bluuebunny/crossref_metadata_2025_split huggingface dataset:
FC 129CHANGES IN PERIPHERAL NK CELLS IN KIDNEY TRANSPLANT RECIPIENTS WITH AND WITHOUT HLA DSA
Authors: Llinas Laura , Redondo Pachon Dolores , Raïch Regué Dàlia , Perez-Saez Maria Jose , Sanz Sara , Arias-Cabrales Carlos , Buxeda Anna , Burballa Carla , López-Botet José Miguel , Pascual Santos Julio , Crespo Marta 
Published: May 2021

Abstract

Background and Aims
Antibody-mediated rejection (ABMR) is a frequent cause of renal allograft loss. There is increasing evidence of the role of Natural Killer (NK) cells in the establishment of ABMR damage. Our group described that patients with donor-specific antibodies (DSA) and ABMR present higher proportions of NKG2A+ NK cell subset in peripheral blood than those without HLA DSA or HLA antibodies.

Method
We selected 177 kidney transplant recipients (KT) with renal biopsies 2011-2017: 77 with ABMR (DSA+: 53, DSA-: 24) and 100 without ABMR (DSA+: 15, DSA-: 85). We assessed graft survival with a median time of follow-up since the renal biopsy of 53 months. In 138 KT we evaluated the peripheral blood NK cell immunophenotyping and its value as a prognostic biomarker.

Results
Graft survival was worse in ABMR-KT at the end of follow-up (p&lt;0.001) independently of DSA detection (p=0.63). Regarding NK cell immunophenotyping, we observed a lower proportion and absolute NK cell count in ABMR+DSA+-KT and ABMR+DSA--KT compared with ABMR-DSA--KT (p=0.027, p=0.017). ABMR+DSA+-KT showed higher proportion of NKG2A+ NK cells compared with ABMR-DSA--KT (p=0.007). All ABMR+ patients, independently of DSA detection, presented lower absolute NKG2A- NK cell count in comparison with ABMR-DSA--KT (p=0.001, p=0.017). Finally, a proportion of NKG2A- &lt;30% was associated with lower graft survival 36 months after graft biopsy with ABMR (p=0.067) (Figure).

Conclusion
Graft survival is worse in ABMR+ compared with ABMR- KT independently of DSA detection. Kidney transplant recipients with ABMR show reduced peripheral absolute numbers of NK cells and NKG2A- NK cells regardless of undetectable DSA. This NK cell phenotype associated with a worse medium-term graft survival in cases with ABMR.
FC 089EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE CARDIOVASCULAR EVENTS BY BASELINE ALBUMINURIA: INTEGRATED ANALYSES FROM THE CANVAS PROGRAM AND CREDENCE TRIAL
Authors: Wheeler David C , Weir Matthew , Gogate Jagadish , Perkovic Vlado , Mahaffey Kenneth W 
Published: May 2021

Abstract

Background and Aims
People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular (CV) disease and major adverse CV events (MACE) that is more common as renal function declines. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of MACE (CV death, nonfatal myocardial infarction [MI], and nonfatal stroke) in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trials, respectively.

Method
This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of canagliflozin compared with placebo on MACE were assessed in subgroups defined by baseline urinary albumin:creatinine ratio (UACR; &lt;30, 30-300, and &gt;300 mg/g). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using stratified (by study) Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity. Interaction P values were calculated by including the terms of treatment group, baseline UACR, and their interaction in the model.

Results
A total of 14,543 participants from the CANVAS Program (N = 10,142) and CREDENCE (N = 4,401) were included, with mean estimated glomerular filtration rate of 70.3 mL/min/1.73 m2 and median (interquartile range) UACR of 501.0 (8.4-523.6) mg/g. Among participants with baseline UACR measurements, 7038 (48.8%), 2762 (19.1%), and 4634 (32.1%) participants had baseline UACR &lt;30, 30-300, and &gt;300 mg/g, respectively. Rates of MACE and its components increased as UACR increased (Figure). Canagliflozin reduced the risk of MACE compared with placebo in the overall population (HR, 0.83; 95% CI, 0.75, 0.92), with consistent effects observed across UACR subgroups (interaction P value = 0.42). Canagliflozin also reduced the risk of the individual components of CV death (HR, 0.84; 95% CI, 0.72, 0.97), nonfatal MI (HR, 0.83; 95% CI, 0.70, 0.99), and nonfatal stroke (HR, 0.84; 95% CI, 0.69, 1.03), independent of baseline UACR (interaction P values = 0.40, 0.88, and 0.69, respectively). Canagliflozin was generally well tolerated in the CANVAS Program and the CREDENCE trial, with consistent results on safety outcomes across UACR subgroups.

Conclusion
Event rates of MACE and its components increased with higher UACR. Canagliflozin reduced the risk of MACE and its components in participants with T2DM and high CV risk or CKD in the CANVAS Program and CREDENCE trial, with consistent benefits observed regardless of baseline UACR.
FC 091URINARY CCL5 MRNA, A POTENTIAL BIOMARKER FOR PROGRESSION OF TYPE 2 DIABETIC NEPHROPATHY
Authors: Feng Songtao , Gao Yueming , Cao Jingyuan , Yin Di , Lv Linli , Liu Bicheng 
Published: May 2021

Abstract

Background and Aims
In recent years, it has been found that targeted mRNA detection of sediment cells in urine can be used as novel biomarkers for the diagnosis of diabetic nephropathy (DN). However, its value in predicting the progression of DN is not clear. The purpose of this study is to seek for urinary mRNA markers that evaluate the prognosis of DN through systems biological screening, clinical verification and prospective studies.

Method
GEO database and “Nephroseq” platform were searched, and the transcriptome data of DN glomeruli and tubules and their clinical information were obtained. Weighted gene co-expression network analysis (WGCNA) combined with gene ontology (GO) annotation and KEGG pathway enrichment analysis were used to screen the hub genes negatively related to eGFR, and the hub genes were used as candidate markers for mRNA detection in urine sediment in DN patients. A total of 91 patients with DN diagnosed by renal biopsy were included, and 60 patients with type 2 diabetes and 61 healthy people were selected as the control groups. The mRNA expression of candidate molecules was detected by Taqman probe quantitative PCR, and the correlation between mRNA expression and eGFR and urinary protein levels were analyzed. Patients with DN were followed up for a median time of 21 months, and the primary end point was defied as end stage renal disease or eGFR decreasing by more than 50%. Multivariate Cox regression was used to evaluate the value of mRNA in predicting DN progression.

Results
GSE30528 and GSE30529 datasets were selected for analysis, including mRNA expression data of 9 cases of DN and 13 cases of normal glomeruli; and 10 cases of DN and 12 cases of normal tubules respectively. The clinical data of the patients in this study, including gender, race, age and eGFR, were searched on the Nephroseq platform. The gene modules negatively related to eGFR were screened by WGCNA. GO and KEGG analysis showed that the main function of the gene modules in both datasets were related to the activation of inflammatory cells and chemokines pathway. Through the screening of hub genes and the comparison of expression levels, CCL5, CXCL1, CXCL6 and CXCL12 were finally obtained as candidate genes. Quantitative PCR showed that the levels of CCL5 and CXCL1 was significantly increased in DN group, CCL5 was negatively correlated with eGFR and positively correlated with urinary protein level, while CXCL1 was negatively correlated with eGFR, but had no significant correlation with urinary protein level. Multivariate Cox regression showed that eGFR, urinary protein level, degree of renal fibrosis and urinary CCL5 were independent risk factors of primary end point.

Conclusion
The activation of chemokine signal pathway in renal tissue is involved in the progression of DN. Urinary CCL5 mRNA can independently predict the prognosis of DN and may be served as a novel biomarker for the progression of DN.
FC 092EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY INJURY AND VASCULAR CALCIFICATION IN DIABETIC NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL
Authors: Trakarnvanich Thananda , Satirapoj Bancha , Suraamornkul Swangjit , Chiranantawat Thanit , Sanpatchayapong Anoma , Chaimon Torpong 
Published: May 2021

Abstract

Background and Aims
Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and contain pleiotropic actions on kidney injury, albuminuria and vascular inflammation especially in animal models. We plan to evaluate the efficacy of potent DPP4-inhibitors (gemigliptin) in response to these aspects in diabetic nephropathy patients.

Method
This is a multi-center, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to gemigliptin 50 mg daily and standard care of diabetes mellitus for 6 months. The changes of coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), markers of vascular calcification and markers of tubular renal injury were evaluated at baseline and 6 months.

Results
Overall 182 patients completed the study. Significantly reductions in hemoglobinA1C level were seen at month 6 with gemigliptin group (-0.67%) vs. control group (-0.15%; P=0.048). Changes of CAC score, CAVI, estimated GFR and proteinuria did not significantly difference in the both groups during 6 months of study. However, biomarkers of vascular calcification including serum bone alkaline phosphatase and biomarkers of kidney injury including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr improved significantly after gemigliptin treatment when compared to the control group. No serious adverse event was found during study.

Conclusion
Our study shows that gemigliptin has significant benefits on biomarkers of renal tubular injury and vascular calcification in patients with diabetic nephropathy, but gemigliptin does not affect on renal function and coronary calcification compared with control. The larger and longer follow-up will be essential to determine these beneficial effects.
Lessons Learned From Implementation of SARS-CoV-2 Screening in K-12 Public Schools in Massachusetts
Authors: Ciaranello Andrea , Goehringer Cathryn , Nelson Sandra B , Ruark Liz J , Pollock Nira R 
Published: June 2021

AbstractIn-person learning provides substantial benefits for K-12 school students. Risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among educators, staff, students, and household members can be markedly reduced by mitigation measures including masking, ventilation, and hygiene. In addition to these measures, where community transmission is moderate to high, regular SARS-CoV-2 screening testing is recommended by recent Centers for Disease Control and Prevention (CDC) guidance for unvaccinated K-12 students and staff, and supported financially by CDC and Department of Health and Human Services initiatives. Screening can provides an added layer of risk reduction, as well as data and reassurance about in-school transmission. Financial and logistical constraints have challenged implementation of screening in public schools. We report lessons learned from a collaborative of public K-12 schools implementing and evaluating screening programs, including details of population screened, site of specimen collection, assay selection, pooled testing, and resources needed. This work supported the development of a state-wide screening program and led to dissemination of online technical resources that may support other public schools in implementing CDC guidance.
Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Infusions in High-Risk Outpatients
Authors: Piccicacco Nicholas , Zeitler Kristen , Montero Jose , Kumar Ambuj , Lakshmi Seetha , Kim Kami , Wein David , Vasey Tiffany , Vasey Matthew , Oxner Asa 
Published: June 2021

Abstract

Background
Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19–related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance.

Methods
This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA’s Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19–related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events.

Results
Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14–.38]; P &lt; .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (P = .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment.

Conclusions
Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.
The chloroplast ribosomal protein large subunit 1 interacts with viral polymerase and promotes virus infection
Authors: Cheng De-Jie , Xu Xiao-Jie , Yan Zhi-Yong , Tettey Carlos Kwesi , Fang Le , Yang Guang-Ling , Geng Chao , Tian Yan-Ping , Li Xiang-Dong 
Published: May 2021

Abstract
Chloroplasts play an indispensable role in the arms race between plant viruses and hosts. Chloroplast proteins are often recruited by plant viruses to support viral replication and movement. However, the mechanism by which chloroplast proteins regulate potyvirus infection remains largely unknown. In this study, we observed that Nicotiana benthamiana ribosomal protein large subunit 1 (NbRPL1), a chloroplast ribosomal protein, localized to the chloroplasts via its N-terminal 61 amino acids (transit peptide), and interacted with tobacco vein banding mosaic virus (TVBMV) nuclear inclusion protein b (NIb), an RNA-dependent RNA polymerase. Upon TVBMV infection, NbRPL1 was recruited into the 6K2-induced viral replication complexes in chloroplasts. Silencing of NbRPL1 expression reduced TVBMV replication. NbRPL1 competed with NbBeclin1 to bind NIb, and reduced the NbBeclin1-mediated degradation of NIb. Therefore, our results suggest that NbRPL1 interacts with NIb in the chloroplasts, reduces NbBeclin1-mediated NIb degradation, and enhances TVBMV infection.
Federalism, Defunding the Police, and Democratic Values: A Functional Accountability Framework for Analyzing Police Reform Proposals
Authors: Sinclair J Andrew , Love Maya , Gutiérrez-Vera María 
Published: May 2021

AbstractThis article examines recent proposals to “defund the police” using a perspective informed by literature on agency termination and political accountability. These concepts allow us to build a framework for categorizing such proposals based on the assignment of functions to organizations. These proposals operate in the context of a federal system which can shape the character of each category, make some choices more or less feasible, influence where functions may be assigned, and create political incentives out of the complex geography of conflict. We use examples from Minneapolis, New York, Los Angeles, and Seattle to illustrate our framework. We conclude by offering a preliminary analysis of why these cities tend towards adopting one of the alternatives we outline.
Interventricular systolic asynchrony predicts prognosis in patients with systemic sclerosis-associated pulmonary arterial hypertension
Authors: Lai Jinzhi , Guo Xiaoxiao , Zhao Jiuliang , Wang Hui , Tian Zhuang , Wang Qian , Li Mengtao , Fang Quan , Fang Ligang , Liu Yongtai , Zeng Xiaofeng 
Published: May 2021

Abstract

Objective
Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH.

Methods
Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV.

Results
Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan–Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001).

Conclusion
In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.
Severe Coronavirus Disease Pneumonia in Pediatric Patients in a Referral Hospital
Authors: Ozcan Serhan , Emeksiz Serhat , Perk Oktay , Uyar Emel , Kanik Yüksek Saliha 
Published: May 2021

ABSTRACT

Objective
We aimed to evaluate the characteristics and outcomes of critically ill children managed in an intensive care unit because of coronavirus disease (COVID-19) pneumonia with respiratory support requirements.

Methods
We performed a single-center retrospective observational study in a pediatric intensive care unit (PICU) with 32 beds in Ankara City Hospital, Ankara, Turkey, from 13 March 2020 to 31 December 2020. Patients who needed positive-pressure ventilation (PPV) therapy for COVID-19 pneumonia were included in the study. Demographic, clinical and laboratory data were extracted from the patients’ electronic medical records. As outcomes, the hospitalization rate of all pediatric patients diagnosed as having with COVID-19 by Polymerase Chaın Reactıon(PCR), PICU admission rate for COVID-19 pneumonia among all hospitalized patients, PPV support rate, intensive care hospitalization duration (days), total hospitalization duration (days), survival rate and tracheotomy requirement were evaluated.

Results
During the study period, 7033 children tested positive for COVID-19 in PCR tests. Of these patients, 1219 were hospitalized for COVID-19. Seventeen patients needed PPV support because of COVID-19 pneumonia. High proportion (65%) of patients admitted to the PICU had comorbid diseases. Noninvasive ventilation was applied in 15 patients (88%). The hospitalization rate among the children with COVID-19 was 17%, of whom 1.6% were admitted to the PICU. Mortality rates were 0.056% of all the cases and 0.32% of the hospitalized patients in our hospital.

Conclusion
The presence of a comorbid disease could be a sign of severe disease in children with higher lethality. Very few children required PPV support because of severe COVID-19 pneumonia.
Total Hip Arthroplasty for Acute Femoral Neck Fractures: Who Should Perform the Operation—Adult Reconstructive or Trauma Surgeons?
Authors: Thomas John C. , Haidukewych George J. 
Published: May 2021

Objective:
To compare the results and complications of a large consecutive series of total hip arthroplasty (THA) performed for acute femoral neck (FN) fracture by adult reconstructive (AR) and trauma (T) surgeons to determine if there is a difference in outcomes.

Design:
Retrospective chart review.

Setting:
Level 1 trauma center.

Patients:
One hundred forty-nine consecutive patients who presented to our institution with displaced FN fractures treated by THA were included in this study.

Intervention:
All patients were treated with THA.

Main Outcome Measurements:
Implant survival, 90-day complications, 90-day readmission, 1-year complications.

Results:
For the group as a whole, the major surgical complication rate (defined as dislocation, deep infection, loosening, fracture) was significantly higher for T surgeons (20%) than for AR surgeons (7%) (P = 0.021). AR surgeons had significantly less radiographic component malpositioning 12% versus 3% (P = 0.024). Mortality and readmission rates were similar between the 2 cohorts at all time points. Implant survivorship was significantly higher at 1 year for AR surgeons (P = 0.05).

Conclusions:
THA for acute FN fracture performed by AR surgeons demonstrated higher rates of accurate radiographic component positioning, significantly lower major complication rates at 90 days and 1 year, and greater implant survival at 1 year.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Primary Versus Secondary Radiotherapy for Heterotopic Ossification Prevention About the Elbow
Authors: Geller Joseph S. , Allegra Paul R. , Seldon Crystal S. , Spieler Benjamin O. , Cohen Lara L. , Barnhill Spencer W. , Huntley Samuel R. , De La Zerda Alberto , Samuels Stuart , Wang Lora , Isrow Derek , Wolfson Aaron H. , Yechieli Raphael L. 
Published: May 2021

Objectives:
To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow.

Design:
Retrospective chart review.

Setting:
Level 1 trauma center.

Patients/Participants:
Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included.

Intervention:
All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery.

Main Outcomes Measurements:
The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint.

Results:
Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified.

Conclusions:
Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.