bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression of functionally-related genes coevolves across fungal species: detecting coevolution of gene expression using phylogenetic comparative methods
Authors: Cope Alexander L. , O’Meara Brian C. , Gilchrist Michael A. 
Published: May 2020

Abstract
Background
Researchers often measure changes in gene expression across conditions to better understand the shared functional roles and regulatory mechanisms of different genes. Analogous to this is comparing gene expression across species, which can improve our understanding of the evolutionary processes shaping the evolution of both individual genes and functional pathways. One area of interest is determining genes showing signals of coevolution, which can also indicate potential functional similarity, analogous to co-expression analysis often performed across conditions for a single species. However, as with any trait, comparing gene expression across species can be confounded by the non-independence of species due to shared ancestry, making standard hypothesis testing inappropriate.

Results
We compared RNA-Seq data across 18 fungal species using a multivariate Brownian Motion phylogenetic comparative method (PCM), which allowed us to quantify coevolution between protein pairs while directly accounting for the shared ancestry of the species. Our work indicates proteins which physically-interact show stronger signals of coevolution than randomly-generated pairs. Interactions with stronger empirical and computational evidence also showing stronger signals of coevolution. We examined the effects of number of protein interactions and gene expression levels on coevolution, finding both factors are overall poor predictors of the strength of coevolution between a protein pair. Simulations further demonstrate the potential issues of analyzing gene expression coevolution without accounting for shared ancestry in a standard hypothesis testing framework. Furthermore, our simulations indicate the use of a randomly-generated null distribution as a means of determining statistical significance for detecting coevolving genes with phylogenetically-uncorrected correlations, as has previously been done, is less accurate than PCMs, although is a significant improvement over standard hypothesis testing. These methods are further improved by using a phylogenetically-corrected correlation metric.

Conclusions
Our work highlights potential benefits of using PCMs to detect gene expression coevolution from high-throughput omics scale data. This framework can be built upon to investigate other evolutionary hypotheses, such as changes in transcription regulatory mechanisms across species.
Long non-coding RNAs in the alkaline stress response in sugar beet (Beta vulgaris L.)
Authors: Zou Chunlei , Wang Yubo , Wang Bin , Liu Dan , Liu Lei , Gai Zhijia , Li Caifeng 
Published: May 2020

Abstract
Background
Long noncoding RNAs (lncRNAs) play crucial roles in regulating numerous biological processes in which complicated mechanisms are involved. Nonetheless, little is known about the number, features, sequences, and possible effects of lncRNAs on plant responses to alkaline stress.

Results
Leaf samples collected based on the control Beta vulgaris L., as well as those under short-term and long-term alkaline treatments, were subjected to high-throughput RNA sequencing, through which a total of 8535 lncRNAs with reliable expression were detected. Of these lncRNAs, 102 and 49 lncRNA expression profiles were altered after short- and long-term alkaline stress, respectively. Moreover, 7 lncRNAs were recognized as precursors to 17 previously identified miRNAs. Four lncRNAs responsive to alkaline stress were estimated as targets for 8 miRNAs. Moreover, computational analysis predicted 4318 potential target genes as lncRNAs responsive to alkaline stress. Analysis of functional annotations showed that the abovementioned possible target genes were involved in various bioprocesses, such as kinase activity, structural constituents of ribosomes, the ribonucleoprotein complex and protein metabolic processes. Association analysis provided convincing proof of the interplay of specific candidate target genes with lncRNAs.

Conclusion
LncRNAs likely exert vital roles during the regulation of the alkaline stress response and adaptation in plants through interaction with protein-coding genes. The findings of this study contribute to comprehensively examining lncRNAs in Beta vulgaris L. and shed more light on the possible roles and modulating interplays of lncRNAs responsive to alkaline stress, thereby laying a certain basis for functional analyses of these types of Beta vulgaris L. lncRNAs in the future.
Adherence to guidelines across different specialties to prevent infections in patients undergoing immunosuppressive therapies
Authors: Chadwick David R. , Sayeed Laila , Rose Matthew , Budd Emily , Mohammed Mo , Harrison Sarah , Azad Jaskiran , Maddox Jamie 
Published: May 2020

Abstract
Background
Substantial numbers of patients are now receiving either immunosuppressive therapies or chemotherapy. There are significant risks in such patients of developing opportunistic infections or re-activation of latent infections, with higher associated morbidity and mortality. The aim of this quality improvement project was to determine how effective 5 different specialties were in assessing and mitigating risks of developing opportunistic infections or re-activation of latent infections in patients undergoing immunosuppressive therapies.

Methods
This was a single centre audit where records of patients attending clinics providing immunosuppressive therapies were reviewed for the following: evidence of screening for blood-borne virus [BBV] infections, varicella and measles immunity, latent/active TB or hypogammaglobulinaemia, and whether appropriate vaccines had been advised or various infection risks discussed. These assessments were audited against both national and international guidelines, or a cross-specialty consensus guideline where specific recommendations were lacking. Two sub-populations were also analysed separately: patients receiving more potent immunosuppression and black and minority ethnic [BME] patients,.

Results
For the 204 patients fulfilling the inclusion criteria, BBV, varicella/measles and latent TB screening was inconsistent, as was advice for vaccinations, with few areas complying with specialty or consensus guidelines. Less than 10% of patients in one specialty were tested for HIV. In BME patients screening for HIV [60%], measles [0%] and varicella [40%] immunity and latent [30%] or active [20%] TB was low. Only 38% of patients receiving potent immunosuppression received Pneumocystis prophylaxis, with 3 of 4 specialties providing less than 15% of patients in this category with prophylaxis.

Conclusions
Compliance with guidelines to mitigate risks of infection from immunosuppressive therapies was either inconsistent or poor for most specialties. New approaches to highlight such risks and assist appropriate pre-immunosuppression screening are needed.
Association of preeclampsia with infant APOL1 genotype in African Americans
Authors: Miller Anna K. , Azhibekov Timur , O’Toole John F. , Sedor John R. , Williams Scott M. , Redline Raymond W. , Bruggeman Leslie A. 
Published: May 2020

Abstract
Background
Black women in the United States and Africa are at an increased risk for preeclampsia. Allelic variants in the gene for apolipoprotein LI, APOL1, are found only in populations of African ancestry, and have been shown to contribute significant risk for kidney disease. Recent studies suggest these APOL1 variants also may contribute risk for preeclampsia.

Methods
The association of preeclampsia with carriage of APOL1 risk alleles was evaluated in a case-control study of deliveries from black women at a single center in Cleveland, Ohio that included gross and histopathologic evaluations of placental tissues (395 cases and 282 controls). Using logistic regression models, associations between fetal APOL1 genotype and preeclampsia were evaluated using several case definitions based on prematurity and severity of preeclampsia, with uncomplicated term pregnancies as controls. Associations between APOL1 genotype and pathological features were also examined.

Results
The infant APOL1 genotype was significantly associated with preeclampsia in a dominant inheritance pattern with odds ratio of 1.41 (P=0.029, 95% CI 1.037, 1.926). Stratifying preeclampsia cases by preterm birth, significant associations were detected for both recessive (O.R.=1.70, P=0.038) and additive (O.R.=1.33, P=0.028) inheritance patterns. APOL1 genotype, however, was not significantly associated with pathological changes or other perinatal observations.

Conclusions
Preeclampsia appears to be another disease associated with APOL1 variants, however, further studies are needed to increase confidence in the mode of inheritance. By understanding the association of APOL1 variants with preeclampsia, genetic screening tests for APOL1 may be useful to predict at-risk pregnancies and targeted interventions may be developed to improve pregnancy outcomes.
Ten-year outcome of Eculizumab in kidney transplant recipients with atypical hemolytic uremic syndrome– a single center experience
Authors: Kant Sam , Bhalla Anshul , Alasfar Sami , Alachkar Nada 
Published: May 2020

Abstract
Background
Atypical hemolytic uremic syndrome (aHUS) can result in severe kidney dysfunction, secondary to thrombotic microangiopathy. Eculizumab has been used to treat this disorder, and has resulted in favourable outcomes in both, native and transplanted kidneys. There is limited long term follow up data in kidney transplant recipients (KTRs) who received prevention and treatment with Eculizumab. We report our long term follow up data from our center to address safety and efficacy of this therapy in KTRs.

Methods
We performed a retrospective analysis of KTRs between January 2009 and December 2018. Clinical diagnosis of aHUS established with presence of thrombotic microangiopathy, acute kidney injury, absence of alternate identifiable etiology. We reviewed clinical data, including genetic testing for complement factor mutations, post-transplant course, and response to therapy including therapeutic and prophylactic use of eculizumab.

Results
Nineteen patients with aHUS received a total of 36 kidney transplants; 10 of them had 2 or more prior kidney transplants. Median age at time of last transplant was 37 years (range 27–59), 72% were female (n = 14), 78% Caucasian (n = 15), with 61% had live donor transplant (n = 12) as the last transplant. Eculizumab prophylaxis was given to 10/19 (56%) at the time of transplantation, with no aHUS recurrence during the follow up. Median duration of follow up was 46 (range 6–237) months. Mean estimated glomerular filtration rate (eGFR) at the time of last follow up was 59.5 ml/min/m2. No infections secondary to encapsulated organisms or other major infectious complications occurred during the follow up.

Conclusions
Eculizumab prophylaxis is safe and effective in KTRs with aHUS. Long term follow up demonstrates that it may be possible to discontinue prophylaxis carefully in selected patients with no evidence of complement mutations.
Implementation of a quality improvement strategy to increase outpatient kidney transplant referrals
Authors: Farouk Samira S. , Atallah Sara , Campbell Kirk N. , Vassalotti Joseph A. , Uribarri Jaime 
Published: May 2020

Abstract
Background
Kidney transplantation remains the optimal therapy for patients with end stage kidney disease (ESKD), though a small fraction of patients on dialysis are on organ waitlists. An important barrier to both preemptive kidney transplantation and successful waitlisting is timely referral to a kidney transplant center. We implemented a quality improvement strategy to improve outpatient kidney transplant referrals in a single center academic outpatient nephrology clinic.

Methods
Over a 3 month period (July 1–September 30, 2016), we assessed the baseline kidney transplantation referral rate at our outpatient nephrology clinic for patients 18–75 years old with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73m2 (2 values over 90 days apart). Charts were manually reviewed by two reviewers to look for kidney transplant referrals and documentation of discussions about kidney transplantation. We then performed a root cause analysis to explore potential barriers to kidney transplantation. Our intervention began on July 1, 2017 and included the implementation of a column in the electronic medical record (EMR) which displayed the patient’s last eGFR as part of the clinic schedule. In addition, physicians were given a document listing their patients to be seen that day with an eGFR of < 20 mL/min/1.73m2. Annual education sessions were also held to discuss the importance of timely kidney transplant referral.

Results
At baseline, 54 unique patients with eGFR ≤20 ml/min/1.73 m2 were identified who were seen in the Clinic between July 1, 2016 and September 30, 2016. 29.6% (16) eligible patients were referred for kidney transplantation evaluation. 69.5% (37) of these patients were not referred for kidney transplant evaluation. 46.3% (25) did not have documentation regarding kidney transplant in the EMR. nephrologist’s most recent note. Following the intervention, 66 unique patients met criteria for eligibility for kidney transplant evaluation. Kidney transplant referrals increased to 60.6% (p <  0.001).

Conclusions
Our pilot implementation study of a strategy to improve outpatient kidney transplant referrals showed that a free, simple, scalable intervention can significantly improve kidney transplant referrals in the outpatient setting. This intervention targeted the nephrologist’s role in the transplant referral, and facilitated the process of patient recognition and performing the referral itself without significantly interrupting the workflow. Next steps include further investigation to study the impact of early referral to kidney transplant centers on preemptive and living donor kidney transplantation as well as successful waitlisting.
Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer
Authors: Sawada Masashi , Kasuga Akiyoshi , Mie Takafumi , Furukawa Takaaki , Taniguchi Takanobu , Fukuda Koshiro , Yamada Yuto , Takeda Tsuyoshi , Kanata Ryo , Matsuyama Masato , Sasaki Takashi , Ozaka Masato , Sasahira Naoki 
Published: May 2020

Abstract
Background
There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival.

Methods
From 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion).

Results
In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively.

Conclusions
The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.
Socio-demographic, environmental and behavioural risk factors of diarrhoea among under-five children in rural Ethiopia: further analysis of the 2016 Ethiopian demographic and health survey
Authors: Ferede Melkamu Molla 
Published: May 2020

Abstract
Background
Diarrhoea is one of the major contributors to death among under-five children in Ethiopia. Studies conducted in different countries showed that rural children are more severely affected by diarrhoea than urban children. Thus, this study was aimed to identify the socio-demographic, environmental and behavioural associated risk factors of the occurrence of diarrhoea among under-five children in rural Ethiopia.

Methods
Data for the study was drawn from the 2016 Ethiopian Demographic and Health Survey. A total of 8041 under-five children were included in the study. Binary logistic regression was used to assess the association of occurrence of diarrhoea with socio-demographic, environmental and behavioural factors among under-five children.

Results
Children aged 6–11 months (AOR:3.5; 95% CI: 2.58–4.87), 12–23 months (AOR: 3.1; 95% CI: 2.33–4.04) and 24–35 months (AOR: 1.7; 95% CI: 1.26–2.34) as compared to > 35 months were significantly associated with an increasing prevalence of diarrhoea. Children in Afar region (AOR: 1.92; 95% CI: 1.01–3.64) and Gambela region (AOR: 2.12; 95% CI: 1.18, 3.81) were significantly associated with an increasing prevalence of diarrhoea, but a decreasing prevalence in Somali region (AOR: .42; 95% CI: (.217–.80) as compared to Tigray region. Increasing prevalence of diarrhoea was also significantly associated with male children (AOR: 1.3; 95% CI: 1.05–1.58); households who shared toilet facilities with other households (AOR: 1.4; 95% CI: 1.09–1.77); fourth birth order (AOR: 1.81; 95% CI: 1.17–2.79), and fifth and above birth order (AOR: 1.85; 95% CI: 1.22, 2.81) as compared to first order; and mother’s current age 35–49 years in a household with ≥3 under-five children (AOR: 4.7; 95% CI: 1.64–13.45) as compared to those maternal ages of 15–24 years in a household with ≤2 under-five children.

Conclusion
The age of a child, sex of a child, region, birth order, toilet facilities shared with other households and the interaction effect of the number of under-five children with mother’s current age are identified as associated risk factors for diarrhoea occurrence among under-five children in rural Ethiopia. The findings show the need for planning and implementing appropriate prevention strategies considering these risk factors for rural under-five children.
Mismatch between self-perceived and calculated cardiometabolic disease risk among participants in a prevention program for cardiometabolic disease: a cross-sectional study
Authors: Stol D. M. , Hollander M. , Damman O. C. , Nielen M. M. J. , Badenbroek I. F. , Schellevis F. G. , de Wit N. J. 
Published: May 2020

Abstract
Background
The rising prevalence of cardiometabolic diseases (CMD) calls for effective prevention programs. Self-assessment of CMD risk, for example through an online risk score (ORS), might induce risk reducing behavior. However, the concept of disease risk is often difficult for people to understand. Therefore, the study objective was to assess the impact of communicating an individualized CMD risk score through an ORS on perceived risk and to identify risk factors and demographic characteristics associated with risk perception among high-risk participants of a prevention program for CMD.

Methods
A cross-sectional analysis of baseline data from a randomized controlled trial conducted in a primary care setting. Seven thousand five hundred forty-seven individuals aged 45–70 years without recorded CMD, hypertension or hypercholesterolemia participated. The main outcome measures were: 1) differences in cognitive and affective risk perception between the intervention group - who used an ORS and received an individualized CMD risk score- and the control group who answered questions about CMD risk, but did not receive an individualized CMD risk score; 2) risk factors and demographic characteristics associated with risk perception.

Results
No differences were found in cognitive and affective risk perception between the intervention and control group and risk perception was on average low, even among high-risk participants. A positive family history for diabetes type 2 (β0.56, CI95% 0.39–0.73) and cardiovascular disease (β0.28, CI95% 0.13–0.43), BMI ≥25 (β0.27, CI95% 0.12–0.43), high waist circumference (β0.25, CI95% 0.02–0.48) and physical inactivity (β0.30, CI95% 0.16–0.45) were positively associated with cognitive CMD risk perception in high-risk participants. No other risk factors or demographic characteristics were associated with risk perception.

Conclusions
Communicating an individualized CMD risk score did not affect risk perception. A mismatch was found between calculated risk and self-perceived risk in high-risk participants. Family history and BMI seem to affect the level of CMD risk perception more than risk factors such as sex, age and smoking. A dialogue about personal CMD risk between patients and health care professionals might optimize the effect of the provided risk information.

Trial registration
Dutch trial Register number NTR4277, registered 26th Nov 2013.