bluuebunny/crossref_metadata_2025 huggingface dataset:
Seminoma in a Transverse Testicular Ectopia: A Rare Case Report
Authors: Altay Canan , Kefi Aykut , Tuna Burcin , Secil Mustafa
Published: May 2020

Transverse testicular ectopia (TTE) is an extremely rare congenital anomaly of the testis, characterized by migration of one testis toward the contrary hemiscrotum. TTE is usually associated with other testicular abnormalities such as persistent Mullerian duct syndrome, hypospadias, true hermaphroditism, and scrotal anomalies. Testicular sonography is the main initial diagnostic modality, followed by magnetic resonance imaging of the scrotum. These imaging modalities are important for determination of TTE and characterization of the testicular lesions. This case report provides the high-resolution ultrasonography, Doppler ultrasonography, magnetic resonance imaging, and diffusion-weighted imaging findings of a young man with seminoma in the transverse testicular ectopia. In addition, data on tumor stiffness, obtained with point shear-wave sonoelastography, are presented.
Search for multiple myeloma risk factors using Mendelian randomization
Authors: Went Molly , Cornish Alex J. , Law Philip J. , Kinnersley Ben , van Duin Mark , Weinhold Niels , Försti Asta , Hansson Markus , Sonneveld Pieter , Goldschmidt Hartmut , Morgan Gareth J. , Hemminki Kari , Nilsson Björn , Kaiser Martin , Houlston Richard S.
Published: May 2020

The etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls. Odds ratios (ORs) per 1 standard deviation increase in each phenotype were estimated under an inverse variance weighted random effects model. A Bonferroni-corrected threshold of P = 2 × 10−4 was considered significant, whereas P < .05 was considered suggestive of an association. Although no significant associations with MM risk were observed among the 249 phenotypes, 28 phenotypes showed evidence suggestive of association, including increased levels of serum vitamin B6 and blood carnitine (P = 1.1 × 10−3) with greater MM risk and ω-3 fatty acids (P = 5.4 × 10−4) with reduced MM risk. A suggestive association between increased telomere length and reduced MM risk was also noted; however, this association was primarily driven by the previously identified risk variant rs10936599 at 3q26 (TERC). Although not statistically significant, increased body mass index was associated with increased risk (OR, 1.10; 95% confidence interval, 0.99-1.22), supporting findings from a previous meta-analysis of prospective observational studies. Our study did not provide evidence supporting any modifiable factors examined as having a major influence on MM risk; however, it provides insight into factors for which the evidence has previously been mixed.
Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma
Authors: Alonso Rafael , Cedena María-Teresa , Wong Sandy , Shah Nina , Ríos-Tamayo Rafael , Moraleda José M. , López-Jiménez Javier , García Cristina , Bahri Natasha , Valeri Antonio , Sánchez Ricardo , Collado-Yurrita Luis , Martin Thomas , Wolf Jeffrey , Lahuerta Juan-José , Martínez-López Joaquín
Published: May 2020

Lenalidomide is an immunomodulatory drug approved for maintenance treatment in newly diagnosed multiple myeloma, and it has been shown to improve progression-free survival (PFS) and, in several studies, overall survival. Nevertheless, the impact of prolonged treatment with lenalidomide on the kinetics of minimal residual disease (MRD) and its prognostic impact have not been studied in depth. To obtain better knowledge in this regard, we retrospectively analyzed 139 patients who received lenalidomide maintenance in real-world clinical practice and whose MRD levels were observed during the treatment period by multiparametric flow cytometry or next-generation sequencing with a sensitivity of at least 10−4. Lenalidomide maintenance correlated with an increased depth of the disease response, with 38.1% of patients achieving maximal response during maintenance. Moreover, 34.3% of patients who were MRD positive after induction treatment achieved MRD-negative status during maintenance and ultimately had improved PFS. Sequential MRD assessments identified patients with progressively decreasing MRD levels who also had better PFS outcomes, compared with patients not showing a decreasing pattern of MRD. These results support the role of maintenance therapy, not only to sustain, but also to increase the depth of disease response with a PFS benefit. In addition, MRD monitoring during maintenance identifies patients with better prognosis and may help in their clinical management.
Competitive tight-binding inhibition of VKORC1 underlies warfarin dosage variation and antidotal efficacy
Authors: Li Shuang , Liu Shixuan , Liu Xiaoran Roger , Zhang Mengru Mira , Li Weikai
Published: May 2020

Dose control of warfarin is a major complication in anticoagulation therapy and overdose is reversed by the vitamin K antidote. Improving the dosage management and antidotal efficacy requires mechanistic understanding. Here we find that effects of the major predictor of warfarin dosage, SNP −1639 G>A, follow a general correlation that warfarin 50% inhibitory concentration decreases with cellular level of vitamin K epoxide reductase (VKORC1), suggesting stoichiometric inhibition. Characterization of the inhibition kinetics required the use of microsomal VKORC1 with a native reductant, glutathione, that enables effective warfarin inhibition in vitro. The kinetics data can be fitted with the Morrison equation, giving a nanomolar inhibition constant and demonstrating that warfarin is a tight-binding inhibitor. However, warfarin is released from purified VKORC1-warfarin complex with increasing amount of vitamin K, indicating competitive inhibition. The competition occurs also in cells, resulting in rescued VKORC1 activity that augments the antidotal effects of vitamin K. Taken together, warfarin is a competitive inhibitor that binds VKORC1 tightly and inhibits at a stoichiometric (1:1) concentration, whereas exceeding the VKORC1 level results in warfarin overdose. Thus, warfarin dosage control should use VKORC1 level as a major indicator, and improved antidotes may be designed based on their competition with warfarin.
Impacts of local population history and ecology on the evolution of a globally dispersed pathogen
Authors: Castillo Andreina I. , Chacón-Díaz Carlos , Rodríguez-Murillo Neysa , Coletta-Filho Helvecio D. , Almeida Rodrigo P. P.
Published: May 2020

Background

Pathogens with a global distribution face diverse biotic and abiotic conditions across populations. Moreover, the ecological and evolutionary history of each population is unique.Xylella fastidiosais a xylem-dwelling bacterium infecting multiple plant hosts, often with detrimental effects. As a group,X. fastidiosais divided into distinct subspecies with allopatric historical distributions and patterns of multiple introductions from numerous source populations. The capacity ofX. fastidiosato successfully colonize and cause disease in naïve plant hosts varies among subspecies, and potentially, among populations. Within Central America (i.e. Costa Rica) twoX. fastidiosasubspecies coexist: the native subsp.fastidiosaand the introduced subsp.pauca. Using whole genome sequences, the patterns of gene gain/loss, genomic introgression, and genetic diversity were characterized within Costa Rica and contrasted to otherX. fastidiosapopulations.

Results

Within Costa Rica, accessory and core genome analyses showed a highly malleable genome with numerous intra- and inter-subspecific gain/loss events. Likewise, variable levels of inter-subspecific introgression were found within and between both coexisting subspecies; nonetheless, the direction of donor/recipient subspecies to the recombinant segments varied. Some strains appeared to recombine more frequently than others; however, no group of genes or gene functions were overrepresented within recombinant segments. Finally, the patterns of genetic diversity of subsp.fastidiosain Costa Rica were consistent with those of other native populations (i.e. subsp.paucain Brazil).

Conclusions

Overall, this study shows the importance of characterizing local evolutionary and ecological history in the context of world-wide pathogen distribution.
Correction to: Sex-specific changes in gene expression in response to estrogen pollution around the onset of sex differentiation in grayling (Salmonidae)
Authors: Selmoni Oliver M. , Maitre Diane , Roux Julien , Wilkins Laetitia G. E. , Marques da Cunha Lucas , Vermeirssen Etienne L. M. , Knörr Susanne , Robinson-Rechavi Marc , Wedekind Claus
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

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

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

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

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

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

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

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

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.
Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017
Authors: Kuwabara Yuki , Kinjo Aya , Fujii Maya , Imamoto Aya , Osaki Yoneatsu , Jike Maki , Otsuka Yuichiro , Itani Osamu , Kaneita Yoshitaka , Minobe Ruriko , Maezato Hitoshi , Higuchi Susumu , Yoshimoto Hisashi , Kanda Hideyuki
Published: May 2020

Background

From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users.

Methods

The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined.

Results

In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users.

Conclusions

The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking.
Development and validation of a nomogram to predict perioperative blood transfusion in patients undergoing total knee arthroplasty
Authors: Hu Chuan , Wang Yuan-he , Shen Rui , Liu Chuan , Sun Kang , Ye Lin , Ye Jian-jun , Yang Xu , Tian Shao-qi , Yu Teng-bo
Published: May 2020

Background

The need for a transfusion is one of the adverse events following total knee arthroplasty (TKA), and accurately predicting this need remains challenging for arthroplasty surgeons. The purpose of the present research is to study the preoperative predictors of transfusion risk in patients following TKA and develop a nomogram.

Methods

The nomogram was developed based on a training set of 5402 patients who underwent TKA at the Affiliated Hospital of Qingdao University between September 2013 and November 2018. The independent predictors of transfusion were identified by univariate, LASSO, and binary logistic regression analyses. Then, a nomogram was established based on these independent predictors. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were selected to evaluate the nomogram. The results were validated using an independent set of 1116 patients who underwent TKA between December 2018 and September 2019. In addition, we also carried out subgroup analyses in the training and testing sets based on the independent predictors.

Results

Five independent predictors were identified by multivariate analysis and were used to establish the nomogram. The AUCs of the nomogram were 0.884 (95% CI: 0.865–0.903) and 0.839 (95% CI, 0.773–0.905) in the training and testing sets, respectively. In both the training and testing sets, the calibration curve indicated that the prediction by the nomogram was highly consistent with the actual observation, and the DCA indicated that the nomogram had a favorable level of clinical usefulness. In addition, the AUC of the nomogram was significantly higher than the AUC of any independent predictor for predicting transfusion risk following TKA, and the subgroup analysis showed good performance in 20 subgroups.

Conclusion

Lower preoperative Hb levels, simultaneous bilateral TKA, lower BMI, older age, and coronary heart disease were identified as independent predictors of postoperative transfusion in patients following TKA. A nomogram incorporating the above five predictors could accurately predict the transfusion risk.
Autologous adipose tissue injection versus platelet-rich plasma (PRP) injection in the treatment of knee osteoarthritis: a randomized, controlled study – study protocol
Authors: Bąkowski Paweł , Kaszyński Jakub , Wałecka Joanna , Ciemniewska-Gorzela Kinga , Bąkowska-Żywicka Kamilla , Piontek Tomasz
Published: May 2020

Background

Knee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients’ quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. Up to date there is no prospective randomized controlled studies demonstrating effectiveness and role of adipose tissue injections in OA treatment. The purpose of this study is to assess functional and clinical changes among patients with symptomatic knee OA treated with intra-articular injections of autologous adipose tissue or platelet rich plasma (PRP) and to compare efficacy of both therapeutic methods.

Methods

This is a prospective, randomized, controlled study. Patients who meet inclusion criteria will be allocated to Fat Tissue group or PRP group randomly. Subjects will receive an intra articular injection with autologous adipose tissue and PRP respectively. Patients will be assessed five times: before treatment and 1, 3, 6 and 12 months after the treatment. The assessment consists of patient reported outcome measures (The Knee injury and Osteoarthritis Outcome Score, International Knee Documentation Committee 2000, the Western Ontario and McMaster Universities Osteoarthritis Index, the Health Questionnaire EQ- 5D- 5 L), three functional tests (The Timed Up and Go Test, The 5 Times Sit to Stand Test, The 10 m Walk Test) and Maximal Isometric Voluntary Contraction.

Discussion

This study protocol has several strengths and weaknesses. One of strongest point of this study is the wide, multidimensional functional assessment which will give a large amount of objective data. On the other hand, lack of blinding has to be considered as a risk of both subject and investigator bias.

Trial registration

name of registry: ClinicalTrials.gov, trial registration number: NCT04321629, retrospectively registered on date of registration.
Whole genome sequence comparison of avian pathogenic Escherichia coli from acute and chronic salpingitis of egg laying hens
Authors: Poulsen Louise Ladefoged , Kudirkiene Egle , Jørgensen Steffen Lynge , Djordjevic Steven Philip , Cummins Max Laurence , Christensen Jens Peter , Christensen Henrik , Bisgaard Magne , Thøfner Ida
Published: May 2020

Background

Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity.

Results

From the core- and accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis.

Conclusion

Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.
Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum
Authors: Huber Robert J.
Published: May 2020

The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.
Identification and validation of an individualized autophagy-clinical prognostic index in gastric cancer patients
Authors: Qiu Jieping , Sun Mengyu , Wang Yaoqun , Chen Bo
Published: May 2020

Background

The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer.

Methods

GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 204 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinic-pathological features and prognostic gene signatures, a nomogram was established to predict individual survival probability.

Results

GO analysis showed that the 28 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 28 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573–2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients.

Conclusions

This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.
Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage
Authors: Liu Jingyuan , Liu Yao , Xiang Pan , Pu Lin , Xiong Haofeng , Li Chuansheng , Zhang Ming , Tan Jianbo , Xu Yanli , Song Rui , Song Meihua , Wang Lin , Zhang Wei , Han Bing , Yang Li , Wang Xiaojing , Zhou Guiqin , Zhang Ting , Li Ben , Wang Yanbin , Chen Zhihai , Wang Xianbo
Published: May 2020

Background

Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19.

Methods

The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness.

Results

The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process.

Conclusions

We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.