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Wei Liu,1,* Di-Jun Lu,1,* Xiao-Wen Li,1 Yu-Liang Zhang,2 Ming-Hua Shi,2 Xu-Dong Wang1 1Department of Emergency, Aerospace Center Hospital, Beijing, 100049, People’s Republic of China; 2Department of Emergency, Keyouqianqi People’s Hospital, Inner Mongolia, 137400, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu-Dong Wang, Department of Emergency, Aerospace Center Hospital, No. 15 of Yuquan Street, Haidian District, Beijing, 100049, People’s Republic of China, Tel +86 10 59971968, Fax +86 10 59971199, Email xudongwang59@163.comObjective: To summarize the characteristics of patients calling the 120 emergency number for pre-hospital first aid in Keyouqian Banner, Hinggan League.Methods: The clinical data of adult patients with pre-hospital first aid from 2016 to 2018 were retrospectively analyzed.Results: There were 2711 cases with pre-hospital first aid. Males significantly outnumbered females. Young and middle-aged patients comprised 81.5%. Patients were mainly Han and Mongolians. Most injuries and illnesses occurred at home and on the road. The time to arrival of medical services was 30.34 ± 28.29 minutes. The proportion of pre-hospital first aid for trauma was the highest, followed by diseases concerning the cardiovascular and neurological systems. The proportion of patients with improved medical conditions after onsite first aid was 43.3%, the proportion with unchanged conditions was 51.7%, and the total mortality rate was 3.9%.Conclusion: The disease spectrum, ethnic distribution, age at onset, and pre-hospital first aid capabilities for outpatients were analyzed. These results may facilitate the establishment of a pre-hospital first aid system for the local prevention and control of acute and critical illnesses, increase the success rate of the region’s pre-hospital first aid services, and improve the prognosis.Keywords: Keyouqian Banner, Inner Mongolia, pre-hospital first aid, emergency medical service, epidemiological analysis

Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection., Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan-Meier overall survival and progression-free survival estimates were calculated., Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression., Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation., (© 2024 The Authors.)

Background: The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in oropharyngeal cancer incidence worldwide., Methods: We analyzed cancer incidence data between 1993 and 2012 from 42 countries using the Cancer Incidence in Five Continents database volumes V through XI. Trends in oropharyngeal cancer incidence were compared with oral cavity cancers and lung squamous cell carcinomas using log-linear regression and age period-cohort modeling., Results: In total, 156 567 oropharyngeal cancer, 146 693 oral cavity cancer, and 621 947 lung squamous cell carcinoma patients were included. Oropharyngeal cancer incidence increased (P < .05) in 19 and 23 countries in men and women, respectively. In countries with increasing male oropharyngeal cancer incidence, all but 1 had statistically significant decreases in lung squamous cell carcinoma incidence, and all but 2 had decreasing or nonsignificant net drifts for oral cavity cancer. Increased oropharyngeal cancer incidence was observed both in middle-aged (40-59 years) and older (≥60 years) male cohorts, with strong nonlinear birth cohort effects. In 20 countries where oropharyngeal cancer incidence increased for women and age period-cohort analysis was possible, 13 had negative or nonsignificant lung squamous cell carcinoma net drifts, including 4 countries with higher oropharyngeal cancer net drifts vs both lung squamous cell carcinoma and oral cavity cancer (P < .05 for all comparisons)., Conclusions: Increasing oropharyngeal cancer incidence is seen among an expanding array of countries worldwide. In men, increased oropharyngeal cancer is extending to older age groups, likely driven by human papillomavirus-related birth cohort effects. In women, more diverse patterns were observed, suggesting a complex interplay of risks factors varying by country, including several countries where female oropharyngeal cancer increases may be driven by HPV., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Elective neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery, based largely on historical series. It is unclear if this is necessary for all patients in the modern era., Methods: Patients with cN0 oropharynx, larynx, and hypopharynx cancers diagnosed from 2010-2015 undergoing primary surgery were identified in the National Cancer Data Base., Results: Inclusion criteria were met by 4117 cN0 patients. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, p < 0.001). Histologic grade strongly predicted pN+ (OR 2.58, 95% CI 1.88-3.59, p < 0.001). A nomogram predicted less than 10% of cN0 patients had pN+ risk <15%., Conclusion: LVI and grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancer. Even in the modern era, pN+ rates warrant neck dissection for cN0 patients., Level of Evidence: 3 Laryngoscope, 133:1660-1666, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Recently, several phase I and phase II clinical trials of antisense oligodeoxynucleotides (ASOs) targeting to the commonly shared conserved sequences of HBV transcripts brought us some promising results. Particularly in the report of phase IIb clinical trial of Bepirovirsen (GSK3228836), approximately 9-10% patients with low baseline serum HBsAg (> 100 IU/ml & < 3 000 IU/ml) achieved functional cure after 24 weeks' of Bepirovirsen treatment. After reviewing the results of other clinical trials, one would be impressed to know that ALG-020572 (Aligos), RO7062931 (Roche) and GSK3389404 (GSK) all failed to sufficiently suppress serum HBsAg expression though the hepatocyte-targeted delivery of these ASOs were enhanced via N-acetyl galactosamine conjugation. Bepirovirsen enabled some patients to achieve sustained disappearance of serum HBsAg. The analysis of its distribution in different tissues of patients after drug administration showed that only a few fractions of ASOs entered liver tissues and far fewer eventually entered hepatocytes. Taking into consideration that only a few hepatocytes could be expected positive for HBsAg staining among these participants with low serum HBsAg level. We suspect that the mechanistic contribution of ASOs declining the serum HBsAg is not only via directly acting on the HBV transcripts in hepatocytes, but also via entering non-parenchymal cells such as Kupffer cells and resulting in stimulation and activation of innate immunity. Eventually the serum HBsAg declines in most participants and even disappears in a small fraction of patients with low baseline HBsAg level, via attack the infected hepatocytes evidenced by the aberrant elevation of ALT. Nevertheless, the functional cure of CHB remains a challenging issue and more efforts are needed.

Pteropus dasymallus is widely distributed on islands throughout the western edge of the Pacific Ocean. The Formosan flying fox, P. d. formosus , is an endemic subspecies in Taiwan found mainly on Lyudao; it was previously thought to have been extirpated. Since 2005, intensive surveys have been conducted to investigate the residency, population size and plant resource utilization of P. dasymallus in Taiwan. Interviews were carried out to investigate its former abundance and the causes of population decline. In Taiwan, P. dasymallus is in a state of ongoing oceanic dispersal and colonization and has considerably expanded its geographic range. In addition to remaining in its historic habitat on Lyudao, P. dasymallus has also established colonies on Gueishan Island and in Hualien on Taiwan's main island in the past few decades. The total population size is estimated to be 240 individuals, and this number is on the rise. Approximately three-quarters of the entire population (73.64%) was found on Gueishan Island. The sex ratio was strongly skewed toward males. A total of 40 plant species were recorded as being used by the flying fox for food, roosts or perches. More agricultural and horticultural plant species were used by the flying fox in urban Hualien. According to the interviews, flying foxes were abundant on Lyudao, but their number dramatically declined from the 1970s to the mid-1980s, mainly due to commercial hunting. Maintaining a sufficient population size and genetic variability is fundamental to the long-term survival of the flying fox. Enforcing conservation laws, restoring habitats, controlling invasive species and improving public awareness are the main steps in the recovery and sustainability of the flying fox population.

Sociodemographic and lifestyle factors may play a role in determining whether patients with clinically localized prostate cancer (PC) are managed with active surveillance (AS), radical prostatectomy (RP), or radiation therapy (RT); however, these relationships have not been well examined. In a cross-sectional study conducted within an equal access healthcare system, multivariable adjusted regression analysis revealed that living with a spouse or partner was associated with a 65% lower chance of being managed by RT (P = 0.001) and 57% lower risk of being managed by AS (P = 0.042) compared with RP. No other sociodemographic or lifestyle factors were independently associated with treatment modality., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: A better understanding of the relationship between the spread of head and neck squamous cell carcinoma (HNSCC) to regional lymph nodes (LNs) and the frequency and manner of treatment failure should help design better treatment intensification strategies. In this study, we evaluated the relationship between recurrence patterns, mortality, and number of pathologically positive (+) LNs in HNSCC in 3 prospective randomized controlled trials., Methods and Materials: We performed a secondary analysis of 947 patients with HNSCC enrolled in RTOG 9501 (n = 410), RTOG 0234 (n = 203), and EORTC 22931 (n = 334) undergoing surgery and postoperative radiation ± systemic therapy. Multivariable models were constructed for overall survival (OS), disease-free survival (DFS), locoregional relapse (LRR), and distant metastases (DM). Restricted cubic splines were used to model the nonlinear relationship between +LN number and outcomes., Results: In multivariable analysis, OS and DFS decreased with each +LN without plateau, most pronounced up to 5 +LNs (OS: hazard ratio [HR], 1.21 per +LN; 95% confidence interval [CI], 1.10-1.34; P < .001; DFS: HR per +LN, 1.19; 95% CI, 1.08-1.30; P < .001) and more gradually beyond this (OS: HR per +LN, 1.02; 95% CI, 1.01-1.06; P < .001; DFS: HR per +LN, 1.04; 95% CI, 1.02-1.06; P < .001). In contrast to LRR risk, which increased sharply up to 5 +LNs (HR per +LN, 1.28; 95% CI, 1.10-1.50; P < .001) but plateaued beyond this (HR per +LN, 1.00; 95% CI, 0.96-1.04; P = .98), DM risk increased continuously with increasing +LNs (≤5 +LNs: HR per +LN, 1.10; 95% CI, 1.01-1.20; P = .04; >5 +LNs: HR per +LN, 1.05; 95% CI, 1.02-1.08; P = .003)., Conclusions: In high-risk resected HNSCC, increased mortality was associated with increased +LN count. LRR and DM risk both increased in parallel up to 5 +LNs, but only DM continued to increase for further +LN increases. These differing recurrence patterns can help inform design of future treatments., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors., Methods: We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses., Results: Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites., Conclusions: Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose/objectives: Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies., Materials/methods: Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement., Results: Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42)., Conclusion: Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Chemoradiation is considered the standard of care for locally advanced cervical cancer. While brachytherapy (BT) boost is associated with improved survival and less toxicity compared to external beam radiation therapy (EBRT) boost, it is unclear why many patients do not receive a BT boost. In this study, we compared sociodemographic and baseline patient characteristics between patients receiving EBRT boost versus BT boost., Methods: We analyzed patients in the National Cancer Database diagnosed between 2004 and 2016 with FIGO stage IIB-IVA cervical cancer treated with nonpalliative doses of chemoradiation. Logistic regression analysis was utilized to evaluate BT utilization over time and by other clinicopathological and sociodemographic factors., Results: Overall, 5764 patients were evaluated, of which 4937 (86%) underwent BT boost. Using multivariable logistic regression, higher FIGO stage was a significant predictor for utilization of EBRT versus BT boost, with odds ratio 2.92 (95% confidence interval [CI] 2.04-4.16; p < 0.001), 2.68 (95%CI 2.22-3.24; p < 0.001), and 4.51 (95%CI 3.05-6.67; p < 0.001) for IIIA, IIIB, and IVA, respectively, compared to IIB. Increased utilization of EBRT boost was also associated with community cancer facility types, lower income (based on zip code), earlier year of diagnosis, and higher comorbidity score., Conclusions: In FIGO stage IIB-IVA cervical cancer patients treated with nonpalliative doses of chemoradiation, overall utilization of BT is 86%. Higher FIGO stage, community cancer facilities, lower income, earlier year of diagnosis, and higher comorbidity score were significant predictors of EBRT boost utilization. Future studies are needed to better understand reasons for this as higher FIGO stage patients are the mostly likely to benefit from a BT boost., (Published by Elsevier Inc.)

Importance: Given the evolving patterns of lymph node evaluation for cutaneous melanoma, it is unclear whether the current nodal classification system will continue to accurately reflect prognosis in the modern era. Existing nodal staging for cutaneous melanoma was developed primarily for patients undergoing completion lymph node dissection (CLND) for node-positive disease and does not produce groups with continuously increasing mortality., Objective: To develop and validate a modified nodal classification system for cutaneous melanoma., Design, Setting, and Participants: This retrospective cohort analysis included 105 785 patients with cutaneous melanoma undergoing surgery and nodal evaluation from January 1, 2004, to December 31, 2015, in the National Cancer Database. Extent of lymph node dissection was available for patients diagnosed in 2012 and onward. Multivariable models were generated with number of positive lymph nodes modeled using restricted cubic splines. A modified nodal classification system was derived using recursive partitioning analysis (RPA). The proposed lymph node classification system was validated in 85 499 patients from the Surveillance, Epidemiology, and End Results (SEER-18) database. Data were analyzed from April 9, 2020, to May 28, 2021., Main Outcomes and Measures: Overall survival., Results: Among the 105 785 patients included in the analysis (62 496 men [59.1%]; mean [SD] age, 59.9 [15.5] years), number of positive lymph nodes (hazard ratio [HR] per lymph node for 0 to 2 positive lymph nodes, 2.48 [95% CI, 2.37-2-61; P < .001]; HR per lymph node for ≥3 positive lymph nodes, 1.10 [95% CI 1.07-1.13; P < .001]), clinically detected metastases (HR, 1.35; 95% CI, 1.27-1.42; P < .001), and in-transit metastases (HR, 1.48; 95% CI, 1.34-1.65; P < .001) were independently associated with mortality. An RPA-derived system using these variables demonstrated continuously increasing mortality for each proposed lymph node classification group, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 2.72 (95% CI, 2.58-2.86) for N1b, 3.79 (95% CI, 3.51-4.08) for N2a, 4.56 (95% CI, 4.22-4.92) for N2b, 6.15 (95% CI, 5.59-6.76) for N3a, and 8.25 (95% CI, 7.64-8.91) for N3b in the proposed system (P < .001). By contrast, the current American Joint Committee on Cancer (AJCC) nodal classification system produced a more haphazard mortality profile, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 3.81 (95% CI, 3.53-4.12) for N1b, 2.59 (95% CI, 2.30-2.93) for N1c, 2.71 (95% CI, 2.56-2.87) for N2a, 4.51 (95% CI, 4.17-4.87) for N2b, 3.44 (95% CI, 2.60-4.55) for N2c, 6.06 (95% CI, 5.51-6.67) for N3a, 8.15 (95% CI, 7.54-8.81) for N3b, and 6.90 (95% CI, 5.60-8.49) for N3c. As a sensitivity analysis, the proposed system continued to accurately stratify patients when excluding those undergoing CLND for microscopic lymph node metastases. This system was validated for overall survival and cause-specific mortality in SEER-18. Last, a new overall staging system for node-positive patients was developed by RPA and demonstrated improved concordance vs the AJCC, 8th edition system (C statistic, 0.690 [95% CI, 0.689-0.691] vs 0.666 [95% CI, 0.666-0.668])., Conclusions and Relevance: The findings of this cohort study suggest that a modified nodal classification system can accurately stratify mortality risk in cutaneous melanoma in an era of increasing use of sentinel lymph node biopsy without CLND and should be considered for future staging systems.

Purpose: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein., Methods and Materials: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed., Results: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], -0.83 to 1.59 cm), -3.22 cm (IQR, -5.12 to -1.84 cm), and 0.9 cm (IQR, -1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of -3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively., Conclusions: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted., (© 2021 The Authors.)

Hepatitis B virus (HBV) is an important pathogen that causes different liver diseases such as viral hepatitis and liver cirrhosis. HBV pregenomic RNA (pgRNA) plays a crucial role in HBV life cycle, which is not only the translation template of core (C) and polymerase (P), but also the template of reverse transcription. The ratio of P protein to core protein is tightly regulated. Since P and core are both translated by pgRNA and the open reading frame (ORF) of P is located downstream of the ORF of core, how to initiate P protein translation is a key scientific question. Previous studies suggest that P can be translated through different mechanisms, such as leaky scanning and reinitiation. In this review, we summarized the proposed mechanisms relevant to the translation of polymerase from HBV pgRNA through literature review and derivation.

Gait maturation in infants develops gradually through several phases. However, external factors such as childrearing practices, especially the wearing of diapers, may affect an infant's motor development. This study investigated the influence of different bulk stresses on the gait of toddlers wearing a disposable diaper. Twenty-six healthy toddlers (age: 19.2 ± 0.9 months) participated in this study. We measured the joint kinematics (pelvis angle and hip-joint angle) and spatiotemporal parameters (step length and step width) of the toddlers' gait under four dress conditions (wearing Type A&#95;WET, Type A&#95;DRY, and Type B&#95;WET diapers and naked). Type B&#95;WET had a higher bulk stress than Type A&#95;WET, and Type A&#95;DRY had lower stress than Type A &#95; WET. Our results indicate that the walk of toddlers when wearing a diaper differs from that when naked. This difference is due to the effect of the bulk of the diaper on the lower limb. A high bulk stress has a greater influence than that of a low bulk stress on joint dynamics and step width. Therefore, our findings suggest that wearing diapers with high bulk stress may inhibit the natural gait patterns of toddlers., (© 2021. The Author(s).)

Magnetic covalent organic framework nanocomposite denoted as Fe 3 O 4 @TAPB-Tp with core-shell structure was fabricated via a simple template-mediated precipitation polymerization method at mild conditions. The polyimine network shell was created through the polymerization of 1,3,5-tris(4-aminophenyl)-benzene (TAPB) and 1,3,5-triformyl-phloroglucinol (Tp) in tetrahydrofuran (THF) by the Schiff-base reaction. Featuring with large specific surface area (163.19 m 2 g -1 ), good solution dispersibility, and high stability, the obtained Fe 3 O 4 @TAPB-Tp exhibited high adsorption capacities and fast adsorption for zearalenone and its derivatives (ZEAs). The adsorption isotherms showed multilayer adsorption dominated at low concentration and monolayer adsorption at high concentration between the interface of ZEAs and Fe 3 O 4 @TAPB-Tp. With the Fe 3 O 4 @TAPB-Tp as sorbent, a magnetic solid-phase extraction-ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for simultaneous adsorption and detection of five ZEAs in complex samples. The proposed method displayed favorable linearity, low limits of detection (0.003 ~ 0.018 μg kg -1 ), and good repeatability (2.37~10.4%). The developed method has been applied for real sample analysis, with recoveries of 81.27~90.26%. These results showed that Fe 3 O 4 @TAPB-Tp has a good application potential for the adsorption of ZEAs in food samples. Magnetic covalent organic framework nanocomposite (Fe 3 O 4 @TAPB-Tp) were quickly fabricated at mild conditions and used as effective adsorbent for magnetic solid-phase extraction of zearalenone and its derivatives (ZEAs) from food samples prior to ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis.

Background: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain., Methods: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed., Results: Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate-grade (hazard ratio [HR] 1.16, 95% CI 1.07-1.26, P < .001) and high-grade (HR 1.38, 95% CI 1.26-1.52, P < .001) tumors had worse survival than low-grade tumors. This magnitude was comparable to other well-established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(-) oropharynx cancer., Conclusions: The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients., (© 2020 Wiley Periodicals LLC.)

Background: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies., Objective: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC)., Methods: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality., Results: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients., Limitations: Potential selection bias from a retrospective data set., Conclusion: In MCC, women have improved survival compared with men, driven by MCC-related mortality., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for the number of metastatic LNs, which is a primary driver of survival in multiple cancers., Objective: To determine the impact of the number of metastatic LNs on survival in MCC., Methods: Patients with MCC undergoing surgery were identified from the National Cancer Database (NCDB). The association between metastatic LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived by using recursive partitioning analysis. MCC patients undergoing surgery in the Surveillance, Epidemiology, and End Results (SEER) Program were used as validation cohort., Results: Among 3670 patients in the NCDB, increasing metastatic LN number was associated with decreased survival (P < .001). Mortality risk increased continuously with each additional positive LN when using multivariable, nonlinear modeling. According to a novel staging system derived via recursive partitioning analysis, the hazard ratio for death in multivariable regression compared with patients without LN involvement was 1.24 (P = .049), 2.08 (P < .001), 3.24 (P < .001), and 6.13 (P < .001) for the proposed N1a (1-3 metastatic LNs with microscopic detection), N1b (1-3 metastatic LNs with macroscopic detection), N2 (4-8 metastatic LNs), and N3 (≥9 metastatic LNs), respectively. This system was validated in the SEER cohort and showed improved concordance compared with the American Joint Committee on Cancer, Eighth Edition., Limitations: Retrospective design., Conclusions: Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: In response to the COVID-19 pandemic, there has been a rapid growth in the use of telehealth/telemedicine that will likely be sustained in the postpandemic setting. Mobile health applications (apps) can be used as part of the telehealth encounter to monitor patient-reported outcomes (PROs) and enhance patient-provider communication., Methods and Materials: A systematic review was performed of mobile health apps with symptom trackers. We searched the iOS App Store and Android Google Play using the words cancer , oncology , and symptom tracker . Apps were included if they incorporated a symptom tracking function that could allow patients with cancer to record symptoms and PROs. Apps were evaluated using the mobile apps rating scale, which includes engagement, functionality, aesthetics, information, and app subjective quality., Results: The initial search yielded 1189 apps, with 101 apps eligible after title and description screening. A total of 41 apps met eligibility criteria and were included in this study. The majority of apps (73%, n = 30) were general health/pain symptom trackers, and 27% (n = 11) were cancer-specific. The app quality mean scores assessed using the mobile apps rating scale ranged from 2.43 to 4.23 (out of 5.00). Only 1 app has been trialed for usability among patients with cancer., Conclusions: Although various symptom tracking apps are available, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients to optimize PRO assessment and integration with telehealth/telemedicine encounters to increase symptom recognition and enhance patient-provider communication is urgently needed.

Background: Radiotherapy (RT) without chemotherapy is considered a standard of care for the management of American Joint Committee on Cancer (AJCC) 7th edition (7E) T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC). Recent data suggests concurrent chemoradiation (CCRT) may benefit these patients but did not include human papillomavirus (HPV) status. Given the radiosensitivity differences between HPV-positive versus HPV-negative OPSCC, the effect of chemotherapy may differ in these patients., Methods: We analyzed patients in the National Cancer Database diagnosed between 2010 and 2015 with AJCC 7E stage cT1-2N1M0 OPSCC and known HPV status undergoing definitive RT or CCRT., Results: Overall, 1964 patients were included, including 1297 (66%) HPV-positive and 667 (34%) HPV-negative patients. 66% received CCRT and 34% received RT alone. In multivariate analysis, CCRT was associated with improved survival compared with RT alone (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.57-0.87; P = 0.001). In propensity score-matched cohorts, 4-year overall survival was 87.4% vs 78.4% in HPV-positive patients receiving CCRT and RT alone, respectively (P = 0.002), and 65.5% vs 58.9% in HPV-negative patients, respectively (P = 0.2). There was no evidence that HPV-positivity diminished the association between CCRT and longer survival (HR, 0.57; 95% CI, 0.42-0.81) versus what was observed in HPV-negative patients (HR, 0.86; 95% CI, 0.64-1.16) (interaction P = 0.06)., Conclusions: CCRT is associated with improved survival in AJCC 7E T1-2N1 OPSCC. Despite the radiosensitivity of HPV-positive OPSCC, the association of CCRT with improved survival for T1-2N1 HPV-positive OPSCC was at least as strong, if not stronger, than what was observed in HPV-negative patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest related to this work. ZSZ was on the external advisory board for the Scripps Proton Therapy Center and has consulted for EMD Serono. All other authors have no disclosures., (Copyright © 2020. Published by Elsevier Ltd.)

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data., Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer., Design, Setting, and Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020., Main Outcomes and Measures: Overall survival., Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10)., Conclusions and Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.

Purpose: The American Brachytherapy Society (ABS) consensus guidelines for high-dose-rate (HDR) prostate brachytherapy suggest 11 different dose constraints for the urethra. The purpose of this study is to evaluate whether a single urethral constraint of D0.1 cm 3  < 110% could meet all the proposed ABS urethral constraints and to evaluate the heterogeneity and similarities of other portions of the dose-volume histogram (DVH) when only optimizing to a single constraint., Methods: This is a retrospective study of 18 consecutively treated HDR prostate brachytherapy patients treated between May 2018 to November 2018. Nine patients underwent HDR brachytherapy combined with external beam radiation therapy, and nine underwent HDR brachytherapy as monotherapy. Additional DVH values were extracted for the whole, proximal, middle, and distal urethra and compared for differences., Results: None of the ABS suggested constraints were violated when optimizing the urethra D0.1 cm 3 dose to be less than 110% of the prescription. An evaluation of the DVHs for the whole, proximal, middle, and distal urethra showed a large variation in the shape of the remainder of the DVH for all parts of the urethra. The largest standard deviations in dose to the whole and middle urethra were at the V14 dose level, and that to the proximal and distal urethra were at the V10 dose level., Conclusion: A single urethral dose constraint of D0.1 cm 3  < 110% can meet all the proposed ABS constraints. There is high variability in other parts of the urethra DVH when only using a single constraint. Additional data is needed to determine ideal constraints for the entirety of the urethra DVH., (Published by Elsevier Inc.)

In this study, the seed polysaccharides (PCSP) was ultrasonic-assisted extracted from Pouteria campechiana and optimized by response surface method (RSM). After separation and purification by DEAE-52 cellulose column and Sephadex G-75 glucan gel column, the pure polysaccharide component of PCSPa-1 was obtained, and its structure and antioxidant activity were analyzed. The results showed that the optimal parameters of PCSP with maximum yields (15.94%) were ultrasonic temperature of 79 °C, ultrasonic time of 69 min, and liquid to material ratio of 41 mL/g. The molecular weight of PCSPa-1 was 67900 Da. PCSPa-1 consisted of glucose and mannose with a molar ratio of 86.65:4.62, and the glycosidic bond mainly included →4)-α-d-Glc(1→ and →6)-α-d-Glc(1→. Scanning electron microscopy showed that PCSPa-1 was a strip structure with a smooth surface. In addition, PCSPa-1 had strong scavenging capacity to 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis- (3-ethylbenzthiaz oline-6-sulphonic acid) (ABTS), hydroxyl radical, and superoxide radical. Polysaccharides of Pouteria campechiana seeds could be exploited as a natural antioxidant., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Competing Interests: Authors disclosure of potential conflicts of interest The authors have nothing to disclose.

Objectives: The United States has a heterogenous health insurance landscape for patients <65 years. We sought to characterise the impact of primary payer on overall survival (OS) in insured patients younger than 65 with head and neck squamous cell carcinoma (HNSCC) treated with definitive radiotherapy., Design/study/participants: The National Cancer Database was queried for patients <65 years old diagnosed from 2004 to 2014 undergoing definitive radiotherapy ± chemotherapy for cancers of the nasopharynx, oropharynx, hypopharynx and larynx. Uninsured patients and oropharyngeal cancers without known HPV status were excluded., Main Outcome: Overall survival., Results: Overall, 27 292 insured patients were identified, including 17 060 (62.5%) with private insurance. Median follow-up was 52.1 months. In multivariable models, patients receiving Medicaid (HR = 1.66, 95% CI 1.57-1.75, P < .001), Medicare (HR = 1.64, 95% CI 1.55-1.73, P < .001) and other government insurance (HR = 1.44, 95% CI 1.29-1., P < .001) had independently increased mortality in comparison to those with private insurance. In propensity score-matched cohorts, 5-year OS was 65.5% vs 50.6% for privately vs government-insured patients, respectively (P < .001). In multivariable subgroup analysis, private insurance was associated with improved survival in all subgroups. However, the magnitude of this effect was most pronounced in patients with HPV-positive oropharyngeal cancer vs non-HPV-related cancer (interaction P < .001), younger patients (interaction P = .001), and those without comorbidity (interaction P < .001)., Conclusions: Patients <65 with HNSCC undergoing definitive radiation with private health insurance have markedly longer survival relative to patients with government-sponsored insurance. This illustrates that increasing access to care may be necessary, but is not sufficient, to mitigate the significant disparities in the US healthcare system., (© 2019 John Wiley & Sons Ltd.)

Background: Patients with clinical stage I human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy., Methods: The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV-positive OPSCC (AJCC seventh edition stage T1-2N0-2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy., Results: The current analysis included 4473 patients with HPV-positive stage I OPSCC with a median follow-up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645-0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node-positive stage I disease (stage III-IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557-0.835 [P < .001]), but not for patients with N0 disease (stage I-II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011-2.681 [P = .05]). Similar results were noted among propensity score-matched cohorts., Conclusions: Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node-positive, but not lymph node-negative, AJCC eighth edition stage I HPV-positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients., (© 2019 American Cancer Society.)

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has dramatically increased in incidence and prevalence among patients aged 70 and older. There are virtually no data regarding outcomes in this population, and thus optimal therapy, including the role of chemotherapy for those undergoing radiotherapy (RT), remains unclear., Methods: The National Cancer Database was queried for older adults (defined as age 70 years and older) with locally advanced OPSCC (cT1-2N1-3, cT3-4N0-3) diagnosed from 2010 to 2014 with known HPV-status undergoing definitive RT alone or chemoradiation (CRT)., Results: Overall, 1,965 older adults with locally advanced OPSCC met inclusion criteria, including 1,141 HPV-positive (58%) and 824 HPV-negative (42%) patients. 1,211 patients (62%) received CRT. In multivariable analysis, CRT was associated with improved survival in older patients when compared to RT alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.64-0.86, P < 0.001). CRT was associated with improved survival in both HPV-positive (HR = 0.80, 95% CI: 0.64-1.00, P = 0.05) and HPV-negative (HR = 0.69, 95% CI: 0.56-0.85, P < 0.001) subgroups. There was no significant interaction between HPV status and the impact of CRT on survival (P interaction = 0.57)., Conclusions: Despite the radiosensitivity of HPV-positive OPSCC and the challenges in delivering CRT to older adults, CRT was associated with improved survival in older patients with HPV-positive OPSCC, similar in magnitude to the benefit in HPV-negative patients. As the incidence of HPV-positive OPSCC in older patients continues to increase, further studies are needed to investigate optimal therapeutic strategies in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Recent evaluation of female representation in major radiation oncology organizations was published by Knoll et al. (IJROBP, 2018) but did not include information about the American Brachytherapy Society (ABS). The objective of this study is to assess trends in gender diversity in the ABS., Materials and Methods: Publicly available information from the ABS and American Society for Radiation Oncology (ASTRO) websites were used to determine the proportion of women in various leadership positions and receiving awards and honors. The data were organized by comparing female representation up until 2004 and then from 2005 until current as was done in the article of Knoll et al. to facilitate comparisons with ASTRO., Results: Of the 579 US physician members of the ABS, 155 (27%) are women. There has been an increase in the proportion of female ABS presidents and female Hensche Award recipients between 1978-2004 and 2005-2018. There was a significant difference in the female makeup of the editorial board of the main journals for the ABS (18%) and ASTRO (43%) (p = 0.02). Two other prominent differences between the ABS and ASTRO, however not statistically significant, were the female representation of 2018 fellows (10% vs. 26%, respectively) and recipients of each organization's highest honor between 2005 and 2017 (25% vs. 6%, respectively)., Conclusions: Over the past decade, there has been an increase in women representation in the ABS presidency and Henschke awardees. Representation still remains low, relative to ASTRO, in other areas suggesting room for further improvement. Exploring these trends is imperative in developing potential solutions to improve gender diversity in the field of brachytherapy., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence among older adults. However, the role of human papillomavirus (HPV) in driving this trend and its prognostic significance in this population have not been established., Methods: The National Cancer Database was queried for patients with OPSCC diagnosed from 2010 to 2015 undergoing either surgery or radiotherapy (RT) with known HPV status. Older adults were defined as those aged 70 years or older., Results: Among 43,427 OPSCC patients, the proportion of HPV-positive OPSCC increased from 45.1% to 63.3% in older adults (P < 0.001). In 19,358 patients meeting the inclusion criteria for survival analyses, HPV positivity was associated with improved survival for older adults undergoing either definitive RT (hazard ratio [HR] = 0.63, 95% confidence interval [CI] 0.55-0.72, P < 0.001) or surgery (HR = 0.37, 95% CI 0.25-0.53, P < 0.001) in multivariable analysis. In propensity score-matched cohorts, 3-year overall survival was 69.1% versus 55.5% (P < 0.001) in older adults with HPV-positive and HPV-negative OPSCC undergoing definitive RT, respectively, and 88.5% versus 69.1% (P = 0.001) for older adults undergoing surgery. Although HPV positivity was associated with improved survival among all age groups receiving RT, the magnitude of the effect diminished with increasing age (interaction P < 0.001). No interaction between age and the impact of HPV status on survival was seen for surgical patients (interaction P = 0.72)., Conclusions: The epidemiologic landscape of HPV-positive OPSCC is evolving, with a dramatic increase in the proportion of HPV-associated OPSCC among patients 70 years or older. HPV remains a powerful predictor of improved survival in elderly patients, but with less pronounced effect on older adults undergoing definitive RT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Two loci concurrent mutations in non-exclusion paternity case were reported based on 19 STR loci available from Goldeneye™ DNA ID System 20A (Peoplespot, Beijing, China). When 9508 family trios with Paternity index (PI) threshold of >10,000 was analyzed, 14 families show mutations at two loci. The paternity was confirmed by using an additional 19 STR markers. When the probability of occurrence of two mutations was compared with the expected probability deduced from binomial model, the observed mutational probability was significantly larger than the expectation. However, the characteristics of mutations agree with those reported previously. Our result indicates that larger samples is still need to estimate mutation rates accurately and reveal the relationship between mutations with multiple loci and the characterization of human mutations based on microsatellites., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Prophylactic cranial irradiation (PCI) improves survival for small-cell lung cancer (SCLC). Evidence for PCI in limited-stage SCLC largely derives from studies requiring only chest x-ray (CXR) to determine remission status. We analyzed thoracic chemoradiation therapy (TCRT) outcomes according to imaging modality to determine which patients benefitted most from PCI., Patients and Methods: All limited-stage SCLC patients who received TCRT as well as PCI at our institution were reviewed. Imaging between TCRT end and PCI start was characterized as complete (CR), partial (PR), or other response., Results: Thirty-eight consecutive patients were assessed for TCRT response before PCI with CXR (n = 21), chest computed tomography (CT; n = 27), and/or positron emission tomography (PET)/CT (n = 11). CR was identified on 71% of CXRs, 41% of CT scans, and 18% of PET/CT scans. Median survival was 28.3 months for the entire cohort and did not differ for patients who had CXR alone versus CT and/or PET/CT for restaging (P = .78) or those with PR using any modality versus CR using all modalities (22.6 months vs. 45.5 months; P = .22). CT CR patients had numerical but not statistically significant improved 2-year (P = .18) and 3-year (P = .13) survival compared with CT PR., Conclusion: CXR remains an appropriate modality to assess TCRT response before PCI in limited-stage SCLC. Advanced imaging did not inform the decision to offer PCI in this study. Because of similar excellent survival profiles independent of imaging modality and TCRT response, this analysis suggests limited-stage SCLC patients with PR using any modality should not be denied PCI, akin to standards for extensive-stage SCLC., (Published by Elsevier Inc.)

Knowledge of population structure is very important for forensic genetics. However, the population substructure in Central-Southern China Han nationality has still not been fully described. In this study, we investigated the genetic diversity of 15 forensic autosomal STR loci from 6879 individuals in 12 Han populations subdivided by administrative provinces in Central-Southern China. The statistical analysis of genetic variation showed that genetic differentiation among these populations was very small with a F st value of 0.0009. The Discriminant Analysis of Principal Components (DAPC) showed that there were no obvious population clusters in Central-Southern China Han population. In practice, the population structure effect in Central-Southern China Han population can be negligible in forensic identification and paternity testing., (Copyright © 2017. Published by Elsevier B.V.)

Competing Interests: Competing interests: None declared.

Short tandem repeat (STR) analysis is a primary tool in forensic casework. Population data and mutation rates of STRs are very important for paternity testing and forensic genetics. However, the population data and mutation rates of STRs in Han nationality based on large samples have still not been fully described in China. In this study, the allelic frequencies, forensic parameters, and mutation rate of 19 STR loci (D19S433, D5S818, D21S11, D18S51, D6S1043, D3S1358, D13S317, D7S820, D16S539, CSFIPO, PentaD, vWA, D8S1179, TPOX, Penta E, TH01, D12S391, D2S1338, and FGA) based on the Goldeneye™ DNA ID System 20A in Southern China Han nationality among seven provinces were investigated. Furthermore, population stratification of Southern China Han nationality among seven provinces was established. The multidimensional scaling (MDS) plot based on genetic distances (Fst) showed that the studied populations can be clustered into two major groups. However, relationships among populations were weak (Fst < 0.0043). A total of 376 cases of mutation were detected from the 19 selected loci in 15,396 meioses. The average mutation rate for the 19 loci was estimated to be 1.3 × 10 -3 per meiosis. The mutation was mainly single step; the paternal mutation rate was higher than the maternal; and paternal mutation rate increases with paternal age.

In this study, a panel of 13 STR loci locate on chromosome 3, 4, and 17 (D3S2402, D3S2452, D3S1766, D3S4554, D3S2388, D3S3051, D3S3053, D4S2404, D4S2364, AC001348A, AC001348B, D17S975, and D17S1294) were assessed for pairwise kinship analysis. Map distances between these STR loci ranged from 0.07 cM to 97.03 cM. The population genetic study of Chinese Han population showed that linkage disequilibrium exists in two clusters of closely linked markers (D4S2404-D4S2364 and D17S975-D17S1294), in which the recombination fractions were 0.0026 and 0.0001, respectively. The recombination fractions derived from the Rutgers Map for the closely linked markers (genetic distance < 0.5 cM) were significant underestimates in comparison to those of direct observation of STR transmissions in families. When effect of linkage on pairwise kinship testing was evaluated by comparing likelihood ratio (LR) values taking linkage into account, overall LR values increased. But extremely low LRs were also observed. Finally, the power of the 13 STR loci to discriminate relationship among full-sibs, half-sibs, grandparent-grandchild, uncle-niece, and unrelated pairs was assessed with a category fraction. The results showed that about 72.64% of full-sib pairs and about 82.84% of unrelated pairs could be classified correctly. But the category fractions of second-degree relationships drastically reduced to 7.34-35.48%. If only pairs of grandparent-grandchild, half-sibs, and uncle-niece were distinguished, the category fraction was 0.5512, 0.1147, and 0.4362, respectively. Our study results demonstrated that linked STRs were helpful to differentiate the most frequent relationships in pairwise kinship analysis., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the relationship of muscle mass and muscle function with age., Methods and Study Design: The study including 415 participants (aged 60-99 years). Upper (UMM) and lower (LMM) limbs muscle mass and whole body fat free mass (FFM) were measured by bioelectrical impedance analysis. The appendicular skeletal muscle mass (ASM) index (ASM/height2) was calculated. Muscle function was assessed by measuring hand grip strength (HGS) and gait speed., Results: Using ASM index cutoff values we found that higher prevalence of sarcopenia in women than in men (33.5% vs 23.6%, p=0.025). In the upper limb, HGS (β=-0.809) declined more rapidly with age than did UMM (β=-0.592) in men, but not in women (β=-0.389 and β=-0.486 respectively). In the lower limb, gait speed declined more rapidly than LMM in both men (β=-0.683 vs β=-0.442) and women (β=-1.00 vs β=-0.461). The variance of UMM explained 28-29% of the variance of HGS, and LMM explained 7-8% of the variance of gait speed in women and men respectively. In addition to the common predictors (BMI and age), the specific predictors were smoking, exercise and education for FFM and ASM, and smoking, drinking and exercise for HGS (p<0.05)., Conclusions: Loss of muscle function is greater than the decline of muscle mass particularly in the upper limbs in men. However, women are more prone to have low muscle mass than the men. Exercise programs need to be designed gender specifically.

Adequate postnatal growth is important for young bats to develop skilled sensory and locomotor abilities, which are highly associated with their survival once independent. This study investigated the postnatal growth and development of Scotophilus kuhlii in captivity. An empirical growth curve was established, and the postnatal growth rate was quantified to derive an age-predictive equation. By further controlling the fostering conditions of twins, the differences in the development patterns between pups that received maternal care or were hand-reared were analyzed to determine whether the latter developed in the same manner as their maternally reared counterparts. Our results indicate that both forearm length and body mass increased rapidly and linearly during the first 4 weeks, after which the growth rate gradually decreased to reach a stable level. The first flight occurred at an average age of 39 days with a mean forearm length and body mass of 92.07% and 70.52% of maternal size, respectively. The developmental pattern of hand-reared pups, although similar to that of their maternally reared twin siblings, displayed a slightly faster growth rate in the 4th and 5th weeks. The heavier body mass of hand-reared pups during the pre-fledging period may cause higher wing loading, potentially influencing the flight performance and survival of the bats once independent., (© 2015 Wiley Periodicals, Inc.)

TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism.TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.

The aim of this study was to investigate a 13 non-CODIS STR loci database using three national populations from China. A new multiplex PCR system that simultaneously amplified 13 loci in the same PCR reaction was developed. This multiplex system included the 13 STR markers (D3S2402, D3S2452, D3S1766, D3S4554, D3S2388, D3S3051, D3S3053, D4S2364, D4S2404, AC001348A, AC001348B, D17S975, and D17S1294), which were successfully analyzed by using 441 DNA samples from three national populations in China (154 Mongol, 177 Kazakh, and 110 Uigur). Allele frequencies and mutation rates of the 13 non-CODIS STR loci were investigated. A total of 4-10 alleles at each locus were observed and altogether 84, 88, and 87 alleles for the all selected loci were found in the Mongol, Kazakh, and Uigur, respectively. Eight mutations were detected from the 13 selected loci in 9880 meioses in kinship cases. These results indicate that this multiplex system may provide significant polymorphic information for kinship testing and relationship investigations., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We show that tourism activities severely impact the ecology of Orchid Island, its natural resources, and the culture of the Tao tribe. For example, highway widening, in response to the increased traffic volumes caused by tourism, required many Pandanus trees to be cut and removed, which has placed the coconut crabs in danger of extinction. To promote eco-tourism, observation trips to observe Elegant Scops owls and Birdwing butterflies have taken place, which has affected the breeding of these two protected species. The Elegant Scops owls- and Birdwing butterflies-related tourism activities also break the "evil spirits" taboo of the Tao people and have caused the disappearance of the specifications for using traditional natural resources, causing natural ecosystems to face the threat of excessive use. In addition to promoting and advocating aboriginal tourism of the Tao people on Orchid Island, the Taiwanese government should help the Tao people to develop a management model that combines traditional regulations and tourism activities.

The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci) provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST) and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu's inbred populations. Inbreeding values (FIS) show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE) or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates is required if discernible levels of co-ancestry exist. In the reference group, optimum assignment accuracy was achievable achieved through a combination of different markers by ranking the heterozygosity, FST and allelic number of close lineage populations.

Recombination fractions between forensic STRs can be extrapolated from the International HapMap Project, but the concordance between recombination fractions predicated from genetic maps and derived from observation of STR transmissions in families is still ambiguous for autosomal STRs because of limited family studies. Therefore, the main goal of this study is to compare recombination fractions estimated by pedigree analysis with those derived from HapMap phase SNP data. Genotypes of nine autosomal STR pairs (TPOX-D2S1772, D5S818-CSF1PO, D7S3048-D7S820, D8S1132-D8S1179, TH01-D11S2368, vWA-D12S391, D13S325-D13S317, D18S51-D18S1364, and D21S11-PentaD) from 207 two-generation families with two to five children (the number of families with five, four, three, and two children was 2, 3, 20, and 182, respectively) were used to analyze the recombination. The linkage analysis showed that significant linkage was observed at six STR pairs (D5S818-CSF1PO, D8S1132-D8S1179, TH01-D11S2368, vWA-D12S391, D13S325-D13S317, and D18S51-D18S1364) with genetic distances <36.22 cM in HapMap. Their recombination fractions calculated from family data were very close to those derived from HapMap. However, three STR pairs of TPOX-D2S1772, D7S3048-D7S820, and D21S11-PentaD showed no significant linkage with genetic distances from 43.38 to 91.49 cM. Our results indicate that recombination fractions extrapolated from HapMap can provide a substitute if empirical data are unavailable for the linkage STR pair with a genetic distance spanned <36.22 cM., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)