bluuebunny/crossref_metadata_2025 huggingface dataset:
Press Ganey: Patient-Centered Communication Drives Provider and Hospital Revenue
Authors: Abu-Ghname Amjed , Davis Matthew J. , Shook Joan E. , Reece Edward M. , Hollier Larry H.
Published: January 2021

Background:

Spurred on in part by government policies that base a portion of reimbursement around patient satisfaction, in 2016, Texas Children’s Hospital instituted a patient-focused communication course entitled Breakthrough Communication. The aim of this study is to examine the effect of this training on provider-specific Press Ganey scores within the Department of Surgery, and to assess whether changes in Press Ganey scores correlate to hospital volume and revenue.

Methods:

The intervention period was defined as calendar year 2017. Full-time faculty between 2016 and 2018 who completed the course in 2017 and had at least 10 returned Press Ganey surveys before and after the course were included in this study. Patient volume and revenue were analyzed. A subgroup analysis was conducted to compare participant against nonparticipant plastic surgeons.

Results:

For the 56 surgeons who met the inclusion criteria, mean provider Press Ganey ratings increased from 92.0 to 94.3 following participation (p = 0.003). When compared to before intervention, clinical encounters increased by 26.2 percent, the number of patients increased by 26.0 percent, payments increased by 25.2 percent, and charges increased by 21.2 percent. In our subgroup analysis, there was a relative increase of 11 percent in the number of patients and 10 percent in the number of encounters for participant plastic surgeons. Participants reported 113 percent increases in charges and 71 percent increases in payments, whereas nonparticipants had decreases of 10 percent in charges and 4 percent in payments.

Conclusion:

The authors’ findings indicate that improving surgeons’ patient-centered communication skills is associated with an increase in patient satisfaction and an accompanying increase in both volume and reimbursements.
An Analgesic Regimen for Opioid Reduction in Elective Plastic Surgery: A Randomized Prospective Study
Authors: Newman Ashley , Davison Steven P.
Published: January 2021

Background:

Prescription opioid misuse has been recognized as a national epidemic. The implications of this problem are especially important to consider, as postoperative opioid abuse can give rise to true addiction for surgical patients. The concept of enhanced recovery after surgery is increasingly used across various specialties to decrease the overabundance of postoperative opioid use.

Methods:

This study prospectively examined 143 patients undergoing cosmetic elective surgery. Patients were randomized into one of two groups based on postoperative pain management regimen: multimodal (enhanced recovery after surgery) analgesia or traditional opioid analgesia. Data regarding postoperative pain scores, amount of postoperative opioids consumed, and duration of postoperative pain pill use were analyzed.

Results:

Multimodal (enhanced recovery after surgery) regimen patients experienced a 13.0 percent reduction in their pain scores after admission to the postanesthesia care unit and a 34.2 percent reduction in pain score at discharge, compared with traditional opioid patients (p = 0.049 and p = 0.0036, respectively). Enhanced recovery after surgery patients experienced a 35 percent reduction in the number of pills taken in the postoperative period and an 18.4 percent reduction in the duration of consumption (p = 0.0007 and p = 0.0539, respectively).

Conclusions:

The results demonstrate that multimodal postoperative pain management is an important tool for decreasing the amount of opioids prescribed and needed in the postoperative period. The overprescribing of opioids after surgery is a precursor to abuse and the increase in the national opioid reservoir.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Use of Immediate Obturator Prosthesis as a Rehabilitation Option in Cases of Squamous Cell Carcinoma
Authors: Ramirez Iago , Munhoz Maira F.V. , Freitas Deyves J. , Haddad Marcela F.
Published: January 2021

Maxillary defects caused by surgical resection generate abnormal communication between the nasal and oral cavities, hindering proper eating and phonetics, and causing aesthetic damage. Prosthetic intervention is necessary to rehabilitate these patients, in order to block communication and allow correct speech and swallowing functions. This article reports the manufacture of an immediate palatal obturator prosthesis after hemimaxillectomy due to the surgical removal of an intraoral squamous cell carcinoma, which guaranteed better conditions for postoperative recovery, as well as better adaptation to the definitive prosthesis and the use of the prosthetic apparatus.
Practice Habits, Knowledge, and Attitudes of Hepatologists to Alcohol Use Disorder Medication: Sobering Gaps and Opportunities
Authors: Cotter Thomas G. , Ayoub Fares , King Andrea C. , Reddy Kapuluru Gautham , Charlton Michael
Published: January 2021

Background:

The prevalence of alcohol use disorder (AUD) and alcohol-associated liver disease is increasing in the United States. Efficacious AUD pharmacotherapies, while available, are, for protean reasons, underutilized. Hepatology providers may be in a position to bridge the pharmacotherapeutic gap between availability and utilization of AUD pharmacotherapies. Our aim was to ascertain the current practice, knowledge and attitudes of hepatology physicians in the United States, and identify opportunities on how to increase AUD medication prescribing.

Methods:

A web-based survey, developed by an expert panel, was administered to hepatology physicians working at all transplant centers in the United States.

Results:

The survey response rate was 131/658 (20%). There was significant support (two-thirds of respondents) for hepatology providers prescribing AUD medications; however, only 1 in 4 was comfortable prescribing these medications. The majority felt additional education is needed to prescribe AUD medications. The practice of hepatology providers prescribing AUD medications is common, with >50% of respondents having done so. Baclofen was the most popular medication prescribed. Hepatology providers perceived suboptimal ancillary addiction services. Although AUD prescribers had higher rates of AUD pharmacotherapy knowledge compared with nonprescribers, approximately 50% still had inadequate knowledge.

Conclusions:

AUD medication prescribing is a common practice among hepatology providers who appear eager to increase this practice through more education as they attempt to bridge the pharmacotherapeutic gap. This informative survey provides guidance for professional societies on how best to disseminate the requisite education required to optimize the care of patients with AUD.
Recurrent Hepatocellular Carcinoma in an Adult With Alagille Syndrome Treated With Liver Resection Followed by Liver Transplantation: A Rare Case Report
Authors: Galvez Daniel , Ruch Brianna , Sharma Aadi , Sydnor Malcom , Levy Marlon , Sharma Amit
Published: January 2021

Alagille syndrome (AGS) is a disorder that affects the liver, heart, kidneys, and skeleton. Development of hepatocellular carcinoma (HCC) is rare in AGS. A 41-y-old male with AGS presented with a 6 × 8-cm HCC and underwent transarterial chemoembolization (TACE) followed by right hepatic lobectomy. One year later, he developed HCC recurrence within Milan’s criteria and received a deceased donor liver transplant. An interposition donor iliac artery graft from the supraceliac aorta to the donor hepatic artery was needed due to celiac axis occlusion noted on TACE. He subsequently underwent a Roux-en-Y hepaticojejunostomy for a bile leak. Surveillance imaging for HCC revealed a 3-cm pseudoaneurysm of his aortoiliac vascular anastomosis, 3 mo posttransplant. An infrarenal aortic jump graft to the donor hepatic artery and ligation of supraceliac aortic conduit was performed, followed by aortic stent-graft placement to occlude the pseudoaneurysm. He received a deceased donor kidney transplant 13 mo after the liver transplant. He remains HCC free with excellent liver and renal allograft function. Adults with AGS undergoing liver transplantation for HCC need special consideration due to related vascular, cardiac, and renal anomalies.
Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy
Authors: Kant Sam , Bromberg Jonathan , Haas Mark , Brennan Daniel
Published: January 2021

Background.

Approximately 15% of kidney transplant recipients (KTRs) develop BK viremia (BKV), with 1%–10% developing BK virus-associated nephropathy (BKVAN), which histologically resembles rejection. The Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study showed that donor-derived cell-free DNA (dd-cfDNA) levels <1% have a negative predictive value of 85% for active allograft rejection. Using data from this study, we evaluated the association of dd-cfDNA with plasma BK viral loads and biopsy findings to determine if dd-cfDNA can distinguish asymptomatic BKV from BKVAN.

Methods.

Data on dd-cfDNA, plasma BK viral loads, and biopsy findings from patients from the DART study were retrospectively examined. BKV was defined as 500–10 000 copies/mL. Presumptive BKVAN was defined as BK >10 000 copies/mL.

Results.

Of 102 participants with biopsies, 10 patients with BKV and BKVAN had paired dd-cfDNA, and viral loads available for analysis. Patients diagnosed with BKV and BKVAN had a median dd-cfDNA of 0.58% (IQR 0.43–1.15) and 3.38% (IQR 2.3–4.56, P = 0.001), respectively. dd-cfDNA titers correlated with BK PCR viral loads (R = 0.874, P = 0.01) and the presence of histologic evidence of BKVAN (100% sensitivity, 50% specificity). Five of 7 patients with BKVAN, but only 2 of 7 with BKV, had biopsies meeting Banff criteria for T-cell–mediated rejection. Median dd-cfDNA in nonrejection patients was 0.43% versus 2.84% in rejection patients (P = 0.001).

Conclusion.

Higher dd-cfDNA titers were associated with higher BK viral loads, biopsy-diagnosed BVAN, as well histologic changes meeting Banff criteria for as T-cell–mediated rejection. dd-cfDNA may be a useful noninvasive test to assess for progression of BKV to BKVAN.
Donor HLA−DR Drives the Development of De Novo Autoimmunity Following Lung and Heart Transplantation
Authors: Jankowska−Gan Ewa , Agashe Vrushali V. , Lema Diego A. , Zhou Ying , Gonzalez Bosc Laura , Sullivan Jeremy A. , Greenspan Daniel S. , Burlingham William J.
Published: January 2021

Background.

Individuals harbor preexisting HLA−DR/DQ−restricted responses to collagen type V (ColV) mediated by Th17 cells under Treg control, both specific to peptides that bind to inherited HLA class II antigens. Yet after transplant, the donor−DR type somehow influences graft outcome. We hypothesized that, long after a lung or heart allograft, the particular HLA−DR type of the mismatched transplant donor transforms the specificity of the “anti−self” response. This could explain why, over long term, certain donor DRs could be more immunogenic than others.

Methods.

We analyzed 7 HLA−DR15neg patients who had received a lung allograft from a DR15+ donor. To determine the mechanism of acquired specificity in self−reactivity, we analyzed the kinetics of DR1 (host) and DR15 (donor) peptide restriction in a heart transplant model using DR−transgenic mice.

Results.

Beyond 1.5 years post-lung transplant, all patients tested had acquired DR15−restricted immune responses to ColV peptides. These responses were either unrestrained Th17 type (n = 4) or Th17 controlled by Treg arising early (<5 y) or late (>7 y) after transplant (n = 4). Treg suppression via conventional (transforming growth factor−β [TGF−β]) and extracellular vesicle−associated (IL−35) cytokines correlated with superior outcomes. Naïve DR1 and DR15 transgenic mice had preexisting DR−restricted responses, exclusively to ColV fragments containing DR1− or DR15−binding peptides. When HLA−DR1 transgenic recipients of a HLA−DR15 heart developed ColV reactivity post-transplant, mice that acutely rejected (20–25 d) responded only to the DR1−restricted ColV peptide epitope. In animals whose grafts survived long term, we could detect acquisition of DR from the transplant donor onto the surface of recipient dendritic cells, and immune responses against a donor DR15–restricted ColV peptide.

Conclusions.

These results might explain how certain donor HLA−DR types redirect host immune responses to novel peptides of critical self−antigens. Unless regulated, such responses may predispose the allograft to chronic rejection.
Ethical Decision Diagrams on Donation After Cardiocirculatory Death Heart Transplantation Considering Organ Preservation Techniques
Authors: Saemann Lars , Karck Matthias , Korkmaz-Icöz Sevil , Wenzel Folker , Szabó Gábor
Published: January 2021

Background.

To overcome organ shortage, some centers accept hearts from cardiocirculatory determined death (DCD) donors for heart transplantation (HTx). DCD-HTx is attached with special ethical conflicts on the donor, family, and recipient side. Ethically motivated decisions also have to be made considering organ preservation techniques. However, ethical decision diagrams, which can be applied to find a final answer on the complex field of ethical questions, have not been developed yet.

Methods.

In an interdisciplinary group of clinical ethicists, transplantation surgeons, transplantation researchers, and perfusionists, after review of relevant literature, we focused on crucial ethical aspects on DCD-HTx in general and separated ethical conflicts with regard to the individual perspective of the donor, family, and recipient.

Results.

The leading aspect of discussion in the donor perspective mainly deals with the standoff period and with the definition of death. The perspective of recipients focuses on the wish to say farewell after the patient is deceased. In the recipient perspective ethical questions regarding organ procurement techniques occur.

Conclusions.

Ethical decision-making on DCD-HTx is complex, but it can be processed in a structured way by applying the decision diagrams that we have developed.
Early Detection of Alzheimer’s Disease with Low-Cost Neuropsychological Tests: A Novel Predict-Diagnose Approach using Recurrent Neural Networks
Authors: Mukherji Devarshi , Mukherji Manibrata , Mukherji Nivedita ,   Alzheimer’s Disease Neuroimaging Initiative
Published: January 2021

Alzheimer’s Disease (AD) is the most expensive and currently incurable disease that affects a large number of the elderly globally. One in five Medicare dollars is spent on AD-related tests and treatments. Accurate AD diagnosis is critical but often involves invasive and expensive tests that include brain scans and spinal taps. Recommending these tests for only patients who are likely to develop the disease will save families of cognitively normal individuals and hospitals from unnecessary expenditures. Moreover, many of the subjects chosen for clinical trials for AD therapies never develop any cognitive impairment and prove not to be ideal candidates for those trials. It is thereby critical to find inexpensive ways to first identify individuals who are likely to develop cognitive impairment and focus attention on them for in-depth testing, diagnosing, and clinical trial participation. Research shows that AD is a slowly progressing disease. This slow progression allows for early detection and treatment, but more importantly, gives the opportunity to predict the likelihood of disease development from early indications of memory lapses. Neuropsychological tests have been shown to be effective in identifying cognitive impairment. Relying exclusively on a set of longitudinal neuropsychological test data available from the ADNI database, this paper has developed Recurrent Neural Networks (RNN) to diagnose the current and predict the future cognitive states of individuals. The RNNs use sequence prediction techniques to predict test scores for two to four years in the future. The predicted scores and predictions of cognitive states based on them showed a high level of accuracy for a group of test subjects, when compared with their known future cognitive assessments conducted by ADNI. This shows that a battery of neuropsychological tests can be used to track the cognitive states of people above a certain age and identify those who are likely to develop cognitive impairment in the future. This ability to triage individuals into those who are likely to remain normal and those who will develop cognitive impairment in the future, advances the quest to find appropriate candidates for invasive tests like spinal taps for disease identification, and the ability to identify suitable candidates for clinical trials.
Improving executive, behavioural and socio-emotional competences in very preterm young adolescents through a mindfulness-based intervention: study protocol and feasibility
Authors: Siffredi Vanessa , Liverani Maria Chiara , Smith Mariana Magnus , Meskaldji Djalel Eddine , Stuckelberger-Grobéty Françoise , Freitas Lorena G. A. , Albuquerque Jiske De , Savigny Emilie , Gimbert Fanny , Hüppi Petra Susan , Merglen Arnaud , Tolsa Cristina Borradori , Hà-Vinh Leuchter Russia
Published: January 2021

Background

(VPT) children and adolescents exhibit executive, behavioural and socio-emotional difficulties that persists into adulthood. Previous research suggests that mindfulness-based intervention (MBI) may specifically target the development of theses competences. The objective of the current study is to describe the study protocol and to evaluate the feasibility of a clinical trial on a MBI program to enhance executive, behavioural and socio-emotional competences in a cohort of VPT young adolescents.

Methods

164 VPT young adolescents from 10 to 14 years old, born before 32 gestational weeks, were invited to participate in an MBI program of 8 weekly sessions in groups of up to 8 participants, lasting 1h30. Participant were enrolled in a randomised controlled trial (RCT) or in a pre-post intervention designs depending of their availability. Satisfaction and attendance measures of the MBI were collected using self-reported questionnaires and registration of attendance.

Results

Of the 63 participants who were enrolled in the study (38.2% of families invited to participate), 52 (82.5%) completed all assessments. Once enrolled, acceptability was high as shown by the high attendance rate in the sessions and the feedback evaluation questionnaire.

Discussion

To our knowledge, this is the first study to investigate the feasibility of an MBI study in VPT born young adolescents. Our findings suggest that an MBI study is feasible and show a high acceptability among participants. The use of an RCT design in our study constitutes the gold standard for testing the efficacy of such intervention in VPT young adolescents. If effective, the MBI program could potentially be a valuable tool for improving executive, behaviour and socio-emotional competences in the vulnerable VPT population.

Trial registration

ClinicalTrials,NCT04638101. Registered 19 November 2020 - Retrospectively registered,https://clinicaltrials.gov/show/NCT04638101.
Childhood Conduct History is Linked to Amygdalohippocampal Changes in Healthy Adults: A Neuroimaging Behavioral Study
Authors: Abdolalizadeh AmirHussein , Moradi Kamyar , Dabbagh Ohadi Mohammad Amin , Mirfazeli FatemehSadat , Rajimehr Reza
Published: January 2021

Background

Conduct Disorder (CD) is defined as aggressive, antisocial, and rule-breaking behavior during childhood, and a major risk factor for developing an antisocial personality disorder. However, nearly half the patients develop into seemingly normal status. We aimed to identify psychiatric, emotional, and brain volumetric and functional footprints of childhood CD in healthy young adults with a prior history of CD.

Methods

40 subjects with a prior history of CD (CC) and 1166 control subjects (HC) were identified from the Human Connectome Project. Their psychiatric, emotional, impulsivity, and personality traits were extracted. An emotion task fMRI activation of amygdala and hippocampus, as well as whole-brain and hippocampal/amygdalar segmentation volumetry were analyzed. We then statistically assessed the between-group differences and associations between the assessments and the hippocampal or amygdala nuclei measurements.

Results

After correcting for multiple comparisons, we found higher anger aggression, antisocial personality problems, aggressive and rule-breaking behaviors, anxiety, attention-deficit/hyperactivity, intrusive, externalizing, neuroticism, and lower agreeableness in the CC group. The neuroimaging analysis also revealed larger subregions of the left hippocampus in CC group. Significant group × assessment association was found for aggression and left hippocampal presubiculum and basal nuclei of left amygdala.

Discussion

Healthy young adults with a prior history of CD still exhibit some forms of antisocial-like behavior, without evidence of emotional recognition disturbances, and with larger left hippocampal subregions. These larger hippocampal and amygdala volumes may play a protective role in CC subjects.
Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil
Authors: da Silva Francisco Ronaldo , Benites L. Felipe , Lamarca Alessandra P , de Almeida Luiz G P , Hansen Alana Witt , Gularte Juliana Schons , Demoliner Meriane , Gerber Alexandra L , de C Guimarães Ana Paula , Antunes Ana Karolina Eisen , Heldt Fagner Henrique , Mallmann Larissa , Hermann Bruna , Ziulkoski Ana Luiza , Goes Vyctoria , Schallenberger Karoline , Fillipi Micheli , Pereira Francini , Weber Matheus Nunes , de Almeida Paula Rodrigues , Fleck Juliane Deise , Vasconcelos Ana Tereza R , Spilki Fernando Rosado
Published: January 2021

Emergence of novel SARS-CoV-2 lineages are under the spotlight of the media, scientific community and governments. Recent reports of novel variants in the United Kingdom, South Africa and Brazil (B.1.1.28-E484K) have raised intense interest because of a possible higher transmission rate or resistance to the novel vaccines. Nevertheless, the spread of B.1.1.28 (E484K) and other variants in Brazil is still unknown. In this work, we investigated the population structure and genomic complexity of SARS-CoV-2 in Rio Grande do Sul, the southernmost state in Brazil. Most samples sequenced belonged to the B.1.1.28 (E484K) lineage, demonstrating its widespread dispersion. We were the first to identify two independent events of co-infection caused by the occurrence of B.1.1.28 (E484K) with either B.1.1.248 or B.1.91 lineages. Also, clustering analysis revealed the occurrence of a novel cluster of samples circulating in the state (named VUI-NP13L) characterized by 12 lineage-defining mutations. In light of the evidence for E484K dispersion, co-infection and emergence of VUI-NP13L in Rio Grande do Sul, we reaffirm the importance of establishing strict and effective social distancing measures to counter the spread of potentially more hazardous SARS-CoV-2 strains.

Highlights

The novel variant B.1.1.28 (E484K) previously described in Rio de Janeiro is currently spread across the southernmost state of Brazil;

The novel variant VUI-NP13L was also identified by causing a local outbreak in Rio Grande do Sul;

B.1.1.28 (E484K) is able to establish successful coinfection events co-occurring simultaneously with different lineages of SARS-CoV-2.
Weekly SARS-CoV-2 sentinel in primary schools, kindergartens and nurseries, June to November 2020, Germany
Authors: Hoch Martin , Vogel Sebastian , Kolberg Laura , Dick Elisabeth , Fingerle Volker , Eberle Ute , Ackermann Nikolaus , Sing Andreas , Huebner Johannes , Rack-Hoch Anita , Schober Tilmann , Both Ulrich von
Published: January 2021

A 12-week sentinel programme monitored SARS-CoV-2 in primary schools, kindergartens and nurseries. Out of 3169 oropharyngeal swabs, only two tested positive on rRT-PCR while general incidence rates were surging. Thus, children attending respective institutions are not significantly contributing to the pandemic spread when appropriate infection control measures are in place.
ACoRE: Accurate SARS-CoV-2 genome reconstruction for the characterization of intra-host and inter-host viral diversity in clinical samples and for the evaluation of re-infections
Authors: Marcolungo Luca , Beltrami Cristina , Esposti Chiara Degli , Lopatriello Giulia , Piubelli Chiara , Mori Antonio , Pomari Elena , Deiana Michela , Scarso Salvatore , Bisoffi Zeno , Grosso Valentina , Cosentino Emanuela , Maestri Simone , Lavezzari Denise , Iadarola Barbara , Paterno Marta , Segala Elena , Giovannone Barbara , Gallinaro Martina , Rossato Marzia , Delledonne Massimo
Published: January 2021

We report Accurate SARS-CoV-2 genome Reconstruction (ACoRE), an amplicon-based viral genome sequencing workflow for the complete and accurate reconstruction of SARS-CoV-2 sequences from clinical samples, including suboptimal ones that would usually be excluded even if unique and irreplaceable. We demonstrated the utility of the approach by achieving complete genome reconstruction and the identification of false-positive variants in >170 clinical samples, thus avoiding the generation of inaccurate and/or incomplete sequences. Most importantly, ACoRE was crucial to identify the correct viral strain responsible of a relapse case, that would be otherwise mis-classified as a re-infection due to missing or incorrect variant identification by a standard workflow.
Epidemic Overdispersion Strengthens the Effectiveness of Mobility Restrictions
Authors: Großmann Gerrit , Backenköhler Michael , Wolf Verena
Published: January 2021

Human mobility is the fuel of global pandemics. In this simulation study, we analyze how mobility restrictions mitigate epidemic processes and how this mitigation is influenced by the epidemic’s degree of dispersion.

We find that (even imperfect) mobility restrictions are generally efficient in mitigating epidemic spreading. Notably, the effectiveness strongly depends on the dispersion of the offspring distribution associated with the epidemic. We also find that mobility restrictions are useful even when the pathogen is already prevalent in the whole population. However, also a delayed implementation is more efficient in the presence of overdispersion. Conclusively, this means that implementing green zones is easier for epidemics with overdispersed transmission dynamics (e.g., COVID-19). To study these relationships at an appropriate level of abstraction, we propose a spatial branching process model combining the flexibility of stochastic branching processes with an agent-based approach allowing a conceptualization of locality, saturation, and interaction structure.
Validation of the short Mood and Feelings Questionnaire in young adulthood
Authors: Eyre Olga , Jones Rhys Bevan , Agha Sharifah Shameem , Wootton Robyn E , Thapar Ajay K , Stergiakouli Evie , Langley Kate , Collishaw Stephan , Thapar Anita , Riglin Lucy
Published: January 2021

Background

Depression often onsets in adolescence and is associated with recurrence in adulthood. There is a need to identify and monitor depression symptoms across adolescence and into young adulthood. The short Mood and Feelings Questionnaire (sMFQ) is commonly used to measure depression symptoms in adolescence but has yet to be validated in young adulthood. This study aimed to (1) examine whether the sMFQ is a valid assessment of depression in young adults, and (2) identify cut-points that best capture a DSM-5 diagnosis of depression at age 25.

Methods

The sample included young people who took part in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 25 (n=4098). Receiver Operating Characteristic analyses were used to examine how well the self-rated sMFQ discriminates between cases and non-cases of DSM-5 Major Depressive Disorder (MDD) classified using the self-rated Development and Well Being Assessment. Sensitivity and specificity values were used to identify cut-points on the sMFQ.

Results

The sMFQ had high accuracy for discriminating MDD cases from non-cases at age 25. The commonly used cut-point in adolescence (≥12) performed well at this age, best balancing sensitivity and specificity. However, a lower cut-point (≥10) may be appropriate in some contexts, e.g. for screening, when sensitivity is favoured over specificity.

Limitations

ALSPAC is a longitudinal population cohort that suffers from non-random attrition.

Conclusions

The sMFQ is a valid measure of depression in young adults in the general population. It can be used to screen for and monitor depression across adolescence and early adulthood.
Single nuclei profiling identifies cell specific markers of skeletal muscle aging, sarcopenia and senescence
Authors: Perez Kevin , McGirr Julia , Limbad Chandani , Doi Ryosuke , Nederveen Joshua P , Nilsson Mats I , Tarnopolsky Mark , Campisi Judith , Melov Simon
Published: January 2021

Aging is accompanied by a loss of muscle mass and function, termed sarcopenia, which causes numerous morbidities and economic burdens in human populations. Mechanisms implicated in age-related sarcopenia include inflammation, muscle stem cell depletion, mitochondrial dysfunction and loss of motor neurons, but whether there are key drivers of sarcopenia is not yet known. To gain deeper insights into age-related sarcopenia, we performed transcriptome profiling on lower limb muscle biopsies from 72 young, old and sarcopenic subjects using bulk RNA-seq (N = 72) and single-nuclei RNA-seq (N = 17). This combined approach revealed novel changes in gene expression that occur with age and sarcopenia in multiple cell types comprising mature skeletal muscle. Notably, we found increased expression of the genes MYH8 and PDK4, and decreased expression of the gene IGFN1, in old muscle. We validated key genes in fixed human muscle tissue using digital spatial profiling. We also identified a small population of nuclei that express CDKN1A, present only in aged samples, consistent with p21-driven senescence in this subpopulation. Overall, our findings identify unique cellular subpopulations in aged and sarcopenic skeletal muscle, which will facilitate the development of new therapeutic strategies to combat age-related sarcopenia.
Clinical impact of the Predict Prostate risk communication tool in men newly diagnosed with non-metastatic prostate cancer: a multi-centre randomised controlled trial
Authors: Thurtle David , Jenkins Val , Freeman Alex , Pearson Mike , Recchia Gabriel , Tamer Priya , Leonard Kelly , Pharoah Paul , Aning Jonathan , Madaan Sanjeev , Goh Chee , Hilman Serena , McCracken Stuart , Ilie Petre Cristian , Lazarowicz Henry , Gnanapragasam Vincent
Published: January 2021

Introduction

Predict Prostate is a freely-available online personalised risk communication tool for men newly diagnosed with non-metastatic prostate cancer. Its accuracy has been assessed in multiple validation studies but the clinical impact of the tool on patient decision-making had not previously been evaluated.

Methods

A multi-centre randomised controlled trial was performed across 8 UK centres, wherein newly diagnosed men considering either active surveillance or radical treatment, were randomised to either standard of care (SOC) information or SOC and presentation of Predict Prostate. Validated questionnaires were completed assessing impact of the tool on decisional conflict, uncertainty, anxiety and understanding of survival.

Results

156 patients were included; mean age 67 years (range 44-80) and PSA of 6.9ng/ml (range 0.5-59.8). 81 were randomised to the Predict Prostate arm, and 75 to SOC information only. Mean decisional conflict scores were 26% lower in the Predict Prostate group (mean = 15.9) than in the SOC group (mean = 21.5) (p=0.01). Scores on the ‘effective decision’, ‘uncertainty’ and ‘value clarity’ subscales all indicated that the Predict Prostate group felt more informed and clear about their decision (all p<0.05). There was no significant difference in anxiety between the two groups.

Patient perceptions of 15-year prostate cancer specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower among men in the Predict Prostate group (p<0.0001). 58% of men reported the Predict Prostate estimates for PCSM were lower than expected, and 35% reported being less likely to select radical treatment. Over 90% of patients in the Predict Prostate group found it useful and 94% would recommend it to others.

Conclusion

Predict Prostate reduces decisional conflict and uncertainty in non-metastatic prostate cancer and shifts patient perceptions around prognosis to be more realistic. This is the first randomised study of such a tool in this context; it demonstrates Predict Prostate can directly inform the complex decision-making process in prostate cancer.
Training for object recognition with increasing spatial frequency: A comparison of deep learning with human vision
Authors: Avberšek Lev Kiar , Zeman Astrid , Op de Beeck Hans P.
Published: January 2021

The ontogenetic development of human vision, and the real-time neural processing of visual input, both exhibit a striking similarity – a sensitivity towards spatial frequencies that progress in a coarse-to-fine manner. During early human development, sensitivity for higher spatial frequencies increases with age. In adulthood, when humans receive new visual input, low spatial frequencies are typically processed first before subsequently guiding the processing of higher spatial frequencies. We investigated to what extent this coarse-to-fine progression might impact visual representations in artificial vision and compared this to adult human representations. We simulated the coarse-to-fine progression of image processing in deep convolutional neural networks (CNNs) by gradually increasing spatial frequency information during training. We compared CNN performance, after standard and coarse-to-fine training, with a wide range of datasets from behavioural and neuroimaging experiments. In contrast to humans, CNNs that are trained using the standard protocol are very insensitive to low spatial frequency information, showing very poor performance in being able to classify such object images. By training CNNs using our coarse-to-fine method, we improved the classification accuracy of CNNs from 0% to 32% on low-pass filtered images taken from the ImageNet dataset. When comparing differently trained networks on images containing full spatial frequency information, we saw no representational differences. Overall, this integration of computational, neural, and behavioural findings shows the relevance of the exposure to and processing of input with a variation in spatial frequency content for some aspects of high-level object representations.
Association of patients’ past misdiagnosis experiences with trust in their current physician: the TRUMP2-Net study
Authors: Suzuki Ryo , Yajima Nobuyuki , Sakurai Kosuke , Oguro Nao , Wakita Takafumi , Thom David H. , Kurita Noriaki
Published: January 2021

Background

Previous qualitative research has described that past misdiagnosis experiences may reduce patients’ own and their families’ trust in healthcare.

Objective

To quantify the associations between patients’ or family members’ misdiagnosis experiences and the former’s trust in their current physicians.

Design

A cross-sectional online survey.

Participants

Adult Japanese people with non-communicable diseases (cancer, diabetes, depression, heart disease, and connective tissue disease), recruited using a web-based panel survey.

Main Measures

The misdiagnosis experiences of patients and their family members were measured as exposures. The former’s trust in their current physicians was measured using the Japanese version of the 11-item Trust in Physicians Scale modified by Thom, which was translated and validated by us for this study.

Key Results

A total of 661 patients with a mean age of 62.7 years were analyzed. Overall, 23.2% had a history of misdiagnosis and 20.4% had a family member who had been misdiagnosed. The internal consistency (Cronbach’s α) was 0.91. The factor analysis suggested unidimensionality with all 11 loadings being higher than 0.40. In a multivariable-adjusted general linear model, patients’ and family members’ misdiagnosis experiences were associated with lower confidence in their current physicians (mean difference −4.30, 95%CI −8.12 to −0.49 and −3.20, 95%CI −6.34 to −0.05, respectively). An additive effect was suggested for the associations of patients’ and family’s experience of misdiagnosis on trust (P for interaction = 0.494).

Conclusions

The individuals’ and family members’ misdiagnosis experiences were associated with reduced trust in their current physicians. Interventions specifically targeting misdiagnosed patients are needed to restore patients’ confidence in their current physicians.
Description of a community paediatric strategy offering a package of services to prevent malnutrition among children in one health district in Mali
Authors: Roederer Thomas , Llosa Augusto E. , Shepherd Susan , Defourny Isabelle , Lacharité Michel-Olivier , Okonta Chibuzo , Magassa Mahamadou , Traoré Modibo , Schaefer Myrto , Grais Rebecca F.
Published: January 2021

Background

We present results from an intervention case study, the Soins Preventifs de l’Enfant (SPE) project, in Konséguéla health area, Mali. The intervention involved a network of community health workers providing a comprehensive preventive/therapeutic package, ultimately aiming at reducing under 24-month mortality. Associated costs were documented to assess the feasibility of replication and scale-up.

Methods

SPE program monitoring data were obtained from booklets specific to the program between 2010 and 2014. Data included sex, age, vaccination status, anthropometric measurements, Ready-To-Use-Supplementary Food distribution, morbidities reported by the mother between visits, hospitalizations over 18 months of follow-up. Cross-sectional surveys in the district of Koutiala, of which Konséguéla is one health area, were conducted yearly between 2010 and 2014 for comparison, using difference-in-difference approach. Ethical approval was granted from the Malian Ethical Committee.

Results

Global and Severe Acute Malnutrition prevalences decreased over time in Konséguéla as well as in the rest of the district, but the difference between areas was not significant. Children reaching 24 months were 20% less stunted in Konséguéla than children the same age outside (p<0.001). Mortality rates significantly decreased more in Konséguéla, while vaccination coverage for all antigens significantly increased in the meantime. The package cost approximately USD 95 per child per year; 56% of which was for the RUSF.

Conclusion

The results of this case study suggest a sustained impact of a community based, comprehensive health package on major child health indicators. Most notably, while improvements in acute malnutrition were found in the district as a whole, those in the intervention area were more pronounced. Trends for other indicators suggest additional benefits.
Immune cells in bronchoalveolar lavage fluid of Ugandan adults who resist versus those who develop latent Mycobacterium tuberculosis infection
Authors: Thiel Bonnie A. , Worodria William , Nalukwago Sophie , Nsereko Mary , Sanyu Ingvar , Rejani Lalitha , Zawedde Josephine , Canaday David H , Stein Catherine M , Chervenak Keith A , Malone LaShaunda L , Kiyemba Ronald , Silver Richard F , Johnson John L , Mayanja-Kizza Harriet , Boom W Henry
Published: January 2021

Background

The search for immune correlates of protection against Mycobacterium tuberculosis (MTB) infection in humans is limited by the focus on peripheral blood measures. Bronchoalveolar lavage (BAL) can safely be done and provides insight into cellular function in the lung where infection is first established. In this study, blood and lung samples were assayed to determine if heavily MTB exposed persons who resist development of latent MTB infection (RSTR) vs those who develop latent MTB infection (LTBI), differ in the make-up of resident BAL innate and adaptive immune cells.

Methods

Bronchoscopy was performed on 21 healthy long-term Ugandan RSTR and 25 LTBI participants. Immune cell distributions in BAL and peripheral blood were compared by differential cell counting and flow cytometry.

Results

The bronchoscopy procedure was well tolerated with few adverse reactions. Differential macrophage and lymphocyte frequencies in BAL differed between RSTR and LTBI. When corrected for age, this difference lost statistical significance. BAL CD4+ and CD8+ T cells were almost entirely composed of effector memory T cells in contrast to PBMC, and did not differ between RSTR and LTBI. BAL NKT, γδ T cells and NK cells also did not differ between RTSR and LTBI participants. There was a marginally significant increase (p=0.034) in CD8 T effector memory cells re-expressing CD45RA (TEMRA) in PBMC of LTBI vs RSTR participants.

Conclusion

This observational case-control study comparing unstimulated BAL from RSTR vs LTBI, did not find evidence of large differences in the distribution of baseline BAL immune cells. PBMC TEMRA cell percentage was higher in LTBI relative to RSTR suggesting a role in the maintenance of latent MTB infection. Functional immune studies are required to determine if and how RSTR and LTBI BAL immune cells differ in response to MTB.
Stepwise Oxidations Play Key Roles in the Structural and Functional Regulations of DJ-1
Authors: Song In-Kang , Kim Mi-Sun , Ferrell James E. , Shin Dong-Hae , Lee Kong-Joo
Published: January 2021

DJ-1 is known to play neuroprotective roles by eliminating reactive oxygen species (ROS) as an antioxidant protein. However, the molecular mechanism of DJ-1 function has not been well elucidated. This study explored the structural and functional changes of DJ-1 in response to oxidative stress. We found that Cys46 is also reactive cysteine residue in DJ-1, which was identified employing an NPSB-B chemical probe that selectively reacts with redox sensitive cysteine sulfhydryl. Peroxidatic Cys46 readily formed an intra-disulfide bond with resolving Cys53, which was identified with nanoUPLC-ESI-q-TOF tandem mass spectrometry (MS/MS) employing DBond algorithm under the non-reducing condition. We also found that Cys46-Cys53 disulfide crosslinking affects the oxidative state of the third Cys106, which shows the crosstalk among three cysteine residues of DJ-1. Furthermore, we demonstrated that DJ-1 C46A mutant, not forming Cys46-Cys53 intra-disulfide bond, lost structural stability of DJ-1 employing hydrogen/deuterium exchange-mass spectrometry (HDX-MS) analysis. All three Cys mutants lost antioxidant activities in SN4741 cell, a dopaminergic neuronal cell, unlike wild type DJ-1. These findings suggest that DJ-1 regulates its structure and activities by concerted oxidative modifications of three cysteine residues. These studies broaden the understanding of regulatory mechanisms of DJ-1 that operate under oxidative conditions.
Soil causes gut microbiota to flourish and total serum IgE levels to decrease in mice
Authors: Zhou Dongrui , Li Na , Yang Fan , Zhang Honglin , Bai Zhimao , Dong Yangyang , Li Mengjie , Zhu Wenyong , Fei Zhongjie , Xiao Pengfeng , Sun Xiao , Lu Zuhong
Published: January 2021

Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil, soil microbes (in lieu of environmental microbes), or non-sterilized soil. Metagenomic sequencing results showed the intake of sterile soil i.e. inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune globulin E (IgE) levels induced by 2-4-dinitrofluorobenzene(DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential “prebiotic” promoting the reproduction and growth of some intestinal microorganisms that harbor bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.
DNA metabarcoding reveals adaptive seasonal variation of individual trophic traits in a critically endangered fish
Authors: Villsen Kurt , Corse Emmanuel , Meglécz Emese , Archambaud-Suard Gaït , Vignes Hélène , Ereskovsky Alexander V. , Chappaz Rémi , Dubut Vincent
Published: January 2021

Dietary studies are critical for understanding foraging strategies and have important applications in conservation and habitat management. We applied a robust metabarcoding protocol to characterize the diet of the critically endangered freshwater fishZingel asperand conducted modelling and simulation analyses to characterize and identify some of the drivers of individual trophic trait variation in this species. We found that intra-specific competition and ontogeny had minor effects on the trophic niche ofZ. asper. Instead, our results suggest that the majority of trophic niche variation was driven by seasonal variation in ecological opportunity (in our case, the seasonal variation in the availability of preferred prey types). Overall, our results are in line with the optimal foraging theory and suggest thatZ. asperis specialized on a few ephemeropteran prey species (Baetis fuscatusandEcdyonurus) but adapts its foraging by becoming more opportunistic as its favoured prey seasonally decline. Despite the now widespread usage of metabarcoding, very few studies have attempted to study inter- and intra-populational individual trophic traits variation with metabarcoding data. This study illustrates how metabarcoding data obtained from feces can be combined with modelling and simulation approaches to test hypotheses in the conventional analytic framework of trophic analysis.
Pre-mRNA processing entropy in a mouse model of trauma
Authors: Jentzsch Maximilian S. , Fredericks Alger M. , Machan Jason T. , Ayala Alfred , Monaghan Sean F.
Published: January 2021

Purpose

Next generation sequencing has expanded our understanding of many disease processes, including trauma and critical illness. Many studies focus identifying a small set of genes or proteins that are aberrantly expressed. Our objective was to determine whether global differences in pre-mRNA processing entropy, or disorder, could offer novel insights in the setting of critical illness.

Methods

We used an established murine model of trauma that consisted of hemorrhagic shock and cecal ligation and puncture. In our first experiment mice exposed to trauma were compared to controls. In our second experiment, survival 14 days after exposure to trauma was studied. Using deep RNA sequencing we determined entropy values for every pre-mRNA processing event identified. We then used principal component analysis (PCA) to conduct unsupervised classification of the data.

Results

Mice exposed to trauma separated from controls using PCA. Similarly, mice that did not survive 14 days post exposure clustered closely together on PCA.

Conclusion

Our results suggest that there is a substantial difference in global pre-mRNA processing entropy in mice exposed to trauma vs. controls, and that pre-mRNA processing entropy may be helpful in predicting mortality. The method introduced here is easily transferrable to other disease processes and samples.