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Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity, their development is hindered by the limitations of neoantigens identification, low immunogenicity, and weak immune response. Cyclophosphamide (CTX) not only directly kills tumors but also causes immunogenic cell death, providing a promising source of antigens for cancer vaccines. Herein, a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed. First, CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity, and then 3 days later, PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses. The results confirm that this combined strategy reduces the toxicity of CTX, and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth, prolong survival, and significantly improve the tumor cure rate. Moreover, a long-lasting immune memory response is observed in the mice. About 90% of the cured mice survive for at least 60 days after being re-inoculated with tumors, and the distant tumor growth is also well inhibited. Hence, this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines., Graphical abstract Image 1, Highlights • PLEL based-CTX hydrogel system avoided the rapid clearance of CTX and reduced systemic toxicity. • PLEL-assisted tumor lysate vaccine was cheap, safe, and contained all tumor antigens. • This strategy promoted the maturation and activation of DCs, enhanced cancer-specific CD8+ T cell responses. • PLEL-assisted combination strategy achieved a good tumor inhibition effect and generate a lasting immune memory. . • This local administration strategy could kill tumors that could not be detected or removed surgically in the clinic.

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74–0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73–0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.

Summary COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. Purpose No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. Method We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital’s electronic prescription platform and patients’ pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. Results A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836–3.448); p

To evaluate the effects of intravenous iodinated contrast medium (ICM) administration on the deterioration of renal function (DRF), new renal replacement therapy (RRT) induction and mortality of hospitalized acute kidney injury (AKI) patients. Adult hospitalized patients undergoing a contrast-enhanced or unenhanced CT scan within 7 days after AKI diagnosis from January 2015 to December 2019 were identified in this retrospective study. Propensity score matching was performed. Outcomes in 7 and 30 days after CT scan were compared between the contrast and non-contrast groups. Additional analyses were also performed in patients stratified by SCr levels at AKI diagnosis, times and time of CT scan, and in patients without chronic kidney disease or RRT requirement prior to CT scan. In total, 1172 pairs were generated after 1:1 propensity score matching from 1336 cases exposed to ICM and 2724 unexposed. No significant differences were found in the outcomes between the two groups: DRF, 7.8% vs 9.0% (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.62–1.11) in 7 days, 5.1% vs 5.4% (OR 0.93, 95%CI 0.64–1.34) in 30 days; new RRT induction, 2.3% vs 3.3% (OR 0.72,95%CI 0.43–1.18) in 7 days, 4.2% vs 4.5% (OR 0.95,95%CI 0.64–1.41) in 30 days; and mortality, 3.9% vs 4.8% (OR 0.83,95%CI 0.56–1.22) in 7 days, 9.0% vs 10.2% (OR 0.88,95%CI 0.68–1.15) in 30 days. Subset analyses showed similar results. Intravenous ICM administration during AKI duration did not increase the risks of DRF, new RRT induction, and mortality in 7 and 30 days after CT scan. • Intravenous ICM administration in hospitalized AKI patients does not increase the risks of deterioration of renal function, RRT induction, and mortality in 7 and 30 days after CT scan. • The effects of intravenous ICM on adverse outcomes are minimal even in AKI patients with high level of SCr values or multiple CT scans.

Fast development of combination of nanotechnology with traditional Chinese medicine (TCM) broadens the field of application of TCM. Besides, it increases the research ideas and contributes to TCM modernization. As expected, TCM will be developed into the nanodrug delivery system by nanotechnology with careful design, which will enhance the medicinal value of TCM to cure and prevent disease based on benefits brought by nanometer scale. Here, formulations, relevant preparations methods, and characteristics of nano-TCM were introduced. In addition, the main excellent performances of nano-TCM were clearly elaborated. What is more, the review was intended to address the studies committed to application of nanotechnology in TCM over the years, including development of Chinese medicine active ingredients, complete TCM, and Chinese herbal compounds based on nanotechnology. Finally, this review discussed the safety of nano-TCM and presented future development trends in the way to realize the modernization of TCM. Overall, using the emerging nanotechnology in TCM is promising to promote progress of TCM in international platform. Recent researches on modernization of traditional Chinese medicine (TCM) urged by nanotechnology are introduced, and formulations, advantages, and applications of nano-TCM are reviewed to provide strong proofs.

Background Microwave ablation (MWA) and radiofrequency ablation (RFA) have recently attracted interest as minimally invasive treatment modalities for papillary thyroid carcinoma (PTC). However, the ablation outcomes of T1N0M0 PTC are not well characterized. Purpose To evaluate the efficacy and safety of thermal ablation (MWA or RFA) of solitary T1N0M0 PTC in patients who were ineligible for (due to presence of comorbid cardiovascular disease, renal failure, other malignancy, etc) or who refused surgery. Materials and Methods This was a retrospective multicenter study of 847 patients (660 women) who underwent thermal ablation for PTC (673 T1a, 174 T1b) between March 2015 and March 2020; of these patients, 645 underwent MWA and 202 underwent RFA. The mean age of patients was 46 years ± 11 (standard deviation) (age range, 18-81 years); the mean follow-up time was 22 months ± 13 (range, 6-60 months). Changes in tumor size and volume and the rates of technical success, tumor disappearance, disease progression, and complications were assessed. Results The technical success rate was 100%. Relative to preablation measurements, the maximum diameter and volume of the ablation zone increased during the 1st month after ablation (P < .001), whereas there was no difference by the 3rd month; subsequently, the tumors showed reduction in size at 6, 9, and 12 months (all P < .001). Complete disappearance of tumors occurred in 68% of patients (577 of 847; 69% [466 of 673] in the T1a group vs 64% [111 of 174] in the T1b group; P < .001). The postablation disease progression rate was 1.1% (nine of 847 patients; 0.9% [six of 673 patients] in the T1a group vs 1.7% [three of 174 patients] in the T1b group; P = .54). The overall complication rate was 3.4% (29 of 847 patients; 2.7% [18 of 673 patients] in the T1a group vs 6.3% [11 of 174 patients] in the T1b group; P = .02). Conclusion This multicenter study provided evidence that thermal ablation is an effective and safe treatment option in selected -patients with solitary T1N0M0 papillary thyroid carcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baek and Cho in this issue.

Mandarin classifiers are a complex system, but little is known about how Mandarin-speaking children manage to learn the system. Based on the extant literature, we explored potential factors influencing the comprehension and production of Mandarin shape classifiers, including classifier-based semantic categorization and errors pertaining to the semantic strategies, input frequency of classifier-noun combinations, and vocabulary knowledge. In total, 138 typically developing monolingual Mandarin-speaking children between ages 4;1 and 6;5 completed an object categorization task, shape classifier comprehension and production tasks, and a vocabulary test. The results showed that classifier-based categorization did not significantly relate to classifier knowledge, but children’s comprehension errors were mostly selecting an object that is perceptually similar to the target object. Estimated input frequency of classifier-noun combinations was significantly related to classifier comprehension, and there was differential accuracy for different classifier-noun combinations, which may indicate item-by-item learning of individual classifier-noun pairings. Mandarin-speaking children may take a combined approach by sorting semantic features for different classifiers and learning individual classifier-noun combinations. The interplay of the two approaches can be very complex and should be further investigated in future studies. Vocabulary knowledge was significantly related to classifier comprehension and production, indicating common traits between classifier learning and noun learning.

In evaluating foot and ankle soft tissue masses, comprehensive epidemiological data, especially clinical predictors of malignancy, is essential knowledge. Our aim was to assess these data in a cohort of patients that have undergone surgical excision of foot and ankle soft tissue tumours and pseudo-tumours over a 10-year period.A retrospective review of foot and ankle soft tissue tumours and pseudo-tumours excised in a tertiary hospital from 1 Jan 2006 to 31 Dec 2016 was performed. Uni- and multivariable analyses via logistic regression were conducted for all independent variables to identify their relationship with malignancy. Applying receiver operating characteristic (ROC) curves and Youden's Index to significant variables, we attempted to identify optimal threshold values to predict malignancy of the soft tissue mass.A total of 623 tumours and pseudo-tumours were analysed, and majority were benign (n = 605, 97.1%). The most common pseudo-tumour, benign, and malignant tumours were ganglion cysts (n = 289, 90.3%), plantar fibromas (n = 54, 18.9%) and pleomorphic undifferentiated sarcomas (n = 4, 22.2%), respectively. Increasing age (P = 0.036), larger size of mass (P0.001) and male gender (P = 0.017) were significant predictors of malignancy. ROC and Youden's Index analyses identified optimal threshold values of 4.0 cm (area under curve [AUC] = 87.6%) for size of mass and 66 years (AUC = 60.7%) for age.Majority of foot and ankle soft tissue masses are benign. Increasing age, larger size of mass and male gender are significant predictors of malignancy. The threshold value in predicting malignancy is 4.0 cm for size of mass and 66 years for age.

BACKGROUND Gastric intestinal metaplasia (GIM) is a precancerous lesion of the stomach, which severely affects human life and health. Currently, a variety of endoscopic techniques are used to screen/evaluate GIM. Traditional white-light endoscopy (WLE) and acetic-acid chromoendoscopy combined with magnifying endoscopy (ME-AAC) are the interventions of choice due to their diagnostic efficacy for GIM. Optical-enhanced magnifying endoscopy (ME-OE) is a new virtual chromoendoscopy technique to identify GIM, which combines bandwidth-limited light and image enhancement processing technology to enhance the detection of mucosal and vascular details. We hypothesized that ME-OE is superior to WLE and ME-AAC in the evaluation of GIM. AIM To directly compare the diagnostic value of WLE, ME-AAC, and ME-OE for detection of GIM. METHODS A total of 156 patients were subjected to consecutive upper gastrointestinal endoscopy examinations using WLE, ME-AAC, and ME-OE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of the three endoscopy methods in the diagnosis of GIM were evaluated. Moreover, the time to diagnosis with ME-AAC and ME-OE was analyzed. Two experts and two non-experts evaluated the GIM images diagnosed using ME-OE, and diagnostic accuracy and intra- and inter-observer agreement were analyzed. RESULTS GIM was detected in 68 of 156 patients (43.6%). The accuracy of ME-OE was highest (91.7%), followed by ME-AAC (86.5%), while that of WLE (51.9%) was lowest. Per-site analysis showed that the overall diagnostic accuracy of ME-OE was higher than that of ME-AAC (P = 0.011) and WLE (P < 0.001). The average diagnosis time was lower in ME-OE than in ME-AAC (64 ± 7 s vs 151 ± 30 s, P < 0.001). Finally, the inter-observer agreement was strong for both experts (k = 0.862) and non-experts (k = 0.800). The internal consistency was strong for experts (k = 0.713, k = 0.724) and moderate for non-experts (k = 0.667, k = 0.598). CONCLUSION For endoscopists, especially experienced endoscopists, ME-OE is an efficient, convenient, and time-saving endoscopic technique that should be used for the diagnosis of GIM.

Objectives This review aims to describe the principles underlying different types of inductively coupled plasma mass spectrometry (ICP-MS), and major technical advancements that reduce spectral interferences, as well as their suitability and wide applications in clinical laboratories. Methods A literature survey was performed to review the technical aspects of ICP-MS, ICP-MS/MS, high-resolution ICP-MS, and their applications in disease diagnosis and monitoring. Results Compared to the atomic absorption spectrometry and ICP-optical emission spectrometry, ICP-MS has advantages including improved precision, sensitivity and accuracy, wide linear dynamic range, multielement measurement capability, and ability to perform isotopic analysis. Technical advancements, such as collision/reaction cells, triple quadrupole ICP-MS, and sector-field ICP-MS, have been introduced to improve resolving power and reduce interferences. Cases are discussed that highlight the clinical applications of ICP-MS including determination of toxic elements, quantification of nutritional elements, monitoring elemental deficiency in metabolic disease, and multielement analysis. Conclusions This review provides insight on the strategies of elemental analysis in clinical laboratories and demonstrates current and emerging clinical applications of ICP-MS.

Introduction: Foreign workers (FWs) on work permit face unique health challenges and potential barriers to healthcare. We aimed to examine the epidemiology, attendance patterns, disposition, and adherence to follow-up, by FWs on work permit to two emergency departments (EDs) in Singapore. Methods: In this retrospective observational study, we included consecutive FWs on work permit who registered at the EDs of two public restructured hospitals from 1 May 2016 to 31 October 2016. Data obtained from electronic medical records included patient demographics, triage acuity, disposition, ED diagnoses and bill information. Results: There were 6,429 individual FWs on work permit who contributed to 7,157 ED visits over the 6-month study period, with male predominance (72.7%, 4672/6429), and median age of 31 (interquartile range 26 to 38) years. A high proportion of these FWs were triaged to low-acuity status compared to the general ED population (66.9% versus 45.9%, P

Flexible electronics has recently captured extensive attention due to its intriguing functionalities and great potential for influencing our daily life. In addition, with the increasing demand for green energy, photoelectrochemical (PEC) water splitting is a clean process that directly converts solar energy to chemical energy in the form of hydrogen. Thus the development of flexible green energy electronics represents a new domain in the research field of energy harvesting. In this work, we demonstrate the BiVO4 (BVO)/WO3/ITO/muscovite heterostructure photoelectrode for water splitting with flexible characteristics. The performance of BVO was modified by specific crystal facets, and the BVO/WO3 bilayer exhibited superior performance of 33% enhanced PEC activity at 1 V vs Ag/AgCl compared with pure BVO due to the proper staggered band alignment. Moreover, excellent mechanical stability was verified by a series of bending modes. This study demonstrates a pathway to a flexible photoelectrode for developing innovative devices for solar fuel generation.

Background The aim of this study was to discuss the safety and efficacy of administering reduced doses (3 mg) of pegylated recombinant human granulocyte‐colony stimulating factor (PEG‐rhG‐CSF) at approximately 24 h or up to three days following treatment with etoposide and cisplatin (EP). Methods A total of 104 cycles from 31 patients were divided into a PEG‐rhG‐CSF prophylaxis group (PP‐Group) and a control group (No‐PP‐Group). The PP‐Group received a reduced dose of 3 mg of PEG‐rhG‐CSF within a minimum of 15 h and a maximum of 72 h following EP chemotherapy, while the rest did not receive any G‐CSF prophylaxis (No‐PP‐Group). For both groups, complete blood counts, incidence of febrile neutropenia (FN), grade III or IV neutropenia, and the use of antibiotics to treat neutropenia were recorded. Results There was statistically no significant difference in the incidence of FN (0% vs. 1.4%, p = 1), antibiotic use due to neutropenia (0% vs. 2.7%, p = 0.881), estimated lowest mean marginal (EM) platelet (106.56 × 109/L vs. 127.70 × 109/L, p = 0.056) and hemoglobin (110.48 g/L vs. 110.14 g/L, p = 0.906) levels between the two groups. However, when compared with the No‐PP‐group, the white blood cell count in the PP‐group was significantly higher (EM means: 4.95 × 109/L vs. 2.80 × 109/L, p, Even though cisplatin is slowly metabolized by the body, the routine administration time of PEG‐rhG‐CSF following cisplatin was safe. A reduced dose (3 mg) of PEG‐rhG‐CSF was also effective in preventing grade III and IV neutropenia.

Background We evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC). Methods This retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR). Results In total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7–12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor. Conclusions First-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

BACKGROUND Intrahepatic portosystemic venous shunt (IPSVS) is a rare hepatic disease with different clinical manifestations. Most IPSVS patients with mild shunts are asymptomatic, while the patients with severe shunts present complications such as hepatic encephalopathy. For patients with portal hypertension accompanied by intrahepatic shunt, portal hypertension may lead to hemodynamic changes that may result in exacerbated portal shunt and increased shunt flow. CASE SUMMARY A 57-year-old man, with the medical history of chronic hepatitis B and liver cirrhosis, was admitted to our hospital with abnormal behavior for 10 mo. He had received the esophageal varices ligation and entecavir therapy 1 year ago. Comparing with former examination results, the degree of esophageal varices was significantly reduced, while the right branch of the portal vein was significantly expanded and tortuous. Meanwhile, abdominal ultrasound presented the right posterior branch of portal vein connected with the retrohepatic inferior vena cava. The imaging findings indicated the diagnosis of IPSVS and hepatic encephalopathy. Instead of radiologic interventions or surgical therapies, this patient had only accepted symptomatic treatment. No recurrence of hepatic encephalopathy was observed during 1-year follow-up. CONCLUSION Hemodynamic changes may exacerbate intrahepatic portosystemic shunt. The intervention or surgery should be carefully applied to patients with severe portal hypertension due to the risk of hemorrhage.

Background and aim Patients with functional dyspepsia (FD) often have concomitant anxiety and depression. Mindfulness-based cognitive therapy (MBCT) combines the principles of cognitive behavioral therapy and mindfulness. It is a group-based therapy and has been shown to be efficacious in functional gastrointestinal disorders. There are no randomized controlled trials (RCTs) evaluating MBCT in FD. We aimed to evaluate feasibility and efficacy of MBCT in FD management. Methods We performed a mixed-method single-center pilot randomized trial of 28 patients fulfilling ROME-III criteria for FD. Fifteen patients were randomized to an 8-week MBCT program while 13 underwent treatment-as-usual (TAU). Patients completed questionnaires at baseline and at week 8. Two focus-groups were conducted. Feasibility of recruitment, acceptability of randomization, procedures and intervention, handout compliance and feasibility of quantitative measures were assessed. The primary outcome was subjective-clinical-assessment of FD symptoms (SCA-FD). Secondary outcome measures included Short-form Nepean Dyspepsia Index (SF-NDI), subjective-clinical-assessment of general health (SCA-GH), EuroQoL-Visual Analog Scale (EuroQoL-VAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21). Results Twelve of 15 patients in the MBCT group completed the program. There was a trend towards symptom improvement, with 90% in the MBCT group reporting improvement in SCA-FD compared with 45% in TAU(P = 0.063). Patients who underwent MBCT reported greater improvement in SF-NDI (mean change: -8.8 (SD: 7.5) vs -0.7 (7.2), P = 0.018) and DASS-21 (-19.8 (29.5) vs -5.5 (6.6) P = 0.13) compared with TAU. There was no difference in SCA-GH and EuroQoL-VAS. Based on SCA-FD improvement, the eventual RCT will require 50 patients (25 in each group). Conclusions Mindfulness-based cognitive therapy is likely efficacious for FD, and it would be feasible to conduct a RCT.

Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

Establishing a session key (SSK) is very important for real-world deployment in open networks, which enables secure communication between remote parties. In the past, some authenticated key exchange (AKE) protocols have been proposed to generate a SSK, but the certificate management issue is inhered in the traditional public key infrastructure and must be addressed. To tackle this issue, the identity (ID)-based concept is added to AKE, called ID-AKE. Indeed, the security of the existing AKE/ID-AKE protocols is gaining increasing importance due to some new types of attacks, namely, side-channel attacks. In such attacks, adversaries could obtain secret keys’ partial information during the execution of cryptographic protocols (including AKE/ID-AKE). To withstand such attacks, many leakage-resilient ID-AKE (LR-ID-AKE) protocols resisting side-channel attacks have been proposed. However, these existing LR-ID-AKE protocols have no efficient solution to revoke compromised users. In this article, the first LR-ID-AKE protocol with an efficient revocation mechanism, called LR-RID-AKE, is proposed. The proposed protocol is not only as secure as existing LR-ID-AKE protocols but also able to efficiently revoke compromised users from the system.

Transparent VO2/muscovite heterostructures have attracted considerable attention because of their unique chemical and physical properties and potential practical applications. In this paper, we investigated the influence of uniaxial mechanical strain on the optical properties of VO2/muscovite heterostructures through Raman scattering and optical transmittance measurements. Under applied strain, linear shifts in peak positions of Raman-active phonon modes at approximately 340, 309, and 391 cm-1 were observed. The extracted Gruneisen parameter values were approximately between 0.44 and 0.57. Furthermore, a pronounced strain-induced change in the metal-insulator transition (MIT) temperature was observed, which decreased under compressive strain and increased under tensile strain. The rates of MIT temperature variation reached 4.5 °C per % and 7.1 °C per % at a wavelength of 1200 nm during heating and cooling processes, respectively. These results demonstrate that the modulation of the optical properties of VO2/muscovite heterostructures is controllable and reversible through strain engineering, opening up new opportunities for applications in flexible and tunable photonic devices.

Gigahertz field-effect transistors (FETs) have been the imperative need for the development of nanoelectronics based on atomically thin transition metal dichalcogenides (TMDs). Yet, WS2 FETs workin...

Do chronic fluoxetine treatments reduced footshock-induced posttraumatic stress disorder (PTSD) symptoms, including fear and comorbid depression, in the situational reminder phase? Moreover, are the subareas of the medial prefrontal cortex (mPFC), including the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), and basolateral amygdala (BLA), involved in the fluoxetine amelioration of PTSD symptoms? These two crucial issues were addressed in the present study. All mice were injected with chronic fluoxetine or normal saline treatments for the adaptation (14 days), footshock fear conditioning (1 day), and situational reminder (3 days) phases. After adaptation, the mice were subjected to footshock (2 mA, 10 seconds) or nonfootshock and stayed 2 min in a footshock box for 2 min for fear conditioning. Later, they were placed in the footshock box for 2 min in the situational reminder phase. In the final session of the situational reminder phase, a forced swimming test (FST) and immunohistochemical staining were conducted. The results indicated that footshock induced fear and comorbid depression. Meanwhile, chronic fluoxetine treatments reduced fear and depression behaviors. The Cg1, PrL, IL, and BLA were seemingly to increase c-Fos expression after footshock-induced PTSD symptoms in the situational reminder phase. The fluoxetine treatments reduced only the BLA’s c-Fos expression. The findings suggest that BLA contributes to the fluoxetine amelioration of PTSD symptoms; however, the mPFC, including the Cg1, PrL, and IL, did not mediate PTSD symptoms’ amelioration stemming from fluoxetine. The present data might help us to further understand the neural mechanism of fluoxetine treatments in PTSD symptoms.

Purpose This study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes. Methods Arterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses. Results Compared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus. Discussion Cerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.

Objective To evaluate the use of direct to consumer Prefabricated adjustable thermoplastic mandibular advancement devices (PAT-MADs) (MyTAP™, Airway Management Inc), its effectiveness in the treatment of OSA, feasibility and short-term adherence. Methods In sum, 50 patients with diagnosed mild-moderate OSA on formal polysomnography (PSG) were fitted with a PAT-MAD (MyTAP™, Airway Management Inc). Sleep indices included the apnea–hypopnea index (AHI), hypopnea index (HI), apnea index (AI); oxygen desaturation index (ODI), and the lowest 02 saturation (Lsat) were measured with a Level 3 home sleep apnea test (HSAT) pre versus post treatment. Quality of life (QOL) surveys of Epworth sleepiness scale (ESS), Pittsburg sleep quality index (PSQI), Functional outcomes of sleep quality-10 (FOSQ10) and satisfaction surveys were administered. Results Over three months, indices showed a trend towards improvement. Results were statistically significant when stratified into groups who achieved cure and success. Moreover, there was a mean improvement in AHI: −12.7 ± 9.3, AI: −5.7 ± 8.2, HI: −6.3 ± 3.7, ODI: −11.2 ± 8.6 for responders with a success rate of 41%. Out of QOL surveys, ESS showed a decrease of −1.41 [−2.52, −0.3] (p = 0.017) when controlled for age and body mass index (BMI). Up to 68.8% of patients found that the device was useful in alleviating snore symptoms. Adherence rate was reported at 59%. Conclusion Titratable PAT-MAD is an economical and effective option for a patient of Chinese descent. It has the potential to serve as a device for trial use and means of selection before proceeding with customized MADs. Further studies will be required to substantiate other factors which influence the recommendation of MADs for patients with this demographic.

BACKGROUND: Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI. METHODS: A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9-12) and severe (GCS score, ≤8) TBI. RESULTS: The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38-0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11-0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04-0.88; p = 0.034). CONCLUSION: In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE: Therapeutic, level IV.

Supplemental Digital Content is available in the text., Background: Clinical laboratories have traditionally used a single critical value for thrombocytopenic events. This system, however, could lead to inaccuracies and inefficiencies, causing alarm fatigue and compromised patient safety. Objectives: This study shows how machine learning (ML) models can provide auxiliary information for more accurate identification of critical thrombocytopenic patients when compared with the traditional notification system. Research Design: A total of 50,505 patients’ platelet count and other 26 additional laboratory datasets of each thrombocytopenic event were used to build prediction models. Conventional logistic regression and ML methods, including random forest (RF), artificial neural network, stochastic gradient descent (SGD), naive Bayes, support vector machine, and decision tree, were applied to build different models and evaluated. Results: Models using logistic regression [area under the curve (AUC)=0.842], RF (AUC=0.859), artificial neural network (AUC=0.867), or SGD (AUC=0.826) achieved the desired average AUC>0.80. The highest positive predictive value was obtained by the SGD model in the testing data (72.2%), whereas overall, the RF model showed higher sensitivity and total positive predictions in both the training and testing data and outperformed other models. The positive 2-day mortality predictive rate of RF methods is as high as 46.1%—significantly higher than using the traditional notification system at only 14.8% [χ2(1)=81.66, P

Background Pneumocystis pneumonia (PCP) is a disease caused by the opportunistic infection of the fungus Pneumocystis jirovecii. Several PCR methods have been developed to aid in the diagnosis of PCP. In this study, we evaluated the performance of a real-time PCR in the diagnosis of PCP, in patients with various underlying diseases. Methods Ninety-seven BAL samples and 94 sputum samples from 191 patients were used in the study. Patients were classified as PCP (121 patients) or non-PCP (70 patients) based on their clinical and radiological presentations. Results Real time PCR amplified the P. jirovecii mitochondrial large-subunit rRNA gene with a detection limit of 68 copies of DNA per reaction. Non-PCP pathogens including 32 different fungi and bacteria were also evaluated. Overall, 71.9% of the samples from PCP patients and 14.5% of those from non-PCP patients were positive for the PCR test with a CT value of the real-time PCR below 45. The main underlying diseases of the patients were hematological or solid malignancies (47.1%) and HIV infection (8.9%). The CT values of the test were significantly lower in BAL samples from PCP patients than those from non-PCP patients (p = 0.024). No non-PCP patient had a CT value below 30, whereas samples from 24.8% of PCP patients with underlying diseases had a CT value below 30. Conclusion Since false positive PCR results were obtained, perhaps due to colonization, we suggest that the diagnosis of PCP should be based on a combination of clinical symptoms, underlying diseases, and PCR results.

Background:Personal protective equipment (PPE) are essential for medical personnel responding to hazardous materials (HAZMAT) incidents. However, their impermeable design causes increased physiological strain and reduced thermoregulation, limiting work times and causing heat-related illnesses (HRI). Use of wearable cooling devices slow heat accumulation and have been shown to reduce thermal and cardiovascular strain in such situations.Methods:This was a prospective clinical evaluation to determine the tolerability and effectiveness of the CarbonCool cooling system – a half-body cooling vest – in participants undergoing a HAZMAT decontamination recertification. Physiological measurements (heart rate [HR], weight, temperature, and blood pressure) and participant feedback were obtained. The main outcome of interest was participants’ tolerability of the cooling vest.Results:A total of 23 healthy participants were recruited, with 10 randomized to the intervention group and 13 in the control group. Mean age in the control and intervention group was 35.5 years old (SD = 7.8) and 30.0 years old (SD = 6.2), respectively. Qualitative feedback obtained from participants regarding safety, mobility, and cooling efficacy was largely positive. Difference of before-after temperature and HR was 0.3°C (SD = 0.8) and 11.5bpm (SD = 13.6) in the control group compared to 0.0°C (SD = 0.5) and 0.0bpm (SD = 6.4) for the intervention group.Conclusion:This clinical evaluation showed that the CarbonCool cooling vest is safe and tolerable in participants wearing PPE. Further trials with sample size powered to detect physiological outcomes are needed to assess the effect of the cooling vest on a subject’s endurance to heat stress.

There has been a growing interest in urgent-start peritoneal dialysis (PD) in patients with end-stage kidney disease to avoid central venous catheter use and its complications. This study aimed to compare clinical outcomes between urgent-start PD (defined as PD commencement within 2 weeks of PD catheter insertion) and conventional-start PD. This was a single-centre retrospective cohort study of all incident PD patients at Singapore General Hospital between January 2017 and February 2018. The primary outcome was dialysate leak. Secondary outcomes included catheter malfunction, catheter readjustment, exit-site infection, peritonitis, technique and patient survival. A total of 187 incident PD patients were included. Of these, 66 (35%) initiated urgent-start PD. Dialysate leak was significantly higher in urgent-start PD compared with conventional-start PD groups (7.6% versus 0.8%; p = 0.02) whilst catheter malfunction (4.5% vs. 3.3%; p = 0.70) and catheter readjustment (1.5% vs. 2.5%; p = 1.00) were comparable between the two groups. Exit-site infection was comparable (IRR: 0.66 95% CI 0.25–1.74) whilst peritonitis was significantly higher in urgent-start PD compared with conventional-start PD (incidence risk ratio (IRR) 3.10, 95% confidence interval (CI) 1.29–7.44). Time to first episode of peritonitis, particularly Gram-positive peritonitis was significantly shorter with urgent-start PD. Technique survival (hazards ratio (HR) 1.95, 95% CI 0.89–4.31) and patient survival (HR 1.46, 95% CI 0.44–4.87) were comparable between the two groups. Urgent-start PD was associated with higher risks of dialysate leak and peritonitis but comparable technique and patient survival compared to conventional-start PD.

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function. In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of ~85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL., Graphical abstract Image 1, Highlights • A biomaterial-based strategy was used to improve a tumor cell-based vaccine. • The immunocompetence improved vaccine (Man-EG7/CH@CpG), which can target DCs, displayed an antitumor function. • In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. • The regimen which incorporated DOX with Man-EG7/CH@CpG further improved the therapeutic effect of lymphoma.

To compare the similarities and differences of early CT manifestations of three types of viral pneumonia induced by SARS-CoV-2 (COVED-19), SARS-CoV (SARS) and MERS-CoV (MERS) using a systemic review. Methods Electronic database were searched to identify all original articles and case reports presenting chest CT features for adult patients with COVID-19, SARS and MERS pneumonia respectively. Quality of literature and completeness of presented data were evaluated by consensus reached by three radiologists. Vote-counting method was employed to include cases of each group. Data of patients' manifestations in early chest CT including lesion patterns, distribution of lesions and specific imaging signs for the three groups were extracted and recorded. Data were compared and analyzed using SPSS 22.0. Results A total of 24 studies were included, composing of 10 studies of COVED-19, 5 studies of MERS and 9 studies of SARS. The included CT exams were 147, 40, and 122 respectively. For the early CT features of the 3 pneumonias, the basic lesion pattern with respect to “mixed ground glass opacity (GGO) and consolidation, GGO mainly, or consolidation mainly” was similar among the 3 groups (χ2 = 7.966, p > 0.05). There were no significant differences on the lesion distribution (χ2= 13.053, p > 0.05) and predominate involvement of the subpleural area of bilateral lower lobes (χ2 = 4.809, p > 0.05) among the 3 groups. The lesions appeared more focal in COVID-19 pneumonia at early phase (χ2= 23.509, p < 0.05). The proportions of crazy-paving pattern (χ2 = 23.037, p < 0.001), organizing pneumonia pattern (p < 0.05) and pleural effusions (p < 0.001) in COVID-19 pneumonia were significantly lower than the other two. Although rarely shown in the early CT findings of all three viral pneumonias, the fibrotic changes were more frequent in SAKS than COVID-19 and MERS (χ2 = 6.275, P

Purpose The Forgotten Joint Score (FJS-12) is a scoring system initially created to assess post arthroplasty outcomes. It has since been used to evaluate Anterior Cruciate Ligament surgery outcomes. Our study aims to evaluate the applicability and validity of the FJS-12 in post Anterior Cruciate Ligament reconstructed patients, and to assess correlation with established Patient Reported Outcome Measure Scores in the same population. Design Case series, level 3 evidence. Methods We conducted a cross sectional study across patients who had undergone Anterior Cruciate Ligament reconstruction and carried out the FJS-12 questionnaire by phone interview. Patients who had undergone primary Anterior Cruciate Ligament reconstruction were considered for the study. Results The average Forgotten Joint Score-12 for all 82 patients was 71.4 (±22.9), which corresponded to a normal distribution. The average Lysholm and Tegner score at the 2-year post-operative visit was 93.5 ± 9.5 and 5.8 ± 1.8 respectively and the distribution was non-normal. We noticed a large ceiling effect of 42.7% in the Lysholm scores, but only 8.4% in FJS-12. There was a weak correlation with Lysholm and a positive correlation with Tegner. Conclusions Forgotten Joint Score-12 seems to be a promising patient reported outcome measure that can be used in evaluating post Anterior Cruciate Ligament reconstruction outcomes. It is more discerning than traditional scores and is easy to administer thus it can used in the clinical follow-up of patients. With the scores being normally distributed, it makes for a meaningful PROMS and would allow more accurate application of parametric statistical tests.

The prevalence of skin cancer is rising along with the rapid population aging in recent years. Traditional therapies, such as surgical treatment, radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, may accompany serious side effects, limiting their clinical benefits. According to the biological characteristics of skin cancer, we have already established two kinds of synergetic systems of photothermal therapy (microneedle) and chemotherapy, containing gold nanorods (GNR). Although the microneedle system exhibited great potential for skin cancer treatment, the system could be still improved further. So, we designed a near-infrared light-responsive 5-fluorouracil (5-Fu) and indocyanine green (ICG) loaded monomethoxy-poly (ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticle (5-Fu-ICG-MPEG-PCL), and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system (HA MN) to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers, including human epidermoid cancer and melanoma. In this system, hyaluronic acid, the microneedle carrier, possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant; 5-Fu is recommended by FDA for skin cancer treatment; ICG, a photothermal agent, possesses a strong photothermal ability and is approved by FDA for its use in the human body. We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin, and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer, improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer., Graphical abstract Image 1, Highlights • A near-infrared responsive dissolvable microneedle enables a single-dose cure for human epidermoid cancer and melanoma.

We study how cultural norms from overseas affect corporate transparency. Using cultural background information on board directors, we document that corporations with directors with culture from overseas have greater corporate transparency. Specifically, we show that firms with directors with foreign cultural background have more voluntary information disclosure, more analyst coverage, more accurate earnings forecast and less earnings management. Moreover, these firms are more likely to choose Big 4 auditors. We also find that the relationship between culture from overseas and corporate transparency are more strongly positive when the directors have foreign experience from more incorruptible countries or districts. Our findings provide evidence on how directors spread transparency cultural norms rooted in their hearts to firms in developing countries.

We propose herein an extended power forecasting-based coordination dispatch method for PV power generation microgrid with plug-in EVs (PVEVM) to improve the local consumption of renewable energy in the microgrid by guiding electric vehicle (EV) orderly charging. In this method, we use a clustering algorithm and neural network to build a power forecasting model (PFM) based on real data which can effectively characterise the uncertainty of PV power generation and EV charging load. Based on the interaction between the energy control centre (ECC) of the PVEVM and the EV users, a one-leader multiple-follower Stackelberg game is formulated, and the Stackelberg equilibrium is determined by using a power forecasting-based genetic algorithm (GA). As a main contribution of this paper, the PV power generation and EV charging load output from the PFM are used to generate a better quality initial population of the GA to improve its performance. A case study using real data from the Aifeisheng PV power station in China and EV charging stations in the UK verifies the good performance of the proposed extended coordination dispatch algorithm.

Nowadays the most intriguing features of wave-particle complementarity of single-photons are exemplified by the famous Wheeler’s delayed-choice experiment with linear optics, nuclear magnetic resonance, and integrated photonic device systems in the optical platform. Until now, the delayed-choice experiments are demonstrated by either massless photons or massive particles, such as atoms, however, there is no report demonstrating Wheeler’s ideas in a hybrid system which consists of photons and atoms simultaneously. Here, we demonstrate a Wheeler’s delayed-choice experiment in an interface of light and atomic memory, in which the cold atomic memory makes the heralded single-photon divided into a superposition of atomic collective excitation and leaked pulse, thus acting as memory-based beam-splitters. We observe the intermediate states between particle and wave behavior by changing the relative proportion of the quantum random number generator, the second memory efficiency, and the relative storage time of two memories. The reported results confirm Bohr’s view that it makes no sense to illustrate the wave-like or particle-like behavior of light and matter before the measurement happens, and are helpful for improving our comprehension of the complementarity principle under the interface of light-atom interaction.

Background:Current literature suggests a higher rate of rotator cuff disease development in patients with dyslipidemia (DL). Moderate to high levels of DL are associated with higher rates of retear and revision surgery after arthroscopic rotator cuff repair. Statins protect against development of rotator cuff disease and mitigate the need for rotator cuff repair.Purpose:We aimed to investigate the influence of DL and statin use on postoperative functional outcomes.Study Design:Cohort study; Level of evidence, 3.Methods:Between 2010 and 2016, 266 patients underwent arthroscopic double-row rotator cuff repair for atraumatic full-thickness tears. Evaluation was conducted preoperatively and at 3, 6, 12, and 24 months postoperatively. Three functional outcome measures were used (Constant Shoulder Score [CSS], Oxford Shoulder Score [OXF], and University of California, Los Angeles, Shoulder Rating Scale [UCLASS]), as well as a visual analog scale (VAS) for pain. DL and non-DL were classified through screening of health and assessment of lipid levels within 6 months of surgery (triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein). Patients with DL were divided into statin users and nonusers. Types and dosages of statins were recorded, and intensity and equivalency charts were employed for standardization. Mann-Whitney U test and Pearson chi-square test were used for analysis. Generalized estimating equations and linear mixed models were used to examine the influence of DL and statin dosage, respectively on percentage change of postoperative outcome scores.Results:Increased age was associated with a higher incidence of DL ( P < .001), and 86% of the DL group was taking statins. The DL group also exhibited poorer scores preoperatively (CSS, P = .001; OXF, P = .032). No significant difference in scores was elicited between the DL and non-DL groups at 24 months. However, patients with DL experienced greater percentage improvement of CSS and OXF from preoperative baseline than did patients without DL ( P = .008 and P = .034, respectively) at 24 months. There was no significant difference in 24-month functional outcomes between statin users and nonusers. No statistically significant change of CSS; OXF; UCLASS; or VAS was noted with increasing statin doses at 24 months.Conclusion:Patients with DL with perioperative statin usage did not have poorer 24-month functional outcomes after arthroscopic rotator cuff surgery compared with those in patients without DL.

The recent adjunctive catheter-directed thrombolysis (ATTRACT) trial rose a controversy about the treatment effect of catheter-directed thrombolysis (CDT) in deep venous thrombosis (DVT). In fact, most studies including the ATTRACT trial did not perform subgroup analysis of catheterization approaches. Different approaches would confound the conclusions. Therefore, a single-center retrospective analysis was performed to compare the differences between the antegrade (AGA) and retrograde (RGA) approaches. Total 217 DVT patients treated with CDT were enrolled from January 2010 to December 2017, with mean age of 55.3 years (67 received antegrade approach, 150 received retrograde approach). The clot burden reduction by segment was evaluated. The mean access establishment time and thrombolytic time were compared. The patency of the iliofemoral vein at 6 months was evaluated. The rate of PTS, quality of life and venous insufficiency were assessed at 1 year. AGA group showed better thrombolytic effect in popliteal and femoral vein than RGA group. The rate of iliofemoral clot burden reduction in RGA group was mostly at Grade II, while most were at Grade III in AGA group. The retrograde approach showed better thrombolysis effect in iliofemoral DVT than popliteal to iliac DVT. The RGA group reported longer mean access establishment time (5.4 ± 1.8 vs 27.0 ± 7.5 min, p

The current gold standard for diagnosis of obstructive sleep apnea (OSA) is overnight in laboratory polysomnography (PSG). However, PSGs are expensive, labor-intensive, and have long wait times. An ambulatory sleep study device, the WatchPAT, has been shown to have high correlation for sleep indices measured compared with PSG (AASM, 2016). Use of the WatchPAT could potentially lead to shorter waiting times and earlier diagnosis of OSA (Lancet Resp Med 3:310–8, 2015). Our study aimed to investigate if WatchPAT reduces time to diagnosis and treatment of OSA in a tertiary healthcare setting. A secondary aim was to investigate the cost-benefit of an ambulatory sleep study. All patients who underwent diagnostic sleep studies in a single tertiary institution from 2014 to 2017 were retrospectively reviewed. Baseline characteristics and time from ordering of sleep study to prescription of continuous positive airway pressure were recorded. Data were categorized into two groups by type of diagnostic sleep study, PSG, and WatchPAT. The time to treatment and cost for diagnosis of OSA were compared between groups with the Paired T test/Wilcoxon signed-rank test. Of 1898 patients who had diagnostic sleep studies over a 4-year period, 1660 patients (88%) underwent PSG and 238 patients (12%) underwent WatchPAT. Patients in the WatchPAT group had a shorter time to diagnosis (21 days versus 79.8 days, p < 0.001) and treatment (46.3 days versus 118.4 days, p < 0.001) compared to the PSG group. Cost-benefit calculation showed that this earlier treatment led to cost-saving of US $1179.50 per patient. An ambulatory sleep study is an option for earlier access to diagnosis and treatment of OSA with the potential of considerable cost savings.

Objectives The accuracy of FRAX® as a screening tool to identify osteoporosis and how it compares with tools such as Osteoporosis Self-Assessment Tool for Asians (OSTA), in Southeast Asian women has so far been unexplored. We aimed to determine the FRAX® thresholds that accurately identify densitometric osteoporosis and to compare its performance with that of OSTA for this purpose. Methods Singaporean postmenopausal women (n = 1056) were evaluated. FRAX® Major Osteoporotic Fracture Probability (MOFP), Hip Fracture Probability (HFP) scores, and OSTA indices were calculated. Receiver operating characteristic (ROC) curves were constructed and via the Youden index, the optimal cut-off points of balanced sensitivity and specificity for dual energy X-ray absorptiometry (DXA)-defined osteoporosis were identified and the performance characteristics were compared. Results A FRAX® MOFP threshold of ≥3.7% had sensitivity, specificity, positive predictive value and negative predictive value of 0.78 (0.73–0.83), 0.63 (0.59–0.66), 0.4 (0.36–0.44), and 0.9 (0.87–0.92), respectively in identifying osteoporosis. The corresponding values for a HFP threshold of ≥0.6% were 0.85 (0.80–0.89), 0.58 (0.55–0.62), 0.39 (0.35–0.43), and 0.92 (0.9–0.94) and that for an OSTA index cut-off of ≤ −1.2 were 0.76 (0.70–0.81), 0.74 (0.71–0.77), 0.48 (0.43–0.54), and 0.91 (0.88–0.93). The area under the ROC curves were 82.8% (79.9%–85.6%), 77.6% (74.2%–81%), and 79.6% (76.5%–82.8%) for OSTA, MOFP, and HFP thresholds respectively. Conclusions FRAX® and OSTA perform comparably in identifying osteoporosis in our population. OSTA has only 2 parameters and may be simpler to use. However, FRAX® may also have a role in primary screening to identify the postmenopausal woman to be referred for DXA scanning and may help facilitate fracture risk reduction discussions with the patient.

The large bandgap and high p-type conductivity of sp2-bonded boron nitride (BN) make the compound very attractive for deep ultraviolet light-emitting diodes (DUV LEDs). However, integrating the pro...

Background ABO blood system has many subgroups. In A group, A1 phenotype and A2 phenotype are more common, and A2 is caused by deletion or substitution in A1 allele (ABO*A1.01). Methods Based on standard ABO serological test, the subject was identified as A2 phenotype. Direct sequencing and ABO gene cloning were performed to analyze the allele. Results The subject had one A1v allele (ABO*A1.02) and one O allele. The haplotype sequencing analysis of each allelic clone demonstrated that allele 1 was A1v (ABO*A1.02) allele with nt543 variation (543 G > C) and allele 2 was O1v allele (ABO*O.01.02) with nt261 deletion and nt220 variation. Conclusion The 543 G > C nucleotide substitution of the present A1v allele (ABO*A1.02) shares the same sequence variation site with Ax allele (ABO*AW.33) (543 G > T), and both 543 G > C and 543 G > T nucleotide substitutions encode the same amino acid change of tryptophan to cysteine. Mechanism, such as allelic enhancement, has been proposed to explain this controversial phenotype-genotype relationship. But in present case, there has been no B allele to enhance the expression of Ax to that expected of A2, so there could be another novel underlying mechanism to be investigated.

Previous investigations showed inconsistent results for associations between vitamin D and knee osteoarthritis (OA). The present study aimed to make a systematic review and meta-analysis for the association between vitamin D and knee OA.We systematically searched for articles published in the databases PubMed, Web of Science, EMBASE, Medline, and Google Scholar through July 2019. All statistical analyses were made using STATA 12.0 software. The Q test and IThe study indicated that there were no significant associations between serum levels of 25-hydroxy (OH) vitamin D and prevalence, incidence or progression of knee radiographic OA (ROA), and joint space narrowing (JSN). However, a subgroup study showed significant associations of low vitamin D levels with the progression of knee OA. Additionally, the present study showed no significant effect of vitamin D supplementation on knee OA.The results do not support that serum levels of 25(OH) vitamin D are associated with the risks of knee OA, except perhaps with progression of knee OA. In addition, vitamin D supplementation may not have a clinically significant effect on pain control or structure (tibial cartilage volume and JSW) progression in patients with knee OA. Longer-term clinical trials are essential to explore the effect of vitamin D supplementation on knee OA.Frühere Untersuchungen ergaben inkonsistente Ergebnisse für Assoziationen zwischen Vitamin D und Knie-Osteoarthritis (Knie-OA). Die vorliegende Studie zielte auf eine systematische Überprüfung und Metaanalyse des Zusammenhangs zwischen Vitamin D und Knie-OA ab.Wir haben systematisch nach Artikeln gesucht, die in folgenden Datenbanken (PubMed, Web of Science, EMBASE, Medline und Google Scholar) bis Juli 2019 veröffentlicht wurden. Alle statistischen Analysen wurden mit der Software STATA 12.0 durchgeführt. Der Q-Test und IDie Studie ergab, dass keine signifikanten Zusammenhänge zwischen dem Serumspiegel von 25-Hydroxy-Vitamin D (25-OH-Vitamin D) und der Prävalenz, Inzidenz oder Progression von radiografischem OA (ROA) und Gelenkspaltverengung (JSN) im Knie bestehen. Eine Subgruppenstudie zeigte jedoch signifikante Assoziationen niedriger Vitamin-D-Spiegel mit dem Fortschreiten der Knie-OA. Zusätzlich zeigte die vorliegende Studie keinen signifikanten Effekt der Vitamin-D-Supplementierung auf die Knie-OA.Die Ergebnisse belegen nicht, dass Serumspiegel von 25-OH-Vitamin D mit dem Risiko einer Knie-OA assoziiert waren, außer vielleicht mit dem Fortschreiten der Knie-OA. Darüber hinaus hat eine Vitamin-D-Supplementierung möglicherweise keinen klinisch signifikanten Einfluss auf die Schmerzkontrolle oder den Strukturverlauf (Tibiaknorpelvolumen und JSW) bei Patienten mit Knie-OA. Langfristige klinische Studien sind unerlässlich, um die Wirkung der Vitamin-D-Supplementierung auf die Knie-OA zu untersuchen.

Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.

Introduction: Percutaneous renal biopsy remains critical for the workup of renal allograft dysfunction but is associated with the risk of bleeding. Prophylactic intravenous desmopressin has been proposed to reduce bleeding risk in native renal biopsies, but its efficacy in the renal transplant population is unclear and adverse events such as severe hyponatraemia have been reported. Materials and Methods: We conducted a single-centre retrospective cohort study involving adult (≥21 years old) renal transplant recipients with impaired renal function (serum creatinine ≥150 μmol/L) who underwent ultrasound-guided renal allograft biopsies from 2011‒2015 to investigate the effect of prebiopsy desmopressin on the risk of bleeding and adverse events. Results: Desmopressin was administered to 98 of 195 cases who had lower renal function, lower haemoglobin and more diuretic use.Postbiopsy bleeding was not significantly different between the 2 groups (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.26‒2.43, P = 0.68) but desmopressin increased the risk of postbiopsy hyponatraemia (sodium [Na]

Primary central nervous system lymphoma (PCNSL) presenting with atypical radiological findings often leads to delayed diagnosis. We aim to characterize the radiological features and apparent diffusion coefficient (ADC) values of PCNSL with atypical neuroimaging presentation in our local population. We retrospectively reviewed all patients with histological diagnosis of CNS lymphoma at our tertiary center from 2005 to 2016. We screened all initial pre-treatment MRIs and excluded cases with typical imaging findings of contrast-enhancing lesions without intra-lesional susceptibility and central non-enhancement. Additional exclusion criteria included (i) relapsed PCNSL, (ii) secondary CNS lymphoma, and (iii) positive HIV status. Two independent raters scored MRI and CT scans at presentation. We computed ADC values in the tumors by 2 methods: single region of interest (ROI1) and multiple ROI (ROI2). Sixteen (25.4%) of 63 patients with CNS lymphoma met inclusion criteria. There were 8 men; median age was 61 (range 22–81) years. Histological diagnoses were diffuse large B cell lymphoma (n = 14) and intravascular lymphoma (n = 2). Fifteen (93%) patients had enhancing lesions (5 solitary; 10 multifocal); most enhancing lesions had T1 hypointense (67%) and T2 mixed (53%) signals, and 6 (40%) had central non-enhancing regions. Nine (56%) patients had lesions with susceptibility. Using the ROI methods, median values for minimum ADC and mean ADC ranged 0.65–0.71 × 10–3 mm2/s and 0.79–0.84 × 10–3 mm2/s respectively. PCNSL with atypical radiological features represented one-fourth of our histologically diagnosed lymphoma cases; low ADC values in atypical lesions should prompt clinicians to consider early biopsy for definitive diagnosis.

Objective To determine potential prognostic factors for survival, need for feeding and ventilation support in motor neuron diseases (MND) patients in a multi-racial Asian population. Methods One hundred and four MND patients from the Singapore General Hospital (SGH) between January 2004 and December 2017 were reviewed. All relevant clinical data, demographic information were collected. Kaplan-Meier and cox regression model were performed to identify potential prognostic factors for crucial outcomes (survival, need for feeding support and ventilation support). Results Mean age of onset was 59.54± 10.91 years, Mean age of onset in Malays was significantly younger than that of other ethnic groups (Malay: 54.18±12.95years; Non-Malay: 60.39±10.38years, p=0.035). Fifty six of the male and 33of the female were diagnosed with ALS (90.3% vs 78.6% p=0.048). Mean overall survival duration from symptom onset was significantly longer in female than male patients (female: 39.2± 29.04 months; male: 29.4± 24.06months, P=0.03). Bulbar onset was a significant risk predictor for both the need of feeding support (HR=3.87, p

The study investigated how pediatric speech-language pathologists (SLPs) applied telepractice to compensate for the loss of in-person services and the dynamics of telepractice use during the COVID-19 pandemic in a rural state. We conducted interviews with 10 SLPs and then a statewide survey in which 51 SLPs participated. The qualitative interviews revealed themes including changes in service environment due to the pandemic (e.g., transition to telepractice, losing clients), challenges in the transition to telepractice (e.g., limited training, difficulty engaging clients), worsening wellbeing of clinicians and clients, and SLPs’ perspectives and suggestions towards telepractice in the future. Survey results showed service disruptions and transition dynamics during the pandemic. SLPs’ weekly caseloads reduced from an average of 42.3 clients prior to the pandemic to 25.9 and 23.4 from March to May and from June to September 2020, respectively, and then recovered to 37.2 clients from October to December 2020. In contrast, the number of telepractice caseloads sharply increased from 0.2 clients per week prior to the pandemic to 14.8 from March to May 2020. The weekly telepractice caseloads then declined to 5.5 clients from June to September and 7.9 clients from October to December 2020. In the months right after the pandemic outbreak (i.e., March to May), client children struggled with treatment gains and behavioral wellbeing. However, their outcomes gradually improved by October to December and approached pre-pandemic levels. About one-third of the SLPs reported that they would be more likely or much more likely to use telepractice in the future regardless of the pandemic. However, only about a quarter perceived telepractice as comparable to in-person services. We concluded that the transition from in-person services to telepractice substantially mitigated service disruptions right after the pandemic outbreak and that telepractice’s substitute role evolved over time.

Background: The associations of the consumption of cruciferous vegetables (CVs) and their bioactive components, isothiocyanates (ITCs), with ovarian cancer (OC) mortality have been unclear, owing to limited studies and inconsistent findings. To date, no studies have evaluated these associations among Chinese patients with OC. This study aims to provide more evidence indicating the relationships of pre-diagnosis CVs and ITC intake with OC survival.Methods: We examined the associations of pre-diagnosis CV and ITC intake with OC mortality in a hospital-based cohort (n = 853) of Chinese patients with epithelial OC between 2015 and 2020. Pre-diagnosis dietary information was evaluated with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021 via medical records and active follow-up. The associations were examined with the Cox proportional hazards model, adjusted for potential confounders, and stratified by menopausal status, residual lesions, histological type, and body mass index (BMI).Results: During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), we observed 130 deaths. The highest tertile of total CV intake was associated with better survival than the lowest tertile intake [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.98, p trend < 0.05]. In addition, higher intake of ITCs from CVs was associated with better survival (HRT3VS.T1 = 0.59, 95% CI = 0.36–0.99, p trend = 0.06). Significant inverse associations were also observed for subgroup analyses stratified by menopausal status, residual lesions, histological type, and BMI, although not all associations showed statistical significance.Conclusion: Increasing pre-diagnosis consumption of CVs and ITCs was strongly associated with better survival in patients with OC.

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.

Background: Kasabach–Merritt syndrome (KMS) is characterized by large hemangiomas and persistent thrombocytopenia, which may result in visceral hemorrhage and disseminated intravascular coagulation. This study aimed to evaluate the value of transarterial embolization (TAE) in neonatal KMS patients.Patients and Methods: The clinical course of 11 neonates with KMS who underwent TAE in the Department of Neonatology, Anhui Provincal Children's Hospital, Anhui Medical University, China, were reviewed retrospectively.Results: Eleven neonates with KMS (nine male and two female) were admitted to our hospital between the age of 1 h and 6 days. All were born with progressively enlarged hemangiomas and persistent thrombocytopenia. The largest lesion had its maximum size reached at 15 × 8 × 8 cm. Eight patients had cutaneous hemangiomas (1 right face, one oropharynx, one left upper arm, two back, one left lumbar, one right lower leg, and one right thigh), and three patients had liver hemangiomas. All 11 patients underwent TAE. Nine patients underwent two TAEs, and two patients underwent only one embolization procedure. They all obtained >80% devascularization of their lesions without a major complication. The platelet count increased at 2–5 days after treatment and reached normal count and coagulation profile at 18–28 days after the TAE.Conclusions: TAE is a safe and effective alternative therapy for neonatal KMS patients.