Hybrid measurement of respiratory aerosol reveals a dominant coarse fraction resulting from speech that remains airborne for minutes

Accurate measurements of the size and quantity of aerosols generated by various human activities in different environments are required for efficacious mitigation strategies and accurate modeling of respiratory disease transmission. Previous studies of speech droplets, using standard aerosol instrumentation, reported very few particles larger than 5 μm. This starkly contrasts with the abundance of such particles seen in both historical slide deposition measurements and more recent light scattering observations. We have reconciled this discrepancy by developing an alternative experimental approach that addresses complications arising from nucleated condensation. Measurements reveal that a large volume fraction of speech-generated aerosol has diameters in the 5- to 20-μm range, making them sufficiently small to remain airborne for minutes, not hours. This coarse aerosol is too large to penetrate the lower respiratory tract directly, and its relevance to disease transmission is consistent with the vast majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiating in the upper respiratory tract. Our measurements suggest that in the absence of symptoms such as coughing or sneezing, the importance of speech-generated aerosol in the transmission of respiratory diseases is far greater than generally recognized.

Respiratory tract infections are caused by a wide range of pathogenic organisms (1), including a large array of respiratory viruses, such as influenza virus, rhinovirus, measles virus, respiratory syncytial virus, adenovirus, and most recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In all these diseases, person-to-person spread involves respiratory droplets, which originate from the mucus layer that covers the epithelium of the respiratory tract or from oral fluid present in the mouth, mostly as saliva. Thus, characterizing respiratory droplets is essential to understanding respiratory pathogen transmission and will inform effective public health policies to curb infections. Four mechanisms for droplet generation are generally considered: breathing, speaking (singing, laughing, etc.), coughing, and sneezing (2). Considering the well-recognized importance of asymptomatic transmission of SARS-CoV-2 (3), our study focuses on the first two of these mechanisms.As highlighted by Wells (4) and Duguid (2) nearly a century ago, the vast majority of respiratory droplets are smaller than ca. 100-μm diameter and fully dehydrate once entering the atmosphere. These desiccated droplets can remain airborne for minutes to hours before landing on solid surfaces. If generated by a person infected by a respiratory virus, they will contain virions that can remain viable and infectious for many hours (5, 6). Upon inhalation, airborne particles can reach different parts of the respiratory tract depending on their size: coarse aerosols with diameter D ≳ 5 μm (7) deposit in the upper respiratory tract (URT), and fine aerosols with D < 5 μm can penetrate deep into the lower respiratory tract (LRT). Many viral pathogens, including SARS-CoV-2, influenza, rhinovirus, and measles virus, can infect both URT and LRT epithelia (1, 8, 9), with URT infections typically associated with mild initial symptoms and LRT infections possibly resulting in life-threatening pneumonia (1, 10–13). Direct infection of the LRT, before the adaptive immune system has been triggered by vaccination or a preceding URT infection, presents a greater risk.An URT infection also can expand into the LRT through microaspiration of oropharyngeal fluids (14, 15). The extent to which inhalation of self-generated URT cough, speech, or sneeze aerosols may contribute to this migration remains unknown. However, it has been argued that this pathway could be significant because an infected carrier is invariably at the center of their own speech aerosol cloud, which results in strongly elevated exposure (16). The risk of migration from the URT to the LRT rises with the viral load and the viability of the virus, which peak around and just prior to the onset of symptoms, respectively (17, 18). For the original Wuhan strain of the SARS-CoV-2 virus, the onset of symptoms occurs about 5 days after the initial infection (17, 19), but it occurs somewhat earlier for the more infectious delta and omicron variants (20).To evaluate the risk of LRT infection, it is important to know the size distribution of particles generated by various respiratory activities. For talking, coughing, and sneezing, studies historically relied on slide sampling techniques of increasing sophistication, followed by microscope observation (2, 21, 22). Droplets generated by breathing or vowel sounds are numerous but very small (≲2 μm) and thus more difficult to evaluate with those classical methods. Instead, such small droplets are now commonly quantified by aerosol detection equipment, such as optical particle sizers (OPSs), based on light scattering (22, 23); aerodynamic particle sizers (APSs), based on the time-of-flight measurement in an accelerating flow field (24); and scanning mobility particle sizers that derive a particle’s size from its mobility in an electric field and are best suited for very small sizes (≲1 μm) (25, 26). APS instruments are less efficient at detecting medium-sized liquid particles, and undercounts as high as 75% for 10-μm droplets have been reported (27).There is some confusion in the literature about the hydration state of reported sizes of respiratory aerosol particles, which shrink by a factor of γ upon evaporation of their aqueous content, thus by a factor of γ³ in volume. After full dehydration, a particle’s radius is determined by its amount of nonvolatile matter. Estimates for γ vary substantially: Nicas et al. (28) proposed γ = 2 for breath particles, based on data extracted from breath condensate by Effros et al. (29) that indicated a high fraction (ca. 8% wt/vol) of glycoproteins, presumably mucins. Holmgren et al. (30) reported γ = 2.4 for breath particles when the relative humidity (RH) is reduced from 99.5% in the small airways to 75%. Bagheri et al. (26) observed γ = 4.5 for singing particles in a diffusion dryer or γ = 4 for large saliva droplets observed directly by microscope imaging. Some of those measurements were conducted directly at the mouth opening, observing the hydrated state using light scattering or holographic imaging techniques (26, 31). Clearly, the concentration of pathogens in dehydrated particles scales with γ³ relative to the originating airway lining fluid (ALF) or saliva. However, the high uncertainty in the applicable γ value, which is frequently not even reported, prevents accurate estimates of airborne virus concentrations.Recently, we and others demonstrated that speech particles can be readily observed by simple video recordings of light scattering by these particles (32–35). Such recordings not only present a visually compelling warning to the public but also provide opportunities to monitor particles before, during, and after dehydration. Those light scattering measurements focused on particles larger than a few microns due to technical sensitivity issues. The intensity of scattered light scales with the square of a particle’s diameter, causing a dynamic range problem and rendering it more challenging to observe the smallest particles, especially in the presence of larger particles. Inexpensive, fast consumer cameras typically use 10- to 12-bit analog-to-digital converters (ADCs), thereby limiting dynamic range; while detectors with an increased ADC range are available, their speed is often insufficient for high-speed recording.Here, we aim to evaluate the entire range of speech droplet sizes produced during different breathing and speaking protocols. To do so, we combined video-recorded light scattering and an OPS to evaluate droplets from 0.3 to 100 μm. Our data show a continuous spectrum that lacks previously reported gaps in the size distribution (36). Our measurements confirm that the gravitational settling rate for dehydrated particles larger than 5 μm steeply increases with size, but considering the high numbers, volumes, and airborne lifetimes of those particles, they are likely to be a dominant factor in transmission of disease.     

升降汤加减治疗食管癌术后胃肠功能紊乱的疗效观察

目的 探讨对食管癌术后胃肠功能紊乱患者采用升降汤进行治疗的效果及对生活质量的影响。方法 选取2015年1月—2019年1月在我院进行食管癌手术的患者,遴选术后出现胃肠功能紊乱及符合纳入标准的患者60例作为本研究对象,根据随机原则分为对照组（30例,采用西药治疗）与观察组（30例,采用西药联合升降汤加减治疗）,比较两组患者的治疗效果及生活质量。结果 经过不同方案的治疗后,与对照组比较,观察组患者总有效率与生活质量更高,差异有统计学意义（P <0.05）;与对照组比较,观察组患者临床症状评分与并发症发生率的更低,差异有统计学意义（P <0.05）。观察组患者经治疗后肠鸣音恢复时间、首次排便时间及首次排气时间较对照组更短,差异有统计学意义（P <0.05）。结论 食管癌术后胃肠功能紊乱患者采用升降汤加减进行治疗后,能有效改善患者的临床症状,提高生活质量,且治疗后的并发症率较低,可在临床上进行推广使用。     

Can the patient pinpoint where the ingested fish bone is impacted?: A single-center,retrospective study

Among the plethora of foreign body impactions, fish bones are common examples that patients may struggle to properly disclose in clinical situations. This study investigated whether patients could pinpoint where the ingested fish bone was lodged. In addition, we investigated the differences between fish bone and other foreign bodies, the usefulness of computed tomography (CT), and the related risk factors for hospitalization. The cases of patients who underwent an endoscopic removal of fish bone between April 2008 and April 2020 were retrospectively reviewed. The clinical outcomes, X-ray scan, CT, and complications of each patient were investigated. A total of 96 patients were included in this study. The mean size of the impacted fish bone was 23.78 mm, and most were found in the upper esophagus (n = 38). There was a weak correlation between pain location and the actual lesion location (r = 0.419, P < .001). Compared to those of other foreign bodies, the location of impacted fish bones was different (P < .001), the X-ray detection rate of fish bones was lower (P < .001), and the complication incidence was higher (P = .030). CT (95.89%) showed higher sensitivity than X-ray scanning (11.24%) (P < .001). Foreign body size (P = .004) and door-to-endoscopy time (P = .029) were related to admission. Patients only managed to point out the approximate location of the ingested fish bone. CT detected fish bones well, but scans should include at least the entire esophagus instead of solely the area where pain is felt. Fish bone impaction has different clinical characteristics from other foreign bodies. Endoscopic removal without delay can reduce the admission rates.     

奈达铂联合氟尿嘧啶治疗晚期食管肿瘤的近期疗效观察

目的:探讨奈达铂(NDP)联合氟尿嘧啶(5-FU)组成NF方案治疗晚期食道肿瘤的近期疗效和毒副反应。方法:64例病人随机分为NF方案组和PF方案组各32例,前者接受NDP 5-FU化疗,后者予顺铂(PDD) 5-FU,即PF方案化疗,根据WHO标准评价疗效和毒副反应。结果:NF方案组有效率为56·2%,PF方案组有效率50%;骨髓抑制:NF方案组白细胞减少为56·2%,PF方案组为50%,其中血小板减少在NF方案组为12·5%,而PF方案组为0,胃肠道反应两组发生率分别为25%和50%。结论:奈达铂联合氟尿嘧啶组成的NF方案治疗晚期食道肿瘤毒副作用小,疗效较高,值得临床上进一步推广应用。     

Endoscopic features of esophageal high-grade intraepithelial neoplasia dominated by cytological atypia

Little is known about esophageal high-grade intraepithelial neoplasia dominated by cytological atypia (HGINc). We aimed to elucidate the endoscopic features of HGINc compared with esophageal high-grade intraepithelial neoplasia dominated by architectural atypia (HGINa). All patients pathologically diagnosed as esophageal high-grade intraepithelial neoplasia after endoscopic submucosal dissection at our center between January 2018 and December 2019 were included in this study. According to the pathological diagnosis, the patients were divided into two groups: HGINa group and HGINc group. Basic characteristics and endoscopic information were collected in detail. Data were analyzed statistically. Binary logistic regression was performed and a predictive model for HGINc was established. Then we evaluated its predictive value and built a nomogram for clinical application. A total of 175 patients were included in this study (126 with HGINa and 49 with HGINc). Among 228 lesions found in all patients, there were 148 HGINa and 80 HGINc. The independent relevant factors for HGINc were tobacco and alcohol usage, color, and gross type. To predict risk of HGINc, a three-factor model (TFM) was established with a highest area under curve (AUC) as 0.869 (95% CI, 0.852, 0.939). When the cut-off value was set as 0.3569184, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for HGINc was 81.14%, 88.75%, 77.03%, 67.62%, and 92.68%, respectively. HGINc differs greatly in endoscopic features from HGINa in our study. It’s important to reduce misdiagnosis that our model was established with good predictive value for clinical application.     

Cancer stem-like cells contribute to paclitaxel resistance in esophageal squamous cell carcinoma

Objective: To examine the role of esophageal squamous cell carcinoma (ESCC) stem cells in paclitaxel resistance through the molecular characterization of ESCC stem cells. Methods: A resistant cell line (RR-ECl09) of cells were established using intermittent induction and time increments of high-dose paclitaxel in a human esophageal squamous cell carcinoma line (EC109). The multidrug resistance of RR-ECl09 cells to anticancer agents was evaluated by MTT assay. The RR-EC109 and EC109 cells were used for sphere formation assays, clonogenicity assays, stem cell gene expression, and the expression of epithelial-mesenchymal transition markers. Results: The RR-EC109 cells were established over 7 months. RR-ECl09 cells had 67.258 fold resistance to paclitaxel. The percentage of sphere formation and clone proliferation ability of RR-EC109 cells was higher than that of EC109 cells (P < 0.05). The amount of side population cells in RR-EC109 cells was higher than that of EC109 cells (P < 0.05). RR-EC109 cells produced more mRNA for Bmi1, Nanog, Oct4, Sox2, ABCG2, Nestin, and Ki-67 than EC109 cells (P < 0.05). E-cadherin expression was lower in RR-EC109 cells than in EC109 cells, while N-cadherin, Snail, and Twist expressions were higher in RR-EC109 cells than in EC109 cells (P < 0.05). Conclusions: Cancer stem cell (CSC)-like cells exist among paclitaxel-resistant cells in ESCC and may play a role in ESCC drug resistance.     

一种用于噪声估计的改进最小值搜索方法

含噪语音短时功率谱的最小值搜索是噪声估计的基础。为了提高非平稳噪声估计的准确性,减小噪声水平上升时的噪声估计延时,提出了一种同时使用大、小两个搜索窗进行并行搜索的方法,最小值搜索的最终结果由两个并行搜索结果和基于噪声分类的语音存在二值判决共同决定。实验结果表明：对于高度非平稳的噪声,该方法能够有效地减小噪声估计的延时问题,显著提高增强后语音的质量。     

血浆SEPTIN9甲基化水平检测有助于食管癌诊断和放疗敏感性预测

目的 探讨血浆mSEPT9对食管癌诊断的应用价值及其与放疗敏感性的关系。方法 选取2019年1月~2020年12月在蚌埠医学院第一附属医院放疗科接受根治性放疗的72例食管癌患者,运用PCR法分别检测患者放疗前及放疗后血浆mSEPT9,另以体检中心20例健康人作为对照。用受试者工作特征曲线（ROC曲线）评价mSEPT9对食管癌的诊断价值。用χ2检验分析mSEPT9与食管癌患者临床病理特征的关系。根据放疗疗效将食管癌患者分为放疗敏感组和不敏感组,比较放疗前两组患者mSEPT9差异。动态观察食管癌患者放疗前后mSEPT9变化,分别评价不同放疗敏感性组放疗前后mSEPT9差异。结果 mSEPT9诊断食管癌的灵敏度为62.5%,特异度为100%,ROC曲线下面积为0.813。mSEPT9与食管癌患者淋巴结转移、临床分期有关（P<0.05）,与性别、年龄、侵犯部位、肿瘤长度、分化程度、浸润程度等无关（P>0.05）。放疗敏感组mSEPT9阳性率低于放疗不敏感组（53.06% vs 82.61%,P=0.016）。72例患者放疗后mSEPT9阳性率较放疗前显著下降（30.56% vs 62.5%,P<0.001）,其中放疗敏感组放疗后mSEPT9阳性率较放疗前显著下降（14.29% vs 53.06%,P<0.001）,不敏感组放疗后mSEPT9阳性率较放疗前无显著性差异（65.22% vs 82.61%,P=0.125）。结论 检测血浆mSEPT9有助于食管癌患者诊断和放疗敏感性预测。     

河南食管癌高发区人群食管癌和癌旁组织磷酸化酪氨酸蛋白的变化

目的：探讨食管癌和癌旁组织磷酸化酪氨酸蛋白的变化。方法：17例食管癌切除标本，采用组织病理学和Western印迹技术研究食管癌和癌旁正常组织及各级病变组织中磷酸化酪氨酸蛋白的变化。结果：癌旁正常上皮、基底细胞过度增生、不典型性增生和鳞癌中存在75000，60000和55000 3条区域蛋白，75000最明显。75000区域蛋白半定量结果表明癌与癌旁组织间差异无统计学意义。结论：磷酸化酪氨酸蛋白是食管癌变多阶段演进过程中常见的蛋白类型，意义当需更多的研究证实。     

Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center,single-arm clinical trial (ESONICT-2)

BackgroundMore and more evidence has confirmed the efficacy and safety of immunotherapy drugs, such as camrelizumab and pembrolizumab. There are several phase-I/II studies showing that toripalimab has an acceptable safety profile and promising clinical activity in patients with advanced solid tumors. To further confirm its efficacy and safety, the aim of the study was to evaluate toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsThis study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase II trial (registration number: ChiCTR2100052784). The patients eligible for inclusion criteria at Fujian Medical University Union Hospital from October 2019 to October 2020 were included in this study. Patients who were suitable for surgery underwent minimally invasive esophagectomy (MIE) within 4–6 weeks after neoadjuvant therapy. Pathological complete response (pCR) and adverse events (AEs) were the primary end points. Secondary endpoints included R0 resection rate, major pathological response (MPR), interval to surgery, and 30-day complications.ResultsA total of 20 patients were enrolled from October 2019 to October 2020. All patients successfully completed 2 cycles of neoadjuvant therapy. Treatment-related AEs were common during neoadjuvant therapy, with leucopenia the most frequently occurring AE (4/20, 25%). With respect to immune-related AEs, immune dermatitis occurred in 2 patients, including 1 patient with grade I and 1 patient with grade III. Based on radiologic evaluation, the objective response rate (ORR) was 70% (14/20). Twelve patients underwent McKeown MIE. The pCR rate of the primary tumor was 16.7% (2/12), and the MPR rate of the primary tumor was 5/12 (41.7%). The mean interval to surgery was 33.2 days, and no patients experienced delayed surgery due to treatment-related AEs. Pneumonia was the most common 30-day postoperative complication (3/12, 25%). Anastomotic leakage (AL) only occurred in 1 patient during the hospital stay. There were no treatment- or surgery-related deaths.ConclusionsBased on our results, toripalimab combined with docetaxel and cisplatin as a novel neoadjuvant therapy was safe and effective in locally advanced ESCC.