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INTRODUCTION: Collegiate mental health continues to be a worrisome public health concern among college students in the U.S. The unprecedented COVID-19 pandemic has caused an upward trend of mental health crises, especially among lesbian, gay, bisexual, and transgender (LGBTQ+) college students. The objective of this study was to assess the mental health statuses, attitudes towards disease control and mitigation measures, and coping strategies among this vulnerable group. METHODS: A web-based survey was conducted at a medium-sized public university in the mid-Atlantic region during the summer and fall of 2021 when COVID-19 was still a major public health concern. The survey was distributed through the listservs of the college and was advertised through campus-wide social media. Descriptive and inferential statistics including a t-test for the differences in group means and a logit regression model for comparing the groups were used. RESULTS: Our final sample is composed of 611 students with 79% of the respondents identifying as straight, and 20% in the LGBTQ+ group. Our results showed that LGBTQ+ students exhibited higher levels of anxiety and fear compared to the non-LGBTQ+ groups. Also, a large proportion of LGBTQ+ students were negatively impacted by the pandemic as compared to the non-LGBTQ+ groups (p = 0.05), while they generally have more positive views on the public health measures to alleviate the adverse impacts from COVID-19 (p = 0.001). CONCLUSIONS: Public health emergency management should adopt appropriate strategies and adapt their services to support the mental health needs of LGBTQ+ students. Our study highlighted the need to design tailored health promotion programs and enhance support systems for LGBTQ+ college students during similar emergencies.
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Objective: To investigate the clinical characteristics and correlated factors of preoperative sleep disorders in patients undergoing various types of cardiac surgery. Methods: The data of patients at the Structural Heart Surgery Center of Beijing Anzhen Hospital, Capital Medical University, from April 2023 to February 2024 were retrospectively collected. Patients were categorized into five groups based on cardiac surgical diagnosis: coronary heart disease, valvular disease, large vessel disease, congenital heart disease, and others. Each group was further subdivided into normal sleep (NS) and sleep disorder (SD) groups based on the Pittsburgh Sleep Quality Index (PSQI) scores. Demographic information, cognitive function, psychiatric symptoms, and other relevant data were collected. Clinical characteristics were compared between groups, and factors associated with preoperative sleep disorders were analyzed using multivariate logistic regression. Results: A total of 1 016 patients aged (58.6±12.7) years were included in the study, including 701 males and 315 females. The incidence of SD was 45.6% (463/1 016). Multivariate logistic regression analysis showed that aging was a risk factor for sleep disorders in patients with coronary heart disease (OR=1.050, 95%CI: 1.026-1.077) and valvular disease (OR=1.033, 95%CI: 1.013-1.053). High Self-rating Depression Scale (SDS) score was a risk factor for sleep disorders in patients with valvular disease (OR=1.050, 95%CI: 1.013-1.091). High score on the Montreal Cognitive Assessment (MoCA) subitem-abstraction ability was a protective factor for sleep disorders in patients with coronary heart disease (OR=0.695, 95%CI: 0.490-0.981). Conclusions: The risk factors of preoperative sleep disorders in cardiac surgery patients vary based on the type of cardiac disease. Aging, depression and abstraction ability correlate with sleep disorders in cardiac surgical patients.
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Procedimentos Cirúrgicos Cardíacos , Transtornos do Sono-Vigília , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Idoso , Doença das Coronárias/cirurgia , Período Pré-Operatório , Modelos LogísticosRESUMO
The recent advances in mass spectrometry (MS) technologies have enabled comprehensive lipid profiling in biological samples. However, the robustness and efficiency of MS-based lipidomics is compromised by the complexity of biological samples. High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a technology that can continuously transmit one type of ion, independent of mass-to-charge ratio. Here we present the development and application of LC-FAIMS-MS/MS based platform for untargeted lipidomics. We used 3 optimally balanced compensation voltages, i.e., 29 V, 34 V and 39 V, to analyse all subclasses of glycerophospholipids. The reproducibility of the method was evaluated using reference standards. The reproducibility of retention times ranged from 0.9 to 1.5 % RSD; whereas RSD values of 5-10 % were observed for peak areas. More importantly, the coupling of a FAIMS device can significantly improve the robustness and efficiency. We exploited this NPLC-FAIMS-HRMS to analyze the serum lipid profiles in mice infected intranasally with Acinetobacter baumannii. The temporal profiles of serum lipids after A. baumannii inoculation were obtained for 4 h, 8 h and 24 h. We found that nearly all ether PC and ether PE lipids were significantly decreased 8 h after inoculation. The resultant volcano plot illustrated the distribution of 28 increased and 28 decreased lipid species in mouse sera 24 h after inoculation. We also found that a single ether PE composition can comprise multiple isomeric structures, and the relative abundance of each isomer could be quantified using the newly developed NPLC-FAIMS-PRM method.
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Objective: To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data. Methods: Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019. Results: During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, Pï¼0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, Pï¼0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion: The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.
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Neoplasias , Humanos , China/epidemiologia , Masculino , Feminino , Neoplasias/mortalidade , Neoplasias/epidemiologia , Taxa de Sobrevida , Criança , Adolescente , Adulto , Pré-Escolar , Lactente , Adulto Jovem , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/epidemiologia , População Rural/estatística & dados numéricos , Neoplasias Pancreáticas/mortalidade , Recém-Nascido , Neoplasias Pulmonares/mortalidade , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/epidemiologia , Fatores Sexuais , Neoplasias Hepáticas/mortalidade , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/epidemiologia , Sistema de Registros , População Urbana/estatística & dados numéricos , Fatores EtáriosRESUMO
Objective: To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction. Method: This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops. Results: Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis. Conclusion: Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.
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Anastomose Cirúrgica , Gastrectomia , Jejuno , Laparoscopia , Neoplasias Gástricas , Humanos , Gastrectomia/métodos , Laparoscopia/métodos , Anastomose Cirúrgica/métodos , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Jejuno/cirurgia , Esôfago/cirurgia , Pessoa de Meia-Idade , Masculino , Estômago/cirurgia , FemininoRESUMO
Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of Gi-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778. Our structures reveal a conserved recognition pattern of pasireotide in SSTRs attributed to the binding with a conserved extended binding pocket, distinct from SST14, octreotide, and lanreotide. Together with mutagenesis analyses, our structures further reveal the dynamic feature of ligand binding pockets in SSTR1 and SSTR3 to accommodate divergent agonists, the key determinants of ligand selectivity lying across the orthosteric pocket of different SSTR subtypes, as well as the molecular mechanism underlying diversity and conservation of receptor activation. Our work provides a framework for rational design of subtype-selective SSTR ligands and may facilitate drug development efforts targeting SSTRs with improved therapeutic efficacy and reduced side effects.
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Microscopia Crioeletrônica , Receptores de Somatostatina , Somatostatina , Humanos , Sítios de Ligação , Ligantes , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Ligação Proteica , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/química , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/ultraestrutura , Somatostatina/metabolismo , Somatostatina/análogos & derivados , Somatostatina/químicaRESUMO
OBJECTIVE: To develop a multiplex PCR assay for simultaneous detection of four intestinal parasites, including Giardia duodenalis, Cryptosporidium parvum, Enterocytozoon bieneusi and Moniezia, and to preliminarily evaluate its detection efficiency. METHODS: Four pairs of specific primers were designed based on the conserved sequences of the corresponding genes of G. duodenalis (GenBank accession number: XM_001710026.2), C. parvum (GenBank accession number: XM_626998.1), E. bieneusi (GenBank accession number: KJ719492.1) and Moniezia (GenBank accession number: OM296991.1) retrieved from the GenBank database, and a multiplex PCR assay for simultaneous detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia was developed and optimized. A total of 116 fresh goat stool samples were collected from four goat farms in Zhanjiang City, Guangdong Province during the period from October to December 2022, including 96 samples used for evaluating the detection efficacy of the multiplex PCR assay, and 20 samples as baseline controls for sample testing. Genomic DNA extracted from 96 goat stool samples was tested using the single-target PCR assay and the developed multiplex PCR assay, and the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex PCR assay were evaluated for detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia DNA in goat stool samples with the single-target PCR assay as the gold standard. RESULTS: The multiplex PCR assay developed in this study allowed simultaneous amplification of specific gene fragments of G. duodenalis, C. parvum, E. bieneusi and Moniezia, with 1 400, 755, 314 bp and 585 bp in sizes, respectively, and the detection limit was 102 and higher copies of parasite DNA clones, while the multiplex PCR assay was negative for gene amplification of Schistosoma japonicum, Fasciola hepatica, Echinococcus granulosus, Blastocystis hominis and Homalogaster paloniae. Single-target PCR assay and the developed multiplex PCR assay were employed to test DNA samples extracted from 96 goat stool samples, and single-target PCR assay tested positive in 40 goat stool samples (41.67%), including 39 positive samples tested with the multiplex PCR assay, with a mean coincidence rate of 97.50% (39/40). The multiplex PCR assay tested positive for G. duodenalis DNA in 26 goat stool samples (27.10%), C. parvum DNA in 22 samples (22.90%), E. bieneusi DNA in 24 samples (25.00%), and Moniezia in 9 samples (9.40%), which was consistent with the detection using the single-target PCR assay. The sensitivity, negative predictive value, and positive predictive value of the multiplex PCR assay were 96.15%, 95.83%, 100.00% and 100.00%, 98.90%, 98.92%, 100.00% and 100.00%, 100.00%, 100.00%, 100.00% and 100.00% for detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia DNA in goat stool samples, respectively, if the single-target PCR assay served as the gold standard. CONCLUSIONS: A highly sensitive and specific multiplex PCR assay has been developed for simultaneous detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia in goats, which is suitable for rapid, large-scale screening of intestinal parasites in sheep stool samples.
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Doenças das Cabras , Cabras , Reação em Cadeia da Polimerase Multiplex , Animais , Cabras/parasitologia , Reação em Cadeia da Polimerase Multiplex/métodos , Doenças das Cabras/parasitologia , Doenças das Cabras/diagnóstico , Cryptosporidium/isolamento & purificação , Cryptosporidium/genética , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/veterinária , Enteropatias Parasitárias/parasitologia , Fezes/parasitologia , Giardia/isolamento & purificação , Giardia/genética , Taenia/genética , Taenia/isolamento & purificação , Sensibilidade e EspecificidadeRESUMO
Objective: To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF). Methods: A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed. Results: A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion: Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.
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Insuficiência Intestinal , Nutrição Parenteral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Insuficiência Intestinal/diagnóstico , Insuficiência Intestinal/terapia , Adolescente , Resultado do Tratamento , Adulto Jovem , DesnutriçãoRESUMO
Under certain symmetry-breaking conditions, a superconducting system exhibits asymmetric critical currents, dubbed the "superconducting diode effect." Recently, systems with the ideal superconducting diode efficiency or unidirectional superconductivity have received considerable interest. In this work, we report the study of Al-InAs nanowire-Al Josephson junctions under microwave irradiation and magnetic fields. We observe an enhancement of superconducting diode effect under microwave driving, featured by a horizontal offset of the zero-voltage step in the voltage-current characteristic that increases with microwave power. Devices reach the unidirectional superconductivity regime at sufficiently high driving amplitudes. The offset changes sign with the reversal of the magnetic field direction. Meanwhile, the offset magnitude exhibits a roughly linear response to the microwave power in dBm when both the power and the magnetic field are large. The signatures observed are reminiscent of a recent theoretical proposal using the resistively shunted junction (RSJ) model. However, the experimental results are not fully explained by the RSJ model, indicating a new mechanism for unidirectional superconductivity that is possibly related to nonequilibrium dynamics or dissipation in periodically driven superconducting systems.
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Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide-receptor system.
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Objective: To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma. Methods: Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children's Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed. Results: The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group (P<0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions: There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Criança , Glioma/patologia , Glioma/genética , Glioma/diagnóstico por imagem , Feminino , Pré-Escolar , Masculino , Adolescente , Lactente , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mutação , Recém-Nascido , Astrocitoma/genética , Astrocitoma/patologia , Astrocitoma/diagnóstico por imagem , Proteínas Proto-Oncogênicas B-raf/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Therapeutic antibodies are at the forefront of biotherapeutics, valued for their high target specificity and binding affinity. Despite their potential, optimizing antibodies for superior efficacy presents significant challenges in both monetary and time costs. Recent strides in computational and artificial intelligence (AI), especially generative diffusion models, have begun to address these challenges, offering novel approaches for antibody design. This review delves into specific diffusion-based generative methodologies tailored for antibody design tasks, de novo antibody design, and optimization of complementarity-determining region (CDR) loops, along with their evaluation metrics. We aim to provide an exhaustive overview of this burgeoning field, making it an essential resource for leveraging diffusion-based generative models in antibody design endeavors.
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Objective: To investigate the safety and efficacy of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction. Methods: It was a randomized controlled trial. A total of 180 patients with great saphenous vein dysfunction were enrolled prospectively, and scheduled for surgical treatment in 9 hospitals, including the Second Affiliated Hospital of Naval Medical University, Shanghai Oriental Hospital Affiliated to Tongji University, Xuanwu Hospital Capital Medical University, the First Hospital of Hebei Medical University, Ganzhou People's Hospital, Shanxi Bethune Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, and Zhongshan Hospital Affiliated to Xiamen University, from June to October 2022. Using a random number table method, the subjects were divided into an experimental group and a control group, with 90 cases in each group. The patients of experimental group received treatment with varicose vein sealant kit, while the patients of control group received radiofrequency ablation. The main outcome measure was the complete closure rate of the great saphenous vein in both groups of patients 3 months after surgery. The secondary outcome measures were the complete closure rate of the great saphenous vein in both groups of patients immediately after surgery and 6 months after surgery, the operation time for closing the main trunk of the great saphenous vein, pain score, venous clinical severity score (VCSS), Aberdeen varicose veins questionnaire (AVVQ) at different times before and after surgery, and the incidence of complications in both groups of patients. The non inferiority threshold for the two treatment methods is set at "-10.00%". Results: A total of 177 patients were ultimately enrolled. There were 89 cases in the experimental group, including 38 males and 51 females, with a median age [M (Q1, Q3)] of 59.7(49.6, 66.7) years, and 88 cases in the control group, including 30 males and 58 females, with a median age of 57.2(46.9, 65.9) years. A total of 174 patients completed a 3-month follow-up, and 167 patients completed a 6-month follow-up. The closure time of the main saphenous vein in the experimental group was (22.1±11.1) min, which was longer than the control group, which was (18.7±9.8) min (P=0.031). The complete closure rate of the great saphenous vein immediately after surgery in both the experimental group and the control group was 100%. The complete closure rates of the great saphenous vein at 3 months after surgery were 98.8% (85/86) and 98.9% (87/88), respectively. The lower limit of the 95%CI for the difference between the two groups was -3.19%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The complete closure rates of the great saphenous vein at 6 months after surgery were 97.6% (81/83) and 100% (84/84), the lower limit of the 95%CI for the difference between the two groups was -5.71%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The immediate pain scores after complete anesthesia awakening of the experimental group and the control group were both 1.0 (0, 2.0), with no statistically significant difference (P=0.365). The incidence of bruising in the experimental group and the control group one week after surgery was 61.2% (52/85) and 67.1% (57/85), respectively, with no statistically significant difference (P=0.181). There was no statistically significant difference in VCSS and AVVQ scores between groups before surgery and at 1, 3, and 6 months after surgery (all P>0.05). There was no statistically significant difference in the incidence of complications such as deep vein thrombosis, phlebitis, pain, and subcutaneous hematoma in the lower limbs 3 months after surgery (all P>0.05). Conclusion: The varicose vein sealant kit is safe and effective in treating great saphenous vein dysfunction, and can achieve a complete closure rate of great saphenous vein that is not inferior to traditional radiofrequency ablation.
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Veia Safena , Varizes , Insuficiência Venosa , Humanos , Veia Safena/cirurgia , Varizes/cirurgia , Insuficiência Venosa/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Ablação por Cateter/métodosRESUMO
Eukaryotic TIR (Toll/interleukin-1 receptor protein) domains signal via TIR-TIR interactions, either by self-association or by interaction with other TIR domains. In mammals, TIR domains are found in Toll-like receptors (TLRs) and cytoplasmic adaptor proteins involved in pro-inflammatory signaling. Previous work revealed that the MAL TIR domain (MALTIR) nucleates the assembly of MyD88TIR into crystalline arrays in vitro. A microcrystal electron diffraction (MicroED) structure of the MyD88TIR assembly has previously been solved, revealing a two-stranded higher-order assembly of TIR domains. In this work, it is demonstrated that the TIR domain of TLR2, which is reported to signal as a heterodimer with either TLR1 or TLR6, induces the formation of crystalline higher-order assemblies of MyD88TIR in vitro, whereas TLR1TIR and TLR6TIR do not. Using an improved data-collection protocol, the MicroED structure of TLR2TIR-induced MyD88TIR microcrystals was determined at a higher resolution (2.85â Å) and with higher completeness (89%) compared with the previous structure of the MALTIR-induced MyD88TIR assembly. Both assemblies exhibit conformational differences in several areas that are important for signaling (for example the BB loop and CD loop) compared with their monomeric structures. These data suggest that TLR2TIR and MALTIR interact with MyD88 in an analogous manner during signaling, nucleating MyD88TIR assemblies unidirectionally.
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Fator 88 de Diferenciação Mieloide , Receptor 2 Toll-Like , Receptor 2 Toll-Like/química , Receptor 2 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/química , Fator 88 de Diferenciação Mieloide/metabolismo , Humanos , Domínios Proteicos , Modelos Moleculares , Receptor 6 Toll-Like/química , Receptor 6 Toll-Like/metabolismo , Receptor 1 Toll-Like/química , Receptor 1 Toll-Like/metabolismo , Cristalografia por Raios X/métodos , Receptores de Interleucina-1/química , Receptores de Interleucina-1/metabolismo , Multimerização ProteicaRESUMO
Objective: To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2). Methods: Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results: The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband's mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions: Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.
Assuntos
RNA Polimerases Dirigidas por DNA , Disostose Mandibulofacial , Criança , Feminino , Humanos , Audiometria de Tons Puros , RNA Polimerases Dirigidas por DNA/genética , Sequenciamento do Exoma , Disostose Mandibulofacial/complicações , Disostose Mandibulofacial/diagnóstico , Disostose Mandibulofacial/genética , Mutação , Linhagem , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/genéticaRESUMO
OBJECTIVES: To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. METHODS: This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate-level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. RESULTS: Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver-operating-characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. CONCLUSIONS: The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate-level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Neoplasias do Endométrio , Sensibilidade e Especificidade , Ultrassonografia , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Ultrassonografia/métodos , Pessoa de Meia-Idade , Adulto , Radiologistas , Competência Clínica , Endométrio/diagnóstico por imagem , Endométrio/patologia , Idoso , Neoplasias Uterinas/diagnóstico por imagem , Curva ROC , Reprodutibilidade dos TestesAssuntos
Hemorragia Gastrointestinal , Humanos , Estudos Retrospectivos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Duodenopatias/cirurgia , Varizes/cirurgia , Varizes/complicações , Idoso , Doença AgudaRESUMO
Objective: This study evaluates the agreement between a new low-load sleep monitoring system, QSA600, based on millimeter-wave radar technology, and polysomnography (PSG) in diagnosing obstructive sleep apnea (OSA). Methods: A total of 155 subjects were recruited for a parallel agreement study in the sleep laboratory of the Department of Otorhinolaryngology Head and Neck Surgery at Shanghai Sixth People's Hospital from July to September 2023. The subjects underwent simultaneous monitoring with both PSG and the QSA600 system. One hundred and forty-five subjects consisting of 75 males and 70 females included in the final analysis, with an average age of (35.30±12.41) years, an average height of (168.23±8.08) cm, and an average weight of (68.28±13.74) kg. The subjects were divided into four groups based on the apnea-hypopnea index (AHI): <5.0 events/h (non-OSA group, 39 cases), ≥5.0-<15.0 events/h (mild OSA group, 47 cases), ≥15.0-<30.0 events/h (moderate OSA group, 25 cases), and≥30.0 events/h (severe OSA group, 34 cases). Intraclass correlation coefficients (ICC), Pearson correlation coefficients (r), and Bland-Altman analysis were employed to assess the agreement between the two monitoring techniques regarding AHI and other parameters. Sensitivity and specificity of the QSA600 in diagnosing OSA were evaluated at different AHI thresholds. Statistical analyses were conducted using MATLAB R2022a. Results: Using AHI 5 events/h, 15 events/h and 30 events/h as thresholds, the sensitivity for diagnosing mild, moderate, and severe OSA was 88.68%, 89.83% and 97.06%, respectively. The specificity was 94.87%, 98.84% and 99.10%, respectively. The areas under the receiver operating characteristic (ROC) curve was 0.973 4, 0.990 9 and 0.999 5, respectively. The comparison of key indicators between QSA600 and PSG diagnostic results revealed:a Pearson correlation coefficient of 0.987 2(P<0.001) between the AHI measurement values. The mean difference between the Bland-Altman measurement values of the two was -1.43(95%CI:-8.74-5.88) events/h and the ICC between the two was 0.985 0(95%CI: 0.975 4-0.990 4). Conclusions: As a new low-load sleep monitoring system, QSA600 demonstrates high concordance with traditional PSG in diagnosing OSA and stratifying its severity, which has promising potential for clinical application. (Clinical trial registration number: NCT06038006).