bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of suvorexant for trauma-related insomnia
Authors: Mellman Thomas A , Birku Kiya , Sandhu Ishaan , Lavela Pewu , Kobayashi Ihori
Published: March 2022

Study Objectives

Effective pharmacological treatments for sleep disturbance related to trauma with and without co-occurring posttraumatic stress disorder (PTSD) are needed. There is debate regarding what effects on rapid eye movement sleep (REMS) would be beneficial. Suvorexant is the first dual orexin receptor antagonist (DORA) approved for the treatment of insomnia. In contrast to most psychotropic agents, DORAs can enhance REMS while reducing arousal. We evaluated 6 weeks of suvorexant treatment for trauma-related insomnia in a double-blind, placebo-controlled clinical trial with clinical and polysomnographic evaluation.

Methods

Participants with insomnia that followed a traumatic event were recruited from the community. Representation of current, past-only, and never having met criteria for PTSD was similar and most participants had experienced trauma-related nightmares. Participants were randomly assigned to receive suvorexant or placebo, initially at 10 mg and increased to 20 mg after 1 week, if tolerated. Polysomnography was obtained for screening, at baseline, and at 2 weeks of treatment.

Results

The thirty-seven evaluable participants had significant improvement of PTSD and insomnia symptoms, however, there were no significant interactions with treatment condition. Medication was well tolerated with only one dropout being related to side effects. Within the suvorexant group increased REM segment duration correlated with concurrent PTSD symptom reduction. Nightmares remitted in all of the participants who received suvorexant and all but one of those receiving placebo.

Conclusions

A robust placebo response undermined detecting a medication effect. Further evaluation of DORAs for trauma-related insomnia, as well as factors contributing to placebo-response, are warranted.
Association between hospital-diagnosed sleep disorders and suicide: a nationwide cohort study
Authors: Høier Nikolaj Kjær , Madsen Trine , Spira Adam P , Hawton Keith , Eriksen Benros Michael , Nordentoft Merete , Erlangsen Annette
Published: March 2022

Study Objectives

Sleep disorders are related to mental disorders. Yet few studies have examined their association with suicide. We examined whether males and females diagnosed with sleep disorders had higher rates of suicide than individuals not diagnosed with sleep disorders.

Methods

In a cohort study, nationwide data on all males and females aged over 15 years living in Denmark during 1980–2016 were analyzed. Sleep disorders were identified through diagnoses recorded during contacts to somatic hospitals. Incidence rate ratios (IRR) were estimated using Poisson regression models and adjusted for covariates.

Results

In all, 3 674 563 males and 3 688 164 females were included, of whom 82 223 (2.2%, mean age: 50.2 years, SD: 17.5) males and 40 003 (1.1%, mean age: 50.6 years, SD: 19.9) females had sleep disorder diagnoses. Compared with those with no sleep disorders, the adjusted IRR for suicide were 1.6 (95% CI, 1.4 to 1.7) and 2.2 (95% CI, 1.8 to 2.6) for males and females with sleep disorders, respectively. Excess rates for narcolepsy were found for males (IRR: 1.2, 95% CI, 1.0 to 1.5) and females (IRR: 3.3, 95% CI, 3.0 to 4.1), and for sleep apnea in males (IRR: 1.8, 95% CI, 1.5 to 2.2). A difference with respect to age and sex was observed (p < 0.001) between males and females. Males and females had IRR of 4.1 (95% CI, 3.1 to 5.5) and 7.0 (95% CI, 4.8 to 10.1), during the first 6 months after being diagnosed with a sleep disorder.

Conclusions

Sleep disorders were associated with higher suicide rates even after adjusting for preexisting mental disorders. Our findings suggest attention toward suicidality in patients with sleep disorders is warranted.
sRNA Analysis Evidenced the Involvement of Different Plant Viruses in the Activation of RNA Silencing-Related Genes and the Defensive Response AgainstPlum pox virusof ‘GF305’ Peach Grafted with ‘Garrigues’ Almond
Authors: Rodamilans Bernardo , Oliveros Juan C. , San León David , Martínez-García Pedro J. , Martínez-Gómez Pedro , García Juan A. , Rubio Manuel
Published: March 2022

Plum pox virus (PPV) causes sharka disease in Prunus trees. Peach (P. persica) trees are severely affected by PPV, and no definitive source of genetic resistance has been identified. However, previous results showed that PPV-resistant ‘Garrigues’ almond (P. dulcis) was able to transfer its resistance to ‘GF305’ peach through grafting, reducing symptoms and viral load in PPV-infected plants. A recent study tried to identify genes responsible for this effect by studying messenger RNA expression through RNA sequencing in peach and almond plants, before and after grafting and before and after PPV infection. In this work, we used the same peach and almond samples but focused the high-throughput analyses on small RNA (sRNA) expression. We studied massive sequencing data and found an interesting pattern of sRNA overexpression linked to antiviral defense genes that suggested activation of these genes followed by downregulation to basal levels. We also discovered that ‘Garrigues’ almond plants were infected by different plant viruses that were transferred to peach plants. The large amounts of viral sRNA found in grafted peaches indicated a strong RNA silencing antiviral response and led us to postulate that these plant viruses could be collaborating in the observed “Garrigues effect.”
Both-Ear Method for the Analysis of Audiometric Data
Authors: Chen Chen , Zhang Ning , Curhan Gary C. , Curhan Sharon G. , Wang Molin
Published: March 2022

Objective:

Single-ear hearing measurements, such as better-ear, worse-ear or left/right ear, are often used as outcomes in auditory research, yet, measurements in the two ears of the same individual are often strongly but not perfectly correlated. We propose a both-ear method using the Generalized Estimating Equation approach for analysis of correlated binary ear data to evaluate determinants of ear-specific outcomes that includes information from both ears of the same individual.

Design:

We first theoretically evaluated bias in odds ratio (OR) estimates based on worse-ear and better-ear hearing outcomes. A simulation study was conducted to compare the finite sample performances of single-ear and both-ear methods in logistic regression models. As an illustrative example, the single-ear and both-ear methods were applied to estimate the association of Dietary Approaches to Stop Hypertension adherence scores with hearing threshold elevation among 3135 women, aged 48 to 68 years, in the Nurses’ Health Study II.

Results:

Based on statistical theories, the worse-ear and better-ear methods could bias the OR estimates. The simulation results led to the same conclusion. In addition, the simulation results showed that the both-ear method had satisfactory finite sample performance and was more efficient than the single-ear method. In the illustrative example, the confidence intervals of the estimated ORs for the association of Dietary Approaches to Stop Hypertension scores and hearing threshold elevation using the both-ear method were narrower, indicating greater precision, than for those obtained using the other methods.

Conclusions:

The worse-ear and better-ear methods may lead to biased estimates, and the left/right ear method typically results in less-efficient estimates. In certain settings, the both-ear method using the Generalized Estimating Equation approach for analyses of audiometric data may be preferable to the single-ear methods.
Internal Joint Stabilizer: A Safe Treatment for Traumatic Elbow Instability
Authors: Fene Evan S. , Grewal Ishvinder S. , Eakin John L. , Sanders Drew Thomas , Starr Adam Jennings
Published: March 2022

Objectives:

To report early results of the “Internal Joint Stabilizer of the Elbow” (IJS-E) in the treatment of terrible triad injuries and other unstable traumatic elbow dislocations.

Design:

Retrospective cohort study.

Setting:

Level 1 trauma center.

Patients/Participants:

Seventeen patients with traumatic elbow instability treated with IJS-E over a 2-year period; 7 of whom sustained terrible triad-type injuries.

Interventions:

Open reduction internal fixation with the “IJS-E”.

Main Outcome Measures:

Elbow stability and arc of motion were assessed radiographically and clinically. Disabilities of the Arm, Shoulder and Hand scores were collected by telephone.

Results:

All elbows were radiographically stable at the time of IJS-E removal. Mean time of follow-up was 9 months from index operation (range, 2.5–24 months). Mean elbow arc of motion was restored to flexion-extension 92 degrees (range, 5–125; SD, 31 degrees) and forearm pronation-supination 139 degrees (range, 0–180; SD, 48 degrees). Mean Disabilities of the Arm, Shoulder and Hand score was 22.2 (range, 7.5–45.7; SD, 13.3) for patients at least 1 month from surgery on the ipsilateral extremity. Five patients (30%) developed complications, and —2 (12%) required revision for implant failure.

Conclusions:

The IJS-E offered reliable treatment of traumatic elbow instability, particularly terrible triad-type injuries. It permited early range of motion and was effective in restoring elbow stability. We believe that the use of this relatively novel system should be further explored.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Autologous Cell Harvesting System as Adjunct for Soft-tissue Reconstruction of Necrotizing Soft Tissue Infection
Authors: Collins Reagan A. , Van Spronsen Nicole R. , Couch Brandon R. , Garcia Liza M. , Griswold John A. , Bharadia Deepak R.
Published: March 2022

Necrotizing soft tissue infections (NSTIs) cause rapidly progressing destruction of skin and soft tissue, leaving large soft tissue defects and necessitating complex reconstruction. RECELL, an autologous cell harvesting device, provides a regenerative epidermal suspension (RES) from a small split-thickness skin biopsy for the substitution of (or in addition to) split-thickness skin grafting (STSG). We present a case of a 56-year-old man with extensive NSTI managed by serial debridement, leading to a degloving injury to the right upper extremity, axilla, flank and back, which was later reconstructed using RES application in conjunction with STSG and Integra placement. At his 2-week hospital follow-up, the patient was healing well with limited right upper extremity range of motion, but continued improvement seen with physical and occupational therapy. Due to the patient’s significant soft tissue defect, a unique reconstructive plan was required using both Integra and RECELL in conjunction with STSG. RECELL, in conjunction with STSG, should be considered for the treatment of significant soft tissue defects such as those found in NSTI.
Human Frontalis Muscle Innervation and Morphology
Authors: Welter Laura , Bramke Silvia , May Christian Albrecht
Published: March 2022

Background:

Due to its clinical importance and due to a suggestion regarding the afferent innervation, the microscopic appearance of the frontalis muscle was investigated.

Methods:

From seven human cadavers, serial sections of the frontalis muscle were studied using light microscopy. Immunhistochemistry was performed using antibodies against collagen XXII and neurofilament.

Results:

The macroscopic appearance of the muscle was in accordance with the literature. At both insertion sides, the muscle fiber endings expressed collagen XXII, a marker for myotendinous junctions, although no tendons were present at the origin side. Neuromuscular junctions were seen in the middle part of the muscle belly (insertion of the nerve fibers of the facialis nerve) and in the cranial part toward the galea aponeurotica (possible afferent fibers?).

Conclusions:

This study summarizes the microscopic appearance of the frontalis muscle. It is a first example that collagen XXII can be expressed even without tendon formation. It confirms the absence of corpuscular afferent neuronal structures within the muscle.
Challenges in the Selection of Medical Equipment at a Regional Hospital in Ghana: The Perspective of End Users
Authors: Bart-Plange Akofa , Antwi Ethel Asante , Scott Cornelia , Ofori Philomina P.
Published: March 2022

Despite the advances made in implementing healthcare technologies, health facilities in low-middle income countries still grapple with ineffective technologies because of the challenges faced during selection. This study investigated this from the end-users' (n = 110) perspective at the Eastern Regional Hospital in Ghana. The study revealed that inadequate financial resources, lack of transparent technical needs assessment, activities of external donor agencies, growing political influence, and inadequate technical support staff were factors that influenced the selection of appropriate healthcare technology in the hospital. Healthcare facilities need to use a more inclusive strategy in selecting their healthcare technologies. In-house technical teams need to be involved in the process, from needs assessment to decommissioning, for technologies to be used optimally throughout their lifecycle.
A Comparison Study for Cardiac Arrhythmias Noise Cancellation Techniques
Authors: Mohamed Tamador Elkhansaa J. , Mustafa Zeinab A. , Amien Magdi B. M. , Ibraheem Banazier A.
Published: March 2022

The electrocardiogram (ECG), which represents the electrical activity of the heart, is always chosen as the basic signal for diagnosing cardiac abnormalities and detecting the patient's states. Generally, the various filters are applied (preprocessing) to denoise the artifacts from ECG signal. This step makes the decision making and diagnosis simpler and faster. The most common noise sources are power line interference and baseline wandering. This article discusses different filtering techniques used to denoise the ECG signals. Electrocardiogram signals were downloaded from the MIT-BIH Arrhythmia Database. The MIT-BIH Database was the first set of standard test materials that is generally available to evaluate arrhythmia detection. To remove baseline wander, 4 filters were designed. The filters are a fourth-order high-pass Butterworth filter, a second-order finite impulse response Hamming window, an finite impulse response rectangular window with length L, and an finite impulse response Hanning window. To extract the power line interference (60 Hz), 4 filters were designed: a second-order digital bandpass Butterworth filter, a second-order finite impulse response filter, a Chebyshev filter, and an finite impulse response notch filter with Hanning window. Finally, 5 parameters were used to evaluate filter performance; the parameters are frequency response, phase response, average filter delay (group delay), phase delay, and signal-to-noise ratio. The results show that, for baseline wander filters, a fourth-order high-pass Butterworth filter removes more noise and has no time delay. Power line interference filters have the same signal-to-noise ratio approximately.
Patient Characteristics Associated With Missed Appointments in Pediatric Subspecialty Clinics
Authors: Jones Michael K. , O'Connell Nathaniel S. , Skelton Joseph A. , Halvorson Elizabeth E.
Published: March 2022

Objectives:

Missed appointments negatively affect patients, providers, and health systems. This study aimed to (1) quantify the percentage of missed appointments across 14 pediatric subspecialties in a tertiary-care children's hospital and (2) identify patient characteristics associated with missed appointments in those subspecialties.

Methods:

We extracted patient characteristics from 267,151 outpatient appointments, between January 1, 2013, and December 31, 2018, across 14 subspecialty clinics. Medical complexity was categorized using the Pediatric Medical Complexity Algorithm. The primary outcome was appointment nonattendance. Cancellations, imaging/laboratory visits, patients older than 18 years, and duplicate visits were excluded. Characteristics associated with nonattendance were analyzed with chi-square tests and included in the multivariable model if p < .1. Missing data were addressed using random forest imputation, and assuming data were “missing at random.” Variables were considered statistically significant if p < .05.

Results:

Of the 128,117 scheduled appointments analyzed, 23,204 (18.1%) were missed. In the multivariable model, clinical nutrition had the greatest subspecialty odds of missed appointments, whereas cardiology had the lowest. Patient characteristics most strongly associated with missed appointments were public insurance, history of >2 missed appointments, appointment lead time, lesser medical complexity, Black race/ethnicity, and fewer medications.

Conclusions:

Clinical characteristics including lesser medical complexity and fewer medications are associated with missed appointments in pediatric subspecialties.
Development of a Practice-based Community Outreach Intervention to Prevent Inequities in COVID-19 Vaccinations
Authors: Gonzalez Christopher J. , Meltzer Kerry , Jabri Assem , Zhu Jifeng (Jeff) , Lau Jennifer D. , Pelzman Fred , Tung Judy
Published: March 2022

Despite disproportionately higher rates of morbidity and mortality from COVID-19 among Black and Hispanic adults in the United States, ethnoracial disparities in vaccination rates emerged rapidly. The objective of this quality improvement study was to rapidly develop and implement an equity-focused community outreach intervention that facilitated COVID-19 vaccine appointments. Using the Plan-Do-Study-Act model, this multipronged, primary care-based outreach intervention developed call/recall systems that addressed vaccine hesitancy and facilitated real-time vaccine scheduling. Through 5058 calls to 2794 patients, 1519 patients were successfully reached. Of the 750 patients eligible for vaccine scheduling, 129 (17.2%) had a vaccine appointment scheduled by the caller and 72 (9.6%) indicated a plan to self-schedule. Low confidence in the vaccine was the most cited reason for declining assistance with a vaccine appointment. Primary care practices may wish to consider introducing similar outreach interventions in the future to address ethnoracial inequities in vaccination distribution.
Evaluation of a Disposable Vascular Pressure Device for Pre- and Postmembrane Pressure Monitoring During Venovenous Extracorporeal Membrane Oxygenation
Authors: Lauria Michael J. , Shaffer Jamie , Crandall Cameron S. , Marinaro Jonathan L.
Published: March 2022

Membrane pressure monitoring during extracorporeal membrane oxygenation (ECMO) is integral to monitoring circuit health. We compared a disposable vascular pressure device (DVPD) to the transducer pressure bag arterial line (TPBAL) monitoring system to determine whether the DVPD can reliably and accurately monitor membrane pressures during venovenous extracorporeal membrane oxygenation (VV ECMO). We analyzed existing quality assurance data collected at a single center as part of routine circuit performance monitoring and process improvement on a convenience sample of four VV ECMO circuits. We placed and zeroed a DVPD in line with the pre- and postmembrane TPBAL setups in coordination with a standard transducer setup. We recorded DVPD and TPBAL pressure measurements every 4 hours for 2.5 days on the four separate VV ECMO circuits. We compared the standard and DVPD pressures using Bland–Altman plots and methods that accounted for repeated measures in the same subject. We recorded 58 pre/postmembrane pressures. Mean membrane pressure values were similar in the DVPD (pre: 208 mmHg [SD, 50.8]; post: 175 mmHg [46.3]) compared to the standard TPBAL setup (pre: 205 mmHg [52.0]; post: 177 mmHg [46.3]). Using Bland–Altman methods, premembrane pressures were found to be 2.2 mmHg higher (95% confidence interval [CI]: −5.3 to 9.7) in the standard TPBAL setup compared to DVPD and 1.8 mmHg higher (95% CI: −5.3 to 8.9) than the postmembrane pressures. The DVPD provided an accurate measurement of circuit pressure as compared to the TPBAL setup. Across the range of pre- and postmembrane pressures, both methods reliably agreed. Future trials should investigate DVPD accuracy in different environments such as prehospital field cannulation or critical care transport of ECMO patients.
Percutaneous Pulmonary Artery Cannulation to Treat Acute Secondary Right Heart Failure While on Veno-venous Extracorporeal Membrane Oxygenation
Authors: Ivins-O’Keefe Kelly M. , Cahill Michael S. , Mielke Arthur R. , Sobieszczyk Michal J. , Sams Valerie G. , Mason Phillip E. , Read Matthew D.
Published: March 2022

Right heart failure (RHF) is a common, yet difficult to manage, complication of severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) that is associated with increased mortality. Reports of the use of percutaneous mechanical circulatory support devices for concurrent right heart and respiratory failure are limited. This series describes the percutaneous cannulation of the pulmonary artery for conversion from veno-venous to veno-pulmonary artery return ECMO in 21 patients who developed secondary RHF. All patients cannulated between May 2019 and September 2021 were included. Either a 19 or 21 French venous cannula was placed percutaneously into the pulmonary artery via the internal jugular or subclavian vein, providing a total of 821 days of support (median 23 [4–71] days per patient) with flows up to 6 L/min. Five patients underwent cannulation at the bedside, with the remainder performed in the cardiac catheterization laboratory. Pulmonary artery cannulation occurred after 12 [8.5–23.5] days of ECMO support. Vasoactive infusion requirements decreased significantly within 24 hours of pulmonary artery cannula placement (p = 0.0004). Nonetheless, 75% of these patients expired after a median of 12 [4–63] days of support, with three patients found to have had significant pericardial effusions peri-arrest. This cannulation technique may be an effective alternative to veno-arterial ECMO cannulation or the placement of a dual-lumen cannula for the treatment of RHF.
Preoperative Computed Tomography Assessment of Risk of Right Ventricle Failure After Left Ventricular Assist Device Placement
Authors: Scott Anderson , Kligerman Seth , Hernandez Hernandez Diana , Kim Paul , Tran Hao , Pretorius Victor , Adler Eric , Contijoch Francisco
Published: March 2022

Identification of patients who are at a high risk for right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is of critical importance. Conventional tools for predicting RVF, including two-dimensional echocardiography, right heart catheterization (RHC), and clinical parameters, generally have limited sensitivity and specificity. We retrospectively examined the ability of computed tomography (CT) ventricular volume measures to identify patients who experienced RVF after LVAD implantation. Between September 2017 and November 2021, 92 patients underwent LVAD surgery at our institution. Preoperative CT-derived ventricular volumes were obtained in 20 patients. Patients who underwent CT evaluation had a similar demographics and rate of RVF after LVAD as patients who did not undergo cardiac CT imaging. In the study cohort, seven of 20 (35%) patients experienced RVF (2 unplanned biventricular assist device, 5 prolonged inotropic support). Computed tomography–derived right ventricular end-diastolic and end-systolic volume indices were the strongest predictors of RVF compared with demographic, echocardiographic, and RHC data with areas under the receiver operating curve of 0.79 and 0.76, respectively. Computed tomography volumetric assessment of RV size can be performed in patients evaluated for LVAD treatment. RV measures of size provide a promising means of pre-LVAD assessment for postoperative RV failure.
Symptom Clusters and Key Symptoms Among Midlife Perimenopausal and Postmenopausal Women With and Without Metabolic Syndrome
Authors: Min Se Hee , Yang Qing , Docherty Sharron L. , Im Eun-Ok , Hu Xiao
Published: March 2022

Background

Midlife perimenopausal and postmenopausal women with metabolic syndrome experience multiple symptoms concurrently.

Objective

The study objectives were to examine the relationship among symptoms through network visualization and identify and compare symptom clusters and key symptoms across symptom occurrence and symptom severity dimensions in midlife perimenopausal and postmenopausal women with and without metabolic syndrome.

Methods

Cross-sectional data from the Study of Women’s Health Across the Nation (Visit 5) were used for analysis. A machine-learning-based network analysis and the Walktrap algorithm were used to fulfill the study objectives.

Results

The number and types of symptom clusters differed between the groups. Midlife perimenopausal and postmenopausal women with metabolic syndrome experienced the psychological/somatic/genital cluster (key symptom: frequent mood change), the sleep/urinary cluster (sleep disturbance), and the vasomotor cluster (cold sweat) in the symptom occurrence dimension and the psychological/somatic/sexual cluster (anxiety), the sleep/urinary cluster (sleep disturbance), and the vasomotor/genital cluster (night sweat) in the symptom severity dimension. In contrast, midlife perimenopausal and postmenopausal women without metabolic syndrome experienced the psychological cluster (anxiety), the sleep/somatic/genitourinary cluster (sleep disturbance), and the vasomotor cluster (night sweat) in the symptom occurrence dimension and the psychological/somatic cluster (anxiety), the sleep/urinary cluster (sleep disturbance), the vasomotor cluster (night sweat), and the sexual/genital cluster (vaginal dryness) in the symptom severity dimension.

Discussion

The study findings may serve as a knowledge basis for effective assessment and management of symptom clusters and key symptoms in clinical settings and provide directions for future development of targeted symptom management interventions.
Sirolimus (Rapamycin) Induced Mucosal Healing in Anti-Tumor Necrosis Factor Refractory Pediatric Ulcerative Colitis
Authors: Kellermayer Richard , Chang Andrew , Patel Kalyani
Published: March 2022

Sirolimus (rapamycin) has been sparsely reported in the treatment of pediatric ulcerative colitis (PUC). Mucosal healing has not been examined in responders to the drug. We describe a case of infliximab refractory PUC where rapamycin induced sustained clinical remission along with mucosal healing. We conclude that rapamycin should be positioned into the expanding treatment repertoire of PUC.
The Risk of Colonic Strictures with Colitis Following Hemolytic Uremic Syndrome: A Case Report of a Toddler
Authors: Cagil Yasemin , Tan Serena , Fadell Michael , Husain Sohail , Ming Yeh Ann
Published: March 2022

Gastrointestinal manifestations of hemolytic uremic syndrome (HUS) are rare in pediatrics, but can have significant impact on the course of the disease. While various infectious etiologies are associated with HUS, Enterohemorrhagic Escherichia coli (EHEC) has been a focus of interest in its role in post-diarrheal HUS. We report a previously healthy 3-year-old boy who presented with bloody diarrhea, was found to be EHEC positive, and developed gastrointestinal complications of HUS including chronic colitis and strictures. The case illustrates that, though rare, HUS can have long-term gastrointestinal effects.
Kiyoshi Nagai. 25 June 1949—27 September 2019
Authors: Newman Andy , Luisi Ben
Published: March 2022

Kiyoshi Nagai pioneered research in several areas of structural and molecular biology in an innovative and imaginative style. His initial work was on haemoglobin, the oxygen carrier in blood. He devised new methods to express haemoglobin in bacteria, thereby enabling specific changes to be made in the amino acid sequence to test theories about the structure, function and evolution of the molecule. Later his focus changed to the structure of RNA–protein complexes. His major project became the elucidation of the structure of the spliceosome, the complex molecular machine that removes the intervening sequences from newly synthesized messenger RNA to create the correct template for translation into protein. Elucidation of this centrally important process required multiple techniques in molecular biology and structure determination. This memoir describes his scientific achievements and personal manner, which was marked by a passion to understand the workings of nature. He was an exemplary figure and mentor with a compassionate demeanour who continues to encourage and inspire multiple generations of scientists.
Finding the right fit: evaluation of short-read and long-read sequencing approaches to maximize the utility of clinical microbiome data
Authors: Gehrig Jeanette L. , Portik Daniel M. , Driscoll Mark D. , Jackson Eric , Chakraborty Shreyasee , Gratalo Dawn , Ashby Meredith , Valladares Ricardo
Published: March 2022

A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota’s impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches. We leveraged samples from participants enrolled in a phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their utility for generating clinical microbiome data. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active-ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations. Finally, compositionally similar bacterial metagenome-assembled genomes (MAGs) were recovered from short-read and long-read metagenomic methods, although a greater number and more complete MAGs were recovered from long reads. Despite higher costs, both amplicon and metagenomic long-read approaches yielded added microbiome data value in the form of higher confidence taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.
Prevalence of intraventricular haemorrhage and determinants of its early outcomes among preterm neonates at the newborn unit of a teaching hospital in Western Kenya
Authors: Sisenda Gloria Namubuya , Njuguna Festus Muigai , Nyandiko Winstone Mokaya
Published: March 2022

Intraventricular haemorrhage (IVH) screened using cranial ultrasounds (cUS) is a major cause of morbidity and mortality among preterm neonates. Despite the adverse neonatal outcomes attributed to IVH, there are limited studies conducted in sub-Saharan Africa on IVH occurrence and determinants of early outcomes. This study assessed the proportion of neonates with IVH, its determinants and the early outcomes of preterm neonates with the condition. A prospective descriptive study conducted at the newborn unit of Moi Teaching and Referral Hospital in Western Kenya between March 2020 to March 2021. The neonates sampled systematically had their clinical characteristics and that of their mothers collected from medical records. A cUS screening was conducted on the third and fourteenth day of life while hydrocephalus was screened using serial weekly measurements of head circumference and mortality assessed within the first 28 days of life. Bivariate analysis was used to test for an association between patient characteristics, occurrence of IVH and early outcomes. Confounders were controlled using a multivariate logistic regression model. We enrolled 201 pre-term neonates of whom 105 (52.2%) were male and 68 (33.8%) had IVH. Among neonates with IVH, 46 (67.6%) had mild while 22 (32.4%) had severe IVH. Antenatal steroids significantly reduced the risk of IVH while extreme/very low gestational age and extremely low birthweight significantly increased the risk of IVH two and three-fold respectively. Neonates with thrombocytopenia and on mechanical ventilation were significantly more likely to be diagnosed with IVH. Early outcomes of IVH were hydrocephalus (4.0%) and mortality (19.1%). Intraventricular haemorrhage was seen in one-third of neonates enrolled with majority of them presenting with the lower IVH grades. The IVH risk significantly increased among neonates with very low gestational age and extremely low birthweight but was lowered by antenatal steroid use. Mortality rates were significantly higher among neonates with thrombocytopenia.
Assessment of prescribing in under-five pediatric outpatients in Nigeria: an application of the POPI (Pediatrics: Omission of Prescription and Inappropriate Prescription) tool
Authors: Ahwinahwi Ufuoma Shalom , Odili Valentine U , Nwachukwu Destiny Obiajulu
Published: March 2022

Background

Ensuring the right drug for the right clinical condition in children under five years of age will dramatically reduce morbidity and mortality rates in developing countries where these values are alarmingly high. This study evaluated prescribing in children under the age of five attending pediatric outpatient clinics at three Central hospitals in Delta State, Nigeria, using the Pediatics: Omission of Prescriptions and Inappropriate Prescription (POPI) tool.

Methods

This was a prospective descriptive study of prescriptions made to children from 0 to 59 months who attended the clinics between August and November 2018.Prescriptions were evaluated using the POPI tool, occurrence of potentially inappropriate prescriptions and prescribing omissions were reported as percentages and inappropriate prescription types and prescription omissions were also reported as frequencies. Relationship between inappropriate prescriptions, omissions of prescriptions, and categorical variables of age group and sex, p <.05 were considered significant.

Results

A total of 1,327 prescriptions from the three centers were analyzed. There was a preponderance of infants (> 1 month-12 months of age) in the study (43.0%) and a somewhat even gender distribution. Exactly 29.8% of all the prescriptions studied had at least one occurrence of inappropriate prescription. The use of H1 antagonists with sedative or atropine-like effects accounted for the majority of inappropriate prescriptions (49.5%), while the prescription of drinkable amoxicillin or other antibiotics in doses other than mg was the most frequent omission of prescription (97.2%). There was a significant relationship between the occurrence of inappropriate prescription and age group (p> 0.001).

Conclusion

The occurrence of inappropriate prescriptions and omissions of prescriptions was high and effectively detected by the POPI tool. Measures should be taken to improve prescribing in order to reduce morbidity and mortality in children below five years.
QTLs analysis for cold tolerance in rice (Oryza sp.) at the seedling stage using F2 population developed from cross between the genotypes NERICA L-19 and Diamante
Authors: Effa Effa Branly Wilfried , Manneh Baboucarr
Published: March 2022

Rice (Oryza sp.) is the most important food crop of the developing world and the staple food of more than half of the world population. It is produced in about 110 countries, including Africa under traditional production systems where field conditions are often variable and yield is low. This is due to the preponderance of abiotic stresses such as cold in these systems. The aim of this study was to identify QTLs associated with cold tolerance at the seedling stage. It was obtained: a phylogenetic tree showing individuals tolerant and sensitive to cold in the Sahel conditions at the seedling stage; 5 majors QTLs associated with cold tolerance located on chromosome 4; QTLs associated with cold tolerance at the seedling stage using F2 population developed from cross between NERICA L-19 X Diamante. All these results are interesting, because to pass local varieties sensitive to cold tolerant varieties through the identification of QTLs associated with cold tolerance that might be introduced. This will enable African producers; especially small producers which have low resource to buy a plant material adapted to the cold period to optimize their rice yields.
Gill developmental program in the teleost mandibular arch
Authors: Thiruppathy Mathi , Gillis J. Andrew , Crump J. Gage
Published: March 2022

Whereas no known living vertebrate possesses gills derived from the jaw-forming mandibular arch, it has been proposed that the jaw arose through modifications of an ancestral mandibular gill. Here we show that the zebrafish pseudobranch, which regulates blood pressure in the eye, develops from mandibular arch mesenchyme and first pouch epithelia and shares gene expression, enhancer utilization, and developmental gata3 dependence with the gills. Combined with work in chondrichthyans, our findings in a teleost fish point to the presence of a mandibular pseudobranch with serial homology to gills in the last common ancestor of jawed vertebrates, consistent with a gill origin of vertebrate jaws.
Inherent Dynamics of Maltose Binding Protein (MBP) are Immune to the Native Environment
Authors: Thoma Johannes , Burmann Björn M.
Published: March 2022

Biophysical characterizations of proteins typically rely on a reductionistic approach, studying proteins in a highly purified from and in absence of their natural cellular environment. Little is known about how the highly crowded conditions prevalent within living cells influence the dynamic structures proteins on the molecular level. To address this outstanding question, we characterize here the dynamic behavior of the periplasmic model protein MBP fromEscherichia coli in situ, confined in the native lumen of bacterial outer membrane vesicles. To this end we determine the dynamics of side-chain methyl groups of MBP across several timescales and compare them to purifiedin vitroMBP. We find that the inherent dynamics of MBP are surprisingly insensitive to the native cellular environment and that the molecular motion of the protein is mainly impacted on a global level.
DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types
Authors: Shireby Gemma , Dempster Emma , Policicchio Stefania , Smith Rebecca G , Pishva Ehsan , Chioza Barry , Davies Jonathan P , Burrage Joe , Lunnon Katie , Seiler-Vellame Dorothea , Love Seth , Thomas Alan , Brookes Keeley , Morgan Kevin , Francis Paul , Hannon Eilis , Mill Jonathan
Published: March 2022

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles of tau in the neocortex. Utilizing extensive neuropathology data from the Brains for Dementia Research (BDR) cohort we performed the most systematic epigenome-wide association study (EWAS) of multiple measures of AD neuropathology yet undertaken, profiling DNA methylation in two cortical regions from 631 donors. We meta-analyzed our results with those from previous studies of DNA methylation in AD cortex (total n = 2,013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated with AD pathology including methylomic variation at novel loci not previously implicated in dementia. We subsequently characterized DNA methylation in purified nuclei populations - enriched for neurons, oligodendrocytes and microglia - exploring the extent to which cortex AD-associated DMPs reflect differences manifest in specific cell populations. We find that the majority of DMPs identified in ‘bulk’ cortex tissue actually reflect DNA methylation differences occurring in non-neuronal cells, with dramatically increased effect sizes observed in microglia-enriched nuclei populations. Our study highlights the power of utilizing multiple measures of neuropathology to identify epigenetic signatures of AD and the importance of characterizing disease-associated variation in purified neural cell-types.
Integration of visual and antennal mechanosensory feedback during head stabilization in hawkmoths
Authors: Chatterjee Payel , Prusty Agnish Dev , Mohan Umesh , Sane Sanjay P.
Published: March 2022

During flight maneuvers, insects exhibit compensatory head movements which are essential for stabilizing the visual field on their retina, reducing motion blur, and supporting visual self-motion estimation. In Diptera, such head movements are mediated via visual feedback from their compound eyes that detect retinal slip, as well as rapid mechanosensory feedback from their halteres - the modified hindwings that sense the angular rates of body rotations. Because non-Dipteran insects lack halteres, it is not known if mechanosensory feedback about body rotations plays any role in their head stabilization response. Diverse non-Dipteran insects are known to rely on visual and antennal mechanosensory feedback for flight control. In hawkmoths, for instance, reduction of antennal mechanosensory feedback severely compromises their ability to control flight. Similarly, when the head movements of freely-flying moths are restricted, their flight ability is also severely impaired. The role of compensatory head movements as well as multimodal feedback in insect flight raises an interesting question: in insects that lack halteres, what sensory cues are required for head stabilization? Here, we show that in the nocturnal hawkmoth Daphnis nerii, compensatory head movements are mediated by combined visual and antennal mechanosensory feedback. We subjected tethered moths to open-loop body roll rotations under different lighting conditions, and measured their ability to maintain head angle in the presence or absence of antennal mechanosensory feedback. Our study suggests that head stabilization in moths is mediated primarily by visual feedback during roll movements at lower frequencies, whereas antennal mechanosensory feedback is required when roll occurs at higher frequency. These findings are consistent with the hypothesis that control of head angle results from a multimodal feedback loop that integrates both visual and antennal mechanosensory feedback, albeit at different latencies. At adequate light levels, visual feedback is sufficient for head stabilization. However, under dark conditions, antennal mechanosensory feedback is essential for the control of head movements.

Highlights

Visual feedback contributes to head stabilization primarily during slower body rotation in hawkmoths.

Antennal mechanosensors contribute to head stabilization primarily during faster body roll.

Antennal mechanosensory feedback in head stabilization is mediated via Johnston’s organ.

Restricting head movements affects flight control.
Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings
Authors: de Paula Jonas Jardim , Pereira de Paiva Rachel Elisa Rodrigues , e Silva Nathália Gualberto Souza , Rosa Daniela Valadão , de Souza Duran Fabio Luis , Coimbra Roney Santos , de Souza Costa Danielle , Dutenhefner Pedro Robles , Dutra Oliveira Henrique Soares , Camargos Sarah Teixeira , Mendes Vasconcelos Herika Martins , de Oliveira Carvalho Nara , da Silva Juliana Batista , Silveira Marina Bicalho , Malamut Carlos , Oliveira Derick Matheus , Molinari Luiz Carlos , de Oliveira Danilo Bretas , Januário José Nélio , Silva Luciana Costa , De Marco Luiz Armando , Magalhães Queiroz Dulciene Maria de , Meira Wagner , Busatto Geraldo , Miranda Débora Marques , Romano-Silva Marco Aurélio
Published: March 2022

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.
General Framework for Evaluating Outbreak Prediction, Detection, and Annotation Algorithms
Authors: Abbood Auss , Ghozzi Stéphane
Published: March 2022

The COVID-19 pandemic has highlighted and accelerated the use of algorithmic-decision support for public health. The latter’s potential impact and risk of bias and harm urgently call for scrutiny and evaluation standards. One example is the early detection of local infectious disease outbreaks. Whereas many statistical models have been proposed and disparate systems are routinely used, each tai-lored to specific data streams and use, no systematic evaluation strategy of their performance in a real-world context exists.

One difficulty in evaluating outbreak prediction, detection, or annotation lies in the scales of different approaches: How to compare slow but fine-grained genetic clustering of individual samples with rapid but coarse anomaly detection based on aggregated syndromic reports? Or alarms generated for different, overlapping geographical regions or demographics?

We propose a general, data-driven, user-centric framework for evaluating hetero-geneous outbreak algorithms. Discrete outbreak labels and case counts are defined on a custom data grid, associated target probabilities are then computed and compared with algorithm output. The latter is defined as discrete “signals” are generated for a number of grid cells (the finest available in the benchmarking data set) with different weights and prior outbreak information from which then estimated outbreak label probabilities are derived. The prediction performance is quantified through a series of metrics, including confusion matrix, regression scores, and mutual information. The dimensions of the data grid can be weighted by the user to reflect epidemiological criteria.