bluuebunny/crossref_metadata_2025 huggingface dataset:
Degeneracies between self-interacting dark matter and supernova feedback as cusp-core transformation mechanisms
Authors: Burger Jan D , Zavala Jesús , Sales Laura V , Vogelsberger Mark , Marinacci Federico , Torrey Paul
Published: April 2022

We present a suite of 16 high-resolution hydrodynamic simulations of an isolated dwarf galaxy (gaseous and stellar disc plus a stellar bulge) within an initially cuspy dark matter (DM) halo, including self-interactions between the DM particles; as well as stochastic star formation and subsequent supernova feedback (SNF), implemented using the stellar feedback model SMUGGLE. The simulations start from identical initial conditions, and we regulate the strength of DM self-interactions and SNF by systematically varying the self-interacting DM (SIDM) momentum transfer cross-section and the gas density threshold for star formation. The DM halo forms a constant density core of similar size and shape for several combinations of those two parameters. Haloes with cores that are formed due to SIDM (adiabatic cusp-core transformation) have velocity dispersion profiles that are closer to isothermal than those of haloes with cores that are formed due to SNF in simulations with bursty star formation (impulsive cusp-core transformation). Impulsive SNF can generate positive stellar age gradients and increase random motion in the gas at the centre of the galaxy. Simulated galaxies in haloes with cores that were formed adiabatically are spatially more extended, with stellar metallicity gradients that are shallower (at late times) than those of galaxies in other simulations. Such observable properties of the gas and the stars, which indicate either an adiabatic or an impulsive evolution of the gravitational potential, may be used to determine whether observed cores in DM haloes are formed through DM self-interactions or in response to impulsive SNF.
Brightest cluster galaxies trace weak lensing mass bias and halo triaxiality in the three hundred project
Authors: Herbonnet Ricardo , Crawford Adrian , Avestruz Camille , Rasia Elena , Giocoli Carlo , Meneghetti Massimo , von der Linden Anja , Cui Weiguang , Yepes Gustavo
Published: April 2022

Galaxy clusters have a triaxial matter distribution. The weak-lensing signal, an important part in cosmological studies, measures the projected mass of all matter along the line of sight, and therefore changes with the orientation of the cluster. Studies suggest that the shape of the brightest cluster galaxy (BCG) in the centre of the cluster traces the underlying halo shape, enabling a method to account for projection effects. We use 324 simulated clusters at four redshifts between 0.1 and 0.6 from ‘The Three Hundred Project’ to quantify correlations between the orientation and shape of the BCG and the halo. We find that haloes and their embedded BCGs are aligned, with an average ∼20 degree angle between their major axes. The bias in weak lensing cluster mass estimates correlates with the orientation of both the halo and the BCG. Mimicking observations, we compute the projected shape of the BCG, as a measure of the BCG orientation, and find that it is most strongly correlated to the weak-lensing mass for relaxed clusters. We also test a 2D cluster relaxation proxy measured from BCG mass isocontours. The concentration of stellar mass in the projected BCG core compared to the total stellar mass provides an alternative proxy for the BCG orientation. We find that the concentration does not correlate to the weak-lensing mass bias, but does correlate with the true halo mass. These results indicate that the BCG shape and orientation for large samples of relaxed clusters can provide information to improve weak-lensing mass estimates.
Can 595-nm Pulsed Dye Laser in Conjunction With an Optical Clearing Agent Improve the Treatment of Port-Wine Stains?
Authors: Yu Wenxin , Chen Yanyu , Cen Qingqing , Zhu Jiafang , Lin Xiaoxi
Published: April 2022

BACKGROUND

Studies have demonstrated that glycerol can act as an optical clearing agent (OCA) to increase the light penetration through the skin and laser deposition to the target chromophore, thus potentially increasing the efficacy of laser treatment.

OBJECTIVE

To evaluate whether a pulsed dye laser (PDL) in combination with an OCA can increase the efﬁcacy in treating port-wine stains (PWSs).

METHODS

Thirteen patients with untreated PWSs underwent 3 treatment sessions at 6-week intervals. Each PWS was divided into OCA + PDL sites (PDL treatment after topical use of 0.5 mL hydrous glycerol for 5 minutes), PDL sites, and untreated sites. The chromametric evaluation and visual evaluation (VAS) of the efﬁcacy and the assessment of side effects were conducted 3 months after the ﬁnal treatment.

RESULTS

Visual evaluation was 2.69 versus 2.07 (p = .025) and 3.38 versus 3.07 (p = .04) for OCA + PDL and PDL-only sites after the first and second sessions. After the third session, the chromameter and VAS indicated no significant difference between the 2 sites. Permanent side effects were not observed.

CONCLUSION

Greater efficacy was observed after the first 2 treatments on the OCA + PDL sites. Although after multiple sessions, the OCA + PDL treatment did not improve efficacy over just PDL alone.
Dietary Antioxidant Insufficiency Is Associated With Increased Inflammatory Markers and Poorer Health-Related Quality of Life in Patients With Heart Failure
Authors: Wu Jia-Rong , Song Eun Kyeung , Moser Debra K. , Lennie Terry A.
Published: April 2022

Background

Antioxidant insufficiency, elevated inflammatory markers, and poor health-related quality of life (HRQOL) are prevalent in patients with heart failure (HF).

Objective

The objective of this study was to examine the associations among dietary antioxidant intake, inflammatory markers, and HRQOL in patients with HF.

Methods

This was a secondary analysis of 265 patients with HF who completed a 4-day food diary. We assessed intake of 10 antioxidants: alpha carotene, beta carotene, beta cryptoxanthin, lutein, zeaxanthin, lycopene, vitamins C and E, zinc, and selenium. Antioxidant insufficiency was reflected by a measured level for each antioxidant that was below the estimate average requirement or lower than median for antioxidants without an estimate average requirement. Inflammatory markers including serum C-reactive protein, cytokines (interleukins 6 and 10), tumor necrosis factor-alpha, and soluble receptors (sTNFR1 and sTNFR2) were assessed with enzyme immunoassay. Health-related quality of life was measured using the Minnesota Living with Heart Failure at 12 months.

Results

Dietary antioxidant insufficiency predicted C-reactive protein (β = 0.135, P = .032) and interleukin 10 (β = −.155, P = .027). Patients with higher antioxidant insufficiency had higher C-reactive protein and lower interleukin 10. Both antioxidant insufficiency (β = 0.13, P = .049) and higher C-reactive protein (β = 0.16, P = .019) were independently associated with poorer HRQOL while adjusting for covariates.

Conclusions

Dietary antioxidant insufficiency was associated with increased markers of inflammation and poorer HRQOL. Improvement of diet quality among patients with HF may be a fruitful area of research for enhancing HRQOL.
Slips, Trips, and Falls: A Quality Improvement Initiative
Authors: Peir Gene H. , Fink Alia , Mantasas Nick , Cheng Jenhao J. , Worten Katherine , Shah Rahul K.
Published: April 2022

Introduction:

Employee safety and the reduction of Days Away, Restricted, or Transferred are a focus of the Solutions for Patient Safety Network. One significant contributor to the Days Away, Restricted, or Transferred rate at Children’s National Hospital is employee slips, trips, or falls.

Methods:

Children’s National Hospital implemented a multidisciplinary quality improvement with executive leadership vision and support. We implemented quality techniques (including Key Driver Diagrams, Pareto Charts, and continuous Plan-Do-Study-Act) and designed novel Environmental Services interventions.

Results:

Children’s National Hospital achieved a 44.3% reduction in monthly average reported slips, trips, or fall events from baseline and sustained over a 2-year study period.

Conclusion:

A leadership-driven multidisciplinary approach to quality initiatives with team leaders capable of making and enacting real-time policy changes led to novel interventions and a successful reduction of employee slips, trips, and falls events over time, which are broadly generalizable.
A 15-Year Review of Clinical Practice Patterns in Carpal Tunnel Syndrome Based on Continuous Certification by the American Board of Plastic Surgery
Authors: Sasson Daniel C. , Yuksel Selcen S. , Shah Nikhil D. , Kearney Aaron M. , Kalliainen Loree K. , Gosain Arun K.
Published: April 2022

Background:

The American Board of Plastic Surgery has been collecting practice data on carpal tunnel syndrome treatment since 2004 as part of its Continuous Certification Program. These data allow plastic surgeons to compare their surgical experience to national trends and analyze those trends in relation to current evidence-based medicine.

Methods:

Data on carpal tunnel syndrome treatment from 2004 to 2014 were compared to those from 2015 to 2020. National practice trends observed in these data were evaluated relative to current literature regarding evidence-based practices.

Results:

A total of 11,090 carpal tunnel syndrome cases were included from 2004 to 2020. Electrodiagnostic and imaging studies were performed on most patients despite adding little sensitivity and specificity when physical examination tests are performed and not being considered cost-effective. An open “mini” approach has remained the most common surgical technique in carpal tunnel release for the last 15 years, with growing usage (53 percent versus 59 percent, p < 0.001). Splinting has decreased significantly over the last 15 years, from usage in 39 percent of patients to 28 percent (p < 0.001). Formal postoperative hand therapy has declined from 27 percent of patients to 22 percent (p < 0.001). Despite their low efficacy, 63 percent of patients received one or more perioperative doses of antibiotics.

Conclusions:

Analysis of the Continuous Certification Program tracer data from the American Board of Plastic Surgery provides an excellent overview of current practice and its development over the 15 years since its inception. This analysis provides insight into how effectively plastic surgeons have remained aligned with developments in best practices in treating carpal tunnel syndrome.
Continuous Monitoring Detected Respiratory Depressive Episodes in Proximity to Adverse Respiratory Events During the PRODIGY Trial
Authors: Kor Jennifer J. , Sprung Juraj , Khanna Ashish K. , Weingarten Toby N.
Published: April 2022

Purpose

The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial was a multicenter prospective trial conducted to develop a risk prediction score for opioid-induced respiratory depressive (OIRD) episodes. Several subjects in the PRODIGY trial developed critical respiratory depressive events, which were qualified as reportable adverse events (AEs). In this study, we determine whether those patients also had an episode of OIRD as detected by continuous capnography and pulse oximetry leading up to the critical clinical event.

Methods

Blinded capnography and pulse oximetry data from PRODIGY patients who had critical respiratory depressive AE were reviewed. The occurrence and timing of OIRD episodes were recorded in relationship to the AE.

Results

Of the 1335 subjects in PRODIGY, 7 patients had 8 reportable pulmonary AE and 187 OIRDs (150 apnea episodes, 14 bradypnea episodes, 23 hypoxic episodes) with median 12 (5–19.5) OIRDs per patient. Five patients were monitored before the AE, and multiple preceding OIRD episodes were detected. One patient had 2 AE, the first (hypoxemia) was recognized upon application of pulse oximetry. This patient subsequently had multiple OIRDs until the second AE occurred (somnolence requiring naloxone administration). Another patient’s AE (hypotension and bradypnea) was recognized upon monitor application and subsequently had many OIRD episodes.

Conclusions

In the PRODIGY trial, patients who had a pulmonary AE had multiple preceding OIRDs detected by continuous capnography and pulse oximetry. When monitoring was initiated before the AE, numerous OIRDs, mostly apneic episodes preceded AE, suggesting continuous monitoring of both ventilation and oxygenation may allow for early detection and possible prediction of future clinical decompensation.
Solid Organ Donation and Transplantation Activity in the Eurotransplant Area During the First Year of COVID-19
Authors: Putzer Gabriel , Gasteiger Lukas , Mathis Simon , van Enckevort Arjan , Hell Tobias , Resch Thomas , Schneeberger Stefan , Martini Judith
Published: April 2022

Background.

Transplantation activity during the first wave of the coronavirus disease 2019 (COVID-19) pandemic was severely affected worldwide. This retrospective analysis aimed to assess the impact of COVID-19 on organ donations and transplantations in the Eurotransplant region during the first 12 mo of the pandemic. Specifically, we compared donor and transplantation numbers during both waves to determine whether transplant systems adapted to this new reality.

Methods.

All reported organ donations and transplantations from March 1, 2015, to February 28, 2021, were collected from the Eurotransplant International Foundation registry. The observation period from 2020 to 2021 was divided into three 4-mo periods, which were then compared with the corresponding periods of the preceding 5 y. COVID-19 cases for Eurotransplant countries were retrieved from the OurWorldInData.org database.

Results.

Overall, the number of organ donors decreased by 18.3% (P < 0.0001) and the number of organ transplantations by 12.5% (P > 0.0001) compared with previous years. Pancreas transplantation was the most affected, followed by kidney, liver, heart, and lung transplant. In detail, during period 1, the number of organ donors decreased by 26.2% (P < 0.0001) and the number of organ transplantations by 16.5% (P < 0.0001), in period 2 by 5.5% (P < 0.0091) and 4.9% (P < 0.0001), and in period 3 by 23.1% (P < 0.0001) and 16.4% (P < 0.0001), respectively.

Conclusions.

Organ donation and transplantation decreased drastically also during the second wave; however, despite the severity of the second wave, the decline was comparable with that of the first wave.
Therapeutic efficacy of four antiviral drugs in treatment of COVID-19: A protocol for systematic review and Network Meta-analysis
Authors: Zhang Liang-kun , Gu Wen-chao , Li Ling , Jian Chen
Published: April 2022

Introduction

The COVID-19 pandemic has resulted in a global crisis in public health, however, there are still no safe and effective drugs to resist COVID-19 until now. We will use network meta-analysis to analysis available evidence from RCTs to compare the safety and efficacy of four antiviral drugs (including Ribavirin, Arbidol, Chloroquine Phosphate and Interferon) alone or in combination, in patients with COVID-19 on the basis of standard treatment, to reveal the robustness and strength of evidence for relative efficacy against COVID-19, which will provide better evidence for future clinical decision-making.

Methods

Using English and Chinese search strategies to search 8 databases including PubMed, Web of Science, Embase, the Cochrane Library, CNKI, CBM, WANFANG Database and VIP. In addition, manual search for references in publications has been supplemented by electronic search. To enhance the effectiveness of this study, only randomized controlled trials of four antiviral drugs (Ribavirin, Arbidol, Chloroquine Phosphate, Interferon) used alone or in combination with the primary therapy shall be included.

Analysis

The nucleic acid turning negative, complete absorption of lung inflammation, adverse reactions, aggravation and death shall be the primary outcome measures; whereas temperature return to normal, hospitalization, and positive rate after discharge will be the secondary outcomes. To ensure the quality of the systematic evaluation of this study, study screening, data extraction and quality evaluation will be carried out independently by two reviewers, and any differences will be resolved through consultation between them or by a third reviewer.

Ethics and dissemination

This systematic review will evaluate the efficacy of four antiviral drugs (Ribavirin, Arbidol, Chloroquine Phosphate and Interferon) for Covid-19 in adults. Since all included data will be obtained from published articles, it does not require ethical approval and will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42022300104.
Effectiveness of convalescent plasma therapy in COVID-19 patients with haematological malignancies
Authors: Shibeeb Sapha , Ajaj Ilham , Al-Jighefee Hadeel , Abdallah Atiyeh
Published: April 2022

Background

Immunocompromised patients, including those with haematological malignancies, are among the high-risk group to develop severe coronavirus disease 2019 (COVID-19) complications. The effectiveness of passive immunotherapy with convalescent plasma (CP) on such patients diagnosed with COVID-19 has not been reviewed. Therefore, the aim of this review was to systematically appraise the current evidence for the efficacy of this therapy in haematological malignancies patients with COVID-19 infection.

Methods

A comprehensive search was conducted up-to October 2021, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis were performed using Microsoft Excel 365 and GraphPad Prism software.

Results

17 studies met the inclusion criteria; these records included 258 COVID-19 patients with haematological malignancies and treated with CP therapy (CPT). The main findings from the reviewed data suggests CPT may be associated with improved clinical outcomes including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, (c) improved hospital discharge time, and recovery after 1 month of CP therapy. Furthermore, treatment with convalescent plasma was not associated with development of adverse events.

Conclusion

Owing to its safety and beneficial effects in improving clinical outcomes, CPT appears to be an effective supportive therapeutic option for haematological malignancy patients infected with COVID-19.
Quantifying the relationship between SARS-CoV-2 wastewater concentrations and building-level COVID-19 prevalence at an isolation residence using a passive sampling approach
Authors: Acer Patrick T. , Kelly Lauren M. , Lover Andrew A. , Butler Caitlyn S.
Published: April 2022

SARS-CoV-2 RNA can be detected in the excreta of individuals with COVID-19 and has demonstrated a positive correlation with various clinical parameters. Consequently, wastewater-based epidemiology (WBE) approaches have been implemented globally as a public health surveillance tool to monitor the community-level prevalence of infections. Over 270 higher education campuses monitor wastewater for SARS-CoV-2, with most gathering either composite samples via automatic samplers (autosamplers) or grab samples. However, autosamplers are expensive and challenging to manage with seasonal variability, while grab samples are particularly susceptible to temporal variation when sampling sewage directly from complex matrices outside residential buildings. Prior studies have demonstrated encouraging results utilizing passive sampling swabs. Such methods can offer affordable, practical, and scalable alternatives to traditional methods while maintaining a reproducible SARS-CoV-2 signal. In this regard, we deployed tampons as passive samplers outside of a COVID-19 isolation unit (a segregated residence hall) at a university campus from February 1, 2021 – May 21, 2021. Samples were collected several times weekly and remained within the sewer for a minimum of 24 hours (n = 64). SARS-CoV-2 RNA was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) targeting the viral N1 and N2 gene fragments. We quantified the mean viral load captured per individual and the association between the daily viral load and total persons, adjusting for covariates using multivariable models to provide a baseline estimate of viral shedding. Samples were processed through two distinct laboratory pipelines on campus, yielding highly correlated N2 concentrations. Data obtained here highlight the success of passive sampling utilizing tampons to capture SARS-CoV-2 in wastewater coming from a COVID-19 isolation residence, indicating that this method can help inform public health responses in a range of settings.

Highlights

Daily SARS-CoV-2 RNA loads in building-level wastewater were positively associated with the total number of COVID-19 positive individuals in the residence

The variation in individual fecal shedding rates of SARS-CoV-2 extended four orders of magnitude

Wastewater sample replicates were highly correlated using distinct processing pipelines in two independent laboratories

While the isolation residence was occupied, SARS-CoV-2 RNA was detected in all passive samples
Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants
Authors: Emmenegger Marc , Fiedler Sebastian , Brugger Silvio D. , Devenish Sean R. A. , Morgunov Alexey S. , Ilsley Alison , Ricci Francesco , Malik Anisa Y. , Scheier Thomas , Batkitar Leyla , Madrigal Lidia , Rossi Marco , Lynn Andrew K. , Saleh Lanja , von Eckardstein Arnold , Knowles Tuomas P. J. , Aguzzi Adriano
Published: April 2022

The B.1.1.529 (omicron) variant has rapidly supplanted most other SARS-CoV-2 variants. Using microfluidics-based antibody affinity profiling (MAAP), we have recently shown that current therapeutic monoclonal antibodies exhibit a drastic loss of affinity against omicron. Here, we have characterized affinity and IgG concentration in the plasma of 39 individuals with multiple trajectories of SARS-CoV-2 infection and/or vaccination as well as in 2 subjects without vaccination or infection. Antibody affinity in patient plasma samples was similar against the wild-type, delta, and omicron variants (KA ranges: 122±155, 159±148, 211±307 μM-1, respectively), indicating a surprisingly broad and mature cross-clade immune response. We then determined the antibody iso- and subtypes against multiple SARS-CoV-2 spike domains and nucleoprotein. Postinfectious and vaccinated subjects showed different profiles, with IgG3 (p = 0.002) but not IgG1, IgG2 or IgG4 subtypes against the spike ectodomain being more prominent in the former group. Lastly, we found that the ELISA titers against the wildtype, delta, and omicron RBD variants correlated linearly with measured IgG concentrations (R=0.72) but not with affinity (R=0.29). These findings suggest that the wild-type and delta spike proteins induce a polyclonal immune response capable of binding the omicron spike with similar affinity. Changes in titers were primarily driven by antibody concentration, suggesting that B-cell expansion, rather than affinity maturation, dominated the response after infection or vaccination.
Mortality in Switzerland in 2021
Authors: Locatelli Isabella , Rousson Valentin
Published: April 2022

Objective

To analyze mortality trends in Switzerland in 2021, the second year of the COVID-19 pandemic.

Methods

Using data from the Swiss Federal Statistical Office, we compared mortality in Switzerland in 2021 with that of previous years in terms of standardized weekly deaths, standardized (annual) mortality rates (overall and stratified by age and sex) and life expectancy.

Results

After a favorable first half of the year and a fairly standard second half in terms of mortality in Switzerland, the year 2021 ended with a wave of deaths of moderate intensity related to the 5th wave of COVID-19. Overall, and after a notable increase in mortality in 2020 (+9.2% compared to 2019), the pre-pandemic mortality level was approximately recovered in 2021 (+0.6% compared to 2019). Life expectancy, after declining by 10 months for men and 6 months for women in 2020, returned in 2021 to levels slightly above those of 2019 for women (85.7 years, +0.1 years from 2019) and regained 2018 levels for men (81.6 years, still -0.3 years from 2019). The age group responsible for the small remaining loss for men was the 50-70 age group, which had similar mortality in 2020 and 2021.

Conclusions

The second year of the COVID-19 pandemic in Switzerland was characterized by an approximate return to pre-pandemic mortality levels, with a faster recovery for women than for men compared to 2020.
Time series cross-correlation between home range and number of infected people during the medium-term of the COVID-19 pandemic in a suburban city
Authors: Kato Haruka , Takizawa Atsushi
Published: April 2022

Control of human mobility is among the most effective measures to prevent the spread of coronavirus disease 2019 (COVID-19). This study aims to clarify the correlation between home range and the number of people infected with SARS-CoV-2 during the medium-term of the COVID-19 pandemic in Ibaraki City. Home ranges are analyzed by the Minimum Convex Polygon method using mobile phone GPS location history data. We analyzed the time series cross-correlation between home range lengths and the number of infected people. Results reveal a slight positive correlation between home range and the number of infected people after one week during the medium-term of the COVID-19 pandemic. Regarding home range length, the cross-correlation coefficient is 0.4030 even at a lag level of six weeks, which has the most significant coefficient. Thus, a decrease in home range is only one of the indirect factors contributing toward a reduction in the number of infected people. This study makes a significant contribution to the literature by evaluating key public health challenges from the perspective of controliing the spread of the COVID-19 infectuion. Its findings has implications for policy makers, practitioners, and urban scientists seeking to promote urban sustainability.
Pelagic seabirds reduce risk by flying into the eye of the storm
Authors: Lempidakis Emmanouil , Shepard Emily L. C. , Ross Andrew N. , Matsumoto Sakiko , Koyama Shiho , Takeuchi Ichiro , Yoda Ken
Published: April 2022

Cyclones can cause mass mortality of seabirds, sometimes wrecking thousands of individuals. The few studies to track pelagic seabirds during cyclones show they tend to circumnavigate the strongest winds. We tracked adult shearwaters in the Sea of Japan over 11 years and find that the response to cyclones varied according to the wind speed and direction. In strong winds, birds that were sandwiched between the storm and mainland Japan flew away from land and towards the eye of the storm, flying within ≤ 30 km of the eye and tracking it for up to 8 hours. This exposed shearwaters to some of the highest wind speeds near the eye wall (≤ 21 m s-1), but enabled them to avoid strong onshore winds in the storm’s wake. Extreme winds may therefore become a threat when an inability to compensate for drift could lead to forced landings and collisions. Birds may need to know where land is in order to avoid it. This provides additional selective pressure for a map sense and could explain why juvenile shearwaters, which lack a map sense, instead navigating using a compass heading, are susceptible to being wrecked. We suggest that the ability to respond to storms is influenced by both flight and navigational capacities. This may become increasingly pertinent due to changes in extreme weather patterns.

Significance Statement

Cyclones can cause billions of dollars of damage and loss of human life. They can also cause mass mortality and strandings in seabirds. We used GPS tracking data from streaked shearwaters breeding in the world’s most active cyclone basin to understand how seabirds respond to these systems. Birds varied their response according to the wind speed and direction, generally flying towards the eye of the cyclone in strong winds. This surprising strategy enables dynamic soaring birds to control their exposure to risky wind vectors that could drift them onshore. Nonetheless, birds may need to know where land is in order to avoid it. Juveniles lack this “map sense”, making them susceptible to wrecking in some scenarios.
Automated Deep Brain Stimulation programming based on electrode location – a randomized, cross-over trial using a data-driven algorithm
Authors: Roediger Jan , Achtzehn Johannes , Busch Johannes L. , Dembek Till A. , Krämer Anna-Pauline , Schneider Gerd-Helge , Krause Patricia , Horn Andreas , Kühn Andrea A.
Published: April 2022

Background

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly effective in controlling motor symptoms in patients with Parkinson’s Disease (PD). However, correct selection of stimulation parameters is pivotal to treatment success and currently follows a time-consuming and demanding trial-and-error process. We conducted a double-blind, ran-domized, cross-over, non-inferiority trial to assess treatment effects of stimulation parameters suggested by a recently published algorithm (StimFit) based on neuroimaging data.

Methods

The trial was carried out at Charité – Universitätsmedizin, Berlin, Germany and enrolled 35 PD patients treated with directional octopolar electrodes targeted at the STN. All patients had undergone DBS programming according to our centers standard of care (SoC) treatment before study recruitment. Based on perioperative imaging data DBS electrodes were reconstructed and StimFit was applied to suggest optimal stimulation settings. Patients underwent motor assessments using MDS-UPDRS-III during OFF-medication and in OFF-and ON-stimulation states under both conditions, StimFit and SoC parameter settings that were double blinded and randomized in a 1:1 ratio. The primary endpoint of this study was the absolute mean difference between MDS-UPDRS-III scores under StimFit and SoC stimulation, with a non-inferiority margin of five points.

Findings

STN DBS resulted in mean MDS-UPDRS-III improvements of 48 % for SoC and 43 % with StimFit as compared to OFF-stimulation condition. The mean difference between MDS-UPDRS-III scores under StimFit and SoC stimulation was not significant (1.6 points), and non-inferiority was established. In six patients (17 %) initial programming of StimFit settings resulted in acute side-effects and amplitudes were reduced until side-effects disappeared.

Interpretation

Automated data-driven algorithms can predict stimulation parameters which lead to motor symptom control comparable to standard of care treatment. This approach could significantly decrease the time necessary to obtain optimal treatment parameters thereby fostering the design of more complex DBS electrodes. Long-term data including effects on quality of life require further investigation.
Genetic and environmental factors underlying parallel changes in body mass index and alcohol consumption: a 36-year longitudinal study of adult twins
Authors: Drouard Gabin , Silventoinen Karri , Latvala Antti , Kaprio Jaakko
Published: April 2022

Background

The genetic and environmental underpinnings of simultaneous changes in weight and alcohol consumption are poorly known.

Objective

We sought to quantify the environmental and genetic components underlying parallel changes in weight and alcohol consumption, and to investigate potential covariations between them.

Methods

The analysis comprised 4461 adult participants (58% women) from the Finnish Twin Cohort. Four measures of alcohol consumption and body mass index (BMI) were available over a 36-year follow-up. Trajectories of each trait were described by growth factors, defined as intercepts (i.e., baseline) and slopes (i.e., change over follow-up), using Latent Growth Curve Modeling. Growth values were used for male (190 MZ pairs, 293 DZ pairs) and female (316 MZ pairs, 487 DZ pairs) same-sex complete twin pairs in multivariate twin modeling. The variance and covariance of growth factors were then decomposed into genetic and environmental components.

Results

The baseline heritabilities were similar in men (BMI: h2=79%; alcohol consumption: h2=49%) and women (h2=77%; h2=45%). Heritabilities of BMI change were similar in men (h2=52%) and women (h2=57%), but higher in men for change in alcohol consumption (h2=45%) than in women (h2=31%). Significant genetic correlations between BMI at baseline and change in alcohol consumption were observed in both men (r =-0.17(95% Confidence Interval: -0.29,-0.04)) and women (r=-0.18(−0.31,-0.06)). The genetic components of baseline and longitudinal change were correlated for both BMI and alcohol consumption with sex differences. Non-shared environmental factors affecting changes in alcohol consumption and BMI were correlated in men (r=0.18(0.06,0.30)). Among women, non-shared environmental factors affecting baseline alcohol consumption and the change in BMI were correlated (r=-0.11(−0.20,-0.01)).

Conclusions

We provide evidence of genetic correlations between BMI and change in alcohol consumption. Independent of genetic effects, change in BMI and change in alcohol consumption covary.
Prevalence and correlates of urogenital schistosomiasis in school going children in Maramba compound of Livingstone District, Zambia
Authors: Kapanga Shike , Mulemena John Amos , Kamvuma Kingsley , Phiri Christopher Newton , Chanda Warren
Published: April 2022

Background

Schistosomiasis is an acute and chronic parasitic disease that is caused by trematode worms (blood flukes) of the genus Schistosoma. Schistosoma haematobium (S. haematobium) is known to cause urogenital schistosomiasis. The disease is the second most common socio-economically devastating tropical parasitic disease after malaria in Africa. In Zambia, it affects over a million school going children, mostly in rural communities due to unsafe water and inadequate sanitation facilities. This study aimed to determine the presence of S. haematobium in urine specimens of school going children in Maramba compound of Livingstone and establish factors associated with the acquisition and spread of the parasite.

Methods

A structured questionnaire was administered on all children with signed consent from their guardians/parents and afterward spot urine specimens were collected in sterile containers for macroscopically/microscopically examination by an independent laboratory technologist.

Results

A total of 173 school going children participated in the study. Parasitic eggs were detected in 6 specimens providing a prevalence of 3.47% (p<0.01) and this had a strong association with presence of microscopic red blood cells (p<0.01), dysuria (p=0.026), washing in a stream (p=0.01), and the perception on bilharzia acquisition (p<0.01).

Conclusion

The prevalence of urogenital schistosomiasis among school going children in Maramba compound was 3.47%, and the correlates of the infection included washing in a stream, older age and poor knowledge on schistosomiasis. Participants that had schistosomiasis often presented with hematuria and lacked knowledge on disease acquisition, health effects and preventive measures. This calls for more robust sensitization of school going children and periodic screening to curb the disease.
Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis
Authors: Baskaran Pranetha , Mihaylov Simeon R. , Vinsland Elin , Shah Kriti , Granat Lucy , Ultanir Sila K. , Tee Andrew R. , Murn Jernej , Bateman Joseph M.
Published: April 2022

Mechanistic target of rapamycin (mTOR) is a protein kinase that integrates multiple inputs to regulate anabolic cellular processes. mTOR complex I (mTORC1) has key functions in growth control, autophagy and metabolism. Much less is known about the signalling components that act downstream of mTORC1 that regulate cellular morphology, a vital determinant of cellular function. Here we show that the RNA-binding protein Unkempt, a key regulator of cellular morphogenesis, is a novel substrate mTORC1. We find that Unkempt phosphorylation is regulated by nutrient levels and growth factors via mTORC1. Furthermore, Unkempt physically interacts with and is directly phosphorylated by mTORC1 through binding to the regulatory-associated protein of mTOR, Raptor. Phosphorylation of Unkempt, which we find is mTORC1-dependent in cultured mammalian cell lines as well as in primary tissues, occurs largely within the highly serine-rich intrinsically disordered region of Unkempt. Importantly, mutation analysis of this region indicates that phosphorylation inhibits the ability of Unkempt to induce a bipolar morphology. Our findings reveal a novel molecular link between mTORC1 signalling and cellular morphogenesis.
Dissecting brain grey and white matter microstructure: a novel clinical diffusion MRI protocol
Authors: Schiavi Simona , Palombo Marco , Zacà Domenico , Tazza Francesco , Lapucci Caterina , Castellan Lucio , Costagli Mauro , Inglese Matilde
Published: April 2022

Soma and Neurite Density Image (SANDI) is an advanced diffusion magnetic resonance imaging (dMRI) signal model devised to probe in vivo microstructural information from both grey and white matter. However, this model requires multi-shell acquisitions that include b-values that are at least 6 times higher than those used in clinical practice. Here we present a 10-minute acquisition protocol that enables to acquire the necessary images for SANDI modelling on a clinical 3T scanner. We demonstrate the feasibility and assess the repeatability and reproducibility of our approach by computing microstructural metrics of SANDI and other state-of-the-art models on five healthy subjects and we present its potential clinical impact on five subjects affected by multiple sclerosis with relapsing-remitting course. Our results suggest that SANDI is a repeatable, reproducible, feasible, and practical method to characterize both white and grey matter tissues in both the healthy brain and in neurological diseases.
Probing the Drug Dynamics and Mode-of-Action of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells
Authors: Shen Po-Ting , Huang Steven H. , Huang Zhouyang , Wilson Justin J. , Shvets Gennady
Published: April 2022

Infrared spectroscopy has drawn considerable interests in biological applications, but the measurement of live cells is impeded by the attenuation of infrared light in water. Metasurfaceenhanced infrared reflection spectroscopy (MEIRS) had been shown to mitigate the problem, enhance the cellular infrared signal through surface-enhanced infrared absorption, and encode the cellular vibrational signatures in the reflectance spectrum at the same time. In this study, we used MEIRS to study the dynamic response of live cancer cells to a newly developed chemotherapeutic metal complex with distinct modes of action (MoAs): tricarbonyl rhenium isonitrile polypyridyl (TRIP). MEIRS measurements demonstrated that administering TRIP resulted in long-term (several hours) reduction in protein, lipid, and overall refractive index signals, and in short-term (tens of minutes) increase in these signals that was consistent with the induction of endoplasmic reticulum stress. The unique tricarbonyl IR signature of TRIP in the bio-orthogonal spectral window was monitored in real time, and was used as an infrared tag to detect the precise drug delivery time that was shown to be closely correlated with the onset of the phenotypic response. These results demonstrate that MEIRS is an effective label-free real-time cellular assay capable of detecting and interpreting the early phenotypic responses of cells to IR-tagged chemotherapeutics.
Drought selection onArabidopsispopulations and their microbiomes
Authors: Karasov Talia L. , Neumann Manuela , Shirsekar Gautam , Monroe Grey ,   PATHODOPSIS Team, Weigel Detlef , Schwab Rebecca
Published: April 2022

Microbes affect plant health, stress tolerance1and life history2. In different regions of the globe, plants are colonized by distinct pathogenic and commensal microbiomes, but the factors driving their geographic variation are largely unknown3. We identified and measured the core leaf microbiome ofArabidopsis thalianain its native range, from almost 300 populations across Europe. Comparing the distribution of the approximately 500 major bacterial phylotypes, we discovered marked, geography-dependent differences in microbiome composition withinA. thalianaand betweenA. thalianaand other Brassicaceae, with two distinct microbiome types segregating along a latitudinal gradient. The differences in microbiome composition mirror the spatial genetics ofA. thaliana, with 52-68% of variance in the first two principal coordinates of microbiome type explained by host genotype. Microbiome composition is best predicted by drought-associated metrics that are well known to be a major selective agent onA. thalianapopulations. The reproducible and predictable associations between specific microbes and water availability raise the possibility that drought not only directly shapes genetic variation inA. thaliana, but does so also indirectly through its effects on the leaf microbiome.
Growth limitation via chemically complex carbohydrates reduces sensitivity of synthetic human gut communities to perturbations
Authors: Loss Erin Ostrem , Thompson Jaron , Cheung Kevin Pak , Qian Yili , Venturelli Ophelia S.
Published: April 2022

Dietary fiber affects the composition and functions of microbial communities that reside in the human gut. However, we lack a detailed and quantitative understanding of how these nutrients shape microbial community dynamics, interaction networks and systems-level properties. Using synthetic human gut communities coupled to computational modeling, we dissect the effects of varied fiber types or their constituent sugars on community assembly and sensitivity to perturbations. By quantifying carbohydrate chemical complexity, we demonstrate that microbial growth decreases as a function of complexity. We further demonstrate that the balance of species occupying distinct metabolic niches is altered by the presence of chemically complex carbohydrates. The frequency of negative inter-species interactions is reduced in the presence of complex carbohydrates. Communities grown in complex carbohydrates reproducibly assemble from a wide range of initial species abundances and display reduced sensitivity to invasion. Resource competition is identified as a key mechanism influencing the response of communities to perturbations. The strength of resource competition can promote sensitivity of community assembly to variations in initial species proportions and impact community resistance to invasion. By limiting microbial growth, complex carbohydrates promote the expansion of species occupying niches beyond carbohydrate utilization, shape the distribution of inter-species interactions, which in turn determines the community’s response to perturbations.
Use of a novel knock-in allele of Pkd1 identifies nicotinamide nucleotide dehydrogenase as a mitochondrial binding partner of polycystin-1
Authors: Lin Cheng-Chao , Menezes Luis F. , Pearson Elisabeth , Zhou Fang , Ishimoto Yu , Anderson D. Eric , Germino Gregory G.
Published: April 2022

The localization and function of Polycystin-1, the protein encoded by the gene most commonly mutated in autosomal dominant polycystic kidney disease, remains controversial. We have recently reported that its C-terminus is cleaved and traffics to the mitochondria rather than to the nucleus as had been previously described, and we found that absence of PC1 resulted in fragmented mitochondrial networks and increased mitochondrial membrane potential. Direct visualization of PC1 in mitochondria was only possible, however, after over-expression of recombinant, fluorescently labeled-PC1 in a cell culture system. To resolve the issue, we generated a new mouse model with three copies of the HA epitope and eGFP knocked-in frame into the endogenous mouse Pkd1 gene by CRISPR/Cas9. We show that the modified allele is fully functional but the eGFP-tagged protein cannot be detected without antibody amplification methods. We were, however, able to use nanobody-coupled beads and large quantities of tissue to isolate a PC1 interactome and verify nicotinamide nucleotide transhydrogenase (Nnt) as a mitochondrial partner, linking PC1 to regulation of reactive oxygen species levels in the mitochondria. Loss of Nnt function had no significant effect on renal cystic disease in Pkd1 mutants but treatment of young mice with early onset cystic disease with n-acetyl-cysteine (NAC) provided modest benefit only in the Nnt+/+ genetic background. These studies suggest that new methods and brighter tags will be required to track endogenous PC1, but this new mouse model will be a valuable resource for characterizing the protein interactome of endogenous PC1. The data also support our prior findings that the PC1 C-terminus localizes to mitochondria and regulates their function.
A Leak K+Channel TWK-40 Regulates Rhythmic Motor Program inC. elegans
Authors: Yue Zhongpu , Li Yi , Yu Bin , Xu Yueqing , Chen Lili , Chitturi Jyothsna , Meng Jun , Hung Wesley , Tian Yuhang , Mouridi Sonia El , Zhang Cuntai , Boulin Thomas , Zhen Mei , Gao Shangbang
Published: April 2022

Leak potassium (K+) currents, conducted by two-pore domain K+(K2P) channels, are critical for the stabilization of the membrane potential. The effect of K2Pchannels on motor rhythm remains enigmatic. We show here that the K2PTWK-40 regulates the rhythmic defecation motor program (DMP) inCaenorhabditis elegans. Disrupting TWK-40 suppresses the expulsion defects ofnlp-40andaex-2mutants. By contrast, a gain-of-function (gf) mutant oftwk-40significantly reduces the expulsion frequency per DMP cycle.In situwhole-cell patch clamping demonstrates that TWK-40 forms an outward current that hyperpolarize the resting membrane potential of DVB neuron. In addition, TWK-40 substantially contributes to the rhythmic activity of DVB. Specifically, DVB Ca2+oscillations exhibit obvious defects intwk-40mutants. Expression of TWK-40(gf) in DVB recapitulates the expulsion deficiency of thetwk-40(gf)mutant, and inhibits DVB Ca2+oscillations in both wild-type andtwk-40(lf)animals. Moreover, DVB innervated enteric muscles also exhibit rhythmic Ca2+defects. Taken together, these results demonstrate that TWK-40 is an essential neuronal inhibitor of DMP, thus revealing a cellular mechanism linking leak K2Pchannels with rhythmic motor activity.
Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas
Authors: Esmaeili Vahid , Oryshchuk Anastasiia , Asri Reza , Tamura Keita , Foustoukos Georgios , Liu Yanqi , Guiet Romain , Crochet Sylvain , Petersen Carl C.H.
Published: April 2022

Excitatory and inhibitory neurons in diverse cortical regions are likely to contribute differentially to the transformation of sensory information into goal-directed motor plans. Here, we investigate the relative changes across mouse sensorimotor cortex in the activity of putative excitatory and inhibitory neurons - categorized as regular or fast spiking according to their action potential waveform - comparing before and after learning of a whisker detection task with delayed licking as perceptual report. Surprisingly, we found that the whisker-evoked activity of regular versus fast spiking neurons changed in opposite directions after learning in primary and secondary whisker motor cortices, while it changed similarly in primary and secondary orofacial motor cortices. Our results suggest that changes in the balance of excitation and inhibition in local circuits concurrent with changes in the long-range synaptic inputs in distinct cortical regions might contribute to performance of delayed sensory-to-motor transformation.