Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

PURPOSE: The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. METHODS: ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. DISCUSSION: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Proximity Between Screw and Endplate of Upper Instrumented Vertebra Using a Cortical Bone Trajectory Screw can Increase Radiographic Adjacent Segment Degeneration Risks in Patients With Lumbar Spinal Stenosis.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To determine the proximity between screw and endplate of the upper instrumented vertebra (UIV) using a cortical bone trajectory (CBT) screw as a predictive factor for radiographic adjacent segment degeneration (ASD) in patients surgically treated with transforaminal lumbar interbody fusion (TLIF) with CBT screws (CBT-TLIF) with lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: The risk factors for radiographic ASD after CBT-TLIF remain unknown. METHODS: Among patients surgically treated with CBT-TLIF at a single institute, 239 consecutive patients (80 males and 159 females) were enrolled. ASD was defined by the presence of one or more of the following three radiologic criteria on the adjacent segment: >3 mm anteroposterior translation, >10° segmental kyphosis, or >50% loss of disc height comparing immediate postoperative and 1-year follow-up radiographs. Clinical and radiological features associated with the development of ASD were retrospectively measured. Univariate and multivariate analyses were performed to identify risk factors associated with radiographic ASD. RESULTS: Radiographic ASD was observed in 71 (29.7%) cases at 1-year postoperative follow-up. The preoperative Pfirrmann grade of the adjacent segment (>grade 2), multi-level fusion (>2 levels), and proximity between the tip of CBT screws and endplate on the UIV were significantly associated with radiographic ASD (OR = 3.98, 95% CI [1.06-15.05], P=0.042 versus OR = 3.03, 95% CI [1.00-9.14], P=0.049 versus OR = 0.53, 95% CI [0.40-0.72], P<0.001). The cut-off value of the distance between the tip of the screw and endplate on UIV for radiographic ASD was approximately 2.5 mm (right-sided CBT screw; cut-off value 2.48 mm/ left-sided CBT screw; cut-off value 2.465 mm). CONCLUSION: Radiographic adjacent segment degeneration progression can occur when the cortical trajectory bone screw is close to the endplate of the upper instrumented vertebrae in patients with lumbar spinal stenosis undergoing fusion surgery.

BiVi-GAN: Bivariate Vibration GAN.

In the domain of prognosis and health management (PHM) for rotating machinery, the criticality of ensuring equipment reliability cannot be overstated. With developments in artificial intelligence (AI) and deep learning, there have been numerous attempts to use those methodologies in PHM. However, there are challenges to applying them in practice because they require huge amounts of data. This study explores a novel approach to augment vibration data-a primary component in traditional PHM methodologies-using a specialized generative model. Recognizing the limitations of deep learning models, which often fail to capture the intrinsic physical characteristics vital for vibration analysis, we introduce the bivariate vibration generative adversarial networks (BiVi-GAN) model. BiVi-GAN incorporates elements of a physics-informed neural network (PINN), emphasizing the specific vibration characteristics of rotating machinery. We integrate two types of physical information into our model: order analysis and cross-wavelet transform, which are crucial for dissecting the vibration characteristics of such machinery. Experimental findings show the effectiveness of our proposed model. With the incorporation of physics information (PI) input and PI loss, the BiVi-GAN showed a 70% performance improvement in terms of JS divergence compared with the baseline biwavelet-GAN model. This study maintains the potential and efficacy of complementary domain-specific insights with data-driven AI models for more robust and accurate outcomes in PHM.

Oncologic Outcomes of Immediate Breast Reconstruction in the Setting of Neoadjuvant Chemotherapy: A Long-term Follow-up Study of a Matched Cohort.

PURPOSE: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. METHODS: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. RESULTS: After propensity score matching, 95 patients who underwent IBR following SSM/NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5-181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. CONCLUSION: Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

Alveolar macrophage phagocytosis-evading inhaled microgels incorporating nintedanib-PLGA nanoparticles and pirfenidone-liposomes for improved treatment of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory and fibrotic response-driven lung disease that is difficult to cure because it manifests excessive profibrotic cytokines (e.g., TGF-ß), activated myofibroblasts, and accumulated extracellular matrix (ECM). In an attempt to develop an inhalation formulation with enhanced antifibrotic efficacy, we sought to fabricate unique aerosolizable inhaled microgels (µGel) that contain nintedanib-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs; n-PN) and pirfenidone-liposomes (p-LP). The aero-µGel was ∼12 µm, resisted phagocytosis by alveolar macrophages in vitro and in vivo, and protected inner-entrapped n-PN and p-LP. The n-PN/p-LP@aero-µGel caused enhanced/extended antifibrotic efficacy in a bleomycin-induced pulmonary fibrosis mouse presumably due to prolonged lung residence. Consequently, the results obtained by intratracheal aerosol insufflation of our n-PN/p-LP@aero-µGel twice a week were much better than those by as many as seven doses of single or mixed applications of n-PN or p-LP. The antifibrotic/pharmacokinetic results for the n-PN/p-LP@aero-µGel included reduced fibrosis progression, restored lung physiological functions, deactivated myofibroblasts, inhibited TGF-ß progression, and suppressed ECM component production (collagen I and α-SMA) along with prolonged lung retention time. We believe that our n-PN/p-LP@aero-µGel increased the local availability of both nintedanib and pirfenidone due to evasion of alveolar macrophage phagocytosis and prolonged lung retention with reduced systemic distribution. Through this approach, our inhalation formulation subsequently attenuated fibrosis progression and improved lung function. Importantly, these results hold profound implications in the therapeutic potential of our n-PN/p-LP@aero-µGel to serve as a clinically promising platform, providing significant advancements for improved treatment of many respiratory diseases including IFP.

Daphnetin Alleviates Bleomycin-Induced Pulmonary Fibrosis through Inhibition of Epithelial-to-Mesenchymal Transition and IL-17A.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-ß-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-ß signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Objective: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer.

In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane-coated, silica-layered NaErF4@NaLuF4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO2-PFC/Ce6@RAW-Man/PTX: ∼61 nm; -11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX were able to release O2 and generate 1O2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5-1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane.

Progesterone Receptor Expression Level Predicts Prognosis of Estrogen Receptor-Positive/HER2-Negative Young Breast Cancer: A Single-Center Prospective Cohort Study.

BACKGROUND: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. METHODS: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). RESULTS: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p = 0.0033, p = 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. CONCLUSION: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.

Oral intake of collagen peptide NS improves hydration, elasticity, desquamation, and wrinkling in human skin: a randomized, double-blinded, placebo-controlled study.

Collagen hydrolysate, which contains bioactive peptides, is used as a dietary supplement for the refinement of elasticity, hydration, desquamation, and wrinkling of aging human skin. Here, we conducted a double-blind, randomized, and placebo-controlled oral administration study on the effects of a collagen peptide (CPNS) containing dipeptides, including Gly-Pro and Pro-Hyp, on skin wrinkling, desquamation, elasticity, and hydration. Our results show that an intake of 1650 mg per day of CPNS for 12 weeks had beneficial effects on skin health in a cohort of women aged from 30 to 60 years (n = 100). Compared with the placebo group, skin desquamation, hydration, skin wrinkling, and elasticity were significantly improved after 4, 4, 12, and 12 weeks of administration, respectively. In a safety test of CPNS ingestion, none of the participants showed any side effects during the clinical study period. These results demonstrate that the low molecular weight bioactive peptides contained in CPNS, such as Gly-Pro and Pro-Hyp, exert positive effects on skin hydration, elasticity, desquamation, and wrinkling.

Accountable survival contrast-learning for optimal dynamic treatment regimes.

Dynamic treatment regime (DTR) is an emerging paradigm in recent medical studies, which searches a series of decision rules to assign optimal treatments to each patient by taking into account individual features such as genetic, environmental, and social factors. Although there is a large and growing literature on statistical methods to estimate optimal treatment regimes, most methodologies focused on complete data. In this article, we propose an accountable contrast-learning algorithm for optimal dynamic treatment regime with survival endpoints. Our estimating procedure is originated from a doubly-robust weighted classification scheme, which is a model-based contrast-learning method that directly characterizes the interaction terms between predictors and treatments without main effects. To reflect the censorship, we adopt the pseudo-value approach that replaces survival quantities with pseudo-observations for the time-to-event outcome. Unlike many existing approaches, mostly based on complicated outcome regression modeling or inverse-probability weighting schemes, the pseudo-value approach greatly simplifies the estimating procedure for optimal treatment regime by allowing investigators to conveniently apply standard machine learning techniques to censored survival data without losing much efficiency. We further explore a SCAD-penalization to find informative clinical variables and modified algorithms to handle multiple treatment options by searching upper and lower bounds of the objective function. We demonstrate the utility of our proposal via extensive simulations and application to AIDS data.

Deep-learning based spatio-temporal generative model on assessing state-of-health for Li-ion batteries with partially-cycled profiles.

Accurately estimating the state-of-health (SOH) of lithium-ion batteries is emerging as a hot topic because of the rapid increase in electric appliance usage. However, versatile applicability to various battery compositions and diverse cycling conditions, and prediction only with partial data still remain challenges. In this paper, a Deep-learning-based Graphical approach to Estimation of Lithium-ion batteries SOH (D-GELS) was developed to predict the SOH covering three cathode materials, LiFePO4, LiNiCoAlO2, and LiNiCOMnO2. D-GELS shows an accurate performance for SOH prediction, less than 0.012 of RMSE, was predicted regardless of cathode materials, and its applicability was confirmed. Furthermore, D-GELS was capable of predicting the SOH using partially-cycled data, since less than 0.046 of RMSE was observed even with 50% of the image missing. When using partially-cycled profiles, significant economic benefits can be seen in used battery management, as the number of assessed batteries increases greatly, leading to cost savings.

Theophylline Attenuates BLM-Induced Pulmonary Fibrosis by Inhibiting Th17 Differentiation.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the effective treatment of IPF. In this study, we investigated the effect of theophylline, which has long been used for the treatment of asthma, on pulmonary fibrosis. The administration of theophylline attenuated the fibrotic changes of lung tissues and improved mechanical pulmonary functions in bleomycin (BLM)-induced pulmonary fibrosis. Theophylline treatment suppressed IL-17 production through inhibiting cytokines controlling Th17 differentiation; TGF-ß, IL-6, IL-1ß, and IL-23. The inhibition of IL-6 and IL-1ß by theophylline is mediated by suppressing BLM-induced ROS production and NF-κB activation in epithelial cells. We further demonstrated that theophylline inhibited TGF-ß-induced epithelial-to-mesenchymal transition in epithelial cells through suppressing the phosphorylation of Smad2/3 and AKT. The inhibitory effects of theophylline on the phosphorylation of Smad2/3 and AKT were recapitulated in BLM-treated lung tissues. Taken together, these results demonstrated that theophylline prevents pulmonary fibrosis by inhibiting Th17 differentiation and TGF-ß signaling.

Analysis of medical service utilization for post-stroke sequelae in Korea between 2016 and 2018: a cross-sectional study.

In this retrospective cross-sectional observational study, the medical service utilization of post-stroke sequelae patients was examined using a national patient sample. The Korean Health Insurance Review and Assessment Service-National Patients Sample database was used to investigate the medical service utilization of 19,562 patients, diagnosed with post-stroke sequelae of cerebrovascular disease (I69) in Korea between January 2016 and December 2018. We compared the demographic characteristics, diagnosis code subtypes, frequency of healthcare utilization, medical costs, and comorbidities of standard care (SC) and Korean medicine (KM) users. Overall, patients aged ≥ 65 years accounted for the highest percentage, and utilization of medical services increased among patients aged ≥ 45 years. Outpatient care was higher among SC (79.23%) and KM (99.38%) users. Sequelae of cerebral infarction accounted for the highest percentage of diagnosis subtypes. Physical therapy and rehabilitation therapy were most frequent in SC, whereas injection/procedure and acupuncture were most frequent in KM. Cerebrovascular circulation/dementia drugs were prescribed most frequently in SC. Circulatory, digestive, endocrine, and metabolic disorders were the most common comorbidities in SC, whereas musculoskeletal and connective tissue disorders were most common in KM. Overall, SC and KM users showed differences in the number of medical service claims, cost of care, and comorbidities. Our findings provide basic research data for clinicians, researchers, and policy makers.

Comparative profiling of canonical and non-canonical small RNAs in the rice blast fungus, Magnaporthe oryzae.

RNA interference (RNAi) is divided into canonical, Dicer-dependent and non-canonical, Dicer-independent pathways according to Dicer protein dependency. However, sRNAs processed in a Dicer-independent manner have not been reported in plant pathogenic fungi, including Magnaporthe oryzae. We comparatively profiled the Dicer-dependent and -independent sRNAs of M. oryzae. Dicer-dependent sRNAs were 19-24-nt in length, had low strand-specificity, and showed a preference for uracil at the 5'-end. By contrast, Dicer-independent sRNAs presented irregular patterns in length distribution, high strand-specificity, and a preference for cytosine at the penultimate position. Dicer-dependent sRNA loci were mainly associated with LTR-transposons, while Dicer-independent sRNAs were associated with protein-coding genes and transposons. We identified MoERI-1, a non-canonical RNAi component, and profiled the sRNA and mRNA transcriptomes of ΔMoeri-1 at the mycelia and conidiation stages, as the mutant showed increased conidiation. We found that genes involved in conidiation and cell cycle were upregulated by MoERI-1 deletion. Furthermore, a comparison between sRNA and mRNA transcriptome revealed that MoERI-1-dependent sRNAs mediate the regulation of gene expression. Overall, these results showed that M. oryzae has non-canonical RNAi pathways distinct to the Dicer-dependent manner and exploits MoERI-1-dependent sRNAs to regulate the conidiation process.

Efficacy and Safety of COVID-19 Treatment Using Convalescent Plasma Transfusion: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.

When Bigger Is Not Greener: Ensuring the Sustainability of Power-to-Gas Hydrogen on a National Scale.

As the prices of photovoltaics and wind turbines continue to decrease, more renewable electricity-generating capacity is installed globally. While this is considered an integral part of a sustainable energy future by many nations, it also poses a significant strain on current electricity grids due to the inherent output variability of renewable electricity. This work addresses the challenge of renewable electricity surplus (RES) utilization with target-scaling of centralized power-to-gas (PtG) hydrogen production. Using the Republic of Korea as a case study, due to its ambitious plan of 2030 green hydrogen production capacity of 0.97 million tons year-1, we combine predictions of future, season-averaged RES with a detailed conceptual process simulation for green H2 production via polymer electrolyte membrane (PEM) electrolysis combined with a desalination plant in six distinct scale cases (0.5-8.5 GW). It is demonstrated that at scales of 0.5 to 1.75 GW the RES is optimally utilized, and PtG hydrogen can therefore outperform conventional hydrogen production both environmentally (650-2210 Mton CO2 not emitted per year) and economically (16-30% levelized cost reduction). Beyond these scales, the PtG benefits sharply drop, and thus it is answered how much of the planned green hydrogen target can realistically be "green" if produced domestically on an industrial scale.

Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma.

PURPOSE: Surgical margin status is a surrogate marker for residual tumors after breast-conserving surgery (BCS). A comparison of ipsilateral breast tumor recurrence (IBTR) rates between re-excision combined with radiotherapy (excision with RTx) and RTx alone, following the confirmation of ductal carcinoma in situ (DCIS) in the resection margin after BCS, has not been reported previously. Therefore, in the present study, the clinical characteristics of DCIS involvement in the surgical resection margin between excision with RTx and RTx alone were investigated, and the IBTR rate was compared. METHODS: We analyzed 8,473 patients treated with BCS followed by RTx between January 2013 and December 2019. Patients were divided into 2 groups based on surgical resection margin status in permanent pathology, and superficial and deep margins were excluded. Patients who underwent re-excision with DCIS confirmed in the resection margin were identified and the IBTR rate was examined. RESULTS: Among 8,473 patients treated with BCS, 494 (5.8%) had positive surgical resection margins. The median follow-up period was 47 months. Among the 494 patients with a positive resection margin, 368 (74.5%) had residual DCIS at the surgical resection margin in the final pathology. Among those with confirmed DCIS at the resection margin, 24 patients (6.5%) were re-excised, and 344 patients (93.5%) underwent RTx after observation. The IBTR rates were 4.2% and 1.2% in the re-excision and observation groups, respectively. IBTR-free survival analysis revealed no significant difference between the excision with RTx and RTx-only groups (p = 0.262). CONCLUSION: The IBTR rate did not differ between the excision with RTx and RTx-only groups when DCIS was confirmed at the resection margins. This suggests that RTx and close observation without re-excision could be an option, even in cases where minimal involvement of DCIS is confirmed on surgical resection.

Sustainable biopolyol production via solvothermal liquefaction silvergrass saccharification residue: Experimental, economic, and environmental approach.

With the rising environmental concern, sustainable chemistry should be accomplished by considering technical, economic, and environmental factors that guarantee the successful implementation of new alternative products. Hence, we performed the integrated techno-economic and life cycle assessment for two-step solvothermal liquefaction (two-pot synthesis) and simplified solvothermal liquefaction (one-pot synthesis) based on experiment results. Based on the itemized cost estimation, the unit biopolyol production costs obtained from the two-pot synthesis and one-pot synthesis were 10.0 $ kg-1 and 2.89 $ kg-1, respectively. To provide techno-economic guidelines for biopolyol production, profitability analysis, and uncertainty analysis were used to identify the economic feasibility of the proposed processes. In addition, the life cycle assessment results indicated that biopolyol production via the two-pot synthesis leads to a slightly lower greenhouse gas emission compared with the one-pot synthesis, which further required the use of an analytic hierarchy process to determine the best process for biopolyol production depending on the different weight points in the economic and environmental aspects. From these results, we can provide the technical performance, economic feasibility, and environmental impact of lab-scale biopolyol production from silvergrass residue, a low-cost waste of biomass saccharification.