bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractive Outcomes After Descemet Membrane Endothelial Keratoplasty + Cataract/Intraocular Lens Triple Procedure: A Fellow Eye Comparison
Authors: Augustin Victor A. , Weller Julia M. , Kruse Friedrich E. , Tourtas Theofilos
Published: November 2020

Purpose:

Descemet membrane endothelial keratoplasty is often combined with phacoemulsification and intraocular lens implantation (DMEK + cataract/IOL triple procedure) in phakic patients. This procedure results in a refractive shift that is difficult to predict. The aim of this study was to evaluate the hypothesis that the refractive shift in the second eye follows the shift in the first eye.

Methods:

In this retrospective, single-center, consecutive case series, the refractive outcomes of 254 eyes of 127 patients who underwent DMEK + cataract/IOL triple procedure in both eyes for Fuchs endothelial corneal dystrophy have been analyzed. Main outcome measures were spherical equivalent outcome (shift calculations), best spectacle-corrected visual acuity, central corneal thickness, and posterior simulated keratometry.

Results:

The mean best spectacle-corrected visual acuity before surgery was 0.51 ± 0.24 and increased to 0.19 ± 0.15 (logMAR) after surgery (P < 0.001). After surgery, a mean hyperopic shift of 0.98 ± 0.89 D was observed. The refractive shift was 1.03 ± 0.93 D and 0.92 ± 1.02 D, in the first and second eyes, respectively (P = 0.435). In a paired analysis, the mean difference of the refractive shift between the first and second eyes was 0.49 ± 0.43 D.

Conclusions:

In our fellow eye comparison, the refractive shift after DMEK + cataract/IOL triple procedure in the second eye was comparable with the shift in the first eye. As a consequence, the refractive outcome of the first eye might serve as a reference for optimizing the refractive target in the second eye. Further studies investigating the influence of corneal parameters on refractive shift are needed for a more predictable lens power selection.
Burden of Tuberculosis in South African Children During Treatment for Underlying Malignancies
Authors: Naidu Gita , Izu Alane , Madimabe Metsekae Richard , Poyiadjis Stelios , MacKinnon Diane , Rowe Biance , Madhi Shabir Ahmed
Published: November 2020

Background:

Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer.

Methods:

Children with cancer were enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings.

Results:

We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death.

Conclusions:

Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.
Chapter 6: Attritional Glenoid Bone Loss in the Shoulder: Operative Considerations
Authors: Sparavalo Sara , Wong Ivan
Published: November 2020

Patients with recurrent anterior shoulder instability often have glenoid bone loss present in addition to soft tissue pathologies. It is known that patients with significant glenoid bone loss are best treated with a boney augmentation procedure as opposed to a soft tissue Bankart repair because of the high rate of recurrent instability that results from a Bankart repair. Although the Latarjet technique has been the gold-standard treatment for patients with glenoid bone loss because of the low incidence of recurrent instability, it has a high complication rate and a steep learning curve. Herein, the authors present the technique and outcomes for arthroscopic anatomic glenoid reconstruction that has a similar complication rate to the Bankart repair but with a low recurrence rate similar to the Latarjet. This procedure is safe, has a short learning curve, low recurrence rate, and positive patient-reported outcomes.
Mental Health and Social Care Professionals After a Patient Suicide: Interrelation Between Support Needed, Sought, and Received
Authors: CASTELLI DRANSART DOLORES ANGELA , HEEB JEAN-LUC , GULFI ALIDA
Published: November 2020

This article investigates the support needed, sought, and received by professionals following a patient suicide. A self-administered questionnaire about the consequences of patient suicide and support issues was completed by 704 professionals. Profiles of support were defined using a 3-dimensional, 8-fold typology based on need for, search for, and sufficiency of support. Stress reactions, professionals’ characteristics, relationship with the patient, training, and providers of support were used to characterize the profiles. Most professionals acknowledged receiving sufficient support to manage the aftermath of patient suicide. Almost two thirds of the respondents who received sufficient support reported either not needing or seeking support or both needing and seeking support. Almost 1 in 10 respondents who reported needing and seeking support received insufficient support. Stress reactions were highest among professionals who needed but did not receive sufficient support. Professionals who did not need or seek support were less often in a relationship with the patient at the time of the suicide and less frequently felt close to or responsible for the patient than those who needed and sought support. Trained professionals were overrepresented among those who reported receiving sufficient support while they were less likely to report needing and seeking support or receiving insufficient support. Findings concerning support and its relationship to risk and protective factors suggest the need to adopt a multidimensional approach that distinguishes among support needed, sought, and received. Although an association may exist between perceived stress and need for support, involvement of professionals in the patient relationship may also be linked with the search for support, while training may be associated with receipt of sufficient support.
Bostwick Autoderm and Implant Technique: Improved Outcomes for Obese Patients in Immediate Breast Reconstruction
Authors: Danker Sara , Schmitt Mike , Smith Ning , Chong H. Jonathan , Sandholm Patricia H. , Murphy Jennifer A. , Ladizinsky Daniel A.
Published: November 2020

Background:

The Bostwick autoderm technique uses the patient’s own deepithelialized mastectomy flap for lower pole coverage of an implant, similar to the use of acellular dermal matrix. The skin is closed over the autoderm flap in a Wise pattern. Unlike acellular dermal matrix, autoderm is perfused tissue that offers immediate protection for the implant. Because of this extra protective vascularized layer, implants can often be salvaged in cases of wound breakdown.

Methods:

A retrospective review of 370 patients and 592 immediate implant reconstructed breasts was performed.

Results:

Four hundred twenty-two (71 percent) were reconstructed with autoderm, 93 (16 percent) with total muscle coverage, and 77 (13 percent) with acellular dermal matrix. Higher body mass index patients were overrepresented in the autoderm group. Ninety-one of the reconstructions in the autoderm group (21.3 percent) were performed on patients with a body mass index greater than 35 kg/m2 compared to four (4.3 percent) in the total muscle coverage group and two (2.6 percent) in the acellular dermal matrix group. Despite this higher proportion of obese patients, the complication rate in the autoderm group was similar to that of the acellular dermal matrix group. The implant loss rate for all reconstructions was 3.4 percent. There were 17 losses (4 percent) in the autoderm group, zero in the total muscle coverage group, and 20 (3.4 percent) in the acellular dermal matrix group. There were 15 patients and 28 breasts that had prepectoral reconstruction.

Conclusion:

The autoderm flap is a safe, reliable, and resource-conscientious technique for immediate, implant-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Reduced structural covariance connectivity of defaut mode network and salience network in MRI-normal focal epilepsy
Authors: Shu Ting , Xiao Xinlan , Long Zhiliang , Zhang Ran
Published: November 2020

Neuroimaging studies have found altered functional connectivity of default mode network (DMN) and salience network (SN) in patients with focal epilepsy (FE). However, the structural basis underlying the functional connectivity disturbance in the patients is still unclear. Sixteen MRI-normal FE and 22 healthy controls were included in the current study. The T1 structural image of each participant was obtained. Seed-based structural covariance connectivity was employed to investigate changes of structural covariance connectivity of DMN and SN in FE patients. We further evaluated gray matter volume changes of brain areas showing altered structural connectivity in the patients. We found that patients with FE showed reduced connectivity of posterior cingulate cortex and left medial prefrontal cortex, hippocampus and orbitofrontal cortex, and reduced connectivity of right fronto-insula cortex with left insula, orbitofrontal cortex, opercum part of inferior frontal cortex and right medial prefrontal cortex compared with healthy controls. Moreover, those brain areas showing significant reduced structural covariance connectivity in patients with FE also had a loss of gray matter volume, indicating that reduced structural connectivity of DMN and SN might be associated with gray matter atrophy in the patients. Those results highlight the crucial role of DMN and SN in the pathology of patients with FE, and provided structural basis for the functional disturbance of the two networks in this disease.
Repeated and single maternal separation specifically alter microglial morphology in the prefrontal cortex and neurogenesis in the hippocampus of 15-day-old male mice
Authors: Reshetnikov Vasiliy , Ryabushkina Yulia , Kovner Anna , Lepeshko Arina , Bondar Natalia
Published: November 2020

Early-life adversity impairs neuronal plasticity of the developing brain. In rodents, brain maturation processes, including neuro- and synaptogenesis, myelination, microglial maturation, and hypothalamic–pituitary–adrenal (HPA) axis development continue in the postnatal period. In our study, two models of early-life stress were used: repeated maternal separation (MS) from postnatal day (PND) 2 to PND14 for 3 h daily and single maternal deprivation (MD) on PND9 for 24 h. Effects of each type of early-life stress on neuron density, neurogenesis, microglial morphology, and HPA axis programming were studied in 15-day-old male mice. Neither early-life stress paradigm affected the expression of stress-related genes (Crh, Avp, Crhr1, Crhr2, Nr3c1, and Nr3c2) and the serum level of corticosterone on PND15. Immunohistochemical analysis was performed on slices of the hippocampus and prefrontal cortex (PFC) with antibodies against a marker of mature neurons (NeuN), of microglia (Iba1), proliferating cells (Ki67), and immature neurons (DCX). We found higher density of ameboid microglia and intermediate microglia in the PFC in groups MS and MD, respectively, than in a control group. In both stressed groups, a higher number of Ki67-positive cells was noted in the dentate gyrus. Thus, in mice, the process of transformation of ameboid microglia into ramified ones as well as a neurogenesis reduction take place during the second postnatal week, whereas early-life stress can disturb these processes in a stress- and region-dependent manner.
Creatine kinase levels in psychotic patients who use cannabinoids
Authors: Fruman Amir , Stryjer Refael , Weizman Shira , Shelef Assaf
Published: November 2020

Elevated serum levels of creatine kinase enzymes have been found in brain injuries and psychosis. Cannabinoid use is associated with increased frequency and duration of hospitalizations. We examined whether creatine kinase levels differ in psychotic cannabinoid users and the association between creatine kinase levels and clinical measures (duration of hospitalization and need for mechanical restraint). Computerized medical records of 124 men hospitalized due to acute psychotic episodes were reviewed. Creatine kinase levels and various clinical measures at admission were documented. Cannabis users were significantly younger than nonusers. Duration of illness was longer among nonusers. Log creatine kinase among cannabinoid users (N = 32) was numerically higher compared to nonusers (N = 92) (5.6 ± 1 vs. 5.2 ± 0.9, respectively). Significantly higher rate of elevated creatine kinase levels (creatine kinase > 195 U/l) was detected in the cannabinoid users compared to nonusers (59.4% vs. 38%, respectively; P < 0.04). No association was found between creatine kinase levels and use of mechanical restraints and hospitalization days. Higher rate of elevated creatine kinase levels was observed in hospitalized psychotic cannabinoid users, possibly due to a cannabis activity at peripheral or brain tissues. Studies in larger, more diverse clinical populations are needed to confirm this finding and to clarify the biological mediators of elevated creatine kinase levels in psychotic cannabinoid users.
A genetic window to auditory-verbal problems in bipolar disorder
Authors: Benítez-Burraco Antonio
Published: November 2020

Bipolar disorder is a high prevalent psychiatric condition entailing recurrent episodes of elevated mood and depression, but also diverse cognitive problems. One deficit observed in patients concerns to auditory-verbal processing. Being a hereditary condition with a complex genetic architecture, it is not clear which genes contribute to this deficit. We show that candidates for bipolar disorder significantly overlap with candidates for clinical conditions resulting from a deficit in the phonological loop of working memory, particularly, developmental dyslexia and specific language impairment. The overlapping genes are involved in aspects of brain development and function (particularly, brain oscillations) potentially underlying phonological processing and accordingly, emerge as promising candidates for auditory-verbal deficits in bipolar disorder.
Ice giant seismology: prospecting for normal modes
Authors: Friedson A. James
Published: November 2020

The properties of ice giant normal mode oscillations, including their periods, spatial structure, stratospheric amplitudes and relative influence on the external gravity field, are surveyed for the purpose of formulating the best strategy for their eventual detection. Measurement requirements for detecting a normal mode's periodic pressure and temperature variations, including a possible stratospheric signal, and its effect on the external gravity field, are discussed in terms of its radial velocity amplitude at the 1 bar pressure level. It is found that for reasonable amplitudes, detection of the pressure and temperature variations of ice giant normal modes presents an extraordinary technical challenge. The prospects for detecting their gravitational influence on an orbiting spacecraft are more promising, with requirements that lie within the range of current technology.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Convective storms and atmospheric vertical structure in Uranus and Neptune
Authors: Hueso R. , Guillot T. , Sánchez-Lavega A.
Published: November 2020

The ice giants Uranus and Neptune have hydrogen-based atmospheres with several constituents that condense in their cold upper atmospheres. A small number of bright cloud systems observed in both planets are good candidates for moist convective storms, but their observed properties (size, temporal scales and cycles of activity) differ from moist convective storms in the gas giants. These clouds and storms are possibly due to methane condensation and observations also suggest deeper clouds of hydrogen sulfide (H
2
S) at depths of a few bars. Even deeper, thermochemical models predict clouds of ammonia hydrosulfide (NH
4
SH) and water at pressures of tens to hundreds of bars, forming extended deep weather layers. Because of hydrogen’s low molecular weight and the high abundance of volatiles, their condensation imposes a strongly stabilizing vertical gradient of molecular weight larger than the equivalent one in Jupiter and Saturn. The resulting inhibition of vertical motions should lead to a moist convective regime that differs significantly from the one occurring on nitrogen-based atmospheres like those of Earth or Titan. As a consequence, the thermal structure of the deep atmospheres of Uranus and Neptune is not well understood. Similar processes might occur at the deep water cloud of Jupiter in Saturn, but the ice giants offer the possibility to study these physical aspects in the upper methane cloud layer. A combination of orbital and
in situ
data will be required to understand convection and its role in atmospheric dynamics in the ice giants, and by extension, in hydrogen atmospheres including Jupiter, Saturn and giant exoplanets.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
The underexplored frontier of ice giant dynamos
Authors: Soderlund K. M. , Stanley S.
Published: November 2020

TheVoyager 2flybys of Uranus and Neptune revealed the first multipolar planetary magnetic fields and highlighted how much we have yet to learn about ice giant planets. In this review, we summarize observations of Uranus’ and Neptune’s magnetic fields and place them in the context of other planetary dynamos. The ingredients for dynamo action in general, and for the ice giants in particular, are discussed, as are the factors thought to control magnetic field strength and morphology. These ideas are then applied to Uranus and Neptune, where we show that no models are yet able to fully explain their observed magnetic fields. We then propose future directions for missions, modelling, experiments and theory necessary to answer outstanding questions about the dynamos of ice giant planets, both within our solar system and beyond.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Neptune and Uranus: ice or rock giants?
Authors: Teanby N. A. , Irwin P. G. J. , Moses J. I. , Helled R.
Published: November 2020

Existing observations of Uranus and Neptune’s fundamental physical properties can be fitted with a wide range of interior models. A key parameter in these models is the bulk rock:ice ratio and models broadly fall into ice-dominated (ice giant) and rock-dominated (rock giant) categories. Here we consider how observations of Neptune’s atmospheric temperature and composition (H2, He, D/H, CO, CH4, H2O and CS) can provide further constraints. The tropospheric CO profile in particular is highly diagnostic of interior ice content, but is also controversial, with deep values ranging from zero to 0.5 parts per million. Most existing CO profiles imply extreme O/H enrichments of >250 times solar composition, thus favouring an ice giant. However, such high O/H enrichment is not consistent with D/H observations for a fully mixed and equilibrated Neptune. CO and D/H measurements can be reconciled if there is incomplete interior mixing (ice giant) or if tropospheric CO has a solely external source and only exists in the upper troposphere (rock giant). An interior with more rock than ice is also more compatible with likely outer solar system ice sources. We primarily consider Neptune, but similar arguments apply to Uranus, which has comparable C/H and D/H enrichment, but no observed tropospheric CO. While both ice- and rock-dominated models are viable, we suggest a rock giant provides a more consistent match to available atmospheric observations.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
The exoplanet perspective on future ice giant exploration
Authors: Wakeford H. R. , Dalba P. A.
Published: November 2020

Exoplanets number in their thousands, and the number is ever increasing with the advent of new surveys and improved instrumentation. One of the most surprising things we have learnt from these discoveries is not that small-rocky planets in their stars habitable zones are likely to be common, but that the most typical size of exoplanets is that not seen in our solar system—radii between that of Neptune and the Earth dubbed mini-Neptunes and super-Earths. In fact, a transiting exoplanet is four times as likely to be in this size regime than that of any giant planet in our solar system. Investigations into the atmospheres of giant hydrogen/helium dominated exoplanets has pushed down to Neptune and mini-Neptune-sized worlds revealing molecular absorption from water, scattering and opacity from clouds, and measurements of atmospheric abundances. However, unlike measurements of Jupiter, or even Saturn sized worlds, the smaller giants lack a ground truth on what to expect or interpret from their measurements. How did these sized worlds form and evolve and was it different from their larger counterparts? What is their internal composition and how does that impact their atmosphere? What informs the energy budget of these distant worlds? In this we discuss what characteristics we can measure for exoplanets, and why a mission to the ice giants in our solar system is the logical next step for understanding exoplanets.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Atmospheric implications of the lack of H
3
+
detection at Neptune
Authors: Moore L. , Moses J. I. , Melin H. , Stallard T. S. , O’Donoghue J.
Published: November 2020

H
3
+
has been detected at all of the solar system giant planets aside from Neptune. Current observational upper limits imply that there is far less H
3
+
emission at Neptune than rudimentary modelling would suggest. Here, we explore via modelling a range of atmospheric conditions in order to find some that could be consistent with observational constraints. In particular, we consider that the upper atmosphere might be much cooler than it was during the 1989 Voyager 2 encounter, and we examine the impact of an enhanced influx of external material that could act to reduce H
3
+
density. Resulting ionosphere models that are consistent with existing H
3
+
observational constraints have an exospheric temperature of 450 K or less, 300 K lower than the Voyager 2 value. Alternatively, if a topside CO influx of 2 × 10
8
 cm
−2
 s
−1
is imposed, the upper atmospheric temperature can be higher, up to 550 K. The potential cooling of Neptune’s atmosphere is relevant for poorly understood giant planet thermospheric energetics, and would also impact aerobreaking manoeuvers for any future spacecraft. Such a large CO influx, if present, could imply Triton is a very active moon with prominent atmospheric escape, and/or that Neptune’s rings significantly modify its upper atmosphere, and the introduction of so much exogenic material would complicate interpretation of the origin of species observed in Neptune’s lower atmosphere.

This article is part a discussion meeting issue ‘Future exploration of ice giant systems’.
Does total triage and remote-by-default consulting impact vulnerable groups: A pilot study
Authors: Verity Aaminah , Naidu Dharmendra , Tzortziou-Brown Victoria
Published: November 2020

Background

COVID-19 mandated a rapid and dramatic transformation of general practice. ‘Total Triage’ (TT), where all consultations should be triaged first, and ‘Remote-by-Default’ (RbD) consulting, where a clinician should consult remotely unless there is a “clinical exception”, were advised. It is unclear how these new ways of working were implemented in practice, and how they impacted vulnerable patients.

Aim

To assess the impact of TT and RbD on vulnerable patients and identify mitigation strategies.

Design and Setting

A mixed methods service evaluation in Lewisham, London, an area of high deprivation.

Method

Three parallel datasets were collected and analysed: Semi-structured interviews with stakeholders working with vulnerable groups and qualitative data from forums with black and ethnic minority patients, a survey of General Practitioners exploring implementation of TT and RbD, and a mystery shopper exercise reviewing access and messaging of ten practices.

Results

Barriers to access for vulnerable patients included challenges navigating the new model, difficulty engaging with remote consultations and digital exclusion. There was wide variation in messaging regarding changes to services and the practical application of TT and RbD. Potential solutions included clearer practice guidance and patient messaging, more consistent implementation, and identification and recording of patient access needs to enable better tailoring of care provision.

Conclusion

This pilot study identified perceived and actual barriers to accessing general practice for vulnerable patients following the rapid introduction of TT and RbD consulting. It proposes immediate steps to mitigate some of these impacts and highlights the need for further research in this area.

How This Fits In

The rapid and widespread adoption, recommended by NHS England, of total triage and remote-by-default consulting in general practice has yet to be evaluated. We provide a first look at how these changes are impacting those with historic difficulties in accessing primary care under the traditional GP model. We also provide some local recommendations that can be implemented easily at practice level and beyond, to mitigate the impact of these changes whilst making recommendations for further research to corroborate these findings widely.
Non applicability of validated predictive models for intensive care admission and death of COVID-19 patients in a secondary care hospital in Belgium
Authors: Parisi Nicolas , Janier-Dubry Aurore , Ponzetto Ester , Pavlopoulos Charalambos , Bakalli Gaetan , Molinari Roberto , Guerrier Stéphane , Mili Nabil
Published: November 2020

Objective

To set up simple and reliable predictive scores for intensive care admissions and deaths in COVID-19 patients. These scores adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guidelines.

Design

Monocentric retrospective cohort study run from early March to end of May in Clinique Saint-Pierre Ottignies, a secondary care hospital located in Ottignies-Louvain-la-Neuve, Belgium. The outcomes of the study are (i) admission in the Intensive Care Unit and (ii) death.

Data sources

All patients admitted in the Emergency Department with a positive RT-PCR SARS-CoV-2 test were included in the study. Routine clinical and laboratory data were collected at their admission and during their stay. Chest X-Rays and CT-Scans were performed and analyzed by a senior radiologist.

Methods

A recently published predictive score conducted on a large scale was used as a benchmark value (Liang score)1. Logistic regressions were used to develop predictive scores for (i) admission to ICU among emergency ward patients; (ii) death among ICU patients on 40 clinical variables. These models were based on medical intuition and simple model selection tools. Their predictive capabilities were then compared to Liang score.

Results

Our results suggest that Liang score may not provide reliable guidance for ICU admission and death. Moreover, the performance of this approach is clearly outperformed by models based on simple markers. For example, a logistic regression considering only the LDH yields to similar sensitivity and greater specificity. Finally, all models considered in this study lead to levels of specificity under or equal to 50%.

Conclusions

In our experience, the results of a predictive score based on a large-scale Chinese study cannot be applied in the Belgian population. However, in our small cohort it appears that LDH above 579 UI/L and venous lactate above 3.02 mmol/l may be considered as good predictive biological factors for ICU admission. With regards to death risk, NLR above 22.1, tobacco abuse status and80 % ofrespiratory impairment appears to be relevant predictive factors. A predictive score for admission to ICU or death is desperately needed in secondary hospitals. Optimal allocation of resources guided by evidence-based indicators will best guide patients at time of admission and avoid futile treatments in intensive care units.
The role of children in the transmission chain of SARS-CoV-2: a systematic review and update of current evidence
Authors: Suk Jonathan E. , Vardavas Constantine , Nikitara Katerina , Phalkey Revati , Leonardi-Bee Jo , Pharris Anastasia , Wiltshire Emma , Funk Tjede , Ferland Lisa , Bundle Nick , Semenza Jan C.
Published: November 2020

Decisions on school closures and on safe schooling during the COVID-19 pandemic should be evidence-based. We conducted a systematic literature review to assess child-to-child and child-to-adult SARS-CoV-2 transmission and to characterise the potential role of school closures on community transmission. 1337 peer-reviewed articles published through August 31, 2020 were screened; 22 were included in this review. The literature appraised provides sufficient evidence that children can both be infected by and transmit SARS-CoV-2 in community, household and school settings. Transmission by children was most frequently documented in household settings, while examples of children as index cases in school settings were rare. Included studies suggested that school closures may help to reduce SARS- CoV-2 transmission, but the societal, economic, and educational impacts of prolonged school closures must be considered. In-school mitigation measures, alongside continuous surveillance and assessment of emerging evidence, will promote the protection and educational attainment of students and support the educational workforce.
Efficacy of broflanilide (VECTRON™ T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors
Authors: Ngufor Corine , Govoetchan Renaud , Fongnikin Augustin , Vigninou Estelle , Syme Thomas , Akogbeto Martin , Rowland Mark
Published: November 2020

The rotational use of insecticides with different modes of action for indoor residual spraying (IRS) is recommended for improving malaria vector control and managing insecticide resistance. A more diversified portfolio of IRS insecticides is required; insecticides with new chemistries which can provide improved and prolonged control of insecticide-resistant vector populations are urgently needed. Broflanilide is a newly discovered insecticide being considered for malaria vector control. We investigated the efficacy of a wettable powder (WP) formulation of broflanilide (VECTRON™ T500) for IRS on mud and cement wall substrates in WHO laboratory and experimental hut studies against pyrethroid-resistant malaria vectors in Benin, in comparison with pirimiphos-methyl CS (Actellic® 300CS). There was no evidence of cross-resistance to pyrethroids and broflanilide in CDC bottle bioassays. In laboratory cone bioassays, mortality of susceptible and pyrethroid-resistantA. gambiaes.l. with broflanilide WP treated substrates was >80% for 6-14 months. At application rates of 100mg/m2and 150 mg/m2, mortality of wild pyrethroid-resistantA. gambiaes.l. entering treated experimental huts in Covè, Benin was 57%-66% with broflanilide WP and did not differ significantly from pirimiphos-methyl CS (57-66% vs. 56%, P>0.05). Mosquito mortality did not differ between the two application rates and local wall substrate-types tested (P>0.05). Throughout the 6-month hut trial, monthly wall cone bioassay mortality on broflanilide WP treated hut walls remained >80% for both susceptible and resistant strains ofA. gambiaes.l.. Broflanilide shows potential to significantly improve the control of malaria transmitted by pyrethroid-resistant mosquito vectors and would thus be a crucial addition to the current portfolio of IRS insecticides.

One Sentence Summary

VECTRON™ T500, a new wettable powder formulation of broflanilide developed for indoor residual spraying, showed high and prolonged activity against wild pyrethroid-resistant malaria vectors, on local wall substrates, in laboratory bioassays and experimental household settings in Benin.
DeepCOMBI: Explainable artificial intelligence for the analysis and discovery in genome-wide association studies
Authors: Mieth Bettina , Rozier Alexandre , Rodriguez Juan Antonio , Höhne Marina M.-C. , Görnitz Nico , Müller Klaus-Robert
Published: November 2020

Deep learning algorithms have revolutionized data science in many fields by greatly improving prediction performances in comparison to conventional approaches. Recently, explainable artificial intelligence (XAI) has emerged as a novel area of research that goes beyond pure prediction improvement. Knowledge embodied in deep learning methodologies is extracted by interpreting their results. We investigate such explanations to explore the genetic architectures of phenotypes in genome-wide association studies. Instead of testing each position in the genome individually, the novel three-step algorithm, called DeepCOMBI, first trains a neural network for the classification of subjects into their respective phenotypes. Second, it explains the classifiers’ decisions by applying layerwise relevance propagation as one example from the pool of XAI techniques. The resulting importance scores are eventually used to determine a subset of most relevant locations for multiple hypothesis testing in the third step. The performance of DeepCOMBI in terms of power and precision is investigated on generated datasets and a 2007 WTCCC study. Verification of the latter is achieved by validating all findings with independent studies published up until 2020. DeepCOMBI is shown to outperform ordinary raw p-value thresholding as well as other baseline methods. Moreover, two novel disease associations (rs10889923 for hypertension and rs4769283 for type 1 diabetes) were identified.
Longitudinal Auditory Pathophysiology Following Mild Blast Induced Trauma
Authors: Han Emily X. , Fernandez Joseph M. , Swanberg Caitlin , Shi Riyi , Bartlett Edward L.
Published: November 2020

Blast-induced hearing difficulties affect thousands of veterans and civilians. The long-term impact of even a mild blast exposure on the central auditory system is hypothesized to contribute to lasting behavioral complaints associated with mild blast traumatic brain injury (bTBI). Although recovery from mild blast has been studied separately over brief or long time windows, few, if any, studies have investigated recovery longitudinally over short-term and longer-term (months) time windows. Specifically, many peripheral measures of auditory function either recover or exhibit subclinical deficits, masking deficits in processing complex, real-world stimuli that may recover differently. Thus, examining the acute time course and pattern of neurophysiological impairment using appropriate stimuli is critical to better understanding and intervention of bTBI-induced auditory system impairments. Here, we compared auditory brainstem response, middle-latency auditory evoked potentials, and envelope following responses. Stimuli were clicks, tone pips, amplitude modulated tones in quiet and in noise, and speech-like stimuli (iterated rippled noise pitch contours) in adult male rats subjected to mild blast and sham exposure over the course of two months. We found that blast animals demonstrated drastic threshold increases and auditory transmission deficits immediately after blast exposure, followed by substantial recovery during the window of 7-14 days post-blast, though with some deficits remaining even after two months. Challenging conditions and speech-like stimuli can better elucidate mild bTBI-induced auditory deficit during this period. Our results suggest multiphasic recovery and therefore potentially different time windows for treatment, and deficits can be best observed using a small battery of sound stimuli.

New and Noteworthy

Few studies on blast-induced hearing deficits go beyond simple sounds and sparsely track post-exposure. Therefore, the recovery arc for potential therapies and real-world listening is poorly understood. Evidence suggested multiple recovery phases over 2 months post-exposure. Hearing thresholds largely recovered within 14 days and partially explained recovery. However, mid-latency responses, responses to AM in noise, and speech-like pitch sweeps exhibited extended changes, implying persistent central auditory deficits and the importance of subclinical threshold shifts.
The tuning of tuning: how adaptation influences single cell information transfer
Authors: Zeldenrust Fleur , Calcini Niccolò , Yan Xuan , Bijlsma Ate , Celikel Tansu
Published: November 2020

Sensory neurons reconstruct the world from action potentials (spikes) impinging on them. To effectively transfer information about the stimulus to the next processing level, a neuron needs to be able to adapt its working range to the properties of the stimulus. Here, we focus on the intrinsic neural properties that influence information transfer in cortical neurons and how tightly their properties need to be tuned to the stimulus statistics for them to be effective. We start by measuring the intrinsic information encoding properties of putative excitatory and inhibitory neurons in L2/3 of the mouse barrel cortex. Excitatory neurons show high thresholds and strong adaptation, making them fire sparsely and resulting in a strong compression of information, whereas inhibitory neurons that favour fast spiking transfer more information. Next, we turn to computational modelling and ask how two properties influence information transfer: 1) spike-frequency adaptation and 2) the shape of the IV-curve. We find that a subthreshold (but not threshold) adaptation, the ‘h-current’, and a properly tuned leak conductance can increase the information transfer of a neuron, whereas threshold adaptation can increase its working range. Finally, we verify the effect of the IV-curve slope in our experimental recordings and show that excitatory neurons form a more heterogeneous population than inhibitory neurons. These relationships between intrinsic neural features and neural coding that had not been quantified before will aid computational, theoretical and systems neuroscientists in understanding how neuronal populations can alter their coding properties, such as through the impact of neuromodulators. Why the variability of intrinsic properties of excitatory neurons is larger than that of inhibitory ones is an exciting question, for which future research is needed.

Author summary

Intracellular information transfer from synaptic input to output spike train is necessarily lossy. Here, we explicitly measure the mutual information between a neuron’s input and spike output and show that information transfer is more lossy and heterogeneous for excitatory than for inhibitory neurons. By using computational modelling we show that the shape of the input-output curve as well as how fast a neuron adapts to its input collectively determine the rate of information loss. These insights will help both experimentalists and modellers in designing and simulating experiments that investigate how network coding properties can adapt to the environment, for instance through the effects of neuromodulators.
SPHERIOUSLY?The challenges of estimating spherical pore size non-invasively in the human brain from diffusion MRI
Authors: Afzali Maryam , Nilsson Markus , Palombo Marco , Jones Derek K
Published: November 2020

The Soma and Neurite Density Imaging (SANDI) three-compartment model was recently proposed to disentangle cylindrical and spherical geometries, attributed to neurite and soma compartments, respectively, in brain tissue. The approach could also enable estimation of microstructure parameters such as the apparent size (radius) of the soma. There are some recent advances in diffusion-weighted MRI signal encoding and analysis (including the use of multiple so-called ‘b-tensor’ encodings and analysing the signal in the frequency-domain) that have not yet been applied in the context of SANDI. In this work, using: (i) ultra-strong gradients; (ii) a combination of linear, planar, and spherical b-tensor encodings; and (iii) analysing the signal in the frequency domain, three main challenges to robust estimation of soma size were identified:

First, the Rician noise floor in magnitude-reconstructed data biases estimates of soma properties in a non-uniform fashion. It may cause overestimation or underestimation of the soma size and density. This can be partly ameliorated by accounting for the noise floor in the estimation routine.

Second, even when using the strongest diffusion-encoding gradient strengths available for human MRI, there is anempiricallower bound on the spherical signal fraction and pore-size that can be detected and estimated robustly. For the experimental setup used here, the lower bound on the signal fraction was approximately 10%. We employed two different ways of establishing the lower bound for spherical radius estimates in white matter. The first, examining power-law relationships between the DW-signal and diffusion weighting in empirical data, yielded a lower bound of 7μm, while the second, pure Monte Carlo simulations, yielded a lower limit of 3μmand in this low radii domain, there is little differentiation in signal attenuation.

Third, if there is sensitivity to the transverse intra-cellular diffusivity in cylindrical structures, e.g., axons and cellular projections, then trying to disentangle two diffusion-time-dependencies using one experimental parameter (i.e., change in frequency-content of the encoding waveform) makes spherical pore-size estimates particularly challenging.

We conclude that due to the aforementioned challenges spherical pore size estimates may be biased when the corresponding signal fraction is low, which must be considered when using them as biomarkers in clinical/research studies.
Obligate mutualistic cooperation limits evolvability
Authors: Pauli Benedikt , Oña Leonardo , Hermann Marita , Kost Christian
Published: November 2020

Cooperative mutualisms are widespread in nature and play fundamental roles in many ecosystems. Due to the often obligate nature of these interactions, the Darwinian fitness of the participating individuals is not only determined by the information encoded in their own genomes, but also the traits and capabilities of their corresponding interaction partners. Thus, a major outstanding question is how obligate cooperative mutualisms affect the ability of organisms to respond to environmental change with evolutionary adaptation. Here we address this issue using a mutualistic cooperation between two auxotrophic genotypes ofEscherichia colithat reciprocally exchange costly amino acids. Amino acid-supplemented monocultures and unsupplemented cocultures were exposed to stepwise increasing concentrations of different antibiotics. This selection experiment revealed that metabolically interdependent bacteria were generally less able to adapt to environmental stress than autonomously growing strains. Moreover, obligate cooperative mutualists frequently regained metabolic autonomy, thus resulting in a collapse of the mutualistic interaction. Together, our results identify a limited evolvability as a significant evolutionary cost that individuals have to pay when entering into an obligate mutualistic cooperation.
Clonal expansion of personalized anti-tumor T cells from circulation using tumor organoid-immune co-cultures
Authors: Meng Qingda , Xie Shanshan , Gray G. Kenneth , Li Weilin , Huang Ling , Akshinthala Dipikaa , Dezfulian Mohammad H. , Ferrer Elizabeth , Conahan Catherine , Del Pino Sofia Perea , Grossman Joseph , Elledge Stephen , Hidalgo Manuel , Muthuswamy Senthil K
Published: November 2020

Tumor-specific cytotoxic T cells are effective tools for cancer immunotherapy, but the ability to generate them continues to be a challenge. Furthermore, there are no compelling approaches to empirically identify tumor-targeting T cells and T cell receptors by exploiting the multitude of antigens on tumor cell surfaces. Here, we use patients’ peripheral blood and autologous tumor organoids to enrich tumor-specific cytotoxic T cells with patient-specific killing mechanisms and a tissue-resident memory phenotype. We further demonstrate that these organoid-primed T (opT) cells undergo several orders of magnitude of clonal expansion and express T cells receptors and check-point proteins unique to each patient. Importantly, transferring the TCRs to heterologous T cells was sufficient to confer tumor recognition in a patient-specific manner. Thus, we report a patient-specific and antigen-agnostic platform for expansion of tumor-targeting T cells and identification of cancer-targeting TCRs from the peripheral blood of pancreatic cancer patients that can be exploited for immunotherapy applications.