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Functional defecatory disorders (FDDs) are highly prevalent around the world. Biofeedback is an effective treatment for FDDs. Traditionally, this treatment is performed by clinicians in a limited number of hospitals because of procedure-related expenses and a need for a dedicated procedure room. To make the biofeedback therapy more widely available, we have designed a novel wireless, smartphone-based biofeedback device, with the ultimate goal of performing the therapy at home. The aim of this pilot study was to investigate whether the developed device can be employed to treat patients with FDDs in a clinical setting, prior to employing it in a home setting. From March 2018 to July 2018, we performed the biofeedback therapy using the newly developed wireless, smartphone-based device in patients with FDDs 30 min daily during weekdays for 2 weeks. A Visual Analogue Scale (VAS) for bowel satisfaction, Patient Assessment of Constipation‐Symptoms (PAC‐SYM), Patient Assessment of Constipation Quality of Life (PAC-QOL), and a balloon expulsion test were assessed at baseline and after the therapy. Thirteen patients were recruited and ten of them (mean age 70.3 ± 8.9 years, female:male ratio: 3:7) completed the study. Spontaneous bowel movements, complete spontaneous bowel movements, and VAS were all significantly increased after the therapy compared with baseline, respectively (6.5 ± 4.3 vs. 1.5 ± 2.2, p = 0.006; 3.1 ± 2.2 vs. 0.2 ± 0.6, p = 0.002; 49.5 ± 31.0 vs. 12.0 ± 9.2, p = 0.003). There was a significant decrease in the PAC-SYM and PAC-QoL after the biofeedback therapy (0.7 ± 0.6 vs. 1.4 ± 0.3, p = 0.001; 0.7 ± 0. 6 vs. 1.5 ± 0.4, p = 0.001). The therapy reduced the balloon expulsion time significantly (83.9 ± 68.8 s vs. 160.0 ± 36.7 s, p = 0.002). No obvious adverse events related to the procedure itself occurred. Biofeedback training using the newly developed wireless, smartphone-based device is feasible in the clinic setting, and it seems to be a promising method for improving constipation and related symptoms in patients with FDDs. These findings could be used to develop a much-needed, home-based, suitably powered, randomized, controlled clinical trial.

Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors in adults and has high mortality and relapse rates. Over the past few years, great advances have been made in the diagnosis and treatment of GBM, but unfortunately, the five-year overall survival rate of GBM patients is approximately 5.1%. Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) is a major oncogenic protein in tumors and can promote evil development of GBM. Snail1, a key inducer of the epithelial-mesenchymal transition (EMT) transcription factor, is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumors remains unclear. Our study aimed to investigate the mechanism of IKBKE regulating Snail1 in GBM. First, we analyzed the correlation between the expression of IKBKE and the tumor grade and prognosis through public databases and laboratory specimen libraries. Second, immunohistochemistry (IHC) and western blot were used to detect the correlation between IKBKE and Snail expression in glioma samples and cell lines. Western blot and immunofluorescence (IF) experiments were used to detect the quality and distribution of IKBKE and Snail1 proteins. Third, In situ animal model of intracranial glioma to detect the regulatory effect of IKBKE on intracranial tumors. In this study, Our study reveals a new connection between IKBKE and Snail1, where IKBKE can directly bind to Snail1, translocate Snail1 into the nucleus from the cytoplasm. Downregulation of IKBKE results in Snail1 destabilization and impairs the tumor cell migration and invasion capabilities. Our studies suggest that the IKBKE-Snail1 axis may serve as a potential therapeutic target for GBM treatment.

We aimed to evaluate the comparative effectiveness and applicability of using calf circumference (CC), strength, need for assistance with walking, rising from a sitting position, climbing stairs, and the incidence of falls (SARC-F), as well as SARC-F plus CC (SARC-CalF) and the Ishii test, for assessing sarcopenia in older adult nursing home occupants. In this cross-sectional study, the diagnostic criteria of the AWGS2019 were used as the standard, and the accuracy of the four screening methods determined by indicators, including sensitivity, specificity, receiver operating characteristic (ROC) curve, positive predictive values (PPV), and negative predictive values (NPV). One hundred and ninety-nine older adults, 97 male and 102 female, were included. The prevalence of sarcopenia was 48.7%. Over all the participants, the sensitivity and specificity of CC were 74.22% and 51.96%, respectively, and 40.21% and 83.33%, respectively, for SARC-F. The use of SARC-CalF raised the SARC-F sensitivity (71.14%) while reducing the specificity (60.78%). The Ishii test had a sensitivity of 89.7% and a specificity of 74.51%. The PPV and NPV of CC, SARC-F, SARC-CalF, Ishii test were 0.6/0.68, 0.7/0.59, 0.55/0.63, and 0.77/0.88, respectively. The areas under the curve for CC, SARC-F, SARC-CalF, and the Ishii test were 0.67(95%CI, 0.59–0.74), 0.71(95%CI, 0.64–0.79), 0.71(95%CI, 0.64–0.79), and 0.86 (95% CI,0.81–0.92), respectively. The sensitivity and specificity of CC, SARC-F, SARC-CalF, and the Ishii test for sarcopenia screening in males were 71.69%/56.41%, 29.31%/79.49%, 67.24%/64.10%, and 94.83%/56.41%, respectively, and in females were 79.49%/49.21%, 56.41%/85.71%, 76.92%/58.73%, and 82.05%/85.71%, respectively. The PPV and NPV of CC, SARC-F, SARC-CalF, and the Ishii test in males were 0.71/0.56, 0.68/0.43, 0.74/0.57, and 0.76/0.88, respectively, while in females the values were 0.49/0.79, 0.71/0.76, 0.54/0.8, and 0.78/0.89, respectively. The areas under the curve for CC, SARC-F, SARC-CalF, and the Ishii test in males were 0.7(95%CI, 0.59–0.8), 0.63(95%CI, 0.52–0.75), 0.68(95%CI, 0.57–0.8), and 0.86(95% CI, 0.78–0.94), respectively, and in females 0.69(95%CI, 0.58–0.8), 0.81(95%CI, 0.72–0.89), 0.76(95%CI, 0.67–0.86), and 0.85 (95%CI, 0.77–0.94), respectively. The overall screening ability of the Ishii test for sarcopenia was superior to that of the CC, SARC-F, and SARC-CalF in older adults in nursing homes.

Microribonucleic acids (miRNAs) are small non-coding ribonucleic acids (ncRNAs), which can affect recognition of homologous sequences and interfere with transcription. It plays key roles in the initiation, development, resistance, metastasis or recurrence of cancers. Identifying circulatory indicators will positively improve the prognosis and quality of life of patients with early cancer. Previous studies have shown that miRNA is highly involved in cancer. In addition, miRNA derived from cancers can be encapsulated as exosomes and further extracted into circulatory systems to realize malignant functions. It indicates that circulating exosome-derived miRNAs have the potential to replace conventional biomarkers as cancer derived exosomes carrying miRNAs can be identified by specific markers and might be more stable and accurate for early diagnosis.

Purpose Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. Methods In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. Findings After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC0–∞ and Cmax were 1200 (274) h · ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h · ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of Cmax, AUC0–t, and AUC0–∞ were 64% (54%–76%), 80% (76%–85%), and 80% (76%–85%), respectively. The median (range) Tmax was prolonged from 1.5 (1–3) hours in the fasted condition to 2 (1.5–6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. Implications In the present study, the consumption of a high-fat meal prior to henagliflozin administration was associated with reductions in AUC0–∞ and Cmax of 19.4% and 36.4%, respectively. However, based on the analysis of the pharmacokinetic/pharmacodynamic findings on henagliflozin, this slight change may not have clinical significance. Mass balance of henagliflozin in humans was achieved with ∼75% of the administered dose recovered in excretions within 4 days after administration whether in the fasted or fed state. These findings suggest that henagliflozin tablets can be administered with or without food.

Summary A best evidence topic was written according to a structured protocol. The question addressed was: ‘Does continuation of antifibrotics before lung transplantation (LTx) influence post-transplant outcomes in patients with idiopathic pulmonary fibrosis (IPF) with regard to mortality, bronchial anastomotic dehiscence, reoperation for bleeding and wound complications, primary graft dysfunction or longer-term survival and allograft rejection?’ A total of 261 articles were found using the reported search strategy, of which 7 represented the best evidence to answer the clinical question. Six out of 7 studies demonstrated equivalent post-transplant survival among IPF patients on antifibrotics before LTx compared with controls. Five out of 6 studies showed no increase in the risk of major bleeding, wound or bronchial anastomotic complications. One bi-institutional study found a higher incidence of early bronchial anastomotic dehiscence, but this difference was not statistically significant after longer term follow-up. In a study that only included IPF patients who underwent single LTx, a lower incidence of grade 3 primary graft dysfunction was reported in the antifibrotic group compared with controls. Overall, to date, only small (N, A best evidence topic was constructed according to a structured protocol.

Demographic and clinical findings of patients with mucocutaneous morphea have not been well characterized, to our knowledge.To determine the demographic and clinical characteristics of morphea patients with mucocutaneous lesions who were enrolled in the Morphea in Adults and Children cohort.Cross-sectional study of 735 patients in the Morphea in Adults and Children cohort from 2007 to 2018.A total of 4.6% of linear morphea patients had oral involvement versus 2.4% among the entire cohort, whereas 10.3% of generalized morphea patients had genital involvement versus 3.7% among the entire cohort. Patients with genital lesions were older at disease onset than those with oral morphea (57 versus 11.5 years; P .001) and had more frequent extragenital lichen sclerosus et atrophicus (59.2% versus 5.6%; P = .004).Selection bias and limited number of affected subjects.Oral morphea lesions predominate in younger patients with facial linear morphea, whereas genital lesions predominate in postmenopausal women with overlying extragenital lichen sclerosus et atrophicus.

The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.

Objective In response to COVID-19, the informatics community united to aggregate as much clinical data as possible to characterize this new disease and reduce its impact through collaborative analytics. The National COVID Cohort Collaborative (N3C) is now the largest publicly available HIPAA limited dataset in US history with over 6.4 million patients and is a testament to a partnership of over 100 organizations. Materials and Methods We developed a pipeline for ingesting, harmonizing, and centralizing data from 56 contributing data partners using 4 federated Common Data Models. N3C data quality (DQ) review involves both automated and manual procedures. In the process, several DQ heuristics were discovered in our centralized context, both within the pipeline and during downstream project-based analysis. Feedback to the sites led to many local and centralized DQ improvements. Results Beyond well-recognized DQ findings, we discovered 15 heuristics relating to source Common Data Model conformance, demographics, COVID tests, conditions, encounters, measurements, observations, coding completeness, and fitness for use. Of 56 sites, 37 sites (66%) demonstrated issues through these heuristics. These 37 sites demonstrated improvement after receiving feedback. Discussion We encountered site-to-site differences in DQ which would have been challenging to discover using federated checks alone. We have demonstrated that centralized DQ benchmarking reveals unique opportunities for DQ improvement that will support improved research analytics locally and in aggregate. Conclusion By combining rapid, continual assessment of DQ with a large volume of multisite data, it is possible to support more nuanced scientific questions with the scale and rigor that they require.

Objective To determine the prevalence, risk factors and burden of symptomatic pelvic organ prolapse (POP) in adult Chinese women. Design A nationwide cross‐sectional study. Setting Six geographic regions of mainland China. Participants Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method from February 2014 through March 2016. Methods We conducted a nationwide epidemiological survey. ‘Symptomatic POP’ was determined by a screening questionnaire and physical examination. Main outcome measurements Prevalence, odds ratio (OR). Results A total of 55 477 women (response rate, 92.5%; mean age, 45.1 years old) were included. The prevalence of symptomatic POP was 9.6% (95% CI 9.3–9.8%) and it increased with age in each stage (P 50 vs 20‐29 years old in symptomatic POP‐Q stage II or higher, OR increased from 1.34 [95% CI 1.32–1.45] to 7.34 [95% CI 4.34–12.41]) and multiple vaginal deliveries (multiparous [≥3] vs nulliparous in symptomatic POP‐Q stage II or higher, OR increased from 1.91 [1.71–2.13] to 2.78 [2.13–3.64]). Conclusions We found a lower prevalence of symptomatic POP than that found in other surveys. The main type of symptomatic POP was anterior compartment prolapse, indicating that it should be considered first. Older age and multiple vaginal deliveries increased the odds of each type of symptomatic POP. Tweetable abstract The prevalence of female symptomatic pelvic organ prolapse (POP) was 9.6% in China. It is related to old age and multiple vaginal deliveries., Tweetable abstract The prevalence of female symptomatic pelvic organ prolapse (POP) was 9.6% in China. It is related to old age and multiple vaginal deliveries.

Joint denervation has been proposed as a less invasive option for surgical management of hand arthritis that preserves joint anatomy while treating pain and decreasing postoperative recovery times. The purpose of this systematic review was to investigate the efficacy and safety of surgical joint denervation for osteoarthritis in the joints of the hand. EMBASE, MEDLINE, and PubMed databases were searched from January 2000 to March 2019. Studies of adult patients with rheumatoid arthritis or osteoarthritis of the hand who underwent joint denervation surgery were included. Two reviewers performed the screening process, data abstraction, and risk of bias assessment (Methodological Index for Non-Randomized Studies). This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO (#125811). Ten studies were included, 9 case series and 1 cohort study, with a total of 192 patients. In all studies, joint denervation improved pain and hand function at follow-up (M = 36.8 months, range = 3-90 months). Pooled analysis of 3 studies on the first carpometacarpal joint showed a statistically significant ( P < .001) reduction in pain scores from baseline (M = 6.61 ± 2.03) to postoperatively (M = 1.69 ± 1.27). The combined complication rate was 18.8% (n = 36 of 192), with neuropathic pain or unintended sensory loss (8.8%, n = 17 of 192) being the most common. This review suggests that denervation may be an effective and low-morbidity procedure for treating arthritis of the hand. Prospective, comparative studies are required to further understand the outcomes of denervation compared with traditional surgical interventions.

Background: Targeted therapies have largely improved prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Yet, disease can still progress rapidly for some patients in the first two years after diagnosis. Our study aimed to establish a nomogram model to predict 2-year breast cancer-specific survival (BCSS) in early HER2-positive breast cancer patients. Patients and Methods: A total of 32,481 HER2-positive patients derived from Surveillance, Epidemiology, and End Results (SEER) database were included in the construction of nomogram. Concordance index (C-index) and calibration curve were used to evaluate the discrimination ability and predictive accuracy. We also tested the model in 804 patients from Shanghai Jiao Tong University Breast Cancer Data Base (SJTU-BCDB).Results: Age, estrogen receptor (ER) status, progesterone receptor (PR) status, histologic type, T stage and N stage were selected to construct the nomogram according to multivariable analysis. The 2-year BCSS rate was 95% and 60% for patients at low risk (13 scores) respectively. The C-index of model derived from SEER database is 0.81 (95%CI 0.79-0.83). Sensitivity analysis was performed in patients undergoing breast surgeries with the C-index of 0.81 (95%CI 0.79-0.83). Validation in 804 patients from SJTU-BCDB showed respective C-index of 0.77 (95%CI, 0.62-0.92) in total population, 0.67 (95%CI 0.44-0.90) in patients receiving anti-HER2 therapy and 0.90 (95%CI 0.81-0.90) in those without targeted therapy.Conclusions: The novel nomogram can predict 2-year survival outcome in HER2-positive patients independent of receiving anti-HER2 therapy or not and help clinicians to adjust therapeutic strategies for those patients with higher risk. Citation Format: Li Zhu, Mengdi Chen, Jiayi Wu. A novel prognostic nomogram for 2-year survival in HER2-positive patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-39.

Background: The association between 21-gene recurrence score (RS) and host factors such as overweight remains unclear for breast cancer patients. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic predictive value of RS between overweight or non-overweight patients.Patients and methods: Luminal-like patients receiving surgery between January 2009 and December 2018 in the Comprehensive Breast Health Center, Shanghai Ruijin Hospital, with 21-gene RS results were retrospectively retrieved. Association and subgroup analysis between BMI and 21-gene RS were conducted. Single-gene expression in 21-gene RS panel was compared between overweight and non-overweight groups. Recurrence-free survival (RFS) and overall survival (OS) were calculated according to RS category and BMI status.Results: Among 1876 patients included, 442 (23.56%), 995 (53.04%) and 439 (23.40%) were classified into low, intermediate and high risk groups. RS category was significantly differently distributed between overweight and non-overweight patients (P=0.035). Overweight patients had a trend of lower RS score than patients with normal weight (25.13 vs 26.17, P=0.080). The effect of BMI on RS significantly varied according to age (P=0.012) and menstruation status (P Citation Format: Yiwei Tong, Weiqi Gao, Jiayi Wu, Siji Zhu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Xiaosong Chen. Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-38.

Background Alflutinib is a novel irreversible and highly selective third-generation EGFR inhibitor currently being developed for the treatment of non-small cell lung cancer patients with activating EGFR mutations and EGFR T790M drug-resistant mutation. Alflutinib is mainly metabolized via CYP3A4 to form its active metabolite AST5902. Both alflutinib and AST5902 contribute to the in vivo pharmacological activity. The aim of this study was to investigate the effects of rifampicin (a strong CYP3A4 inducer) on the pharmacokinetics of alflutinib and AST5902 in healthy volunteers, thus providing important information for drug-drug interaction evaluation and guiding clinical usage. Methods This study was designed as a single-center, open-label, and single-sequence trial over two periods. The volunteers received a single dose of 80 mg alflutinib on Day 1/22 and continuous doses of 0.6 g rifampicin on Day 15–30. Blood sampling was conducted on Day 1–10 and Day 22–31. The pharmacokinetics of alflutinib, AST5902, and the total active ingredients (alflutinib and AST5902) with or without rifampicin co-administration were respectively analyzed. Results Co-administration with rifampicin led to 86% and 60% decreases in alflutinib AUC0-∞ and Cmax, respectively, as well as 17% decrease in AST5902 AUC0-∞ and 1.09-fold increase in AST5902 Cmax. The total active ingredients (alflutinib and AST5902) exhibited 62% and 39% decreases in AUC0-∞ and Cmax, respectively. Conclusions As a strong CYP3A4 inducer, rifampicin exerted significant effects on the pharmacokinetics of alflutinib and the total active ingredients (alflutinib and AST5902). The results suggested that concomitant strong CYP3A4 inducers should be avoided during alflutinib treatment. This trial was registered at http://www.chinadrugtrials.org.cn . The registration No. is CTR20191562, and the date of registration is 2019-09-12.

CT-guided treatment delivery can improve target localization in mediastinal lymphoma patients treated with "butterfly" intensity-modulated radiotherapy and deep-inspiration breath hold. Although daily CT imaging adds additional radiation exposure, its use may be justified given the greater normal tissue sparing enabled by PTV margin reduction.

AIM To investigate whether mono-exponential and bi-exponential diffusion-weighted imaging (DWI)-related parameters of the primary tumour can evaluate the status of lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) in patients with cervical carcinoma preoperatively. MATERIALS AND METHODS Eighty patients with cervical carcinoma were enrolled, who underwent preoperative multi b-value DWI and radical hysterectomy. They were classified into LVSI(+) versus LVSI(–) and LNM(+) versus LNM(–) according to postoperative pathology. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) were calculated from the whole tumour (_whole) and tumour margin (_margin). All parameters were compared between LVSI(+) and LVSI(–) and between LNM(+) and LNM(–). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic performance of these parameters. RESULTS f_margin and D∗_whole showed significant differences in differentiating LVSI(+) from LVSI(–) tumours (p=0.002, 0.008, respectively), while LNM(+) tumours presented with significantly higher ADC_margin than that of LNM(–) tumours (p=0.009). The other parameters were not independent related factors with the status of LVSI or LNM according to logistic regression analysis (p>0.05). The area under the ROC curve of f_margin combined with D∗_whole in discriminating LVSI(+) from LVSI(–) was 0.826 (95% confidence interval [CI]: 0.691–0.961), while ADC_margin in differentiating LNM(+) from LNM(–) was 0.788 (95% CI: 0.648–0.928). CONCLUSIONS The parameters generated from mono-exponential and bi-exponential DWI of the primary cervical carcinoma could help discriminate its status regarding LVSI (f_margin and D∗_whole) and LNM (ADC_margin).

Objective To study the relationship between various electrodiagnostic modalities in acute facial palsy. Setting Academic tertiary care center. Patients One‐hundred and six patients who presented with traumatic or non‐traumatic acute facial paralysis (House‐Brackmann, HB, grade 6/6) between 2008 and 2017 and underwent acute electrodiagnostic testing. Intervention Electroneurography (ENoG) using nasolabial fold (NLF) or nasalis muscle (NM) methods, and volitional electromyography (EMG) in all patients. Main outcome measures Percent degeneration of ipsilateral facial nerve compound muscle action potentials (CMAP) on NLF‐ and NM‐ENoG, presence or absence of muscle unit potentials (MUPs) on EMG. Results Extent of facial nerve degeneration measured by NLF‐ and NM‐ENoG were highly correlated (r = 0.85, P, This is an original study that defines outcomes for electrodiagnostic testing in acute facial palsy and compares two methods. Electrodiagnostic testing is often used by clinicians to prognosticate outcomes for patients with acute facial palsy and determine candidacy for facial nerve decompression. This study describes one of the largest cohorts of patients to date with acute facial paralysis (House‐Brackmann 6/6) and detailed electrodiagnostic testing, consisting of two methods of electroneurography (ENoG) and electromyography (EMG).

Background and purpose Apatinib is a small-molecule tyrosine kinase inhibitor for the treatment of recurrent or progressive advanced-stage gastric adenocarcinoma or gastroesophageal junction cancer. The in vitro inhibition studies suggested that apatinib exerted potent inhibition on CYP3A4 and CYP2C9. To evaluate the potential of apatinib as a perpetrator in CYP450-based drug-drug interactions in vivo, nifedipine and warfarin were, respectively, selected in the present study as the probe substrates of CYP3A4 and CYP2C9 for clinical drug-drug interaction studies. Since hypertension and thrombus are common adverse effects of vascular targeting anticancer agents, nifedipine and warfarin are usually coadministered with apatinib in clinical practice. Methods A single-center, open-label, single-arm, and self-controlled trial was conducted in patients with advanced solid tumors. The patients received a single dose of 30 mg nifedipine on Day 1/14 and a single dose of 3 mg warfarin on Day 3/16. On Day 9-21, the subjects received a daily dose of 750 mg apatinib, respectively. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, respectively, investigated. Results Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC0-48h and Cmax of nifedipine by 83% (90% confidence interval [CI] 1.46-2.31) and 64% (90% CI 1.34-2.01), respectively. Similarly, coadministration with apatinib contributed to the significant increases of AUC0-t and Cmax of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), respectively. Conclusion Concomitant apatinib administration resulted in significant increases in systemic exposure to nifedipine and S-warfarin. Owing to the risk of pharmacokinetic drug-drug interactions based on CYP3A4/CYP2C9 inhibition by apatinib, caution is advised in the concurrent use of apatinib with either CYP2C9 or CYP3A4 substrates.

Ferroelectrics exhibit polarization tunable resistance switching behaviors, which are promising for next-generation non-volatile memory devices. For technological applications, thinner nanoscale arrays are expected, which feature with higher density and larger ON/OFF (RON/OFF) ratios in the metal/ferroelectrics/semiconductor heterojunction. Here, we acquire high density BiFeO3 (BFO) nano-islands around 10 nm in thickness displaying a high RON/OFF ratio of 103, comparable to the tunnel junctions. Moreover, both the macroscopic and microscopic resistive switching behaviors of the present BiFeO3 films reveal an unexpected the filamentary-type resistive switching which is modified by the charged domain walls in nano-islands dominated by the center-type domains. Particularly, the charged domain walls spontaneously formed within the BFO nano-islands are proposed as the conductive paths based on the redistribution of carriers under the applied voltages. Potential applications for memories with large RON/OFF ratios of such kind of configurable charged domain walls are demonstrated.

Based on the basic theories of Poole Frenkel (P-F) emission, Fowler Nordheim (F-N) tunnel and Ohmic transport models, the linear relationship between breakdown voltage (BV) and leakage, I-V and accelerated stress test (AST) characteristics of a-Si dielectric layers are analyzed by the manufactured metal-to-metal (MTM) anti-fuse cells in details. The effects of different ion implant conditions on the amorphization degree of a-Si films are characterized by X-Ray diffraction (XRD). Meanwhile, the influence of annealing and ion implant process on the electrical properties of a-Si thin films are studied. Lastly, it is found that the implantation of E15 Si, Ar and SiF3 ions can promote the further amorphization of a-Si films, effectively improve the BV uniformity, reduce the leakage current and enhance the reliability of MTM anti-fuse cells. Especially, SiF3 ion implantation can reduce the leakage current of MTM anti-fuse cells by two orders of magnitude, which is mainly attributed to a-Si conductive band being greatly elevated by strong negative F ions, and it results in the increase of the potential barrier of a-Si/metal interface. Therefore, it can be further proved that SiF3 ion implant process may promote modification of a-Si films.

Aims Dysfunctional innate immune function and inflammation contributes to the pathogenesis of obesity-associated hypertension, in which macrophage infiltration in the perivascular adipose tissue (PVAT) plays a key role. However, the mechanisms behind it are not well understood. Class A1 scavenger receptor (SR-A1) is one of the major pattern recognition receptors in modulating macrophage activity, and here, we aimed to investigate its role in obesity-associated hypertension. Methods and results Both diet-induced and genetic obesity were generated in mice. Deficiency in SR-A1 aggravated the obesity-induced blood pressure (BP) elevation and endothelial dysfunction in mice. The BP-elevating effect of SR-A1 deficiency was blocked by the down-regulation of vascular endothelial growth factor B (VEGF-B) in obese mice. Overexpression of VEGF-B raised BP in the obese mice but not in normal mice. Administration of fucoidan, a ligand of SR-A1, lowered BP, and VEGF-B levels in Sr-a1+/+ but not in Sr-a1−/− obese mice. Conclusion These results reveal a new link between PVAT and vascular biology in obesity orchestrated by the SR-A1/VEGF-B axis in macrophages. SR-A1 and VEGF-B may be promising therapeutic targets in the treatment of obesity-associated hypertension.

Bioinspired electronics are rapidly promoting advances in artificial intelligence. Emerging AI applications, e.g., autopilot and robotics, increasingly spur the development of power devices with new forms. Here, we present a strain-controlled power device that can directly modulate the output power responses to external strain at a rapid speed, as inspired by human reflex. By using the cantilever-structured AlGaN/AlN/GaN-based high electron mobility transistor, the device can control significant output power modulation (2.30–2.72 × 103 W cm−2) with weak mechanical stimuli (0–16 mN) at a gate bias of 1 V. We further demonstrate the acceleration-feedback-controlled power application, and prove that the output power can be effectively adjusted at real-time in response to acceleration changes, i.e., ▵P of 72.78–132.89 W cm−2 at an acceleration of 1–5 G at a supply voltage of 15 V. Looking forward, the device will have great significance in a wide range of AI applications, including autopilot, robotics, and human-machine interfaces., Designing intelligent power devices that can directly control the output power modulation responses to external stimuli at a rapid speed remains a challenge. Here, the authors report a strain-controlled power device by using the cantilever-structured AlGaN/AlN/GaN HEMT to emulate human reflex process.

BACKGROUND The diagnosis of brain metastasis involves high morbidity and mortality and remains an unmet clinical need in spite of being the most common tumor in the brain. Exclusion of these cancer patients from clinical trials is a major cause of their limited therapeutic options. MATERIAL AND METHODS We report a novel drug-screening platform (METPlatform) based on organotypic cultures which allows identifying effective anti-metastasis agents in the presence of the organ microenvironment. We have applied this approach to clinically relevant stages of brain metastasis using both experimental models and human tumor tissue (by performing patient-derived organotypic cultures - PDOCs -). We have also used METPlatform to perform unbiased proteomics of brain metastases in situ to identify potential novel mediators of this disease and explore resistance mechanisms to targeted therapy. Finally, we have exploited METPlatform as “avatars” to predict response to therapy in patients with primary brain tumors. RESULTS We identified heat shock protein 90 (HSP90) as a promising therapeutic target for brain metastasis. DEBIO-0932, a blood-brain barrier permeable HSP90 inhibitor, shows high potency against mouse and human brain metastases from different primary origin and oncogenomic profile at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis of brain metastases treated with the chaperone inhibitor revealed non-canonical clients of HSP90 as potential novel mediators of brain metastasis and actionable mechanisms of resistance driven by autophagy. Combined therapy using HSP90 and autophagy inhibitors showed synergistic effects compared to sublethal concentrations of each monotherapy, demonstrating the potential of METPlatform to design and test rationale combination therapies to target metastasis more effectively. Finally, we show that brain tumor PDOCs predict the response of the corresponding patient to standard of care, thus proving the potential of METPlatform for improving personalized care in cancer. CONCLUSION Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples and questions the rationale of excluding patients with brain metastasis from clinical trials. We envision that METPlatform will be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.

We describe a patient who presented with erythematous papules and hair loss solely limited to the eyebrows. Clinicians should be aware of this presentation of leukemia cutis and consider this diagnosis in a patient with a history of CLL.

The clinical features and patient impact of morphea, an inflammatory disorder of the skin and soft tissue, remain poorly characterized. While numerous clinical classification schemes are in use, there is little work systematically examining latent clinical and quality of life features within these clinical subtypes. In an effort to address this gap, prior work from our group revealed that the Padua Criteria performed best in grouping patients into consistent subtypes, however we did not perform in depth analysis of subsets that may exist within these subtypes.

OBJECTIVE To estimate the incidence of urinary incontinence (UI), including its subtypes stress UI (SUI), urgency UI (UUI) and mixed UI (MUI), and to examine risk factors for de novo SUI and UUI in Chinese women. DESIGN Nationwide longitudinal study. SETTING Six geographic regions of China. PARTICIPANTS Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method. METHODS This study was conducted between May 2014 and March 2016, with follow up in 2018. Data on demographics, medical history, lifestyle and physiological and anthropometric information were collected. MAIN OUTCOME MEASUREMENTS Incidence, rate ratio (RR). RESULTS Analyses included 24 985 women (mean age 41.9 years).The follow-up response rate was 55.5%, median follow-up time was 3.7 years. The standardised incidences of UI, SUI, UUI and MUI were 21.2, 13.1, 3.0 and 5.1 per 1000 person-years, respectively. Risk factors for de novo SUI included delivery pattern (vaginal spontaneous delivery RR 2.12, 95% CI 1.62-2.78 and instrumental delivery RR 3.30, 95% CI 1.99-5.45), high body mass index (BMI) (overweight RR 1.52, 95% CI 1.33-1.74 and obesity RR 1.67, 95% CI 1.32-2.11), cigarette smoking (RR 1.54, 95% CI 1.12-2.12), chronic cough (RR 1.44, 95% CI 1.17-1.76), diabetes (RR 1.33, 95% CI 1.10-1.60) and older age (50-59 years RR 1.49, 95% CI 1.16-1.90 and 60-69 years RR 1.61, 95% CI 1.22-2.13).The risk factors significantly associated with de novo UUI were age (RR increased from 1.21, 95% CI 0.74-1.99, at 30-39 years to 6.3, 95% CI 3.85-10.30, at >70 years) and diabetes (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS The incidence of female UI is 21.2 per 1000 person-years in China. Delivery (vaginal spontaneous delivery, instrumental delivery), high BMI, cigarette smoking, chronic cough, diabetes and older age were risk factors. TWEETABLE ABSTRACT The incidence of female urinary incontinence was 21.2 per 1000 person-years in China. Delivery, BMI, diabetes and old age are risk factors.

The National Geomatics Atlas is the first volume of the new century edition of the National Huge Atlas of the People's Republic of China, and is one of the important achievements of this research and development project. The National Geomatics Atlas consists of four thematic map groups and one place name index, such as the sequence map group, the political terrain map group, the land cover map group and the city map group. The research object of this paper is the thematic maps, which are mainly distributed in the sequence map group, the land cover map group and the city map group. This paper is aimed at the design and compilation of thematic maps, including a brief introduction of thematic maps selection, layout design, thematic map technical process, and thematic symbol design.

INTRODUCTION Noise oversensing encountered in patients with Abbott Tendril leads in our hospital triggered an internal investigation. METHODS We retrospectively analyzed patients with a Tendril lead model 1688, 1788, 1888, and 2088. Most leads were connected to Abbott generators. To exclude a primary generator issue as the cause of noise oversensing, we enrolled a cohort of patients in whom Medtronic CapSureFix leads model 4076 and 5076 were prospectively connected to similar Abbott generators. RESULTS A total of 1063 Tendril leads were implanted in 869 patients. Noise was encountered in 66 leads (6.2%) during a follow-up of 3.9 years. Most affected leads had normal impedance and only a few of these patients were symptomatic. Reprogramming was attempted in 44 of 66 (67%), and reduced oversensing in 34 of 44 (77%) of these patients. Seventeen malfunctioning leads (1.5%) were replaced, including 16 of 66 (24%) of those with noise. Of the four leads with noise extracted and returned to the manufacturer, lead to device abrasion was identified in two and inner insulation breach in one. None of the 145 Medtronic CapSureFix leads connected to Abbott generators had noise during a follow-up of 3.6 years. CONCLUSION Noise oversensing was relatively common in Tendril leads, but was not detected in Medtronic leads despite connecting to Abbott generators. Although the majority of the affected leads did not show abnormal impedance, outer or inner insulation breach was identified in three of the four returned leads. As patients with affected leads are generally asymptomatic, most of them can be managed conservatively.

Although Sn-Pb perovskites sensing near-ultraviolet-visible-near-infrared light could be an attractive alternative to silicon in photodiodes and imaging, there have been no clear studies on such devices constructed on metal/silicon substrates, hindering their direct integration with complementary metal-oxide semiconductor (CMOS) and silicon electronics. Typically, high surface roughness and severe pinholes of Sn-rich binary perovskites make it difficult for them to fulfill the requirements of efficient photodiodes and imaging. These issues cause inherently high dark current and poor (dark and photo-) current uniformity. Herein, we propose and demonstrate the room-temperature crystallization in the Sn-rich binary perovskite system to effectively control film crystallization kinetics. With experimental and theoretical studies of the crystallization mechanism, we successfully tune the density and location of nanocrystals in precursor films to achieve compact nanocrystals, which coalesce into high-quality (smooth, dense, and pinhole-free) perovskites with intensified preferred orientation and decreased trap density. The high-quality perovskites reduce dark current and improve (dark and photo-) current uniformity of perovskite photodiodes on CMOS-compatible metal/silicon substrates. Meanwhile, self-powered devices achieve a high responsivity of 0.2 A/W at 940 nm, a large dynamic range of 100 dB, and a fast fall time of 2.27 μs, exceeding those of most silicon-based imaging sensors. Finally, a 6 × 6 pixel integrated photodiode array is successfully demonstrated to realize the imaging application. The work contributes to understanding the fundamentals of the crystallization of Sn-rich binary perovskites and advancing perovskite integration with Si-based electronics.

The rapid development of 3D laser scanning and 3D printing technology provides new technologies and ideas for cultural relic protection and reproduction. Aiming at the requirement of equal proportional reproduction of large-scale grottoes, this paper takes the point cloud data of the 18th Cave of Yungang Grottoes obtained by 3D laser scanning as an example, and proposes a data processing and reproduction block partitioning method for equal proportion reproduction. The Cyclone, Geomagic and AutoCAD software were used to construct the 3D model of the grotto, and the 3D printing technology was used to realize the secondary design and model print. Among them, the research focuses on the modeling of massive point clouds and the method of model partitioning based on voxels. It can meet the requirements of movable and assembly while realizing the equal proportional reproduction of the whole grotto. The research results and application can be a good reference for the future grotto reproduction work.

Proper function of pharyngeal dilator muscles, including the genioglossus muscle of the tongue, is required to maintain upper airway patency. During sleep, the activity of these muscles is suppressed, and as a result individuals with obstructive sleep apnea experience repeated episodes of upper airway closure when they are asleep, in particular during rapid-eye-movement (REM) sleep. Blocking cholinergic transmission in the hypoglossal motor nucleus (MoXII) restores REM sleep genioglossus activity, highlighting the importance of cholinergic transmission in the inhibition of hypoglossal motor neurons (HMNs) during REM sleep. Glutamatergic afferent input from neurons in the parahypoglossal (PH) region to the HMNs is critical for MoXII respiratory motor output. We hypothesized that state-dependent cholinergic regulation may be mediated by this pathway. Here we studied the effects of cholinergic transmission in HMNs in adult male and female mice using patch-clamp recordings in brain slices. Using channelrhodopsin-2-assisted circuit mapping, we first demonstrated that PH glutamatergic neurons directly and robustly activate HMNs (PHGlut→ HMNs). We then show that carbachol consistently depresses this input and that this effect is presynaptic. Additionally, carbachol directly affects HMNs by a variable combination of muscarinic-mediated excitatory and inhibitory responses. Altogether, our results suggest that cholinergic signaling impairs upper airway dilator muscle activity by suppressing glutamatergic input from PH premotoneurons to HMNs and by directly inhibiting HMNs. Our findings highlight the complexity of cholinergic control of HMNs at both the presynaptic and postsynaptic levels and provide a possible mechanism for REM sleep suppression of upper airway muscle activity.SIGNIFICANCE STATEMENTIndividuals with obstructive sleep apnea can breathe adequately when awake but experience repeated episodes of upper airway closure when asleep, in particular during REM sleep. Similar to skeletal postural muscles, pharyngeal dilator muscles responsible for maintaining an open upper airway become hypotonic during REM sleep. Unlike spinal motoneurons controlling postural muscles that are inhibited by glycinergic transmission during REM sleep, hypoglossal motoneurons that control the upper airway muscles are inhibited in REM sleep by the combination of monoaminergic disfacilitation and cholinergic inhibition. In this study, we demonstrated how cholinergic signaling inhibits hypoglossal motoneurons through presynaptic and postsynaptic muscarinic receptors. Our results provide a potential mechanism for upper airway hypotonia during REM sleep.

This paper presents a study on the stability of a mine entry of an innovative approach to non-pillar coal mining—gob-side entry retaining using cantilever beam theory (GERMC). This method is on the rise in China and it has shown to increase the coal seam rate of recycling and mining productivity. The method utilizes the caved-in material resulting from the mining activities to fill the gob area and ensure the stability of the roof of the already mined area. The caved-in material will form the gob-side wall of the retained entry. This characteristic is unique to this method. Thus, there are not many studies that analyze the stability of the filling material and of the gob-side entry wall under these circumstances, which is a vital element for the safety of the mining operations. This paper studies the stability of the gob-side retained entry of the Hongjingta underground coal mine in China. The authors perform the analysis using a discrete fracture network (DFN) model developed by the Massachusetts Institute of Technology (MIT), GEOFRAC, in combination with the discrete-element method (DEM) software UDEC. GEOFRAC estimates the rock blocks (fracture networks) in the filling body, from fracture traces measured along the gob-side wall of the entry. Statistical methods are used to estimate the fracture intensity and the mean fracture areas, which are inputs to the DFN. The generated fracture networks are then inputted into the DEM code, UDEC, to evaluate the stability of the mine-retained entry. For this study, we developed two types of models in UDEC, one considering the fractures generated by the DFN model and another considering the gob-filling material as a continuum. This methodology—combined DFN–DEM—is unique and provides a more realistic representation of the gob-filling material by considering the fractures in the filling body and by estimating those fractures (interfaces between rock blocks) using field data. In addition to this, we also considered the effects of uncertainties that are associated with estimating three-dimensional (3-D) fractures’ networks/rock blocks from two-dimensional (2-D) field data. Finally, the results of the simulations were compared with the measurements from the mine and are in good agreement.

On space remote sensing stereo mapping field, the angle variation between the star sensor’s optical axis and the earth observation camera’s optical axis on-orbit affects the positioning accuracy, when optical mapping is without ground control points (GCPs). This work analyses the formation factors and elimination methods for both the star sensor’s error and the angles error between the star sensor’s optical axis and the earth observation camera’s optical axis. Based on that, to improve the low attitude stability and long calibration time necessary of current satellite cameras, a method is then proposed for real-time on-orbit calibration of the angles between star sensor’s optical axis and the earth observation camera’s optical axis based on the principle of auto-collimation. This method is experimentally verified to realize real-time on-orbit autonomous calibration of the angles between the star sensor’s optical axis and the earth observation camera’s optical axis.

Although it has been well established that G protein plays pivotal roles in physiologic or pathologic conditions, including cancer formation, its role in breast cancer, especially specific subunits, remains largely unknown. Our work aimed to evaluate the correlation of the G protein alpha subunit (GNAS) with breast cancer and to investigate the underlying molecular mechanism. The expression of GNAS was determined by breast tumor tissue microarray of 150 patients with complete follow-up information. The correlation between GNAS expression and clinical features was assessed. CCK8, EdU incorporation, flow cytometry, wound healing, transwell, western blot and tumor formation assays were carried out in nude mice to study the biological function of GNAS and the underlying molecular mechanism in breast cancer by silencing GNAS using a specific siRNA. High GNAS expression showed a close correlation with a reduced overall survival (p = 0.021), frequent distal metastasis (p = 0.026), advanced clinical stage (p = 0.001), stronger cell proliferation (ki67+ positive cell rate, p = 0.0351) and enhanced cancer cell migration, which was further confirmed by in vitro and in vivo assays and might be dependent on the PI3K/AKT/Snail1/E-cadherin axis. The data suggested that GNAS promoted breast cancer cell proliferation and migration (EMT) through the PI3K/AKT/Snail1/E-cadherin signaling pathway. These findings also indicate that GNAS can serve as a potential prognostic indicator and novel therapeutic target in breast cancer.

Background The comparison between relatively intact nanoscale extracellular vesicle-derived DNA (nEV-DNA) and fragmented circulating cell-free DNA (cfDNA) in mutation detection among patients with non-small-cell lung cancer (NSCLC) has not been carried out yet, and thus deserves investigation. Patients and methods Both nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFRE19del/T790M/L858R mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR). Results Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity. Conclusions nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.

Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs and has significant clinical sequelae. Management of SSc cutaneous disease remains challenging and often is driven by extracutaneous manifestations. Methotrexate is the typical first-line therapy for patients with early progressive cutaneous disease. However, in patients with diffuse progressive skin disease and inflammatory arthritis, methotrexate or rituximab monotherapy should be considered. First-line therapy for patients with concomitant myositis includes methotrexate or intravenous immunoglobulin (IVIG). For patients with both cutaneous findings and interstitial lung disease, studies have suggested the efficacy of mycophenolate mofetil or rituximab. Second-line therapies, including UVA-1 phototherapy, IVIG, or rituximab, can be considered in patients with disease refractory to first-line treatments. Clinical trials investigating the utility of emerging therapies such as abatacept and tocilizumab in the treatment of SSc are under way, and preliminary results are promising. Nonetheless, all patients with SSc benefit from a gentle skin-care regimen to alleviate pruritis, which is a commonly reported symptom. Additional cutaneous manifestations of SSc include telangiectasias, calcinosis cutis, microstomia, and Raynaud's phenomenon. Telangiectasia may be managed with camouflage techniques, pulse dye laser, and intense pulse light. Calcinosis cutis therapy is guided by the size of the calcium deposits, although treatment options are limited. Mouth augmentation and oral stretching exercises are recommended for patients with reduced oral aperture. Raynaud's phenomenon is treated with a combination of lifestyle modification and calcium channel blockers, such as amlodipine. Overall, SSc is a clinically heterogenous disease that affects multiple organ systems. Providers should assess extracutaneous involvement and use evidence-based recommendations to select the most appropriate therapy for patients with SSc.

Purpose To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. Methods and Materials CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. Results The study cohort was comprised of 70 patients with T1–4 N0–1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5–V70, D40–D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. Conclusions We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.

To compare the ability of Frailty Phenotype (FP), FRAIL and Frailty Index (FI) to predict adverse outcomes. A prospective cohort study. A senior community in Beijing, China. A total of 188 older adults aged 65 years or older (mean age 84.0 ± 4.4 years, 58.5% female). Frailty was evaluated by FP, FRAIL and FI. The agreement between scales was assessed by Cohen kappa coefficient. The predictive value of the three scales for adverse outcomes during one-year follow-up period were analyzed using decision curve analysis(DCA) and receiver operating characteristic curve (ROC) analysis. Frailty ranged from 25% (FRAIL) to 42.6% (FI). The agreement between scales was moderate to good (Cohen’s kappa coefficient 0.44∼0.61). DCA showed though the curves of the scales overlapped across all relevant risk thresholds, clinical treating had a higher net benefit than “treat all” and “treat none” when risk of unplanned hospital visits ≥30%, risk of functional decline or falls ≥15%. The three scales had similar predictive value for unplanned hospital visits (area under ROC, AUC 0.63, 0.64 and 0.69). FRAIL and FI had similar predictive value for functional decline (AUC 0.63,0.65). FI had predictive value for falls (AUC 0.65). All three scales showed clinical utility but FRAIL may be best in practice because it is simple. Multidimensional measures of frailty are better than unidimensional for prediction of adverse outcomes among older adults.

Importance Numerous classification systems for morphea subtypes exist, but none have been systematically evaluated for their ability to categorize patients with morphea into demographically and clinically coherent groups. Although some subtypes, such as linear morphea, are present across all the classification schemes, others list unique subtypes. This creates confusion among investigators and practitioners and impairs accurate categorization of patients for study and clinical evaluation. Objective To evaluate how frequently the commonly used morphea classification systems categorize patients with morphea into clinically relevant subtypes using cross-sectional analysis of 2 large patient cohorts. Design, setting, and participants This cross-sectional study comprised 944 adults and children from 2 prospective cohorts-the Morphea in Adults and Children at the University of Texas Southwestern Medical Center (Dallas, Texas), which enrolled participants from July 20, 2007, to September 21, 2018, and the National Registry for Childhood-Onset Scleroderma at the University of Pittsburgh (Pittsburgh, Pennsylvania), which enrolled participants from October 23, 2002, to November 13, 2018. Main outcomes and measures Patient demographic characteristics, morphea subtype, quality-of-life measures, disease activity, and damage as measured by Localized Scleroderma Cutaneous Assessment Tool scores during initial visits. Results A total of 944 participants (444 patients with adult-onset morphea and 500 patients with pediatric-onset morphea; 741 female participants [78%]; median age at onset, 16 years [interquartile range, 8-44 years]) were included in this study. Most participants were White (723 [77%]) and had the linear (474 [50%]) or generalized subtype of morphea (244 [26%]). With the use of the previously published Padua criteria, most patients were classified to have linear morphea (474 [50%]), followed by generalized morphea (244 [26%]), plaque morphea (141 [15%]), mixed morphea (38 [4%]), and pansclerotic morphea (3 [0.3%]). Overall, the Padua criteria successfully classified 900 patients (95%) in comparison with the Peterson criteria (533 [56%]) and the European Dermatology Forum classification (487 [52%]). Conclusions and relevance In this cross-sectional study of morphea subtype classification systems, the Padua criteria performed best in classifying patients into subgroups with cohesive demographic and clinical features, supporting its widespread use. However, they have ambiguities that might lead to misclassification, particularly in terms of generalized and pansclerotic morphea and descriptors such as morphea profunda. Consensus-based approaches are needed to address these ambiguities and develop a unified classification scheme.

BackgroundThe majority of U.S. reports of COVID-19 clinical characteristics, disease course, and treatments are from single health systems or focused on one domain. Here we report the creation of the National COVID Cohort Collaborative (N3C), a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative U.S. cohort of COVID-19 cases and controls to date. This multi-center dataset supports robust evidence-based development of predictive and diagnostic tools and informs critical care and policy.Methods and FindingsIn a retrospective cohort study of 1,926,526 patients from 34 medical centers nationwide, we stratified patients using a World Health Organization COVID-19 severity scale and demographics; we then evaluated differences between groups over time using multivariable logistic regression. We established vital signs and laboratory values among COVID-19 patients with different severities, providing the foundation for predictive analytics. The cohort included 174,568 adults with severe acute respiratory syndrome associated with SARS-CoV-2 (PCR >99% or antigen ConclusionsThis is the first description of an ongoing longitudinal observational study of patients seen in diverse clinical settings and geographical regions and is the largest COVID-19 cohort in the United States. Such data are the foundation for ML models that can be the basis for generalizable clinical decision support tools. The N3C Data Enclave is unique in providing transparent, reproducible, easily shared, versioned, and fully auditable data and analytic provenance for national-scale patient-level EHR data. The N3C is built for intensive ML analyses by academic, industry, and citizen scientists internationally. Many observational correlations can inform trial designs and care guidelines for this new disease.

Background Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease with clinical sequelae such as itching, dyspigmentation and scarring. Objectives We applied a previously described modular analysis approach to assess the molecular heterogeneity of patients with CLE. Methods Whole-blood transcriptomes of RNA sequencing data from a racially and ethnically diverse group of patients with CLE (n = 62) were used to calculate gene co-expression module scores. An unsupervised cluster analysis and k-means clustering based on these module scores were then performed. We used Fisher's exact tests and Kruskal-Wallis tests to compare characteristics between patient clusters. Results Six unique clusters of patients with CLE were identified from the cluster analysis. We observed that seven inflammation modules were elevated in two clusters of patients with CLE. Additionally, these clusters were characterized by interferon, neutrophil and cell-death signatures, suggesting that interferon-related proteins, neutrophils and cell-death processes could be driving the inflammatory response in these subgroups. Three different clusters had a predominant T-cell signature, which were supported by lymphocyte counts. Conclusions Our data support a diverse molecular profile in CLE that further adds to the clinical variations of this skin disease, and may affect disease course and treatment selection. Future studies with a larger and diverse cohort of patients with CLE are warranted to confirm these findings.

Maintenance management is an important part of the life-cycle management of concrete structures. The pivotal responsibility of a decision-maker in charge of maintenance management is to fully understand the conditions of structures. Accordingly, comprehensive analyses on concrete structures based on a variety of information and knowledge offered by different groups are urgently required. An efficient information communication approach by changing the information communication modes between an expert and a non-expert is proposed based on knowledge management (KM) and building information modeling (BIM) technology. First KM is adopted to describe the process of professional knowledge transferring from an expert to a non-expert. Then, BIM technology is employed to build up an integrated information sharing platform, by which the transferred knowledge can be stored and accessed. Finally, a case study on the evaluation of chloride ion penetration into concrete is carried out to demonstrate the implementation process of the proposed approach. The approach helps to improve efficiency of transferring and sharing knowledge between an expert and a non-expert with information technology, which is also of great significance to explore the application of information technology in maintenance management.