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Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10–5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10−2), Lactobacillus (P = 2.11 × 10−2), Prevotella 7 (P = 4.28 × 10−2), and RuminococcaceaeUCG004 (P = 4.34 × 10−2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10−3) and RuminococcaceaeUCG004 (P = 4.99 × 10−2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10−2), Holdemania (P = 1.22 × 10−2), and Lactococcus (P = 3.39 × 10−2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10−2) and Actinomyces (P = 3.62 × 10−3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition. [ABSTRACT FROM AUTHOR]

Background: The effect of radiotherapy waiting time after last induction chemotherapy (IC‐RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. Methods: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. Results: The IC‐RT was a risk factor for the post‐treatment progression of LANPC (OR = 1.017 95%CI: 1.003–1.031), For patients with LANPC, the IC‐RT > 40 days significantly reduced 5‐year PFS (70% vs. 55%; p = 0.0012), 5‐year OS (84% vs. 73%; p = 0.028), 5‐year DMFS (80% vs. 66%; p = 0.003), 5‐year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC‐RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57–4.6), OS (HR = 2.55; 95%CI: 1.29–5.03), DMFS (HR = 3.07; 95%CI: 1.64–5.76) and LRFS (HR = 2.26; 95%CI: 1.21–4.21). Conclusion: The prognosis of patients will be adversely affected if the IC‐RT exceeds 40 days, especially for stage IVa patients. [ABSTRACT FROM AUTHOR]

Background: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-d-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9–11) vs. 11 (95% CI 10–12) vs. 9 (95% CI 8–12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8–10) vs. 10 (95% CI 9.48–11) vs. 8.708 (95% CI 7.51–11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11–13) vs. 13 (95% CI 12–14) vs. 12 (95% CI 10–14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs. [ABSTRACT FROM AUTHOR]

Objectives: To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). Methods: A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)–derived AEF (AEFS) and DECT-derived AEF (AEFD) were calculated. Correlation between AEFD and AEFS was determined using Pearson's correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEFS, and conventional features + AEFD). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Results: Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEFD (1.14 vs 0.48; p < 0.001) and AEFS (1.08 vs 0.38; p < 0.001) than non-metastatic LNs. AEFD correlated well with AEFS (r = 0.802; p < 0.001), and exhibited comparable performance with AEFS (AUC, 0.867 vs 0.852; p = 0.628). Combining CT image features with AEFS (model 2) and AEFD (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p < 0.001). Conclusions: AEFD correlated well with AEFS, and exhibited comparable performance with AEFS. Integrating qualitative CT image features with both AEFS and AEFD could further improve the ability in diagnosing cervical LN metastasis in PTC. Clinical relevance statement: Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. Key Points: • Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)–derived AEF (AEFS) than non-metastatic LNs in patients with papillary thyroid cancer. • DECT-derived AEF (AEFD) correlated significantly with AEFS, and exhibited comparable performance with AEFS. • Integrating qualitative CT images features with both AEFS and AEFD could further improve the differential ability. [ABSTRACT FROM AUTHOR]

Summary: The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome. Myelin oligodendrocyte glycoprotein (MOG) antibodies and N-methyl-d -aspartate receptor (NMDAR) antibodies can be concurrently detected in certain patients, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) is a cerebrovascular disease with unknown cause. Patients with MMD disease usually experience transient neurological events (TNEs) after revascularization surgery. This retrospective single-center study was aimed to explore the risk factors of postoperative TNEs after surgical revascularization in patients with MMD. Methods: We selected 324 patients who underwent surgical revascularization between January 2017 and September 2022 in our center. The perioperative characteristics of the patients were recorded and the outcome was TNEs after surgery. An analysis of risk factors contributing to postoperative TNEs by using logistic regression model. Results: Three hundred twelve patients were enrolled, and the incidence of postoperative TNEs was 34% in our study. Males were more likely to suffer from postoperative TNEs (OR = 2.344, p = 0.002). Preoperative ischemic presentation (OR = 1.849, p = 0.048) and intraoperative hypotension (OR = 2.332, p = 0.002) were associated with postoperative TNEs. Compared to patients with blood type O, patients with blood type A (OR = 2.325, p = 0.028), B (OR = 2.239, p = 0.027) and AB (OR = 2.938, p = 0.019) had a significantly higher incidence of postoperative TNEs. A risk prediction model for postoperative TNEs was established, and the established risk prediction area under the receiver operating characteristic curve (ROC) of the model was 0.741. Conclusions: Males, preoperative ischemic presentation and intraoperative hypotension were associated with postoperative TNEs. We also found a possible link between postoperative TNEs and ABO blood types after surgical revascularization for moyamoya patients. [ABSTRACT FROM AUTHOR]

Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3–5. The primary outcome was hospital death of AKI patients. A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8–13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3–20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1–5.9%, p = 0.825). The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. registration number ChiCTR-ECH-13003934 [ABSTRACT FROM AUTHOR]

Background: The multiple symptoms of Sjögren's syndrome lead patients affected by this disease to seek medical advice from different medical disciplines and specialists. Diagnoses are often made many years after initial onset, resulting in mental and physical exhaustion and misunderstandings. Purpose: This study was designed to explore the health-seeking experiences of patients with Sjögren's syndrome. Methods: Qualitative research methods and purposive sampling were used. Fourteen patients with Sjögren's syndrome were interviewed by the first author, and the collected data were analyzed using content analysis. Results: Four themes were revealed from the data, including: (1) distressing symptoms; (2) difficulty in diagnosis; (3) concerns about drug side effects; and (4) facing the disease. The participants initially sought medical attention when they began experiencing early onset symptoms that caused discomfort or annoyance. Their doctors' failure to provide proper diagnoses during the long health-seeking process caused a great deal of suffering to the participants. Although related medications should be taken for life, the participants reported taking lower-than-prescribed dosages out of fear of side-effects. The participants explored their process of coping with the disease, which began with denial and ended with acceptance. By learning from their health-seeking process, participants realized that they needed to take proper care of themselves, adapt to life with their disease, and control related symptoms. Conclusions/ Implications for Practice: To facilitate the early diagnosis of Sjögren's syndrome, healthcare professionals should improve their awareness of this condition and refer patients with related symptoms to rheumatologists and immunologists. Effective early diagnosis and treatment can help these patients reduce the time and effort involved in unproductive doctor's visits, allowing them to better continue as productive members of society and to maintain a good quality of life. [ABSTRACT FROM AUTHOR]

Backgrounds: Peripheral arterial disease (PAD) is an increasingly prevalent and highly morbid pathology affecting the older population. Infra‐inguinal bypass (IIB) surgery remains a robust revascularization option in these patients. This study aimed to identify modifiable predictors associated with graft patency and functional outcomes in contemporary Australian vascular surgical practice. Methods: A retrospective analysis of patients undergoing IIB between 2010 and 2020 at a tertiary vascular surgery centre in Australia was performed. Data regarding patient demographics, co‐morbidities, pre‐operative investigations, bypass characteristics, and discharge outcomes were collected. Surveillance ultrasound scans were reviewed to gain information on graft patency and compliance up to 2 years post‐operatively. The primary outcome was graft failure. Secondary outcomes were mobility status and amputation‐free survival at 1 year. Results: A total of 239 IIBs were performed on 207 patients during the 10‐year period. Significant predictors for primary graft occlusion included regional referral (P < 0.01), low pre‐operative haemoglobin level (P < 0.01), post‐operative transfusion requirement (P = 0.02), use of prosthetic conduit (P < 0.01) and non‐compliance to ultrasound surveillance (P < 0.01). Patients with a thrombosed graft were 2.4 times more likely to experience deterioration in mobility status (P < 0.01) and 8.6 times more likely to have major limb amputation or death at 1 year. The amputation‐free survival was 88.3% at 1 year. Conclusion: Optimization of pre‐operative haemoglobin level for IIB should be advocated in clinical practice in order to reduce the risk of graft failure, deterioration in ambulatory function, major limb amputation and mortality. [ABSTRACT FROM AUTHOR]

Transplant renal artery stenosis (TRAS) represents a significant vascular complication subsequent to renal transplantation. This pathology is associated with grave implications including graft dysfunction and mortality. Early identification and therapeutical intervention are imperative for preserving graft longevity and achieving optimal clinical outcomes. We detail the case of a male in his 20s, following renal transplantation, who encountered recurrent TRAS, aetiologically linked to mechanical arterial kinking. Initial management using endovascular techniques yielded insufficient resolution. Consequently, the persistence of endovascular-resistant stenosis necessitated a surgical bypass intervention using the great saphenous vein, granting a 2-year period devoid of restenosis. The existing literature emphasises the indispensability of discerning the appropriate juncture for transitioning from endovascular to surgical management in TRAS cases. The robustness and durability of bypass grafts present an efficacious therapeutical strategy in contemporaneous practice. [ABSTRACT FROM AUTHOR]

Chitosan is an environmentally friendly biomolecule with great potential for application in metal corrosion protection. First, Chitosan benzaldehyde schiff base (CTSB) and 8‐hydroxyquinoline functionalized chitosan benzaldehyde schiff base (HQ‐CTSB) were synthesized from chitosan, benzaldehyde, and 8‐hydroxyquinoline as high‐efficiency and environment‐friendly corrosion inhibitors. The structures of the synthesized products were characterized by infrared spectroscopy. The corrosion of N80 steel was tested using electrochemical measurements and analysis by varied concentrations of CTSB and HQ‐CTSB in a hydrochloric acid solution. The PDP results confirmed that both CTSB and HQ‐CTSB corrosion inhibitors were mixed corrosion inhibitors. Furthermore, the EIS findings revealed that the corrosion inhibition efficiency of the two inhibitors was 87.11% and 98.52% at 800 mg/L, respectively. According to SEM and XPS analyses, the CTSB and HQ‐CTSB molecules bonded to the surface of N80 steel and formed a surface protective layer. Density functional theory (DFT) calculations showed that CTSB and HQ‐CTSB have multiple active sites that may become adsorbent on the metal surface. And molecular dynamics (MD) simulations showed that corrosion inhibitors CTSB and HQ‐CTSB lie flat on the surface of Fe(110). The theoretical calculation agreed well with the experimental results. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically. [ABSTRACT FROM AUTHOR]

Purpose: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi. [ABSTRACT FROM AUTHOR]

Bi2Sr2CaCu2O8+δ (BSCCO) single crystals are promising for high-temperature superconducting electronic devices with ultimate performance. Recently, tailoring superconductivity in ultra-thin BSCCO locally has received wide attention and interest. In this work, we focus on controlling the superconductivity of the uppermost CuO2 double layer of the BSCCO crystal. Gold electrodes are deposited onto the freshly cleaved BSCCO surface by a high-vacuum in situ evaporation technique at room temperature, and then surface Josephson junctions (SJJs) between the two outermost superconducting CuO2 double layers are fabricated as a probe to evaluate the superconductivity of the uppermost double layer. We find that the junction transition temperature Tc′ as well as its critical current density jc depend systematically and reproducibly on the deposition rate of the gold electrode. The electric properties of the SJJs, spanning the range from completely degraded to almost as good as the intrinsic Josephson junctions inside the bulk, systematically reveal the evolutionary process of superconductivity of the uppermost BSCCO layer, extending the range for practical applications. [ABSTRACT FROM AUTHOR]

Purpose: To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto's thyroiditis (HT). Material and methods: A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann–Whitney U test, Student's T-test, and Spearman correlation analyses, respectively, as appropriate. Results: HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p < 0.001). The volume was larger in male than that in female in overall study population and No-HT group (p = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p < 0.05). TPOAb and TgAb also correlated positively with IC in HT group (p = 0.002 and 0.007, respectively). Conclusion: DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid. [ABSTRACT FROM AUTHOR]

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay. Our study revealed several age-related features of NSAE. Generally speaking, male-dominant onset of seizures and memory dysfunctions had more diagnostic significance for the late-onset group. The prodromal symptoms, onset of psychiatric symptoms and central hypoventilation might be specific for those with younger-onset. Notably, in consideration of the higher severity and more frequent requirement for ICU admission, more attention is needed for the younger-onset patients, especially for those with anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the value of texture analysis (TA) of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differential diagnosis between sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC). Methods: Forty-two patients with sinonasal SCC and 30 patients with NHL were retrospectively enrolled. TAs were performed on T2-weighted image (T2WI), apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted image (T1WI). Texture parameters, including mean value, skewness, kurtosis, entropy and uniformity were obtained and compared between sinonasal SCC and NHL groups. Receiver-operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic value and identify the independent TA parameters. Results: The mean value and entropy of ADC, and mean value of contrast-enhanced T1WI were significantly lower in the sinonasal NHL group than those in the SCC group (all P < 0.05). ROC analysis indicated that the entropy of ADC had the best diagnostic performance (AUC 0.832; Sensitivity 0.95; Specificity 0.67; Cutoff value 6.522). Logistic regression analysis showed that the entropy of ADC (P = 0.002, OR = 26.990) was the independent parameter for differentiating sinonasal NHL from SCC. Conclusion: TA parameters of conventional MRI and DWI, particularly the entropy value of ADC, might be useful in the differentiating diagnosis between sinonasal NHL and SCC. [ABSTRACT FROM AUTHOR]

The Yunnan province of China is a typical humid region but with several severe region-wide droughts. Drought indices are generally used to identify and characterize drought events, and then play a key role in drought prediction. Therefore, a novel prediction model was proposed to predict a comprehensive drought indicator (meteorological composite index, MCI) in Yunnan province. This model combined the recurrent neural networks (RNN) based on a gated recurrent neural unit (GRU) and convolutional neural networks (CNN) with optimization using the modified particle swarm optimization (PSO) algorithm. In this model, pre-processed predictor data were input into the GRU module to extract the time features of the sequences. Furthermore, the feature matrices were input into the CNN module to extract the deep local features and the inter-relationship of the predictors. The model was trained and used to predict the monthly MCI drought index of the representative five stations of Yunnan province from 1960 to 2020. The combined model was evaluated by comparison with traditional machine learning models such as the least absolute shrinkage and selection operator (LASSO) and random forest (RF), and the traditional GRU model. The results show significantly improved skills in root mean square error, mean absolute error and Nash–Sutcliffe efficiency coefficient. This novel method was valuable for the monthly drought prediction in Yunnan province and related climate-risk management. [ABSTRACT FROM AUTHOR]

A new esterase gene, est6, was discovered in an activated sludge metagenomic library. The 729-bp gene encodes a 242-amino acid protein (designated Est6) with a molecular mass of 26.1 kDa. Est6 shared only a moderate identity to a putative hydrolase with the highest BLASTP analysis score. Most of the closely related proteins are uncharacterized and are predicted from genome sequencing data of microorganisms or metagenomic DNA sequences. The phylogenetic analysis of Est6 showed that the protein was assigned to family VI esterases/lipases. The catalytic triad of Est6 was predicted to be Ser135, Asp188, and His219, with Ser135 in a typically conserved pentapeptide (GFSQG) of family VI members, which was further confirmed by site-directed mutagenesis. The est6 gene was overexpressed successfully in its soluble form in Escherichia coli and then purified to its tag-free form and homogeneity by affinity chromatography. The purified Est6 in pH 8.0 buffer was active as a monomer. The optimal conditions for Est6 activity were at a temperature of 45 °C and pH of 8.0 when using p-nitrophenyl acetate as a substrate. The enzyme was stable over wide temperature and pH ranges, and it exhibited activity in the presence of organic solvents, metal cations, or detergents. Furthermore, the enzyme showed significant regioselectivity in the spectrophotometric analysis. In conclusion, Est6 might have the potential for applications in biotechnological processes. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE. Methods: A cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE. Results: This survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest diffIculty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management. Conclusion: Our study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication. [ABSTRACT FROM AUTHOR]

This research applies the method of moments quantile regression (MQR) to probe the effects of formal (market and nonmarket) and informal environmental regulations ([ERs] education [EDU] and green technology [TEC]) on the six components of ecological footprint (EF). We investigate whether ERs are feasible tools for lessening environmental degradation by examining the ER-induced environmental Kuznets curve (EKC) hypothesis. Results reveal that the nonmarket-based ER-induced EKC hypotheses are generally supported for carbon, fish, and forest footprints, signifying that when the three EFs reach a specific threshold level the nonmarket-based ER saliently helps to move toward an environmental-friendly condition. Nonmarketbased ER and EDU are most efficient in reducing grazing land. However, we show that ER increases carbon footprint consumption, and ER is not completely effective to solve environmental degradation. Our analysis affirms the usage of MQR estimates, suggesting that the six types of EFs exhibit a nonlinearly response with ER across EF quantiles. Specifically, the U-shape links are present in the forest-EDU and graze-NMKT nexus in the subsample of developing countries, implying that the EKC hypothesis is not valid for developing country. Therefore, government should encourage different ERs to reduce different types of environmental degradation. [ABSTRACT FROM AUTHOR]

Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case–control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019– 1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427– 0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥ 16 years (adjusted OR = 1.745, 95% CI = 1.103– 2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021– 2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676– 0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans. [ABSTRACT FROM AUTHOR]

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD), and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4‐NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune‐associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4‐NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)‐like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM‐like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4‐NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most‐updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4‐NMOSD/MOGAD. Treatment cautions including drug‐drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the attributable mortality of new-onset acute kidney injury (AKI). Methods: The data in the present study were derived from a multi-center, prospective cohort study in China that was performed at 18 Chinese ICUs. A propensity-matched analysis was performed between matched patients with and without AKI selected from all eligible patients to estimate the attributable mortality of new-onset AKI. Results: A total of 2872 critically ill adult patients were eligible. The incidence of new-onset AKI was 29.1% (n = 837). After propensity score matching, 788 patients with AKI were matched 1:1 with 788 controls (patients without AKI). Thirty-day mortality was significantly higher among the patients with AKI than among their matched controls (25.5% versus 17.4%, p < 0.001). Subgroup analysis in terms of AKI classification showed that there was no significant difference (p = 0.509) in 30-day mortality between patients with stage 1 AKI and their matched controls. The attributable mortality values of stage 2 and stage 3 AKI were 12.4% [95% confidence interval (CI) 2.6–21.8%, p = 0.013] and 16.1% (95% CI 8.2–23.8%, p < 0.001), respectively. The attributable mortality of persistent AKI was 15.7% (95% CI 8.8–22.4%, p = 0.001), while no observable difference in 30-day mortality was identified between transient AKI patients and their matched non-AKI controls (p = 0.229). Conclusion: The absolute excess 30-day mortality that is statistically attributable to new-onset AKI is substantial (8.1%) among general ICU patients. However, neither stage 1 AKI nor transient AKI increases 30-day mortality. [ABSTRACT FROM AUTHOR]

Objectives: The current study evaluates the performance of dual-energy computed tomography (DECT) derived extracellular volume (ECV) fraction based on dual-layer spectral detector CT for diagnosing cervical lymph nodes (LNs) metastasis from papillary thyroid cancer (PTC) and compares it with the value of ECV derived from conventional single-energy CT (SECT). Methods: One hundred and fifty-seven cervical LNs (81 non-metastatic and 76 metastatic) were recruited. Among them, 59 cervical LNs (27 non-metastatic and 32 metastatic) were affected by cervical root artifact on the contrast-enhanced CT images in the arterial phase. Both the SECT-derived ECV fraction (ECVS) and the DECT-derived ECV fraction (ECVD) were calculated. A Pearson correlation coefficient and a Bland–Altman analysis were performed to evaluate the correlations between ECVD and ECVS. Receiver operator characteristic curves analysis and the Delong method were performed to assess and compare the diagnostic performance. Results: ECVD correlated significantly with ECVS (r = 0.925; p <0.001) with a small bias (−0.6). Metastatic LNs showed significantly higher ECVD (42.41% vs 22.53%, p <0.001) and ECVS (39.18% vs 25.45%, p <0.001) than non-metastatic LNs. By setting an ECVD of 36.45% as the cut-off value, optimal diagnostic performance could be achieved (AUC = 0.813), which was comparable with that of ECVS (cut-off value = 34.99%; AUC = 0.793) (p = 0.265). For LNs affected by cervical root artifact, ECVD also showed favorable efficiency (AUC = 0.756), which was also comparable with that of ECVS (AUC = 0.716) (p = 0.244). Conclusions: ECVD showed a significant correlation with ECVS. Compared with ECVS, ECVD showed comparable performance in diagnosing metastatic cervical LNs in PTC patients, even though the LNs were affected by cervical root artifacts on arterial phase CT. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene–gene and gene–environment interactions in AR. Methods: A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case–control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene–gene and gene–environment interactions. Results: In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene–gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene–environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction. Conclusion: The genetic polymorphisms of TLR2 and CD14 and gene–gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene–environment interactions and AR. [ABSTRACT FROM AUTHOR]

Background: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration: MEXCOVID, NCT04276987. [ABSTRACT FROM AUTHOR]

What kinds of countries are likely to be prosperous and have a sustainable environment at the same time? How might countries reorient their policy setting to be more capable of suppressing environmental degradation? To explore these questions, this research examines data from 99 countries for 2006–2017, takes the six major forms of ecological footprint (EF) as indicators of environmental quality, and probes the environmental Kuznets curve (EKC) hypothesis via quantile regression approach. We find that tourism development leads to greater environmental degradation, with tourism development particularly corresponding to more usage of carbon absorption land and cropland. The lower the country security is, the better is the environmental quality. Economic complexity also worsens environmental quality. However, country security weakens the negative influence of tourism development and economic complexity on environmental quality, specifying that better country security stalls the negative impact of tourism and economic complexity on environmental quality. Results mostly support the tourism- and country security–induced EKC hypotheses in fishing footprint, whereas economic complexity–induced EKC is generally validated in cropland footprint. Finally, we present that tourism arrivals, economic complexity, and country security have varying impacts across diverse ecological footprint quantiles. [ABSTRACT FROM AUTHOR]

Background: Pre-existing chronic pain has been associated with severe postoperative pain. In this study, we sought to prospectively analyse the association between the duration of chronic low back pain and the intensity of acute postoperative pain after lumbar fusion surgery. Methods: A total of 330 patients who underwent lumbar fusion surgery were divided into three groups (chronic low back pain less than 1 year, one to 5 years, and more than 5 years) based on the duration of chronic pain. On the first postoperative day, the maximum pain scores of each patient were recorded during the day and at night. Bivariate correlation and logistic regression were performed to identify relationships between acute postoperative pain and related variables (age, sex, smoking history, body mass index, operation history, duration of surgery, level of preoperative pain, aetiology of back pain, Self-rating Anxiety Scale, Self-rating Depression Scale, FRAIL scale, and duration of chronic low back pain). If the postoperative pain score was > 3 when the patient reported was at rest, the patients were treated with postoperative intravenous self-controlled analgesia or rescue analgesics if necessary. Results: There was an association between severe acute postoperative pain and the duration of chronic low back pain. In terms of VAS day, multivariable logistic regression showed the duration of chronic low back pain was not statistically significant (OR = 2.48, 95% CI: 0.900 to 6.828, p = 0.0789). The result is uncertain because the confidence interval included the null after controlling for SAS, SDS, BMI, and aetiology of back pain. In terms of VAS night, patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year (OR = 3.546, 95% CI: 1.405 to 8.95, p = 0.0074). Hospital stay, the pain score on the day of discharge and the pain score after 3 months displayed no significant difference among the three groups (P > 0.05). However, the need for postoperative rescue analgesics was different among the three groups (P < 0.05). Conclusion: The longer the duration of chronic pain was, the higher the incidence of moderate to severe acute postoperative pain was and the greater the amount of analgesics required after surgery. Trial registration: This study was registered at the Chinese Clinical Trial Registration Center (http://www.chictr.org.cn/index.aspx, clinical trial number: ChiECRCT20200165, date of registration: July 6, 2020). [ABSTRACT FROM AUTHOR]

Background: Secondary aortoenteric fistula is a rare, highly morbid and often difficult to diagnose, cause of gastrointestinal bleeding. It is associated with prior aortic surgery or placement of a synthetic aortic graft. Our case features staged hybrid endovascular stent-grafting, graft excision, aortoplasty using a bovine pericardial patch, extra-anatomical bypass and complex bowel repair.Case Report: An 82-year-old man presented with gastrointestinal bleeding and Streptococcus Anginosus bacteraemia, with previous aorto-bi-iliac bypass surgery for left common iliac occlusive disease 15 years ago. Computed tomography angiography (CTA), gastroscopy, colonoscopy, capsule endoscopy and enteroscopy identified no bleeding source. Repeat CTA showed gas locules and stranding around the graft and the third part of the duodenum, concerning for fistulous communication. On the next day, a Zenith TX2 thoracic 28x80mm stent-graft was deployed into the infrarenal aorta. On laparotomy, a fistula was present between the Dacron graft and fourth part of the duodenum. The Dacron graft was excised, followed by aortic patching with bovine pericardium. A right-to-left femoral-femoral crossover graft was constructed. CT at one-month post-laparotomy showed no signs of perigraft endoleak and interval resolution of gas locules. He was transferred to a rehabilitation facility on the 34th post-operative day with a multidisciplinary follow-up arranged.Discussion: Aortoduodenal fistula is a challenging entity to diagnose and should be suspected in patients with GI bleeding and prior aortic surgery. Endovascular repair alone is a less invasive option but with higher re-infection and late failure rates. Liberal use of appropriate imaging modalities, a judicious repair strategy, long-term follow-up and multidisciplinary approach are critical for its management. [ABSTRACT FROM AUTHOR]

Background: A20, a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3), plays a vital role in the negative regulation of inflammation and immunity. Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20 (HA20). Since HA20 was first described in 2016, a number of new cases have been described in this literature, however, the disease and its pathogenesis are poorly understood. This review seeks to improve clinical recognition of this disorder, and promote both earlier diagnosis and initiation of targeted therapies to improve patients' outcomes. Methods: We reviewed 26 papers about A20 and HA20, and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20. Additionally, we discussed the pathogenesis and treatment of HA20. Results: A total of 24 pathogenic variants of A20 had been reported. There was significant clinical heterogeneity, even among those with the same variants in TNFAIP3. Prior to receiving a molecular diagnosis of HA20, patients had been diagnosed with Behcet's disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, and even adult-onset Stills' disease. The patients with HA20 that presented with inflammatory signatures in NF-κB signaling were mostly responsive to treatment. Conclusions: HA20 is a monogenic autoinflammatory disease with highly variable clinical manifestations. This extensive heterogeneity makes it difficult to set a clinical diagnostic criteria, and genetic sequencing is necessary for a definitive diagnosis of HA20. [ABSTRACT FROM AUTHOR]

The vector transformation and pole reduction from the total-field anomaly are significant for the interpretation. We examined these industry-standard processing procedures in the Fourier domain. We propose a novel iteration algorithm for regional magnetic anomalies transformations to derive the vertical-component data from the total-field measurements with the variation in the core-field direction over the region. Additionally, we use the same algorithm to convert the calculated vertical-component data into the corresponding data at the pole and realize the processing of differential reduction to the pole (DRTP). Unlike Arkani-Hamed's DRTP method, the two types of iterative algorithms have the same forms, and DRTP is realized by implementing this algorithm twice. The synthetic model's calculation results show that the method has high accuracy, and the field data processing confirms its practicality. [ABSTRACT FROM AUTHOR]

This research crucially investigates COVID-19 variables' impacts on the changing distributions of travel and leisure industry returns across 65 countries via a quantile regression model that uses daily data from December 2019 to May 2020 to provide early evidences from a panel of countries. We find that the change rate in COVID-19 deaths exerts more substantial negative effects on industry returns at majority quantiles than does the impact from the number of confirmed cases. The latter number only saliently and negatively influences the lowest return quantiles, revealing a nonlinear effect of confirmed cases. The study identifies a V-shape correlation between the number of cases recovered and travel and leisure industry returns (i.e. a negative impact at the lower quantiles, but a positive impact at higher quantiles) across return quantiles. This likely denotes that confirmed cases grow exponentially and that their effect may overwhelm the impact of the number of recovered cases. Lastly, this study presents a positive correlation between government response stringency index and returns. [ABSTRACT FROM AUTHOR]

Under the new background of climate change, it is very important to identify the characteristics of drought in North China. Based on the daily meteorological drought comprehensive index from 494 national meteorological stations in North China during 1961–2019, the drought processes and their intensity are identified by applying the "extreme" intensity–duration (EID) theory. Then, the stage variation characteristics of the drought trend, the average drought intensity, and the drought frequency are analyzed. The results show that among the five drought intensity indices the process maximum intensity demonstrates the greatest correlation coefficient with the disaster rate of drought in North China. Therefore, the process maximum intensity of drought is selected as the annual drought intensity to analyze the drought characteristics in North China. According to the climate warming trends, the study period is divided into three stages, that is, 1951–84 (stage I), 1985–97 (stage II), and 1998–2019 (stage III). The comprehensive results show that the drought intensity in North China has significant stage characteristics. In stage I, the drought shows an increasing trend in most parts of North China, but its average intensity is relatively weaker, with a lower severe drought frequency. The drought also shows an increasing trend in most parts in stage II, with a more significant increase rate than that in stage I, and the average drought intensity is the strongest and the severe drought frequency is the highest. In stage III, the drought shows a decreasing trend in some areas, and the average intensity is the weakest, with a lower severe drought frequency. Significance Statement: In this paper, we develop a drought intensity formula, the maximum intensity of drought, based on the "extreme" intensity–duration theory. The maximum intensity of drought was then calculated and selected as an annual drought intensity to analyze the drought characteristics in North China. We found that the annual drought intensity better captured the extremity and the patterns of drought process than that obtained with single indices and comprehensive indices. The results show a decreasing trend of drought in North China after 1998. [ABSTRACT FROM AUTHOR]

Quaternary salt was an efficient additive for hydrate formation, which usually achieves the effect of improving hydrate phase equilibrium conditions by filling the hydrate cage. The effect of quaternary salt on phase equilibrium conditions of gas hydrates such as CH4 and CO2 was mainly relate to the concentration of quaternary salt. In terms of methane hydrate, TiPeAF and TiAAB had significant effects on phase equilibrium under the same phase equilibrium pressure: the phase equilibrium temperature of the system with TiPeAF (0.315%) and TiAAB (0.438%) was 20 K and 22 K higher than pure water system respectively. TBANO3, TAAB and TAAC had little effect on phase equilibrium: the phase equilibrium temperature was 10 K lower than that of the system with TBAB and TBAC. For CO2 hydrate, the phase equilibrium temperature of TiAAB system was 29 K higher than pure water system, and that of TBAF system was 26 K higher than that of pure water system. In addition, the combination of quaternary salt and other additives had a better improvement effect on the phase equilibrium conditions of hydrate: the phase equilibrium temperature of hydrate in the combination system of TBAB (0.05%) and NaCl (0.03%) was 10 K higher compared with the system which adding TBAB only. [ABSTRACT FROM AUTHOR]

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer.Methods: Through integrated quantitative proteomic strategy, we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro.Results: We identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments.Conclusion: This study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer. [ABSTRACT FROM AUTHOR]

Social Assistive Robotics is increasingly being used in care settings to provide psychosocial support and interventions for the elderly with cognitive impairments. Most of these social robots have provided timely stimuli to the elderly at home and in care centres, including keeping them active and boosting their mood. However, previous investigations have registered shortcomings in these robots, particularly in their ability to satisfy an essential human need: the need for companionship. Reports show that the elderly tend to lose interests in these social robots after the initial excitement as the novelty wears out and the monotonous familiarity becomes all too familiar. This paper presents our research facilitating conversations between a social humanoid robot, Nadine, and cognitively impaired elderly at a nursing home. We analysed the effectiveness of human–humanoid interactions between our robot and 14 elderly over 29 sessions. We used both objective tools (based on computer vision methods) and subjective tools (based on observational scales) to evaluate the recorded videos. Our findings showed that our subjects engaged positively with Nadine, suggesting that their interaction with the robot could improve their well-being by compensating for some of their emotional, cognitive, and psychosocial deficiencies. We detected emotions associated with cognitively impaired elderly during these interactions. This study could help understand the expectations of the elderly and the current limitations of Social Assistive Robots. Our research is aligned with all the ethical recommendations by the NTU Institutional Review Board. [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM)‐induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM‐induced AR risk. Methods: Forty‐three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case‐control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM‐induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM‐induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut‐off value of total IgE for the diagnosis of HDM‐induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype‐Tissue Expression (GTEx) database. Results: We found that rs754466 in DLG5 was significantly associated with a decreased HDM‐induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, p = 3.25 × 10−4, PFDR = 3.93 × 10−2). The rs754466 A allele reduced the risk of HDM‐induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. Conclusion: Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM‐induced AR. [ABSTRACT FROM AUTHOR]

Information and communication technologies (ICTs) have transformed the travel and leisure sector worldwide, yet until now there are no studies presenting international evidence of the different impacts of ICTs (i.e., Internet usage, secure Internet servers, mobile cellular subscriptions, high-technology export, communications as well as computer, and fixed broadband subscriptions) on tourism development (i.e., international traveler arrivals, increased international tourism receipts, and travel and leisure sector returns) by considering countries with different tourism development processes (e.g., high or low tourism development quantile). It is possible that ICTs have diverse or non-linear impacts on countries undergoing varying tourism development processes. Using international data based on a new panel quantile approach, this research thus aims to explore whether ICTs affect tourism development and looks into the possible asymmetric and non-linear relationships among the many variables. Results show that increasing mobile cellular subscriptions, secure Internet servers, and fixed broadband subscriptions have greater positive effects on traveler arrivals. ICTs also asymmetrically and non-linearly influence tourism across different quantiles. Non-global financial sub-periods and developing nations gain benefits from ICTs' establishment. Lastly, there are geographic differences in the ICTs-tourism nexus. [ABSTRACT FROM AUTHOR]