Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

Construction of A Smart Hospital Innovation Platform Using the Internet + Technology.

Objective: This study aims to investigate the practical application of "Internet + technology" leveraging medical big data to enhance the development of a smart hospital platform. Specifically, the focus is on optimizing patient care processes, refining medical data management systems, and enhancing operational efficiency within the hospital setting. Methods: With the help of traditional Internet and mobile Internet technology, we analyzed the patient behavior big data accumulated in our hospital for many years, simplified the diagnosis and treatment links, refined the service connotation, and improved patient satisfaction before, during and after diagnosis; With the help of barcode, RFID and 5G networks, the links that are easy to produce medical security incidents can be monitored to improve medical quality, such as digital operating room system, establishment of multidisciplinary consultation center (MDT), electronic medical record system based on digital signature, etc.; Integrate the existing data of human resources, equipment and consumables, drugs, general supplies and finance, establish the hospital ERP system, introduce BI, and realize the dynamic monitoring of revenue and cost; Artificial intelligence technologies such as natural language processing (NLP) and machine learning are used to extract, clean, transform and analyze a large number of hospital medical information data to form a medical data platform, which can assist the hospital knowledge base to be applied in diagnosis and treatment, clinical research, clinical medicine, clinical medicine and other fields. The effectiveness of these technologies was assessed through a comprehensive analysis of their impact on patient care processes, medical data management, and overall operational efficiency within the hospital setting. Results: The study yielded significant outcomes across three critical domains. Firstly, in patient care, the implementation of expanded mobile medical services, mobile applications for records and rounds, and the establishment of digital signature-based records and intelligent surgical assistance enhanced accessibility and quality of care. Secondly, operational efficiency was notably improved through the integration of ERP and BI systems, streamlining resource management and surgical procedures. Lastly, advancements in data management, including the development of a medical data platform and the deployment of AI technologies, facilitated efficient analysis and utilization of clinical data. Quantitatively, reductions in patient visit time and medical costs were observed, alongside improved diagnostic accuracy facilitated by comprehensive records. These findings collectively underscore the transformative impact of "Internet + technology" integration on hospital operations and patient outcomes. Conclusion: The integration of "Internet + technology" in a smart hospital setting has demonstrated numerous benefits. This study has revealed novel findings regarding the tangible improvements in patient outcomes and hospital efficiency resulting from technology integration. Specifically, the implementation of mobile medical services, digital records, and AI-driven systems has led to significant reductions in patient visit times and medical costs. Moreover, the streamlining of operational processes through ERP and BI systems has enhanced resource management and surgical procedures. These findings underscore the transformative potential of technology in revolutionizing healthcare delivery, ultimately leading to better patient care and operational effectiveness in smart hospital environments.

Association of greenness surrounding school with aggression among adolescents: A multi-site study in China.

Association of greenness surrounding school with aggression among adolescents was not well understood. This study aimed to investigate the associations of greenness surrounding school with adolescents' total and sub-types of aggression and explore potential mediators underlying these associations. A multi-site study of 15,301 adolescents aged 11-20 years were recruited through a multistage, random cluster sampling across 5 representative provinces in mainland China. Satellite-derived Normalized Difference Vegetation Index (NDVI) values within circular buffers of 100 m, 500 m, and 1000 m surrounding school were used to indicate the adolescents' greenness exposure. We used the Chinese version of Buss and Warren's Aggression Questionnaire to assess total and sub-types of aggression. Daily concentrations of PM2.5, and NO2 were obtained from the China High Air Pollutants datasets. Per IQR increment of NDVI 100 m and 500 m surrounding school was associated with lower odds of total aggression; odds ratio [OR] with 95% CI was 0.958 (0.926-0.990) for the 100 m buffer and 0.963 (0.932-0.996) for the 500 m buffer, respectively. Similar associations can be observed in two sub-types of aggression, including verbal (NDVI 100 m: 0.960 (0.925-0.995); NDVI500m: 0.964 (0.930-0.999)) and indirect aggression (NDVI 100 m: 0.956 (0.924-0.990); NDVI500m: 0.953 (0.921-0.986)). There were no sex and age differences in the associations of school surrounding greenness with aggression, except that the beneficial associations of greenness exposure with total aggression (0.933(0.895-0.975) vs.1.005(0.956-1.056)), physical aggression (0.971(0.925-1.019) vs.1.098(1.043-1.156)), and hostility (0.942(0.901-0.986) vs.1.016(0.965-1.069)) were greater among participants aged ≥16 years than those aged<16 years. PM2.5 (proportion mediated estimates: 0.21; 95% CI: 0.08, 0.94) and NO2 (-0.78, 95% CI: -3.22, -0.37) mediated the association of NDVI 500 m surrounding school with total aggression. Our data indicated that exposure to greenness in school surroundings was associated with reduced aggression, particularly in verbal and indirect aggression. The presence of PM2.5 and NO2 partially mediated these associations.

Unraveling the molecular basis underlying nine putative splice site variants of von Willebrand factor.

Approximately 10% of von Willebrand factor (VWF) gene variants are suspected to disrupt messenger RNA (mRNA) processing, the number of which might be underestimated due to the lack of transcript assays. In the present study, we provided a detailed strategy to evaluate the effects of nine putative splice site variants (PSSVs) of VWF on mRNA processing as well as protein properties and establish their genotype-phenotype relationships. Eight of nine PSSVs affected VWF splicing: c.322A>T, c.1534-13_1551delinsCA, and c.8116-2del caused exon skipping; c.221-2A>C, c.323+1G>T, and c.2547-13T>A resulted in the activation of cryptic splice sites; c.2684A>G led to exon skipping and activation of a cryptic splice site; c.2968-14A>G created a new splice site. The remaining c.5171-9del was likely benign. The efficiency of nonsense-mediated mRNA decay (NMD) was much higher in platelets compared to leukocytes, impairing the identification of aberrant transcripts in 4 of 8 PSSVs. The nonsense variant c.322A>T partially impaired mRNA processing, leaking a small amount of correct transcripts with c.322T (p.Arg108*), while the missense variant c.2684A>G totally disrupted normal splicing of VWF, rather than produced mutant protein with the substitution of Gln895Arg. The results of this study would certainly add novel insights into the molecular events behind von Willebrand disease.

MiR-151b inhibits osteoblast differentiation via downregulating Msx2.

PURPOSE: MicroRNA-151b (miR-151b) showed altered expression in ovariectomized rat model of osteoporosis. This study established an ovariectomy-induced osteoporotic rat model to investigate the role of miR-151b in osteoblasts. METHODS: Eighteen female Sprague-Dawley (SD) rats were divided randomly into Sham and OVX group (n = 9). The transfections with different miRNAs and expression vectors were confirmed by RT-qPCR. The protein expression of Msx2 was detected by Western blots. The interaction between miR-151b and Msx2D was evaluated by RNA pull-down and dual luciferase reporter assay. RESULTS: The expression of miR-151b was significantly increased in femoral tissues of ovariectomy-induced osteoporotic rats. The expression of osteogenesis marker genes including RUNX2, ALP, OCN, OSX, and Msx2 were all significantly increased in osteogenic medium (OM) incubated primary osteoblasts and MC3T3-E1 cells. The interaction between miR-151b and Msx2 was confirmed by luciferase reporter assay and RNA pull-down. Moreover, overexpression of miR-151b significantly inhibited Msx2 in both MC3T3-E1 cells and primary osteoblasts, while miR-151b inhibitor had the opposite effect on the expression of Msx2. In addition, in primary osteoblasts and MC3T3-E1 cells, miR-151b overexpression, or Msx2 silence significantly decreased the expression of OSX, ALP, RUNX2, and OCN. CONCLUSION: MiR-151b could inhibit osteoblast proliferation, differentiation, and mineralization via downregulating Msx2 in both MC3T3-E1 cells and primary osteoblasts. MiR-151b might serve as a novel therapeutic target for osteoporosis. ABBREVIATIONS: miR-151b: microRNA-151b; miRNAs: microRNAs; Msx2: Msh homeobox 2; MAPK: mitogen-activated protein kinase; STAT: signal transducer and activator of transcription; SD: Sprague-Dawley; BMD: bone mineral density; qRT-PCR: quantitative reverse transcription PCR; MTT: methyl thiazolyl tetrazolium; OVX: ovariectomy; ALP: alkaline phosphatase.

Submuscular Implant-Based Breast Reconstruction Using a Musculofascial Pocket Formed by the Pectoralis Major Muscle and the Serratus Anterior Muscle Fascia: A Novel Surgical Approach.

BACKGROUND: Subpectoral implant-based breast reconstruction following mastectomy commonly severs the inferior border of the pectoralis major muscle for better projection of the lower pole. This can affect a patient's postoperative motor function and result in animation deformity. Implant-based breast reconstruction using partial muscle coverage with an acellular dermal matrix (ADM) can be costly. There is an unmet clinical need for a novel surgical method for submuscular implant-based breast reconstruction. METHODS: We describe an innovative technique for submuscular implant-based breast reconstruction following mastectomy. The approach utilizes the serratus anterior muscle fascia connected to the lateral margin of the pectoralis major muscle to form a lateral tissue pocket for implant coverage. This method preserves the inferior border of the pectoralis major muscle and minimizes the size of ADM coverage. Patient satisfaction on the BREAST-Q Reconstruction Module and complications were assessed 12 months after surgery. RESULTS: The novel surgical design was safe and used minimal ADM (6 × 5cm2). Mean satisfaction with breasts was 61 ± 4.7 (range, 48-73), mean psychosocial well-being was 66 ± 10 (range, 50-93), and mean sexual well-being was 47 ± 7.8 (range, 27-70). Animation deformity was avoided by preserving the inferior border of the pectoralis major muscle. Rates of revision (7.6%) and postsurgical seroma (3.4%) were low, and capsular contracture was minimal. CONCLUSIONS: Submuscular implant-based breast reconstruction following mastectomy utilizing the serratus anterior muscle fascia connected to the lateral margin of the pectoralis major muscle to form a lateral tissue pocket for implant coverage is safe, feasible, and generates good aesthetic outcomes.

Navigating through motherhood in pregnancy and postpartum periods during the COVID-19 pandemic: A systematic review and qualitative meta-synthesis.

AIM: The aim of this work is to critically appraise and synthesize the qualitative studies on the experiences, perspectives, and consequences of pregnant women experiencing motherhood during the COVID-19 pandemic. BACKGROUND: The COVID-19 pandemic has posed a threat to the health of pregnant women. Such a pandemic disrupted their routine care, as well as normal daily life. However, little is known about their coping strategies to the changes brought by COVID-19. EVALUATION: A qualitative systematic review was conducted according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist. A meta-aggregative approach rooted in pragmatism and Husserlian transcendental phenomenology was used to synthesize the findings. Dependability and credibility of both study findings and synthesized findings were appraised by Joanna Briggs Institute (JBI) ConQual process. KEY ISSUES: Key issues include (a) pregnant women experienced changes in routine care, (b) pregnant women used a range of strategies to cope with the consequence of the pandemic, (c) pregnant women struggled to embrace motherhood, and (d) pregnant women received different levels of social support. CONCLUSION: Facing challenges caused by the pandemic, pregnant women used a variety of strategies to cope with and adapt to the changes, but sometimes the adaption is limited. Emotional, instrumental, and informational support should be provided to them in an accessible way. IMPLICATIONS FOR NURSING MANAGEMENT: As an essential part of policymakers, nursing managers should consider the balance between restriction and the accessibility of maternity care. It is also crucial for them to consider how to provide necessary support in an accessible way.

CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients.

Breast cancer (BC) prognosis and therapeutic sensitivity could not be predicted efficiently. Previous evidence have shown the vital roles of CDKN1C in BC. Therefore, we aimed to construct a CDKN1C-based model to accurately predicting overall survival (OS) and treatment responses in BC patients. In this study, 995 BC patients from The Cancer Genome Atlas database were selected. Kaplan-Meier curve, Gene set enrichment and immune infiltrates analyses were executed. We developed a novel CDKN1C-based nomogram to predict the OS, verified by the time-dependent receiver operating characteristic curve, calibration curve and decision curve. Therapeutic response prediction was followed based on the low- and high-nomogram score groups. Our results indicated that low-CDKN1C expression was associated with shorter OS and lower proportion of naïve B cells, CD8 T cells, activated NK cells. The predictive accuracy of the nomogram for 5-year OS was superior to the tumour-node-metastasis stage (area under the curve: 0.746 vs. 0.634, p < 0.001). The nomogram exhibited excellent predictive performance, calibration ability and clinical utility. Moreover, low-risk patients were identified with stronger sensitivity to therapeutic agents. This tool can improve BC prognosis and therapeutic responses prediction, thus guiding individualized treatment decisions.

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer.

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

Cross-reactivity between MUC1 antigen and MCA: false elevation of serum CA 15-3 level in pregnant and lactating women by Ma695-Ma552-based assay.

PURPOSE: Cancer antigen 153 (CA 15-3) is one of the most commonly used biomarkers of breast cancer. However, elevated CA 15-3 is reported in pregnant and lactating women more frequently on Beckman DxI 800 immunoassay system (Ma695-Ma552 antibody pair) than on Abbott ARCHITECT system (115D8-DF3 antibody pair) in laboratory methodological evaluation. We conducted this study in order to figure out the reason behind this phenomenon. METHODS: Serum CA 15-3 concentration was analyzed in 426 subjects, including 180 patients with breast cancer, 121 patients with benign breast disease, and 125 healthy volunteers (45 pregnant and 80 non-pregnant women). CA 15-3 assay was further validated using another cohort of 112 pregnant or postpartum women. Immunological cross reaction was analyzed by Western blotting and immunoprecipitation. RESULTS: The serum CA 15-3 level was abnormally higher in almost 95% of the pregnant and lactating women detected using Ma695-Ma552 antibody pair (median: 71.4 U/mL) than that detected using 115D8-DF3 antibody pair (median: 16.5 U/mL). Western blotting and immunoprecipitation indicated that such a significant difference was mainly due to the cross reaction between monoclonal antibody Ma552 and mucin-like carcinoma-associated antigen (MCA). CONCLUSIONS: The CA 15-3 assay using 115D8-DF3 antibody pair is more suitable for monitoring therapy in pregnancy-associated breast cancer.

Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.

Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.

Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC50=0.62 ± 0.04 and 1.92 ± 0.09 µM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO2 will result in a moderate to dramatic decrease in potency.

Telomere length as a modifier in the relationship between phthalate metabolites exposure and glucose homeostasis.

Given the rising concern over the potential impact of environmental factors on metabolic heath, we conducted a cross-sectional analysis among 645 adults aged 20 and older in the National Health and Nutrition Examination Survey (NHANES), examining the association between nine phthalate metabolites (Mono-n-butyl phthalate (MBP), Mono-ethyl phthalate (MEP), Mono-(2-ethyl)-hexyl phthalate (MEHP), Mono-benzyl phthalate (MBzP), Mono-n-methyl phthalate (MnMP), Mono-(3-carboxy propyl) phthalate (MCPP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-isobutyl phthalate (MiBP)) and six glucose homeostasis indices (fasting glucose, fasting insulin, hemoglobin A1C (HbA1C), homeostatic model assessment of insulin resistance (HOMA-IR), single Point Insulin Sensitivity Estimator (SPISE), and HOMA-ß). Latent Class Analysis identified three phthalate metabolites exposure patterns: high MEP-low MEOHP (n = 282), high MBzP-low MEHHP (n = 214), and high MEHHP, MEOHP (n = 149). The high MBzP-low MEHHP and high MEHHP, MEOHP, versus the high MEP-low MEOHP, exposure groups showed significantly higher levels of fasting insulin (ß = 0.126, 95% CI: 0.023-0.228), SPISE (ß = 0.091, 95% CI: 0.018-0.164), and HOMA-IR (ß = 0.091, 95% CI: 0.018-0.164). In the shorter telomere length group, high MEHHP, MEOHP exposure showed an increase in SPISE levels (ß = 0.153, 95% CI: 0.037-0.269), while in the overweight/obese subgroup, high MEHHP, MEOHP exposure was significantly positively associated with HOMA-IR (ß = 0.392, 95% CI: 0.150-0.735). Bayesian kernel machine regression analyses showed positive associations between higher combined phthalate exposure and increased glucose homeostasis indices (fasting glucose, HbA1C, fasting insulin, SPISE, and HOMA-IR). The quantile of g-calculation analysis also supported the positive associations with HbA1C, HOMA-IR, and fasting insulin. Our findings indicate that phthalate exposure was positively associated with glucose homeostasis indices, which strengthen the call for proactive measures to reduce phthalate exposure and mitigate potential risks to glucose metabolism.

Associations of diet quality and daily free sugar intake with depressive and anxiety symptoms among Chinese adolescents.

BACKGROUND: Assessing diet quality has been challenging, and the associations of diet quality and daily free sugar intake with depressive and/or anxiety symptoms have shown inconsistency. METHODS: A total of 1749 students aged 12-16 years were recruited using stratified random cluster sampling across three cities in China. The overall Global Dietary Recommendations (GDR) score, a novel indicator of diet quality, was constructed using the low-burden Diet Quality Questionnaire. Free sugar intake, including from beverages and foods, was measured using the Food Frequency Questionnaire. Daily free sugar intake was divided into low, medium, and high categories based on the latest version of the dietary guidelines for Chinese residents. Binomial and multinominal logistic regression analyses were used to examine the associations of the overall GDR score and daily free sugar intake categories or different sources of free sugar intake with depressive and/or anxiety symptoms. RESULTS: The overall GDR score was negatively associated with depressive symptoms (adjusted odds ratio[aOR] = 0.92, 95%CI: 0.87-0.98) and anxiety symptoms (0.95, 0.90-0.99), particularly with comorbid depression and anxiety (0.90, 0.84-0.97). Conversely, daily free sugar intake was positively associated with symptoms of depression and/or anxiety, the multiple aOR for symptoms depression or anxiety were significantly increased with higher daily free sugar intake (all Ptrend < 0.05). Both free sugar from beverages and from foods were positively associated with depressive and/or anxiety symptoms. These associations were consistent between males and females. LIMITATIONS: Cross-sectional design and self-reported symptoms. CONCLUSIONS: Diet quality was negatively associated with symptoms of depression or anxiety, especially with comorbid symptoms among adolescents. Daily free sugar intake, regardless of its sources, was positively associated with symptoms of depression and/or anxiety.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Labor Migration of Parents and Aggression Among Their Offspring in China.

Importance: In China, parental labor migration often leaves children behind and is potentially adversely associated with children's health. However, the association between parental migration and aggression among their offspring remains largely underexplored. Objective: To investigate the associations of parental labor migration with total and subtypes of aggression among their offspring as well as potential sex differences therein. Design, Setting, and Participants: This cross-sectional study was conducted from February to October 2015 among students aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from December 1, 2022, to August 1, 2023. Exposures: Parental migration, including migration status (yes or no), pattern (father, mother, or both), and the child's age at the initial parent-child separation. Main Outcomes and Measures: Total and subtypes of aggression (including physical aggression [PA], verbal aggression [VA], indirect aggression [IA], anger, and hostility) were measured using the Chinese version of the Buss-Warren Aggression Questionnaire. Binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of parental migration by total and subtypes of aggression. Results: A total of 15 301 participants (7900 [51.6%] male and 7401 [48.4%] female) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of these participants, 5961 (39.0%) experienced parental migration; 2451 (16.0%) met the criteria for total aggression, 2407 (15.7%) for PA, 2283 (14.9%) for VA, 2899 (18.9%) for IA, 2307 (15.1%) for anger, and 2564 (16.8%) for hostility. Parental migration was associated with total aggression (aOR, 1.11; 95% CI, 1.01-1.22); no significant association between parental migration and subtypes of aggression was found except for PA (aOR, 1.14; 95% CI, 1.03-1.25). Compared with children whose parents did not migrate, the aORs for total aggression and PA for participants whose father migrated were 1.12 (95% CI, 1.01-1.28) and 1.15 (95% CI, 1.03-1.29), respectively; for participants with both parents having migrated, the aORs were 1.16 (95% CI, 1.02-1.31) and 1.12 (95% CI, 1.04-1.24), respectively. Compared with children whose parents did not migrate, children who experienced initial separation from 1 or both parents at adolescence had an aOR for total aggression of 1.20 (95% CI, 1.04-1.36), children who experienced initial separation from 1 or both parents at school age or adolescence had an aOR for PA of 1.15 (95% CI, 1.01-1.32) and 1.26 (95% CI, 1.04-1.51), respectively. No sex differences were found in these associations. Conclusions and Relevance: In this cross-sectional study of Chinese children and adolescents, we found that parental migration, mainly of the father or both parents or an initial separation at adolescence or school age from 1 or both parents, was associated with higher odds of total aggression and PA among offspring. These associations were similar between male and female participants.

Taming neonatal hypoxic-ischemic brain injury by intranasal delivery of plasminogen activator inhibitor-1.

BACKGROUND AND PURPOSE: Plasminogen activator inhibitor-I (PAI-1), a ≈50-kDa serine protease inhibitor, markedly reduces the extravascular toxicity of tissue-type plasminogen activator in experimental hypoxic-ischemic (HI) brain injury of newborns. However, the current treatment with PAI-1 requires intracerebroventricle injection to cross the blood-brain barrier, which is an invasive procedure of limited clinical potential. Thus, we tested whether intranasal administration of PAI-1 can bypass blood-brain barrier and mitigate neonatal HI brain injury. METHODS: Rat pups were subjected to HI, with or without lipopolysaccharide pre-exposure, followed by intranasal delivery of a stable-mutant form of PAI-1 (CPAI). RESULTS: Immunoblotting showed that CPAI sequentially entered the olfactory bulbs and cerebral cortex after intranasal delivery and reduced ≈75% of brain atrophy in HI or lipopolysaccharide-sensitized HI injury. Mechanistically, CPAI attenuated HI-induced plasminogen activators and lipopolysaccharide/HI-induced nuclear factor-κB signaling, neuroinflammation, and blood-brain barrier permeability. CONCLUSIONS: Intranasal delivery of CPAI is an effective treatment of experimental HI brain injury of newborns. Clinical application of this experimental therapy merits further investigation.

Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis.

PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Classification of temporal lobe epilepsy based on neuropsychological tests and exploration of its underlying neurobiology.

Objective: To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests. Methods: Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests. Results: We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups. Conclusion: These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.

Improving Tumor Classification by Reusing Self-predicted Segmentation of Medical Images as Guiding Knowledge.

Differential diagnosis of tumors is important for computer-aided diagnosis. In computer-aided diagnosis systems, expert knowledge of lesion segmentation masks is limited as it is only used during preprocessing or as supervision to guide feature extraction. To improve the utilization of lesion segmentation masks, this study proposes a simple and effective multitask learning network that improves medical image classification using self-predicted segmentation as guiding knowledge; we call this network RS 2-net. In RS 2-net, the predicted segmentation probability map obtained from the initial segmentation inference is added to the original image to form a new input, which is then reinput to the network for the final classification inference. We validated the proposed RS 2-net using three datasets: the pNENs-Grade dataset, which tested the prediction of pancreatic neuroendocrine neoplasm grading, and the HCC-MVI dataset, which tested the prediction of microvascular invasion of hepatocellular carcinoma, and ISIC 2017 public skin lesion dataset. The experimental results indicate that the proposed strategy of reusing self-predicted segmentation is effective, and RS 2-net outperforms other popular networks and existing state-of-the-art studies. Interpretive analytics based on feature visualization demonstrates that the improved classification performance of our reuse strategy is due to the semantic information that can be acquired in advance in a shallow network.