bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateralized Periodic Discharges in a Patient With Dural Arteriovenous Fistula: SPECT and DWI Studies Suggest They are Ictal
Authors: Dericioglu Nese , Volkan Bilge , Gocmen Rahsan , Arat Anil
Published: April 2021

Lateralized periodic discharges (LPDs) are unilateral electroencephalography (EEG) waveforms, recurring at regular intervals. There has been a long-lasting debate about whether they represent ictal or interictal phenomena. Very few patients in the literature have been investigated with multimodal functional imaging techniques. Here, we present a 58-year-old male patient with symptomatic epilepsy who had cerebral venous sinus thrombosis in the right temporo-parietal area and dural arteriovenous fistula (dAVF) over the left fronto-parietal region. He developed acute speech disturbances and altered mental status after a generalized tonic–clonic seizure. Video-EEG monitoring (VEEGM) demonstrated LPDs over the left fronto-central area, overlapping in part with the dAVF. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences revealed restricted diffusion compatible with cytotoxic edema, whereas single-photon emission computed tomography (SPECT) indicated hyperperfusion in the same region, leading to the conclusion that he was having possible nonconvulsive status epilepticus (NCSE). An increase in antiseizure medications led to gradual improvement in clinical status and the disappearance of LPDs.
Study on the load-sharing characteristics of face-gear four-branching split-torque transmission system
Authors: Hao Dong , Hao-qin Zhang , Xiao-long Zhao , Ling-ling Duan
Published: April 2021

In order to solve the load-sharing characteristics of face-gear four-branching split-torque transmission system (FGFBSTTS), the static load-sharing mechanical analysis model was established. In the model, the deformation coordination conditions of torsional angle and torque balance condition were considered. By using Loaded Tooth Contact Analysis (LTCA) technology of face gear and herringbone gear, the time-varying meshing stiffness was calculated. The influences of manufacturing errors, installation errors, I-stage pinion floating, II-stage pinion spline clearance floating, and radial limit ring clearance floating on the load-sharing characteristics are analyzed. The results show that the LTCA technology is more accurate to reflect the load-sharing characteristics of each meshing position. When the I-stage pinion and the II-stage pinion floated at the same time, the best load-sharing characteristics can be obtained. The load-sharing characteristics affected by manufacturing errors showed obvious periodic change. The radial limit ring plays a better auxiliary role in load-sharing characteristics. The theoretical results were compared with the experiments to verify the correctness of the theoretical analysis. The research results can provide a theoretical basis for the optimal design of the load-sharing structure, error control, and assembly of the face gear four branch transmission system.
Top-down influences on working memory representations of faces: Evidence from dual-target visual search
Authors: Dunn James Daniel , Kemp Richard Ian , White David
Published: April 2021

Variability in appearance across different images of the same unfamiliar face often causes participants to perceive different faces. Because perceptual information is not sufficient to link these encounters, top-down guidance may be critical in the initial stages of face learning. Here, we examine the interaction between top-down guidance and perceptual information when forming memory representations of unfamiliar faces. In two experiments, we manipulated the names associated with images of a target face that participants had to find in a search array. In Experiment 1, wrongly labelling two images of the same face with different names resulted in more errors relative to when the faces were labelled correctly. In Experiment 2, we compared this cost of mislabelling with the established “dual-target search cost,” where searching for two targets produces more search errors relative to one target. We found search costs when searching for two different faces, but not when searching for mislabelled images of the same face. Together, these results suggest that perceptual and semantic information interact when we form face memory representations. Mislabelling the identity of perceptually similar faces does not cause dual representations to be created, but rather it impedes the process of forming a single robust representation.
Endurance in extreme work environments
Authors: Cham Belinda S. , Boeing Alexandra A. , Wilson Micah K. , Griffin Mark A. , Jorritsma Karina
Published: April 2021

Extreme work environments are inherently stressful and involve challenging working and living conditions. In contexts ranging from space exploration to disaster response, people must sustain performance under pressure, and function with limited resources. In this paper we develop the concept of endurance for extreme work environments, which we define as the capacity to sustain performance at high levels for safe and effective operations over extended durations (e.g., a mission, operation, deployment, or expedition). We integrate diverse streams of literature (e.g., work stress, recovery, and sleep) to describe endurance in terms of short- and long-term energy management processes as individuals interact with their work-life system (i.e. work, non-work, and sleep environment). We conclude with theoretical and practical implications for a better understanding of endurance, such as considering multiple time perspectives, and the role that researchers, practitioners, and organizations can play in optimizing endurance in the field.
The Impact of Clinical Presentation on Survival in Patients Requiring Hemodialysis Catheters for Acute and Unplanned Dialysis: A Prospective Observational Study
Authors: Talbot Benjamin , Lin Ray , Li Qiang , Jun Min , Kotwal Sradha , Sen Shaundeep , Gallagher Martin
Published: April 2021

Background:

Most studies addressing hemodialysis initiation with a dialysis catheter focus on patients entering maintenance dialysis programs and exclude other patients, such as those with acute kidney injury (AKI), making interpretation and application of the results difficult for clinicians managing patients at the time of dialysis commencement.

Objective:

To compare the survival of all patients requiring a catheter for hemodialysis access according to the nature of clinical presentation.

Design:

Prospective observational.

Setting:

An Australian tertiary renal unit.

Patients:

All patients requiring a central venous catheter (CVC) for hemodialysis access between 2005 and 2015.

Measurements:

Baseline comorbidities, demographics, and nature of clinical presentation. Data regarding each episode of dialysis access insufficiency and each CVC were collected. The primary outcome was all-cause mortality.

Methods:

Patients were classified into 1 of 3 groups based on physician assessment at the time of presentation: patients believed to have AKI with expected renal recovery (AKI), patients considered to be entering the maintenance dialysis program without a functioning dialysis access (Maintenance Dialysis), patients unable to perform peritoneal dialysis, or use their existing hemodialysis access (Access Failure). Time-split multivariable Cox regression analyses were used to compare survival between groups.

Results:

A total of 557 eligible patients had complete prospective data regarding CVC use and were included in the analyses. The majority of patients were in the AKI (246/557, 44%) and Maintenance Dialysis groups (182/557, 33%) compared with the Access Failure group (129/557, 23%). During a median follow-up of 3 years, 302 (54%) of the 557 patients died. Following adjustment, risk of all-cause mortality was higher in the AKI group (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.31-3.60, P = .001) during the first 2 years after catheter insertion and lower in years 2 to 4 (HR: 0.42, 95% CI: 0.20-0.88, P = .02) than in the reference Maintenance Dialysis group. No difference in mortality risk between the Access Failure and reference group was found.

Limitations:

Single-center study. Possible residual confounding owing to the observational study design.

Conclusions:

Patients requiring acute or unplanned hemodialysis experience high mortality, and the nature of clinical presentation does influence outcomes. Most notable is the greater early mortality experienced by patients with AKI compared to other patient groups. Prospective definition of the nature of unplanned dialysis initiation is important to accurately measure and improve outcomes in this high-risk patient population.

Human Research Ethics Committee Approval Number

CH62/6/2017-042.
Effect of Infant Massage on Salivary Oxytocin Level of Mothers and Infants with Normal and Disordered Bonding
Authors: Moussa Suaad , Fawaz Lubna , Ibrahim Walaa , Fathelbab Elsayed Mona , Mostafa Ahmed Marwa
Published: April 2021

Maternal-infant bonding is an affective maternal-driven process that occurs primarily to her infant. Prophylactic interventions or treatment of disordered bonding include infant massage. Evidence suggests that oxytocin plays an important role in facilitation of mother–infant bonding. Main objective is to assess the effect of infant massage on salivary oxytocin level of mothers and their infant during postpartum period. And to assess the difference of oxytocin level in normal and disordered maternal-infant bonding. This study is a quasi-experimental study, carried out on 37 pairs of mothers and their infants from second to sixth month postpartum, attending Basateen Gharb primary health care center (PHC) in Albasateen district, Cairo, Egypt. Postpartum Bonding Questionnaire (PBQ) was used to differentiate between mothers with normal and disordered bonding. Pre and post massage salivary samples were taken from mothers and their infants. Tappan’s technique of infant massage was used. Results showed that 48.6% (N = 18) of mothers had disordered maternal infant bonding. Mothers and infants with normal bonding showed a positive relationship with their salivary oxytocin level post massage. On the other hand, mothers and infants with disordered bonding showed no change in their salivary oxytocin level post massage. Salivary oxytocin level in male infants has decreased post massage, while oxytocin level in female infants has increased post massage in mothers with normal bonding. We concluded that infant massage increases salivary oxytocin level in mothers and infants with normal bonding and it has no effect on salivary oxytocin level of mothers and infants with disordered bonding.
A Rare Inflammatory Myofibroblastic Tumor of the Mitral Valve With Systemic Embolism in a Child
Authors: Vijayakumar Niranjan , Thattaliyath Bijoy , Dundar Bilge , Karimi Mohsen , Badheka Aditya , Chegondi Madhuradhar
Published: April 2021

Inflammatory myofibroblastic tumors (IMTs) represent mesenchymal tumors that occur in the lungs, abdomen, or pelvis. Cardiac IMTs are rare, usually right-sided, and when left-sided can cause sudden cardiac death by coronary occlusion. We report a child with symptoms of embolization to the right kidney and the femoral artery, and a mobile mass in the left atrium attached to the mitral valve. Upon surgical removal, histopathology revealed IMT. Our case illustrates a unique presentation of systemic thromboembolism.
A Year in the Social Life of a Teenager: Within-Persons Fluctuations in Stress, Phone Communication, and Anxiety and Depression
Authors: Rodman Alexandra M. , Vidal Bustamante Constanza M. , Dennison Meg J. , Flournoy John C. , Coppersmith Daniel D. L. , Nook Erik C. , Worthington Steven , Mair Patrick , McLaughlin Katie A.
Published: April 2021

Stressful life events (SLEs) are strongly associated with the emergence of adolescent anxiety and depression, but the underlying mechanisms remain poorly understood, especially at the within-persons level. We investigated how adolescent social communication (i.e., frequency of calls and texts) following SLEs relates to changes in internalizing symptoms in a multitimescale, intensive, year-long study ( N = 30; n = 355 monthly observations; n ≈ 5,000 experience-sampling observations). Within-persons increases in SLEs were associated with receiving more calls than usual at both the month and moment levels and making more calls at the month level. Increased calls were prospectively associated with worsening internalizing symptoms at the month level only, suggesting that SLEs rapidly influence phone communication patterns, but these communication changes may have a more protracted, cumulative influence on internalizing symptoms. Finally, increased incoming calls prospectively mediated the association between SLEs and anxiety at the month level. We identify adolescent social communication fluctuations as a potential mechanism conferring risk for stress-related internalizing psychopathology.
‘Absolute’ inter-observer classifications agreement for proximal humeral fractures with a single shoulder anteroposterior X-ray
Authors: Martínez-Sola Rocío , León-Muñoz Vicente J , Najem-Rizk Antoine Nicolas , Soler-Vasco Beatriz , Arrieta-Martínez Carlos J , López-Sorroche Eva , Cárdenas-Grande Encarnación , Salmerón-Vélez Guillermo , Ruiz-Molina José Ángel , Martínez-Martínez Francisco , Santonja-Medina Fernando
Published: April 2021

Purpose:

Several studies have been carried out, and there is no classification for proximal humeral fractures (PHF) exempted from variability in interpretation and with questioned reliability. In the present study, we investigated the ‘absolute diagnostic reliability’ of the most currently used classifications for PHFs on a single anterior-posterior X-ray shoulder image.

Methods:

Six orthopaedic surgeons, with varying levels of experience in shoulder pathology, evaluated radiographs from 30 proximal humeral fractures, according to the ‘absolute reliability’ criteria. Each of the observers rated each fracture according to Neer, Müller/AO and Codman-Hertel’s classification systems.

Results:

The overall inter-observer agreement (κ) has been 0.297 (CI95% 0.280 to 0.314) for the Neer’s classification system, 0.206 (CI95% 0.193 to 0.218) for the Müller/AO classification system, and 0.315 (CI95% 0.334 to 0.368) for the Codman-Hertel classification system. We found loss of agreement in Neer’s classification as the study progressed, low agreement in the AO classification, and stable values in the different evaluations with the best degree of agreement for Codman-Hertel classification, with a moderate agreement in the second evaluation among the six evaluators.

Conclusion:

The Neer, AO, and Hertel-Codman classification systems for PHF with a single radiographic projection have a difficult interpretation for orthopaedic surgeons of varying levels of experience, and therefore substantial agreements are not obtained.
Do Narcotic Use, Physical Therapy Location, or Payer Type Predict Patient-Reported Outcomes After Anterior Cruciate Ligament Reconstruction?
Authors:   Cleveland Clinic Sports Health, Karnuta Jaret M. , Dalton Sarah , Bena James , Farrow Lutul D. , Featherall Joseph , Jones Morgan H. , Miniaci Anthony A. , Parker Richard D. , Rosneck James T. , Saluan Paul , Strnad Greg , Spindler Kurt P. , Williams James S. , Oak Sameer R.
Published: April 2021

Background:

Opioid use and public insurance have been correlated with worse outcomes in a number of orthopaedic surgeries. These factors have not been investigated with anterior cruciate ligament reconstruction (ACLR).

Purpose/Hypothesis:

To evaluate if narcotic use, physical therapy location, and insurance type are predictors of patient-reported outcomes after ACLR. It was hypothesized that at 1 year postsurgically, increased postoperative narcotic use would be associated with worse outcomes, physical therapy obtained within the authors’ integrated health care system would lead to better outcomes, and public insurance would lead to worse outcomes and athletic activity.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

All patients undergoing unilateral, primary ACLR between January 2015 and February 2016 at a large health system were enrolled in a standard-of-care prospective cohort. Knee injury and Osteoarthritis Score (KOOS) and the Hospital for Special Surgery Pediatric–Functional Activity Brief Scale (HSS Pedi-FABS) were collected before surgery and at 1 year postoperatively. Concomitant knee pathology was assessed arthroscopically and electronically captured. Patient records were analyzed to determine physical therapy location, insurance status, and narcotic use. Multivariable regression analyses were used to identify significant predictors of the KOOS and HSS Pedi-FABS score.

Results:

A total of 258 patients were included in the analysis (mean age, 25.8; 51.2% women). In multivariable regression analysis, narcotic use, physical therapy location, and insurance type were not independent predictors of any KOOS subscales. Public insurance was associated with a lower HSS Pedi-FABS score (–4.551, P = .047) in multivariable analysis. Narcotic use or physical therapy location was not associated with the HSS Pedi-FABS score.

Conclusion:

Increased narcotic use surrounding surgery, physical therapy location within the authors’ health care system, and public versus private insurance were not associated with disease-specific KOOS subscale scores. Patients with public insurance had worse HSS Pedi-FABS activity scores compared with patients with private insurance, but neither narcotic use nor physical therapy location was associated with activity scores. Physical therapy location did not influence outcomes, suggesting that patients be given a choice in the location they received physical therapy (as long as a standardized protocol is followed) to maximize compliance.
Does Probe-Tube Verification of Real-Ear Hearing Aid Amplification Characteristics Improve Outcomes in Adults? A Systematic Review and Meta-Analysis
Authors: Almufarrij Ibrahim , Dillon Harvey , Munro Kevin J.
Published: April 2021

This systematic review, the first on this topic, aimed to investigate if probe-tube verification of real-ear hearing aid amplification characteristics improves outcomes in adults. The review was preregistered in the Prospective Register of Systematic Reviews and performed in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. After assessing more than 1,420 records from seven databases, six experimental studies (published between 2012 and 2019) met the inclusion criteria; five were included in the meta-analyses. The primary outcome of interest (hearing-specific, health-related quality of life) was not reported in any study. There were moderate and statistically significant positive effects of probe-tube real-ear measurement (REM), compared with the manufacturer’s initial fit, on speech intelligibility in quiet settings (standardized mean difference [SMD]: 0.59) and user’s final preference (proportion difference: 52.2%). There were small but statistically significant positive effects of REM on self-reported listening abilities (SMD: 0.22) and speech intelligibility in noise (SMD: 0.15). The quality of evidence for these outcomes ranged from high to very low. The findings show that REMs improve outcomes statistically, but this is based on a small number of studies and a limited number of participants. It is currently unclear if the benefits are of material importance because minimum clinically important differences have not been established for most of the outcomes. Ultimately, there needs to be a cost-effectiveness analysis to show that statistically significant benefits, which exceed the minimum clinically important difference, are worth the cost involved.
Transformative Learning in Mastery-Oriented CS0 Course
Authors: Lakshminarayanan Srinivasan , Rao N. J. , G. K. Meghana
Published: April 2021

The introductory programming course, commonly known as CS1 and offered as a core course in the first year in all engineering programs in India, is unique because it can address higher cognitive levels, metacognition and some aspects of the affective domain. It can provide much needed transformative experiences to students coming from a system of school education that is dominantly performance-driven. Unfortunately, the CS1 course, as practiced in almost all engineering programs, is also performance-driven because of a variety of compulsions. This paper suggests that the inclusion of a course CS0 can bring about transformative learning that can potentially make a significant difference in the quality of learning in all subsequent engineering courses. The suggested instruction design of this course takes the advantage of the unique features of a course in programming. The proposed CS0 course uses “extreme apprenticeship” and “guided discovery” methods of instruction. The effectiveness of these instruction methods was established through the use of the thematic analysis, a well-known qualitative research method, and the associated coding of transformative learning experiences and instruction components.
Emerging Evidence for cAMP-calcium Cross Talk in Heart Atrial Nanodomains Where IP3-Evoked Calcium Release Stimulates Adenylyl Cyclases
Authors: Burton Rebecca-Ann B. , Terrar Derek A.
Published: April 2021

Calcium handling is vital to normal physiological function in the heart. Human atrial arrhythmias, eg. atrial fibrillation, are a major morbidity and mortality burden, yet major gaps remain in our understanding of how calcium signaling pathways function and interact. Inositol trisphosphate (IP3) is a calcium-mobilizing second messenger and its agonist-induced effects have been observed in many tissue types. In the atria IP3 receptors (IR3Rs) residing on junctional sarcoplasmic reticulum augment cellular calcium transients and, when over-stimulated, lead to arrhythmogenesis. Recent studies have demonstrated that the predominant pathway for IP3 actions in atrial myocytes depends on stimulation of calcium-dependent forms of adenylyl cyclase (AC8 and AC1) by IP3-evoked calcium release from the sarcoplasmic reticulum. AC8 shows co-localisation with IP3Rs and AC1 appears to be nearby. These observations support crosstalk between calcium and cAMP pathways in nanodomains in atria. Similar mechanisms also appear to operate in the pacemaker region of the sinoatrial node. Here we discuss these significant advances in our understanding of atrial physiology and pathology, together with implications for the identification of potential novel targets and modulators for the treatment of atrial arrhythmias.
Parent-Child Mindfulness-Based Training: A Feasibility and Acceptability Study
Authors: Guenther Courtney H. , Stephens Rebecca L. , Ratliff Macy L. , Short Sarah J.
Published: April 2021

Stress in young children can interfere with academic achievement. To help address stress and aid in developing beneficial lifelong coping skills, educational systems are more widely incorporating programs that teach social and emotional regulation, such as mindfulness-based programs. The effects of these programs may be strengthened through parental support in the home environment. This study examined the feasibility and acceptability of a new Parent-Child Mindfulness-Based Training (PC-MBT) program, which delivered mindfulness-based training to parents and children simultaneously in the home environment. This study also implemented a working memory training after PC-MBT to assess the feasibility of completing two trainings sequentially. Healthy children, ages 8-10 ( n = 14), and their parents participated in the PC-MBT program. They met with an instructor at home and online each week for 6 weeks and were provided resources including books, worksheets, audio recordings, and daily practices to reinforce mindfulness skills. A control group ( n = 8) participated in the working memory training only. All PC-MBT and control children, except one, participated in the working memory training. All PC-MBT assigned families completed the PC-MBT program, and a majority utilized all types of the mindfulness training materials. A majority of participants also reported high levels of enjoyment and understanding of the PC-MBT program. This study establishes the feasibility and acceptability of the PC-MBT program and lays the foundation for future studies to assess program efficacy in healthy and clinical populations as well as the utility of PC-MBT to improve engagement and outcomes of other cognitive training programs.
Wiskott–Aldrich syndrome with normal platelet volume in a low-income setting: a case report
Authors: Mawalla William Frank , Iddy Hamisa , Kindole Christine Aloyce , Nasser Ahlam , Schuh Anna
Published: April 2021

Wiskott–Aldrich syndrome (WAS) is a rare immunodeficiency X-linked genetic disorder. It is often featured with a clinical triad of thrombocytopenia with low mean platelet volume, eczematoid dermatitis and recurrent infections. The clinical manifestation of WAS, depending on the underlying variant, shows wide heterogeneity. We present a case of a 10-month-old boy who came in with a history of recurrent fever, skin lesions since birth and episodes of bloody diarrhoea. He had severe anaemia and thrombocytopenia (with normal mean platelet volume). Genetic analysis revealed the patient to be hemizygous for a pathogenic WAS gene splice variant (NM_000377.2:c.360+1G>A). He was managed with supportive treatment and regular follow up, but died 4 months later. As it is a rare genetic disease, the diagnosis of WAS can easily be missed, especially in settings with scarce healthcare resources that do not have easy access to genetic testing. Thus, a high index of suspicion is needed when a male child presents with recurrent infections and bleeding tendencies.

Plain language summary

Management challenges of a rare genetic disorder in a resource-limited country: a case report of Wiskott–Aldrich syndrome in Tanzania Wiskott–Aldrich syndrome (WAS) is a rare inherited disease that mainly affects boys. Patients will typically present with low levels of a single line of little particles of cells that clot the blood called platelets, whole-body skin rashes and recurrent infections. Nevertheless, the clinical presentation can vary between individuals. We present a case of a 10-month-old boy who came in with a history of recurrent fever, skin rash since birth and episodes of bloody diarrhoea. He had very low levels of red blood cells and platelets. Genetic analysis confirmed the patient to have WAS. He was managed with supportive treatment, followed up on a regular clinic but unfortunately died 4 months later. Being a rare genetic disease, the diagnosis of WAS can easily be missed, especially in regions with scarce healthcare resources that do not have easy access to genetic testing. Thus, doctors should suspect WAS in boys presenting with recurrent infections and bleeding problems.
MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axis
Authors: Ren Li-Rong , Yao Ru-Bin , Wang Shi-Yong , Gong Xiang-Dong , Xu Ji-Tao , Yang Kai-Shun
Published: April 2021

Background

Osteoporosis seriously disturbs the life of people. Meanwhile, inhibition or weakening of osteogenic differentiation is one of the important factors in the pathogenesis of osteoporosis. It was reported that miR-27a-3p reduced the symptoms of osteoporosis. However, the mechanism by which miR-27a-3p in osteogenic differentiation remains largely unknown.

Methods

To induce the osteogenic differentiation in MC3T3-E1 cells, cells were treated with osteogenic induction medium (OIM). RT-qPCR was used to evaluate the mRNA expression of miR-27a-3p and CRY2 in cells. The protein levels of CRY2, Runt-related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and the phosphorylation level of extracellular regulated protein kinases (ERK) 1/2 in MC3T3-E1 cells were evaluated by western blotting. Meanwhile, calcium nodules and ALP activity were tested by alizarin red staining and ALP kit, respectively. Luciferase reporter gene assay was used to analyze the correlation between CRY2 and miR-27a-3p.

Results

The expression of miR-27a-3p and the phosphorylation level of ERK1/2 were increased by OIM in MC3T3-E1 cells, while CRY2 expression was decreased. In addition, OIM-induced increase of calcified nodules, ALP content and osteogenesis-related protein expression was significantly reversed by downregulation of miR-27a-3p and overexpression of CRY2. In addition, miR-27a-3p directly targeted CRY2 and negatively regulated CRY2. Meanwhile, the inhibitory effect of miR-27a-3p inhibitor on osteogenic differentiation was reversed by knockdown of CRY2 or using honokiol (ERK1/2 signal activator). Furthermore, miR-27a-3p significantly inhibited the apoptosis of MC3T3-E1 cells treated by OIM. Taken together, miR-27a-3p/CRY2/ERK axis plays an important role in osteoblast differentiation.

Conclusions

MiR-27a-3p promoted osteoblast differentiation via mediation of CRY2/ERK1/2 axis. Thereby, miR-27a-3p might serve as a new target for the treatment of osteoporosis.
Accelerated global sensitivity analysis of genome-wide constraint-based metabolic models
Authors: Nobile Marco S. , Coelho Vasco , Pescini Dario , Damiani Chiara
Published: April 2021

Background

Genome-wide reconstructions of metabolism opened the way to thorough investigations of cell metabolism for health care and industrial purposes. However, the predictions offered by Flux Balance Analysis (FBA) can be strongly affected by the choice of flux boundaries, with particular regard to the flux of reactions that sink nutrients into the system. To mitigate possible errors introduced by a poor selection of such boundaries, a rational approach suggests to focus the modeling efforts on the pivotal ones.

Methods

In this work, we present a methodology for the automatic identification of the key fluxes in genome-wide constraint-based models, by means of variance-based sensitivity analysis. The goal is to identify the parameters for which a small perturbation entails a large variation of the model outcomes, also referred to as sensitive parameters. Due to the high number of FBA simulations that are necessary to assess sensitivity coefficients on genome-wide models, our method exploits a master-slave methodology that distributes the computation on massively multi-core architectures. We performed the following steps: (1) we determined the putative parameterizations of the genome-wide metabolic constraint-based model, using Saltelli’s method; (2) we applied FBA to each parameterized model, distributing the massive amount of calculations over multiple nodes by means of MPI; (3) we then recollected and exploited the results of all FBA runs to assess a global sensitivity analysis.

Results

We show a proof-of-concept of our approach on latest genome-wide reconstructions of human metabolism Recon2.2 and Recon3D. We report that most sensitive parameters are mainly associated with the intake of essential amino acids in Recon2.2, whereas in Recon 3D they are associated largely with phospholipids. We also illustrate that in most cases there is a significant contribution of higher order effects.

Conclusion

Our results indicate that interaction effects between different model parameters exist, which should be taken into account especially at the stage of calibration of genome-wide models, supporting the importance of a global strategy of sensitivity analysis.
Positive natural selection in primate genes of the type I interferon response
Authors: Judd Elena N. , Gilchrist Alison R. , Meyerson Nicholas R. , Sawyer Sara L.
Published: April 2021

Background

The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one.

Results

We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid.

Conclusion

Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.
Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response
Authors: Schlamp Florencia , Delbare Sofie Y. N. , Early Angela M. , Wells Martin T. , Basu Sumanta , Clark Andrew G.
Published: April 2021

Background

Immune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes.

Results

To investigate genome-wide expression dynamics and trade-offs after infection at a high temporal resolution, we performed an RNA-seq time course onD. melanogasterwith 20 time points post Imd stimulation. A combination of methods, including spline fitting, cluster analysis, and Granger causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified Imd-responsive genes and co-expressed, less well characterized genes, with an immediate-early response and sustained up-regulation up to 5 days after stimulation. In contrast, stress response and Toll-responsive genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved.

Conclusions

This high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. The well annotated data set should also serve as a useful resource for further investigation of theD. melanogasterinnate immune response, and for the development of methods for analysis of a post-stress transcriptional response time-series at whole-genome scale.
Long-term outcome of percutaneous transluminal renal angioplasty (PTRA) versus PTRA with stenting (PTRAS) in transplant renal artery stenosis
Authors: Wongpraparut Nattawut , Chaipruckmalakarn Thunyarat , Tongdee Thongtum , Jaspttananon Archan , Vongwiwatana Attapong , Premasathian Nalinee , Anusonadisai Kawin , Pongakasira Rungtiwa
Published: April 2021

Background

Endovascular treatment is standard of care for transplant renal artery stenosis (TRAS). No study has evaluated long-term outcomes compared between percutaneous transluminal renal angioplasty (PTRA) and PTRA with stenting (PTRAS). Accordingly, this study aimed to investigate the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in patients diagnosed with TRAS at Thailand’s largest national tertiary referral center.

Methods

This single-center retrospective study included kidney transplant patients treated for TRAS during January 2001 to June 2019. Clinical success was defined as (1) increase in estimated glomerular filtration rate (eGFR) > 15%, or (2) reduction in mean arterial pressure (MAP) > 15% with no decrease in antihypertensive medication, or no reduction in MAP or reduction in MAP < 15% with decrease in antihypertensive medication. Incidence of kidney transplant graft failure and transplant renal artery stenosis were also collected.

Results

Sixty-five cases of TRAS were identified from 1072 patients who underwent kidney transplantation. The majority (98.5%) had end-to-side anastomosis technique. Thirty-four patients had PTRA, while 31 patients had PTRAS. One-year clinical success according to renal outcome and BP reduction was 78.5% and 49.2%, respectively. Both renal outcome (79.4% vs. 77.4%, p = 0.845) and BP reduction (40.6% vs. 58.1%, p = 0.166) at 1 year were similar between the PTRA and PTRAS groups. Compared between PTRA and PTRAS, event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher for PTRAS at 1 year (82.4% vs. 100%, p = 0.025), but not significantly different at 10 years (73.5% vs. 71%, p = 0.818).

Conclusions

We demonstrated the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in TRAS patients. One-year clinical success was found to be similar between groups. Event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher in PTRAS at 1 year, but similar between groups at 10 years.

Trial registration Thai Clinical Trials Registry, TCTR20200626002. Registered 26 June 2020—Retrospectively registered, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trial search&smenu = fulltext&task = search&task2 = view1&id = 6441
Sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test in community-dwelling older adults aged 65–75 years in Germany: results from the OUTDOOR ACTIVE study
Authors: Albrecht Birte Marie , Stalling Imke , Bammann Karin
Published: April 2021

Background

Physical fitness is a key component of independent living and healthy ageing. For the measurement of physical fitness in older adults, the Senior Fitness Test is a commonly used tool. The objective of this study is to calculate sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test for older adults (65–75 years) in Germany.

Methods

Cross-sectional data of 1657 community-dwelling older adults residing in Bremen, Germany (53% female) were included in this study. Physical fitness was assessed using the following measurements of the Senior Fitness Test battery: 30s-chair stand test, 2 min-step test, sit-and-reach test, and back scratch test. In addition, handgrip strength was measured using a Saehan DHD-3 digital hand dynamometer SH1003. Sex- and age specific normative values were calculated for the 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th, and 99th percentile using the GAMLSS method.

Results

The normative values show differences dependent on sex and age. For handgrip strength, the 30s-chair stand test and the 2 min-step test, normative values were higher for men, while women reached higher values in the sit-and-reach test and the back scratch test. For both, men and women, normative values declined with age.

Conclusions

This study provides sex- and age-specific normative values for handgrip strength and components of the Senior Fitness Test for older adults in Germany. They might be useful for future research and for the application in practice.
Cardiovascular disease and cumulative incidence of cognitive impairment in the Health and Retirement Study
Authors: Covello Allyson L. , Horwitz Leora I. , Singhal Shreya , Blaum Caroline S. , Li Yi , Dodson John A.
Published: April 2021

Background

We sought to examine whether people with a diagnosis of cardiovascular disease (CVD) experienced a greater incidence of subsequent cognitive impairment (CI) compared to people without CVD, as suggested by prior studies, using a large longitudinal cohort.

Methods

We employed Health and Retirement Study (HRS) data collected biennially from 1998 to 2014 in 1305 U.S. adults age ≥ 65 newly diagnosed with CVD vs. 2610 age- and gender-matched controls. Diagnosis of CVD was adjudicated with an established HRS methodology and included self-reported coronary heart disease, angina, heart failure, myocardial infarction, or other heart conditions. CI was defined as a score < 11 on the 27-point modified Telephone Interview for Cognitive Status. We examined incidence of CI over an 8-year period using a cumulative incidence function accounting for the competing risk of death.

Results

Mean age at study entry was 73 years, 55% were female, and 13% were non-white. Cognitive impairment developed in 1029 participants over 8 years. The probability of death over the study period was greater in the CVD group (19.8% vs. 13.8%, absolute difference 6.0, 95% confidence interval 2.2 to 9.7%). The cumulative incidence analysis, which adjusted for the competing risk of death, showed no significant difference in likelihood of cognitive impairment between the CVD and control groups (29.7% vs. 30.6%, absolute difference − 0.9, 95% confidence interval − 5.6 to 3.7%). This finding did not change after adjusting for relevant demographic and clinical characteristics using a proportional subdistribution hazard regression model.

Conclusions

Overall, we found no increased risk of subsequent CI among participants with CVD (compared with no CVD), despite previous studies indicating that incident CVD accelerates cognitive decline.
Chronic diseases in the geriatric population: morbidity and use of primary care services according to risk level
Authors: Barrio-Cortes Jaime , Castaño-Reguillo Almudena , Beca-Martínez María Teresa , Bandeira-de Oliveira Mariana , López-Rodríguez Carmen , Jaime-Sisó María Ángeles
Published: April 2021

Background

Geriatric patients have significant morbidity and greater needs for care and assistance. The objective of this study was to describe the characteristics, morbidity, and use of services in primary care (PC) of patients with chronic diseases older than 65 years according to their risk level assigned by the adjusted morbidity groups (AMG) and to analyse the factors associated with the use of PC services.

Methods

This was a cross-sectional descriptive observational study. Patients older than 65 years from a healthcare service area, classified as chronically ill by the AMG classification system of the PC electronic medical record of the Community of Madrid, were included. Sociodemographic, clinical-care, and PC service utilization variables were collected. Univariate, bivariate and multivariate analyses were done.

Results

A total of 3292 chronic patients older than 65 years were identified, of whom 1628 (49.5%) were low risk, 1293 (39.3%) were medium risk and 371 (11.3%) were high risk. Their mean age was 78.1 (SD = 8.1) years and 2167 (65.8%) were women. Their mean number of chronic diseases was 3.8 (SD = 2), 89.4% had multimorbidity and 1550 (47.1%) were polymedicated. The mean number of contacts/year with PC was 19.5 (SD = 18.2) [men: 19.4 (SD = 19.8); women: 19.5 (SD = 17.4)]. The mean number of contacts/year in people over 85 years was 25.2 (SD = 19.6); in people 76–85 years old, it was 22.1 (SD = 20.3); and in people 66–75 years old, it was 14.5 (SD = 13.9). The factors associated with greater use of services were age (B coefficient [BC] = 0.3; 95%CI = 0.2–0.4), high risk level (BC = 1.9; 95%CI =0.4–3.2), weight of complexity (BC = 0.7; 95%CI = 0.5–0.8), and ≥ 4 chronic diseases (BC = 0.7; 95%CI = 0.3–1.1).

Conclusions

In the geriatric population, we found a high number of patients with chronic diseases and there were three levels of risk by AMG with differences in characteristics, morbidity, and use of PC services. The greatest use of services was by patients with older age, high risk level, greater weight of complexity and ≥ 4 chronic diseases. Further research is needed to develop an intervention model more adapted to the reality of the geriatric population based on risk levels by AMG.
Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients
Authors: Aamir Azizul Hasan , Raja Umar Yousuf , Asghar Ali , Mahar Saeed Ahmed , Ghaffar Tahir , Ahmed Ibrar , Qureshi Faisal Masood , Zafar Jamal , Hasan Mohammad Imtiaz , Riaz Amna , Raza Syed Abbas , Khosa Irshad Ahmed , Khan Jahanzeb , Raza Mahwish , Baqar Jaffer Bin
Published: April 2021

Background

One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic.

Methods

This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients.

Results

A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40–59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin.

Conclusion

Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.