bluuebunny/crossref_metadata_2025 huggingface dataset:
Cochlear Implantation in Children with Autism Spectrum Disorder: A Systematic Review and Pooled Analysis
Authors: Mathew Rajeev , Bryan James , Chaudhry Daoud , Chaudhry Abdullah , Kuhn Isla , Tysome James , Donnelly Neil , Axon Patrick , Bance Manohar
Published: November 2021

Objective:

To determine outcomes following cochlear implantation (CI) in children with autism spectrum disorder (ASD).

Databases Reviewed:

MEDLINE, Embase, Web of science, Cochrane Library, and Clinicaltrial.gov.

Methods:

The review was performed according to the PRISMA statement. Primary outcomes measures were changes in speech perception and speech production scores. Secondary outcome measures included communication mode, device use, parental recommendation of implant, postoperative hyperacusis, and quality of life measures. Pooled analysis of outcomes was performed if possible.

Results:

Twenty-four studies reported on 159 children with ASD. There were improvements in speech perception in 78% of cases and in speech expression in 63% of cases, though the extent of this improvement was variable. Seventy-four percent of children with ASD and CI are nonoral communicators. Intermittent/nonuse rate was 31%. Hearing outcomes are worse compared to children with other disabilities. The vast majority of parents would recommend CI based on their experiences.

Conclusion:

Outcome in children with ASD and CI are highly variable and significantly poorer compared to non-ASD children. Despite this, most parents report positive experiences and the evidence supports the use of CI in children with ASD.
Relationship Between Intraoperative Electrocochleography and Hearing Preservation
Authors: Lenarz Thomas , Buechner Andreas , Gantz Bruce , Hansen Marlan , Tejani Viral D. , Labadie Robert , O’Connell Brendan , Buchman Craig Alan , Valenzuela Carla V. , Adunka Oliver F. , Harris Michael S. , Riggs William J. , Fitzpatrick Douglas , Koka Kanthaiah
Published: November 2021

Objectives:

To compare intraoperative intracochlear electrocochleography (ECochG) with hearing preservation outcomes in cochlear implant (CI) subjects.

Design:

Intraoperative electrocochleography was performed in adult CI subjects who were recipients of Advanced Bionics’ Bionics LLC precurved HiFocus MidScala or straight HiFocus SlimJ electrode arrays. ECochG responses were recorded from the most apical electrode contact during insertion. No changes to the insertions were made due to ECochG monitoring. No information about insertion resistance was collected. ECochG drops were estimated as the change in amplitude from peak (defined as maximum amplitude response) to drop (largest drop) point after the peak during insertion was measured following the peak response. Audiometric thresholds from each subject were obtained before and approximately 1 month after CI surgery. The change in pure tone average for frequencies between 125 Hz and 500 Hz was measured after surgery. No postoperative CT scans were collected as part of this study.

Results:

A total of 68 subjects from five surgical centers participated in the study. The study sample included 30 MidScala and 38 SlimJ electrodes implanted by approximately 20 surgeons who contributed to the study. Although a wide range of results were observed, there was a moderate positive correlation (Pearson Correlation coefficient, r = 0.56, p < 0.01) between the size of the ECochG drop and the magnitude of pure tone average change. This trend was present for both the MidScala and SlimJ arrays. The SlimJ and MidScala arrays produced significantly different hearing loss after surgery.

Conclusion:

Large ECochG amplitude drops observed during electrode insertion indicated poorer hearing preservation. Although the outcomes were variable, this information may be helpful to guide surgical decision-making when contemplating full electrode insertion and the likelihood of hearing preservation.
Horizontal gaze palsy with progressive scoliosis syndrome in a paediatric patient
Authors: Tyradellis Straton , Tsokolas Georgios , Pillai Swati
Published: November 2021

Rationale:

Horizontal Gaze Palsy and Progressive Scoliosis syndrome (HGPPS) is a very rare autosomal recessive disorder that has been reported mainly in consanguineous families. Our aim was to describe a rare case of HGPPS in a pediatric patient.

Patient concerns:

A 3-year-old male child was referred to our pediatric ophthalmology clinic because of squint since he was 6 months old. His parents were concerned that both eyes gradually became more esotropic over the past year. In addition, the child was unable to walk independently and was undergoing physiotherapy for mobility issues.

Diagnoses:

Skeletal examination revealed scoliosis. The child was unable to stand without any support. Orthoptic assessment revealed bilateral horizontal gaze palsy with abduction deficit, convergent squint, and pendular nystagmus. Vertical eye movements were preserved. Convergence was also preserved. Magnetic resonance imaging revealed bilateral hypoplastic sixth nerve nuclei with brainstem hypoplasia, the presence of a deep midline pontine cleft, and a butterfly shaped medulla. The child was referred to the genetic clinic, and mutation in the ROBO 3 gene was confirmed. The patient was diagnosed with HGPPS.

Interventions:

The esotropia was corrected with prisms, and no other surgical intervention was attempted due to the child's general poor health.

Outcomes:

To date, the esotropia has remained stable around 35 to 40 diopters, and its control with prism has been adequate. The total follow-up time from the presenting appointment in our clinic until the most recent appointment was approximately two years.

Lessons:

HGPPS is a rare autosomal recessive syndrome characterized by clinical and radiological findings. Our main learning point is that the diagnosis of HGPPS should be included in the differential diagnosis in children who present with combined symptoms of squint and skeletal abnormalities.
Frequent hypotension during hemodialysis in a patient with cutis laxa
Authors: Song Bin , Zeng Yan , Chen Shijing , Huang Kaisen , He Dingxiu , Jiang Yan
Published: November 2021

Rationale:

Cutis laxa is a rare disorder characterized by redundant, loose, and inelastic skin. Its chief histological feature is the reduction of elastic fibers in the dermal layer. Hypotension on dialysis is defined as a decrease in systolic blood pressure of ≥20 mm Hg or a decrease in mean arterial pressure of 10 mm Hg, accompanied by a clinical event requiring therapeutic intervention.

Patient concerns:

A 49-year-old female patient with cutis laxa who had frequent episodes of hypotension during hemodialysis.

Diagnoses:

A skin biopsy revealed changes typical of cutis laxa. Physical examination of the patient revealed systemic skin laxity with a presenile appearance.

Interventions:

We replaced conventional hemodialysis with hemodiafiltration.

Outcomes:

The hypotension improved after the patient started hemodiafiltration.

Lessons:

Cutis laxa may be a risk factor for hypotension during hemodialysis. Hemodiafiltration increases systemic vascular resistance and norepinephrine plasma levels in patients with cutis laxa, thereby stabilizing blood pressure. In a patient with cutis laxa, replacing conventional hemodialysis with hemodiafiltration resulted in an improvement in hypotension.
Association of a Substance Use Disorder with Infectious Diseases among Adult Home Healthcare Patients with a Venous Access Device
Authors: Byon Ha Do , Ahn Soojung , Yan Guofen , Crandall Mary , LeBaron Virginia
Published: November 2021

Substance use disorders (SUDs) and high incidence of infectious diseases are both critical public health issues. Among patients who use a venous access device (VAD) in home care settings, SUDs may play a role in increasing their risk of having a concurrent infectious disease. This study examined the association of SUD with infectious diseases among adult home healthcare patients with a VAD. We identified adult patients with an existing VAD who were admitted to a home healthcare agency August 1, 2017–July 31, 2018 from the electronic health records of a large Medicare-certified agency. Four serious infectious diseases (endocarditis, epidural abscess, septic arthritis, and osteomyelitis) and SUD related to injectable drugs were identified using relevant ICD-10 codes. Multiple logistic regression was performed to examine the association. Of 416 patients with a VAD, 12% (n = 50) had at least one diagnosis of a serious infectious disease. The percentage of patients who had a serious infectious disease was 40% among those with SUDs, compared with only 11% among those without SUDs. After adjusting for age and sex, the odds of having a serious infectious disease was 3.52 times greater for those with SUDs compared with those without (odds ratio [95% confidence interval], 4.52 [1.48-13.79], n = .008). Our findings suggest that home healthcare patients with a VAD and a documented SUD diagnosis may have an increased risk of having a concurrent serious infectious disease. Therefore, patients with an SUD and a VAD would need more attention from home healthcare providers to prevent a serious infectious disease. Further research is suggested on modalities of care for individuals with an SUD and VAD to reduce the incidence of infectious diseases so that care can be delivered safely and efficiently in a home healthcare setting.
Hospice Staff Comfort with Telehospice
Authors: Cameron Patricia
Published: November 2021

Telehospice has been recognized as a way to meet the needs of hospice patients and their caregivers. The purpose of this study was to examine the comfort of hospice staff using telehospice to connect virtually with patients and caregivers. The hospice in this study uses Alpha Virtual Assist (AVA), which employs a commercial remote patient monitoring platform and a communication platform that focuses on holistic patient and caregiver comfort as well as interpersonal and interprofessional communication. A mixed methods research design was used. An online survey of hospice staff that included quantitative and qualitative items was used to collect data. Forty-four hospice staff agreed to participate. No differences were found in comfort levels with using AVA between nurses and other staff. Three themes emerged from the qualitative responses: Positive responses about AVA; AVA as an assistive device; and Problems with connectivity. Hospice staff were comfortable using telehospice technology and have effectively used this tool with hospice patients and their caregivers before and during the pandemic.
Nurse Residents’ Legacy Letters
Authors: Brown Janelle , Fowler Susan , Mason Tina M.
Published: November 2021

It is important for graduate nurses to reflect on their time in residency programs. Legacy letters, written by oncology nurse residents to future residents, reflect on “what I wish I knew” and “what I learned.” A retrospective, qualitative thematic analysis of 30 letters at a National Cancer Institute-designated comprehensive cancer center in the southeastern United States was conducted. Four themes arose. Understanding these experiences can provide insight to nurse residents and guide improvements for the residency program.
Significance of Single-cell Level Dual Expression of BCL2 and MYC Determined With Multiplex Immunohistochemistry in Diffuse Large B-Cell Lymphoma
Authors: Roh Jin , Yoon Dok Hyun , Lee Yoon Kyoung , Pak Hyo-Kyung , Kim Sang-Yeob , Han Jae Ho , Park Joon Seong , Jeong Seong Hyun , Choi Yoon Seok , Cho Hyungwoo , Suh Cheolwon , Huh Jooryung , Lee Dae Ho , Park Chan-Sik
Published: November 2021

Diffuse large B-cell lymphoma (DLBCL) is a fatal heterogenous neoplasm. Recent clinical trials have failed partly due to nebulous criteria for defining high-risk patients. Patients with double-expresser lymphoma (DEL) have a poor prognosis and are resistant to conventional treatment. However, many diagnostic and clinical controversies still surround DEL partly due to the arbitrariness of criteria for the diagnosis of DEL. In this study, we suggest a refined method for diagnosing DEL by evaluating the concurrent expression of BCL2 and MYC at the single-cell level (dual-protein–expressing lymphoma [DUEL]). For the proof of concept, a multiplex immunofluorescence assay for CD20, BCL2, and MYC was performed and quantitatively analyzed using spectral image analysis in patients. The analysis results and clinical applicability were verified by using dual-color immunohistochemistry performed on 353 independent multicenter patients who had been uniformly treated with standard therapy. DUEL showed significantly worse overall survival (OS) and event-free survival (EFS) (P=0.00011 and 0.00035, respectively). DUEL status remained an independent adverse prognostic variable with respect to the International Prognostic Index risk and the cell of origin. Moreover, the advantage of determining DUEL status by dual-color immunohistochemistry was shown by more robust classification and more homogeneous high-risk subgroup patient identification in both training (n=271) (OS: P<0.0001; EFS: P<0.0001) and validation sets (n=82) (OS: P=0.0087; EFS: P<0.0001). This concept of DUEL is more consistent with carcinogenesis and has greater practical utility, hence it may provide a better basis for both basic and clinical research for the development of new therapeutics.
Paramedic Student Clinical Performance During High-Fidelity Simulation After a Physically Demanding Occupational Task
Authors: MacQuarrie Alex (Sandy) , Hunter Jayden R. , Sheridan Samantha , Hlushak Amanda , Sutton Clare , Wickham James
Published: November 2021

Introduction

Paramedic duties include assessing, treating, and maneuvering patients in physically challenging environments. Whether clinical skills and patient care are affected by these occupational demands is unknown. High-fidelity simulation affords the opportunity to study this in a controlled setting.

Methods

Using a randomized crossover design, 11 regional paramedicine students and graduates (mean ± SD age = 23 ± 2 years) completed two, 20-minute high-fidelity simulations that included cardiopulmonary resuscitation (CPR) immediately after either an acute bout of occupational physical activity (OPA) or a rest period (REST). Heart rate, respiratory rate, and mean arterial pressure were measured throughout. Clinical performance was scored using the Global Rating Score and a patient care record. Measures of CPR efficacy were recorded in the manikin.

Results

There were no significant differences in Global Rating Score (P = 0.07, ES = 0.03) or CPR efficacy between conditions. Patient care record accuracy was higher after the OPA versus REST simulations (mean ± SD = 61.8 ± 12.6% vs. 55.5 ± 12.0%, P = 0.03, ES = 0.5). Mean heart rate was higher during OPA simulations versus REST simulations (121 ± 14 vs. 84 ± 9 beats per minute, P < 0.01, ES = 3.1), as was mean respiratory rate (19 ± 3 vs. 16 ± 3 breaths per minute, P < 0.01, ES = 1.0). Mean arterial pressure was higher for OPA versus REST at simulation start (105 ± 11.3 vs. 95.8 ± 11.8 mm Hg, P = 0.01, Effect Size = 0.8), although not different after simulation.

Conclusions

Paramedicine students including recent graduates performed as well, or better, in a simulated clinical scenario immediately after occupation-specific acute physical exertion compared with a REST, despite higher physiological exertion. Whether this is the case for more experienced but potentially less physically fit paramedics in the workforce warrants investigation.
Visual Fixation on the Thorax Predicts Bystander Breathing Detection in Simulated Out-of-Hospital Cardiac Arrest, but Video Debriefing With Eye Tracking Gaze Overlay Does Not Enhance Postallocation Success Rate
Authors: Pedrotti Marco , Terrier Philippe , Gelin Louis , Stanek Marc , Schirlin Olivier
Published: November 2021

Introduction

Bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest is associated with higher survival rates. Even trained health care staff cannot assess breathing well enough to detect cardiac arrest. Recognition of cardiac arrest by lay rescuers might be overlooked in adult basic life support resuscitation guidelines, which explain what to do, but not how to do it. The 2015 Adult Advanced Life Support Resuscitation Guidelines recommend to “look for chest movement.” We hypothesize (1) that instructing lay rescuers to look for chest movement allows detecting breathing (or lack thereof); (2) that showing a person their own recorded gaze overlay during a video debriefing intervention enhances breathing detection at postallocation; and (3) that the more time spent looking at a cardiac arrest victim's chest, the greater the probability of detecting breathing (or lack thereof).

Methods

Monocentric, blinded, prospective, 2-arm parallel randomized controlled trial with balanced randomization (1:1). The design entailed a preallocation simulation, an intervention (video debriefing with or without gaze overlay), and a postallocation simulation. A follow-up simulation took place after 6 months. The main outcome measured was success in detecting breathing. Participants were all prospective students of a bachelor's degree program in nursing.

Results

All participants performed better at postallocation (success rate at preallocation = 59%, postallocation = 79%, χ2 = 7.22, P < 0.01) regardless of viewing their own gaze overlay during video debriefing. We failed to obtain a sufficient number of participants for the follow-up simulation. Instructing lay rescuers to look for chest movement allows them to detect breathing (or lack thereof). Each second spent looking at the thorax increased the odds of successfully detecting breathing by 38%. Mean thorax gaze duration significantly increased by 5.95 seconds (95% confidence interval = 4.71–7.31) from preallocation (3.46 seconds, SD = 4.16) to postallocation (9.41 seconds, SD = 5.98). Laypersons' median diagnosis time was 15.5 seconds (range = 2–63 seconds), similar to another study (13 seconds, range = 5–40 seconds).

Conclusions

This is the second study in which the median time to decision exceeded the maximum 10 seconds recommended. International guidelines should consider increasing the time allowed for the “check breathing” step of bystander cardiopulmonary resuscitation procedures.
New Injury Severity Score and Trauma Injury Severity Score are superior in predicting trauma mortality
Authors: Chun Magnus , Zhang Yichi , Becnel Chad , Brown Tommy , Hussein Mohamed , Toraih Eman , Taghavi Sharven , Guidry Chrissy , Duchesne Juan , Schroll Rebecca , McGrew Patrick
Published: November 2021

BACKGROUND

Trauma scores are used to give clinicians appropriate quantitative context in making decisions. Studies show that anatomical trauma scores predicted intensive care unit admission better, while physiological trauma scores predicted mortality better. We hypothesize that trauma scores have a hierarchy of efficacies at predicting mortality and operative decision making.

METHODS

We performed a retrospective analysis of our trauma patient database at a level 1 trauma center from 2016 to 2020 and calculated the following trauma scores: Glasgow Coma Scale, Revised Trauma Score, Trauma Injury Severity Score, Injury Severity Score, Shock Index, and New Trauma Injury Severity Score (NISS). Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of trauma scores for predicting mortality.

RESULTS

A total of 738 patients were included (mean ± SD age, 35.7 ± 15.6 years). Area under the curve (AUC) results from the DeLong test showed that NISS predicted mortality the best compared with other trauma scores. New Trauma Injury Severity Score was superior in predicting mortality for penetrating trauma (AUC, 0.86 ± 0.02; p < 0.001) compared with blunt trauma (AUC, 0.73 ± 0.04; p < 0.001). Trauma Injury Severity Score was the best predictor of mortality for patients with gunshot wounds (AUC, 0.83; 95% confidence interval [CI], 0.73–0.92; p < 0.001), motor vehicle accidents (AUC, 0.80; 95% CI, 0.61–1.00; p = 0.01), and falls (AUC, 0.73; 95% CI, 0.61–0.85; p = 0.007).

CONCLUSION

New Trauma Injury Severity Score was the best scoring index for predicting mortality in trauma patients, especially for penetrating trauma. Clinicians should consider incorporating other trauma scores, especially NISS and Trauma Injury Severity Score, in determining injury severity and the likelihood of mortality. These scores can help physicians determine the best course of action in patient management.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; level IV.
Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study
Authors: Esposito Emily C. , Kufera Joseph A. , Wolff Timothy W. , Spalding M. Chance , Simpson Joshua , Dunn Julie A. , Zier Linda , Burruss Sigrid , Kim Paul , Jacobson Lewis E. , Williams Jamie , Nahmias Jeffry , Grigorian Areg , Harmon Laura , Gergen Anna , Chatoor Matthew , Rattan Rishi , Young Andrew J. , Pascual Jose L. , Murry Jason , Ong Adrian W. , Muller Alison , Sandhu Rovinder S. , Appelbaum Rachel , Bugaev Nikolay , Tatar Antony , Zreik Khaled , Hustad Leah , Lieser Mark J. , Stein Deborah M. , Scalea Thomas M. , Lauerman Margaret H.
Published: November 2021

BACKGROUND

Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care.

METHODS

An Eastern Association for the Surgery of Trauma–sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only.

RESULTS

Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without.

CONCLUSION

Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic, Level IV.
Fusibacter ferrireducens sp. nov., an anaerobic, Fe(Ⅲ)- and sulphur-reducing bacterium isolated from mangrove sediment
Authors: Qiu Donghua , Zeng Xiang , Zeng Lingyu , Li Guangyu , Shao Zongze
Published: November 2021

An anaerobic, alkaliphilic, halotolerant, Gram-stain-positive and rod-shaped bacterium, designated Q10-2T, was isolated from mangrove sediment sampled at the Jiulong river estuary, PR China. The cells of strain Q10-2T were motile and 0.5×2–4 µm in size. Strain Q10-2T grew at 8–45 °C (optimum, 32 °C), at pH 7.0–10.5 (optimum, pH 8.5) and in the presence of 0–6 % (w/v) NaCl (optimum, 3 %). It could use complex organic compounds and carbohydrates including d-fructose, d-galactose, d-glucose, d-mannitol, d-xylose, trehalose, lactose, maltose, sucrose and starch as carbon sources and electron donors. It could reduce sulphate, thiosulphate and elemental sulphur to sulphide, but not sulphite. Fe (Ⅲ) citrate, ferrihydrite, haematite and goethite in the presence of glucose as the electron donor were also reduced. Acetate, butyrate, ethanol, CO2 and H2 were end products of glucose fermentation. The predominant cellular fatty acids were composed of C14 : 0, C16 : 0 and summed features containing C16 : 1 ω7c and/or iso-C15 : 0 2-OH and iso-C17 : 1 and/or anteiso-C17 : 1 B. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel strain was most closely related to

Fusibacter paucivorans

DSM 12116T (95.5 % sequence similarity). The genome size of strain Q10-2T was 5.0 Mb, with a G+C content of 37.4 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain Q10-2T and

F. paucivorans

DSM 12116T were 69.1 and 21.8 %, respectively. The combined genotypic and phenotypic data showed that strain Q10-2T represents a novel species of the genus

Fusibacter

, for which the name Fusibacter ferrireducens sp. nov. is proposed. The type strain is Q10-2T (=MCCC 1A16257T=KCTC 15906T).
Protein arginylation is regulated during SARS-CoV-2 infection
Authors: Macedo-da-Silva Janaina , Rosa-Fernandes Livia , de Moraes Gomes Vinicius , Santiago Verônica Feijoli , Molnár Catarina Maria Stanischesk , Barboza Bruno R. , de Sousa Edmarcia Elisa , Durigon Edison Luiz , Marinho Claudio R. F. , Wrenger Carsten , Marie Suely Kazue Nagahashi , Palmisano Giuseppe
Published: November 2021

In 2019, the world witnessed the onset of an unprecedented pandemic. In September 2021, the infection by SARS-CoV-2 had already been responsible for the death of more than 4 million people worldwide. Recently, we and other groups discovered that SARS-CoV-2 infection induces ER-stress and activation of unfolded protein response (UPR) pathway. The degradation of misfolded/unfolded proteins is an essential element of proteostasis and occurs mainly in lysosomes or proteasomes. The N-terminal arginylation of proteins is characterized as an inducer of ubiquitination and proteasomal degradation by the N-end rule pathway. Here we present, for the first time, data on the role of arginylation during SARS-CoV-2 infection. We studied the modulation of protein arginylation in Vero CCL-81 and Calu-3 cells infected after 2h, 6h, 12h, 24h, and 48h. A reanalysis of in vivo and in vitro public omics data combined with immunoblotting was performed to measure the levels of ATE1 and arginylated proteins. This regulation is seen specifically during infections by coronaviruses. We demonstrate that during SARS-CoV-2 infection there is an increase in the expression of the ATE1 enzyme associated with regulated levels of specific arginylated proteins. On the other hand, infected macrophages showed no ATE1 regulation. An important finding revealed that modulation of the N-end rule pathway differs between different types of infected cells. We also confirmed the potential of tannic acid to reduce viral load, and furthermore, to modulate ATE1 levels during infection. In addition, the arginylation inhibitor merbromin (MER) is also capable of both reducing viral load and reducing ATE1 levels. Taken together, these data show the importance of arginylation during the progression of SARS-CoV-2 infection and open the door for future studies that may unravel the role of ATE1 and its inhibitors in pathogen infection.
Neuronal responses in mouse inferior colliculus correlate with behavioral detection of amplitude modulated sound
Authors: van den Berg Maurits M. , Busscher Esmée , Borst J. Gerard G. , Wong Aaron B.
Published: November 2021

Amplitude modulation (AM) is a common feature of natural sounds, including speech and animal vocalizations. Here, we used operant conditioning andin vivoelectrophysiology to determine the AM detection threshold of mice as well as its underlying neuronal encoding. Mice were trained in a Go-NoGo task to detect the transition to AM within a noise stimulus designed to prevent the use of spectral side-bands or a change in intensity as alternative cues. Our results indicate that mice, in comparison with other species, detect high modulation frequencies up to 512 Hz well, but show much poorer performance at low frequencies. Ourin vivomultielectrode recordings in the inferior colliculus (IC) of both anesthetized and awake mice revealed a few single units with remarkable phase-locking ability to 512 Hz modulation, but not sufficient to explain the good behavioral detection at that frequency. Using a model of the population response that combined dimensionality reduction with threshold detection, we reproduced the general band-pass characteristics of behavioral detection based on a subset of neurons showing the largest firing rate change (both increase and decrease) in response to AM, suggesting that these neurons are instrumental in the behavioral detection of AM stimuli by the mice.

New and Noteworthy

The amplitude of natural sounds, including speech and animal vocalizations, often shows characteristic modulations. We examined the relationship between neuronal responses in the mouse inferior colliculus and the behavioral detection of amplitude modulation in sound, and modelled how the former can give rise to the latter. Our model suggests that behavioral detection can be well explained by the activity of a subset of neurons showing the largest firing rate changes in response to AM.
Marked enhancement of neutralizing antibody and IFN-γ T-cell responses by GX-19N DNA booster in mice primed with inactivated vaccine
Authors: Seo Yong Bok , Shin Duckhyang , Suh You Suk , Na Juyoung , Ryu Ji In , Sung Young Chul
Published: November 2021

In response to the COVID-19 pandemic, an unprecedented level of vaccine development has occurred. As a result, various COVID-19 vaccines have been approved for use. Among these, inactivated virus particle (VP) vaccines have been widely used worldwide, but additional vaccination strategies are needed because of the short duration of immune responses elicited by these vaccines. Here, we evaluated homologous and heterologous prime–boost regimens using a VP vaccine and GX-19N DNA vaccine for their ability to enhance the protective immune response against SARS-CoV-2. We demonstrated that a heterologous prime–boost regimen with the VP vaccine and GX-19N DNA vaccine resulted in enhanced SRBD- & N-specific antibody responses, compared to the homologous VP vaccine prime–boost vaccination. In addition, the neutralizing antibody response was significantly improved with the heterologous VP prime–DNA boost regimen, and the neutralizing antibody induced with the heterologous prime–boost regimen did not decrease against the SARS-CoV-2 variant of concern (VOC). The heterologous VP prime–DNA boost regimen not only significantly increased S- and N-specific IFN-γ T-cell responses, but also induced an equivalent level of T-cell response against SARS-CoV-2 VOCs. Our results provide new insights into prophylactic vaccination strategies for COVID-19 vaccination.
Life after mild traumatic brain injury: Widespread structural brain changes associated with psychological distress revealed with multimodal magnetic resonance imaging
Authors: Sibilia Francesca , Custer Rachel M. , Irimia Andrei , Sepehrband Farshid , Toga Arthur , Cabeen Ryan P. ,   the TRACK-TBI Investigators
Published: November 2021

Background

Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain damage and psychological distress after mild TBI (mTBI) using multimodal magnetic resonance imaging (MRI).

Methods

Eighty-nine mTBI patients from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress ∼6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. MRIs were acquired within 2 weeks post-injury. Perivascular spaces (PVS) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in Freesurfer; diffusion imaging indices and multi-fiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates.

Results

Perivascular space fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal- opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization.

Conclusions

This study shows how PVS, cortical, and microstructural damages can predict the onset of depression, anxiety, and somatization symptoms in mTBI patients.
Non-Invasive Prenatal Testing (NIPT) Results for Participants of the eXtraordinarY Babies Study: Screening, Counseling, Diagnosis, and Discordance
Authors: Howell Susan , Davis Shanlee M , Thompson Talia , Brown Mariah , Tanda Tanea , Kowal Karen , Alston Amanda , Ross Judith , Tartaglia Nicole R
Published: November 2021

Sex chromosome aneuploidies (SCAs), including 47,XXY, 47,XXX, 47,XYY, and supernumerary variants, occur collectively in approximately 1/500 livebirths. Clinical phenotypes are highly variable resulting in previous ascertainment rates have been estimated to be only 10-25% during a lifetime. Historically, prenatal SCA diagnoses were incidental findings, accounting for ≤10% of cases, with the majority of diagnoses occurring postnatally during evaluations for neurodevelopmental, medical, or infertility concerns. The initiation of noninvasive prenatal testing (NIPT) in 2012 and adoption into standardized obstetric care provides a unique opportunity to significantly increase prenatal ascertainment of SCAs. However, the impact NIPT has had on ascertainment of SCAs is understudied, particularly for those who may defer diagnostic testing until after birth. This study evaluates the timing of diagnostic testing following positive NIPT in 152 infants with SCAs and potential factors influencing this decision. Eighty-seven (57%) elected to defer diagnostic testing after a positive NIPT until birth, and 8% (7/87) of those confirmed after birth were found to have discordant results on postnatal diagnostic testing, most of which would have influenced genetic counseling.
IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S): a protocol for a randomised controlled feasibility trial of a combined behavioural and pharmacological support intervention
Authors: Mazumdar Papiya , Zavala Gerardo , Aslam Faiza , Muliyala Krishna Prasad , Chaturvedi Santosh Kumar , Kandasamy Arun , Nizami Asad , Haq Baha Ul , Kellar Ian , Jackson Cath , Thomson Heather , McDaid David , Siddiqi Kamran , Hewitt Catherine , Siddiqi Najma , Gilbody Simon , Murthy Pratima , Mdege Noreen
Published: November 2021

Introduction

The prevalence of smoking is high among people living with severe mental illness (SMI). Evidence on feasibility, acceptability and effectiveness of smoking cessation interventions among smokers with SMI is lacking, particularly in low- and middle-income countries. We aim to test the feasibility and acceptability of delivering an evidence-based intervention (i.e., the IMPACT 4S intervention) that is a combination of behavioural support and smoking cessation pharmacotherapies among adult smokers with SMI in India and Pakistan. We will also test the feasibility and acceptability of evaluating the intervention in a randomised controlled trial.

Methods

We will conduct a parallel, open label, randomised controlled feasibility trial among 172 (86 in each country) adult smokers with SMI in India and Pakistan. Participants will be allocated 1:1 to either Brief Advice or the IMPACT 4S intervention. BA comprises a single five-minute BA session on stopping smoking. The IMPACT 4S intervention comprises behavioural support delivered in up to 15 one-to-one, face-to-face or audio/video, counselling sessions, with each session lasting between 15 and 40 minutes; nicotine gum and/or bupropion; and breath carbon monoxide monitoring and feedback. The outcomes are recruitment rates, reasons for ineligibility/non-participation/non-consent of participants, length of time required to achieve required sample size, retention in study and treatments, intervention fidelity during delivery, smoking cessation pharmacotherapy adherence and data completeness. A process evaluation will also be conducted.

Ethics and dissemination

The study has been approved by the University of York’s Health Sciences Research Governance Committee; Health Ministry Screening Committee, India; the Ethics Committee (Behavioural Sciences Division), NIMHANS, Bangalore, India; National Bioethics Committee Pakistan and; Institutional Research and Ethics Forum of Rawalpindi Medical University, Pakistan. Feasibility study results will be disseminated through peer-review articles, and presentations at national and international conferences and policy-engagement forums.

Trial registration

ISRCTN34399445 (Updated 22/03/2021), ISRCTN Registry https://www.isrctn.com/
Point-of-care sample preparation and automated quantitative detection of Schistosoma haematobium using mobile phone microscopy
Authors: Armstrong Maxim , Harris Andrew R. , D’Ambrosio Michael V. , Coulibaly Jean T. , Essien-Baidoo Samuel , Ephraim Richard K.D. , Andrews Jason R. , Bogoch Isaac I. , Fletcher Daniel A.
Published: November 2021

Schistosoma haematobium continues to pose a significant public health burden despite ongoing global control efforts. One of several barriers to sustained control (and ultimately elimination) is the lack of access to highly sensitive diagnostic or screening tools that are inexpensive, rapid, and can be utilized at the point of sample collection. Here, we report an automated point-of-care diagnostic based on mobile phone microscopy that rapidly images and identifies S. haematobium eggs in urine samples. Parasite eggs are filtered from urine within a specialized, inexpensive cartridge that is then automatically imaged by the mobile phone microscope (the “SchistoScope”). Parasite eggs are captured at a constriction point in the tapered cartridge for easy imaging, and the automated quantification of eggs is obtained upon analysis of the images by an algorithm. We demonstrate S. haematobium egg detection with greater than 90% sensitivity and specificity using this device compared to the field gold standard of conventional filtration and microscopy. With simple sample preparation and image analysis on a mobile phone, the SchistoScope combines the diagnostic performance of conventional microscopy with the analytic performance of an expert technician. This portable device has the potential to provide rapid and quantitative diagnosis of S. haematobium to advance ongoing control efforts.
Primary Care Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in School-aged Children: Trends and Disparities During the COVID-19 Pandemic
Authors: Bannett Yair , Dahlen Alex , Huffman Lynne C. , Feldman Heidi M.
Published: November 2021

Importance

Little is known about changes in health care in the first year of the pandemic for the large population of school-aged children with attention-deficit/hyperactivity disorder (ADHD), who were especially impacted by lockdowns, school closures, and remote learning.

Objective

To assess temporal trends in rates of primary care provider (PCP) diagnosis and treatment of school-aged children with ADHD in the first year of the COVID-19 pandemic as compared to pre-pandemic years, and to investigate disparities in care.

Method

We retrospectively analyzed electronic health records from all primary care visits (in-person and telehealth) of children ages 6-17 years seen between 01/2016 and 03/2021 in a community-based primary healthcare network in California (n=77,298 patients). Study Outcomes: (1) # of primary care visits, (2) # of visits with ADHD diagnosis (ADHD-related visits), (3) # of first ADHD diagnoses, (4) # of PCP prescriptions for ADHD medications (stimulants, alpha-2 agonists, atomoxetine), (5) # of first PCP prescriptions of ADHD medications. Interrupted time-series analysis evaluated changes in rates of study outcomes during 4 quarters of the pandemic year (3/15/2020-3/15/2021) compared to pre-pandemic years. Patient demographic characteristics were compared pre-pandemic to pandemic year.

Results

In the first quarter (Q1) of the pandemic year, all primary care visits dropped by 62% (CI 54.9-67.2%); ADHD-related visits dropped by 33% (95% CI 22.2-43.6%). In Q2-4, while all primary care visits remained significantly below pre-pandemic rates, ADHD-related visits returned to pre-pandemic rates. Conversely, rates of first ADHD diagnoses remained at half of pre-pandemic rates throughout the year (Q1-4). ADHD medication prescription rates remained stable throughout the pandemic year. The proportion of patients living in low-income neighborhoods who received ADHD-related care (ADHD-related visits and first ADHD diagnoses) were lower during the pandemic year compared to pre-pandemic years. Females comprised a higher proportion of first ADHD diagnoses compared to pre-pandemic years (34% vs. 28%, absolute standardized difference=0.13, p=0.03).

Conclusion

Ongoing treatment for school-aged children with ADHD was maintained during the pandemic, especially in children from high-income families. Socioeconomic differences in ADHD-related care emphasize the need to improve access to care for all children with ADHD in the ongoing pandemic and beyond.
Contribution of markers of adiposopathy and adipose cell size in predicting insulin resistance in women of varying age and adiposity
Authors: Tremblay Eve-Julie , Tchernof André , Pelletier Mélissa , Chabot Nicolas , Joanisse Denis R. , Mauriège Pascale
Published: November 2021

Adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m2). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participant sample.
Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation
Authors: Cutler Kevin J. , Stringer Carsen , Wiggins Paul A. , Mougous Joseph D.
Published: November 2021

Advances in microscopy hold great promise for allowing quantitative and precise readouts of morphological and molecular phenomena at the single cell level in bacteria. However, the potential of this approach is ultimately limited by the availability of methods to perform unbiased cell segmentation, defined as the ability to faithfully identify cells independent of their morphology or optical characteristics. In this study, we present a new algorithm, Omnipose, which accurately segments samples that present significant challenges to current algorithms, including mixed bacterial cultures, antibiotic-treated cells, and cells of extended or branched morphology. We show that Omnipose achieves generality and performance beyond leading algorithms and its predecessor, Cellpose, by virtue of unique neural network outputs such as the gradient of the distance field. Finally, we demonstrate the utility of Omnipose in the characterization of extreme morphological phenotypes that arise during interbacterial antagonism and on the segmentation of non-bacterial objects. Our results distinguish Omnipose as a uniquely powerful tool for answering diverse questions in bacterial cell biology.
What is the role and value of facilitation within sessions of Case-based Learning (CBL) in undergraduate medicine: Protocol for a scoping review of the literature
Authors: Berg C. , Hammond L. , Howard B. , Diug B. , Sorinola O.
Published: November 2021

Background

CBL involves students working within groups to solve clinical and non-clinical cases which enables the development of communication and team-working skills and promotes a deeper understanding of relevant clinical knowledge. CBL sessions are traditionally supported by an in-person facilitator in face to face settings. The recent COVID-19 pandemic has necessitated moves to online learning in many areas, one of which is CBL, providing good reason to consider the role of the facilitator in CBL and digital opportunities to augment facilitation.

Aims

To understand the role of facilitation within CBL teaching (in face to face and online settings) and the impact that different approaches to facilitation can have on outcomes including student experience and engagement.

Methods

A scoping review will be conducted of four main academic and medical databases: MedLine, Scopus, Excerpta Medica Database (EMBASE) and Education Research Complete (ERC) using a search strategy built around ‘Undergraduate medical students’ (Population), ‘Approaches to facilitation’ (Concept) and ‘Case-based learning’ (Context). Articles will be selected according to pre-determined inclusion and exclusion criteria, with scope for the selection criteria to further develop. Charting from included full text articles will encompass research approach, approach to facilitation and findings about facilitation. A constructivist conceptual framework will be used to guide the synthesis.

Conclusions

Overall, it is hoped that this review will be able to inform the role of facilitation within CBL sessions and the potential impact that this has on attainment, engagement and satisfaction of students, as well as their development of skills such as: teamworking, communication and problem solving.