bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose Dependent Effects of Breynia cernua Against the Paraquat Induced Parkinsonism like Symptoms in Animals’ Model: In Vitro, In Vivo and Mechanistic Studies
Authors: Saadullah Malik , Arif Sania , Hussain Liaqat , Asif Muhammad , Khurshid Umair 
Published: September 2022

The aims and objectives of the study were to evaluate the antiParkinson’s (PD) potential of B cernua (BCE). B cernua (Poir.) Müll. Arg. (B cernua) is a member of the Phyllanthaceae family. HPLC revealed the presence of various phytochemicals. Study was conducted for 40 days. After PD induction by paraquat behavioural studies were carried out. Biochemical parameters such as DPPH, NO-scavenging, Ferrous reducing power, MDA, GSH, CAT, SOD, acetylcholinesterase (AChE), neurotransmitter estimation and TNF-α and IL-6 levels were determined. DPPH, NO-scavenging and Ferrous reducing power assays showed 78.02%, 48.05% and 71.45% inhibitions, respectively. There was significant improvement in motor functions and coordination in a dose-dependent manner (50 < 250 < 500 mg/kg) in PD rat model. Biochemical markers; SOD, CAT, GPx and GSH showed significant restoration ( P < .001) while MDA showed significant decrease ( P < .05). The AChE level was significantly reduced ( P < .05) at 500 mg/kg while neurotransmitters were significantly improved ( P < .001) in a dose-dependent fashion. The ELISA results showed significant ( P < .001) down-regulation of IL-6 and TNF-α level. In conclusion, it is suggested that BCE has the potential to reduce the symptoms of PD.
Role of serum IL-6 and TNF-α in coronavirus disease 2019 (COVID-19) associated renal impairment
Authors: Chen Li-Da , Hu Lan , Song Yang , Huang Ya-Ping , Yang Si-Jiu , Yang Juan , Zhang Xiao-bin 
Published: September 2022

Objectives: Association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and kidney injury has been noted in previous studies. However, the mechanisms remain unknown. The present study aimed to explore the potential mechanisms of kidney injury in COVID-19. Methods: Demographic characteristics, underlying diseases, signs, symptoms, and laboratory data of 100 COVID-19 patients were collected and analyzed in this retrospective study. Patients were divided into three groups: mild, moderate, and severe to critical group. Kidney injury was evaluated by markers including estimated glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen, and cystatin C. Results: A total of 100 patients with 12 mild, 63 moderate, and 25 severe to critical COVID-19 were included in this study. The kidney injury markers including eGFR, serum creatinine, blood urea nitrogen, and cystatin C all worsened significantly with an increase in disease severity. The correlation test showed that cytokines IL-2R, IL-6, IL-8, and tumor necrosis factor (TNF)-α were statistically correlated with eGFR and cystatin C. In multivariate analysis, log IL-6 (β = −0.331, p = .001 for eGFR and β = 0.405, p < .001 for cystatin C) and log TNF-α (β = −0.316, p = .001 for eGFR and β = 0.534, p < .001 for cystatin C) were found to be the major independent predictors of kidney injury. Conclusion: Serum IL-6 and TNF-α levels were the major independent predictors of kidney injury in COVID-19.
Effect of the Shanghai Stroke Service System (4S) on the quality of stroke care and outcomes: A prospective quality improvement project
Authors: Xu Jiawen , Xie Yanan , Fang Kun , Wang Xin , Chen Shengdi , Liu Xueyuan , Zhao Yuwu , Guan Yangtai , Cai Dingfang , Li Gang , Liu Jianmin , Liu JianRen , Zhuang Jianhua , Xian Ying , Shen Haipeng , Li Hao , Wang David Z , Campbell Bruce CV , Parsons Mark W , Dong Yi , Dong Qiang 
Published: September 2022

Background: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. Aim: The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. Methods: The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. Results: The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p < 0.001; all-or-none measure 49.2% vs 44.8% patients; absolute difference 3.5%, 95% CI = [2.7%, 4.2%], p < 0.001). Further analysis of individual KPIs showed an absolute increase in six KPIs ranging from 3.4% to 8.9% (p < 0.001 for all comparisons). Compared with 2015–2017, hospital length of stay was shorter (10.95 vs 11.90 days; absolute difference –1.08, 95% CI = [–1.18, –0.99], p < 0.001), and in-hospital mortality was significantly reduced (risk ratio (RR) = 0.88, 95% CI = [0.79, 0.98], p = 0.01) in 2018–2020. Conclusion: The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. Trial registration: ClinicalTrials.gov identifier: NCT02735226.
The prognostic importance of the angiotensin II/angiotensin-(1–7) ratio in patients with SARS-CoV-2 infection
Authors: Amezcua-Guerra Luis M , del Valle Leonardo , González-Pacheco Héctor , Springall Rashidi , Márquez-Velasco Ricardo , Massó Felipe , Brianza-Padilla Malinalli , Manzur-Sandoval Daniel , González-Flores Julieta , García-Ávila Carlos , Juárez-Vicuña Yaneli , Sánchez-Muñoz Fausto , Ballinas-Verdugo Martha A , Basilio-Gálvez Edna , Paez-Arenas Araceli , Castillo-Salazar Mauricio , Cásares-Alvarado Sergio , Hernández-Diazcouder Adrián , Sánchez-Gloria José L , Tavera-Alonso Claudia , Gopar-Nieto Rodrigo , Sandoval Julio 
Published: September 2022

Background: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1–7) levels in patients with COVID-19 is scarce. Objective: To characterize the Ang II–ACE2–Ang-(1–7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. Methods: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1–7), and Ang-(1–9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). Results: Serum from 74 patients [age: 58 (48–67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10–21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1–7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1–7) concentration was lower in patients who died. The Ang II/Ang-(1–7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1–7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 103/µl (OR = 8.43) were independent predictors of mortality from COVID-19. Conclusion: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II–ACE2–Ang-(1–7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.
“I’m concerned”: A multi-site assessment of emergency medicine resident speaking up behaviors
Authors: Feldman Nicola , Volz Nico , Snow Tim , Wong Lillian , Hock Sara M , Barnes David K , Bentley Suzanne 
Published: September 2022

Introduction According to the Institute of Medicine, 98,000 annual deaths are caused by preventable errors. Speaking up about patient safety or professionalism concerns when they arise allows medical staff to move from bystanders to active participants in the prevention of patient harm. This study assesses the current climate around speaking up for patient safety and unprofessional behavior by Emergency Medicine (EM) resident physicians and compares it to previously published data from other specialties. Methods A multi-site, descriptive, cross-sectional design was utilized based on previously published Speaking Up Climate Safety and Professionalism Scales. EM residents at 3 programs in the United States were surveyed, and their responses were compared to previously published responses from other specialties. Results 102 residents from 3 EM residency programs responded to the survey, yielding a response rate of 54.3%. Responses on the survey fell close to the neutral response (3 on a 5-point Likert scale) on all measures, indicating opportunity for improvement. However, EM responses were significantly more favorable than responses from other specialties on several questions. Conclusion This assessment demonstrates room for improvement on speaking up behaviors among EM residents but also suggests that unique features of EM may contribute to a relatively more positive speaking up climate compared to other specialties, which may inform strategies to increase speaking up behaviors. For example, deliberate practice of situations requiring strong teamwork and strategies to reduce traditional hierarchies may help emulate the climate that tends to occur organically in EM.
Detecting measurable residual disease beyond 10−4 by an IGHV leader-based NGS approach improves prognostic stratification in CLL
Authors: Hengeveld Paul J. , van der Klift Michèle Y. , Kolijn P. Martijn , Davi Frédéric , Kavelaars François G. , de Jonge Evert , Robrecht Sandra , Assmann Jorn L. J. C. , van der Straten Lina , Ritgen Matthias , Westerweel Peter E. , Fischer Kirsten , Goede Valentin , Hallek Michael , Levin Mark-David , Langerak Anton W. 
Published: September 2022

Abstract
The sensitivity of conventional techniques for reliable quantification of minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is limited to MRD 10−4. Measuring MRD &lt;10−4 could help to further distinguish between patients with CLL with durable remission and those at risk of early relapse. We herein present an academically developed immunoglobulin heavy-chain variable (IGHV) leader-based next-generation sequencing (NGS) assay for the quantification of MRD in CLL. We demonstrate, based on measurements in contrived MRD samples, that the linear range of detection and quantification of our assay reaches beyond MRD 10−5. If provided with sufficient DNA input, MRD can be detected down to MRD 10−6. There was high interassay concordance between measurements of the IGHV leader-based NGS assay and allele-specific oligonucleotide quantitative polymerase chain reaction (PCR) (r = 0.92 [95% confidence interval {CI}, 0.86-0.96]) and droplet digital PCR (r = 0.93 [95% CI, 0.88-0.96]) on contrived MRD samples. In a cohort of 67 patients from the CLL11 trial, using MRD 10−5 as a cutoff, undetectable MRD was associated with superior progression-free survival (PFS) and time to next treatment. More important, deeper MRD measurement allowed for additional stratification of patients with MRD &lt;10−4 but ≥10−5. PFS of patients in this MRD range was significantly shorter, compared with patients with MRD &lt;10−5 (hazard ratio [HR], 4.0 [95% CI, 1.6-10.3]; P = .004), but significantly longer, compared with patients with MRD ≥10−4 (HR, 0.44 [95% CI, 0.23-0.87]; P = .018). These results support the clinical utility of the IGHV leader-based NGS assay.
The prevalence of primary headache disorders in children and adolescents in Zambia: a schools-based study
Authors: Kawatu Nfwama , Wa Somwe Somwe , Ciccone Ornella , Mukanzu Misheck , Uluduz Derya , Şaşmaz Tayyar , Yalçın Bengü Nehir Buğdaycı , Wöber Christian , Steiner Timothy J. 
Published: September 2022

Abstract
Background
The Global Campaign against Headache collects data from children (6–11 years) and adolescents (12–17) to inform health and education policies and contribute to the Global Burden of Disease (GBD) study. This survey in Zambia, part of this global enquiry, was the second from sub-Saharan Africa (SSA).

Methods
Following the generic protocol, this was a schools-based cross-sectional survey. We used the child and adolescent versions of the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, self-completed by pupils within classes, in a total of nine schools in Lusaka (urban) and Copperbelt (semi-rural). These two of Zambia’s ten provinces were selected to represent the country’s urban/rural divide. Headache diagnostic questions were based on ICHD-3 except for undifferentiated headache (UdH).

Results
Of 2,759 potential participants, 2,089 (615 children [29.4%], 1,474 adolescents [70.6%]) completed questionnaires (participating proportion 75.7%). Children were therefore under-represented (mean age 13.1 ± 2.8 years), while gender distribution (1,128 [54.0%] male, 961 [46.0%] female) was close to expectation. Observed lifetime prevalence of headache was 97.5%. Gender- and age-adjusted 1-year prevalence estimates were 85.8% for all headache, 53.2% for migraine (definite 17.5%, probable 35.7%), 12.1% for tension-type headache (TTH), 14.8% for UdH, 3.3% for all headache on ≥ 15 days/month and 0.9% for probable medication-overuse headache. Headache durations were short: only 28.6% of participants with any headache, and only 10.5% of those diagnosed as probable migraine, reported usual durations of > 2 h (the threshold for definite migraine). Of the latter, 36.6% reported < 1 h, the duration criterion for UdH. There were weak associations of migraine (definite + probable) with female gender, and of TTH and headache on ≥ 15 days/month with adolescence. Headache yesterday was reported by 22.2% of the sample, 25.5% of those with headache.

Conclusions
Headache disorders among young people are prevalent in Zambia. Among them, migraine is the most common, with UdH also highly prevalent. In this study there were diagnostic uncertainties, which rested to a large extent on the distinction between migraine and UdH among the many participants reporting headache of < 2 h’ duration. Similar uncertainties occurred in the first study in SSA, in Ethiopia. Because of these, we conclude only that migraine affects at least 17.5% of these age groups in Zambia, which is still a large proportion, adult prevalence in an earlier study being 22.9%. Supplementary estimates of attributed burden are needed to inform public-health and educational policies in Zambia.
Analysis of protein kinase C (HcPKC) gene expression and single-nucleotide polymorphisms related to inner shell color traits in Hyriopsis cumingii
Authors: Zhang Mengying , Chen Xiajun , Zhang Jinpan , Guo Baiying , Li Jiale , Bai Zhiyi 
Published: September 2022

Abstract
Background
Protein kinase C (PKC) is a multifunctional serine and PKC can phosphorylate serine residues in the cytoplasmic domain of tyrosinase, thereby regulating the activity of tyrosinase. Activated PKC is bound to the melanosome membrane, and unactivated PKC is free in the cytoplasm of melanocytes. In this study, we study the role of PKC gene in the melanin synthesis pathway and its effect on the color of the nacre of H. cumingii.

Results
In this study, a HcPKC gene in H. cumingii was cloned and its effects on melanin synthesis and nacre color were studied. HcPKC was expressed in both purple and white mussels, and the level of mRNA expression was higher in the purple mussels than in white mussels. Strong and specific mRNA signals were detected in the dorsal epithelial cells of the mantle pallial layer, indicating that HcPKC may be involved in nacre formation. After SNP association with inner shell color related traits, according to the principle that 0.25 < PIC < 0.5 is medium polymorphism and PIC < 0.25 is low polymorphism, the A + 332G site on the HcPKC gene was a site of moderate polymorphism, and the other four sites were low polymorphism sex sites. There was strong linkage disequilibrium among the five loci. A haplotype was constructed and it was found that the frequency of T1 (AGGAA)in the white population was significantly higher than that in the purple population (P < 0.05).

Conclusion
The study found that HcPKC of H. cumingii can be used as a candidate gene related to inner shell color, and some of the SNP sites can be used for molecular-assisted breeding in the spinnaker mussel, providing a reference for cultivating high-quality freshwater pearls.
Unraveling metabolic patterns and molecular mechanisms underlying storability in sugar beet
Authors: Gippert Anna-Lena , Madritsch Silvia , Woryna Patrick , Otte Sandra , Mayrhofer Martina , Eigner Herbert , Garibay-Hernández Adriana , D’Auria John C. , Molin Eva M. , Mock Hans-Peter 
Published: September 2022

Abstract
Background
Sugar beet is an important crop for sugar production. Sugar beet roots are stored up to several weeks post-harvest waiting for processing in the sugar factories. During this time, sucrose loss and invert sugar accumulation decreases the final yield and processing quality. To improve storability, more information about post-harvest metabolism is required. We investigated primary and secondary metabolites of six sugar beet varieties during storage. Based on their variety-specific sucrose loss, three storage classes representing well, moderate, and bad storability were compared. Furthermore, metabolic data were visualized together with transcriptome data to identify potential mechanisms involved in the storage process.

Results
We found that sugar beet varieties that performed well during storage have higher pools of 15 free amino acids which were already observable at harvest. This storage class-specific feature is visible at harvest as well as after 13 weeks of storage. The profile of most of the detected organic acids and semi-polar metabolites changed during storage. Only pyroglutamic acid and two semi-polar metabolites, including ferulic acid, show higher levels in well storable varieties before and/or after 13 weeks of storage. The combinatorial OMICs approach revealed that well storable varieties had increased downregulation of genes involved in amino acid degradation before and after 13 weeks of storage. Furthermore, we found that most of the differentially genes involved in protein degradation were downregulated in well storable varieties at both timepoints, before and after 13 weeks of storage.

Conclusions
Our results indicate that increased levels of 15 free amino acids, pyroglutamic acid and two semi-polar compounds, including ferulic acid, were associated with a better storability of sugar beet taproots. Predictive metabolic patterns were already apparent at harvest. With respect to elongated storage, we highlighted the role of free amino acids in the taproot. Using complementary transcriptomic data, we could identify potential underlying mechanisms of sugar beet storability. These include the downregulation of genes for amino acid degradation and metabolism as well as a suppressed proteolysis in the well storable varieties.
Transcriptomic and alternative splicing analyses provide insights into the roles of exogenous salicylic acid ameliorating waxy maize seedling growth under heat stress
Authors: Guo Jian , Wang Zitao , Qu Lingling , Hu Yifan , Lu Dalei 
Published: September 2022

AbstractBackgroundSalicylic acid (SA) is a phytohormone which works to regulate the abiotic stress response of plants. However, the molecular mechanism by which SA mediates heat tolerance in waxy maize (Zea maysL.sinsensisKulesh) remains unknown.ResultsTwo varieties of waxy maize seedlings, heat-tolerant ‘Yunuo7’ (Y7) and heat-sensitive ‘Suyunuo5’ (S5), were pretreated with SA prior to heat stress (HTS). After treatment, physiological and transcriptomic changes were analyzed. Compared with HTS, the exogenous application of SA enhanced the shoot dry weight, the activities of antioxidant enzymes (e.g., SOD, POD, CAT and APX), and the concentration of endogenous phytohormones (e.g., SA, ABA, IAA, GA3), while decreased the MDA content. Transcriptome analysis showed that the number of differentially expressed genes (DEGs) identified in the control (CK) vs HTS and HTS vs HTS + SA comparisons were more in S5 than in Y7. HTS induced the downregulation of genes involved in photosynthesis and the upregulation of genes encoding heat shock transcription factors (HSFs) and heat shock proteins (HSPs). Compared with HTS, SA pretreatment reversed the expression of 5 photosynthesis-related genes, 26 phytohormone-related genes, and all genes encoding HSFs and HSPs in S5. Furthermore, the number of alternative splicing (AS) events increased under HTS treatment for both varieties, while decreased under SA pretreatment of S5. Differentially spliced genes (DSGs) showed little overlap with DEGs, and DEGs and DSGs differed significantly in functional enrichment.ConclusionsPhysiological and transcriptional together indicated that HTS and SA pretreatment had a greater effect on S5 than Y7. Additionally, it appears that transcriptional regulation and AS work synergistically to enhance thermotolerance in heat-sensitive waxy maize. Our study revealed the regulatory effects and underlying molecular mechanisms of SA on waxy maize seedling under HTS.
Lithium-induced nephropathy; One medication with multiple side effects: a case report
Authors: Zhang Pingchuan , Gandhi Hardik , Kassis Nader 
Published: September 2022

Abstract
Background
Lithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare.

Case presentation
We herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started.

Conclusion
Based on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.