Prediction of lymph node metastasis in stage T1-2 rectal cancers with MRI-based deep learning.

OBJECTIVES: This study aimed to investigate whether a deep learning (DL) model based on preoperative MR images of primary tumors can predict lymph node metastasis (LNM) in patients with stage T1-2 rectal cancer. METHODS: In this retrospective study, patients with stage T1-2 rectal cancer who underwent preoperative MRI between October 2013 and March 2021 were included and assigned to the training, validation, and test sets. Four two-dimensional and three-dimensional (3D) residual networks (ResNet18, ResNet50, ResNet101, and ResNet152) were trained and tested on T2-weighted images to identify patients with LNM. Three radiologists independently assessed LN status on MRI, and diagnostic outcomes were compared with the DL model. Predictive performance was assessed with AUC and compared using the Delong method. RESULTS: In total, 611 patients were evaluated (444 training, 81 validation, and 86 test). The AUCs of the eight DL models ranged from 0.80 (95% confidence interval [CI]: 0.75, 0.85) to 0.89 (95% CI: 0.85, 0.92) in the training set and from 0.77 (95% CI: 0.62, 0.92) to 0.89 (95% CI: 0.76, 1.00) in the validation set. The ResNet101 model based on 3D network architecture achieved the best performance in predicting LNM in the test set, with an AUC of 0.79 (95% CI: 0.70, 0.89) that was significantly greater than that of the pooled readers (AUC, 0.54 [95% CI: 0.48, 0.60]; p < 0.001). CONCLUSION: The DL model based on preoperative MR images of primary tumors outperformed radiologists in predicting LNM in patients with stage T1-2 rectal cancer. KEY POINTS: • Deep learning (DL) models with different network frameworks showed different diagnostic performance for predicting lymph node metastasis (LNM) in patients with stage T1-2 rectal cancer. • The ResNet101 model based on 3D network architecture achieved the best performance in predicting LNM in the test set. • The DL model based on preoperative MR images outperformed radiologists in predicting LNM in patients with stage T1-2 rectal cancer.

Predictive factors of microvascular invasion in patients with intrahepatic mass-forming cholangiocarcinoma based on magnetic resonance images.

PURPOSE: The aim of this retrospective study was to develop and validate a preoperative nomogram for predicting microvascular invasion (MVI) in patients with intrahepatic mass-forming cholangiocarcinoma (IMCC) based on magnetic resonance imaging (MRI). METHODS: In this retrospective study, 224 consecutive patients with clinicopathologically confirmed IMCC were enrolled. Patients whose data were collected from February 2010 to December 2020 were randomly divided into the training (131 patients) and internal validation (51 patients) datasets. The data from January 2021 to November 2021 (42 patients) were allocated to the time-independent validation dataset. Univariate and multivariate forward logistic regression analyses were used to identify preoperative MRI features that were significantly related to MVI, which were then used to develop the nomogram. We used the area under the receiver operating characteristic curve (AUC) and calibration curve to evaluate the performance of the nomogram. RESULTS: Interobserver agreement of MRI qualitative features was good to excellent, with κ values of 0.613-0.882. Multivariate analyses indicated that the following variables were independent predictors of MVI: multiple tumours (odds ratio [OR]) = 4.819, 95% confidence interval [CI] 1.562-14.864, P = 0.006), ill-defined margin (OR = 6.922, 95% CI 2.883-16.633, P < 0.001), and carbohydrate antigen 19-9 (CA 19-9) > 37 U/ml (OR = 2.890, 95% CI 1.211-6.897, P = 0.017). A nomogram incorporating these factors was established using well-fitted calibration curves. The nomogram showed good diagnostic efficacy for MVI, with AUC values of 0.838, 0.819, and 0.874 for the training, internal validation, and time-independent validation datasets, respectively. CONCLUSION: A nomogram constructed using independent factors, namely the presence of multiple tumours, ill-defined margins, and CA 19-9 > 37 U/ml could predict the presence of MVI. This can facilitate personalised therapeutic strategy and clinical management in patients with IMCC.

Moderating effect of organizational climate on the relationship between research motivation and learning engagement among nurses taking part-time master's program: A cross-sectional study.

AIMS: To investigate the moderating effects of perceived organizational climate on the relationship between research motivation and learning engagement in research among nurses pursuing a part-time master's degree. BACKGROUND: Research motivation positively affects learning engagement in research. However, the role of perceived organizational climate has not been explored in nurses taking part-time master's program in China. This study examined the relationships between various types of research motivation and learning engagement in research and whether the perceived organizational climate moderates the relationship between the other variables. METHODS: This cross-sectional one-center study was performed on 230 nurses by assessing learning engagement in research, research motivation and perceived organizational climate. RESULTS: The mean age of participants was 31.3 ± 3.5 years and 91.3% were female. Participants who had been assigned a supervisor showed higher learning engagement in research than those without a supervisor (3.65 ± 0.60 vs. 3.48 ± 0.61; P < 0.001). Participants who had experience conducting research reported higher learning engagement in research than those with no experience (3.30 ± 0.71 vs. 3.14 ± 0.83; P < 0.05). The mean score of learning engagement in research was 3.39 ± 0.63. The mean scores for intrinsic, extrinsic and failure-avoidance motivation were 3.72 ± 0.61, 3.71 ± 0.71 and 3.43 ± 0.70, respectively. As for perceived organizational climate, the mean score was 122.70 out of 148. Learning engagement in research was significantly positively correlated with intrinsic research motivation, extrinsic research motivation and perceived organizational climate scores (r = 0.441, 0.336, 0.307, p < 0.001, respectively). Perceived organizational climate moderated the correlation between intrinsic and extrinsic research motivation and learning engagement in research. CONCLUSION: Nurses taking the master's program perceived a higher level of perceived organizational climate could strengthen the relationship between intrinsic and extrinsic research motivation and learning engagement in research. More organizational support can enhance learning engagement in research by reinforcing intrinsic and extrinsic research motivation. IMPLICATIONS FOR NURSING MANAGEMENT: Universities can assign supervisors promptly. Universities and hospitals can provide education about the importance of research in nursing and reinforce their intrinsic and extrinsic research motivation. Hospitals can adjust policies based on the needs of nurses taking the master's program to provide organizational support, to facilitate the research learning process.

Metabolomics-based response of Salmonella to desiccation stress and skimmed milk powder storage.

The strong survival ability of Salmonella in low-moisture foods (LMFs) has been of public concern, and is considered a threat to people's health. Recently, the development of omics technology has promoted research on the molecular mechanisms of the desiccation stress response of pathogenic bacteria. However, multiple analytical aspects related to their physiological characteristics remain unclear. We explored the physiological metabolism changes of S. enterica Enteritidis exposed to a 24 h-desiccation treatment and a subsequent 3-month desiccation storage in skimmed milk powder (SMP) with an approach of gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS). A total of 8,292 peaks were extracted, of which 381 were detected by GC-MS and 7,911 peaks were identified by LC-MS/MS, respectively. Through analyses of differentially expressed metabolites (DEMs) and key pathways, a total of 58 DEMs emerged from the 24 h-desiccation treatment, which exhibited the highest relevance for five metabolic pathways, involving glycine, serine, and threonine metabolism, pyrimidine metabolism, purine metabolism, vitamin B6 metabolism, and pentose phosphate pathway. After 3-month SMP storage, 120 DEMs were identified, which were related to several regulatory pathways including arginine and proline metabolism, serine and threonine metabolism, ß-alanine metabolism, glycerolipid metabolism, and glycolysis. The analyses of key enzyme activities of XOD, PK, and G6PDH and ATP content provided further evidence that supported the metabolic responses such as nucleic acid degradation, glycolysis, and ATP production played an important role in Salmonella's adaptation to desiccation stress. This study enables a better understanding of metabolomics-based responses of Salmonella at the initial stage of desiccation stress and the following long-term adaptive stage. Meanwhile, the identified discriminative metabolic pathways may serve as potentially useful targets in developing strategies for the control and prevention of desiccation-adapted Salmonella in LMFs.

Synthesis of Two-Dimensional MoO2 Nanoplates with Large Linear Magnetoresistance and Nonlinear Hall Effect.

Two-dimensional (2D) materials with large linear magnetoresistance (LMR) are very interesting owing to their potential application in magnetic storage or sensor devices. Here, we report the synthesis of 2D MoO2 nanoplates grown by a chemical vapor deposition (CVD) method and observe large LMR and nonlinear Hall behavior in MoO2 nanoplates. As-obtained MoO2 nanoplates exhibit rhombic shapes and high crystallinity. Electrical studies indicate that MoO2 nanoplates feature a metallic nature with an excellent conductivity of up to 3.7 × 107 S m-1 at 2.5 K. MoO2 nanoplates display a large LMR of up to 455% at 3 K and -9 T. A thickness-dependent LMR analysis suggests that LMR values increase upon increasing the thickness of nanoplates. Besides, nonlinearity has been found in the magnetic-field-dependent Hall resistance, which decreases with increasing temperatures. Our studies highlight that MoO2 nanoplates are promising materials for fundamental studies and potential applications in magnetic storage devices.

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

More and more clinical trials have explored the role of liquid biopsy in the diagnosis and treatment of EGFR-mutated NSCLC. In certain circumstances, liquid biopsy has unique advantages and offers a new way to detect therapeutic targets, analyze drug resistance mechanisms in advanced patients, and monitor MRD in patients with operable NSCLC. Although its potential cannot be ignored, more evidence is needed to support the transition from the research stage to clinical application. We reviewed the latest progress in research on the efficacy and resistance mechanisms of targeted therapy for advanced NSCLC patients with plasma ctDNA EGFR mutation and the evaluation of MRD based on ctDNA detection in perioperative and follow-up monitoring.

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies.

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on a comprehensive understanding of immunology principles. This model explicitly formulizes the pernicious effect of the antibody, together with a positive feedback stimulation of the virus-antibody complex on the antibody regeneration. Besides providing quantitative insights into antibody and virus dynamics, it demonstrates good adaptivity in recapturing the virus-antibody interaction. It is proposed that the environmental antigenic substances help maintain the memory cell level and the corresponding neutralizing antibodies secreted by those memory cells. A broader application is also visualized in predicting the antibody protection time caused by a natural infection. Suitable binding antibodies and the presence of massive environmental antigenic substances would prolong the protection time against breakthrough infection. The model also displays excellent fitness and provides good explanations for antibody selection, antibody interference, and self-reinfection. It helps elucidate how our immune system efficiently develops neutralizing antibodies with good binding kinetics. It provides a reasonable explanation for the lower SARS-CoV-2 mortality in the population that was vaccinated with other vaccines. It is inferred that the best strategy for prolonging the vaccine protection time is not repeated inoculation but a directed induction of fast-binding antibodies. Eventually, this model will inform the future construction of an optimal mathematical model and help us fight against those infectious diseases.

EMX2OS targeting IGF2BP1 represses Wilms' tumour stemness,epithelial-mesenchymal transition and metastasis.

Wilms' tumour (WT) is the most typical type of renal tumour in children, which has a poor prognosis and high recurrence rate. This study explored whether lncRNA EMX2 opposite strand / antisense RNA (EMX2OS) modulated the stemness, epithelial-mesenchymal transition (EMT) and metastasis of WTcells through the interaction with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The expression levels of EMX2OS, IGF2BP1 and stem cell markers OCT4, Nanog, Sox2 and CD133 were detected by real time quantitative polymerase chain reaction (RT-qPCR). The stemness, migration and invasion of WTcells were determined by sphere formation assay, scratch and transwell assay, respectively. The levels of EMT-related proteins were detected by Western blotting. RNA pull down and RIP assays were utilized to validate the interaction between EMX2OS and IGF2BP1. The tumourigenicity of WTcells in vivo was analysed using a xenograft tumour assay. EMX2OS was downregulated in WT patients, while IGF2BP1 was upregulated. EMX2OS overexpression or IGF2BP1 knockdown suppressed WT cell sphere formation, migration and invasion. Moreover, EMX2OS could directly interact with RNA-binding protein IGF2BP1, and IGF2BP1 overexpression counteracted the inhibitory effect of EMX2OS on WT cell stemness, migration, invasion and EMT. The in vivo tumour growth, stemness and EMT were repressed by EMX2OS through the interaction with IGF2BP1. In conclusion, EMX2OS acted as a tumour suppressor for WT by interacting with IGF2BP1, which might be a novel target for WT diagnosis and therapy.

Dosimetric and clinical analysis of pseudo-progression versus recurrence after hypo-fractionated radiotherapy for brain metastases.

BACKGROUND: The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. METHODS: The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P < 0.05 and associated with recurrence were used to establish a nomogram prediction model and validated by Bootstrap repeated sampling, which was validated in an internal cohort (n = 23) from October 2019 to December 2021. RESULTS: The median follow-up time was 68.4 months (range, 8.9-146.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to pseudo-progression and tumor recurrence were 18.3 months (quartile range, 9.4-27.8 months) and 12.9 months (quartile range, 8.7-19.6 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve values were 0.730 and 0.967 in the training and validation cohorts, respectively. Thirty-one patients received salvage therapy in the tumor recurrence group. The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI 56.8-75.9 months) and 39.6 months (95% CI 29.2-50.0 months, respectively; P = 0.001). CONCLUSIONS: Clinical and dosimetry features of hypo-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hypo-fractionated radiotherapy for brain metastases. Gross tumor volume, biological effective dose, target coverage, and having received targeted therapy or not were factors associated with the occurrence of tumor recurrence, and the individual risk could be estimated by the nomogram effectively.

Terminal Atom-Controlled Etching of 2D-TMDs.

The controlled etching of 2D transition metal dichalcogenides (2D-TMDs) is critical to understanding the growth mechanisms of 2D materials and patterning 2D materials but remains a major comprehensive challenge. Here, a rational strategy to control the terminal atoms of 2D-TMDs etched holes is reported. Using laser irradiation combined with an improved anisotropic thermal etching process under a determined atmosphere, terminal atom-controlled etched hole arrays are created on 2D-TMDs. By adjusting the gas atmosphere during the thermal etching stage, triangular etched hole arrays terminated by the tungsten zigzag (W-ZZ) edge (in an Ar/H2 atmosphere), hexagonal etched hole arrays terminated alternately by the W-ZZ edge and sulfur (selenium) zigzag (S-ZZ or Se-ZZ) edge (in a pure Ar atmosphere), and triangular etched hole arrays terminated by the S-ZZ (Se-ZZ) edge (in an Ar/sulfur [selenium] vapor atmosphere) can be obtained. Density functional theory reveals the forming energy of different edges and the different activities of metal atoms and chalcogenide atoms under different atmospheres, which determine the terminal atoms of the holes. This work may enhance the understanding of the etching and growth of 2D-TMDs. The 2D-TMDs hole arrays constructed by this work may have important applications in catalysis, nonlinear optics, spintronics, and large-scale integrated circuits.

Centimeter-Scale PdS2 Ultrathin Films with High Mobility and Broadband Photoresponse.

2D materials with mixed crystal phase will lead to the nonuniformity of performance and go against the practical application. Therefore, it is of great significance to develop a valid method to synthesize 2D materials with typical stoichiometry. Here, 2D palladium sulfides with centimeter scale and uniform stoichiometric ratio are synthesized via controlling the sulfurization temperature of palladium thin films. The relationship between sulfurization temperature and products is investigated in depth. Besides, the high-quality 2D PdS2 films are synthesized via sulfurization at the temperature of 450-550 °C, which would be compatible with back-end-of-line processes in semiconductor industry with considering of process temperature. The PdS2 films show an n-type semiconducting behavior with high mobility of 10.4 cm2 V-1 s-1 . The PdS2 photodetector presents a broadband photoresponse from 450 to 1550 nm. These findings provide a reliable way to synthesizing high-quality and large-area 2D materials with uniform crystal phase. The result suggests that 2D PdS2 has significant potential in future nanoelectronics and optoelectronic applications.

Evaluation of Anlotinib Combined with Adriamycin and Ifosfamide as Conversion Therapy for Unresectable Soft Tissue Sarcomas.

(1) Background: This study investigated the safety and efficiency of adriamycin and ifosfamide combined with anlotinib (AI/AN) as a neoadjuvant conversion therapy in uSTS. (2) Methods: Patients with uSTS were eligible to receive AI/An, including adriamycin (20 mg/m2/d) and ifosfamide (3 g/m2/d) for the first to the third day combined with anlotinib (12 mg/d) for 2 weeks on/1 week off, all of which combine to comprise one cycle. Surgery was recommended after four cycles of treatment. (3) Results: A total of 28 patients were enrolled from June 2018 to December 2020. The best tumor responses included eight patients with partial responses and 20 with a stable disease. Patients with synovial sarcoma and liposarcoma had a significant decrease in the number of tumors compared with fibrosarcoma (p = 0.012; p = 0.042). The overall response rate and disease control rate were 28.57% and 100%, respectively. In total, 24 patients received surgery, while the rates of limb salvage and R0 resection were 91.67% (n = 22/24) and 87.50% (n = 21/24), respectively. Until the last follow-up visit, the mean PFS and RFS were 21.70 and 23.97 months, respectively. During drug administration, 67.87% of patients had grade ≥3 AEs. No treatment-related death occurred. (4) Conclusions: AI/AN followed by surgery showed favorable efficiency and manageable safety in patients with uSTS. A randomized controlled study with a large cohort should be performed for further investigations.

General low-temperature growth of two-dimensional nanosheets from layered and nonlayered materials.

Most of the current methods for the synthesis of two-dimensional materials (2DMs) require temperatures not compatible with traditional back-end-of-line (BEOL) processes in semiconductor industry (450 °C). Here, we report a general BiOCl-assisted chemical vapor deposition (CVD) approach for the low-temperature synthesis of 27 ultrathin 2DMs. In particular, by mixing BiOCl with selected metal powders to produce volatile intermediates, we show that ultrathin 2DMs can be produced at 280-500 °C, which are ~200-300 °C lower than the temperatures required for salt-assisted CVD processes. In-depth characterizations and theoretical calculations reveal the low-temperature processes promoting 2D growth and the oxygen-inhibited synthetic mechanism ensuring the formation of ultrathin nonlayered 2DMs. We demonstrate that the resulting 2DMs exhibit electrical, magnetic and optoelectronic properties comparable to those of 2DMs grown at much higher temperatures. The general low-temperature preparation of ultrathin 2DMs defines a rich material platform for exploring exotic physics and facile BEOL integration in semiconductor industry.

Eczema among adolescents in Kuwait: Prevalence, severity, sleep disturbance, antihistamine use, and risk factors.

Background: Eczema (atopic dermatitis) is a common inflammatory skin disease that is more prevalent in children and adolescents than adults. In Kuwait, there is a lack of empirical knowledge on eczema epidemiology among adolescents. Therefore, this study aimed to estimate the prevalence of eczema symptoms and severity, assess the frequency of eczema-related nocturnal sleep disturbance and its relation to antihistamine use, and determine factors that are associated with eczema prevalence and eczema-related nocturnal sleep disturbance. Methods: A school-based cross-sectional study enrolled adolescents (n = 3864) aged 11-14 years across Kuwait. Information on eczema symptoms and clinical history, use of antihistamines, parental history of eczema, mode of delivery, and childhood life-style factors and exposures were reported by parents. Current eczema was defined as chronic or chronically relapsing itchy dermatitis with characteristic morphology and distribution in the past 12 months. Among subjects reporting current itchy rash, frequency of nocturnal sleep disturbance due to itchy rash in the past 12 months was reported as: never, <1 night per week, and ≥1 nights per week. Associations were assessed by applying a modified Poisson regression to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). Results: The prevalence estimate of current (past 12 months) itchy rash was 20.5% (735/3593) and current eczema was 10.2% (388/3791), with 19.5% (736/3775) reporting history of ever doctor-diagnosed eczema. Among subjects with current itchy rash, nocturnal sleep disturbance due to itchy rash affected 21.7% (157/724) of participants for <1 night per week and affected 12.7% (92/724) of participants for ≥1 nights per week. Antihistamine use at least once per month increased as the frequency of nocturnal sleep disturbance due to itchy rash increased (Ptrend <0.001). Factors that demonstrated association with current eczema prevalence included underweight body mass index (aPR = 1.71, 95% CI: 1.16-2.53), Cesarean section delivery (1.29, 1.01-1.65), and maternal (1.72, 1.35-2.19) and paternal (1.83, 1.44-2.32) history of eczema. Frequent (≥1 nights per week) nocturnal sleep disturbance was associated with Cesarean section delivery (1.98, 1.37-2.85), exposure to household tobacco smoke (1.70, 1.18-2.47), and dog-keeping (1.93, 1.06-3.52). Conclusions: Eczema symptoms are common among adolescents in Kuwait, with similar epidemiological patterns as those observed in western countries. A large proportion of affected adolescents reported nocturnal sleep disturbance due to itchy rash. Modifiable risk factors were associated increased prevalence of eczema and night awakenings.

Femoral Nerve Block and Local Instillation Analgesia Associated With More Reliable Efficacy in Regional Anesthesia Interventions Within 24 Hours Following Anterior Cruciate Ligament Reconstruction: A Network Meta-Analysis.

PURPOSE: To assess the relative effectiveness of different regional anesthetic techniques (peripheral nerve blocks, local instillation analgesia, including intra-articular, subcutaneous, and periarticular infiltration) in patients undergoing anterior cruciate ligament reconstruction (ACLR). METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception to December 31, 2020. The search was supplemented by manual review of relevant reference lists. Randomized controlled trials of participants after ACLR that compared regional anesthesia interventions were selected. The 2 coprimary outcomes were (1) rest pain scores and (2) cumulative oral morphine equivalent consumption on day 1 (24 hours) post-ACLR. Data were pooled using a Bayesian framework. RESULTS: Of 759 records identified, 46 trials were eligible, evaluating 9 interventions in 3,171 patients. Local instillation analgesia (LIA), including intra-articular, subcutaneous, and periarticular infiltration, had significant improvement in pain relief as compared with placebo (-0.91; 95% CrI -1.45 to -0.37). Femoral nerve block (FNB) also showed significant effects in relieving pain as compared with placebo (-0.70; 95% 95% credible interval [CrI] -1.28 to -0.12). Compared with placebo, a significant reduction in opioid consumption was found in LIA (mean difference -13.29 mg; 95% CrI -21.77 to -4.91) and FNB (mean difference -13.97 mg; 95% CrI -24.71 to -3.04). Femoral and sciatic nerve block showed the greatest ranking for pain relief and opioid consumption without significant evidence (P > .05) to support superiority in comparison with placebo, respectively. CONCLUSIONS: Our meta-analysis shows that FNB and LIA can significantly diminish postoperative pain and reduce opioid consumption following ACLR compared with placebo in the setting of regional anesthesia, and femoral and sciatic nerve block may be the number 1 top-ranked analgesic technique despite high uncertainty. LEVEL OF EVIDENCE: I, Systematic review of Level I studies.

Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.

More or less deadly? A mathematical model that predicts SARS-CoV-2 evolutionary direction.

SARS-CoV-2 has caused tremendous deaths globally. It is of great value to predict the evolutionary direction of SARS-CoV-2. In this paper, we proposed a novel mathematical model that could predict the evolutionary trend of SARS-CoV-2. We focus on the mutational effects on viral assembly capacity. A robust coarse-grained mathematical model is constructed to simulate the virus dynamics in the host body. Both virulence and transmissibility can be quantified in this model. A delicate equilibrium point that optimizes the transmissibility can be numerically obtained. Based on this model, the virulence of SARS-CoV-2 might further decrease, accompanied by an enhancement of transmissibility. However, this trend is not continuous; its virulence will not disappear but remains at a relatively stable range. A virus assembly model which simulates the virus packing process is also proposed. It can be explained why a few mutations would lead to a significant divergence in clinical performance, both in the overall particle formation quantity and virulence. This research provides a novel mathematical attempt to elucidate the evolutionary driving force in RNA virus evolution.

Molecular characteristics and prognostic factors of leptomeningeal metastasis in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM) is emerging as a new management challenge for oncologists and is associated with poor prognosis. This study aimed to investigate the molecular characteristics and prognostic factors of NSCLC-LM. METHODS: This retrospective study included 97 patients with NSCLC-LM between January 2015 and October 2021. Progression-free survival (PFS) and overall survival (OS) were evaluated. Gene mutations were detected by next-generation sequencing (NGS). RESULTS: The median PFS and OS were 8.4 (95 % confidence interval [CI]: 4.839-11.901) and 14.0 (95 % CI: 9.254-18.746) months, respectively. Sixty-seven patients harboured epidermal growth factor receptor-mutated (EGFRm): L858R (34), 19del (29), T790M (13), and G719C with L861Q (1). Other mutations included ALK (5), ROS1 (3), KRAS (1), TP53 (14), MET amplification (6). The detection rate and types of circulating tumour DNA (ctDNA) in the cerebrospinal fluid (CSF) samples were higher than the paired plasma samples. Patients with EGFR mutations had a longer median OS than those without mutations (19.0 vs. 13.0 months, P = 0.015). Patients with gene mutations had shorter median OS than those without mutations, such as ALK (11.8 vs. 19.9 months, P = 0.014), ROS1 (12.7 vs. 19.8 months, P = 0.014), KRAS (4.0 vs. 19.0 months, P = 0.005), TP53 (15.0 vs. 19.0 months, P = 0.014), and MET amplification (6.0 vs. 19.0 months, P = 0.003). Multivariate analysis indicated that MET amplification was an independent predictor of poor survival. Along with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3, LM accompanied with brain parenchymal metastasis (BPM), extracranial disease, and seizures were independent predictors of poor survival, whereas intrathecal chemotherapy, and third-generation EGFR-TKIs were independent predictors of favorable survival. CONCLUSIONS: CSF ctDNA detected using NGS had a high sensitivity for NSCLC-LM, showing high potential in detecting driver and drug-resistant gene mutations. Genomic profiles, combined with clinically relevant prognostic factors, will guide individualised treatments and improve the outcomes of NSCLC-LM patients.

Oral vs. parenteral antibiotic therapy in adult patients with community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Antibiotic therapy is widely used for patients with community-acquired pneumonia (CAP), and yet whether the efficacy of antibiotics differs based on the treatment mode remains unclear. This study aimed to summarize the evidence regarding the efficacy and safety of oral vs. parenteral administration of antibiotic therapy for the treatment of patients with CAP. METHODS: The databases of PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible randomized controlled trials (RCTs) from inception until 11 December 2021. The effectiveness of oral vs. parenteral administration of antibiotic therapy was estimated using a random-effects model. Additional sensitivity, subgroup, and publication bias analyses were performed. RESULTS: Of 912 identified articles, 12 RCTs involving 2158 patients with CAP were included in our pooled analysis. This mostly included trials with low certainty and some concerns regarding risk of bias, including lack of allocation concealment and blinding of participants and personnel. Overall, oral antibiotic therapy did not affect the incidence of clinical success at the end of treatment (relative risk [RR], 1.01; 95% confidence interval [CI], 0.98-1.05; P = 0.417), clinical success at follow-up (RR, 1.02; 95% CI, 0.98-1.06; P = 0.301), or adverse events (RR, 0.87; 95% CI, 0.56-1.35; P = 0.527). Moreover, oral antibiotic therapy had a beneficial effect on the risk of all-cause mortality (RR, 0.58; 95% CI, 0.35-0.96; P = 0.034). CONCLUSIONS: Oral administration of antibiotics is associated with a reduced risk of all-cause mortality compared with parenteral therapy based on RCTs with low to moderate quality. This finding should be verified in further large-scale RCTs.

Thickness-Dependent Topological Hall Effect in 2D Cr5 Si3 Nanosheets with Noncollinear Magnetic Phase.

Antiferromagnets with noncollinear spin order are expected to exhibit unconventional electromagnetic response, such as spin Hall effects, chiral abnormal, quantum Hall effect, and topological Hall effect. Here, 2D thickness-controlled and high-quality Cr5 Si3 nanosheets that are compatible with the complementary metal-oxide-semiconductor technology are synthesized by chemical vapor deposition method. The angular dependence of electromagnetic transport properties of Cr5 Si3 nanosheets is investigated using a physical property measurement system, and an obvious topological Hall effect (THE) appears at a large tilted magnetic field, which results from the noncollinear magnetic structure of the Cr5 Si3 nanosheet. The Cr5 Si3 nanosheets exhibit distinct thickness-dependent perpendicular magnetic anisotropy (PMA), and the THE only emerges in the specific thickness range with moderate PMA. This work provides opportunities for exploring fundamental spin-related physical mechanisms of noncollinear antiferromagnet in ultrathin limit.