT overcorrection leading to a lateral shoulder imbalance. LEVEL OF EVIDENCE: Level III.

Photosynthesis: Genetic Strategies Adopted to Gain Higher Efficiency.

The global challenge of feeding an ever-increasing population to maintain food security requires novel approaches to increase crop yields. Photosynthesis, the fundamental energy and material basis for plant life on Earth, is highly responsive to environmental conditions. Evaluating the operational status of the photosynthetic mechanism provides insights into plants' capacity to adapt to their surroundings. Despite immense effort, photosynthesis still falls short of its theoretical maximum efficiency, indicating significant potential for improvement. In this review, we provide background information on the various genetic aspects of photosynthesis, explain its complexity, and survey relevant genetic engineering approaches employed to improve the efficiency of photosynthesis. We discuss the latest success stories of gene-editing tools like CRISPR-Cas9 and synthetic biology in achieving precise refinements in targeted photosynthesis pathways, such as the Calvin-Benson cycle, electron transport chain, and photorespiration. We also discuss the genetic markers crucial for mitigating the impact of rapidly changing environmental conditions, such as extreme temperatures or drought, on photosynthesis and growth. This review aims to pinpoint optimization opportunities for photosynthesis, discuss recent advancements, and address the challenges in improving this critical process, fostering a globally food-secure future through sustainable food crop production.

Breaking the Barrier: A Study on Multi-drug Resistance in Breast Abscess at an Academic Malaysian Hospital.

BACKGROUND: In recent years, the increase in antibiotics usage locally has led to a worrying emergence of multi-drug resistant organisms (MDRO), with the Malaysian prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) ranging from 17.2 to 28.1% between 1999 and 2017. A study has shown that 7% of all non-lactational breast abscesses are caused by MRSA. Although aspiration offers less morbidities compared to surgical drainage, about 20% of women infected by MRSA who initially underwent aspiration subsequently require surgical drainage. This study is conducted to determine the link between aetiology, antimicrobial resistance pattern and treatment modalities of breast abscesses. METHODS: Retrospective study of reviewing microbiology specimens of breast abscess patients treated at Universiti Malaya Medical Centre from 2015 to 2020. Data collected from microbiology database and electronic medical records were analysed using SPSS V21. RESULT: A total of 210 specimens from 153 patients were analysed. One-fifth (19.5%) of the specimens isolated were MDRO. Lactational associated infections had the largest proportion of MDR in comparison to non-lactational and secondary infections (38.5%, 21.7%, 25.7%, respectively; p = 0.23). Staphylococcus epidermidis recorded the highest number of MDR (n = 12) followed by S. aureus (n = 8). Adjusted by aetiological groups, the presence of MDRO is linked to failure of single aspirations (p = 0.554) and significantly doubled the risk of undergoing surgical drainage for resolution (p = 0.041). CONCLUSION: MDR in breast abscess should be recognised as an increasing healthcare burden due to a paradigm shift of MDRO and a rise of resistance cases among lactational associated infection that were vulnerable to undergo surgical incision and drainage for resolution.

Risk factors for postoperative complaints in patients following lumbar decompression and fusion: Analyses focusing on preoperative symptoms.

BACKGROUND: Several patients complained of residual symptoms following lumbar decompressive surgery for lumbar degenerative disease (LDD). However, few studies analyze this dissatisfaction by focusing on preoperative patients' symptoms. This study was conduct to determine the factors that could predict the patients' postoperative complaints by focusing on their preoperative symptoms. METHODS: Four hundred and seventeen consecutive patients who underwent lumbar decompression and fusion surgery for LDD were included. Postoperative complaint was defined by at least twice same complaint during the outpatient follow-up of 6,12, 18 and 24 months after surgery. A comparative analysis was performed between complaint group (group C, N = 168) and non-complaint group (group NC, N = 249). Demographic, operative, symptomatic, and clinical factors were compared between the groups by univariate and multivariate analyses. RESULTS: The main preoperative chief complaints were radiating pain (318/417, 76.2%). However, most common postoperative complaint was residual radiating pain (60/168, 35.7%) followed by tingling sensation (43/168, 25.6%). The presence of psychiatric disease (adjusted odds ratio [aOR], 4.666; P = 0.017), longer pain duration (aOR, 1.021; P < 0.001), pain to below the knee (aOR, 2.326; P = 0.001), preoperative tingling sensation (aOR, 2.631; P < 0.001), preoperative sensory and motor power decrease (aOR, 2.152 and 1.678; P = 0,047 and 0.011, respectively) were significantly correlated with postoperative patients' complaints in multivariate analysis. CONCLUSIONS: The postoperative patients' complaints could be predicted and explained in advance by checking the preoperative characteristics of patients' symptoms, including the duration and site carefully. This could be helpful to enhance the understanding of the surgical results preoperatively, which could control the anticipation of the patients.

High-Throughput Production of Diverse Xenobiotic Metabolites with Cytochrome P450-Transduced Huh7 Hepatoma Cell Lines.

Precision medicine and exposomics require methods to assess xenobiotic metabolism in human metabolomic analyses, including the identification of known and undocumented drug and chemical exposures as well as their metabolites. Recent work demonstrated the use of high-throughput generation of xenobiotic metabolites with human liver S-9 fractions for their detection in human plasma and urine. Here, we tested whether a panel of lentivirally transduced human hepatoma cell lines (Huh7) that express individual cytochrome P450 (P450) enzymes could be used to generate P450-specific metabolites in a high-throughput manner, while simultaneously identifying the enzymes responsible. Cell-line activities were verified using P450-specific probe substrates. To increase analytical throughput, we used a pooling strategy where 36 chemicals were grouped into 12 unique mixtures, each mixture containing 6 randomly selected compounds, and each compound being present in two separate mixtures. Each mixture was incubated with 8 different P450 cell lines for 0 and 2 hours and extracts were analyzed using liquid chromatography-high-resolution mass spectrometry. Cell lines selectively metabolized test substrates, e.g., pazopanib, bupropion, and ß-naphthoflavone with expected substrate-enzyme specificities. Predicted metabolites from the remaining 33 compounds as well as many unidentified m/z features were detected. We also showed that a specific bupropion metabolite generated by CYP2B6 cells, but not detected in the S9 system, was identified in human samples. Our data show that the chemical mixtures approach accelerated characterization of xenobiotic chemical space, while simultaneously identifying enzyme sources that can be used for scalable generation of metabolites for their identification in human metabolomic analyses. SIGNIFICANCE STATEMENT: High-resolution mass spectrometry (HRMS) enables the detection of exposures to drugs and other xenobiotics in human samples, but chemical identification can be difficult for several reasons. This paper demonstrates the utility of a panel of engineered cytochrome P450-expressing hepatoma cells in a scalable workflow for production of xenobiotic metabolites, which will facilitate their use as surrogate standards to validate xenobiotic detection by HRMS in human metabolomic studies.

BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells.

The use of BMP-2 in orthopedic surgery is limited by uncertainty surrounding its effects on the differentiation of mesenchymal stem cells (MSCs) and how this is affected by cellular aging. This study compared the effects of recombinant human BMP-2 (rhBMP-2) on osteogenic and adipogenic differentiation between senescent and non-senescent MSCs. Senescent and non-senescent MSCs were cultured in osteogenic and adipogenic differentiation medium containing various concentrations of rhBMP-2. The phenotypes of these cells were compared by performing a calcium assay, adipogenesis assay, staining, real-time PCR, western blotting, and microarray analysis. rhBMP-2 induced osteogenic differentiation to a lesser extent (P < 0.001 and P = 0.005 for alkaline phosphatase activity and Ca2+ release) in senescent MSCs regardless of dose-dependent increase in both cells. However, the induction of adipogenic differentiation by rhBMP-2 was comparable between them. There was no difference between these two groups of cells in the adipogenesis assay (P = 0.279) and their expression levels of PPARγ were similar. Several genes such as CHRDL1, NOG, SMAD1, SMAD7, and FST encoding transcription factors were proposed to underlie the different responses of senescent and non-senescent MSCs to rhBMP-2 in microarray analyses. Furthermore, inflammatory, adipogenic, or cell death-related signaling pathways such as NF-kB or p38-MAPK pathways were upregulated by BMP-2 in senescent MSCs, whereas bone forming signaling pathways involving BMP, SMAD, and TGF- ß were upregulated in non-senescent MSCs as expected. This phenomenon explains bone forming dominance by non-senescent MSCs and possible frequent complications such as seroma, osteolysis, or neuritis in senescent MSCs during BMP-2 use in orthopedic surgery.

Comparison of noninvasive screening tools for hepatic fibrosis, association with methotrexate cumulative dose, and risk factors in psoriasis patients.

Methotrexate (MTX) is a first-line systemic psoriasis therapy with risk of liver fibrosis. Noninvasive tools for liver fibrosis screening are Fibroscan®, Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio (APRI) index. To compare Fibroscan®, FIB-4, and APRI in detecting fibrosis, determine association of fibrosis with MTX cumulative dose, and explore risk factors for fibrosis. A case-control study involving psoriasis patients aged ≥18 years with MTX cumulative dose ≥1 g, with age and sex-matched MTX naïve psoriasis patients was performed. Noninvasive tools were used to assess liver fibrosis. Sixty-one patients on MTX and 54 controls participated. Fibroscan® detected fibrosis in 22 (36.1%) patients on MTX compared to 11 (19.6%) controls (p = 0.05). FIB-4 predicted fibrosis in 13 (21.3%) patients on MTX and in 10 (17.9%) controls (p = 0.64) while APRI diagnosed 7 (11.5%) versus 7 (12.5%), p = 0.65. No significant correlation between Fibroscan® assessed liver stiffness and MTX cumulative dose (p = 0.47). Independent risk factors for liver fibrosis were MTX use with raised alanine aminotransferase (OR = 68.56, 95% CI 8.26; 568.86, p < 0.001), diabetes mellitus (OR = 30.35, 95% CI 7.52; 122.42, p < 0.001), and raised BMI (obese patients OR = 8.26, 95% CI 1.73-39.43, p = 0.02; overweight patients OR = 6.29, 95% CI 1.28-30.99, p = 0.01). Liver fibrosis occurred in both MTX naïve and MTX-treated psoriasis patients. Fibroscan® detected higher prevalence of liver fibrosis compared to FIB-4 and APRI. Cumulative MTX does not correlate with fibrosis severity. Fibroscan® is recommended prior to MTX therapy and at regular intervals especially among patients with diabetes and increased BMI.

Lysophosphatidic Acid Receptor 4 Is Transiently Expressed during Cardiac Differentiation and Critical for Repair of the Damaged Heart.

Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3-7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction.

Pulmonary sclerosing pneumocytoma and mortality risk.

BACKGROUND: Surgical resection is usually recommended for the treatment of pulmonary sclerosing pneumocytoma (PSP). However, no comparative study has demonstrated that surgical resection leads to improved outcomes. We aimed to compare all-cause mortality between patients with PSP who underwent surgery or did not and those without PSP. METHODS: Participants aged ≥18 years who had pathologically diagnosed PSP between 2001 to 2018, at 3 hospitals were included. Randomly selected (up to 1:5) age-, sex-, and smoking status-matched controls without PSP who were randomly selected from those who underwent health checkups including chest CT were included. Mortality was compared using Kaplan-Meier estimates and Cox proportional hazards regression models. Literature review of studies reporting PSP was also conducted. RESULTS: This study included 107 patients with PSP (surgery:non-surgery, 80:27) and 520 matched controls. There were no cases of lymph node or distant metastasis, recurrence, or mortality from PSP. No significant difference in all-cause mortality risk was observed between the PSP surgery, PSP non-surgery, and non-PSP groups (log rank test P = 0.78) (PSP surgery vs. non-PSP: adjusted hazards ratio [aHR], 1.80; 95% confidence interval [CI], 0.22-14.6; PSP non-surgery vs. non-PSP: aHR, 0.77; 95% CI, 0.15-3.86; PSP surgery vs. PSP non-surgery: aHR, 2.35; 95% CI, 0.20-28.2). In the literature review, we identified 3469 patients with PSP from 355 studies. Only 1.33% of these patients reported metastasis, recurrence, or death. CONCLUSIONS: All-cause mortality did not differ between patients with PSP and those without, irrespective of undergoing surgery. Our study and the literature review suggest that PSP has less impact on increased mortality risk.

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. METHODS: We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. RESULTS: Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1-82) months. The median age was 55 (range, 33-75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. CONCLUSIONS: The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.

Evaluation of the synergistic impact of needle and forceps biopsy with electromagnetic navigation bronchoscopy: the CONFIDENT-ENB trial design.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an emerging advanced imaging-guided bronchoscopy technique for diagnosing peripheral lung lesions. However, the selection strategy for the optimal biopsy device and whether adopting a multi-tool strategy increases the diagnostic yield remains undetermined. The CONFIDENT-ENB trial (NCT05110131) is a prospective randomized study on ENB, performed in a least-invasive setting. The primary aim is to evaluate whether a combination of needle aspiration and forceps biopsy improves the diagnostic performance, and assess the comparative diagnostic value and discordance of the two devices. METHODS: The trial will recruit 142 participants with lung lesions suspected of malignancy who are eligible for an elective ENB procedure under moderate sedation. Participants will undergo ENB-guided needle aspiration and forceps biopsy in a randomized order without the use of any complementary techniques. All participants will be followed up subsequently for up to 12 months to conclude the final diagnosis of the biopsied lesions. Primary outcomes include the diagnostic yield and sensitivity of each biopsy modality and the diagnostic yield of the combined modalities. DISCUSSION: The CONFIDENT-ENB trial will prospectively evaluate the synergistic effectiveness and comparative accuracy of ENB-guided needle aspiration and forceps biopsy in a least-invasive setting. The results are expected to improve our understanding of the optimal tool-selection strategy for ENB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05110131). Prospectively registered on 5 November 2021.

The medial window technique as a salvage method to insert C2 pedicle screw in the case of a high-riding vertebral artery or narrow pedicle: a technical note and case series.

PURPOSE: To describe the safety and feasibility of C2 medial window screw (C2MWS) as an alternative salvage method for C2 pedicle screws in cases of high-riding vertebral artery (HRVA) or narrow pedicle. METHODS: The C2MWS technique involves screw insertion by intentionally breaching the medial cortex of the pedicle to avoid vertebral artery injury. Twelve patients who underwent C2 screw insertion via the C2MWS were retrospectively reviewed. C2MWS was indicated in cases of high-riding vertebral artery (HRVA) or narrow pedicle (pedicle width ≤ 4 mm). The width of the canal breach by screw, vertebral artery groove (VAG) breach, solid fusion, neck pain visual analogue scale (VAS) score, and Japanese Orthopedic Association (JOA) score were assessed as outcome measurements. RESULTS: C2MWS was indicated due to both HRVA and narrow pedicle for 11 screws, narrow pedicle for one screw, and HRVA for two screws. No screw VAG breach or vertebral artery injury was noted postoperatively. The mean width of canal breach was 2.9 ± 1.3 mm. There were no cases demonstrating neurologic deterioration, and 11 patients (91.7%) demonstrated solid fusion at 1-year follow-up. Furthermore, neck pain VAS and JOA scores significantly improved after the surgery. CONCLUSIONS: The C2MWS technique can provide 3-column fixation while reliably avoiding VA injury. C2MWS could be considered as a salvage alternative method when the insertion of C2 pedicle screw is complicated by HRVA or a narrow pedicle, while there is a need to provide firmer fixation strength than that provided by pars or translaminar screws.

Factors affecting the prognosis of recovery of motor power and ambulatory function after surgery for metastatic epidural spinal cord compression.

OBJECTIVE: Metastatic epidural spinal cord compression (MESCC) causes neurological deficits that may hinder ambulation. Understanding the prognostic factors associated with increased neurological recovery and regaining ambulatory functions is important for surgical planning in MESCC patients with neurological deficits. The present study was conducted to elucidate prognostic factors of neurological recovery in MESCC patients. METHODS: A total of 192 patients who had surgery for MESCC due to preoperative neurological deficits were reviewed. A motor recovery rate ≥ 50% and ambulatory function restoration were defined as the primary favorable endpoints. Factors associated with a motor recovery rate ≥ 50%, regaining ambulatory function, and patient survival were analyzed. RESULTS: About one-half (48.4%) of the patients had a motor recovery rate ≥ 50%, and 24.4% of patients who were not able to walk due to MESCC before the surgery were able to walk after the operation. The factors "involvement of the thoracic spine" (p = 0.015) and "delayed operation" (p = 0.041) were associated with poor neurological recovery. Low preoperative muscle function grade was associated with a low likelihood of regaining ambulatory functions (p = 0.002). Furthermore, performing the operation ≥ 72 hours after the onset of the neurological deficit significantly decreased the likelihood of regaining ambulatory functions (p = 0.020). Postoperative ambulatory function significantly improved patient survival (p = 0.048). CONCLUSIONS: Delayed operation and the involvement of the thoracic spine were poor prognostic factors for neurological recovery after MESCC surgery. Furthermore, a more severe preoperative neurological deficit was associated with a lesser likelihood of regaining ambulatory functions postoperatively. Earlier detection of motor weaknesses and expeditious surgical interventions are necessary, not only to improve patient functional status and quality of life but also to enhance survival.

Standing-Wave Feeding for High-Gain Linear Dielectric Resonator Antenna (DRA) Array.

A novel feeding method for linear DRA arrays is presented, illuminating the use of the power divider, transitions, and launchers, and keeping uniform excitation to array elements. This results in a high-gain DRA array with low losses with a design that is simple, compact and inexpensive. The proposed feeding method is based on exciting standing waves using discrete metallic patches in a simple design procedure. Two arrays with two and four DRA elements are presented as a proof of concept, which provide high gains of 12 and 15dBi, respectively, which are close to the theoretical limit based on array theory. The radiation efficiency for both arrays is about 93%, which is equal to the array element efficiency, confirming that the feeding method does not add losses as in the case of standard methods. To facilitate the fabrication process, the entire array structure is 3D-printed, which significantly decreases the complexity of fabrication and alignment. Compared to state-of-the-art feeding techniques, the proposed method provides higher gain and higher efficiency with a smaller electrical size.

High Light Acclimation Mechanisms Deficient in a PsbS-Knockout Arabidopsis Mutant.

The photosystem II PsbS protein of thylakoid membranes is responsible for regulating the energy-dependent, non-photochemical quenching of excess chlorophyll excited states as a short-term mechanism for protection against high light (HL) stress. However, the role of PsbS protein in long-term HL acclimation processes remains poorly understood. Here we investigate the role of PsbS protein during long-term HL acclimation processes in wild-type (WT) and npq4-1 mutants of Arabidopsis which lack the PsbS protein. During long-term HL illumination, photosystem II photochemical efficiency initially dropped, followed by a recovery of electron transport and photochemical quenching (qL) in WT, but not in npq4-1 mutants. In addition, we observed a reduction in light-harvesting antenna size during HL treatment that ceased after HL treatment in WT, but not in npq4-1 mutants. When plants were adapted to HL, more reactive oxygen species (ROS) were accumulated in npq4-1 mutants compared to WT. Gene expression studies indicated that npq4-1 mutants failed to express genes involved in plastoquinone biosynthesis. These results suggest that the PsbS protein regulates recovery processes such as electron transport and qL during long-term HL acclimation by maintaining plastoquinone biosynthetic gene expression and enhancing ROS homeostasis.