bluuebunny/crossref_metadata_2025 huggingface dataset:
PROLONGED LENGTH OF HOSPITAL STAY AND ASSOCIATED FACTORS AMONG PATIENTS ADMITTED AT A SURGICAL WARD IN SELECTED PUBLIC HOSPITALS ARSI ZONE, OROMIA, ETHIOPIA, 2022
Authors: Fetene Deriba , Tekalegn Yohanis , Abdela Jabir , Aynalem Amdehiwot , Bekele Gezahegn , Molla Ezedin
Published: October 2022

Background

Prolonged length of hospital stay is the most common indicator of poor quality of health care and inefficient utilization of hospital resources. Prolonged hospital stay associated with increased mortality, hospital-acquired infection, and unnecessary utilization of hospital bed and other resources. Predicting length of hospital stay facilitates resource designing and initiates quality improvement activities. However, data regarding the prolonged length of hospital stays, and associated factors were a scarce in Ethiopia.

Methods

A hospital-based cross-sectional study was conducted on a sample of 316 adult patients from December 1 to January 10, 2022. A consecutive sampling technique was used during sampling procedure. A structured questionnaire was used to collect data regarding sociodemographic factors, clinical factors, medication factors, and behavioral factors through interview, medical record review and by using check list. The data was entered into the epidata4.6 version and exported to SPSS Version25 for binary logistic regression analysis. To identify factors associated with outcome variable, candidate variables (p<0.25) were fitted to multivariable analysis, and those with P-values<0.05 were considered as factors associated with prolonged length of hospital stay. Odds ratio with corresponding 95% CI was used to indicate the strength of association of variables with prolonged length of hospital stay.

Result

One fourth (24.7%) of the study participants experienced a prolonged length of stay at surgical ward. The odd of a prolonged length of hospital stay was high among patients who had comorbid condition [AOR=4.59, at 95% CI= (2.46-8.56)], who developed surgical site infection [AOR=5.02 at 95% CI= 1.97-12.80)], and who developed hospital acquired pneumonia during hospital stay [AOR= 3.43 at 95% CI= (1.36-8.64)].

Conclusion and recommendation

Near to quarter of the study participants’ experienced prolonged length of hospital stays. Comorbid condition, surgical site infection, and hospital acquired pneumonia were factors associated with prolonged length of hospital stay at surgical ward. Quality of care could be improved by adjusting surgical ward environment to prevent hospital acquired infection and focus on managing complication after surgery. Health care provider should be educating surgical patient about the risk of comorbidity on wound healing and early diagnosis and prevention of comorbid condition.
A common variant that alters SUN1 degradation associates with hepatic steatosis and metabolic traits in multiple cohorts
Authors: Upadhyay Kapil K. , Du Xiaomeng , Chen Yanhua , Zhao Raymond , Speliotes Elizabeth K. , Brady Graham F.
Published: October 2022

Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) represent a genetically and phenotypically diverse entity with no approved therapy, making it imperative to define the spectrum of pathways contributing to its pathogenesis. Rare variants in genes encoding nuclear envelope proteins cause lipodystrophy that includes early-onset NASH; we hypothesized that common variants in nuclear envelope-related genes might also contribute to hepatic steatosis and NASH. In an association meta-analysis of nuclear envelope-related coding variants in three large cohorts (N>120,000 participants), rs6461378 (SUN1H118Y) was the top steatosis-associated variant (P<0.001). In ancestrally distinct validation cohorts, rs6461378 positively associated with NASH-related metabolic traits including increased serum fatty acids, decreased HDL, type 2 diabetes, hypertension, and cardiovascular disease. SUN1 H118Y was subject to increased proteasomal degradation relative to wild-type SUN1 in Huh7 cells, and SUN1 H118Y-expressing cells exhibited insulin resistance and increased lipid accumulation. Collectively, these data support a potential causal role for rs6461378 in NASH and metabolic disease.

Lay Summary

A common genetic variant that leads to an amino acid change in the nuclear envelope protein SUN1 was found to positively associate with hepatic steatosis in a meta-analysis of genomic data from multiple large cohorts. Follow-up studies in separate validation cohorts demonstrated strong positive associations with metabolic traits that are linked to nonalcoholic fatty liver disease, including insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease. Testing of this variant in cell culture demonstrated biochemical differences from wild-type SUN1, with increased proteasomal degradation of the H118Y variant, decreased sensitivity to insulin, and increased lipid accumulation, suggesting that this is a functional variant with a potential causal role in human disease.
TUBB4Bvariants specifically impact ciliary function, causing a ciliopathic spectrum
Authors: Mechaussier Sabrina , Dodd Daniel O , Yeyati Patricia L , McPhie Fraser , Attard Thomas , Shoemark Amelia , Gupta Deepesh K , Zariwala Maimoona A , Legendre Marie , Bracht Diana , Wallmeier Julia , Gui Miao , Anderson Jacob R , Fassad Mahmoud R , Parry David A , Tennant Peter A , Meynert Alison , Wheway Gabrielle , Fares-Taie Lucas , Black Holly A , Mitri-Frangieh Rana , Faucon Catherine , Kaplan Josseline , Patel Mitali , McKie Lisa , Megaw Roly , Gatsogiannis Christos , Mohamed Mai A , Aitken Stuart , Gautier Philippe , Reinholt Finn R , Hirst Robert A , O’Callaghan Chris , Heimdal Ketil , Bottier Mathieu , Escudier Estelle , Crowley Suzanne , Descartes Maria , Jabs Ethylin W , Kenia Priti , Amiel Jeanne , Blümlein Ulrike , Rogers Andrew , Wambach Jennifer A , Wegner Daniel J , Fulton Anne B , Kenna Margaret , Rosenfeld Margaret , Holm Ingrid A , Quigley Alan , Cassidy Diana M , von Kriegsheim Alex ,   Scottish Genomes Partnership,   Genomics England Research Consortium,   Undiagnosed Diseases Network, Papon Jean-Francois , Pasquier Laurent , Murris Marlène S , Chalmers James D , Hogg Clare , Macleod Kenneth , Urquhart Don S , Unger Stefan , Aitman Timothy J , Amselem Serge , Rozet Jean-Michel , Amselem Serge , Leigh Margaret W , Knowles Michael R. , Omran Heymut , Mitchison Hannah M , Brown Alan , Marsh Joseph A , Welburn Julie P I , Horani Amjad , Rozet Jean-Michel , Perrault Isabelle , Mill Pleasantine
Published: October 2022

Cilia are small microtubule-based structures found on the surface of most mammalian cells, which have key sensory and sometimes motile functions. Primary ciliary dyskinesia (PCD) is a type of ciliopathy caused by defects in motile cilia. The genetic basis of PCD is only partially understood. Studying a cohort of 11 human patients with PCD, we find thatde novomutations inTUBB4B, a beta tubulin isotype, cause three distinct classes of ciliopathic disease.In vivostudies in mice show thatTubb4bplays a specific role in cilia, building centrioles and axonemes in multiciliated cells. Examining the effects of specific TUBB4B variants in cells and in mice, we further demonstrate that distinctTUBB4Bmutations differentially affect microtubule dynamics and cilia formation in a dominant negative manner. Finally, structure-function studies reveal that different TUBB4B mutations disrupt distinct tubulin interfaces. Importantly, these molecular differences correlate with disease features. We show that tubulin heterodimer-impairing TUBB4B variants underlie nonsyndromic PCD, whilst additional renal and sensorineural ciliopathic features in a syndromic PCD subtype arise from microtubule lumenal interface-impaired TUBB4B variants. These findings suggest that specific tubulin isotypes have distinct and non-redundant subcellular functions, and demonstrate that human tubulinopathies can be drivers of ciliopathic syndromes.
Health System Determinants of Hypertension Care and Outcomes in Sub-Saharan Africa: A Systematic Review
Authors: Byiringiro Samuel , Ogungbe Oluwabunmi , Commodore-Mensah Yvonne , Adeleye Khadijat , Sarfo Fred Stephen , Himmelfarb Cheryl R.
Published: October 2022

Background

Hypertension is a significant global health problem, particularly in Sub-Saharan Africa (SSA). Despite the effectiveness of medications and lifestyle interventions in reducing blood pressure, shortfalls across health systems continue to impede progress in achieving optimal hypertension control rates. The current review explores health system factors contributing to hypertension outcomes in SSA.

Methods

The World Health Organization health systems framework guided the literature search and discussion of findings. We searched PubMed, CINAHL, and Embase databases for studies published between January 2010 and June 2022 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed studies for risk of bias using the tools from Joanna Briggs Institute.

Results

Thirty-nine studies clustered in 10 SSA countries met inclusion criteria. Health system determinants included human resource factors such as providers’ knowledge and adherence to hypertension treatment guidelines (n=21) and task sharing and shifting strategies (n=10). The second health system factors explored in service delivery were the health facility type and capacity (n=7) and hypertension service accessibility by cost, place, and time of services (n=15). A quarter of the included studies explored supply chain management for access to essential equipment and medicines. An additional set of studies addressed quality improvement strategies involving cross-integration of services (n=7) and various strategies of gauging the systems for better hypertension outcomes (n=8).

Conclusion

A combination of multiple rather than solo system interventions may yield significant improvements in blood pressure outcomes. Health information management and leadership involvement were less explored. Additional research on health system determinants of hypertension is needed to drive global improvements in hypertension outcomes. Future research would benefit from more rigorous implementation type interventional studies comprehensively assessing health system factors that contribute to better hypertension outcomes.
Lessons from web scraping coroners’ Prevention of Future Deaths reports
Authors: Zhang Qingyang , Richards Georgia C.
Published: October 2022

In England and Wales, coroners are required to write Prevention of Future Deaths reports (PFDs) when a death is deemed preventable so that action is taken to avert similar deaths. Since July 2013, PFDs have been openly available via the Courts and Tribunals Judiciary website (https://www.judiciary.uk/subject/prevention-of-future-deaths/). However, their presentation has been insufficient to identify trends and learn lessons. We designed a web scraper to create the Preventable Deaths Tracker (https://preventabledeathstracker.net/). On 22 June 2022, 4001 PFDs were scraped, analysed, and compared to the Office of National Statistics (ONS) preventable mortality statistics. This commentary summarises the key findings and offers recommendations to improve the PFD system so lessons can be learnt to avert preventable deaths.
Quantitative and qualitative effects of live music medicine on anxiety and depression in cancer inpatients
Authors: Rosenheck Michael , Hirsh Robert
Published: October 2022

Background

A growing body of literature suggests that music medicine may decrease anxiety and depression in cancer patients, but the mechanism by which this happens remains speculative. This study analyzes the underlying thematic perspectives by utilizing both quantitative and qualitative assessments. Therefore, the goal of this study is to determine the quantitative effects and underlying thematic perspectives of music medicine on anxiety and depression in cancer inpatients.

Methods and findings

Twenty-four cancer inpatients participated in this prospective cohort study to measure the effects of a private, fifteen-minute, live guitar/singing performance on anxiety and depression. Questions modified from the Hospital Anxiety and Depression Scale (HADS) and a written free response section were used. Independent from age, gender, and relationship to music, music medicine significantly increased patients’ cheerfulness, ability to laugh, relaxation, and decreased worrying thoughts. There was also a trend towards decreased tension, restlessness, feeling slowed down, and increased excitement for the future that failed to reach statistical significance. The most frequently used words within the free response sections were made into a word cloud with the three most common words being music, listening, and made.

Conclusion

This article not only illustrates that music medicine decreases several elements of anxiety and depression in cancer inpatients, but also highlights music’s physiological effects, aesthetic and potentially transcendent properties, intrinsic value, and memorability, through use of a word cloud. Music medicine is a safe and inexpensive mood augmenter that could be more widely used.
The Utility of Cognitive Testing to Predict Real World Commercial Driving Risk
Authors: Scott Daniel , Atkin Alice Elizabeth , Granley Aaron , Singhal Anthony
Published: October 2022

Background

Driving is a complex task which requires numerous cognitive and sensorimotor skills to be performed safely. On-road driver evaluation can identify unsafe drivers but can also be expensive, risky, and time-consuming. Poor performance on off-road measures of cognition and sensorimotor control has been shown to predict on-road performance in privately-licensed light vehicle drivers, but commercial drivers have not yet been studied despite such vehicles generally being larger and heavier, thus increasing risks from unsafe driving.

Method

Commercially-licensed truck, bus, and light vehicle drivers undertook the tablet-based Vitals cognitive screening tool, which measures reaction time, judgement, memory, and sensorimotor control, and also undertook an on-road driving evaluation using their vehicle. Accuracy and reliability of the Vitals tasks on predicting road test outcomes were investigated using a trichotomous classifier (pass, fail, borderline), and task performance was analyzed depending on vehicle type and road test outcome.

Results

Performance on the Vitals tasks predicted on-road performance across all vehicle types. Participants who failed their on-road evaluation also demonstrated lower success on the Judgement task, fewer correctly replicated shapes on the Memory task, and less time on-target in the Control task compared to those who passed.

Conclusion

Performance on cognitive and sensorimotor tasks is a good predictor of future driving performance and driver safety for commercially-licensed drivers. Regardless of vehicle type, stakeholders can use cognitive measures from the Vitals assessment to identify an increased driving risk. Use of the Vitals as a screening tool prior to on-road evaluation can benefit both drivers and evaluators.
Interpretable Deep Learning for Improving Cancer Patient Survival Based on Personal Transcriptomes
Authors: Sun Bo , Chen Liang
Published: October 2022

Precision medicine chooses the optimal drug for a patient by considering individual differences. With the tremendous amount of data accumulated for cancers, we develop an interpretable neural network to predict cancer patient survival based on drug prescriptions and personal transcriptomes (CancerIDP). The deep learning model achieves 96% classification accuracy in distinguishing short-lived from long-lived patients. The Pearson correlation between predicted and actual months-to-death values is as high as 0.937. About 27.4% of patients may survive longer with an alternative medicine chosen by our deep learning model. The median survival time of all patients can increase by 3.9 months. Our interpretable neural network model reveals the most discriminating pathways in the decision-making process, which will further facilitate mechanistic studies of drug development for cancers.
Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or re-initiation in sub- Saharan Africa: a systematic review
Authors: Benade Mariet , Maskew Mhairi , Juntunen Allison , Rosen Sydney
Published: October 2022

Background

As countries in sub-Saharan Africa have scaled up access to antiretroviral therapy (ART) for HIV, patient attrition rates of up to 30% per year have created a large pool of individuals who initiate treatment with prior ART experience (non-naïve re-initiators). Little is known about the proportion of non-naïve re-initiators within the population presenting for treatment initiation.

Methods

We conducted a comprehensive, rapid review of recent peer-reviewed reports that presented data on proportions of adult patients initiating ART who were treatment naïve and non-naive in sub-Saharan Africa. Searching PubMed, EMBASE, Web of Science, and international conference abstracts, we sought studies published after 1 January 2018 with data collected after January 2016, when universal HIV treatment access became the norm. We included clinical trials and observational studies and accepted self-report, laboratory discernment of antiretroviral metabolites, or viral suppression at initiation or previously reported in the medical record as evidence of prior exposure. We report results of each eligible study and identify gaps in the literature.

Results

Of 1,782 articles returned in our initial search, we found nine, describing ten cohorts, that contained sufficient information for the review, of which half were from South Africa. The proportion of the study samples with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample among self-reported naïve patients). The vast majority of studies that were screened did not report proportions of initiators who were non-naïve, and among the few that did, the metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.

Conclusion

The proportion of patients initiating HIV treatment who are truly ART-naïve is not well documented in the literature. From the studies identified, it seems likely that 20% to 50%—and likely at least 30%—of ART patients who present for ART are re-initiators. Standard reporting metrics and diligence in reporting this characteristic of ART initiation cohorts are needed, as is research to understand the reluctance of patients to report prior ART exposure.
Relationships between the auditory nerve’s ability to recover from neural adaptation, cortical encoding of and perceptual sensitivity to within-channel temporal gaps in postlingually deafened adult cochlear implant users
Authors: He Shuman , Yuan Yi , Skidmore Jeffrey
Published: October 2022

Objective

This study assessed the relationships between the auditory nerve’s ability to recovery from neural adaptation, cortical encoding of and perceptual sensitivity to within-channel temporal gaps in postlingually deafened adult cochlear implant (CI) users.

Design

Study participants included 11 postlingually deafened adults with Cochlear™ Nucleus® devices, including three bilaterally implanted participants. In each participant, recovery from neural adaptation of the auditory nerve (AN) was measured using electrophysiological measures of the electrically evoked compound action potential (eCAP) at up to four electrode locations. The electrode pair with the largest difference in the speed of adaptation recovery was selected for assessing within-channel temporal gap detection threshold (GDT). GDTs were measured using both psychophysical and electrophysiological procedures. Psychophysical GDTs were evaluated using a three-alternative, forced-choice procedure, targeting 79.4% correct on the psychometric function. Electrophysiological GDTs were measured using the electrically evoked auditory change complex (eACC) evoked by electrical pulse trains that contained temporal gaps. Objective GDT was defined as the shortest temporal gap that could evoke an eACC. Related-samples Wilcoxon Signed Rank testwas used to compare psychophysical GDTs and objective GDTs measured at all electrode locations. It was also used to compare psychophysical GDTs and objective GDTs measured at the two electrode locations with different speeds or amounts of adaptation recovery of the AN. A Kendall Rank correlation test was used to assess the correlation between GDTs measured using psychophysical or electrophysiological procedures.

Results

Objective GDTs were significantly larger than those measured using psychophysical procedures. There was a significant correlation between objective and psychophysical GDTs. GDTs could not be predicted based on the amount or the speed of adaptation recovery of the AN.

Conclusions

Electrophysiological measure of the eACC can potentially be used to assess within-channel GDT in CI users who cannot provide reliable behavioral responses. The difference in adaptation recovery of the AN is not the primary factor accounting for the across-electrode variation in GDT in individual CI users.
Development and evaluation of a live birth prediction model for evaluating human blastocysts: a retrospective study
Authors: Liu Hang , Zhang Zhuoran , Gu Yifan , Dai Changsheng , Shan Guanqiao , Song Haocong , Li Daniel , Chen Wenyuan , Lin Ge , Sun Yu
Published: October 2022

Background

In infertility treatment, blastocyst morphological grading is commonly used in clinical practice for blastocyst evaluation and selection, but has shown limited predictive power on live birth outcomes of blastocysts. To improve live birth prediction, a number of artificial intelligence (AI) models have been established. Most existing AI models for blastocyst evaluation only used images for live birth prediction, and the area under the receiver operating characteristic (ROC) curve (AUC) achieved by these models has plateaued at ∼0.65.

Methods

This study proposed a multi-modal blastocyst evaluation method using both blastocyst images and patient couple’s clinical features (e.g., maternal age, hormone profiles, endometrium thickness, and semen quality) to predict live birth outcomes of human blastocysts. To utilize the multi-modal data, we developed a new AI model consisting of a convolutional neural network (CNN) to process blastocyst images and a multi-layer perceptron to process patient couple’s clinical features. The dataset used in this study consists of 17,580 blastocysts with known live birth outcomes, blastocyst images, and patient couple’s clinical features.

Results

This study achieved an AUC of 0.77 for live birth prediction, which significantly outperforms related works in the literature. Sixteen out of 103 clinical features were identified to be predictors of live birth outcomes and helped improve live birth prediction. Among these features, maternal age, the day of blastocyst transfer, antral follicle count, retrieved oocyte number, and endometrium thickness measured before transfer are the top five features contributing to live birth prediction. Heatmaps showed that the CNN in the AI model mainly focuses on image regions of inner cell mass and trophectoderm (TE) for live birth prediction, and the contribution of TE-related features was greater in the CNN trained with the inclusion of patient couple’s clinical features compared with the CNN trained with blastocyst images alone.

Conclusions

The results suggest that the inclusion of patient couple’s clinical features along with blastocyst images increases live birth prediction accuracy.

Funding

Natural Sciences and Engineering Research Council of Canada and the Canada Research Chairs Program.
Incidence and predictors of relapse among children with nephrotic syndrome at Assosa zone hospitals, Benishangul Gumuz Region, Northwest Ethiopia, 2022
Authors: Gashaw Yegoraw , Tekeba Berhan , Terefe Bewuketu , Tezera Nega , Wodajo Seid
Published: October 2022

Background

Relapse is the major problem in children with nephrotic syndrome and leads to a substantial burden on the patient and family worldwide, particularly in resource-limited countries like Ethiopia. However, little is known about the incidence of relapse and its predictors among children with nephrotic syndrome in the study area.

Methods

An institution-based retrospective follow-up study was conducted among 354 randomly selected nephrotic syndrome patients admitted from April 2017 to March 2022. Data entry was carried out using Epi-data manager version 4.6.0.6 and Stata software version 14 for data cleaning and analysis. Cox-proportional hazard models were used to identify predictors of relapse. Any variable with a p-value < 0.25 in the bivariable was taken into the multivariable analysis, and then the association and statistical significance were declared at P≤ 0.05.

Results

More than half, 55.8% (82/147), of relapses were recorded in the first six months of follow-up. The incidence of relapse was 82.3 per 1000 child-month-observations, with an overall risk of 1785.9 child-month-observations. In children with nephrotic syndrome, the presence of wasting malnutrition [AHR = 1.93, 95% CI 1.28–2.90], acute respiratory tract infections [AHR = 1.79, 95% CI 1.19–2.71], elevated triglyceride levels [AHR = 2.74, 95% CI 1.48–5.07], and low serum albumin levels [AHR = 4.34, 95% CI 22.18–8.64] were predictors of relapse.

Conclusion and Recommendations

The incidence of relapse among nephrotic syndrome patients was high. The independent predictors of relapse in children with nephrotic syndrome were the presence of acute respiratory tract infections, wasting malnutrition at admission, low serum albumin levels, and elevated serum triglyceride levels. Therefore, intervention to reduce and control earlier relapse should focus on preventing relapse-related complications.
Neonatal resuscitation: an observational study assessing the readiness of service providers in Nepal
Authors: Clark Robert B , Chalise Mala , Dhungana Ranjan P
Published: October 2022

A significant proportion of neonatal mortality, a major public health challenge in low- and middle-income countries, can be attributed to intrapartum-related hypoxic events. This study seeks to assess the determinants of health care providers’ competence in providing newborn resuscitation. A cross-sectional survey of 154 health facilities in Nepal was done. This nested study evaluated the newborn resuscitation knowledge and skills of 462 health care providers by individually assessing a delivery using a 22-item clinical practice observation tool and administering the standard 18-item Helping Babies Breathe Knowledge Check

Significant predictors of provider knowledge included: province (0.085 points higher in Bagmati province, p=0.018); mean availability of essential utilities and resuscitation aids (0.173 points, p<0.001 and 0.187, p= 0.02 respectively); participation in – Latter-day Saint Charities – Safa Sunaulo Nepal (LDSC/SSN) newborn resuscitation training, scale-up and skill retention program (0.676 units higher, p<0.001); and qualifications (0.136 points higher among health providers with Bachelor of Nursing degree, p<0.001, 0.072 points higher among providers with Masters in Nursing degree, p= 0.010 and 0.110 units higher among providers with Senior Auxiliary Nursing Midwife degree,, p=0.001).

Significant factors associated with resuscitation skill included province (0.056 units higher in province 1, p= 0.015 and 0.037 units higher in Sudurpaschim province, p=0.034); delivery caseload (0.066 units higher mean skill score in health facilities with average monthly delivery of more than 120, p= 0.011); availability of newborn resuscitation practice aids (0.093 units higher score in health facilities with resuscitation practice aids, p= 0.008); and participation in LDSC/SSN newborn resuscitation training, scale-up and skill retention program (0.968 units, p< 0.001).

Participation in the LDSC/SSN’ skill retention program was the best predictor of newborn resuscitation knowledge and skills. The LDSC/SSN model of newborn resuscitation training, scale up and skill retention could be one potential cost-effective model to address gaps in resuscitation knowledge and skills among service providers.
Parental Preferences and Reasons for COVID-19 Vaccination Among Their Children
Authors: Sehgal Neil K. R. , Rader Benjamin , Gertz Autumn , Astley Christina M. , Brownstein John S.
Published: October 2022

Background

COVID-19 vaccination rates among children have stalled, while new coronavirus strains continue to emerge. To improve child vaccination rates, policymakers must better understand parental preferences and reasons for COVID-19 vaccination among their children.

Methods and Findings

Cross-sectional surveys were administered online to 30,174 US parents with at least one child of COVID-19 vaccine eligible age (5-17 years) between January 1 and May 9, 2022. Participants self-reported willingness to vaccinate their child and reasons for hesitancy, and answered additional questions about demographics, pandemic related behavior, and vaccination status. Willingness to vaccinate a child for COVID-19 was strongly associated with parental vaccination status (multivariate odds ratio 97.9, 95% confidence interval 86.9-111.0). The majority of fully vaccinated (86%) and unvaccinated (84%) parents reported concordant vaccination preferences for their eligible child. Age and education had differing relationships by vaccination status, with higher age and education positively associated with willingness among vaccinated parents. Among all parents hesitant to vaccinate their children, the two most frequently reported reasons were possible side effects (47%) and that vaccines are too new (44%). Among hesitant parents, parental vaccination status was inversely associated with reported lack of trust in government (p<.001) and scientists (p<.001). Cluster analysis identified three groups of hesitant parents based on their reasons for hesitance to vaccinate, with distinct concerns that may be obscured when analyzed in aggregate.

Conclusion

Factors associated with willingness to vaccinate children and reasons for hesitancy may inform targeted approaches to increase vaccination.
The relationship between electrophysiological measures of the electrically evoked compound action potential and cochlear implant speech perception outcomes
Authors: Skidmore Jeffrey , Oleson Jacob J. , Yuan Yi , He Shuman
Published: October 2022

Objective

This study assessed the relationship between electrophysiological measures of the electrically evoked compound action potential (eCAP) and speech perception scores measured in quiet and in noise in post-lingually deafened adult cochlear implant (CI) users. It tested the hypothesis that how well the auditory nerve (AN) responds to electrical stimulation is important for speech perception with a CI in challenging listening conditions.

Design

Study participants included 24 post-lingually deafened adult CI users. All participants used Cochlear® Nucleus™ CIs in their test ears. In each participant, eCAPs were measured at multiple electrode locations in response to single-pulse, paired-pulse, and pulse-train stimuli. Independent variables included six parameters calculated from the eCAP recordings: the electrode-neuron interface (ENI) index, the neural adaptation (NA) ratio, NA speed, the adaptation recovery (AR) ratio, AR speed, and the amplitude modulation (AM) ratio. The ENI index quantified the effectiveness of the CI electrodes in stimulating the targeted AN fibers. The NA ratio indicated the amount of NA at the AN caused by a train of constant-amplitude pulses. NA speed was defined as the speed/rate of NA. The AR ratio estimated the amount of recovery from NA at a fixed time point after the cessation of pulse-train stimulation. AR speed referred to the speed of recovery from NA caused by previous pulse-train stimulation. The AM ratio provided a measure of AN sensitivity to AM cues. Participants’ speech perception scores were measured using Consonant-Nucleus-Consonant (CNC) word lists and AzBio sentences presented in quiet, as well as in noise at signal-to-noise ratios (SNRs) of +10 and +5 dB. Predictive models were created for each speech measure to identify eCAP parameters with meaningful predictive power.

Results

The ENI index and AR speed had significant bivariate relationships with speech perception scores measured in this study, while the NA ratio, NA speed, the AR ratio, and the AM ratio did not. The ENI index was identified as the only eCAP parameter that had unique predictive power for each of the speech test results. The amount of variance in speech perception scores (both CNC words and AzBio sentences) explained by the eCAP parameters increased with increased difficulty in the listening condition. Over half of the variance in speech perception scores measured in +5 dB SNR noise (both CNC words and AzBio sentences) was explained by a model with only three eCAP parameters: the ENI index, NA speed, and AR speed.

Conclusions

The ENI index is the most informative predictor for speech perception performance in CI users. The response characteristics of the AN to electrical stimulation is more important for speech perception with a CI in noise than it is in quiet.
Oxidative and cardiovascular stress among professional divers in Egypt
Authors: Salah Hanie , El-Gazzar Ragaa M. , Abd El-Wahab Ekram W. , Charl Fahmy
Published: October 2022

Objectives

Professional divers are exposed to unique multifactorial hazards in their working environment and cardiovascular effects are tremendous. Cardiovascular events are aggravated by diving-induced oxidative stress and account for one fourth of diving fatalities. The aim of this study was to assess the oxidative and cardiovascular stress in a group of professional divers in Alexandria, Egypt using a panel of biomarkers.

Methods

A comparative cross-sectional study was conducted between June 2017 and May 2018 at the General Naval Hospital in Alexandria. We recruited 50 professional divers (n=50) and a comparison group of 50 marine seafarers sharing similar maritime environments. Participants were clinically evaluated by electrocardiography (ECG) and assessment of some trace metals (Fe+, Cu+and Zn+) and oxidative stress biomarkers (OSBMs; MDA, TAS, GST, GSH, GR, GPx, SOD and CAT).Results: Significant ECG abnormalities including short corrected QT interval, sinus bradycardia, left ventricular hypertrophy, early repolarization, 1stdegree heart block, intraventricular conduction defect were obvious among divers. The mean levels of FBG, LDH-C, Na+, Ca+, trace metals and OSBMs were significantly higher among professional divers compared to the marine seafarers (p< 0.5).

Conclusion

The risk of CVD in professional divers is alarmingly high and possibly contributed by OS. Including cardiovascular risk assessment in divers’ periodic examinations is of utmost importance.
Association of viral variant and vaccination status with the occurrence of symptoms compatible with post-acute sequelae after primary SARS-CoV-2 infection
Authors: Kahlert Christian R. , Strahm Carol , Güsewell Sabine , Cusini Alexia , Brucher Angela , Goppel Stephan , Möller J. Carsten , Ortner Manuela , Ruetti Markus , Stocker Reto , Vuichard-Gysin Danielle , Besold Ulrike , McGeer Allison , Risch Lorenz , Friedl Andrée , Schlegel Matthias , Vernazza Pietro , Kuster Stefan P. , Kohler Philipp ,   SURPRISE Study Group
Published: October 2022

Importance

Disentangling the effects of different SARS-CoV-2 variants and of vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and potentially reduce the future burden of PASC.

Objective

To determine the association of primary SARS-CoV-2 infection on the frequency of PASC symptoms by viral variant and vaccination status.

Design

Cross-sectional questionnaire and SARS-CoV-2 serology (May/June 2022) performed within a prospective healthcare worker cohort (SURPRISE study).

Setting

Multicenter study in nine healthcare networks from North-Eastern Switzerland.

Participants

Volunteer sample of healthcare workers (HCW) from participating institutions. Of approximately 20’000 eligible participants, 3’870 registered for the cohort and 2’912 were included in this analysis.

Exposures

SARS-CoV-2 infection documented by positive nasopharyngeal swab (>4 weeks ago), stratified by viral variant and vaccination status at time of infection, compared to absence of documented infection (no positive swab, negative serology).

Main Outcome

Sum score of eighteen self-reported PASC symptoms.

Results

Among 2’912 participants (median age 44 years, 81.3% female), SARS-CoV-2 infection was reported by 1’685 (55.9%) participants, thereof 315 (18.7%) during Wild-type, 288 (17.1%) during Alpha/Delta, and 1’082 (64.2%) during Omicron circulation. Mean symptom number in previously infected participants significantly exceeded that of uninfected controls (0.39), but decreased with recency of the viral variant: 1.12 (p<0.001) for Wild-type (median time since infection 18.5 months), 0.67 (p<0.001) for Alpha/Delta (6.6 months), and 0.52 (p=0.005) for Omicron BA.1 (3.1 months) infected participants. After Omicron BA.1 infection, the mean symptom score was 0.49 (p=0.30) for those with ≥3 prior vaccinations and 0.71 (p=0.028) with 1-2 previous vaccinations compared to 0.36 for unvaccinated individuals. Adjusting for confounders, Wild-type (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) showed significant associations with the outcome, whereas Omicron BA.1 infection (aRR 1.29, 95% CI 0.69–2.43) and vaccination before infection (aRR 1.27, 95% CI 0.82–1.94) did not.

Conclusions and Relevance

Previous infection with pre-Omicron variants was the strongest risk factor for reporting PASC symptoms in this HCW cohort. A definite influence of prior vaccination on the prevention of PASC after Omicron BA.1 infection was not measurable.
Systematic development and feasibility testing of a multibehavioural digital prehabilitation intervention for patients approaching major surgery (iPREPWELL): A study protocol
Authors: Durrand J , Livingston R , Tew G , Gillis C , Yates D , Gray J , Greaves CJ , Moore J , O’Doherty A F , Doherty P , Danjoux G , Avery L
Published: October 2022

Improving outcomes for people undergoing major surgery, specifically reducing perioperative morbidity and mortality remains a global health challenge. Prehabilitation involves the active preparation of patients prior to surgery, including support to tackle risk behaviours that mediate and undermine physical and mental health and wellbeing. The majority of prehabilitation interventions are delivered in person, however many patients express a preference for remotely-delivered interventions that provide them with tailored support and the flexibility. Digital prehabilitation interventions offer scalability and have the potential to benefit perioperative healthcare systems, however there is a lack of robustly developed and evaluated digital programmes for use in routine clinical care. We aim to systematically develop and test the feasibility of an evidence and theory-informed multibehavioural digital prehabilitation intervention ‘iPREPWELL’ designed to prepare patients for major surgery. The intervention will be developed with reference to the Behaviour Change Wheel, COM-B model, and the Theoretical Domains Framework. Codesign methodology will be used to develop a patient intervention and accompanying training intervention for healthcare professionals. Training will be designed to enable healthcare professionals to promote, support and facilitate delivery of the intervention as part of routine clinical care. Patients preparing for major surgery and healthcare professionals involved with their clinical care from two UK National Health Service centres will be recruited to stage 1 (systematic development) and stage 2 (feasibility testing of the intervention). Participants recruited at stage 1 will be asked to complete a COM-B questionnaire and to take part in a qualitative interview study and co-design workshops. Participants recruited at stage 2 (up to twenty healthcare professionals and forty participants) will be asked to take part in a single group intervention study where the primary outcomes will include feasibility, acceptability, and fidelity of intervention delivery, receipt, and enactment. Healthcare professionals will be trained to promote and support use of the intervention by patients, and the training intervention will be evaluated qualitatively and quantitatively. The multifaceted and systematically developed intervention will be the first of its kind and will provide a foundation for further refinement prior to formal efficacy testing.
The genetic and phenotypic correlates of mtDNA copy number in a multi-ancestry cohort
Authors: Zaidi Arslan A. , Verma Anurag , Morse Colleen ,   Penn Medicine BioBank, Ritchie Marylyn D. , Mathieson Iain
Published: October 2022

Mitochondrial DNA copy number (mtCN) is often treated as a proxy for mitochondrial (dys)function and disease risk. Pathological changes in mtCN are common symptoms of rare mitochondrial disorders but reported associations between mtCN and common diseases vary considerably across studies. We sought to understand the biology of mtCN by carrying out genome and phenome-wide association studies of mtCN in 30,666 individuals from the Penn Medicine BioBank—a large, diverse cohort of largely African and European ancestry. We estimated mtCN in peripheral blood using exome sequence data, taking into account the effects of blood cell composition, particularly neutrophil and platelet counts. We replicated known genetic associations of mtCN in the PMBB and found that their effect sizes are highly correlated between individuals of European and African ancestry. However, the heritability of mtCN was much higher among individuals of largely African ancestry (h2= 0.3) compared to European ancestry individuals (h2= 0.1). Admixture mapping suggests that there are undiscovered variants underlying mtCN that are differentiated in frequency between individuals with African and European ancestry. We further show that mtCN is associated with many health-related phenotypes. We discovered robust associations between mtDNA copy number and diseases of metabolically active tissues, such as cardiovascular disease and liver damage that were consistent across African and European ancestry individuals. Other associations, such as epilepsy, prostate cancer, and disorders of iron metabolism were only discovered in either individuals with European or African ancestry, but not both. Even though we replicate known genetic and phenotypic associations of mtCN, we demonstrate that they are sensitive to blood cell composition and environmental modifiers, explaining why such associations are inconsistent across studies. Peripheral blood mtCN might therefore be used as a biomarker of mitochondrial dysfunction and disease risk, but such associations must be interpreted with care.
Characterizing the molecular impact ofKMT2Dvariants on the epigenetic and transcriptional landscapes in Kabuki Syndrome
Authors: Jung Youngsook L , Hung Christina , Choi Jaejoon , Lee Eunjung A , Bodamer Olaf
Published: October 2022

Kabuki Syndrome (KS) is a rare, multisystem disorder with a variable clinical phenotype. The majority of KS is caused by dominant loss-of-function mutations inKMT2D(lysine methyltransferase 2D). KMT2D mediates chromatin accessibility by adding methyl groups to lysine residue 4 of histone 3, which plays a critical role in cell differentiation and homeostasis. The molecular underpinnings of KS remain elusive partly due to a lack of histone modification data from human samples. Consequently, we profiled and characterized alterations in histone modification and gene transcription in peripheral blood mononuclear cells (PBMCs) from 33 patients withKMT2Dmutations and 36 unaffected healthy controls. Our analysis identified unique enhancer signatures in H3K4me1 and H3K4me2 in KS compared to controls. Reduced enhancer signals were present for promoter-distal sites of immune-related genes for which co-binding of PBMC-specific transcription factors was predicted; thirty-one percent of super-enhancers of normal blood cells overlapped with disrupted enhancers in KS, supporting an association of reduced enhancer activity of immune-related genes with immune deficiency phenotypes. In contrast, increased enhancer signals were observed for promoter-proximal regions of metabolic genes enriched withEGR1andE2F2motifs, whose transcriptional levels were significantly increased in KS. Additionally, we identified approximately 100 de novo enhancers in genes, such as inMYO1FandAGAP2. Together, our results underscore the effect of KMT2D haploinsufficiency on (dys)regulation of enhancer states and gene transcription and provide a framework for the identification of therapeutic targets and biomarkers in preparation for clinical trial readiness.
Interventions to support parents, families and caregivers in caring for preterm or low birth weight infants at home: a systematic review
Authors: Bedwell C , Actis Danna V , Tate N , Dwan K , Portela A , Lavender T
Published: October 2022

Background

Preterm and low birth weight (LBW) (<2500g) infants are at greater risk of mortality and morbidity. Interventions to support parents to care for their newborn infant in the home may help to improve outcomes.

Objective

To determine what interventions, approaches, or strategies to support mothers/fathers/caregivers and families in caring for preterm or LBW infants in the home have been effective in improving outcomes.

Methods

A comprehensive search of relevant electronic databases, including MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials was completed in September 22. Two reviewers screened papers in Covidence and extracted data from 41 included papers. Quality of papers and certainty of evidence were assessed using CASP and GRADE, respectively.

Results

There is some evidence that support interventions may improve outcomes related to infant mortality, improvements in infant growth, exclusive breastfeeding, infant cognitive development, immunisation uptake, and reduction in maternal stress and depression. However, the overall certainty of evidence is low or very low in the majority of studies.

Conclusions

Interventions providing support for parents to care for infants in the home may improve outcomes for this population. There is a need for well-considered large scale support interventions, prioritised and developed with women and families.
Graph-based Fusion Modeling and Explanation for Disease Trajectory Prediction
Authors: Tariq Amara , Tang Siyi , Sakhi Hifza , Celi Leo Anthony , Newsome Janice M. , Rubin Daniel L. , Trivedi Hari , Gichoy Judy Wawira , Patel Bhavik , Banerjee Imon
Published: October 2022

We propose a relational graph to incorporate clinical similarity between patients while building personalized clinical event predictors with a focus on hospitalized COVID-19 patients. Our graph formation process fuses heterogeneous data, i.e., chest X-rays as node features and non-imaging EHR for edge formation. While node represents a snap-shot in time for a single patient, weighted edge structure encodes complex clinical patterns among patients. While age and gender have been used in the past for patient graph formation, our method incorporates complex clinical history while avoiding manual feature selection. The model learns from the patient’s own data as well as patterns among clinically-similar patients. Our visualization study investigates the effects of ‘neighborhood’ of a node on its predictiveness and showcases the model’s tendency to focus on edge-connected patients with highly suggestive clinical features common with the node. The proposed model generalizes well by allowing edge formation process to adapt to an external cohort.