Immune killer cells treatment for previously treated stage IV NSCLC patients.

The 5-year survival is poor for stage IV non-small cell lung cancer (NSCLC). Recently, cell immunotherapy has emerged as a new treatment strategy. This study aimed to evaluate the efficacy and safety of Immune killer cells (IKC) in patients with stage IV NSCLC after the failure of prior chemotherapy. This study enrolled 26 patients with stage IV NSCLC who failed at least two lines of chemotherapy with or without targeted therapy. The IKC was given alone weekly for 24 weeks. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), pain intensity, quality of life (QOL), and safety. The median PFS for the intent-to-treat (ITT) population (i.e., all enrolled patients) was 3.8 month. In the per-protocol (PP) population (i.e., patients receiving > 12 IKC infusions), the median PFS was 5.6 months. Moreover, the ITT population showed a 1-year survival rate of 60.0%, while that for the PP population was 85.7%. Only 7 out of 200 AEs (3.5%) were related to the IKC infusion, and they were all rated as grade 1 in severity. The IKC infusion was well tolerated. This novel immunotherapy prolonged the PFS and improved the survival compared with historical data. It might be a potential treatment strategy for stage IV NSCLC patient who failed prior chemotherapy.ClinicalTrials.gov identifier: NCT03499834.

Structural basis of the human transcriptional Mediator complex modulated by its dissociable Kinase module.

The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol II and promotes pre-initiation complex (PIC) formation in a manner inhibited by the CKM, which is also implicated in post-initiation control of gene expression. Herein we report cryo-electron microscopy structures of the human complete Mediator and its CKM, which explains the basis for CKM inhibition of cMED-activated transcription. The CKM binds to cMED through an intrinsically disordered region (IDR) in MED13 and HEAT repeats in MED12. The CKM inhibits transcription by allocating its MED13 IDR to occlude binding of Pol II and MED26 to cMED and further obstructing cMED-PIC assembly through steric hindrance with TFIIH and the +1 nucleosome. Notably, MED12 binds to the cMED Hook, positioning CDK8 downstream of the transcription start site, which sheds new light on its stimulatory function in post-initiation events.

Comparison of the Efficacy, Safety, and Quality of Life of Pegylated Liposomal Doxorubicin-Cyclophosphamide versus Epirubicin-Cyclophosphamide in Patients with Early-Stage HER2-Negative Breast Cancer: A Prospective, Randomized, Multicenter, Phase II Study.

INTRODUCTION: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety, and quality of life (QoL) of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: Patients with stage I/II HER2-negative breast cancer received PLD (37.5 mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600 mg/m2) or epirubicin (90 mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600 mg/m2). Randomization was stratified by lymph node and ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and QoL. QoL was assessed using the EORTC-QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: A total of 256 patients were assigned to LC (n = 148) and EC (n = 108). There was no difference in 5-year DFS and OS rate between the two groups. LC-based adjuvant regimens had significantly less alopecia and low-grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects. CONCLUSION: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in the 5-year DFS and OS rates between the two treatment arms. However, low-grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early-stage HER2-negative breast cancer patients.

Structural insights into the assembly of type IIA topoisomerase DNA cleavage-religation center.

The ability to catalyze reversible DNA cleavage and religation is central to topoisomerases' role in regulating DNA topology. In type IIA topoisomerases (Top2), the formation of its DNA cleavage-religation center is driven by DNA-binding-induced structural rearrangements. These changes optimally position key catalytic modules, such as the active site tyrosine of the WHD domain and metal ion(s) chelated by the TOPRIM domain, around the scissile phosphodiester bond to perform reversible transesterification. To understand this assembly process in detail, we report the catalytic core structures of human Top2α and Top2ß in an on-pathway conformational state. This state features an in trans formation of an interface between the Tower and opposing TOPRIM domain, revealing a groove for accommodating incoming G-segment DNA. Structural superimposition further unveils how subsequent DNA-binding-induced disengagement of the TOPRIM and Tower domains allows a firm grasp of the bound DNA for cleavage/religation. Notably, we identified a previously undocumented protein-DNA interaction, formed between an arginine-capped C-terminus of an α-helix in the TOPRIM domain and the DNA backbone, significantly contributing to Top2 function. This work uncovers a previously unrecognized role of the Tower domain, highlighting its involvement in anchoring and releasing the TOPRIM domain, thus priming Top2 for DNA binding and cleavage.

Anesthetic Effect on the Subthalamic Nucleus in Microelectrode Recording and Local Field Potential of Parkinson's Disease.

OBJECTIVES: Anesthetic agents used during deep brain stimulation (DBS) surgery might interfere with microelectrode recording (MER) and local field potential (LFP) and thus affect the accuracy of surgical target localization. This review aimed to identify the effects of different anesthetic agents on neuronal activity of the subthalamic nucleus (STN) during the MER procedure. MATERIALS AND METHODS: We used Medical Subject Heading terms to search the PubMed, EMBASE, EBSCO, and ScienceDirect data bases. MER characteristics were sorted into quantitative and qualitative data types. Quantitative data included the burst index, pause index, firing rate (FR), and interspike interval. Qualitative data included background activity, burst discharge (BD), and anesthetic agent effect. We also categorized the reviewed manuscripts into those describing local anesthesia with sedation (LAWS) and those describing general anesthesia (GA) and compiled the effects of anesthetic agents on MER and LFP characteristics. RESULTS: In total, 26 studies on MER were identified, of which 12 used LAWS and 14 used GA. Three studies on LFP also were identified. We found that the FR was preserved under LAWS but tended to be lower under GA, and BD was reduced in both groups. Individually, propofol enhanced BD but was better used for sedation, or the dosage should be minimized in GA. Similarly, low-dose dexmedetomidine sedation did not disturb MER. Opioids could be used as adjunctive anesthetic agents. Volatile anesthesia had the least adverse effect on MER under GA, with minimal alveolar concentration at 0.5. Dexmedetomidine anesthesia did not affect LFP, whereas propofol interfered with the power of LFP. CONCLUSIONS: The effects of the tested anesthetics on the STN in MER and LFP of Parkinson's disease varied; however, identifying the STN and achieving a good clinical outcome are possible under controlled anesthetic conditions. For patient comfort, anesthesia should be considered in STN-DBS.

Semi-Device-Independently Characterizing Quantum Temporal Correlations.

We develop a framework for characterizing quantum temporal correlations in a general temporal scenario, in which an initial quantum state is measured, sent through a quantum channel, and finally measured again. This framework does not make any assumptions on the system nor on the measurements, namely, it is device independent. It is versatile enough, however, to allow for the addition of further constraints in a semi-device-independent setting. Our framework serves as a natural tool for quantum certification in a temporal scenario when the quantum devices involved are uncharacterized or partially characterized. It can hence also be used for characterizing quantum temporal correlations when one assumes an additional constraint of no-signalling in time, there are upper bounds on the involved systems' dimensions, rank constraints-for which we prove genuine quantum separations over local hidden variable models-or further linear constraints. We present a number of applications, including bounding the maximal violation of temporal Bell inequalities, quantifying temporal steerability, and bounding the maximum successful probability in quantum randomness access codes.

Effects of integrated intrinsic foot muscle exercise with foot core training device on balance and body composition among community-dwelling adults aged 60 and above.

BACKGROUND: Evidence on the effects of plantar intrinsic foot muscle exercise in older adults remains limited. This study aimed to evaluate the effect of an integrated intrinsic foot muscle exercise program with a novel three-dimensional printing foot core training device on balance and body composition in community-dwelling adults aged 60 and above. METHODS: A total of 40 participants aged ≥ 60 years were enrolled in this quasi-experimental, single-group, pretest-posttest design; participants were categorized into two groups, those with balance impairment and those without balance impairment. The participants performed a 4-week integrated intrinsic foot muscle exercise program with a three-dimensional printing foot core training device. The short physical performance battery (SPPB) and timed up and go test were employed to evaluate mobility and balance. A foot pressure distribution analysis was conducted to assess static postural control. The appendicular skeletal muscle mass index and fat mass were measured by a segmental body composition monitor with bioelectrical impedance analysis. The Wilcoxon signed rank test was used to determine the difference before and after the exercise program. RESULTS: Among the 40 enrolled participants (median age, 78.0 years; female, 80.0%; balance-impaired group, 27.5%), the 95% confidence ellipse area of the center of pressure under the eyes-closed condition was significantly decreased (median pretest: 217.3, interquartile range: 238.4; median posttest: 131.7, interquartile range: 199.5; P = 0.001) after the exercise. Female participants without balance impairment demonstrated a significant increase in appendicular skeletal muscle mass index and a decrease in fat mass. Participants in the balance-impaired group exhibited a significant increase in SPPB. CONCLUSIONS: Integrated intrinsic foot muscle exercise with a three-dimensional printing foot core training device may improve balance and body composition in adults aged 60 and above. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05750888 (retrospectively registered 02/03/2023).

Preventing viral relapse with prophylactic tenofovir in hepatitis B carriers receiving chemotherapy: a phase IV randomized study in Taiwan.

BACKGROUND AND AIMS: This study aimed to compare the efficacy of shorter vs. longer tenofovir disoproxil fumarate (TDF) prophylaxis in preventing hepatitis B virus (HBV) relapse in cancer patients with chronic hepatitis B (CHB) undergoing chemotherapy. METHODS: This phase IV, prospective randomized trial enrolled cancer patients with CHB from 2014 to 2019 in Taiwan. Included patients were randomized to receive either 24- (Arm A) or 48-week (Arm B) post-chemotherapy TDF and compared for cumulative incidence of virological and clinical relapse. Logistic regressions were conducted to determine the factors associated with HBV relapse. RESULTS: One hundred patients were randomized, and 41 patients in Arm A and 46 in Arm B completed the TDF treatment. No significant difference was found in cumulative incidence of virological relapse (Arm A: 94.4%, Arm B: 93.1%, p = 0.110) or clinical relapse among patients with baseline HBV DNA > 2000 IU/mL (Arm A: 38.9%, Arm B: 26.7%, p = 0.420) between the two arms. High baseline HBV DNA ≥ 10,000 IU/mL (OR = 51.22) and HBsAg ≥ 1000 IU/mL (OR = 8.64) were independently associated with an increased virological relapse. Alanine aminotransferase (ALT), serum phosphorus, vitamin D, and estimated glomerular filtration rate (eGFR) remained stable throughout the study. CONCLUSIONS: The 24-week preventative TDF has comparable efficacy to the 48-week treatment in virologic and clinical relapse. High baseline HBsAg or HBV DNA is associated with a higher risk of HBV relapse. These findings imply a 24-week duration of TDF treatment with a close monitor for patients with a high baseline viral load. Hepatitis B virus infection is a prominent cause of liver cancer and chronic liver disease and affected millions of people worldwide. When HBV-infected people are exposed to immunosuppressive medication or chemotherapy for cancer, the chance of HBV reactivation rises considerably. This trial showed 24-week tenofovir disoproxil fumarate (TDF) may be sufficient for preventing HBV relapse in cancer patients receiving chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02081469.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

The unexpected fast polymerization during the synthesis of a glycolated polythiophene.

Conjugated polymers with ethylene glycol side chains are emerging as ideal materials for bioelectronics, particularly for application in organic electrochemical transistors (OECTs). To improve the OECT device performance, it is important to develop an efficient synthetic strategy that will provide access to novel high-performing materials besides focusing on molecular design. While a lot of efforts are being devoted to designing of new polymers by modifying the glycol side chains, understanding how their nature affects the polymerization kinetics and eventually the polymer structure and properties is not known. In this work, we have studied the influence of the content of the ethylene glycol side chain and its linkage on the formation of the active Grignard monomer species upon Grignard metathesis in three thiophene derivatives. A strong dependence of the monomer's concentration on polymerization was noted in our study indicating that for synthesizing P3MEEMT, a high-performing OECT material, by Kumada catalyst transfer polymerization (KCTP) a minimum of 0.15 M monomer is needed. Furthermore, kinetic studies by GPC show uncontrolled polymerization behavior contrary to the controlled chain growth characteristics of the KCTP.

Whole-Brain Radiotherapy Alone vs Preceded by Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From Breast Cancer: A Randomized Clinical Trial.

Importance: The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required. Objective: To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT). Design, Setting, and Participants: This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8. Interventions: Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone. Main Outcomes and Measures: The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival. Results: A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment. Conclusions and Relevance: The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02185352.

The influence of chronic renal insufficiency on multi-therapeutic modalities for breast cancer: a single-center experience.

BACKGROUND: Due to the presence of other comorbidities and multi-therapeutic modalities in breast cancer, renally cleared chemotherapeutic regimens may cause nephrotoxicity. The aim of this retrospective study is to compare the chemotherapy types and outcomes in breast cancer patients with or without chronic renal disease. PATIENTS AND METHODS: We retrospectively enrolled 62 female patients with breast cancer and underlying late stages (stage 3b, 4, and 5) of chronic kidney disease (CKD) treated from 2000 to 2017. They were propensity score-matched 1:1 with patients in our database with breast cancer and normal renal function (total n = 124). RESULTS: The main subtype of breast cancer was luminal A and relatively few patients with renal impairment received chemotherapy and anti-Her-2 treatment. The breast cancer patients with late-stage CKD had a slightly higher recurrent rate, especially at the locally advanced stage. The 5-year overall survival was 90.1 and 71.2% for patients without and with late-stage CKD, but the breast cancer-related mortality rate was 88.9 and 24.1%, respectively. In multivariate analyses, dose-reduced chemotherapy was an independent negative predictor of 5-year recurrence-free survival and late-stage CKD was associated with lower 5-year overall survival rate. CONCLUSIONS: Breast cancer patients with late-stage CKD may receive insufficient therapeutic modalities. Although the recurrence-free survival rate did not differ significantly by the status of CKD, patients with breast cancer and late-stage CKD had shorter overall survival time but a lower breast cancer-related mortality rate, indicated that the mortality was related to underlying disease.

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In the phase 3 KEYNOTE-522 study, addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab significantly increased pathologic complete response (pCR) and event-free survival (EFS) vs neoadjuvant chemotherapy in patients with early triple-negative breast cancer. Objective: To evaluate efficacy and safety outcomes for patients enrolled in East/Southeast Asia (Asia) in KEYNOTE-522. Design, Setting, and Participants: KEYNOTE-522, a multicenter, double-blind, randomized clinical trial, enrolled 1174 patients between March 7, 2017, and September 13, 2018. For interim EFS and overall survival (OS) analyses (data cutoff, March 23, 2021), median follow-up was 39.8 months (range, 30.4-46.9 months) for pembrolizumab plus chemotherapy and 40.8 months (range, 30.1-46.9 months) for placebo plus chemotherapy. Data cutoff for pCR analysis was September 24, 2018. This secondary analysis included adults enrolled in Asia with newly diagnosed, previously untreated, nonmetastatic triple-negative breast cancer (tumor stage T1c and nodal stage N1-2 or tumor stage T2-4 and nodal stage N0-2) and Eastern Cooperative Oncology Group performance status of 0 to 1, regardless of programmed cell death ligand 1 (PD-L1) status. Intervention: Patients were randomized 2:1 to 4 cycles of pembrolizumab (200 mg every 3 weeks) or placebo plus carboplatin and paclitaxel and another 4 cycles of pembrolizumab or placebo plus doxorubicin or epirubicin and cyclophosphamide before surgery. After definitive surgery, patients received pembrolizumab or placebo every 3 weeks for 9 cycles or until recurrence or unacceptable toxic effects. Main Outcomes and Measures: The main outcome was pCR (no evidence of primary tumor after neoadjuvant therapy or carcinoma in situ after neoadjuvant therapy and no regional lymph node involvement after neoadjuvant therapy) at the time of definitive surgery and EFS. Results: A total of 216 of 1174 randomized patients (all female; median [range] age, 46.0 [24.0-71.0] years) were from Korea, Japan, Taiwan, and Singapore (136 in the pembrolizumab plus chemotherapy group and 80 in the placebo plus chemotherapy group). Of these patients, 104 (76.5%) in the pembrolizumab plus chemotherapy group and 60 (75.0%) in the placebo plus chemotherapy group had a tumor PD-L1 combined positive score of 1 or greater. Pathologic complete response was 58.7% (95% CI, 46.7%-69.9%) with pembrolizumab plus chemotherapy and 40.0% (95% CI, 26.4%-54.8%) with placebo plus chemotherapy; benefit was observed regardless of PD-L1 status. Thirteen patients (9.6%) in the pembrolizumab plus chemotherapy group and 20 patients (25.0%) in the placebo plus chemotherapy group had EFS events (hazard ratio, 0.35; 95% CI, 0.17-0.71). The 36-month EFS rate was 91.2% (95% CI, 85.0%-94.9%) with pembrolizumab plus chemotherapy and 77.2% (95% CI, 66.3%-85.0%) with placebo plus chemotherapy. Grade 3 to 4 treatment-related adverse events occurred in 109 patients (80.1%) receiving pembrolizumab plus chemotherapy and 64 patients (81.0%) receiving placebo plus chemotherapy. Conclusions and Relevance: In this subgroup analysis of patients enrolled in Asia in KEYNOTE-522, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab led to clinically meaningful improvements in pCR and EFS vs neoadjuvant chemotherapy alone. These findings support the use of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as a standard-of-care therapy for patients in Asian countries with early triple-negative breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03036488.

The correlation with abnormal fetal outcome and a high level of amniotic fluid alpha-fetoprotein in mid-trimester.

OBJECTIVE: To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome. MATERIALS AND METHODS: We retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks' gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes. RESULTS: Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case). CONCLUSION: A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.

Hydrophilic Metabolite Composition of Fruiting Bodies and Mycelia of Edible Mushroom Species (Agaricomycetes).

Mushrooms have two components, the fruiting body, which encompasses the stalk and the cap, and the mycelium, which supports the fruiting body underground. The part of the mushroom most commonly consumed is the fruiting body. Given that it is more time consuming to harvest the fruiting body versus simply the mycelia, we were interested in understanding the difference in metabolite content between the fruiting bodies and mycelia of four widely consumed mushrooms in Taiwan: Agrocybe cylindracea (AC), Coprinus comatus (CC), Hericium erinaceus (HE), and Hypsizygus marmoreus (HM). In total, we identified 54 polar metabolites using 1H NMR spectroscopy that included sugar alcohols, amino acids, organic acids, nucleosides and purine/pyrimidine derivatives, sugars, and others. Generally, the fruiting bodies of AC, CC, and HM contained higher amounts of essential amino acids than their corresponding mycelia. Among fruiting bodies, HE had the lowest essential amino acid content. Trehalose was the predominant carbohydrate in most samples except for the mycelia of AC, in which the major sugar was glucose. The amount of adenosine, uridine, and xanthine in the samples was similar, and was higher in fruiting bodies compared with mycelia, except for HM. The organic acid and sugar alcohol content between fruiting bodies and mycelia did not tend to be different. Although each mushroom had a unique metabolic profile, the metabolic profile of fruiting bodies and mycelia were most similar for CC and HE, suggesting that the mycelia of CC and HE may be good replacements for their corresponding fruiting bodies. Additionally, each mushroom species had a unique polar metabolite fingerprint, which could be utilized to identify adulteration.

Treatment of Myopia with Atropine 0.125% Once Every Night Compared with Atropine 0.125% Every Other Night: A Pilot Study.

(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: -0.29 ± 0.44 vs. -0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = -0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

PURPOSE: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Retrospective comparative case series. METHODS: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used. RESULTS: Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications. CONCLUSIONS: Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.

An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma.

Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that Granulicatella, Peptostreptococcus, Campylobacter, Porphyromonas, Oribacterium, Actinomyces, Corynebacterium, Capnocytophaga, and Dialister were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.