Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample mendelian randomized study.

BACKGROUND: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. METHODS: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs. RESULTS: We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014-2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality. CONCLUSIONS: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders.

Marked increase in tumor transfection with a truncated branched polymer.

BACKGROUND: We previously determined that polyplexes formed by linear H2K peptides were more effective in transfecting tumors in vivo than polyplexes formed by branched H2K4b-20 peptides. Based on trypsin digest and salt displacement studies, the linear H2K polyplexes were less stable than the branched H2K4b-20 polyplexes. Because binding and release of the polymer and DNA from the H2K4b-20 polyplex may account for the ineffectiveness, we investigated whether four-branched histidine-lysine (HK) peptides with varying numbers of amino acids in their branches would be more effective in their ability to increase gene expression in tumors in vivo. METHODS: Linear and branched peptides with multiple -KHHK- motifs were synthesized by solid-phase synthesis. The branched H2K4b-20, -18, -14 and 12 peptides had 20, 18, 14 and 12 amino acids in their branches, respectively. These peptides were examined for their ability to carry luciferase-expressing plasmids to human breast cancer xenografts in a mouse model. With gel retardation and in vivo transfection, the incorporation of a targeting ligand and an endosomal lysis peptide into these polyplexes was also examined. A blocking antibody was pre-injected prior to the polyplexes to determine the role of neuropilin 1 in the uptake of these polyplexes by the tumor. The size of the polyplexes was measured by dynamic light scattering. RESULTS: Of the four negative surface-charge polyplexes formed by the branched carriers, the H2K4b-14 polyplex was determined to be the most effective plasmid delivery platform to tumors. The incorporation of a targeting ligand and an endosomal lysis peptide into H2K4b-14 polyplexes further enhanced their ability to transfect tumors in vivo. Furthermore, after pre-injecting tumor-bearing mice with a blocking antibody to the neuropilin-1 receptor (NRP-1), there was a marked reduction of tumor gene expression with the modified H2K4b-14 polyplexes, suggesting that NRP-1 mediated their transport into the tumor. CONCLUSIONS: The present study established that branched peptides intermediate in length were very efficient in delivering plasmids to tumors in vivo.

Location of a single histidine within peptide carriers increases mRNA delivery.

BACKGROUND: Previously, we determined that four-branched histidine-lysine (HK) peptides were effective carriers of plasmids and small interfering RNA. In the present study, we compared several branched HK carriers and, in particular, two closely-related H3K4b and H3K(+H)4b peptides for their ability as carriers of mRNA. The H3K(+H)4b peptide differed from its parent analogue, H3K4b, by only a single histidine in each branch. METHODS: A series of four-branched HK peptides with varied sequences was synthesized on a solid-phase peptide synthesizer. The ability of these peptides to carry mRNA expressing luciferase to MDA-MB-231 cells was investigated. With gel retardation and heparin displacement assays, the stability of HK polyplexes was examined. We determined the intracellular uptake of HK polyplexes by flow cytometry and fluorescence microscopy. The size and polydispersity index of the polyplexes in several media were measured by dynamic light scattering. RESULTS: MDA-MB-231 cells transfected by H3K(+H)4b-mRNA polyplexes expressed 10-fold greater levels of luciferase than H3K4b polyplexes. With gel retardation and heparin displacement assays, the H3K(+H)4b polyplexes showed greater stability than H3K4b. Intracellular uptake and co-localization of H3K(+H)4b polyplexes within acidic endosomes were also significantly increased compared to H3K4b. Similar to H3K(+H)4b, several HK analogues with an additional histidine in the second domain of their branches were effective carriers of mRNA. When combined with DOTAP liposomes, H3K(+H)4b was synergistic in delivery of mRNA. CONCLUSIONS: H3K(+H)4b was a more effective carrier of mRNA than H3K4b. Mechanistic studies suggest that H3K(+H)4b polyplexes were more stable than H3K4b polyplexes. Lipopolyplexes formed with H3K(+H)4b markedly increased mRNA transfection.

Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer.

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined. Here we found that KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells. Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next-generation AR-targeted therapy. Inhibition of KDM4B significantly inhibited prostate tumor cell growth in xenografts, and improved enzalutamide treatments through suppression of c-Myc. Clinically, KDM4B expression was found upregulated and to correlate with prostate cancer progression and poor prognosis. Our results revealed a novel mechanism of anti-androgen resistance via histone demethylase alteration which could be targeted through inhibition of KDM4B to reduce AR-dependent c-Myc expression and overcome resistance to AR-targeted therapies. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Utility evaluation of HLA-B*13:01 screening in preventing trichloroethylene-induced hypersensitivity syndrome in a prospective cohort study.

OBJECTIVES: Trichloroethylene (TCE) -induced hypersensitivity syndrome (TIHS) is a potentially life-threatening disease. Several genetic susceptibility biomarkers have been found to be associated with TIHS, and this systematic prospective study has been conducted to evaluate the utility of these genetic susceptibility biomarkers in preventing the disease. METHODS: The newly hired TCE-exposed workers were recruited from March 2009 to October 2010. HLA-B*13:01 genotyping and 3-month follow-up procedure were conducted. All workers were monitored for adverse reaction by telephone interview every week. The workers with early symptoms of TIHS were asked to go to the hospital immediately for further examination, diagnosis and treatment. The medical expense record data of patients with TIHS were collected for cost-effectiveness analysis in 2018. RESULTS: Among 1651 workers, 158 (9.57%) were found to carry the HLA-B*13:01 allele and 16 (0.97%) were diagnosed with TIHS. HLA-B*13:01 allele was significantly associated with an increased TIHS risk (relative risk=28.4, 95% CI 9.2 to 86.8). As a risk predictor of TIHS, HLA-B*13:01 testing had a sensitivity of 75%, a specificity of 91.1% and an area under curve of 0.83 (95% CI 0.705 to 0.955), the positive and negative predictive values were 7.6% and 99.7%, respectively. The incidence of TIHS was significantly decreased in HLA-B*13:01 non-carriers (0.27%) compared with all workers (0.97%, p=0.014). Cost-effectiveness analysis showed that HLA-B*13:01 screening could produce an economic saving of $4604 per TIHS avoided. CONCLUSIONS: Prospective HLA-B*13:01 screening may significantly reduce the incidence of TIHS and could be a cost effective option for preventing the disease in TCE-exposed workers.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals.

BACKGROUND: Cancer cells are characterized by aberrant activation of lipid biosynthesis, producing saturated fatty acids and monounsaturated fatty acids via stearoyl-CoA desaturases (SCD) for regulating metabolic and signaling platforms. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. This study aimed to investigate the role of SCD1 inhibition by EGFR inhibitor (Gefitinib)-based anti-tumor therapy of lung cancer both in vitro and in vivo. METHODS: CCK-8 assay was performed to determine cell viability. The SCD1 mRNA level was detected by qPCR. The protein levels were assessed by Western blotting. E-cadherin and N-cadherin levels were determined by immunofluorescence. Apoptosis detection was conducted by flow cytometry. Cell migration or invasion was evaluated by transwell assay. The tumor sizes and tumor volumes were calculated in nude mice by subcutaneous injection of A549 cells transfected with vector of pcDNA3.1-SCD1 or negative control. Expression of Ki-67 was detected by immunohistochemistry. RESULT: SCD1 up-regulated expression was observed in lung cancer cell lines. Cells with overexpressed SCD1 had high IC50 values for Gefitinib in A549 and H1573 cell lines. Overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion, while these effects were counteracted by A939572. Mechanistically, SCD1 promoted the activation of proliferation and metastasis-related EGFR/PI3K/AKT signaling, and up-regulated epithelial to mesenchymal transition (EMT) phenotype in the two cell lines, which was restored by SCD1 inhibition. Furthermore, in spite of EGFR inhibition, overexpression of SCD1 in vivo significantly promoted tumor growth by activating EGFR/PI3K/AKT signaling in tumor tissues, but A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo. CONCLUSION: These findings indicated that inhibition of oncogene SCD1 is required for targeting EGFR therapy in lung cancer.

Three-Dimensional Versus Two-Dimensional Video-Assisted Endoscopic Surgery: A Meta-analysis of Clinical Data.

BACKGROUND: There have been no studies to systematically evaluate the two display (3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in clinical settings; thus, we conducted one to evaluate the safety and efficacy of different visualization systems (two-dimensional and three-dimensional) during endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings. METHODS: A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy, prospective vs. retrospective study, malignant vs. benign diseases) were examined. Meta-regression was conducted to explore the source of heterogeneity. RESULTS: Twenty-three articles were considered in this analysis, of which 7 were thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D display. Overall, significantly shorter operating time (SMD -0.69; p = <0.001), less blood loss (SMD -0.26; p = 0.028) and shorter hospital stays (SMD -0.16; p = 0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity (OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage duration (SMD -0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were similar between the two groups. Comparison of the overall outcomes in each subset showed consistency in all groups. CONCLUSIONS: This up-to-date meta-analysis reveals that the 3D display system is superior to the 2D system in clinical settings with significantly shorter operating time, less blood loss and shorter hospital stay. These findings suggest that, in laparoscopic or thoracoscopic surgeries, 3D endoscopic system is preferable when condition permits. Future efforts should be made on decreasing the side effects of 3D display and increasing its cost-effectiveness.

Common and uncommon adverse cutaneous reactions to erlotinib: a study of 20 Chinese patients with cancer.

OBJECTIVE: This study presented common lesions with systemic toxicities and uncommon adverse cutaneous reactions such as anaphylactic dermatitis in patients undergoing treatment with erlotinib for the benefit of practicing dermatologists and oncologists. METHODS: Adverse cutaneous reactions associated with erlotinib were reported in 20 Chinese patients with cancer. RESULTS: Adverse cutaneous reactions reported included six cases of anaphylactic dermatitis, 12 cases of acneiform rash, nine cases of xerosis, five cases of nail changes and four cases of hair changes. One case of anaphylactic dermatitis manifested as erythema with swelling on the face and neck, and others as erosive and scaly erythema on the fold of skin, or red macules, papules, plaques and pigmentation on the whole body. Clinical details indicated anaphylactic reactions, including a high percentage of eosinophils in the peripheral blood, eosinophilic infiltration in the dermis layer and good response to antihistamines and topical steroids. Systemic toxicities accompanied by cutaneous reactions occurred in five patients including one case of anaphylactic dermatitis and four cases of acneiform rash. Elevated hepatic enzymes were observed among all the patients with grade-3 or grade-4 acneiform rashes. One patient with anaphylactic dermatitis and one with acneiform rash discontinued erlotinib administration due to severe lesions, high fever or severe elevation of hepatic enzymes. CONCLUSIONS: Anaphylactic cutaneous reactions caused by erlotinib are rarely described hitherto. Systemic toxicities should be emphasized especially in cases with severe skin disorders. Timely detection and appropriate early intervention in patients who develop severe cutaneous reaction while on erlotinib therapy should be considered clinically.

Prognosis of primary tracheal tumor: A population-based analysis.

BACKGROUND: To elucidate the survival outcomes of tracheal tumors and to propose the potential stage of tracheal tumors. METHOD: All cases of primary tracheal malignant tumors were extracted from the Surveillance, Epidemiology, and End Results database (SEER) during 1973-2013. The overall survival was calculated using Kaplan-Meier method. Cox regression was utilized to identify the prognostic factors. RESULT: A total of 287 cases were finally included. The median age of the patients was 59 years. Male patients accounted for 56.1%. The median survival was 57 months. Patients were categorized as Extension1 to 4 (E1-4) and N0-N3. E1 group with size <4 cm had the best prognosis. While E1 >4 cm, E2 and E3 <3 cm groups had similar outcomes, which were superior to E3 >3 cm group. E4 was the worst. N0 patients had ideal prognosis, which were better than N1 and N2 patients. The 3-year survival rates of each T category were 74.7%, 57.3%, 28.1%, and 9.1%, respectively. In multivariate analysis, age, histology, tumor size, and extension were independent prognostic factors. CONCLUSION: Patients with old age, large tumor size, advanced extension or no surgery may have worse prognosis. The proposed T category of tracheal tumor incorporating tumor extension and size helped to predict survival outcomes.

Delivery of mRNA with Histidine-Lysine Peptides.

Transfection with mRNA has been considered superior to that with plasmids since the mRNA can be translated to a protein in the cytosol without entering the nucleus. One disadvantage of using mRNA is its susceptibility to enzymatic biodegradability, and consequently, significant research has occurred to determine nonviral carriers that will sufficiently stabilize this nucleic acid for cellular transport. Histidine-lysine peptides (HK) are one such class of mRNA carriers, which we think serves as a model for other peptides and polymeric carrier systems. When the HK peptide and mRNA are mixed and interact through ionic and nonionic bonds, mRNA polyplexes are formed, which can transfect cells. In contrast to linear HK peptides, branched HK peptides protected and efficiently transfected mRNA into cells. After describing the preparation and biophysical characterization of these polyplexes, we will provide protocols for in vitro and in vivo transfection for these mRNA polyplexes.

The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

Background: The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. Methods: We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Results: Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. Conclusion: This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

Distribution of the entomopathogenic fungus Beauveria bassiana in rice ecosystems and its effect on soil enzymes.

Fungal entomopathogens, especially Beauveria bassiana, are often studied within the context of their use in biological pest control; however, there is limited knowledge of their distributions in host plants and soil ecosystem. We examined the distribution of B. bassiana and its influence on rice plants and paddy soils. B. bassiana could only be detected on the foliar surfaces of rice plants within 15 days under Bb-4 (7.5 × 10(4) conidia/mL) and Bb-7 (7.5 × 10(7) conidia/mL) treatments. The endophytic colonization of B. bassiana could not be found in stems, roots, or seeds of rice plants under Bb-4 and Bb-7 treatments. The fungus was found only in the leaves of rice plants under Bb-4 and Bb-7 treatments at 15 days after inoculation. Moreover, B. bassiana was absent from paddy soils under Bb-4 and Bb-7 treatments at all times. Enzyme activity (urease and phosphatase) in the paddy soils of Bb-4 and Bb-7 treatments showed no significant difference from the control. It is possible that B. bassiana was not able to colonize paddy soil. Detailed understanding of distribution and ecological interactions of B. bassiana is helpful for understanding and predicting the effects of fungal entomopathogens on host populations, and the interactions among fungal entomopathogens and other organisms in the community.

[Investigation of non-ionizing radiation hazards from physiotherapy equipment in 16 medical institutions].

OBJECTIVE: To investigate the non-ionizing radiation hazards from physiotherapy equipment in medical institutions and to explore feasible control measures for occupational diseases. METHODS: On-site measurement and assessment of ultra-high-frequency radiation, high-frequency electromagnetic field, microwave radiation, and laser radiation were carried out in 16 medical institutions using the methods in the Measurement of Physical Agents in Workplace (GBZ/T189-2007). RESULTS: All the investigated medical institutions failed to take effective protective measures against non-ionizing radiation. Of the 17 ultra-short wave therapy apparatus, 70.6%, 47.1%, and 17.64% had a safe intensity of ultra-high-frequency radiation on the head, chest, and abdomen, respectively. Of the 4 external high-frequency thermotherapy apparatus, 100%, 75%, and 75%had a safe intensity of high-frequency electromagnetic field on the head, chest, and abdomen, respectively. In addition, the intensities of microwave radiation and laser radiation produced by the 18 microwave therapy apparatus and 12 laser therapeutic apparatus met national health standards. CONCLUSION: There are non-ionizing radiation hazards from physiotherapy equipment in medical institutions, and effective prevention and control measures are necessary.

Utilization of intraoperative indocyanine green fluorescence imaging to identify vascular anatomy in severe pleural adhesions in uniportal video-assisted thoracoscopic surgery: a case report.

Background: Extensive and dense pleural adhesion is a serious challenge in video-assisted thoracoscopic surgery (VATS), in which identification of vessels and their anatomical spaces is difficult. Once critical vessel is damaged while dissecting adhesion in VATS, leading to fatal hemorrhage, the surgeon will have to switch to thoracotomy. This is the first report of a case in which intraoperative indocyanine green (ICG) fluorescence imaging was used to identify critical vessels in severe pleural adhesions in uniportal VATS. Case Description: The patient (67-year-old male) with an 8-year history of tuberculosis and severe mixed ventilation dysfunction underwent a standardized wedge resection due to chest computed tomography (CT) scan that revealed a 2.6-cm nodule in the right upper lung. Intraoperatively, the superior vena cava and azygos vein were successfully identified and safely dissected using ICG fluorescence imaging in the presence of extensive and dense pleural adhesions. The chest drainage tube was removed on postoperative day (POD) 3, and patient was released from hospital on POD 5. The patient recovered well and no complication was observed in the follow-up. Conclusions: The ICG fluorescence imaging is used to illustrate the vessels and help to dissect them safely, which is a feasible, visualizable, and user-friendly method in severe pleural adhesions in uniportal VATS.

BDN-DDI: A bilinear dual-view representation learning framework for drug-drug interaction prediction.

Drug-drug interactions (DDIs) refer to the potential effects of two or more drugs interacting with each other when used simultaneously, which may lead to adverse reactions or reduced drug efficacy. Accurate prediction of DDIs is a significant concern in recent years. Currently, the drug chemical substructure-based learning method has substantially improved DDIs prediction. However, we notice that most related works ignore the detailed interaction among atoms when extracting the substructure information of drugs. This problem results in incomplete information extraction and may limit the model's predictive ability. In this work, we proposed a novel framework named BDN-DDI (a bilinear dual-view representation learning framework for drug-drug interaction prediction) to infer potential DDIs. In the proposed framework, the encoder consists of six stacked BDN blocks, each of which extracts the feature representation of drug molecules through a bilinear representation extraction layer. The extracted feature is then used to learn embeddings of drug substructures from the single drug learning layer (intra-layer) and the drug-pair learning layer (inter-layer). Finally, the learned embeddings are fed into a decoder to predict DDI events. Based on our experiments, BDN-DDI has an AUROC value of over 99% for the warm-start task. Additionally, it outperformed the state-of-the-art methods by an average of 3.4% for the cold-start tasks. Finally, our method's effectiveness is further validated by visualizing several case studies.

Impacts of additional cycles of neoadjuvant immunotherapy on surgery in non-small-cell lung cancer.

OBJECTIVE: Whether cycle number influences the subsequent pathological or surgical outcomes remained unclear. This study aimed to assess the efficacy and surgical safety of neoadjuvant immunochemotherapy-based treatment in the real-world setting. METHODS: Clinical data of patients who received neoadjuvant immunochemotherapy for non-small-cell lung cancer between 2018 and 2021 were collected. Oncological outcomes such as objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR), and surgical outcomes including operating time, intraoperative bleeding, postoperative drainage, and hospital stay were analyzed. RESULTS: In total, 176 patients were included, among whom 102 cases were lung squamous carcinoma (LUSQ). After immunochemotherapy, 98 (56%) of patients achieved ORR. Notably, the ORR (63% vs. 46%, p = 0.039) and pCR (45% vs. 27%, p = 0.022) were significantly higher in patients with LUSQ. For patients who received two, three, four, and five or more cycles, the ORRs were 52%, 67%, 53%, and 50% (p = 0.36). In post hoc analysis, cycle numbers showed no significant association with MPR or pCR (p = 0.14 and p = 0.073). Treatment cycles showed no influence on operating time, postoperative drainage, and hospital stay (p = 0.79, 0.37, and 0.22). Notably, the blood loss index of patients who received more than four cycles was higher than those receiving four or fewer cycles (mean blood loss: two or fewer cycles 153.1, three cycles 113.8, four cycles 137.6, and five or more cycles 293.3, respectively). CONCLUSIONS: This study indicated that cycles of neoadjuvant immunochemotherapy had no significant effect on the feasibility and safety of surgery. Although not statistically significant, patients who received five or more cycles of treatment experienced higher intraoperative blood loss.

Cigarette smoking and thyroid cancer risk: A Mendelian randomization study.

BACKGROUND: The association between cigarette smoking and thyroid cancer has been reported in prospective cohort studies, but the relationship remains controversial. To investigate this potential correlation further, we employed Mendelian randomization methodology to evaluate the causative impact of smoking on thyroid cancer incidence. METHODS: From the genome-wide association study and Sequencing Consortium of Alcohol and Nicotine use, we obtained genetic variants associated with smoking initiation and cigarettes per day (1.2 million individuals). We also extracted genetic variants associated with past tobacco smoking from the UK Biobank (424,960 individuals). Thyroid cancer outcomes were selected from the FinnGen GWAS (989 thyroid cancer cases and 217,803 control cases). Sensitivity analyses employing various approaches such as weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) have been executed, as well as leave-one-out analysis to identify pleiotropy. RESULTS: Using the IVW approach, we did not find evidence that any of the three smoking phenotypes were related to thyroid cancer (smoking initiation: odds ratio (OR) = 1.56, p = 0.61; cigarettes per day: OR = 0.85, p = 0.51; past tobacco smoking: OR = 0.80, p = 0.78). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. CONCLUSIONS: The MR analysis revealed that there may not exist a causative link between smoking exposure and elevated incidence rates of thyroid malignancies.

Incidence and influencing factors of fertility concerns in breast cancer in young women: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the prevalence and influencing factors of fertility concerns in breast cancer in young women. Methods: A literature search on PubMed, Embase, Web of Science, and Cochrane Library databases was conducted up to February 2023 and was analyzed (Revman 5.4 software) in this study. The papers were chosen based on inclusion standards, and two researchers independently extracted the data. The included studies' quality was evaluated using criteria set out by the Agency for Healthcare Research and Quality. To identify significant variations among the risk factors, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were utilized. Results: A total of 7 studies that included 1579 breast cancer in young women were enrolled in the study. The results showed that for breast cancer in young women, the incidence of fertility concerns 53%(95%CI [0.45,0.58]). The results showed that education (2.65, 95% CI 1.65-5.63), full-time work (0.12, 95% CI 1.03-1.93), fertility intentions (7.84, 95% CI 1.50-37.4), depression level (1.25, 95% CI 1.03-1.5), and endocrine therapy (1.32, 95% CI 1.08-1.62) were risk factors for fertility concerns in young women with BC. Having a partner (0.41, 95% CI 0.33-0.5), ≥1 child (0.3, 95% CI 0.22-0.4) were identified as protective factors against fertility concerns in young women with BC. Conclusions: The incidence of fertility concerns in breast cancer in young women is at a moderately high level. We should pay more attention to the risk factors of fertility concerns to help breast cancer in young women cope with their fertility concerns and promote their psychological well-being.