Philipsenfeldman0450

Background Lung cancer (LC) is ranked as a leading cause of cancer-related death worldwide. However, there are still few reliable screening biomarkers for daily clinical practice in LC. Circular RNAs (circRNAs) have been suggested as valuable diagnostic biomarkers in various cancers. In this study, the expression and diagnostic potential of several circRNAs for LC were explored. Methods Seventy-two pairs of LC tissues and adjacent normal lung tissues were collected to measure the relative expression level of circRNAs using quantitative reverse transcription-polymerase chain reaction. In addition, the relationships between circRNAs and the clinicopathological features of LC patients were analyzed. Furthermore, the sensitivities and specificities of the circRNAs were evaluated by receiver operating characteristic (ROC) analysis. Results The expression levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, has_circ_0074368, and has_circ_0000896 were downregulated in LC tissues compared with adjacent normal lung tissues. The lower levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, and has_circ_0000896 were significantly correlated with advanced disease stages. The area under the ROC curves of has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 were 0.833, 0.793, 0.773, 0.730, and 0.645, respectively. Conclusions Has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 are capable of distinguishing LC tissues from normal lung tissues. Besides, the biggest area under the ROC curve value of has_circ_000249 suggests it appears to be a better diagnosis marker for LC patients.Background Esophageal cancer (EC) is the second most common malignant tumor of the digestive system. There is currently no effective noninvasive method for early detection of EC. Methods We performed a prospective cohort study involving 188 EC patients, 125 patients with benign esophageal diseases, and 270 normal subjects to examine the performance of methylated SEPT9 (mSEPT9) and synuclein gamma (SNCG) individually and in combination. Results The sensitivity of mSEPT9 and SNCG for EC was 43.1% (AUC = 0.69) at 95.6% specificity and 41.8% (AUC = 0.79) at 92.6% specificity, respectively. The combined detection increased the sensitivity to 71.8% at 90.3% specificity. The combined detection sensitivity for stage I-IV EC was 66.7%, 58.3%, 75.0%, and 88.2%, respectively. No significant difference in combined sensitivity was found among patients with EC of the upper, middle, and lower esophagus, and no significant difference in sensitivity was found between adenocarcinoma and squamous carcinoma. The sensitivity of highly differentiated EC was found to be higher than that of moderately and poorly differentiated EC with SNCG and combined detection. The sensitivity of SNCG in female patients was significantly higher than that in male patients, leading to the same trend in combined detection. Patients aged 40-49 years showed higher combined sensitivity. The sensitivity of SNCG was much higher than that of existing protein markers for digestive cancers. Furthermore, mSEPT9 was capable of predicting the long-term survival of EC patients with a hazard ratio of 2.65. Conclusion The combined sensitivity of mSEPT7 and SNGG provided significant improvement over any single biomarker for the early detection of EC. mSEPT7 may be useful as a prognostic marker for long-term survival.Objective The standard methods for tri-allelic single nucleotide polymorphism (SNP) genotyping require special equipment and are costly to perform. The aim of this study was to establish a fast, simple, and low-cost method to differentiate among tri-allelic SNPs in general laboratories. Methods Based on the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) typing of bi-allelic SNPs, we developed a penta-primer amplification refractory mutation system-polymerase chain reaction (P-ARMS-PCR) method characterize tri-allelic SNPs. The two most studied tri-allelic SNPs, rs2032582 and rs3091244, were genotyped using P-ARMS-PCR in 110 volunteers, and the results were verified by direct DNA sequencing. Results For rs2032582, there were 20 samples (18.18%) with the GG genotype, 3 (2.73%) with the AA genotype, 24 (21.82%) with the TT genotype, 43 (39.09%) with the GT genotype, 11 (10.00%) with the AG genotype, and 9 (8.18%) with the AT genotype. For rs3091244, there were 67 samples (60.91%) with the CC genotype, 1 (0.91%) with the AA genotype, 8 (7.27%) with the CT genotype, 31 (28.18%) with the CA genotype, and 3 (2.73%) with the AT genotype. The genotypic distributions of rs2032582 (p = 0.482) and rs3091244 (p = 0.492) were in Hardy-Weinberg equilibrium. The DNA sequencing results were entirely consistent with the results of P-ARMS-PCR. Conclusion P-ARMS-PCR is an accurate, rapid, simple, and low-cost characterization method for tri-allelic SNP genotyping of rs2032582 and rs3091244.Aims Autosomal recessive primary microcephaly (MCPH) is a clinically rare and genetically highly heterogeneous developmental disorder. Biallelic variants in the abnormal spindle-like microcephaly-associated (ASPM) gene account for 40% to 68% of all MCPH cases. This study was designed to elucidate the genetic basis of MCPH in an extended family. To highlight recurrent mutations useful in implementing genetic testing programs, we further aimed to carry out a descriptive review of the reported ASPM mutations. Materials and Methods A large inbred kindred with seven affected members was investigated, and detailed clinical and behavioral assessments were carried out. Single nucleotide polymorphism (SNP)-based homozygosity mapping and exome sequencing were performed. Results Affected individuals had characteristic features, including small head, receding forehead, mild to moderate intellectual disability, developmental delay, short stature, apraxia, and behavioral anomalies. We mapped the disease gene locus and detected a rare frameshift deletion c.6854_6855del (p.(Leu2285GlnfsTer32)) in exon 18 of ASPM. A total of 215 mutations in ASPM have been reported in at least 453 families, nearly 50% of which are of Pakistani origin. These mutations can be classified as recurrent, founder or private in Pakistani and other populations. Conclusion SNP-based homozygosity mapping and exome sequencing are essential in delineating the genetically distinct microcephaly types. The highlighted recurrent mutations in ASPM could be useful in implementing genetic testing programs for MCPH.

With the global COVID-19 pandemic, nasopharyngeal swabbing has become commonplace and can occasionally cause discomfort, tearing, and anxiety.

To evaluate whether using a neural distraction device during nasopharyngeal swabbing can mitigate patient discomfort.

Participants were randomized into nasal swab with vibration first (treatment-control or Tc) or nasal swab without vibration first (control-treatment or Ct). Then the swab was repeated with the opposite technique. The vibration device was used to stimulate the infraorbital nerve at the midpupillary line, while a nasopharyngeal swab was performed according to CDC protocol. After each swab, participants filled out a survey to assess pain, discomfort, and tearing. This procedure was replicated on the contralateral nostril for a total of 4 swabs and 4 surveys.

Thirty-four subjects were included in the analysis. IRAK4IN4 In the Ct group, there was a median 1.0-point decrease in pain with the use of vibration (95% CI [-1.8, -0.3]



= 0.0117), 2.5-point decrease (95% CI [-3.0, -0.8],

= 00039) in discomfort, and a 1.0-point decrease (95% CI [-2.6, -0.2]

= 0.0303) in tearing when the vibratory device was used. In the Tc group, there was a median 2.0-point decrease in pain with vibration (95% CI [ -2.7, -1.1],

< 0.0001), 2.3-point decrease in discomfort (95% CI [-3.1, -1.5],

< 0.0001), and a 1.5-point decrease in tearing (95% CI [-2.5, -0.5],

= 0.0037) when vibration was used.

Vibratory stimulation of the infraorbital nerve is safe and effectively reduced pain, discomfort, and tearing during nasopharyngeal swab. Vibration is a reasonable option to minimize patient discomfort during COVID-19 or other microbiological testing.

Vibratory stimulation of the infraorbital nerve is safe and effectively reduced pain, discomfort, and tearing during nasopharyngeal swab. Vibration is a reasonable option to minimize patient discomfort during COVID-19 or other microbiological testing.Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a growing global health problem. HPV16 has been attributed to a majority of HPV-associated HNSCCs. In order to test candidate immunotherapies, we developed a spontaneous HPV16-driven HNSCC model in HLA-A2 (AAD) transgenic mice. We sought to eliminate the confounding effects of dominant HPV antigen presentation through murine major histocompatibility complex class I (MHC-I) via epitope mutagenesis (without compromising tumorigenicity). We generated HPV16 E6(R55K)(delK75) and E7(N53S) expression constructs with mutations in known dominant H-2Db epitopes and characterized their presentation through murine and human MHC-I molecules using in vitro and in vivo activation of HPV16 E6/E7 antigen-specific CD8+ T cells. In addition, we tested the ability of E6(R55K)(delK75) and E7(N53S) for oncogenicity. The mutated E7(N53S) abolished the presentation of murine H-2Db-restricted HPV16 E7 peptide (i.e., amino acids [aa] 49 to 57) cytotHPV16 E6 and E7 remain oncogenic. Our approach is potentially applicable to different human MHC-I transgenic mice for the identification of human MHC-I restricted HPV16 E6/E7-specific CTL epitopes as well as the generation of spontaneous HPV E6/E7-expressing oral/pharyngeal carcinoma.Phytoplankton diversity and community compositions vary across spaces and are fundamentally affected by several deterministic (e.g., environmental selection) and stochastic (e.g., ecological drift) processes. How this suite of different processes regulates the biogeography of phytoplankton remains to be comprehensively explored. Using high-throughput sequencing data and null model analysis, we revealed the ecological processes shaping the latitudinal community structure of three major phytoplankton groups (i.e., diatoms, Synechococcus, and haptophytes) across the Pacific Ocean (70°N, 170°W to 35°S, 170°W). At the basin scale, heterogeneous selection (selection under heterogeneous environmental conditions) dominated the assembly processes of all phytoplankton groups; however, its relative importance varied greatly at the climatic zonal scale, explaining the distinct latitudinal α- and β-diversity among phytoplankton groups. Assembly processes in Synechococcus and haptophyte communities were mainly controlled brocesses (e.g., selection, dispersal, and drift) regulate their global biogeography remains to be comprehensively explored. In this study, we disentangled the ecological processes of three key phytoplankton groups (i.e., diatoms, Synechococcus, and haptophytes) along the same latitudinal gradients in the Pacific Ocean. Heterogeneous selection, by promoting species richness and reducing similarity between communities, was the dominant process shaping the communities of each phytoplankton group at the basin scale. However, its relative importance varied greatly among different phytoplankton groups in different climate zones, explaining the uneven latitudinal α- and β-diversity. We also highlight the importance of identifying key factors mediating the relative importance of assembly processes in phytoplankton communities, which will enhance our understanding of their biogeography in the ocean and future patterns under climate changes.