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To investigate the influence mechanism of weathering in the biogas production from coal, the characteristics of three coal samples with different weathering degrees obtained from the Wuhai mining area in Inner Mongolia and from the Xishan and Jincheng mining areas in Shanxi province were analyzed using the following methods: humic acid (HA) extraction, three-dimensional fluorescence spectroscopy, X-ray photoelectron spectroscopy and X-ray diffractometry. The results showed that the HA content in weathered coal increased with an increase in weathering degree. The content of dissolved organic matter in moderately and intensively weathered coals was clearly higher than that in slightly weathered coals. Meanwhile, the C–C and C–H in the aromatic ring was broken under the action of weathering, thus decreasing the aromaticity. Additionally, the weathering process also intensified the disordering of the directional arrangement of the macromolecular structure, causing the crystallinity of the coal to decrease. These conditions facilitated the degradation and utilization of coal by microorganisms and can be helpful to produce more biogas from coal.

Background Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. Research Question Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? Study Design and Methods This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. Results A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). Interpretation Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02147015; URL: www.clinicaltrials.gov

Background Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. Objectives We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. Methods In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for ∼12 wk to 2691 children with MAM aged 6–59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. Results Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64–1.08) for CSWB w/oil, 1.01 (95% CI: 0.78–1.3) for SC + A, 1.05 (95% CI: 0.82–1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49–0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73–1.6) and 0.96 (95% CI: 0.67–1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. Conclusions The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.

Rationale: Patients with newly diagnosed tuberculosis often have inconsistent glycemic measurements during and after treatment. Distinct glycemic trajectories after the diagnosis of tuberculosis ar...

Objective:To understand how the different data collections methods of the Alberta Health Services Infection Prevention and Control Program (IPC) and the National Surgical Quality Improvement Program (NSQIP) are affecting reported rates of surgical site infections (SSIs) following total hip replacements (THRs) and total knee replacements (TKRs).Design:Retrospective cohort study.Setting:Four hospitals in Alberta, Canada.Patients:Those with THR or TKR surgeries between September 1, 2015, and March 31, 2018.Methods:Demographic information, complex SSIs reported by IPC and NSQIP were compared and then IPC and NSQIP data were matched with percent agreement and Cohen’s κ calculated. Statistical analysis was performed for age, gender and complex SSIs. A P value Results:In total, 7,549 IPC and 2,037 NSQIP patients were compared. The complex SSI rate for NSQIP was higher compared to IPC (THR: 1.19 vs 0.68 [P = .147]; TKR: 0.92 vs 0.80 [P = .682]). After matching, 7 SSIs were identified by both IPC and NSQIP; 3 were identified only by IPC, and 12 were identified only by NSQIP (positive agreement, 0.48; negative agreement, 1.0; κ = 0.48).Conclusions:Different approaches to monitor SSIs may lead to different results and trending patterns. NSQIP reports total SSI rates that are consistently higher than IPC. If systems are compared at any point in time, confidence on the data may be eroded. Stakeholders need to be aware of these variations and education provided to facilitate an understanding of differences and a consistent approach to SSI surveillance monitoring over time.

Background Measures that better describe “healthy” and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed. Objectives We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes. Methods The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6–59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and

Junhui Xu,* Mangju Wang,* Ye Shen, Miao Yan, Weiwei Xie, Bingjie Wang, Huihui Liu, Xinan Cen Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinan CenDepartment of Hematology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing, 100034, People’s Republic of ChinaTel +86-10-83575746Email cenxn@bjmu.edu.cnBackground: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear.Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed.Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P< 0.001), ALP> 187.5IU/L (P=0.032) and ALB< 25g/L (P< 0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb< 25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P< 0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002).Conclusion: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.Keywords: symptomatic multiple myeloma, smoldering multiple myeloma, AL amyloidosis, poor prognostic factor

Objective:Adverse outcomes following Clostridioides difficile infection (CDI) are not often reported for long-term care facility (LTCF) residents. We focused on the adverse outcomes due to CDI identified in Alberta LTCFs.Methods:All positive Clostridioides difficile stool specimens identified by laboratory-identified (LabID) event surveillance in Alberta from 2011 to 2018, along with Alberta Continuing Care Information System, were used to define CDI in Alberta LTCFs. CDI cases were classified as long-term care onset, hospital onset, and community onset. Laboratory records were linked to provincial databases to analyze acute-care admissions and mortality within 30-day post CDI. Age, sex, case classification, episode, and operator type, were investigated using logistic regression.Results:Overall, 902 CDI cases were identified in 762 LTCF residents. Of all CDI events, 860 (95.3%) were long-term care onset, 38 (4.2%) were hospital onset, and 4 (0.4%) were community onset. The CDI rate was 2.0 of 100,000 resident days. In total, 157 residents (20.6%) had 30-day all-cause mortality, 126 CDI cases (14.0%) had 30-day all-cause acute-care admissions. The 30-day all-cause mortality rate was significantly higher in residents aged >80 versus ≤80 years (24.9 vs 12.3 per 100 residents; P < .05). Residents aged >80 years, with hospital-onset CDI, and those staying in private or voluntary LTCFs were more likely to have 30-day all-cause acute-care admissions.Conclusions:The prevalence of CDI adverse outcomes is in LTCFs was found to be high using LabID event surveillance. Annual review of CDI adverse outcomes using LabID event can minimize the burden of surveillance and standardize the process across all Alberta LTCFs.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) conducted large field studies on schistosomiasis control and elimination in Africa. All of these studies, carried out in low-, moderate-, and high-prevalence areas, resulted in a reduction in prevalence and intensity of Schistosoma infection after repeated mass drug administration (MDA). However, in all studies, there were locations that experienced minimal or no decline or even increased in prevalence and/or intensity. These areas are termed persistent hotspots (PHS). In SCORE studies in medium- to high-prevalence areas, at least 30% of study villages were PHS. There was no consistent relationship between PHS and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. In a series of small studies, factors that differed between PHS and villages that responded to repeated MDA as expected included sources of water for personal use, sanitation, and hygiene. SCORE studies comparing PHS with villages that responded to MDA suggest the potential for PHS to be identified after a few years of MDA. However, additional studies in different social-ecological settings are needed to develop generalizable approaches that program managers can use to identify and address PHS. This is essential if goals for schistosomiasis control and elimination are to be achieved.

Regenerative medicine (RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology (RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs (e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single‐dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single‐dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high‐fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration‐time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single‐nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single‐nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single‐dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABCB1 (rs1045642) mutation group, whereas t1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation.

Sepsis is a multiple organ dysfunction elicited by the dysregulated host immune response to microbial infection. Acute respiratory distress syndrome (ARDS) is a serious and acute inflammatory lung injury resulting from sepsis and other severe diseases. The present study aims to investigate the role of S100A12, a pro-inflammatory factor, in the pathophysiologic mechanism underlying the process in sepsis-induced ARDS. In present study, Hematoxylin and Eosin (H&E) Staining was performed to observe pathological changes. Enzyme-Linked Immunosorbent Assay (ELISA) was employed to analyze the levels of inflammatory cytokines. Western blot, immunohistochemistry (IHC) staining and reverse-transcriptase quantitative real-time PCR (RT-qPCR) were performed to determine target gene and protein expression. TUNEL assay and flow cytometry were performed to assay cell apoptosis. We found that the levels of S100A12 and soluble receptor for advanced glycation end-products (sRAGE) are upregulated in the serum of patients with Sepsis-induced ARDS and sepsis mice. Furthermore, higher cell apoptosis rate was observed in lung tissue of sepsis mice. In addition, S100A12 resulted in excessive mucins and the secretion of inflammatory cytokines secretion, and promoted the expression of chemokines and cell adhesion molecules via activating nucleotide-binding oligomerization domain (Nod) -like receptor (NLR) P3 inflammasome pathway in NHBE cells. Finally, S100A12 increased oxidative stress status and cell apoptosis in NHBE cells. Generally, the present study provides evidence that S100A12 is closely related to pathogenesis of sepsis-induced ARDS. Hence, S100A12 may be a useful biomarker of pulmonary injuries for clinical diagnosis of sepsis-induced ARDS.

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis—better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE’s larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE’s Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children’s infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.

Consumer-grade virtual reality (VR) headset is being used with increasing frequency nowadays, however, the effect on visual function is not clear.We here investigate whether using VR headset changes adults' visual function and take into account the possible factors.We compared the uncorrected distant visual acuity (UDVA), uncorrected near visual acuity (UNVA), best corrected visual acuity (BCVA), low contrast visual acuity (LCVA), glare visual acuity (GVA), refractive error (RE), amplitude of accommodation (ACC), and pupil diameter (PD) before and after using VR headset 10 mintues at a time twice per day for 2 successive weeks in 40 volunteers with a mean age of 28.6 years. Differences in these 8 parameters before vs. after VR headset use were analyzed using SPSS 22.0.In our study, we found that the amplitude of accommodation had significantly increased by 0.53 (F = 5.673;It is discovered that using a consumer-grade VR headset 10 minutes at a time twice daily for 2 weeks improved the amplitude of accommodation of adults dramatically, while neither visual acuity nor refractive error was affected.VR: visual reality; UDVA: uncorrected distant visual acuity; UNVA: uncorrected near visual acuity; BCVA: best corrected visual acuity; LCVA: low contrast visual acuity; GVA: glare visual acuity; RE: refractive error; ACC: amplitude of accommodation; PD: pupil diameter; 3D: three-dimensional; VDTS: visual display terminal syndrome; FOV: field of view; SEQ: spherical equivalent diopter.

Objectives This paper is aimed to explore the value of double source CT angiography (DS-CTA) for diagnosing in-stent restenosis in lower limb artery. Methods From January 2016 to October 2018, all patients with stent in lower limb artery in our hospital were investigated by both DS-CTA and digital subtraction angiography. We measured the minimum lumen diameter and the diameter of the proximal normal vessels under each stent placement. The in-stent restenosis is defined as restenosis when the lumen area decreased by more than 50%. Digital subtraction angiography was performed within 1 week after DS-CT scan. Relationship between DS-CTA and digital subtraction angiography for diagnosing in-stent restenosis in lower limb artery was analyzed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA for diagnosis of in-stent restenosis were analyzed with digital subtraction angiography as the reference standard. A total of 68 stents were placed in 51 patients. Among these patients, 27 cases were diagnosed as in-stent restenosis, presenting as endovascular contrast agent bias or crescent filling defect with the lumen area reducing over 50%, 6 cases of which had no significant in-stent restenosis by digital subtraction angiography analysis. Furthermore, 12 cases were occlusion, in which there was no high density contrast agent in stents; the remaining 41 stents were unobstructed and the contrast agent was filled well, 8 cases of which had significant in-stent restenosis by digital subtraction angiography analysis. In addition, four stents were deformed or distorted. Statistical analysis demonstrated the concentrations of DS-CTA and digital subtraction angiography in diagnosing in-stent restenosis for lower limb artery were closely related, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA were 72.4%, 84.6%, 77.8%, 80.5%, and 79.4%, respectively. Conclusion DS-CTA has a potential reliability for diagnosis of in-stent restenosis in lower limb artery, which may be further improved to be used for clinical interventional treatment of vascular diseases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, characterized predominantly by respiratory symptoms, has affected a small subset of children. Neurologic manifestations have been described in adults, including encephalitis/meningitis, encephalopathy, strokes, seizures, and anosmia,1,2 but there are few reports of neurologic manifestations in children with SARS-CoV-2.3

AIM: To evaluate the effects of epidermal growth factor (EGF) on transforming growth factor-beta1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human corneal epithelial cells (HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and mRNAs expression changes of E-cadherin, N-cadherin and Fibronectin (EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism. RESULTS: With treatment of TGF-β1 only, three EMT-relative proteins and mRNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability (TGF-β1≥5 ng/mL, P

Falls are the leading cause of fatal and non-fatal injuries among older adults. Evidence-based fall prevention programs are delivered nationwide, largely supported by funding from the Administration for Community Living (ACL), to mitigate fall-related risk. This study utilizes data from 39 ACL grantees in 22 states from 2014 to 2017. The large amount of missing values for falls efficacy in this national database may lead to potentially biased statistical results and make it challenging to implement reliable variable selection. Multiple imputation is used to deal with missing values. To obtain a consistent result of variable selection in multiply-imputed datasets, multiple imputation-stepwise regression (MI-stepwise) and multiple imputation-least absolute shrinkage and selection operator (MI-LASSO) methods are used. To compare the performances of MI-stepwise and MI-LASSO, simulation studies were conducted. In particular, we extended prior work by considering several circumstances not covered in previous studies, including an extensive investigation of data with different signal-to-noise ratios and various missing data patterns across predictors, as well as a data structure that allowed the missingness mechanism to be missing not at random (MNAR). In addition, we evaluated the performance of MI-LASSO method with varying tuning parameters to address the overselection issue in cross-validation (CV)-based LASSO.

Key Points Question What are the long-term health outcomes associated with COVID-19 infection 1 year after hospital discharge? Findings In this cohort study of 2433 patients who had been hospitalized with COVID-19, the most common symptoms at 1 year after discharge were fatigue, sweating, chest tightness, anxiety, and myalgia. Patients with severe disease had more postinfection symptoms and higher chronic obstructive pulmonary disease assessment test scores. Meaning This study reported prolonged symptoms of COVID-19 and found that severe disease during hospitalization was a risk factor for more symptoms and higher chronic obstructive pulmonary disease assessment test scores., This cohort study investigates 1-year health outcomes and their associated risk factors among COVID-19 survivors in Wuhan, China., Importance The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. Objective To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. Design, Setting, and Participants This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. Exposures COVID-19. Main Outcomes and Measures All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. Results Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P

Importance Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated. Objectives To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19. Design, Setting, and Participants This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts. Main Outcomes and Measures The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts. Results Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient’s symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8). Conclusions and Relevance This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.

Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study. Blood samples were collected before and 2 h after administration for subsequent testing and for the extraction of DNA samples. Voriconazole and voriconazole N-oxide in the plasma were detected by LC-MS/MS. The effect of voriconazole on CYP3A activity was evaluated by the ratio of the endogenous biomarkers 6β-hydroxycortisol and cortisol.During the study period, the overall incidence of adverse reactions was 33.6% (with no deaths). The metabolite type of CYP2C19 and combined use of CYP2C19 enzyme inhibitors both had a significant impact on voriconazole exposure. Voriconazole has a long-lasting and potent inhibitory effect on CYP3A activity. The exposure of CYP3A substrate in combination with metabolic enzyme inhibitors voriconazole could increase. Therefore, the combination uses with voriconazole need to be considered carefully and assessed adequately.

ImportanceUniversities are unique settings with large populations, congregate housing, and frequent attendance of events in large groups. However, the prevalence of previous infection with SARS-CoV-2 in university students, including symptomatic and asymptomatic disease, is unknown.ObjectiveTo determine the prevalence of previous infection, risk factors for infection, and the prevalence of persistent symptoms following infection among university students.DesignThis was a cross-sectional study that surveyed students about demographics, risk factors, and symptoms, and simultaneously tested their saliva for IgA antibodies to SARS-CoV-2. To estimate the prevalence of previous infection we adjusted our intentional sample of a diverse student population for year in school and age to resemble the composition of the entire student body, and adjusted for the imperfect sensitivity and specificity of the antibody test. Univariate and multivariate analysis was used to identify independent risk factors for infection.SettingA large public university in Athens, Georgia between January 22 and March 22, 2021.ParticipantsUndergraduate and graduate students; 488 completed the survey, 432 had a valid antibody result. and 428 had both.ExposurePrevious infection with SARS-CoV-2 based on measurement of IgA antibodies in saliva and adjustment for sample characteristics and test accuracy.Main Outcomes and MeasuresThe primary outcome was the estimated prevalence of previous infection with SARS-CoV-2. Secondary outcomes were independent risk factors for infection, and the prevalence of persistent symptoms among persons reporting a previous symptomatic infection.ResultsThe estimated prevalence of previous infection for 432 participants with valid antibody results was between 41% and 42%. Independent risk factors for infection included male sex, having a roommate with a known symptomatic infection, and having 2 or fewer roommates. More frequent attendance of parties and bars was a univariate risk factor, but not in the multivariate analysis. Of 122 students reporting a previous symptomatic infection, 14 (11.4%) reported persistent symptoms a median of 132 days later.Conclusions and RelevancePrevious infection with SARS-CoV-2, both symptomatic and asymptomatic, was common at a large university. Measures that could prevent resurgence of the infection when students return to campus include mandatory vaccination policies, mass surveillance testing, and testing of sewage for antigen to SARS-CoV-2.Key PointsQuestionWhat is the prevalence of previous infection with SARS-CoV-2 and the prevalence of persistent symptoms in university students?FindingsIn this sample of 432 students who provided saliva for IgA antibodies, we estimate that 41% to 42% had evidence of previous infection. Of 122 reporting a previous symptomatic infection, 14 (11%) were still symptomatic a median of 132 days later.MeaningSymptomatic and asymptomatic infections with SARS-CoV-2 are common among university students, and a significant percentage had persistent symptoms over a long duration.

Background Avian influenza A H7N9 (A/H7N9) is characterized by rapid progressive pneumonia and respiratory failure. Mortality among laboratory-confirmed cases is above 30%; however, the clinical course of disease is variable and patients at high risk for death are not well characterized. Methods We obtained demographic, clinical, and laboratory information on all A/H7N9 patients in Zhejiang province from China Centers for Disease Control and Prevention electronic databases. Risk factors for death were identified using logistic regression and a risk score was created using regression coefficients from multivariable models. We externally validated this score in an independent cohort from Jiangsu province. Results Among 305 A/H7N9 patients, 115 (37.7%) died. Four independent predictors of death were identified: older age, diabetes, bilateral lung infection, and neutrophil percentage. We constructed a score with 0–13 points. Mortality rates in low- (0–3), medium- (4–6), and high-risk (7–13) groups were 4.6%, 32.1%, and 62.7% (Ptrend < .0001). In a validation cohort of 111 A/H7N9 patients, 61 (55%) died. Mortality rates in low-, medium-, and high-risk groups were 35.5%, 55.8, and 67.4% (Ptrend = .0063). Conclusions We developed and validated a simple-to-use, predictive risk score for clinical use, identifying patients at high mortality risk.

Objective Systemic sclerosis (SSc) is a rare debilitating autoimmune disease of the connective tissue. This study aimed to assess the recent prevalence and incidence of SSc across the world. Methods Using a systematic search strategy, PubMed/MEDLINE and EMBASE were searched to identify relevant studies published between 2006 and 2016. Two reviewers independently evaluated studies for inclusion based on inclusion/exclusion criteria and performed data extraction. The review was conducted and reported following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The pooled prevalence of SSc was calculated by meta-analysis using a random-effects model. Results There were 1364 references retrieved using the initial searching strategy, and 20 epidemiological publications were selected for data extraction. The identified studies reported prevalence ranging from 3.8 per 100 000 in Taiwan to 50 per 100 000 in the USA. The prevalence was 23 per 100 000 (95% CI: 16-29 per 100 000; 18 studies) in a pooled sample of 11 574 individuals. Incidence rate of SSc ranges from 0.77 per 100 000 person-years in the Netherlands to 5.6 per 100 000 person-years in the USA. SSc predominates in females with higher prevalence and incidence rates. It is important to note that different methodologies were used to derive these numbers so comparisons were made with caution. Conclusion This review provides an assessment of the current estimates of disease prevalence and incidence of SSc. The epidemiological burdens of SSc vary among different regions of the world. The epidemiological data need to be interpreted with caution considering the methodological differences in deriving these estimates.

Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

Background Uncomplicated episodes of prolonged acute cough are usually viral and self-limited, but despite evidence and recommendations to the contrary, they are often treated with antibiotics. Methods Mixed cross-sectional and prospective observational study of adults 18 years or older presenting to two urgent care centers with a cough of 7 to 56 days as their chief complaint. Factors associated with cough duration and clinical decisions were analyzed by univariate and multivariate logistic regression. Results Of the 125 enrolled patients, 118 (94%) received an antibiotic, 97 (78%) a cough suppressant, 87 (70%) a systemic corticosteroid, and 39 (31%) a chest X-ray (CXR). Longer duration of cough was associated with the presence of self-reported wheezing or noises (adjusted odds ratio 6.29, 95% CI 1.36–29.16) while the presence of both wheezing and crackles on a clinician chest exam was associated with shorter duration (aOR 0.03, 95% CI 0.00–0.27). A clinician was more likely to order a CXR in patients with dyspnea (aOR 3.01, 95% CI 1.21–7.49), less likely to prescribe a systemic corticosteroid in patients with crackles (aOR 0.27, 95% CI 0.09–0.82), and more likely to prescribe a cough suppressant to older patients (1.04 per additional year of age, 95% CI 1.01–1.07). Conclusions Systemic corticosteroids and cough suppressants are being prescribed at high rates in patients with uncomplicated acute cough in the urgent care setting. Additional studies to determine if similar rates are seen in other urgent care centers, or in other contemporary ambulatory settings are warranted.

Background: A systematic review of clinical decision rules to identify patients at low risk for community-acquired pneumonia (CAP) has not been previously presented in the literature. Methods: A systematic review of MEDLINE for prospective studies that used at least 2 signs, symptoms, or point-of-care tests to determine the likelihood of CAP. We included studies that enrolled adults and adolescents in the outpatient setting where all or a random sample of patients received a chest radiograph as the reference standard. We excluded retrospective studies and studies that recruited primarily patients with hospital-acquired CAP. Results: Our search identified 974 articles, 12 of which were included in the final analysis. The simple heuristic of normal vital signs (temperature, respiratory rate, and heart rate) to identify patients at low risk for CAP was reported by 4 studies and had a summary estimate of the negative likelihood ratio (LR−) of 0.24 (95% CI, 0.17 to 0.34) and a sensitivity of 0.89 (95% CI, 0.79 to 0.94). The simple heuristic of normal vital signs combined with a normal pulmonary examination to identify patients at low risk for CAP was reported by 3 studies, and had a summary estimate of LR− of 0.10 (95% CI, 0.07 to 0.13) with an area under the receiver operating characteristic curve of 0.92. Conclusions: Adults with an acute respiratory infection who have normal vital signs and a normal pulmonary examination are very unlikely to have CAP. Given a baseline CAP risk of 4%, these patients have only a 0.4% likelihood of CAP.

Background: The respective and combinatorial roles of surgery, Rituximab and chemotherapy in primary gastric diffuse large B cell lymphoma (PGDLBCL) therapy remained unclear. The purpose of the study was to evaluate present treatment strategies and prognostic factors of PGDLBCL. Methods: 272 cases (from 1994-1 to 2015-12) were retrospectively analyzed. According to the therapy regimen, patients were classified into four groups: chemotherapy (C), chemotherapy + surgery (C+S), Rituximab + chemotherapy (R+C), and Rituximab + chemotherapy + surgery (R+C+S). Results: The 3-year progression-free survival (PFS) and 3-year overall survivals (OS) of the entire cohort were 77.0% and 81.2% respectively (median follow-up time: 44.3 months). Survival of surgery-treated patients was superior to the survival of those receiving drug therapy alone (PFS: 82.6% vs. 74.7%, p=0.015; OS: 87.8% vs. 78.6%, p=0.036). Rituximab showed significant clinical benefit in OS (87.1% vs. 75.0%, p=0.007), especially in advanced-stage or high risk (IPI 3-5) patients. Group C had the lowest PFS and OS among the four groups, while the survival of other three groups were similar (Group C vs. Group C+S vs. Group R+C vs. Group R+C+S: 3-year PFS: 67.2% vs. 81.4% vs. 81.2% vs. 81.8%, p=0.002; 3-year OS: 68.4% vs. 85.4% vs. 87.2% vs. 88.6%, p

Introduction: Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret. Hypothesis: A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD. Methods: We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance ( P -7 ) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model ( Table ). Results: We identified a common missense variant, CST9 rs2983640, in a previously reported locus ( CST3 intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L, P =7.64х10 -92 ; HRS whites: beta=-0.05 mg/L, P =4.71х10 -6 ; HRS African Americans: beta=-0.03 mg/L, P =0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L, P =2.46х10 -91 ). After controlling for the CST3 variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L, P =0.04; UKB GWAS: beta=0.003 mg/L, P =1.47х10 -10 ). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L, P =0.005; conditional effect: beta=0.004 mg/L, P =0.86). The CST9 rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m 2 , P =1.98х10 -6 ) and higher hazard of developing CKD progression independent of the reported CST3 variant ( Table ). Conclusions: We identified a novel missense variant influencing cystatin C level and CKD progression.

ObjectiveAge-dependent asymptomatic and symptomatic transmission dynamics of COVID-19 have not been well quantified due to limited data. MethodsThrough a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. ResultsThe difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.72% lower transmissibility rate than symptomatic cases, and 74.10% (95%CI: 65.85% - 80.72%) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.22% (95%CI: 22.97% - 34.56%). Simulation showed that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate the spreading. ConclusionAsymptomatic COVID-19 cases play a significant role in transmission. Vaccine Strategies prioritizing the population between 30-60 years old are likely to have the most population-level benefits.

Lung cancer screening by computed tomography (CT) reduces mortality but exhibited high false-positive rates. We established a diagnostic classifier combining chest CT features with bronchial transcriptomics. Patients with CT-detected suspected lung cancer were enrolled. The sample collected by bronchial brushing was used for RNA sequencing. The e1071 and pROC packages in R software was applied to build the model. Eventually, a total of 283 patients, including 183 with lung cancer and 100 with benign lesions, were included into final analysis. When incorporating transcriptomic data with radiological characteristics, the advanced model yielded 0.903 AUC with 81.1% NPV. Moreover, the classifier performed well regardless of lesion size, location, stage, histologic type, or smoking status. Pathway analysis showed enhanced epithelial differentiation, tumor metastasis, and impaired immunity were predominant in smokers with cancer, whereas tumorigenesis played a central role in non-smokers with cancer. Apoptosis and oxidative stress contributed critically in metastatic lung cancer; by contrast, immune dysfunction was pivotal in locally advanced lung cancer. Collectively, we devised a minimal-to-noninvasive, efficient diagnostic classifier for smokers and non-smokers with lung cancer, which provides evidence for different mechanisms of cancer development and metastasis associated with smoking. A negative classifier result will help the physician make conservative diagnostic decisions.

Background Intraocular lens (IOL) calculation using traditional formulas for post-corneal refractive surgery eyes can yield inaccurate results. This study aimed to compare the clinical accuracy of the newly developed Zhang & Zheng (ZZ) formula with previously reported IOL formulas. Study design Retrospective study. Methods Post-corneal refractive surgery eyes were assessed for IOL power using the ZZ, Haigis-L, Shammas, Barrett True-K (no history), and ray tracing (C.S.O Sirius) IOL formulas, and their accuracy was compared. No pre-refractive surgery information was used in the calculations. Results This study included 38 eyes in 26 patients. ZZ IOL yielded a lower arithmetic IOL prediction error (PE) compared with ray tracing (P = 0.04), whereas the other formulas had values like that of ZZ IOL (P > 0.05). The arithmetic IOL PE for the ZZ IOL formula was not significantly different from zero (P = 0.96). ZZ IOL yielded a lower absolute IOL PE compared with Shammas (P P = 0.02), Barrett true K (P = 0.03), and ray tracing (P P P = 0.03), Barrett True K (P = 0.02), and ray tracing (P P Conclusions The ZZ IOL formula might offer superior outcomes for IOL power calculation for post-corneal refractive surgery eyes without prior refractive data.

Background: The overall performance of a multiple component vaccine assessed by the vaccine-elicited immune responses across various strains in a repeated vaccination setting has not been well-studied, and the comparison between adults and teenagers is yet to be made.Methods: A human cohort study was conducted at the University of Georgia, with 140 subjects (86 adults and 54 teenagers) repeatedly vaccinated in the 2017/2018 and 2018/2019 influenza seasons. Host information was prospectively collected, and serum samples were collected before and after vaccination in each season. The association between host factors and repeated measures of hemagglutination inhibition (HAI) composite scores was assessed by generalized linear models with generalized estimating equations.Results: The mean HAI composite scores for the entire sample (t = 4.26, df = 139, p < 0.001) and the teenager group (t = 6.44, df = 53, p < 0.001) declined in the second season, while the changes in the adults were not statistically significant (t = −1.14, df = 85, p = 0.26). A mixture pattern of changes in both directions was observed in the adults when stratified by prior vaccination. In addition, the regression analysis suggested an interactive effect of age and BMI on the HAI composite scores in the overall population (beta = 0.005; 95% CI, 0.0008–0.01) and the adults (beta = 0.005; 95% CI, 0.0005–0.01).Conclusions: Our study found distinct vaccine-elicited immune responses between adults and teenagers when both were repeatedly vaccinated in consecutive years. An interactive effect of age and BMI on the HAI composite scores were identified in the overall population and the adults.

Background Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. Methods We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). Results Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. Conclusions These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

Ethnopharmacological relevance Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant. Aim of the study This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research. Methods Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the “herbs-components-targets-disease” network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out. Results The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.

Ye Shen,* Jinping Ou,* Bingjie Wang, Lihong Wang, Junhui Xu, Xinan Cen Department of Hematology, Peking University First Hospital, Beijing, 100034, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinan CenDepartment of Hematology, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaEmail cenxn@bjmu.edu.cnBackground: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival.Methods: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed.Results: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥ 2, tumor mass ≥ 10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥ 10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy (P < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy (P < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both P > 0.05).Conclusion: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.Keywords: diffuse large B-cell lymphoma, gastrointestinal complication, bleeding, obstruction, perforation

Pre-existing health conditions may exacerbate the severity of coronavirus disease 2019 (COVID-19). We aimed to estimate the case-fatality rate (CFR) and rate ratios (RR) for patients with hypertension (HBP) and diabetes mellitus (DM) in the New York state. We obtained the age-specific number of COVID-19 confirmed cases and deaths from public reports provided by the New York State Department of Health, and age-specific prevalence of HBP and DM from the Behavioral Risk Factor Surveillance System 2017. We calculated CFR and RR for COVID-19 patients with HBP and DM based on the reported number of deaths with the comorbidity divided by the expected number of COVID-19 cases with the comorbidity. We performed subgroup analysis by age and calculated the CFR and RR for ages of 18–44, 45–64 and 65+ years, respectively. We found that the older population had a higher CFR, but the elevated RRs associated with comorbidities are more pronounced among the younger population. Our findings suggest that besides the elderly, the young population with comorbidity should also be considered as a vulnerable group.

With the increasing demand for automation in aviation manufacturing, it is significant to realize intelligent manufacturing by using industrial robots for the compliant auxiliary assembly of large aircraft components. Based on the requirements of human-machine collaboration, the characteristics of variable admittance control are analyzed by taking the large aircraft components as the assembly object, and the specific implementation methods of variable admittance control based on operation intention recognition for different phases of the auxiliary assembly process are studied. Later, the force signal processing is simulated and an auxiliary assembly test prototype is built to verify the conclusion. The results show that using the proposed method can effectively improve the phenomenon of reverse acceleration mutation and contact bounce of robot, then the robot’s compliance and assembly efficiency in the process of auxiliary assembly are enhanced.

Importance Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

To investigate the effects of biodegradation of guar gum and its products on the production of biogas from coal, experiments on biogas production from coal were carried out using guar gum at different concentrations. The effects of the changes in biogas production, the biodegradation characteristics of guar gum, and the structure of microbial community on coal-to-biogas conversion were investigated. When both coal and guar gum were used for fermentation, the biomethane production was >79.10% higher than the sum of biomethane produced using each of the substrates. The biodegradation of guar gum caused the dissolved organic matter in the reaction system to increase. After biodegradation, some of the functional groups such as OH, C H, and C C were dissociated from guar gum, resulting in the increase of the surface roughness. Moreover, the contents of hydrogen, carbon and oxygen decreased from 6.82%, 43.03%, and 42.46% to below 3%, 18%, and 28%, respectively. Desulfovibrio has a certain negative effect on the biodegradation, but the addition of guar gum could reduce its amount in the reaction system. In addition, guar gum was found to be beneficial to the growth and reproduction of hydrogenotrophic methanogens. The pathway for methane production was converted from acetic acid or methyl reduction to CO2 reduction. This work provides significant information on the gel breaking of guar gum fracturing fluid by microorganisms in in situ coal seam.

Objectives Human infection with avian influenza virus A(H7N9) remains a big threat and has a great potential to cause a pandemic in the foreseeable future. Antiviral treatment using the neuraminidase inhibitors has been recommended to treat H7N9 patients as early as possible, while evidence-based research on its effectiveness for the specific H7N9 infection was lacking. Methods We reviewed data from all laboratory-confirmed avian influenza A H7N9 cases in Zhejiang province between 2013 and 2017 and fit time-dependent survival models to evaluate the effectiveness of neuraminidase inhibitors treatment as an intervention to reduce death risk. Results The result of our final model indicated that there is no significant association (Odds Ratio = 1.29, 95% Confidence Interval [0.78–2.15]) between time to neuraminidase inhibitors treatment and survivorship after controlling for both age and white cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary complete case analysis. Conclusions . We did not find an association between neuraminidase inhibitors treatment and survival benefit in H7N9 patients across various adjusted models and sensitivity analyses of missing data imputations.

The coronavirus disease 2019 (COVID-19) pandemic may impede global tuberculosis elimination goals. In Jiangsu Province, China, tuberculosis notifications dropped 52% in 2020 compared to 2015–2019. Treatment completion and screening for drug resistance decreased continuously in 2020. Urgent attention must be paid to tuberculosis control efforts during and after the COVID-19 pandemic.

We estimated the case-fatality rate (CFR) and ratios (RR) in adult COVID-19 cases with hypertension and diabetes mellitus in the New York State. We found that the elderly population had a higher CFR, but the elevated CFR ratios associated with comorbidities are more pronounced for the younger population.

Background Rapid point-of-care polymerase chain reaction (PCR) diagnostic tests generally provide a qualitative result of positive or negative only. Additional information about the relative viral load could be calculated. Such quantitative information might be useful for making treatment decisions. Methods We enrolled students at a university health center who presented with cough and 1 additional flu-like symptom from December 2016 to February 2017. Data were collected before, during, and 5 days after the clinic visit. All those enrolled in the study received a point-of-care PCR test (cobas Liat). For those patients that tested positive for influenza A, we investigated correlations between the relative viral load and measures of disease severity and recovery. Results One hundred thirty-five students tested positive for influenza A. We found a positive correlation between viral load and body temperature. Time since symptom onset seemed to have a negative correlation but was not statistically significant. We did not find any correlations between viral load and overall symptom severity or outcomes related to recovery. Conclusions Although we found a correlation between relative viral load and body temperature, for our study population of young, overall healthy adults, we did not find that relative viral load provided additional information that could help in determining treatment and disease outcomes. It could be that viral load does provide useful additional information for other groups of patients, such as young children or older adults. Further studies on those populations are warranted., Rapid point-of-care (POC) PCR tests can generate estimates of viral load. Viral loads at diagnosis using a POC PCR test are associated with body temperature. Among our population, viral load at diagnosis was not predictive of disease severity or recovery.

Purpose By 2020, 70% of people living with HIV in the United States will be greater than 50 years of age. As many as 37% of sexually active older people living with HIV (OPLWH) engage in HIV transmission sexual behaviors. In spite of repeated calls for secondary prevention interventions to reduce condomless sex in OPLWH, no age-appropriate, evidence-based secondary prevention interventions exist for this group. Furthermore, many OPLWH face barriers to engaging in face-to-face secondary prevention services because of HIV- and age-related stigma, comorbid mental and physical health conditions that complicate travel, or geographic isolation. High rates of depression in OPLWH may further complicate engagement in interventions intended to reduce HIV transmissions. Telephone-administered motivational interviewing may be a feasible and efficacious intervention for this population. Methods This randomized controlled trial will test the efficacy of a 5-session telephone-administered motivational interviewing plus behavioral skills training (teleMI+BST) intervention versus a 5-session telephone-administered coping effectiveness training (teleCET) control intervention to reduce condomless sex in OPLWH. A diverse sample of 336 OPLWH will be recruited across the U.S. The primary analysis will test the efficacy of teleMI+BST to reduce occasions of non-condom protected anal and vaginal intercourse with HIV serodiscordant sex partners. Secondary analyses will examine the efficacy of teleMI+BST to reduce depressive symptoms in mildly depressed OPLWH. Conclusion This is the first large-scale RCT intended to reduce HIV sexual transmission risk behavior in OPLWH and will add to the literature on secondary prevention telehealth interventions for people living with HIV. ClinicalTrials.gov Identifier: NCT03004170 . This trial has been conducted by the approval of the Institutional Review Board. Participants provided verbal consent to participate in this trial.

Lirong Liang,1 Changwei Li,2 Ye Shen,2 Hengmo Rong,3 Hang Jing,1 Zhaohui Tong3 1Department of Clinical Epidemiology and Tobacco Dependence Treatment Research, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, GA, USA; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhaohui TongDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel +86-10-85231610Fax +86-10-65060167Email tongzhaohuicy@sina.comBackground and Objective: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. We aimed to evaluate the temporal trends in hospitalization and mortality from acute exacerbation of COPD (AECOPD) and the associated financial costs over a 10-year period in Beijing, China.Methods: Hospital admission records from 2008 to 2017 for all patients aged ≥ 20 years with a primary discharge diagnosis of AECOPD were retrieved from the Beijing Public Health Information Center Database. Joinpoint regression was used to analyze trends and calculate the annual percentage change (APC) and average annual percent change (AAPC) for AECOPD hospitalization and mortality.Results: A total of 337,802 AECOPD cases were recorded from 2008 to 2017. An inverse U-shaped trend in the AECOPD hospitalization rate was observed, showing an increase from 150.2 per 100,000 inhabitants in 2008 to 218.7 per 100,000 inhabitants in 2014 (APC: 5.5%, 95% CI: 2.9– 8.2), before declining to 161.13 per 100,000 inhabitants in 2017 (APC: − 9.7%, 95% CI: − 16.0 to-2.9). In-hospital mortality from AECOPD decreased significantly from 3.91% to 2.21% (AAPC: − 11.4%, 95% CI: − 15.5 to− 7.0). A decline in the median length of hospital stay from 13.0 days in 2008 to 12.0 days in 2017 (Ptrend < 0.001) was accompanied by a decrease in the use of mechanical ventilation from 2012 to 2017 (Ptrend < 0.001). However, the total hospitalization cost per case increased from 15953.5 yuan (USD $2281.4) to 19874.5 yuan ($2842.1) during the same period.Conclusion: AECOPD remains a heavy burdenon the health care system in Beijing. Strategies to better manage COPD and reduce hospitalizations from AECOPD are needed.Keywords: COPD, exacerbation, hospitalization cost, mortality, outcome research

Communicable diseases are often virulent, i.e. they cause morbidity symptoms in those infected. While some symptoms may be transmission-enhancing, other symptoms are likely to reduce transmission potential. For human diseases, the reduction in transmission opportunities is commonly caused by reduced activity. There is limited data regarding the potential impact of virulence on transmission potential. We performed an exploratory data analysis of 324 influenza patients at a university health centre during the 2016/2017 influenza season. We classified symptoms as infectiousness-related or morbidity-related and calculated two scores. The scores were used to explore the relationship between infectiousness, morbidity (virulence), and activity level. We found a decrease in the activity level with increasing morbidity scores. There was no consistent pattern between an activity level and an infectiousness score. We also found a positive correlation between morbidity and infectiousness scores. Overall, we find that increasing virulence leads to increased infectiousness and reduced activity, suggesting a trade-off that can impact overall transmission potential. Our findings indicate that a reduction of systemic symptoms may increase host activity without reducing infectiousness. Therefore, interventions should target both systemic- and infectiousness-related symptoms to reduce overall transmission potential. Our findings can also inform simulation models that investigate the impact of different interventions on transmission.