[Clinical features of congenitally enlarged bony portion of Eustachian tube].

Objective:To investigate the clinical features of patients with congenitally enlarged bony portions of the Eustachian tube（ET）. Methods:The medical history, physical examination, hearing test, temporal bone high resolution computed tomography（HRCT） of six patients（nine ears） with congenitally enlarged bony portion of the ET were retrospectively analyzed. Results:Four patients were men and two were women. The minimum, maximum, and average ages were 5, 21, and（14.7±6.4） years, respectively. Three malformations were bilateral and three were left-sided. Three ears had conductive hearing loss（average bone and air conduction thresholds were 13.7 dB and 71.3 dB）, three had mixed hearing loss（average bone and air conduction thresholds were 27.7 dB and 83.7 dB）, and one had extremely severe sensorineural hearing loss. The average maximum length and width of the enlarged bony ET on temporal bone HRCT were（22.61±2.94） mm and（6.50±2.33） mm, respectively. The enlargement was combined with an external auditory canal malformation in six ears, narrow tympanic cavity in six, tympanic antrum malformation in five, ossicular chain malformation in seven, cochlear malformation in six, helicotrema malformation in three, vestibule widening in two, semicircular canal malformation in three, vestibular window malformation in six, facial nerve abnormality in five, internal auditory meatus malformation in two, low middle cranial fossa in eight, and severe internal carotid artery malformation in one. Conclusion:Bony ET enlargement is a rare congenital middle ear malformation which could combined with other ear malformations. Patients can have no ET dysfunction but different patterns of hearing loss. The defect is usually found unintentionally during imaging, and the HRCT of temporal bone is significant.

microRNA-15a-5p suppresses hypoxia-induced tumor growth and chemoresistance in bladder cancer by binding to eIF5A2.

In various malignant tumors (including bladder cancer) poor prognosis is associated with hypoxia and therapeutic resistance. Evidence indicates that in bladder cancer, microRNAs (miRNAs) have vital functions in acquired drug resistance. However, the involvement of miRNAs in hypoxia-mediated bladder cancer doxorubicin (Dox) resistance is unknown. Herein, we showed that hypoxia and Dox treatment downregulated miR-15a-5p expression. Using UM-UC-3 and J82 bladder cancer cell lines and in vivo mouse models of bladder cancer, we confirmed that miR-15a-5p arrests tumor cell growth and Dox resistance in vitro and in vivo. Furthermore, we determined the interaction between miR-15a-5p and eukaryotic translation initiation factor 5A-2 (eIF5A2) using dual luciferase reporters and quantitative real-time reverse transcription polymerase chain reaction assays. We also showed that a miR-15a-5p agomir repressed EIF5A2 expression in bladder cancer cells, thereby inhibiting the epithelial-mesenchymal transition (EMT) induced by Dox or hypoxia. Moreover, ectopic expression of miR-15a-5p abrogated eIF5A2-mediated Dox resistance in bladder cancer cells. Collectively, these data indicated that hypoxia promotes tumor growth and chemoresistance through the HIF-1α/miR-15a-5p/eIFTA2/EMT pathway. This new finding not only has implications for improving our understanding of the Dox resistance process during bladder cancer progression but also indicates that the miR-15a-5p agomir is a promising tool to prevent Dox resistance in patients with bladder cancer.

Chemical Synthesis of a Branched Nonasaccharide Fragment from Helicobacter pylori Lipopolysaccharide.

A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of ß-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired ß-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.

A new active bone-conduction implant: surgical experiences and audiological outcomes in patients with bilateral congenital microtia.

PURPOSE: First-generation bone bridges (BBs) have demonstrated favorable safety and audiological benefits in patients with conductive hearing loss. However, studies on the effects of second-generation BBs are limited, especially among children. In this study, we aimed to explore the surgical and audiological effects of second-generation BBs in patients with bilateral congenital microtia. METHODS: This single-center prospective study included nine Mandarin-speaking patients with bilateral microtia. All the patients underwent BCI Generation 602 (BCI602; MED-EL, Innsbruck, Austria) implant surgery between September 2021 and June 2023. Audiological and sound localization tests were performed under unaided and BB-aided conditions. RESULTS: The transmastoid and retrosigmoid sinus approaches were implemented in three and six patients, respectively. No patient underwent preoperative planning, lifts were unnecessary, and no sigmoid sinus or dural compression occurred. The mean function gain at 0.5-4.0 kHz was 28.06 ± 4.55-dB HL. The word recognition scores improved significantly in quiet under the BB aided condition. Signal-to-noise ratio reduction by 10.56 ± 2.30 dB improved the speech reception threshold in noise. Patients fitted with a unilateral BB demonstrated inferior sound source localization after the initial activation. CONCLUSIONS: Second-generation BBs are safe and effective for patients with bilateral congenital microtia and may be suitable for children with mastoid hypoplasia without preoperative three-dimensional reconstruction.

Analysis of predictive factors related to long-term hearing and temporal bone development in congenital microtia.

OBJECTIVE: To investigate the predictive factors of long-term hearing threshold and temporal bone development in children with congenital microtia (CM). METHODS: 74 patients (92 ears) with CM enrolled, which all had auditory brainstem response (ABR) results during infancy or toddlerhood, pure tone audiometry (PTA) and high-resolution computed tomography (HRCT) results during childhood or adolescence, and had not undergone any surgery. We compared the relationship between ABR, auditory steady-state response (ASSR), the affected side, auricular morphology, presence of external auditory canal stenosis or atresia, PTA average, mastoid pneumatization, Jarhsdoerfer scores, and wether cholesteatoma exists. RESULTS: The average age of ABR in 92 ears was 2.72 ± 3.52 years old, PTA was 7.26 ± 2.51 and HRCT was 6.91 ± 2.76 years old. ABR-AC was related to PTA average, mastoid pneumatization, Jarhsdoerfer scores, and wether cholesteatoma exists in CM. While ABR-ABG was related to all of these factors except Jarhsdoerfer score, and ABR-BC had no relationship with any of them. ASSR only showed correlation with frequencies of 1, 2 kHz and was related to Jarhsdoerfer score, with no other correlations observed. The impaired ear side showed no relevance. However, auricular morphology was related to all of these factors except wether cholesteatoma exist. External auditory canal stenosis or atresia was related to PTA average, but unrelated to mastoid pneumatization. CONCLUSION: The ABR examination in the infant stage plays a crucial role in predicting the long-term hearing and temporal bone development in patients with CM.

Role of early hearing aid experience in speech recognition in patients with bilateral congenital microtia following Bonebridge implantation: a retrospective cohort study.

PURPOSE: To identify audiological and demographic variables that predict speech recognition abilities in patients with bilateral microtia who underwent Bonebridge (BB) implantation. METHODS: Fifty patients with bilateral microtia and bilateral conductive hearing loss (CHL) who underwent BB implantation were included. Demographic data, preoperative hearing aid use experience, and audiological outcomes (including pure-tone hearing threshold, sound field hearing threshold [SFHT], and speech recognition ability) for each participant were obtained. The Chinese-Mandarin Speech Test Materials were used to test speech recognition ability. The word recognition score (WRS) of disyllabic words at 65 dB SPL signals was measured before and after BB implantation in quiet and noisy conditions. RESULTS: The mean preoperative WRS under quiet and noisy conditions was 10.44 ± 12.73% and 5.90 ± 8.76%, which was significantly improved to 86.38 ± 9.03% and 80.70 ± 11.34%, respectively, following BB fitting. Multiple linear regression analysis revealed that lower preoperative SFHT suggested higher preoperative WRS under both quiet and noisy conditions. Higher age at implantation predicted higher preoperative WRS under quiet conditions. Furthermore, patients with more preoperative hearing aid experience and lower postoperative SFHT were more likely to have higher postoperative WRS under both quiet and noisy testing conditions. CONCLUSIONS: This study represents the first attempt to identify predictors of preoperative and postoperative speech recognition abilities in patients with bilateral microtia with BB implantation. These findings emphasize that early hearing intervention before implantation surgery, combined with appropriate postoperative fitting, contributes to optimal benefits in terms of postoperative speech recognition ability.

EIF5A2 Promotes Doxorubicin Resistance in Bladder Cancer Cells through the TGF-ß Signaling Pathway.

BACKGROUND: Doxorubicin (DOX) is a commonly used chemotherapeutic agent, but bladder cancer (BC) patients often develop resistance that limits therapeutic efficacy. Recent research has demonstrated a link between medication resistance and the expression of eukaryotic translation initiation factor 5A2 (EIF5A2) in tumors. This study aimed to investigate whether EIF5A2 affects the resistance of BC cells to doxorubicin through the transforming growth factor (TGF)-ß signaling pathway. METHODS: Doxorubicin-resistant cells in BC (T24/DOX and 5637/DOX) were constructed, then cell viability was detected by cell counting kit-8 (CCK-8); EIF5A2 mRNA expression was detected using quantitative real-time PCR (qRT-PCR); cell proliferation was detected using clone formation; apoptosis was detected by flow cytometry; and finally, proteins related to the TGF-ß signaling pathway (EIF5A2, TGF-ß1, p-small mothers against decapentaplegic 2 (Smad2)/Smad2, p-Smad3/Smad3) were detected using western blot. RESULTS: EIF5A2 was up-regulated in DOX-resistant BC cells, and DOX intervention promoted proliferation and inhibited apoptosis in DOX-resistant BC cells. si-EIF5A2 reversed the above effects. EIF5A2 resulted in DOX resistance by activating the TGF-ß pathway, and the TGF-ß activator SRI-011381 reversed the inhibitory effect of si-EIF5A2 on DOX resistance. CONCLUSIONS: EIF5A2 promotes DOX resistance in BC cells through the TGF-ß signaling pathway, and EIF5A2 may be a potential counter-resistance therapeutic strategy in BC chemotherapy.

Identification of Superior Haplotypes and Haplotype Combinations for Grain Size- and Weight-Related Genes for Breeding Applications in Rice (Oryza sativa L.).

The identification of superior haplotypes and haplotype combinations is essential for haplotype-based breeding (HBB), which provides selection targets for genomics-assisted breeding. In this study, genotypes of 42 functional genes in rice were analyzed by targeted capture sequencing in a panel of 180 Indica rice accessions. In total, 69 SNPs/Indels in seven genes were detected to be associated with grain length (GL), grain width (GW), ratio of grain length-width (L/W) and thousand-grain weight (TGW) using candidate gene-based association analysis, including BG1 and GS3 for GL, GW5 for GW, BG1 and GW5 for L/W, and AET1, SNAC1, qTGW3, DHD1 and GW5 for TGW. Furthermore, two haplotypes were identified for each of the seven genes according to these associated SNPs/Indels, and the amount of genetic variation explained by different haplotypes ranged from 3.24% to 27.66%. Additionally, three, three and eight haplotype combinations for GL, L/W and TGW explained 25.38%, 5.5% and 22.49% of the total genetic variation for each trait, respectively. Further analysis showed that Minghui63 had the superior haplotype combination Haplotype Combination 4 (HC4) for TGW. The most interesting finding was that some widely used restorer lines derived from Minghui63 also have the superior haplotype combination HC4, and our breeding varieties and lines using the haplotype-specific marker panel also confirmed that the TGW of the lines was much higher than that of their sister lines without HC4, suggesting that TGW-HC4 is the superior haplotype combination for TGW and can be utilized in rice breeding.

Inhibition of GPR30 sensitized gefitinib to NSCLC cells via regulation of epithelial-mesenchymal transition.

Introduction: G-protein coupled receptor 30 (GPR30) is associated with cell metastasis and drug resistance in many different cancer cells. The present study aimed to reveal the sensitivity of GPR30 to gefitinib in non-small cell lung cancer (NSCLC) cells.Methods: Cell viability and proliferation were detected using cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, respectively. Western blotting and quantitative real-time reverse transcription PCR were used to detect GPR30 or epithelial-mesenchyme transition (EMT)-related mRNA and protein expression.Results: The results showed that GPR30 expression is associated with gefitinib sensitivity. G15, as a GPR30 antagonist, reduced GPR30 expression. We chose the maximum concentration of G15 with minimal cytotoxicity to detect cell viability after combined treatment with gefitinib in NSCLC cells, which indicated that G15 could increase sensitivity to gefitinib. However, the effect of G15 on gefitinib sensitivity disappeared after treatment with a small interfering RNA targeting GPR30. Further research showed that G15 or GPR30 siRNA treatment could upregulate E-cadherin and downregulate vimentin levels.Conclusion: Taken together, these data suggested that G15 could enhance NSCLC sensitivity to gefitinib by inhibition of GPR30 and EMT.

[A study of the correlation between glenohumeral joint congruence and stability in recurrent shoulder dislocations].

Objective: To investigate the correlation between glenohumeral joint congruence and stability in recurrent shoulder dislocations. Methods: Eighty-nine patients (89 sides) with recurrent shoulder dislocation admitted between June 2022 and June 2023 and met the selection criteria were included as study subjects. There were 36 males and 53 females with an average age of 44 years (range, 20-79 years). There were 40 cases of left shoulder and 49 cases of right shoulder. The shoulder joints dislocated 2-6 times, with an average of 3 times. The three-dimensional models of the humeral head and scapular glenoid were reconstructed using Mimics 20.0 software based on CT scanning images. The glenoid track (GT), inclusion index, chimerism index, fit index, and Hill-Sachs interval (HSI) were measured, and the degree of on/off track was judged (K value, the difference between HSI and GT). Multiple linear regression was used to analyze the correlation between the degree of on/off track (K value) and inclusion index, chimerism index, and fit index. Results: Multiple linear regression analysis showed that the K value had no correlation with the inclusion index ( P>0.05), and was positively correlated with the chimerism index and the fit index ( P<0.05). Regression equation was K=-24.898+35.982×inclusion index+8.280×fit index, R 2=0.084. Conclusion: Humeral head and scapular glenoid bony area and curvature are associated with shoulder joint stability in recurrent shoulder dislocations. Increased humeral head bony area, decreased scapular glenoid bony area, increased humeral head curvature, and decreased scapular glenoid curvature are risk factors for glenohumeral joint stability.

Absolute quantification of viable Vibrio cholerae in seawater samples using multiplex droplet digital PCR combined with propidium monoazide.

Introduction: Toxigenic Vibrio cholerae serogroup O1 and O139 are the pathogens responsible for the global cholera epidemic. V. cholerae can settle in the water and spread via the fecal-oral route. Rapid and accurate monitoring of live V. cholerae in environmental water has become an important strategy to prevent and control cholera transmission. Conventional plate counting is widely used to detect viable bacteria but requires time and effort. Methods: This study aims to develop a new assay that combines triplex droplet digital PCR (ddPCR) with propidium monoazide (PMA) treatment for quantitatively detecting live V. cholerae O1/O139 and cholera enterotoxin. Specific primers and probes were designed according to the conserved regions of gene rfb O1, rfb O139, and ctxA. The amplification procedures and PMA treatment conditions were optimized. The specificity, sensitivity, and ability of PMA-ddPCR to detect viable bacteria-derived DNA were evaluated in simulated seawater samples. Results and Discussion: The results revealed that the optimal primer concentrations of rfb O1, rfb O139, and ctxA were 1 µM, while the concentrations of the three probes were 0.25, 0.25, and 0.4 µM, respectively. The best annealing temperature was 58°C to obtain the most accurate results. The optimal strategy for distinguishing dead and live bacteria from PMA treatment was incubation at the concentration of 20 µM for 15 min, followed by exposure to a 650-W halogen lamp for 20 min. In pure culture solutions, the limit of detection (LODs) of V. cholerae O1 and O139, and ctxA were 127.91, 120.23 CFU/mL, and 1.5 copies/reaction in PMA-triplex ddPCR, respectively, while the LODs of the three targets were 150.66, 147.57 CFU/mL, and 2 copies/reaction in seawater samples. The PMA-ddPCR sensitivity was about 10 times higher than that of PMA-qPCR. When detecting spiked seawater samples with live bacterial concentrations of 1.53 × 102 and 1.53 × 105 CFU/mL, the assay presented a higher sensitivity (100%, 16/16) than qPCR (50.00%, 8/16) and a perfect specificity (100%, 9/9). These results indicate that the developed PMA-triplex ddPCR is superior to the qPCR regarding sensitivity and specificity and can be used to rapidly detect viable toxigenic V. cholerae O1 and O139 in suspicious seawater samples.

Effect of the Initial Deformity in the Coronal Plane on Postoperative Outcome of Proximal Humeral Fractures.

OBJECTIVE: There is currently no consensus on proximal humerus fractures with an initial deformity in the coronal plane who are better off with plates or nails, so we designed this study. To compare the effect of the initial deformity in the coronal plane of proximal humerus fractures on postoperative outcomes, we compare the maintenance of reduction in procedures utilizing plates and nails, and analyzed the subsequent occurrence of complications to explore whether the initial deformity should dictate the fixation approach. METHODS: The clinical data of patients with proximal humerus fractures who were hospitalized and underwent surgical treatment in our hospital from January 2016 to December 2020 were reviewed. Postoperative functional scores (American Shoulder and Elbow Surgeons, ASES; Constant-Murley Score, CMS), Neck-shaft angle (NSA), Quality of fracture reduction, Deltoid Tuberosity Index (DTI), and complications were compared among cases with initial varus, normal, or valgus deformities. RESULTS: We included 131 patients, 56 males and 75 females, with a mean age of 60.89 ± 5.53 years (range 50-76) and a mean follow-up duration of 16.63 ± 6.78 months (range 12-48). Of these, 29 cases had initial varus displacement, 71 had a normal NSA, and 31 had initial valgus displacement. Seventy-five were treated with a locking plate and 56 with a nail. After open reduction and internal fixation, the NSA was restored to normal (-135°) in all patients in all groups (P > 0.05). There was a significant difference in NSA changes at the last follow-up; 2.93° ± 2.12° in the varus group, 1.77° ± 1.18° in the normal group, and 2.32° ± 1.64° in the valgus group, with the highest change occurring in the varus group. There was no significant difference in the range of motion or functional scores including ASES and CMS among the three groups (P > 0.05). The complication rate of 20.7% in the varus group was significantly higher than the complication rates of 12.7% in the normal and 12.9% in the valgus groups (P < 0.05). CONCLUSIONS: While proximal humerus fractures with initial coronal displacement (varus, normal, and valgus) show similar postoperative functional outcomes, varus fractures have a higher rate of complications. The nail provides better maintenance of reduction than the locking plate, especially in varus fractures.

Clinical and Radiographic Outcomes of Total Elbow Arthroplasty Using a Semi-constrained Prosthesis with a Triceps-preserving Approach over a Minimum Follow-up Period of 4 Years.

OBJECTIVE: Complications related to triceps after total elbow arthroplasty (TEA) have become a major surgical concern. The triceps-preserving approach has the advantage of not disturbing the insertion of triceps but is disadvantaged by the reduced exposure of the elbow joint. The aim of this study was to investigate the clinical and radiological outcomes of TEA with a triceps-preserving approach and to compare the outcomes of TEA to treat arthropathy with that of TEA to treat acute distal humerus fracture. METHODS: From January 2010 to December 2018, 23 patients undergoing primary TEAs were retrospectively reviewed with a mean follow-up time of 92.6 months (range, 52-136 months). Each TEA was performed using the triceps-preserving approach with a semi-constrained Coonrad-Morrey prosthesis. Patient demographics, range of motion (ROM), pain visual analogue scale (VAS), and triceps strength (Medical Research Council [MRC] scale) were compared before and after surgery. The Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, radiographic outcome, and complications were evaluated at follow-up. RESULTS: In total, seven males and 16 females were included in this study, with a mean age of 66.1 years (range:46-85 years). By the last follow-up, pain had been significantly relieved in all patients. The average MEPS in the arthropathy group and fracture group were 90.8 ± 10.3 points (range: 68-98 points) and 91.7 ± 0.4 (range: 76-100 points), respectively. The average DASH of the arthropathy group and fracture group was 37.3 ± 18.8 points (range: 18-52 points) and 38.4 ± 20.1 (range: 16-60 points). At the last follow-up after surgery, the mean flexion arcs in the arthropathy group and fracture group were 100.4° ± 24.1° and 97.8° ± 28.1°, respectively. The mean pro-supination arcs in the arthropathy group and fracture group were 142.4° ± 15.2° and 139.2° ± 17.5°, respectively. There were no significant differences in clinical outcomes between the two groups (P ≥ 0.05). Triceps strength was normal (MRC grade V) in 15 elbows and good in eight elbows. None of the cases experienced weakness of the triceps strength, infection, periprosthetic fractures, or prosthesis breakage. CONCLUSIONS: The clinical and radiographical outcomes of TEA with the triceps-preserving approach were satisfactory in patients with distal humerus fracture, osteoarthritis and rheumatoid arthritis.

A mini review of communicative language testing.

Compared with traditional language testing, which heavily emphasizes psychometric reliability, communicative language testing (CLT), which uses authentic tasks to measure communicative abilities, has long been dominant in language assessment. Given its widely acknowledged advantages and widespread use, CLT has become less controversial in the language assessment field and thus is receiving decreased scholarly attention. However, real-world communication, in which CLT is grounded, evolves over time, suggesting the need to update our understanding of it. To address this need and facilitate the further development of CLT theories and practices, this paper offers an up-to-date review of CLT, including its various approaches, implementation challenges, and suggestions for future research.

Neoadjuvant chemoradiotherapy plus tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): the protocol of a prospective, single-arm, phase II trial.

BACKGROUND: The failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%-48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown. METHODS: Patients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II-IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab. DISCUSSION: The optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma. TRIAL REGISTRATION: This study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov ( NCT04776590 ) on March 1, 2021.

Survival benefit of thoracic radiotherapy plus EGFR-TKIs in patients with non-oligometastatic advanced non-small-cell lung cancer: a single-center retrospective study.

Objectives: The study aims to evaluate the efficacy and safety of thoracic radiotherapy in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treated patients with stage IV non-small-cell lung cancer (NSCLC). Methods: Patients with non-oligometastatic NSCLC harboring EGFR mutations were recruited. All patients received the first-generation TKI treatment with or without radiotherapy. The irradiated sites included primary and/or metastatic lesions. Of all the patients who underwent thoracic radiotherapy, some received radiotherapy before EGFR-TKI resistance, others received radiotherapy after progressive disease. Results: No statistically significant difference was observed in progression-free survival (PFS) (median 14.7 versus 11.2 months, p = 0.075) or overall survival (OS) (median 29.6 versus 40.6 months, p = 0.116) between patients treated with EGFR-TKIs alone and those with additional radiotherapy to any sites. However, EGFR inhibitors with thoracic radiation significantly improved OS (median 47.0 versus 31.0 months, p < 0.001) but not PFS (median 13.9 versus 11.9 months, p = 0.124). Moreover, longer PFS (median 18.3 versus 8.5 months, p < 0.001) was achieved in the preemptive thoracic radiation cohort than in the delayed thoracic radiation cohort. However, OS was similar between the two cohorts (median 40.6 versus 52.6 months, p = 0.124). The lower incidence rate of grade 1-2 pneumonitis occurred in preemptive radiation cohort (29.8% versus 75.8%, p < 0.001). Conclusion: Non-oligometastatic NSCLC patients with EGFR mutations benefited from thoracic radiotherapy while using EGFR inhibitors. Preemptive thoracic radiotherapy could be a competitive first-line therapeutic option due to superior PFS and favorable safety.

Quantum Oppenheimer-Snyder and Swiss Cheese Models.

By considering the quantum Oppenheimer-Snyder model in loop quantum cosmology, a new quantum black hole model whose metric tensor is a suitably deformed Schwarzschild one is derived. The quantum effects imply a lower bound on the mass of the black hole produced by the collapsing dust ball. For the case of larger masses where the event horizon does form, the maximal extension of the spacetime and its properties are investigated. By discussing the opposite scenario to the quantum Oppenheimer-Snyder, a quantum Swiss Cheese model is obtained with a bubble surrounded by the quantum universe. This model is analogous to black hole cosmology or fecund universes where the big bang is related to a white hole. Thus our models open a new window to cosmological phenomenology.

Clinical manifestations and treatment strategies for congenital aural atresia with temporomandibular joint retroposition: a retrospective study of 30 patients.

BACKGROUND: Patients with congenital aural atresia (CAA) can present with concomitant temporomandibular joint (TMJ) retroposition, implying that even with a high Jahrsdoerfer score, canaloplasty and tympanoplasty cannot be performed. Therefore, this study aimed to summarize the clinical manifestations and share our diagnostic and treatment experience of this rare entity, which has not been described previously. METHODS: Thirty patients (30 ears) with CAA and TMJ retroposition without maxillofacial dysplasia were included. Diagnosis was based on patient history, physical examination, pure-tone average test results, and temporal bone high-resolution computed tomography (HRCT) findings. Their Jahrsdoerfer scores and interventions were also recorded. RESULTS: Twenty-four and six patients among the 30 patients (males, n = 15) had CAA and TMJ retroposition on the right and left sides, respectively. Seventeen ears had a normal auricle; most had an enlarged cavum conchae and a large tragus. Twelve ears had an accessory auricle, and two had a preauricular fistula. All external auditory canals had complete atresia, including four with a shallow concavity and four with a small orifice in the cavum conchae. Temporal bone HRCT revealed poor or undeveloped tympanic temporal bone in the diseased ears, atresia in the external auditory canals, and partial/complete occupation of the mandibular condyle with or without soft tissue. The average Jahrsdoerfer score was 8.17. Thirteen patients opted for different surgeries, three wore a bone-conduction hearing aid, and fourteen chose no intervention. CONCLUSIONS: CAA with TMJ retroposition was often unilateral, typically on the right side. Most patients had normal auricles, with an enlarged cavum conchae and a large tragus ("mirror ear"). Even with a high Jahrsdoerfer score, traditional hearing reconstruction surgery could not be performed. Patients can undergo Vibrant Soundbridge or Bonebridge implantation or wear bone-conduction hearing aids to improve hearing levels, or refuse intervention because of mild hearing loss. The TMJ location can be used as a Jahrsdoerfer Grading System supplement for preoperative evaluation.