bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic modifications and the development of kidney graft fibrosis
Authors: Rousselle Thomas , Bardhi Elissa , Maluf Daniel G. , Mas Valeria R.
Published: December 2020

Purpose of review

To outline recent discoveries in epigenetic regulatory mechanisms that have potential implications in the development of renal fibrosis following kidney transplantation.

Recent findings

The characterization of renal fibrosis following kidney transplantation has shown TGFβ/Smad signaling to play a major role in the progression to chronic allograft dysfunction. The onset of unregulated proinflammatory pathways are only exacerbated by the decline in regulatory mechanisms lost with progressive patient age and comorbidities such as hypertension and diabetes. However, significant developments in the recognition of epigenetic regulatory markers upstream of aberrant TGFβ-signaling has significant clinical potential to provide therapeutic targets for the treatment of renal fibrosis. In addition, discoveries in extracellular vesicles and the characterization of their cargo has laid new framework for the potential to evaluate patient outcomes independent of invasive biopsies.

The current review summarizes the main findings in epigenetic machinery specific to the development of renal fibrosis and highlights therapeutic options that have significant potential to translate into clinical practice.
Very Late Onset of Obsessive-Compulsive Disorder
Authors: Fernandes Catarina Pedro , Vilaverde Daniela , Freitas Daniela , Pereira Filipa , Morgado Pedro
Published: December 2020

It is widely agreed that obsessive-compulsive disorder (OCD) is less common among the elderly. However, several studies suggest that a third peak of OCD onset may occur after the age of 65. The onset of OCD in the elderly is unusual and mostly related to nonpsychiatric diagnoses. Nonetheless, some reports have documented late-onset OCD in older adults with no detection of cerebral abnormalities. Such differences in age of onset may be associated with phenotypical differences in disease severity, comorbidity, and treatment response across patients. In this report, we describe the case of late-onset OCD in an 80-year old man with no specific focal brain structural abnormality. The report could improve awareness of the disorder in the elderly and contribute to a better identification of clinical characteristics and additional risk factors of OCD.
Predicting Attention-Shaping Response in People With Schizophrenia
Authors: Beaudette Danielle M. , Gold James M. , Waltz James , Thompson Judy L. , Cherneski Lindsay , Martin Victoria , Monteiro Brian , Cruz Lisa N. , Silverstein Steven M.
Published: December 2020

People with schizophrenia often experience attentional impairments that hinder learning during psychological interventions. Attention shaping is a behavioral technique that improves attentiveness in this population. Because reinforcement learning (RL) is thought to be the mechanism by which attention shaping operates, we investigated if preshaping RL performance predicted level of response to attention shaping in people with schizophrenia. Contrary to hypotheses, a steeper attentiveness growth curve was predicted by less intact pretreatment RL ability and lower baseline attentiveness, accounting for 59% of the variance. Moreover, baseline attentiveness accounted for over 13 times more variance in response to attention shaping than did RL ability. Results suggest attention shaping is most effective for lower-functioning patients, and those high in RL ability may already be close to ceiling in terms of their response to reinforcers. Attention shaping may not be a primarily RL-driven intervention, and other mechanisms of its effects should be considered.
A 3-Month Naturalistic Follow-Up Treatment With Selective Serotonin Reuptake Inhibitors in Frequent Attenders of General Medical Practice
Authors: Carmassi Claudia , Cappelli Andrea , Dell'Oste Valerio , Amatori Giulia , Bertelloni Carlo Antonio , Massimetti Gabriele , Nisita Cristiana , Dell'Osso Liliana
Published: December 2020

Frequent attenders (FAs), defined as patients repeatedly attending general practitioners, frequently exhibit underdiagnosed psychiatric comorbidities, leading to the hypothesis that frequent attendance may be related to an undetected psychiatric burden. This study explores the role of psychiatric comorbidities and psychopharmacological treatment on the clinical outcomes of a cohort of FAs of the general medical practice in Italy. The study included 75 FAs assessed by the Structured Clinical Interview for DSM-5, Clinical Global Impression, Global Assessment Functioning, and Illness Behavior Inventory, administered at baseline (T0) and after 3 months (T1). Data were analyzed on the bases of the presence of any mental disorder and selective serotonin reuptake inhibitor (SSRI) treatment, with respect to other psychopharmacological treatments. Results showed better outcomes among patients with a mental disorder, particularly anxiety, depression, and somatic symptoms disorders, and when under SSRI treatment. Our findings corroborate the role of psychiatric comorbidity on frequent attendance in the context of general clinical practice with a positive outcome when receiving appropriate treatment with SSRI.
Is King-Devick Testing, Compared With Other Sideline Screening Tests, Superior for the Assessment of Sports-related Concussion?
Authors: Arca Karissa N. , Starling Amaal J. , Acierno Marie D. , Demaerschalk Bart M. , Marks Lisa , O’Carroll Cumara B.
Published: December 2020

Background:

Concussion affects almost 4 million individuals annually. There are many sideline screening tools available to assist in the detection of sports-related concussion. The King-Devick (K-D) test in association with Mayo Clinic utilizes rapid number naming to test saccadic eye movements in order to screen for concussion. An ideal screening tool for concussion would correctly identify all athletes with active concussion. The accuracy of K-D testing compared with other sideline screening tools is undetermined.

Objective:

To critically assess current evidence regarding the utility of K-D testing as a sideline screening tool for acute concussion and compare K-D testing to other sideline concussion assessments.

Methods:

The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of concussion neurology and neuro-ophthalmology.

Results:

A recent meta-analysis was selected for critical appraisal. Cohorts analyzing athletes with sports-related concussion were selected, and utilized K-D testing as the main baseline and sideline assessment of concussion. K-D testing was found to have a high sensitivity and specificity for detecting concussion when there was worsening from baseline.

Conclusion:

K-D testing has high sensitivity and specificity for detecting sideline concussion. Compared with other sideline screening tools that do not include vision testing, it has greater accuracy. Screening for concussion is optimized when multiple testing modalities are used in conjunction.
Respiratory Variation in Aortic Blood Flow Velocity in Hemodynamically Unstable, Ventilated Neonates: A Pilot Study of Fluid Responsiveness
Authors: Oulego-Erroz Ignacio , Terroba-Seara Sandra , Alonso-Quintela Paula , Rodríguez-Núñez Antonio
Published: December 2020

Objectives:

To assess whether respiratory variation in aortic blood flow peak velocity can predict preload responsiveness in mechanically ventilated and hemodynamically unstable neonates.

Design:

Prospective observational diagnostic accuracy study.

Setting:

Third-level neonatal ICU.

Patients:

Hemodynamically unstable neonates under mechanical ventilation.

Interventions:

Fluid challenge with 10 mL/kg of normal saline over 20 minutes.

Measurements and Main Results:

Respiratory variation in aortic blood flow peak velocity and superior vena cava flow were measured at baseline (T0), immediately upon completion of the fluid infusion (T1), and at 1 hour after fluid administration (T2). Our main outcome was preload responsiveness which was defined as an increase in superior vena cava flow of at least 10% from T0 to T1. Forty-six infants with a median (interquartile range) gestational age of 30.5 weeks (28–36 wk) were included. Twenty-nine infants (63%) were fluid responders, and 17 (37%) were nonresponders Fluid responders had a higher baseline (T0) respiratory variation in aortic blood flow peak velocity than nonresponders (9% [8.2–10.8] vs 5.5% [3.7–6.6]; p < 0.001). Baseline respiratory variation in aortic blood flow peak velocity was correlated with the increase in superior vena cava flow from T0 to T1 (rho = 0.841; p < 0.001). The area under the receiver operating characteristic curve of respiratory variation in aortic blood flow peak velocity to predict preload responsiveness was 0.912 (95% CI, 0.82–1). A respiratory variation in aortic blood flow peak velocity cut-off point of 7.8% provided a 90% sensitivity (95% CI, 71–97), 88% specificity (95% CI, 62–98), 7.6 positive likelihood ratio (95% CI, 2–28), and 0.11 negative likelihood ratio (95% CI, 0.03–0.34) to predict preload responsiveness.

Conclusions:

Respiratory variation in aortic blood flow velocity may be useful to predict the immediate response to a fluid challenge in hemodynamically unstable neonates under mechanical ventilation. If our results are confirmed, this measurement could be used to guide safe and individualized fluid resuscitation in critically ill neonates.
Demonstration With Three-Dimensional Volumetric Magnetic Resonance Sequences of Deep Peroneal Nerve Compression on Os Intermetatarseum Syndrome
Authors: Sakci Zakir , Aydin Fahri , Tuncer Kutsi , Ogul Hayri
Published: December 2020

The os intermetatarseum is a rare accessory bone of the foot. It is commonly asymptomatic, as are other such accessory bones of the foot. Nevertheless, when it becomes symptomatic, it can cause “os intermetatarseum syndrome.” Reported here is a case of os intermetatarseum syndrome, which is extremely rarely seen. To the best of the authors’ knowledge, there are very few cases of os intermetatarseum syndrome in the literature.
Combining traditional and molecular epidemiology methods to quantify local HIV transmission among foreign-born residents
Authors: Tordoff Diana M. , Buskin Susan , Lechtenberg Richard , Golden Matthew R. , Kerani Roxanne P. , Herbeck Joshua T.
Published: December 2020

Objectives:

We evaluated the ability for molecular epidemiology to augment traditional HIV surveillance beyond the detection of clusters for outbreak investigation. To do this, we address a question of interest to Public Health – Seattle and King County: what proportion of HIV diagnoses among people born outside of the United States are acquired locally?

Design:

King County residents diagnosed with HIV, 2010–2018.

Methods:

We linked HIV-1 pol gene sequences to demographic information obtained from the National HIV Surveillance System, Public Health – Seattle and King County case investigation and partner services interviews. We determined the likely location of HIV acquisition based on HIV testing, travel histories and cluster-based molecular analyses.

Results:

Among 2409 people diagnosed with HIV, 798 (33%) were born outside of the United States. We inferred the location of acquisition for 77% of people born outside of the United States: 26% likely acquired HIV locally in King County (of whom 69% were MSM, 16% heterosexual), and 51% likely acquired HIV outside of King County (primarily outside of the United States). Of this 77% of people for whom we inferred the location of HIV acquisition, 45% were determined using traditional epidemiology methods and an additional 32% were inferred using molecular epidemiology methods.

Conclusion:

We found that the National HIV Surveillance System misclassified the majority of HIV-infected foreign-born residents as ‘new’ local infections, and that these cases contribute to an overestimate of local incidence. Our findings highlight how molecular epidemiology can augment traditional HIV surveillance activities and provide useful information to local health jurisdictions beyond molecular cluster detection.
Effects of HIV voluntary medical male circumcision programs on sexually transmitted infections
Authors: Matoga Mitch , Hosseinipour Mina C. , Jewett Sara , Hoffman Irving F. , Chasela Charles
Published: December 2020

Purpose of review

Evidence of the protective effect of voluntary medical male circumcision (VMMC) against HIV is well established. However, evidence of the protective effect of VMMC against other sexually transmitted infections (STIs) has been inconsistent or scarce across different populations and settings. This review summarizes the current evidence on the effect of VMMC for HIV prevention on acquisition and transmission of other STIs in heterosexual men, women, and men who have sex with men (MSM).

Recent findings

Recent findings continue to strongly support the protective effect of male medical circumcision against acquisition and transmission of herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV) and syphilis infections in heterosexual men and women, and bacterial vaginosis and trichomoniasis in women. There is emerging evidence on the protective effect of VMMC against acquisition of hepatitis B and Mycoplasma genitalium infections in heterosexual men, and HSV-2, HPV, and syphilis in MSM.

Evidence on the protective effect of VMMC against acquisition and transmission of common STIs is available for heterosexual men and women but more evidence is required for MSM. This review supports policy recommendations for the protective benefits of VMMC against STIs.
Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections
Authors: Ogunbodede Olaitan T. , Zablotska-Manos Iryna , Lewis David A.
Published: December 2020

Purpose of review

This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission.

Recent findings

COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities.

In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response.

Video abstract

http://links.lww.com/COID/A31.
Ring Sclerosis in Prostate Cancer
Authors: Marcus Charles , Baum Yoram , Abiodun-Ojo Olayinka A. , Jani Ashesh B. , Schuster David M.
Published: December 2020

Prostate cancer osteoblastic metastases may have different morphologies, and some of these may overlap with certain benign bone lesions. In this series of 5 prostate cancer patients, we describe bone lesions with central lucency and surrounding peripheral sclerosis and their varying appearances on different imaging modalities. Although prostate cancer metastases are commonly associated with sclerotic lesions, they can also present as osteolytic or lucent lesions, and these lesions should be carefully evaluated. The findings emphasize the importance of correlation with prior imaging, comparing findings on different imaging techniques and follow-up to differentiate benign disease from metastatic disease in these situations.
18F-FDG PET/CT for Staging and Response Evaluation in a Rare Case of Childhood Ovarian Primitive Neuroectodermal Tumor
Authors: Sharma Punit , Ghosh Indranil , Khan Enam Murshed
Published: December 2020

Primitive neuroectodermal tumor (PNET) is an aggressive small cell malignancy. Apart from the central nervous system, they can arise from peripheral sites as well. Ovarian PNETs are extremely rare neoplasms. We here present a case of childhood ovarian PNET, where 18F-FDG PET/CT was efficiently used for staging and response evaluation.
Docetaxel-Induced Interstitial Pneumonitis Detected on 68Ga-PSMA PET/CT
Authors: Kumar Sunil , Singh Harmandeep , Das Chandan K. , Kumar Rajender , Mittal Bhagwant Rai
Published: December 2020

68Ga-PSMA PET/CT is a commonly performed procedure in the staging of intermediate- and high-risk prostate cancer after biochemical recurrence. Uptake of 68Ga-PSMA in benign conditions is also reported in the literature. Docetaxel is the mainstay of treatment in high-volume hormone-sensitive prostate cancer and castration-resistant prostate cancer. The major treatment-emergent adverse drug reactions attributed to docetaxel include myelosuppression, alopecia, and asthenia. Interstitial pneumonitis is seen in less than 2% of docetaxel-treated patients. We present a case of metastatic castration-resistant prostate cancer, wherein docetaxel-induced interstitial pneumonitis was detected on 68Ga-PSMA PET/CT, after docetaxel treatment.
18F-FDG PET/CT for Monitoring of Disease Progression in Metastatic Perivascular Epithelioid Cell Tumor
Authors: Holzgreve Adrien , Fabritius Matthias P. , Knösel Thomas , Renz Bernhard W. , Lindner Lars H. , Di Gioia Dorit , Bartenstein Peter , Rübenthaler Johannes , Tiling Reinhold
Published: December 2020

A 38-year-old woman presented for 18F-FDG PET/CT after multiple intra-abdominal surgical resections of a rare recurrent perivascular epithelioid cell tumor of the gastrointestinal tract. A solitary pelvic metastasis was detected, but surprisingly exhibited neither increased glucose consumption nor contrast enhancement on CT. Follow-up 18F-FDG PET/CT staging in the further disease course revealed multiple abdominal metastases, now, however, with markedly increased 18F-FDG uptake and intraoperatively correlating widespread peritoneal sarcomatosis. This case gives preliminary insight into monitoring of disease progression in metastatic perivascular epithelioid cell tumor, although the underlying pathophysiological bases for varying 18F-FDG uptake in PET/CT are not yet fully understood.
Easily Applicable Single-incision Laparoscopic Appendectomy Using Straightforward Instrumental Alignment and Conventional Laparoscopic Instruments
Authors: Chong Eui Hyuk , Cho Hye Jung , Jeong Sung Yub , Kim Woo Ram , Choi Sung Hoon
Published: December 2020

Background:

Laparoscopic appendectomy is one of the most frequently performed operations. As such, single-incision laparoscopic appendectomy (SILA) is indicated as a feasible and safe procedure comparable to conventional laparoscopic appendectomy (CLA). However, novice surgeons face challenges in performing SILA, because the role of the surgeon’s hands is reversed. We introduce an easily applicable technique of SILA by adapting the alignment of CLA.

Methods:

A series of 61 consecutive patients underwent SILA between January 2019 and December 2019 by 4 surgeons at Bundang CHA Medical Center. Acute appendicitis was diagnosed preoperatively by abdomino-pelvis computed tomography or ultrasonography. During the operation, a 3-channel Glove port was used with conventional laparoscopic instruments.

Results:

The study participants consisted of 32 males and 29 females, with a mean age of 26.8 years (range, 4 to 66 y). The mean body mass index was 20.79 kg/m2 (range, 11.89 to 27.04 kg/m2). The mean operation time was 37.5±17.0 minutes. There was only 1 case of conversion with 1 additional port. Eight patients (13.1%) experienced postoperative complications defined by Dindo-Clavien-Strasberg classification: grade 1 wound complication in 7 patients and grade 2 postoperative bowel obstruction in 1 patient. The mean postoperative hospital stay was 2.5±1.3 days.

Conclusion:

Alignment of the instruments during CLA was successfully implemented into a SILA. Our new, easily applicable SILA technique will decrease the learning curve for novice surgeons in performing single-incision laparoscopic surgery.
Association of Patient Race With Type of Pelvic Organ Prolapse Surgery Performed and Adverse Events
Authors: Cardenas-Trowers Olivia O. , Gaskins Jeremy T. , Francis Sean L.
Published: December 2020

Objectives

This study aimed to determine if there are differences in (1) surgical procedures performed for pelvic organ prolapse (POP) and (2) rates of adverse events between racial groups.

Methods

We conducted a retrospective cohort study of women 18 years and older who underwent POP surgery using the 2005–2015 American College of Surgeons National Surgical Quality Improvement Program database. Race was categorized as Black, White, Hispanic, and other minority. Pelvic organ prolapse procedures were organized into 4 groups: (1) hysterectomy without concurrent POP procedures, (2) vaginal wall repair(s) only without apical suspension, (3) apical suspension with or without vaginal wall repair(s), and (4) obliterative procedures. Patient characteristics and rates of adverse events were noted. A multivariable logistic regression model was used to assess the association between patient race and surgical procedures performed for POP.

Results

We identified 48,005 women who met the inclusion criteria. Most women who underwent POP surgery were White (79.6% [n = 38,191]). Although only contributing to 4.7% (2,299) of the cohort, Black women experienced higher complication rates compared with White women (10.7% [246] for Black vs 8.9% [3,417] for White women, P < 0.01). Hispanic and other minority women were less likely to undergo an apical suspension than White women (adjusted odds ratios [aORs], 0.79 [0.75–0.84] for Hispanic women and 0.78 [0.71–0.86] for other minority women; P < 0.001 for both). Obliterative procedures were more likely to be performed in Black, in Hispanic, and especially in other minority women (aORs, 1.53 [1.20–1.92] for Black, 1.33 [1.12–1.58] for Hispanic, and 3.67 [3.04–4.42] for other minority women; P < 0.001 for all).

Conclusions

Racial differences exist among women who undergo POP surgery.
New-Onset Seizures in Three COVID-19 Patients: A Case Series
Authors: Mithani Farhan , Poursheykhi Meryim , Ma Brandy , Smith Robert G. , Hsu Steven H. , Gotur Deepa
Published: December 2020

Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.
Offline perception: an introduction
Authors: Fazekas Peter , Nanay Bence , Pearson Joel
Published: December 2020

Experiences that are self-generated and independent of sensory stimulations permeate our whole life. This theme issue examines their similarities and differences, systematizes the literature from an integrative perspective, critically discusses state-of-the-art empirical findings and proposes new theoretical approaches. The aim of the theme issue is to foster interaction between the different disciplines and research directions involved and to explore the prospects of a unificatory account of offline perception in general.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Interactions between the neural correlates of dispositional internally directed thought and visual imagery
Authors: Karapanagiotidis Theodoros , Jefferies Elizabeth , Smallwood Jonathan
Published: December 2020

Cognition is not always directed to the events in the here and now and we often self-generate thoughts and images in imagination. Important aspects of these self-generated experiences are associated with various dispositional traits. In this study, we explored whether these psychological associations relate to a common underlying neurocognitive mechanism. We acquired resting state functional magnetic resonance imaging data from a large cohort of participants and asked them to retrospectively report their experience during the scan. Participants also completed questionnaires reflecting a range of dispositional traits. We found thoughts emphasizing visual imagery at rest were associated with dispositional tendency towards internally directed attention (self-consciousness and attentional problems) and linked to a stronger correlation between a posterior parietal network and a lateral fronto-temporal network. Furthermore, decoupling between the brainstem and a lateral visual network was associated with dispositional internally directed attention. Critically, these brain–cognition associations were related: the correlation between parietal–frontal regions and reports of visual imagery was stronger for individuals with increased connectivity between brainstem and visual cortex. Our results highlight neural mechanisms linked to the dispositional basis for patterns of self-generated thought, and suggest that accounting for dispositional traits is important when exploring the neural substrates of self-generated experience (and
vice versa
).

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Involuntary autobiographical memories and their relation to other forms of spontaneous thoughts
Authors: Berntsen Dorthe
Published: December 2020

Involuntary autobiographical memories are memories of personal events that come to mind spontaneously—that is, with no conscious initiation of the retrieval process. Such spontaneously arising memories were long ignored in cognitive psychology, which generally has focused on controlled and strategic forms of remembering, studied in laboratory settings. Recent evidence shows that involuntary memories of past events are highly frequent in daily life, and that they represent a context-sensitive, and associative way of recollecting past events that involves little executive control. They operate by constraints that favour recent events and events with a distinct feature overlap to the current situation, which optimizes the probability of functional relevance to the ongoing situation. In addition to adults, they are documented in young children and great apes and may be an ontogenetic and evolutionary forerunner of strategic retrieval of past events. Findings suggest that intrusive involuntary memories observed clinically after traumatic events should be viewed as a dysfunctional subclass of otherwise functional involuntary autobiographical memories. Because of their highly constrained, situation-dependent and automatic nature, involuntary autobiographical memories form a distinct category of spontaneous thought that cannot be equated with mind wandering.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Virtual reality training of lucid dreaming
Authors: Gott Jarrod , Bovy Leonore , Peters Emma , Tzioridou Sofia , Meo Stefano , Demirel Çağatay , Esfahani Mahdad Jafarzadeh , Oliveira Pedro Reis , Houweling Thomas , Orticoni Alessandro , Rademaker Anke , Booltink Diede , Varatheeswaran Rathiga , van Hooijdonk Carmen , Chaabou Mahmoud , Mangiaruga Anastasia , van den Berge Erik , Weber Frederik D. , Ritter Simone , Dresler Martin
Published: December 2020

Metacognitive reflections on one's current state of mind are largely absent during dreaming. Lucid dreaming as the exception to this rule is a rare phenomenon; however, its occurrence can be facilitated through cognitive training. A central idea of respective training strategies is to regularly question one's phenomenal experience: is the currently experienced worldreal, or just a dream? Here, we tested if such lucid dreaming training can be enhanced with dream-like virtual reality (VR): over the course of four weeks, volunteers underwent lucid dreaming training in VR scenarios comprising dream-like elements, classical lucid dreaming training or no training. We found that VR-assisted training led to significantly stronger increases in lucid dreaming compared to the no-training condition. Eye signal-verified lucid dreams during polysomnography supported behavioural results. We discuss the potential mechanisms underlying these findings, in particular the role of synthetic dream-like experiences, incorporation of VR content in dream imagery serving as memory cues, and extended dissociative effects of VR session on subsequent experiences that might amplify lucid dreaming training during wakefulness.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.
Hallucinations as intensified forms of mind-wandering
Authors: Fazekas Peter
Published: December 2020

This paper argues for a novel way of thinking about hallucinations as intensified forms of mind-wandering. Starting from the observation that hallucinations are associated with hyperactive sensory areas underlying the content of hallucinatory experiences and a confusion with regard to the reality of the source of these experiences, the paper first reviews the different factors that might contribute to the impairment of reality monitoring. The paper then focuses on the sensory characteristics determining the vividness of an experience, reviews their relationship to the sensory hyperactivity observed in hallucinations, and investigates under what circumstances they can drive reality judgements. Finally, based on these considerations, the paper presents its main proposal according to which hallucinations are intensified forms of mind-wandering that are amplified along their sensory characteristics, and sketches a possible model of what factors might determine if an internally and involuntarily generated perceptual representation is experienced as a hallucination or as an instance of mind-wandering.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Impact of mass testing during an epidemic rebound of SARS-CoV-2: A modelling study
Authors: Bosetti Paolo , Tran Kiem Cécile , Yazdanpanah Yazdan , Fontanet Arnaud , Lina Bruno , Colizza Vittoria , Cauchemez Simon
Published: December 2020

We used a mathematical model to evaluate the impact of mass testing in the control of SARS-CoV-2. Under optimistic assumptions, we find that one round of mass testing may reduce daily infections by up to 20-30%. As a consequence, very frequent testing would be required to control a quickly growing epidemic if other control measures were to be relaxed. Mass testing is most relevant when epidemic growth remains limited, thanks to a combination of interventions.
MSDC-0602K, A Novel Insulin-Sensitizer Improves Insulinemia and Fatty Liver Disease Alone and in Addition to Liraglutide in Mice
Authors: Kamm Dakota R. , Pyles Kelly D. , Sharpe Martin C. , Healy Laura , Colca Jerry R. , McCommis Kyle S.
Published: December 2020

Aims/hypothesis

Insulin sensitizers and incretin mimetics are antidiabetic agents with vastly different mechanisms of action. Additionally, while thiazolidinedione (TZD) insulin sensitizers are associated with the side-effect of weight gain, glucagon-like peptide-1 receptor agonists (GLP-1RAs) can induce weight loss. We hypothesized that combination therapy with a novel TZD insulin sensitizer and the GLP-1RA Liraglutide would more significantly improve mouse models of diabetes and nonalcoholic steatohepatitis (NASH) compared to individual therapy.

Methods

db/dbmice were treated with the novel TZD MSDC-0602K by oral gavage, Liraglutide (Lira) by s.c. injection, combination 0602K+Lira, or both vehicle solutions. Vehicle-treateddb/+ mice were included as non-obese controls. To assess treatment effects on nonalcoholic fatty liver disease, MS-NASH mice were similarly treated with vehicle, either drug individually, or in combination. Lastly, islets were isolated from C57BL/6J mice to assess glucose-stimulated insulin secretion (GSIS).

Results

0602K-treateddb/dbmice displayed slight weight gain but completely corrected glycemia and markedly improved glucose tolerance. Lira slightly reduced body weights and modestly improved glycemia. 0602K+Lira combination still induced slight weight gain but completely corrected glycemia and improved glucose tolerance beyond leandb/+ levels. As expected, 0602K resulted in reduced plasma insulin, whereas Lira further increased the hyperinsulinemia ofdb/dbmice. Surprisingly, 0602K+Lira treatment reduced plasma insulin and C-peptide to the same extent as mice treated with 0602K alone. 0602K did not directly reduce GSIS in isolated islets, thus the reduced insulinemia with 0602K is likely compensatory due to improved insulin action. In the MS-NASH mouse model, both 0602K or Lira alone improved plasma ALT and AST, and liver histology, but more significant improvements were observed with 0602K+Lira combination therapy. 0602K or 0602K+Lira also increased pancreatic insulin content in bothdb/dband MS-NASH mice.

Conclusions

MSDC-0602K corrected glycemia and reduced insulinemia when given alone, or in combination with Lira. However, 0602K+Lira combination more significantly improved glucose tolerance indb/dbmice, and more significantly improved liver histology in MS-NASH mice.
Spatio-temporal spawning patterns and early growth of Japanese sardine in the western North Pacific during the recent stock increase
Authors: Niino Yohei , Furuichi Sho , Kamimura Yasuhiro , Yukami Ryuji
Published: December 2020

Spatio-temporal patterns in spawning influence growth and survival by affecting the environment experienced by offspring during their early life stages. Therefore, identifying changes in spawning patterns can help researchers understand population dynamics and recruitment fluctuations. The Japanese sardineSardinops melanostictusis a small pelagic fish that undergoes large stock fluctuations. Although spawning patterns are known to change spatially and temporally with stock abundance, little information is available on the processes underlying stock increases. This study aimed to describe changes in spawning pattern and early growth of Japanese sardine during the recent period of stock increase, and to clarify the effects of different spawning periods on offspring growth. We examined trends in egg abundance in the western North Pacific in 2004–2018 and analyzed hatch dates and growth trajectories by otolith microstructure analysis of juveniles from the Kuroshio–Oyashio transitional region (the species’ main nursery area). During the study period, the main spawning area shifted from the western to the eastern part of this region off Japan, and spawning in the eastern part roughly coincided with juvenile hatch dates. Hatch dates also shifted from mid-March at the earliest to February and early March from 2013 onwards. Although early-hatched cohorts (which originate offshore of eastern Japan) experienced slower initial growth, they likely played an important role in the recent stock increase. Successful recruitment of these cohorts may have been facilitated by factors such as early hatching and transport to the nursery, which reduces the frequency of predator encounters.
Precise base editing for thein vivostudy of developmental signaling and human pathologies in zebrafish
Authors: Rosello Marion , Vougny Juliette , Czarny François , Mione Maria Caterina , Concordet Jean-Paul , Albadri Shahad , Del Bene Filippo
Published: December 2020

While zebrafish is emerging as a new model system to study human diseases, an efficient methodology to generate precise point mutations at high efficiency is still lacking. Here we show that base editors can generate C-to-T point mutations with high efficiencies without other unwanted on-target mutations. In addition, we established a new editor variant recognizing an NAA PAM, expanding the base editing possibilities in zebrafish. Using these approaches, we first generated a base change in the ctnnb1 gene, mimicking oncogenic mutations of the human gene known to result in constitutive activation of endogenous Wnt signaling. Additionally, we precisely targeted several cancer-associated genes among which cbl. With this last target we created a new zebrafish dwarfism model. Together our findings expand the potential of zebrafish as a model system allowing new approaches for the endogenous modulation of cell signaling pathways and the generation of precise models of human genetic disease associated-mutations.
Genome based analyses reveals the presence of heterotypic synonyms and subspecies in Bacteria and Archaea
Authors: Madhaiyan Munusamy , Saravanan Venkatakrishnan Sivaraj , See-Too Wah-Seng
Published: December 2020

Term heterotypic synonym refers to different names have been associated with different type strains, however from the opinion of a bacteriologist, different names belongs to the same taxon and term subspecies refers to strains and genetically close organisms that were diverging phenotypically. In this study, sequenced and publicly available genomes in the Edgar 2.0 server were carefully analysed and based on high (>98 %) amino acid identity value, synonyms were putatively identified. The 16S rRNA gene sequence of those species were used for the construction of maximum likelihood based phylogenetic trees to infer the genetic closeness or distance by examining the tree topology and clustering of the organisms within clades. They were further subjected to overall genome related indices like digital DNA-DNA hybridization, average nucleotide identity to confirm the presence of synonyms or subspecies with phenotypic data support. The outcome of this polyphasic taxonomic re-analysis was identification of 40 later heterotypic synonyms and 13 subspecies spread over phylumActinobacteria,Bacteroidetes,Firmicutes,Nitrospirae,ProteobacteriaandThermotogaeand in domainArchaea.
TM6SF2/PNPLA3/MBOAT7 loss-of-function genetic variants impact on NAFLD development and progression both in patients and inin vitromodels
Authors: Longo Miriam , Meroni Marica , Erconi Veronica , Carli Fabrizia , Macchi Chiara , Fortunato Francesco , Ronchi Dario , Sabatini Silvia , Paolini Erika , De Caro Emilia Rita , Alisi Anna , Miele Luca , Soardo Giorgio , Comi Giacomo Pietro , Valenti Luca , Ruscica Massimiliano , Fracanzani Anna L , Gastaldelli Amalia , Dongiovanni Paola
Published: December 2020

Background and aims

The I148M PNPLA3, the rs641738 inMBOAT7/TMC4locus and the E167K TM6SF2 polymorphisms represent the main predisposing factors to non-alcoholic fatty liver disease (NAFLD) development and progression. We previously generated a full knockout ofMBOAT7in HepG2 cells (MBOAT7-/-), homozygous for the I148M PNPLA3. Therefore, we aimed to:1) investigate the synergic impact of the 3 at-risk variants on liver injury and hepatocellular carcinoma (HCC) in a large cohort of NAFLD patients;2) createin vitromodels of genetic NAFLD by silencingTM6SF2in both HepG2 and MBOAT7-/-cells.

Methods

NAFLD patients (n=1380) of whom 121 had HCC were stratified with a semi-quantitative score ranging from 0 to 3 according to the number ofPNPLA3,TM6SF2andMBOAT7at-risk variants.TM6SF2was silenced in HepG2 (TM6SF2-/-) and MBOAT7-/-(MBOAT7-/-TM6SF2-/-) through CRISPR/Cas9.

Results

In NAFLD patients, the additive weight of these mutations was associated with liver disease severity and increased risk to develop HCC. In HepG2 cells,TM6SF2silencing altered lipid composition and induced the accumulation of micro-vesicular LDs, whereas the MBOAT7-/-TM6SF2-/-cells showed a mixed micro/macro pattern of LDs.TM6SF2deletion strongly affected endoplasmic reticulum (ER) and mitochondria ultrastructures thus increasing ER/oxidative stress. Mitochondrial number raised in both TM6SF2-/-and MBOAT7-/-TM6SF2-/-models, suggesting an unbalancing in mitochondrial dynamics and the silencing of bothMBOAT7andTM6SF2impaired mitochondrial activity with a shift towards anaerobic glycolysis. MBOAT7-/-TM6SF2-/-cells also showed the highest proliferation rate.

Conclusions

The co-presence of the 3 at-risk variants impacts on NAFLD course, in both patients and experimental models affecting LDs accumulation, mitochondrial functionality and metabolic reprogramming towards HCC.
Wildfire affects circulating hormone levels and the expression of male sexual plumage in a tropical songbird
Authors: Boersma Jordan , Barron Douglas G. , Baldassarre Daniel T. , Webster Michael S. , Schwabl Hubert
Published: December 2020

Natural disturbances like drought and wildfires are expected to increase in prevalence, so understanding how organisms are affected is a key goal for conservationists and biologists alike. While many studies have illustrated long-term effects of perturbations on survival and reproduction, little is known of short-term effects to physiology and sexual signal expression. Ornamental traits have been proposed as reliable indicators of environmental health, yet studies are lacking in the context of natural disturbances. Here we present short-term responses of male Red-backed Fairywrens (Malurus melanocephalus) to wildfire near the onset of the typical breeding season. Males of this species are characterized by plastic expression of sexual plumage phenotypes in their first breeding season. Using two populations with Fairywren captures before and after separate wildfires we illustrate that wildfire suppressed molt into ornamented plumage, including in third year males that typically show little plasticity in ornamentation. Baseline plasma corticosterone was elevated in males sampled after fire, but condition (furcular fat stores) was unaffected. Although testosterone levels did not decrease following fire, we found a positive correlation between testosterone and plumage ornamentation. In addition, males molting in ornamental plumage had higher circulating levels of testosterone than males molting in unornamented plumage following fire. Collectively, these findings suggest that wildfires inhibit or greatly delay acquisition of ornamentation in young males without exerting obvious effects on condition, but rather through subtle effects on testosterone and corticosterone circulation. This natural experiment also reveals that expression of alternative male reproductive phenotypes in this species is sensitive to environmental conditions and more plastic than previously assumed.
Gating transitions and modulation of a hetero-octameric AMPA glutamate receptor
Authors: Zhang Danyang , Watson Jake F. , Matthews Peter M. , Cais Ondrej , Greger Ingo H.
Published: December 2020

AMPA glutamate receptors (AMPARs) mediate the majority of excitatory transmission in the brain, and enable synaptic plasticity that underlies learning1. A diverse array of AMPAR signaling complexes are established by receptor auxiliary subunits, associating in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here, we determine cryo-electron microscopy structures of the heteromeric GluA1/2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states (at 3.2 and 3.7 Å, respectively). Consequential for gating regulation, two γ8 and two CNIH2 subunits lodge at distinct sites beneath the ligand-binding domains of the receptor tetramer, with site-specific lipids shaping each interaction. Activation leads to a stark asymmetry between GluA1 and GluA2 along the ion conduction path, and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, that promotes the active-state conformation. In addition, both γ8 and CNIH2 pivot towards the pore exit on activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this ER-export factor into a powerful positive AMPAR modulator, capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.
The RelA hydrolase domain: a molecular switch for (p)ppGpp synthesis
Authors: Sinha Anurag Kumar , Winther Kristoffer Skovbo
Published: December 2020

Bacteria synthesize guanosine tetra- and penta phosphate (commonly referred to as (p)ppGpp) in response to environmental stresses. (p)ppGpp reprograms cell physiology and is essential for stress survival, virulence and antibiotic tolerance. Proteins of the RSH superfamily (RelA/SpoT Homologues) are ubiquitously distributed and hydrolyze or synthesize (p)ppGpp. Structural studies have suggested that the shift between hydrolysis and synthesis is governed by conformational antagonism between the two active sites in RSHs. RelA proteins of γ-proteobacteria exclusively synthesize (p)ppGpp and encode an inactive pseudo-hydrolase domain.Escherichia coliRelA synthesizes (p)ppGpp in response to amino acid starvation with cognate uncharged tRNA at the ribosomal A-site, however, mechanistic details to the regulation of the enzymatic activity remain elusive. Here, we show a role of the enzymatically inactive hydrolase domain in modulating the activity of the synthetase domain of RelA. Using mutagenesis screening and functional studies, we identify a loop region (residues 114-130) in the hydrolase domain, which controls the synthetase activity. We show that a synthetase-inactive loop mutant of RelA is not affected for tRNA binding, but binds the ribosome less efficiently than wildtype RelA. Our data support the model that the hydrolase domain acts as a molecular switch to regulate the synthetase activity.
Synchrotron radiation X-ray microtomography for the visualization of intra-cochlear anatomy in human temporal bones implanted with a perimodiolar cochlear implant electrode array
Authors: Sismono Fergio , Mancini Lucia , Leblans Marc , Goyens Jana , De Greve Glynnis , Schneiders Sara , Beckers Karen , Dirckx Joris , De Foer Bert , Zarowski Andrzej
Published: December 2020

Recently, synchrotron radiation computed microtomography (SRµCT) has emerged as a promising tool for non-destructive, in situ visualization of cochlear implant electrode arrays inserted into a human cochlea. Histological techniques have been the `gold standard' technique for accurate localization of cochlear implant electrodes but are suboptimal for precise three-dimensional measurements. Here, an SRµCT experimental setup is proposed that offers the benefit of a high spatial and contrast resolution (isotropic voxel size = 4.95 µm and propagation-based phase-contrast imaging), while visualizing the soft-tissue structures and electrode array of the cochlear implant simultaneously. In this work, perimodiolar electrode arrays have been tested, which incorporate thick and closely spaced platinum–iridium contacts and wiring. These data can assist cochlear implant and hearing research, can be used to verify electrode segmentation techniques for clinical computed tomography or could be utilized to evaluate cochlear implant electrode array designs.