bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: a large population-based longitudinal study
Authors: Zhang Yuan , Yang Rongrong , Dove Abigail , Li Xuerui , Yang Hongxi , Li Shu , Wang Ju , Li Wei-Dong , Zhao Hongyu , Xu Weili , Wang Yaogang
Published: April 2022

Background

Risk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout. Therefore, we aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors.

Methods

Within the UK Biobank, 416,481 gout-free participants (aged 37–74) were identified at baseline. Polygenic risk for gout was assessed and categorized as low (lowest tertile), middle (tertile 2), and high (highest tertile). Healthy lifestyle factors included no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Participants were categorized into three groups according to their number of healthy lifestyle factors: unfavorable (0 or 1), intermediate (any 2), and favorable (3 or 4). Data were analyzed using Cox proportional hazard models.

Results

Over the follow-up (median: 12.1 years), 6206 participants developed gout. Compared to low genetic risk, the hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35–1.54) for middle and 1.77 (1.66–1.89) for high genetic risk. The HRs (95% CIs) of gout were 0.63 (0.59–0.67) for a favorable lifestyle and 0.79 (0.75–0.85) for an intermediate lifestyle, compared to an unfavorable lifestyle. In joint effect analysis, compared to participants with low genetic predisposition and a favorable lifestyle, the HRs (95% CIs) of gout were 2.39 (2.12–2.70)/3.12 (2.79–3.52) in those with middle and high genetic predisposition plus unfavorable lifestyle profiles, and 1.53 (1.35–1.74)/1.98 (1.75–2.24) for those with middle and high genetic predisposition plus favorable lifestyle profiles, respectively. Moreover, compared to an unfavorable lifestyle, the HRs of gout related to a favorable lifestyle was 0.64 (95% CI, 0.56–0.73) for low genetic risk, 0.65 (95% CI, 0.58–0.72) for middle genetic risk, and 0.62 (95% CI, 0.57–0.69) for high genetic risk. There was a significant additive interaction between unfavorable lifestyle and high genetic risk on gout.

Conclusions

Healthy lifestyle was associated with a lower risk of gout and may attenuate the risk of gout related to genetic factors by almost a third.
Severity distribution and treatment of chronic obstructive pulmonary disease in China: baseline results of an observational study
Authors: Yang Ting , Cai Baiqiang , Cao Bin , Kang Jian , Wen Fuqiang , Chen Yahong , Jian Wenhua , Shang Hongyan , Wang Chen
Published: April 2022

Background

Chronic obstructive pulmonary disease (COPD) receives low awareness and is undertreated in China. Understanding the burden and treatment of COPD across the nation is important for improving quality of care for this disease. This study aims to reveal the current situation of COPD severity distribution and management across China.

Methods

Baseline data from REALizing and Improving Management of Stable COPD in China, a multicentre, prospective, longitudinal, observational study, were analysed. Patients diagnosed with COPD as per Global Initiative for Chronic Obstructive Lung Disease 2016 (GOLD 2016) criteria were enrolled from 50 randomly selected hospitals (tertiary, 25; secondary, 25) across six geographical regions. Data were collected in routine clinical settings.

Results

Between 30 June 2017 and 29 January 2019, 5013 patients were enrolled and 4978 included in the full analysis set. Of these, 2459 (49.4%) reported ≥ 1 exacerbation within 12 months prior to study enrolment, with a mean annual rate of 0.9/patient, including 0.2/patient and 0.5/patient leading to emergency room visits and hospitalisation, respectively. Spirometry graded 458 (10.1%), 1886 (41.7%), 1558 (34.5%), and 616 (13.6%) were GOLD stage I–IV, and 536 (11.4%), 1034 (22.0%), 563 (12.0%), and 2566 (54.6%) were classified as GOLD 2016 Group A–D, respectively, without evident regional variations. Inhaled corticosteroids plus long-acting beta2-agonist (ICS/LABA, 1316 [26.4%]), ICS/LABA plus long-acting muscarinic antagonist (ICS/LABA + LAMA, 871 [17.5%]), and LAMA (754 [15.1%]) were prescribed at high rates across all groups and regions. Medications not recommended by GOLD were commonly prescribed (TCM, 578 [11.6%]; others, 951 [19.1%]), and 681 (13.7%) were not given ICS or long-acting bronchodilators.

Conclusions

Disease burden among Chinese COPD outpatients is high. Improved guideline adherence for COPD treatment is needed.

Trial registrationClinicalTrials.gov identifier, NCT03131362.
Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19
Authors: Su Ying , Qiu Ze-song , Chen Jun , Ju Min-jie , Ma Guo-guang , He Jin-wei , Yu Shen-ji , Liu Kai , Lure Fleming Y. M. , Tu Guo-wei , Zhang Yu-yao , Luo Zhe
Published: April 2022

Background

Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19.

Methods

Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, − 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders.

Results

Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (− 3.27% [95% CI, − 5.86 to − 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group.

Conclusions

Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process.

Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247
Active secretion of a thermostable transglutaminase variant in Escherichia coli
Authors: Wang Xinglong , Zhao Beichen , Du Jianhui , Xu Yameng , Zhu Xuewen , Zhou Jingwen , Rao Shengqi , Du Guocheng , Chen Jian , Liu Song
Published: April 2022

Background

Streptomyces mobaraenesis transglutaminase (smTG) is widely used to generate protein crosslinking or attachment of small molecules. However, the low thermostability is a main obstacle for smTG application. In addition, it is still hard to achieve the secretory expression of active smTG in E. coli, which benefits the enzyme evolution. In this study, a combined strategy was conducted to improve the thermostability and secretory expression of active smTG in E. coli.

Results

First, the thermostable S. mobaraenesis transglutaminase variant S2P-S23V-Y24N-S199A-K294L (TGm1) was intracellularly expressed in pro-enzyme form in E. coli. Fusing the pro-region of Streptomyces hygroscopicus transglutaminase (proH) and TrxA achieved a 9.78 U/mL of intracellular smTG activity, 1.37-fold higher than the TGm1 fused with its native pro-region. After in vitro activation by dispase, the TGm1 with proH yielded FRAPD-TGm1, exhibiting 0.95 ℃ and 94.25% increases in melting temperature and half-life at 60 ℃ compared to FRAP-TGm1 derived from the expression using its native pro-region, respectively. Second, the TGm1 with proH was co-expressed with transglutaminase activating protease and chaperones (DnaK, DnaJ, and GrpE) in E. coli, achieving 9.51 U/mL of intracellular FRAPD-TGm1 without in vitro activation. Third, the pelB signal peptide was used to mediate the secretory expression of active TGm in E. coli, yielding 0.54 U/mL of the extracellular FRAPD-TGm1. A script was developed to shuffle the codon of pelB and calculate the corresponding mRNA folding energy. A 1.8-fold increase in the extracellular expression of FRAPD-TGm1 was achieved by the Top-9 pelB sequence derived from the coding sequences with the lowest mRNA folding energy. Last, deleting the gene of Braun’s lipoprotein further increased the extracellular yield of FRAPD-TGm1 by 31.2%, reached 1.99 U/mL.

Conclusions

The stabilized FRAPD-smTG here could benefit the enzyme application in food and non-food sectors, while the E. coli system that enables secretory expression of active smTG will facilitate the directed evolution for further improved catalytic properties. The combined strategy (N-terminal modification, co-expression with chaperones, mRNA folding energy optimization of signal peptide, and lipoprotein deletion) may also improve the secretory expression of other functional proteins in E. coli.
Early versus delay oral feeding for patients after upper gastrointestinal surgery: a systematic review and meta-analysis of randomized controlled trials
Authors: Deng Huachu , Li Baibei , Qin Xingan
Published: April 2022

Purpose

To evaluate the efficacy and safety of early oral feeding (EOF) in patients after upper gastrointestinal surgery through meta-analysis of randomized controlled trials (RCTs).

Methods

We analyzed the endpoints of patients including the length of stay (LOS), time of first exhaust, anastomotic leakage and pneumonia from included studies. And we retrieved RCTs from medical literature databases. Weighted mean difference (WMD), risk ratios (RR) and 95% confidence intervals (CI) were calculated to compare the endpoints.

Results

In total, we retrieved 12 articles (13 trial comparisons) which contained 1771 patients. 887 patients (50.1%) were randomized to EOF group whereas 884 patients (49.9%) were randomized to delay oral feeding group. The result showed that compared with the delay oral feeding group, EOF after upper gastrointestinal surgery significantly shorten the LOS [WMD = − 1.30, 95% CI − 1.79 to − 0.80, I2 = 0.0%] and time of first exhaust [WMD = − 0.39, 95% CI − 0.58 to − 0.20, I2 = 62.1%]. EOF also reduced the risk of pneumonia (RR: 0.74, 95% CI 0.55 to 0.99, I2 = 0.0%). There is no significant difference in the risk of anastomotic leak, anastomotic bleeding, abdominal abscess, reoperation, readmission and mortality.

Conclusions

Overall, compared with the traditional oral feeding, EOF could shorten the LOS and time of first exhaust without increasing complications after upper gastrointestinal surgery.
Genomic and immunological profiles of small-cell lung cancer between East Asians and Caucasian
Authors: Lin Anqi , Zhou Ningning , Zhu Weiliang , Zhang Jiexia , Wei Ting , Guo Linlang , Luo Peng , Zhang Jian
Published: April 2022

The characterization of immunological and genomic differences in small-cell lung cancer (SCLC) between East Asian (EA) and Caucasian patients can reveal important clinical therapies for EA patients with SCLC. By sequencing and analyzing a molecular and immunological dataset of 98-SCLC patients of EA ancestry, immunogenicity, including DNA damage repair alterations and tumor mutation burden (TMB), was found to be significantly higher in the EA cohort than in the Caucasian cohort. The epithelial-mesenchymal transition (EMT) was the signaling signature with the predominant frequency of mutations across all patients in the EA cohort. Analysis of tumor-infiltrated immune cells revealed that resting lymphocytes were significantly enriched in the EA cohort. Compound-targeting analysis showed that topoisomerase inhibitors might be capable of targeting TP53 and RB1 comutations in EA SCLC patients. EA SCLC patients who harbored COL6A6 mutations had poor survival, while Caucasian SCLC patients with OTOF, ANKRD30B, and TECPR2 mutations were identified to have a shorter survival.
Interaction between non-coding RNAs, mRNAs and G-quadruplexes
Authors: Ghafouri-Fard Soudeh , Abak Atefe , Baniahmad Aria , Hussen Bashdar Mahmud , Taheri Mohammad , Jamali Elena , Dinger Marcel E.
Published: April 2022

G-quadruplexes are secondary helical configurations established between guanine-rich nucleic acids. The structure is seen in the promoter regions of numerous genes under certain situations. Predicted G-quadruplex-forming sequences are distributed across the genome in a non-random way. These structures are formed in telomeric regions of the human genome and oncogenic promoter G-rich regions. Identification of mechanisms of regulation of stability of G-quadruplexes has practical significance for understanding the molecular basis of genetic diseases such as cancer. A number of non-coding RNAs such as H19, XIST, FLJ39051 (GSEC), BC200 (BCYRN1), TERRA, pre-miRNA-1229, pre-miRNA-149 and miR-1587 have been found to contain G-quadraplex-forming regions or affect configuration of these structures in target genes. In the current review, we outline the recent research on the interaction between G-quadruplexes and non-coding RNAs, other RNA transcripts and DNA molecules.
Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy
Authors: Liu Cui , Yan Xiangji , Zhang Yujie , Yang Mei , Ma Yana , Zhang Yuanyuan , Xu Qiuran , Tu Kangsheng , Zhang Mingzhen
Published: April 2022

Background

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.

Results

For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (− 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.

Conclusion

Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.
Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis
Authors: Chen Yejia , Li Xiaobo , Lin Xinxin , Liang Hongbin , Liu Xuewei , Zhang Xinlu , Zhang Qiuxia , Zhou Fengyun , Yu Chen , Lei Li , Xiu Jiancheng
Published: April 2022

Background

Thrombotic events cannot be completely prevented by antithrombotics, implicating a therapeutic gap due to inflammation, a not yet sufficiently addressed mechanism. Neutrophil extracellular traps (NETs) are an essential interface between inflammation and thrombosis, but exactly how the NETotic process is initiated and maintained during arterial thrombosis remains incompletely understood.

Methods and results

We found that the plasma concentrations of C5a were higher in patients with ST-elevation myocardial infarction (STEMI) than in patients with angina and higher in mice with left common carotid artery (LCCA) thrombosis induced by FeCl3 than in control mice. We observed that the thrombus area and weight were decreased and that NET formation in the thrombi was reduced in the group treated with the selective C5aR1 receptor inhibitor PMX53 compared with the NaCl group. In vitro, NETosis was observed when C5a was added to neutrophil cultures, and this effect was reversed by PMX53. In addition, our data showed that C5a increased the production of mitochondrial reactive oxygen species (ROS) and that the promotion of NET formation by C5a was mitochondrial ROS (Mito-ROS) dependent. Furthermore, we found that C5a induced the production of Mito-ROS by inhibiting mitochondrial STAT3 activity.

Conclusions

By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis. Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis.
Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments
Authors: Sekino Nobufumi , Selim Magdy , Shehadah Amjad
Published: April 2022

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes cerebral dysfunction in the short and long term and induces disruption of the blood–brain barrier (BBB), neuroinflammation, hypoperfusion, and accumulation of amyloid β (Aβ) and tau protein in the brain. White matter changes and brain atrophy can be detected using brain imaging, but unfortunately, there is no specific treatment that directly addresses the underlying mechanisms of cognitive impairments in sepsis. Here, we review the underlying mechanisms of sepsis-associated brain injury, with a focus on BBB dysfunction and Aβ and tau protein accumulation in the brain. We also describe the neurological manifestations and imaging findings of sepsis-associated brain injury, and finally, we propose potential therapeutic strategies for acute and long-term cognitive impairments associated with sepsis. In the acute phase of sepsis, we suggest using antibiotics (such as rifampicin), targeting proinflammatory cytokines, and preventing ischemic injuries and hypoperfusion. In the late phase of sepsis, we suggest targeting neuroinflammation, BBB dysfunction, Aβ and tau protein phosphorylation, glycogen synthase kinase-3 beta (GSK3β), and the receptor for advanced glycation end products (RAGE). These proposed strategies are meant to bring new mechanism-based directions for future basic and clinical research aimed at preventing or ameliorating acute and long-term cognitive impairments in patients with sepsis.
CyberLimb: a novel robotic prosthesis concept with shared and intuitive control
Authors: Seppich Nicolas , Tacca Nicholas , Chao Kuo-Yi , Akim Milan , Hidalgo-Carvajal Diego , Pozo Fortunić Edmundo , Tödtheide Alexander , Kühn Johannes , Haddadin Sami
Published: April 2022

Background

Existing assistive technologies attempt to mimic biological functions through advanced mechatronic designs. In some occasions, the information processing demands for such systems require substantial information bandwidth and convoluted control strategies, which make it difficult for the end-user to operate. Instead, a practical and intuitive semi-automated system focused on accomplishing daily tasks may be more suitable for end-user adoption.

Methods

We developed an intelligent prosthesis for the Cybathlon Global Edition 2020. The device was designed in collaboration with the prosthesis user (pilot), addressing her needs for the competition and aiming for functionality. Our design consists of a soft robotic-based two finger gripper controlled by a force-sensing resistor (FSR) headband interface, automatic arm angle dependent wrist flexion and extension, and manual forearm supination and pronation for a shared control system. The gripper is incorporated with FSR sensors to relay haptic information to the pilot based on the output of a neural network model that estimates geometries and objects material.

Results

As a student team of the Munich Institute of Robotics and Machine Intelligence, we achieved 12th place overall in the Cybathlon competition in which we competed against state-of-the-art prosthetic devices. Our pilot successfully accomplished two challenging tasks in the competition. During training sessions, the pilot was able to accomplish the remaining competition tasks except for one. Based on observation and feedback from training sessions, we adapted our developments to fit the user’s preferences. Usability ratings indicated that the pilot perceived the prosthesis to not be fully ergonomic due to the size and weight of the system, but argued that the prosthesis was intuitive to control to perform the tasks from the Cybathlon competition.

Conclusions

The system provides an intuitive interface to conduct common daily tasks from the arm discipline of the Cybathlon competition. Based on the feedback from our pilot, future improvements include the prosthesis’ reduction in size and weight in order to enhance its mobility. Close collaboration with our pilot has allowed us to continue with the prosthesis development. Ultimately, we developed a simple-to-use solution, exemplifying a new paradigm for prosthesis design, to help assist arm amputees with daily activities.
The compound LG283 inhibits bleomycin-induced skin fibrosis via antagonizing TGF-β signaling
Authors: Utsunomiya Akira , Chino Takenao , Kasamatsu Hiroshi , Hasegawa Takumi , Utsunomiya Natsuko , Luong Vu Huy , Matsushita Takashi , Sasaki Yoko , Ogura Dai , Niwa Shin-ichiro , Oyama Noritaka , Hasegawa Minoru
Published: April 2022

Background

Systemic sclerosis (SSc) is a collagen disease that exhibits intractable fibrosis and vascular injury of the skin and internal organs. Transforming growth factor-β (TGF-β)/Smad signaling plays a central role in extracellular matrix (ECM) production by α-SMA-positive myofibroblasts. Myofibroblasts may be partially derived from various precursor cells in addition to resident fibroblasts. Recently, our high-throughput in vitro screening discovered a small compound, LG283, that may disrupt the differentiation of epithelial cells into myofibroblasts. This compound was originally generated as a curcumin derivative.

Methods

In this study, we investigated the effect of LG283 on inhibiting fibrosis and its mechanism. The action of LG283 on TGF-β-dependent fibrogenic activity and epithelial-mesenchymal transition (EMT) was analyzed in vitro. The effects of LG283 were also examined in a bleomycin-induced skin fibrosis mouse model.

Results

LG283 suppressed TGF-β-induced expression of ECM, α-SMA, and transcription factors Snail 1 and 2, and Smad3 phosphorylation in cultured human dermal fibroblasts. LG283 was also found to block EMT induction in cultured human epithelial cells. During these processes, Smad3 phosphorylation and/or expression of Snail 1 and 2 were inhibited by LG283 treatment. In the bleomycin-induced skin fibrosis model, oral administration of LG283 efficiently protected against the development of fibrosis and decrease of capillary vessels without significantly affecting cell infiltration or cytokine concentrations in the skin. No apparent adverse effects of LG283 were found. LG283 treatment remarkably inhibited the enhanced expression of α-SMA and phosphorylated Smad3, as well as those of Snail 1 and 2, in the bleomycin-injected skin.

Conclusions

The LG283 compound exhibits antagonistic activity on fibrosis and vascular injury through inhibition of TGF-β/Smad/Snail mesenchymal transition pathways and thus, may be a candidate therapeutic for the treatment of SSc. Although the involvement of EMT in the pathogenesis of SSc remains unclear, the screening of EMT regulatory compounds may be an attractive approach for SSc therapy.
Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis
Authors: Yu Hanjie , Li Mingxiu , Wen Xiaodong , Yang Jie , Liang Xiaojun , Li Xia , Bao Xiaojuan , Shu Jian , Ren Xiameng , Chen Wentian , Li Zheng , Li Yi
Published: April 2022

Background

Osteoarthritis (OA) is the most common form of arthritis and is characterized by the degradation of articular cartilage and inflammation of the synovial membrane. Fucosylation is an important feature of protein N/O-glycosylation and is involved in a variety of pathological processes, including inflammation and cancer. However, whether fucosylation impacts the OA pathological process is unknown.

Methods

Total proteins were extracted from cartilage samples obtained from patients with OA (n= 11) and OA rabbit models at different time points (n= 12). OA-associated abnormal glycopatterns were evaluated by lectin microarrays and lectin blots. The expression of fucosyltransferases involved in the synthesis of α-1,3 fucosylation was assessed by semi-qPCR. The synthesis of α-1,3 fucosylation mediated by FUT10 was interrupted by the transfection of siRNA, and the effect of α-1,3 fucosylation on OA-associated events was assessed. Then, immunoprecipitation and lectin blotting were used to investigate the relationship between the α-1,3 fucosylation level of tumor necrosis factor receptor superfamily member 1A (TNFR1) and OA. Finally, a TNFR1 antibody microarray was fabricated to evaluate the effect of α-1,3 fucosylation on the ability of TNFR1 to bind to tumor necrosis factor-α (TNF-α).

Results

Elevated α-1,3 fucosylation was observed in cartilage from OA patients, rabbit models, and chondrocytes induced by TNF-α (fold change> 2,p< 0.01). Our results and the GEO database indicated that the overexpression of FUT10 contributed to this alteration. Silencing the expression of FUT10 impaired the ability of TNFR1 to bind to TNF-α, impeded activation of the NF-κB and P38/JNK-MAPK pathways, and eventually retarded extracellular matrix (ECM) degradation, senescence, and apoptosis in chondrocytes exposed to TNF-α.

Conclusion

The elevation of α-1,3 fucosylation is not only a characteristic of OA but also impacts the OA pathological process. Our work provides a new positive feedback loop of “inflammation conditions/TNF-α/FUT10/α-1,3 fucosylation of TNFR1/NF-κB and P38/JNK-MAPK pathways/proinflammatory processes” that contributes to ECM degradation and chondrocyte apoptosis.
Associated factors with poor treatment response to initial glucocorticoid therapy in patients with adult-onset Still’s disease
Authors: Kondo Fumiaki , Sugihara Takahiko , Umezawa Natsuka , Hasegawa Hisanori , Hosoya Tadashi , Kimura Naoki , Mori Masaaki , Yasuda Shinsuke
Published: April 2022

Background

High-dose glucocorticoids (GC) are first-line treatment for adult-onset Still’s disease (AOSD); however, some of the patients remain refractory to initial GC therapy, or rapidly relapse. The aim of this study was to identify prognostic factors for poor treatment response to initial GC therapy for AOSD.

Methods

Data on newly diagnosed AOSD patients were extracted from our database (n=71, mean age 51.6 years). The primary outcome was a poor treatment outcome at 4 weeks, which was defined as failure to achieve remission or relapse after achieving remission within 4 weeks, followed by administration of two or more rounds of GC pulse therapy or of any other immunosuppressive drugs.

Results

The initial mean dose ± standard deviation of prednisolone was 0.82 ± 0.23 mg/kg/day, and 34 (47.3%) patients received GC pulse therapy at week 0. Twenty-nine of 71 patients exhibited a poor treatment outcome at 4 weeks (40.8%). The second round of GC pulse therapy or immunosuppressive drugs was added in 17 or 24 of the 29 patients, respectively. These patients had higher baseline white blood cell (WBC) counts, serum ferritin levels, systemic feature score based on clinical symptoms (modified systemic feature score, mSFS), more hemophagocytic syndrome (HPS) over the 4 weeks, and the higher severity score based on modified Pouchot score or severity index of the Japanese Ministry of Health, Labour and Welfare, than the remaining 42 patients. Multivariable logistic regression model identified baseline WBC count as a prognostic factor for poor outcome (odds ratio per 1000/μl increment: 1.12, 95% CI 1.04–1.29), while thrombocytopenia, hyperferritinemia, and mSFS at baseline did not achieve statistical significance. Receiver-operating characteristic curve analysis showed that the optimal cut-off for WBC count was 13,050/μl. The Kaplan-Meier method showed the cumulative rate of poor treatment outcome to be 60.0% in patients with WBC ≥13,050/μl and 23.5% in those with WBC <13,050/μl.

Conclusions

A higher WBC count but not thrombocytopenia, hyperferritinemia, and mSFS at baseline was a significant prognostic factor for poor treatment outcome at week 4 in this retrospective cohort of AOSD patients. Our findings provide important information for determining the initial treatment strategy of newly-diagnosed AOSD.
Predictors of adherence to prescribed exercise programs for older adults with medical or surgical indications for exercise: a systematic review
Authors: Shaw Julia F. , Pilon Sophie , Vierula Matthieu , McIsaac Daniel I.
Published: April 2022

Background and objectives

Prescribed exercise to treat medical conditions and to prepare for surgery is a promising intervention to prevent adverse health outcomes for older adults; however, adherence to exercise programs may be low. Our objective was to identify and grade the quality of predictors of adherence to prescribed exercise in older adults.

Methods

Prospective observational and experimental studies were identified using a peer-reviewed search strategy applied to MEDLINE, EMBASE, Cochrane, and CINAHL from inception until October 6, 2020. Following an independent and duplicate review of titles, abstracts, and full texts, we included prospective studies with an average population age >65 years, where exercise was formally prescribed for a medical or surgical condition. We excluded studies where exercise was prescribed for a chronic musculoskeletal condition. Risk of bias was assessed using the Quality in Prognostic studies tool or Cochrane risk of bias tool, as appropriate. Predictors of adherence were identified and graded for quality using an adaptation of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for predictor studies.

Results

We included 19 observational studies and 4 randomized controlled trials (n=5785) Indications for exercise included cardiac (n=6), pulmonary rehabilitation (n=7), or other (n=10; surgical, medical, and neurologic). Of the 10 studies that reported adherence as the percent of prescribed sessions completed, average adherence was 80% (range 60–98%; standard deviation (SD) 11%). Of the 10 studies that reported adherence as a categorical threshold demarking adherent vs not adherent, average adherence was 57.5% (range 21–83%; SD 21%). Moderate-quality evidence suggested that positive predictors of adherence were self-efficacy and good self-rated mental health; negative predictors were depression (high quality) and distance from the exercise facility. Moderate-quality evidence suggested that comorbidity and age were not predictive of adherence.

Conclusions

These findings can inform the design of future exercise programs as well as the identification of individuals who may require extra support to benefit from prescribed exercise.

Systematic review registration

PROSPERO CRD42018108242
Orthostatic hypotonia as a probably late sequela of SARS-CoV-2 infection in a patient provided with palliative home care: a case report
Authors: Kluczna Agnieszka , Mularska Elżbieta , Dzierżanowski Tomasz
Published: April 2022

Background

The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of the disease and focuses on the treating early complications of the disease. Long-term health consequences of the infection have not yet been fully identified. A special group of patients with comorbidities, including neoplastic disease for whom the interpretation and management of symptoms is a major challenge.

Case presentation

In this case report, we present a 73-year-old woman with recently diagnosed gastric adenocarcinoma in whom we diagnosed orthostatic hypotonia in the aftermath of SARS-CoV-2 infection. We administered thiethylperazine maleate 6.5 mg daily. Additionally, we advised the patient to slowly lift from the recumbent position, raise the headboard, take meals in small portions, and increase fluid intake. These pharmacological and nonpharmacological measures resulted in sustained relief of dizziness and nausea.

Conclusions

The occurrence of orthostatic hypotonia seems a possible late sequela of SARS-CoV-2 infection, and simple measures appeared sufficient to achieve sustained symptom control.
Re-discovering Aurelio Peccei’s contribution to Futures Studies
Authors: Facioni Carolina , Paura Roberto
Published: April 2022

This work aims to enhance the contribution of Aurelio Peccei to Futures Studies and its unaltered relevance in the light of the world’s current scientific issues. Peccei’s contribution in Futures Studies is often identified with his propulsive role in the birth of the Club of Rome (1968) and in the promotion of the report “The Limits to Growth” (1972). Although this would be enough to make him a central figure in the history of Futures Studies, his whole intellectual journey is worth emphasizing. This work focuses on the “epistemic impact” of Peccei in the field research on possible futures. Peccei not only argued the fundamental need to translate complexity into a forecasting model: as an ante litteram anticipator, he dedicated his life to seek a development model respecting both the human tendency towards constant evolution and biosphere. A theoretical impact that allowed many fundamental UN initiatives—from the 1987 Report of the World Commission on Environment and Development to the 2015 Report on Sustainable Development Goals (SDGs)—and also helped the development of a forward-looking social research.
Making peace with disliked others: the effects of a short loving-kindness meditation on implicit and explicit emotional evaluations
Authors: Schroter Franziska Anna , Jansen Petra
Published: April 2022

Background

The main goal of the study was to investigate the effects of a short loving-kindness meditation (LKM) on explicit and implicit evaluations of oneself and disliked public persons. We expected a more positive explicit and implicit evaluation of oneself and a disliked public person after the LKM and a mood improvement.

Methods

Before and after the implementation of a short LKM vs. imagery task, mood, explicit and implicit evaluations were analyzed in 69 students.

Results

Our results demonstrated only a reduction in negative and positive mood in both groups and regarding the explicit and implicit tasks, only a significant main effect of picture and a trend for the time*group interaction for mood, implicit and explicit attitudes with medium effect-sizes.

Conclusions

A possible influence of a short intervention on emotional evaluations should be treated with caution. The claim that a short loving-kindness meditation enhances social connectedness might awake false hopes. This study suggests being careful with the interpretation of single meditation effects and future studies should examine the effects of a long-lasting meditation training on explicit and implicit evaluations of the self and disliked politicians as well as the sustainability of those effects.
Recent advances in the chemo-biological characterization of decalin natural products and unraveling of the workings of Diels–Alderases
Authors: Watanabe Kenji , Sato Michio , Osada Hiroyuki
Published: April 2022

The Diels–Alder (DA) reaction refers to a [4 + 2] cycloaddition reaction that falls under the category of pericyclic reactions. It is a reaction that allows regio- and stereo-selective construction of two carbon–carbon bonds simultaneously in a concerted manner to generate a six-membered ring structure through a six-electron cyclic transition state. The DA reaction is one of the most widely applied reactions in organic synthesis, yet its role in biological systems has been debated intensely over the last four decades. A survey of secondary metabolites produced by microorganisms suggests strongly that many of the compounds possess features that are likely formed through DA reactions, and most of them are considered to be catalyzed by enzymes that are commonly referred to as Diels–Alderases (DAases). In recent years, especially over the past 10 years or so, we have seen an accumulation of a substantial body of work that substantiates the argument that DAases indeed exist and play a critical role in the biosynthesis of complex metabolites. This review will cover the DAases involved in the biosynthesis of decalin moieties, which are found in many of the medicinally important natural products, especially those produced by fungi. In particular, we will focus on a subset of secondary metabolites referred to as pyrrolidine-2-one-bearing decalin compounds and discuss the decalin ring stereochemistry and the biological activities of those compounds. We will also look into the genes and enzymes that drive the biosynthetic construction of those complex natural products, and highlight the recent progress made on the structural and mechanistic understanding of DAases, especially regarding how those enzymes exert stereochemical control over the [4 + 2] cycloaddition reactions they catalyze.
Snakebite victim profiles and treatment-seeking behaviors in two regions of Kenya: results from a health demographic surveillance system
Authors: Larson Peter S. , Ndemwa Morris , Thomas Aleksandra F. , Tamari Noriko , Diela Paul , Changoma Mwatasa , Mohamed Abdullatif , Larson Miles C. , Ketenci Kaan Cem , Goto Kensuke , Kaneko Satoshi
Published: April 2022

Introduction

Snakebites are a major cause of permanent injury and death among poor, rural populations in developing countries, including those in East Africa. This research characterizes snakebite incidence, risk factors, and subsequent health-seeking behaviors in two regions of Kenya using a mixed methods approach.

Methods

As a part of regular activities of a health demographic surveillance system, household-level survey on snakebite incidence was conducted in two areas of Kenya: Kwale along the Kenyan Coast and Mbita on Lake Victoria. If someone in the home was reported to have been bitten in the 5 years previous to the visit, a survey instrument was administered. The survey gathered contextual information on the bite, treatment-seeking behavior and clinical manifestations. To obtain deeper, contextual information, respondents were also asked to narrate the bite incident, subsequent behavior and outcomes.

Results

8775 and 9206 households were surveyed in Kwale and Mbita, respectively. Out of these, 453 (5.17%) and 92 (1.00%) households reported that at least one person had been bitten by a snake in the past 5 years. Deaths from snakebites were rare (4.04%), but patterns of treatment seeking varied. Treatment at formal care facilities were sought for 50.8% and at traditional healers for 53.3%. 18.4% sought treatment from both sources. Victims who delayed receiving treatment from a formal facility were more likely to have consulted a traditional healer (OR 8.8995% CI [3.83, 20.64]). Delays in treatment seeking were associated with significantly increased odds of having a severe outcome, including death, paralysis or loss of consciousness (OR 3.47 95% CI [1.56; 7.70]).

Conclusion

Snakebite incidence and outcomes vary by region in Kenya, and treatment-seeking behaviors are complex. Work needs to be done to better characterize the spatial distribution of snakebite incidence in Kenya and efforts need to be made to ensure that victims have sufficient access to effective treatments to prevent death and serious injury.
Lessons From Implementing a Clinical Research Network in Brazil
Authors: Canedo Jorge Alexandre , Rondão Fabiana , Ferreira Carlos Gil , Ferrari Bruno Lemos , Mathias Clarissa
Published: April 2022

In this article, we discuss the strategy designed by a private oncology group to offer patients access to new technologies and treatments via a recently created research program, and we describe how the patient journey was the motivation for developing standard assistance flows and processes to integrate areas of care. The increase in Brazilians’ life expectancy has raised the incidence of cancer, and it is now the second leading cause of death. Because it is a multifactorial disease, cancer treatment has several challenges. We elected to approach cancer research using a strategic program to obtain national attention and visibility. Starting in 2007, the initial project included three phases: phase I, diagnosis of units in major metropolitan areas; phase II, project design, with a central-office operation model; and phase III, implementation, with launch and integration of research activities at selected units. The foundation of the program was the construction of departmental and interdepartmental flows, standard operating processes, and guidelines (regulatory, ethical, legal, and financial). Recruitment of qualified professionals was another critical, successful determinant. The benefits of an additional central office include improved research-project distribution. Another advantage of the program is attracting and retaining trained professionals with alternative direct or indirect sources of revenue. We increased our corporate and academic partnerships, adhered to deadlines and noted an improvement in turnaround times, and we increased clinical staff engagement and motivation. Some barriers continue to challenge the program's continued expansion, including Brazilian regulatory authority approval, tax inefficiency, and a growing demand for qualified professionals. Research sites offering high-quality care are a reality in Brazil; they offer multiple lines of treatment in the public and private sectors.
Deterioration of Glycemic Control in Youth-Onset Type 2 Diabetes: What Are the Early and Late Predictors?
Authors: Zeitler Philip , El Ghormli Laure , Arslanian Silva , Caprio Sonia , Isganaitis Elvira , Kelsey Megan K , Weinstock Ruth S , White Neil H , Drews Kimberly
Published: April 2022

Objective

We examined predictors of early and late loss of glycemic control in individuals with youth-onset type 2 diabetes, as well as predictors of short-term deterioration in youth from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Methods

Demographic, physical, and biochemical measures at baseline and 48 months, and change over time, were examined in 584 participants separated into those with loss of glycemic control (sustained HbA1c ≥ 8%) before 48 months or at 48 months or later, and those who remained in control until the end of the study (median 6.8 years). Univariate and multivariate models, and receiver operating characteristic curve analyses were performed.

Results

Approximately 45% of youth remained in control at 48 months; of these, 30% subsequently lost glycemic control prior to the end of follow-up. Predictors of early loss of glycemic control included baseline HbA1c, C-peptide index, oral disposition index, proinsulin, and proinsulin to insulin ratio. Predictors of late loss included baseline measures of insulin secretion and change in HbA1c and insulin processing at 48 months. A baseline HbA1c cutoff of ≥ 6.2% was optimally predictive of loss of glycemic control at any time, while an absolute rise in HbA1c > 0.5% related to loss of glycemic control within 3 to 6 months.

Conclusion

This analysis demonstrates that youth with type 2 diabetes at risk for loss of glycemic control, including impending rapid deterioration, can be identified using available clinical measures, allowing for closer monitoring of at-risk youth, and facilitating the design of research on better therapeutic options.
The New System of Mexican Migration: The Role of Entry Mode–Specific Human and Social Capital
Authors: Wassink Joshua , Massey Douglas S.
Published: April 2022

Between 2000 and 2020, undocumented migration declined, temporary labor migration rose, and legal permanent residents arrived at a steady pace—together creating a new system of Mexico–U.S. migration based on the circulation of legal temporary workers and permanent residents. Drawing on data from the U.S. Department of Homeland Security and the Mexican Migration Project, we specify multinomial event-history models to predict the likelihood of departure on first and later trips via four entry categories: no documents, noncompliant tourist visas, temporary work visas, and legal residence visas. The models reveal how the accumulation of entry mode–specific social and human capital powered a system of undocumented migration that emerged between 1965 and 1985, and how that system deteriorated from 1985 to 2000. After 2000, employers took advantage of new visa categories to recruit legal temporary workers, leading to the accumulation of migration-related human and social capital specific to that mode of entry and the emergence of a new system of Mexico–U.S. migration.
Queering Tupac Amaru II
Authors: Roper Danielle M.
Published: April 2022

This study examines the queering of Tupac Amaru in Javier Vargas Sotomayor's La Falsificación de las Túpac (The Falsification of Tupac) to discern how travestismo (transvestism) functions as a methodology and epistemology for working on and against the symbols that underwrite national identity. This essay treats falsification as a central precept of a travesti methodology by paying close attention to the role of fiction, falsity, and fabrication in the production of the hero and the nation. Roper argues that travestismo not only exposes the constructedness of its original but also functions as a tool of dissent and as a space for staging an encounter with the possible.