bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide identification and characterization analysis of RWP-RK family genes reveal their role in flowering time of Chrysanthemum lavandulifolium
Authors: Zhang Qiuling , Li Junzhuo , Wen Xiaohui , Deng Chengyan , Yang Xiuzhen , Dai Silan 
Published: April 2023

Abstract
Background
RWP-RKs are plant specific transcription factors, which are widely distributed in plants in the form of polygenic families and play key role in nitrogen absorption and utilization, and are crucial to plant growth and development. However, the genome-wide identification and function of RWP-RK in Compositae plants are widely unknown.

Results
In this study, 101 RWP-RKs in Chrysanthemum lavandulifolium were identified and tandem repeat was an important way for the expansion of RWP-RKs in Compositae species. 101 RWP-RKs contain 38 NIN-like proteins (NLPs) and 31 RWP- RK domain proteins (RKDs), as well as 32 specific expansion members. qRT-PCR results showed that 7 ClNLPs in leaves were up-regulated at the floral transition stage, 10 ClNLPs were negatively regulated by low nitrate conditions, and 3 of them were up-regulated by optimal nitrate conditions. In addition, the flowering time of Chrysanthemum lavandulifolium was advanced under optimal nitrate conditions, the expression level of Cryptochromes (ClCRYs), phytochrome C (ClPHYC) and the floral integration genes GIGANTEA (ClGI), CONSTANS-LIKE (ClCOL1, ClCOL4, ClCOL5), FLOWERING LOCUS T (ClFT), FLOWERING LOCUS C (ClFLC), SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1 (ClSOC1) also were up-regulated. The expression level of ClCRY1a, ClCRY1c, ClCRY2a and ClCRY2c in the vegetative growth stage induced by optimal nitrate reached the expression level induced by short-day in the reproductive growth stage, which supplemented the induction effect of short-day on the transcription level of floral-related genes in advance.

Conclusions
It was speculated that ClNLPs may act on the photoperiodic pathway under optimal nitrate environment, and ultimately regulate the flowering time by up-regulating the transcription level of ClCRYs. These results provide new perspective for exploring the mechanism of nitrate/nitrogen affecting flowering in higher plants.
Time-trend analysis of the center frequency of the intrinsic mode function from the Hilbert–Huang transform of electroencephalography during general anesthesia: a retrospective observational study
Authors: Obata Yurie , Yamada Tomomi , Akiyama Koichi , Sawa Teiji 
Published: April 2023

Abstract
Background
Anesthesiologists are required to maintain an optimal depth of anesthesia during general anesthesia, and several electroencephalogram (EEG) processing methods have been developed and approved for clinical use to evaluate anesthesia depth. Recently, the Hilbert–Huang transform (HHT) was introduced to analyze nonlinear and nonstationary data. In this study, we assessed whether the changes in EEG characteristics during general anesthesia that are analyzed by the HHT are useful for monitoring the depth of anesthesia.

Methods
This retrospective observational study enrolled patients who underwent propofol anesthesia. Raw EEG signals were obtained from a monitor through a previously developed software application. We developed an HHT analyzer to decompose the EEG signal into six intrinsic mode functions (IMFs) and estimated the instantaneous frequencies (HHT_IF) for each IMF. Changes over time in the raw EEG waves and parameters such as HHT_IF, BIS, spectral edge frequency 95 (SEF95), and electromyogram parameter (EMGlow) were assessed, and a Gaussian process regression model was created to assess the association between BIS and HHT_IF.

Results
We analyzed EEG signals from 30 patients. The beta oscillation frequency range (13–25 Hz) was detected in IMF1 and IMF2 during the awake state, then after loss of consciousness, the frequency decreased and alpha oscillation (8–12 Hz) was detected in IMF2. At the emergence phase, the frequency increased and beta oscillations were detected in IMF1, IMF2, and IMF3. BIS and EMGlow changed significantly during the induction and emergence phases, whereas SEF95 showed a wide variability and no significant changes during the induction phase. The root mean square error between the observed BIS values and the values predicted by a Gaussian process regression model ranged from 4.69 to 9.68.

Conclusions
We applied the HHT to EEG analyses during propofol anesthesia. The instantaneous frequency in IMF1 and IMF2 identified changes in EEG characteristics during induction and emergence from general anesthesia. Moreover, the HHT_IF in IMF2 showed strong associations with BIS and was suitable for depicting the alpha oscillation. Our study suggests that the HHT is useful for monitoring the depth of anesthesia.
External validation of the QLifetime cardiovascular risk prediction tool: population cohort study
Authors: Livingstone Shona , Morales Daniel R. , Fleuriot Jacques , Donnan Peter T. , Guthrie Bruce 
Published: April 2023

Abstract
Background
Prediction of lifetime cardiovascular disease (CVD) risk is recommended in many clinical guidelines, but lifetime risk models are rarely externally validated. The aim of this study was to externally validate the QRiskLifetime incident CVD risk prediction tool.

Methods
Independent external validation of QRiskLifetime using Clinical Practice Research Datalink data, examining discrimination and calibration in the whole population and stratified by age, and reclassification compared to QRISK3. Since lifetime CVD risk is unobservable, performance was evaluated at 10-years’ follow-up, and lifetime performance inferred in terms of performance for in the different age-groups from which lifetime predictions are derived.

Results
One million, two hundreds sixty thousand and three hundreds twenty nine women and 1,223,265 men were included in the analysis. Discrimination was excellent in the whole population (Harrell’s-C = 0.844 in women, 0.808 in men), but moderate to poor stratified by age-group (Harrell’s C in people aged 30–44 0.714 for both men and women, in people aged 75–84 0.578 in women and 0.556 in men). Ten-year CVD risk was under-predicted in the whole population, and in all age-groups except women aged 45–64, with worse under-prediction in older age-groups. Compared to those at highest QRISK3 estimated 10-year risk, those with highest lifetime risk were younger (mean age: women 50.5 vs. 71.3 years; men 46.3 vs. 63.8 years) and had lower systolic blood pressure and prevalence of treated hypertension, but had more family history of premature CVD, and were more commonly minority ethnic. Over 10-years, the estimated number needed to treat (NNT) with a statin to prevent one CVD event in people with QRISK3 ≥ 10% was 34 in women and 37 in men, compared to 99 and 100 for those at highest lifetime risk.

Conclusions
QRiskLifetime underpredicts 10-year CVD risk in nearly all age-groups, so is likely to also underpredict lifetime risk. Treatment based on lifetime risk has considerably lower medium-term benefit than treatment based on 10-year risk.
Stress hyperglycemia ratio: an independent predictor for in-hospital major adverse cardiovascular and cerebrovascular events in patients with st-segment elevation myocardial infarction
Authors: Guo Wen , Zhu Jiajia , Liu Wenxian 
Published: April 2023

AbstractBackgroundTo assess the predictive accuracy of the stress hyperglycemia ratio (SHR) for in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ST-segment elevation myocardial infarction (STEMI).MethodsA total of 1,944 patients were enrolled within 24 h of a new STEMI diagnosis. The SHR was obtained by dividing the blood glucose level at admission by the estimated average glucose. MACCE were defined as acute cerebral infarction, mechanical complications of myocardial infarction, cardiogenic shock, and all-cause death. Patients were then categorized into the MACCE and non-MACCE groups according to the occurrence of in-hospital MACCE. Propensity score matching was used to balance confounding factors, and logistic regression was used to identify the potential predictive factors for MACCE.ResultsA total of 276 patients were included after 1:1 matching, and the confounding factors were balanced between the two groups. The SHR was an independent predictor of in-hospital MACCE (odds ratio = 10.06, 95% confidence interval: 4.16–27.64,P < 0.001), while blood glucose at admission was not. The SHR was also an independent predictor for in-hospital MACCE in nondiabetic patients with STEMI (odds ratio = 11.26, 95% confidence interval: 3.05–55.21,P < 0.001).ConclusionSHR is an independent predictor of in-hospital MACCE in patients with acute STEMI, especially in nondiabetic patients.
Serum neurofilament light chain as a predictive marker of neurologic outcome after cardiac arrest: a meta-analysis
Authors: Wang Shu Li , Li Nan , Feng Shun Yi , Li Yong 
Published: April 2023

Abstract
Objective
Recently, an increasing number of studies have suggested using serum neurofilament light (NfL) chain to predict the neurologic outcome after cardiac arrest. However, the predictive ability of this approach remains inconclusive. Meta-analysis was performed on related studies to assess the ability of serum NfL to predict the neurologic outcome after cardiac arrest.

Materials and methods
PubMed, ScienceDirect and Embase were systematically searched from the date of their inception until June 2022. Data were extracted to calculate the area under the receiver operating characteristic curve (AUC), the sensitivity, the specificity and the publication bias to evaluate the predictive power of serum NfL using Stata 14.0.

Results
Nine studies were included in the present meta-analysis. Seven studies involving 1296 participants reported serum NfL 24 h post arrest for predicting the neurological outcome, and the AUC was 0.92 (77% sensitivity and 96% specificity). Seven studies involving 1020 participants reported serum NfL 48 h post arrest for predicting the neurological outcome, and the AUC was 0.94 (78% sensitivity and 98% specificity). Four studies involving 804 participants reported serum NfL 72 h post arrest for predicting the neurological outcome, and the AUC was 0.96 (90% sensitivity and 98% specificity). No significant publication bias was observed among the included studies.

Conclusion
The present meta-analysis results support the potential use of serum NfL as an early biomarker of neurologic outcome, especially 72 h post arrest.
A new pathway for considering trigger factors based on parallel-serial connection models and displaying the relationships of causal factors in low-probability events
Authors: Hui Liu 
Published: April 2023

Abstract
Background
To determine the effect size of observed factors considering trigger factors based on parallel-serial models and to explore how multiple factors can be related to the result of complex events for low-probability events with binary outcomes.

Methods
A low-probability event with a true binary outcome can be explained by a trigger factor. The models were based on the parallel-serial connection of switches; causal factors, including trigger factors, were simplified as switches. Effect size values of an observed factor for an outcome were calculated as SAR = (Pe-Pn)/(Pe + Pn), where Pe and Pn represent percentages in the exposed and nonexposed groups, respectively, and SAR represents standardized absolute risk. The influence of trigger factors is eliminated by SAR. Actual data were collected to obtain a deeper understanding of the system.

Results
SAR values of < 0.25, 0.25–0.50, and > 0.50 indicate low, medium, and high effect sizes, respectively. The system of data visualization based on the parallel-serial connection model revealed that at least 7 predictors with SAR > 0.50, including a trigger factor, were needed to predict schizophrenia. The SAR of the HLADQB1*03 gene was 0.22 for schizophrenia.

Conclusions
It is likely that the trigger factors and observed factors had a cumulative effect, as indicated by the parallel-serial connection model for binary outcomes. SAR may allow better evaluation of the effect size of a factor in complex events by eliminating the influence of trigger factors. The efficiency and efficacy of observational research could be increased if we are able to clarify how multiple factors can be related to a result in a pragmatic manner.
Characterization of an obese population: a retrospective longitudinal study from real-world data in northern Portugal
Authors: Páscoa Rosália , Teixeira Andreia , Henriques Teresa S. , Monteiro Hugo , Monteiro Rosário , Martins Carlos 
Published: April 2023

Abstract
Background
Obesity is a serious and largely preventable global health problem. Obesity-related electronic health records can be a useful resource to identify and address obesity. The analysis of real-world data from T82-coded (International Classification of Primary Care coding, for obesity) primary care individuals can be an excellent national source of data on obesity’s prevalence, characteristics, and impact on the National Health Service.

Methods
Retrospective longitudinal study, based on a database of electronic medical records, from the Regional Health Administration of northern Portugal. The study objectives were to determine the prevalence of obesity and to characterize an adult obese population in northern Portugal from a bio-demographic point of view along with profiles of comorbidities and the use of health resources. This study used a database of 266,872 patients in December 2019 and screened for diagnostic code T82 from the International Classification of Primary Care.

Results
The prevalence of obesity was 10.2% and the highest prevalence of obesity was in the 65–74 age group (16.1%). The most prevalent morbidities in patients with obesity as coded through ICPC-2 were K86 (uncomplicated hypertension), T90 (non-insulin-dependent diabetes), and K87 (complicated hypertension). Descriptive information showed that T82 subjects used more consultations, medications, and diagnostic tests than non-T82 subjects.

Conclusions
Routine recording of weight and height deserves special attention to allow obesity recognition at an early stage and move on to the appropriate intervention. Future work is necessary to automate the codification of obesity for subjects under 18 years of age, to raise awareness and anticipate the prevention of problems associated with obesity.
Practical strategies need to be implemented, such as the creation of a specific program consultation with truly targeted approaches to obesity.
Use of preventive medication and supplements in general practice in patients in their last year of life: a Retrospective cohort study
Authors: Antonisse Anne , van der Baan Frederieke H. , Grant Matthew , Uyttewaal Gon , Verboeket Cathelijne , Smits-Pelser Hanneke , Teunissen Saskia C. C. M. , Geijteman Eric C. T. 
Published: April 2023

Abstract
Background
Several preventive medications and supplements become inappropriate in the last phase of life due to increased risk of adverse events caused by changed pharmacokinetics, drug-drug interactions, and changed care goals. Information on these preventive medication and supplements use in patients with a life-limiting illness in the home-care setting is limited. The primary aim of this study was to assess the use of four different groups of preventive drugs and supplements, which are inappropriate in adult patients with a life-limiting illness, living at home in the last year of life. The secondary aims were to assess reasons for discontinuing these drugs as documented in the general practitioners’ patient file and whether these reasons affected the time between medication discontinuation and death.

Methods
We performed a retrospective cohort study using the routine primary care database of the Julius General Practitioners’ Network of the University Medical Centre Utrecht, a database consisting of routine care data from GPs from the city of Utrecht and its vicinity. Patients in the homecare setting with a life-limiting illness, diagnosed at least one year before death, were included. Descriptive analyses were used to describe the study population and the frequency of starting, using, and discontinuing medication and supplements in the last year of life.

Results
A total of 458 of 666 included patients (69%) used at least one preventive drug in the last year of life. Vitamins were used by 36% of the patients, followed with 35% using cholesterol-lowering medication, 24% using calcium supplements and 9% using bisphosphonates. Bisphosphonates were discontinued by 70% of the users, calcium supplements by 61%, vitamins by 56% and cholesterol-lowering medication by 48% of the users, with a median interval between day of discontinuation and death of 119, 60, 110 and, 65 days, respectively. The median time between medication or supplement discontinuation and death was longest in patients with side effects and who had medication reviews.

Conclusion
Many patients in their last phase of life in the home-care setting use inappropriate medication and supplements. Timely medication review may contribute to optimise medication use in the last year of life.
The exacerbated hypokalemia in membranous glomerulonephritis due to proximal tubular injury: a neglect issue from a case report and literature review
Authors: Chang Chih-Hao , Yu Hui-Jung , Hou Yi-Chou 
Published: April 2023

Abstract
Background
Membranous glomerulonephritis is the most common primary etiology for the nephrotic syndrome in adults. Beyond the clinical hallmark of nephrotic syndrome such as fluid overloading, dyslipidemia and hypoalbuminemia, the dysregulated homeostasis of potassium and its possible mechanism is seldomly discussed, and its association with the clinical course of membranous GN is lacking.

Case presentation
A 65 year-old female attended to our emergent department for progressive lower leg edema after taking 15-h of flight. Hypoalbuminemia and hyperlipidemia were both noted, and 24-h urinary total protein was up to 17,950 mg/day. Elevated creatin-phospho-kinase developed at the initial presentation with hypokalemia due to excressive renal excretion. Glycosuria without elevated glycated Hemoglobin occurred. The pathology of kidney biopsy revealed subepithelial immunocomplex deposits with spike formation in the electron microscopy and the positive anti-Phosphlipase A2 receptor antibodies(PLA-2R) with hallmark of membranous glomerulonephritis. In the light microscopy, the vacuolization of proximal tubules was noted, which contributed to the potassium wasting. After 1 year following up duration, the patient’s proteinuria persisted after maintenance treatment with calcineurin inhibitor.

Conclusion
Hypokalemia is a neglected issue in the membranous glomerulonephritis. Unlike the previous literature, our patient had the vacuolization of proximal tubule at the initial presentation with hypokalemia, which might contribute the potassium wasting. The proximal tubular damage with hypokalemia might be a predictive factor for membranous glomerulonephritis.
Nirmatrelvir/ritonavir treatment in SARS-CoV-2 positive kidney transplant recipients – a case series with four patients
Authors: Schneider Johanna , Wobser Rika , Kühn Wolfgang , Wagner Dirk , Tanriver Yakup , Walz Gerd 
Published: April 2023

Abstract
Background
Despite vaccination coronavirus disease 2019 (COVID-19)-associated mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains high in kidney transplant recipients. Nirmatrelvir is a protease inhibitor with activity against SARS-CoV-2. Nirmatrelvir reduces the risk for mortality and hospitalization, which is approved for treating adults at risk for severe disease. Nirmatrelvir is metabolized by the cytochrome P-450 (CYP) 3A4 isozyme CYP3A4 and is therefore co-administered with the irreversible CYP3A4 inhibitor ritonavir, which results in a drug interaction with tacrolimus. A limited number of patients with nirmatrelvir/ritonavir and tacrolimus therapy after kidney transplantation have been reported to date. It has been reported that tacrolimus was paused during the five-day nirmatrelvir/ritonavir therapy and subtherapeutic tacrolimus levels were observed after finishing nirmatrelvir/ritonavir in two patients. Therefore, optimization of tacrolimus dosing is urgently needed in transplant recipients receiving nirmatrelvir/ritonavir treatment.

Case presentation
Here, we present our first-hand experience with four patients receiving tacrolimus therapy following kidney transplantation and nirmatrelvir/ritonavir therapy due to COVID-19. Tacrolimus was paused during nirmatrelvir/ritonavir therapy in all patients, which resulted in stable therapeutic tacrolimus levels. Tacrolimus was continued directly after finishing nirmatrelvir/ritonavir to avoid subtherapeutic levels in the first patient treated. This patient received his usual tacrolimus maintenance dose, which resulted in toxic levels. Based on this observation, tacrolimus therapy was continued 24 h after finishing nirmatrelvir/ritonavir treatment at a reduced dose in the subsequent patients. In these patients, therapeutic to supratherapeutic tacrolimus levels were observed despite the therapeutic break and dose reduction.

Discussion and conclusions
Based on altered CYP3A4 metabolism, tacrolimus levels have to be closely monitored after treatment with nirmatrelvir/ritonavir. Our study suggests that tacrolimus treatment should be paused during nirmatrelvir/ritonavir medication and be continued 24 h after completing nirmatrelvir/ritonavir therapy at a reduced dose and under close monitoring. Based on the limited number of patients in this study, results must be interpreted with caution.
Alport syndrome misdiagnosed with IgA nephropathy from familial history: a case report and brief review
Authors: Rahimzadeh Hormat , Ajlou Sanaz , Nili Fatemeh , Razeghi Effat 
Published: April 2023

Abstract
Background
Alport syndrome is a rare inherited disease resulting from a primary disorder of the glomerular basement membrane. This disease results from mutations in genes encoding alpha chains of type IV collagen. In the differential diagnosis of this disease, IgA nephropathy is the most common primary glomerular disease with gross or microscopic hematuria.

Case presentation
A 50-year-old woman was presented with microscopic hematuria and proteinuria of under one gram. Due to the diagnosis of IgA nephropathy in family members, she was treated and followed up for 4 years as a possible case of IgA nephropathy. Eye examination and audiometry were normal. She underwent renal biopsy with an exacerbation of proteinuria. There was no finding in favor of IgA nephropathy in the histological examination, but the findings of electron microscopy and family history favored Alport syndrome.

Conclusions
This case demonstrates the importance of accurate history and electron microscopy in the complete histological evaluation and diagnosis of glomerular disease. Although in most cases the two can be differentiated based on clinical manifestations, laboratory findings, and histopathological examination, sometimes the association of these two diseases in the families involved or the lack of accurate history and complete histological examinations can complicate the diagnosis.