bluuebunny/crossref_metadata_2025 huggingface dataset:
The Geriatric Nutritional Risk Index as a predictor of complications in geriatric trauma patients
Authors: Kregel Heather R. , Murphy Patrick B. , Attia Mina , Meyer David E. , Morris Rachel S. , Onyema Ezenwa C. , Adams Sasha D. , Wade Charles E. , Harvin John A. , Kao Lillian S. , Puzio Thaddeus J.
Published: March 2022

BACKGROUND

Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS

This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI <82), moderate risk (GNRI 82–91), low risk (GNRI 92–98), and no risk (GNRI >98). The primary outcome was mortality. Secondary outcomes included ventilator days, intensive care unit length of stay (LOS), hospital LOS, discharge home, sepsis, pneumonia, and acute respiratory distress syndrome. Bivariate and multivariable logistic regression analyses were performed to determine the association between GNRI risk category and outcomes.

RESULTS

A total of 513 patients were identified for analysis. Median age was 78 years (71–86 years); 24 patients (4.7%) were identified as major risk, 66 (12.9%) as moderate risk, 72 (14%) as low risk, and 351 (68.4%) as no risk. Injury Severity Scores and Charlson Comorbidity Indexes were similar between all groups. Patients in the no risk group had decreased rates of death, and after adjusting for Injury Severity Score, age, and Charlson Comorbidity Index, the no risk group had decreased odds of death (odds ratio, 0.13; 95% confidence interval, 0.04–0.41) compared with the major risk group. The no risk group also had fewer infectious complications including sepsis and pneumonia, and shorter hospital LOS and were more likely to be discharged home.

CONCLUSIONS

Major GNRI risk is associated with increased mortality and infectious complications in geriatric trauma patients. Further studies should target interventional strategies for those at highest risk based on GNRI.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Temporal Speech Parameters Indicate Early Cognitive Decline in Elderly Patients With Type 2 Diabetes Mellitus
Authors: Imre Nóra , Balogh Réka , Gosztolya Gábor , Tóth László , Hoffmann Ildikó , Várkonyi Tamás , Lengyel Csaba , Pákáski Magdolna , Kálmán János
Published: March 2022

Introduction:

The earliest signs of cognitive decline include deficits in temporal (time-based) speech characteristics. Type 2 diabetes mellitus (T2DM) patients are more prone to mild cognitive impairment (MCI). The aim of this study was to compare the temporal speech characteristics of elderly (above 50 y) T2DM patients with age-matched nondiabetic subjects.

Materials and Methods:

A total of 160 individuals were screened, 100 of whom were eligible (T2DM: n=51; nondiabetic: n=49). Participants were classified either as having healthy cognition (HC) or showing signs of MCI. Speech recordings were collected through a phone call. Based on automatic speech recognition, 15 temporal parameters were calculated.

Results:

The HC with T2DM group showed significantly shorter utterance length, higher duration rate of silent pause and total pause, and higher average duration of silent pause and total pause compared with the HC without T2DM group. Regarding the MCI participants, parameters were similar between the T2DM and the nondiabetic subgroups.

Conclusions:

Temporal speech characteristics of T2DM patients showed early signs of altered cognitive functioning, whereas neuropsychological tests did not detect deterioration. This method is useful for identifying the T2DM patients most at risk for manifest MCI, and could serve as a remote cognitive screening tool.
Economic Burden of Chronic Comorbidities Among Community-Dwelling Older Adults With Dementia
Authors: Liu Yi-Shao , Barner Jamie C. , Rascati Karen L. , Bhattacharjee Sandipan
Published: March 2022

Objective:

This study examined the extent to which chronic comorbidities contribute to excess health care expenditures between older adults with dementia and propensity score (PS)-matched nondementia controls.

Methods:

This was a retrospective, cross-sectional, PS-matched case (dementia): control (nondementia) study of older adults (65 y or above) using alternative years data from pooled 2005 to 2015 Medical Expenditure Panel Surveys (MEPS). Chronic comorbidities were identified based on Clinical Classifications System or ICD-9-CM codes. Ordinary least squares regression was utilized to quantify the impact of chronic comorbidities on the excess expenditures with logarithmic transformation. Expenditures were expressed as 2019 US dollars. All analyses accounted for the complex survey design of MEPS.

Results:

The mean yearly home health care expenditures were particularly higher among older adults with dementia and co-occurring anemia, eye disorders, hyperlipidemia, and hypertension compared with PS-matched controls. Ordinary least squares regression models revealed that home health care expenditures were 131% higher (β=0.837, P<0.001) among older adults with dementia compared with matched nondementia controls before adjusting for chronic comorbidities. When additionally adjusting for chronic comorbidities, the percentage increase, while still significant (P<0.001) decreased from 131% to 102%.

Conclusions:

The excess home health care expenditures were partially explained by chronic comorbidities among community-dwelling older adults with dementia.
Do male meadow voles (Microtus pennsylvanicus) always prefer and signal to ‘popular’ females? The role of social information context
Authors: Scauzillo Ryan C. , Ferkin Michael H.
Published: March 2022

For males, the behaviour of rival conspecifics can provide vital information about finding reproductively available females, and which have high-quality phenotypes. While valuable, this information represents sperm competition risk and even the potential for rejection by females. Thus, males should show flexibility in signalling behaviours towards females based on social information acquired with emphasis on the context of that information. We examined male meadow vole scent-marking behaviours and preferences for females based on previously obtained social information across different contexts. Social information context resulted in increased scent marking depending on the social odour pairing. Males scent marked more near a female whose odour had associated with three older rivals than one younger rival. But males marked equally toward a female whose odour had associated with three younger rivals and a female whose odour had associated with one older rival. This demonstrates that social odours are not of all equal value and that males can distinguish differences. Males then use these differences to tailor their signalling towards potentially high-quality phenotype females thereby maximizing their reproductive opportunities.
Nocturnal lighting in animal research should be replicable and reflect relevant ecological conditions
Authors: Aulsebrook Anne E. , Jechow Andreas , Krop-Benesch Annette , Kyba Christopher C. M. , Longcore Travis , Perkin Elizabeth K. , van Grunsven Roy H. A.
Published: March 2022

In nature, light is a key driver of animal behaviour and physiology. When studying captive or laboratory animals, researchers usually expose animals to a period of darkness, to mimic night. However, ‘darkness’ is often poorly quantified and its importance is generally underappreciated in animal research. Even small differences in nocturnal light conditions can influence biology. When light levels during the dark phase are not reported accurately, experiments can be impossible to replicate and compare. Furthermore, when nocturnal light levels are unrealistically dark or bright, the research is less ecologically relevant. Such issues are exacerbated by huge differences in the sensitivity of different light meters, which are not always described in study methods. We argue that nocturnal light levels need to be reported clearly and precisely, particularly in studies of animals housed indoors (e.g. ‘<0.03 lux’ rather than ‘0 lux’ or ‘dark’), and that these light levels should reflect conditions that the animal would experience in a natural context.
Trivially informative semantic context inflates people's confidence they can perform a highly complex skill
Authors: Jordan Kayla , Zajac Rachel , Bernstein Daniel , Joshi Chaitanya , Garry Maryanne
Published: March 2022

Some research suggests people are overconfident because of personality characteristics, lack of insight, or because overconfidence is beneficial in its own right. But other research fits with the possibility that fluent experience in the moment can rapidly drive overconfidence. For example, fluency can push people to become overconfident in their ability to throw a dart, know how rainbows form or predict the future value of a commodity. But surely there are limits to overconfidence. That is, even in the face of fluency manipulations known to increase feelings of confidence, reasonable people would reject the thought that they, for example, might be able to land a plane in an emergency. To address this question, we conducted two experiments comprising a total of 780 people. We asked some people (but not others) to watch a trivially informative video of a pilot landing a plane before they rated their confidence in their own ability to land a plane. We found watching the video inflated people's confidence that they could land a plane. Our findings extend prior work by suggesting that increased semantic context creates illusions not just of prior experience or understanding—but also of the ability to actually do something implausible.
Predicting the spatio-temporal infection risk in indoor spaces using an efficient airborne transmission model
Authors: Lau Zechariah , Griffiths Ian M. , English Aaron , Kaouri Katerina
Published: March 2022

We develop a spatially dependent generalization to the Wells–Riley model, which determines the infection risk due to airborne transmission of viruses. We assume that the infectious aerosol concentration is governed by an advection–diffusion–reaction equation with the aerosols advected by airflow, diffused due to turbulence, emitted by infected people, and removed due to ventilation, inactivation of the virus and gravitational settling. We consider one asymptomatic or presymptomatic infectious person breathing or talking, with or without a mask, and model a quasi-three-dimensional set-up that incorporates a recirculating air-conditioning flow. We derive a semi-analytic solution that enables fast simulations and compare our predictions to three real-life case studies—a courtroom, a restaurant, and a hospital ward—demonstrating good agreement. We then generate predictions for the concentration and the infection risk in a classroom, for four different ventilation settings. We quantify the significant reduction in the concentration and the infection risk as ventilation improves, and derive appropriate power laws. The model can be easily updated for different parameter values and can be used to make predictions on the expected time taken to become infected, for any location, emission rate, and ventilation level. The results have direct applicability in mitigating the spread of the COVID-19 pandemic.
Lagrangian fibrations in coupled resonant oscillators in the paired case of four degrees of freedom containing swinging spring oscillator
Authors: Mazrooei-Sebdani Reza , Yousefi Zahra
Published: March 2022

This paper deals with Lagrangian fibrations in coupled resonant oscillators containing swinging spring oscillators of four degrees of freedom. We will consider the cases with zero angular momenta with

1
:
1

and

1
:
2

(Fermi) resonances. Moreover, we also consider a coupled spatial swinging spring oscillator with a harmonic oscillator. Actually, they make different four degrees of freedom Hamiltonian resonances, i.e.

1
:
2
:
1
:
1

and

1
:
2
:
1
:
2

resonances. We will obtain the third-order normalization of these Hamiltonian resonances. We consider the linear Casimir energy and we approximate models by normal forms. Then our models are Liouville integrable. For one case with zero angular momentum and coupled swinging spring, we will identify Hopf fibration. The relative equilibria and normal modes are identified in the space of orbits. Our analysis is based on affecting energy levels in oscillators. These energy levels have been marked with distinguished parameters which show the constants of motions or integrals.
A comprehensive analysis of different 7T SRAM topologies to design a 1R1 W bit interleaving enabled and half select free cell for 32 nm technology node
Authors: Rawat Bhawna , Mittal Poornima
Published: March 2022

In this paper, a single-ended, dual port, 1R1 W seven transistor-based static random access memory bit cell is presented. The cell is designed based on a detailed review of various pre-existing 7T cells. All the cells in the paper are evaluated at 32 nm technology and supply voltage of 0.8 V. The static analysis reveals that the hold/read noise margins for the proposed cell are 324 mV each, whereas the write margin is 488 mV. Successful read and write operation for the cell requires a pulse-width of 5 ps and 0.14 ns, respectively. The temperature variation and process corner analysis are used to justify the reliability for the proposed cell. The former analysis yields 0.15 and 0.24 mV/°C variation in the HSNM/RSNM, and WM for the cell. The current ratio for the cell is comparatively higher than other cells. The leakage power consumption for the cell is 256 pW, while its read and write power consumption are 6 µW and 1.9 µW, respectively. Also, the cell is half select disturbance-free and therefore supports bit-interleaving. This ensures the increased reliability for the cell. All the aforementioned merits for the cells are achieved with a minimal layout area of 0.553 µm2.
Trait-based approaches to global change ecology: moving from description to prediction
Authors: Green Stephanie J. , Brookson Cole B. , Hardy Natasha A. , Crowder Larry B.
Published: March 2022

Trait-based approaches are increasingly recognized as a tool for understanding ecosystem re-assembly and function under intensifying global change. Here we synthesize trait-based research globally (n= 865 studies) to examine the contexts in which traits may be used for global change prediction. We find that exponential growth in the field over the last decade remains dominated by descriptive studies of terrestrial plant morphology, highlighting significant opportunities to expand trait-based thinking across systems and taxa. Very few studies (less than 3%) focus on predicting ecological effects of global change, mostly in the past 5 years and via singular traits that mediate abiotic limits on species distribution. Beyond organism size (the most examined trait), we identify over 2500 other morphological, physiological, behavioural and life-history traits known to mediate environmental filters of species' range and abundance as candidates for future predictive global change work. Though uncommon, spatially explicit process models—which mechanistically link traits to changes in organism distributions and abundance—are among the most promising frameworks for holistic global change prediction at scales relevant for conservation decision-making. Further progress towards trait-based forecasting requires addressing persistent barriers including (1) matching scales of multivariate trait and environment data to focal processes disrupted by global change, and (2) propagating variation in trait and environmental parameters throughout process model functions using simulation.
The quality characteristics of plant-based muffins prepared with
different contents of Actinidia arguta powder
Authors: Kim Jungsoo , Kim Jiyoon , Jeong Saeul , Kim Minhyun , Park Sanghyeok , Moon Jong Tae , Moon Kwang-Deog
Published: March 2022

Despite the high intake convenience and functionality of Actinidia
arguta, its practical utilization remains limited; therefore, the
development of new products is necessary to increase the industrial significance
of Actinidia arguta. Also, as the vegetarian population
increases rapidly, various plant-based products are required. This study, the
most optimum contents of Actinidia arguta powder (AP) was
selected by analyzing the quality of plant-based muffins added by different
amounts of AP (0%, 10%, 15%, and 20% (w/w) based on wheat flour). The muffin
height and volume decreased significantly by adding AP. AP10 exhibited the
lowest water holding capacity of flour, which affected the moisture content,
baking loss, and yield. As AP increased, pH decreased and DPPH radical
scavenging increased (p<0.05). In sensory evaluation AP10, and AP15
presented the high scores, while AP20 was the lowest. Smell scores was increased
by adding AP. AP15 had the highest in appearance and texture. As a result, 15%
of AP is the optimum concentration for producing plant-based muffins. Although
lower in appearance quality than AP0, AP15 has satisfied preferences and
functional needs. It is expected to increase the consumption of
Actinidia arguta.
Culture and function-related characteristics of six acetic acid
bacterial strains isolated from farm-made fermented vinegars
Authors: Kim Sun Hee , Kim Joo-Yeon , Jeong Woo Soo , Gwon Hee-Min , Kim So Young , Yeo Soo-Hwan
Published: March 2022

The present study evaluated the cultural and functional characteristics of six
strains of acetic-acid bacteria (AAB), namely, GHUR-A11-2, SR-A24, GY-A26,
GHF-A37, JS-B7, and JS-C1, which were isolated from farm-made fermented
vinegars. The six bacterial strains exhibited high acetic acid production
capability via the decomposition of CaCO3, and they were identified
as Acetobacter pasteurianus based on the 16S rDNA sequences.
The initial pH and optimal growth temperature for acetic acid production were
determined to be 4.0 and 30°C, respectively; however, some strains of AAB
presented reasonable growth even at 40°C. Four bacterial strains (except
SR-A24 and GHF-A37) exhibited alcohol degradation activities of more than 90%.
Bacillus cereus presented high susceptibility to the
antibacterial activity of the six strains of AAB. The antioxidant activity
evaluated using DPPH and ABTS was 5–15 times and 4–5 times higher
for the six strains of AAB than that for the control group, respectively.
GHUR-A11-2, SR-A24, and JS-C1 exhibited higher ACE activities, with inhibition
rates of 154%-175%, as compared to those exhibited by the positive control of
0.1% captopril (inhibition rate of 138%). Furthermore, the fibrinolysis activity
of SR-A24 (93.3%) was markedly higher than that of 0.5 U plasmin. Four bacterial
strains (except GHF-A37 (75.3%) and JS-B7 (68.0%)), exhibited
α-glucosidase inhibition activities of more than 100%. It was concluded
that the six strains of AAB exhibited excellent physiologically active
characteristics, which facilitated their use as seed strains for the synthesis
of high-efficiency functional vinegar by harnessing the functional
characteristics that fit the scientific basis.
High-frame-rate analysis of knee cartilage deformation by spiral dualMRI and relaxation mapping
Authors: Lee Woowon , Miller Emily Y. , Zhu Hongtian , Luetkemeyer Callan M. , Schneider Stephanie E. , Neu Corey P.
Published: March 2022

Purpose

Daily activities including walking impose high frequency cyclic forces on cartilage and repetitive compressive deformation. Analyzing cartilage deformation during walking would provide spatial maps of displacement, strain, and enable viscoelastic characterization, which may serve as imaging biomarkers for early cartilage degeneration when the damage is still reversible. However, the time-dependent biomechanics of cartilage is not well described, and how defects in the joint impact the viscoelastic response is unclear.

Methods

We used spiral acquisition with displacement encoding MRI to quantify displacement and strain maps at a high frame rate (40 ms; 25 frames/sec) in tibiofemoral joints. We also employed relaxometry methods (T1, T1ρ, T2, T2*) on the cartilage.

Results

Normal and shear strains were concentrated on the tibiofemoral contact area during loading, and the defected joint exhibited larger compressive strains. We also determined a positive correlation between the change of T1ρ in cartilage after cyclic loading and increased compressive strain on the defected joint. Viscoelastic behavior was quantified by the time-dependent displacement, where the damaged joint showed increased creep behavior compared to the intact.

Conclusions

Our results indicate that spiral scanning with displacement encoding can quantitatively differentiate the damaged from intact joint using the strain and creep response. The viscoelastic response identified with this methodology could serve as biomarkers to detect defects in joints in vivo and facilitate the early diagnosis of joint diseases such as osteoarthritis.
Wireless networks of injectable microelectronic stimulators based on rectification of volume conducted high frequency currents
Authors: García-Moreno Aracelys , Comerma-Montells Albert , Tudela-Pi Marc , Minguillon Jesus , Becerra-Fajardo Laura , Ivorra Antoni
Published: March 2022

Objective

To develop and in vivo demonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable.

Approach

These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics.

Main results

The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum-iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions.

Significance

These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. This paves the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.
Synapse type-specific molecular nanoconfigurations of the presynaptic active zone in the hippocampus identified by systematic nanoscopy
Authors: Sakamoto Hirokazu , Kimpara Naoya , Namiki Shigeyuki , Hamada Shun , Ohtsuka Toshihisa , Hirose Kenzo
Published: March 2022

Neurotransmitters are released by exocytosis from synaptic vesicles at the active zone in the presynaptic terminal. The scaffold of the active zone consists of only a few evolutionarily conserved proteins, including RIM, CAST/ELKS, and RIM-BP, and tethers Munc13 and Ca2+ channels. The molecular principles that enable these proteins to mediate synaptic diversity have remained unclear. Here, we identified synapse type-specific molecular nanoconfigurations in the active zone by systematic quantification of active zone proteins using nanoscopy at two types of excitatory synapses and two types of inhibitory synapses in the rat hippocampal CA3 region. Quantitative analysis revealed that Munc13 content was particularly varied among the various synapse types and that the physical proximity of Ca2+ channels to the active zone scaffolds correlated with the efficacy of neurotransmitter release. We propose that the active zone is a flexible supramolecular assembly that can tune its composition and spatial configuration to adjust neurotransmitter release.
A comprehensive mechanistic model of adipocyte signaling with layers of confidence
Authors: Lövfors William , Jönsson Cecilia , Olofsson Charlotta S. , Cedersund Gunnar , Nyman Elin
Published: March 2022

Adipocyte cellular signaling, normally and in type 2 diabetes, is far from fully studied. We have earlier developed detailed dynamic mathematical models for some well-studied, and partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response. For a broader coverage of the response, large-scale phosphoproteomic data is key. There exists such data for the insulin response of adipocytes, as well as prior knowledge on possible protein-protein interactions associated with a confidence level. However, methods to combine detailed dynamic models with large-scale data, using information about the confidence of included interactions, are lacking. In our new method, we first establish a core model by connecting our partially overlapping models of adipocyte cellular signaling with focus on: 1) lipolysis and fatty acid release, 2) glucose uptake, and 3) the release of adiponectin. We use the phosphoproteome data and prior knowledge to identify phosphosites adjacent to the core model, and then try to add the adjacent phosphosites to the model. The additions of the adjacent phosphosites is tested in a parallel, pairwise approach with low computation time. We then iteratively collect the accepted additions into alayer, and use the newly added layer to find new adjacent phosphosites. We find that the first 15 layers (60 added phosphosites) with the highest confidence can correctly predict independent inhibitor-data (70-90 % correct), and that this ability decrease when we add layers of decreasing confidence. In total, 60 layers (3926 phosphosites) can be added to the model and still keep predictive ability. Finally, we use the comprehensive adipocyte model to simulate systems-wide alterations in adipocytes in type 2 diabetes. This new method provide a tool to create large models that keeps track of varying confidence.
Integrated platform for multi-scale molecular imaging and phenotyping of the human brain
Authors: Park Juhyuk , Wang Ji , Guan Webster , Gjesteby Lars A. , Pollack Dylan , Kamentsky Lee , Evans Nicholas B. , Stirman Jeff , Gu Xinyi , Zhao Chuanxi , Marx Slayton , Kim Minyoung E. , Choi Seo Woo , Snyder Michael , Chavez David , Su-Arcaro Clover , Tian Yuxuan , Park Chang Sin , Zhang Qiangge , Yun Dae Hee , Moukheiber Mira , Feng Guoping , Yang X. William , Keene C. Dirk , Hof Patrick R. , Ghosh Satrajit S. , Frosch Matthew P. , Brattain Laura J. , Chung Kwanghun
Published: March 2022

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multi-scale details of individual cells in the human organ-scale system. To address this challenge, we developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain, by integrating novel chemical, mechanical, and computational tools. The platform includes three key tools: (i) a vibrating microtome for ultra-precision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), (ii) a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and (iii) a computational pipeline for reconstructing 3D connectivity across multiple brain slabs (UNSLICE). We demonstrated the transformative potential of our platform by analyzing human Alzheimer’s disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

One-Sentence Summary

We developed an integrated, scalable platform for highly multiplexed, multi-scale phenotyping and connectivity mapping in the same human brain tissue, which incorporated novel tissue processing, labeling, imaging, and computational technologies.
Overlap across psychotic disorders: A functional network connectivity analysis
Authors: Dini Hossein , Bruni Luis E. , Ramsøy Thomas Z. , Calhoun Vince D. , Sendi Mohammad S. E.
Published: March 2022

Functional network connectivity has previously been shown to distinguish patient groups from healthy controls (HC). However, the overlap across schizophrenia (SZ), bipolar (BP), and schizoaffective disorder (SAD) is not clear yet. This study focuses on finding overlap across these three psychotic disorders using dynamic FNC (dFNC) and compares it with static FNC (sFNC). We used resting-state fMRI, demographics, and clinical information from the Bipolar– Schizophrenia Network on Intermediate Phenotypes cohort. The data includes three groups of patients with schizophrenia (SZP, N=102), bipolar (BPP, N=102), and schizoaffective (SADP, N=102), their relatives SZR (N=102), BPR (N=102), SADR (N=102), and HC (N=118) groups. After estimating each individual’s dFNC, we put them into three identical states. We estimated five different features, including occupancy rate (OCR), number of transitions, the total number of transitions, and the total distance traveled. Finally, the extracted features are tested statistically across patients and HC groups. In addition, we explored the link between the clinical scores and the extracted features. We found that the OCR difference between SZP and SZR in state2, between BPP and HC in state1, and between SADP and HC in state2. Also, state2 OCR separates SZP from BPP, state 3 OCR separates BPP from SZP and SADP. Moreover, the OCR and traveled distance feature extracted from SZ and BP could significantly predict PANSS Total and PANSS General scores. Finally, combined distance features of all disorders showed a significant relationship to PANSS Total and PANSS General scores.
Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in adolescents in Taiwan: A double-blind, randomized, placebo-controlled phase 2 trial
Authors: Liu Luke Tzu-Chi , Chiu Cheng-Hsun , Chiu Nan-Chang , Tan Boon-Fatt , Lin Chien-Yu , Cheng Hao-Yuan , Lin Meei-Yun , Lien Chia-En , Chen Charles , Huang Li-Min
Published: March 2022

Background

MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on the prefusion spike protein S-2P and adjuvanted with CpG 1018 and aluminum hydroxide. Although MVC-COV1901 has been licensed for emergency use for adults in Taiwan, the safety and immunogenicity of MVC-COV1901 in adolescents remained unknown. As young people play an important role in SARS-CoV-2 transmission and epidemiology, a vaccine approved for adolescents and eventually, children, will be important in mitigating the COVID-19 pandemic.

Methods

This study is a prospective, double-blind, multi-center phase 2 trial evaluating the safety, tolerability and immunogenicity of two doses of the SARS-CoV-2 vaccine MVC-COV1901 in adolescents. Healthy adolescents from age of 12 to 17 years were recruited and randomly assigned (6:1) to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. The primary outcomes were safety and immunogenicity from the day of first vaccination (Day 1) to 28 days after the second vaccination (Day 57), and immunogenicity of MVC COV1901 in adolescents as compared to young adult vaccinees in terms of neutralizing antibody titers and seroconversion rate. The secondary outcomes were safety and immunogenicity of MVC-COV1901 as compared to placebo in adolescents in terms of immunoglobulin titers and neutralizing antibody titers over the study period.

Results

Between July 21, 2021 and December 22, 2021, a total of 399 adolescent participants were included for safety evaluation after enrollment to receive at least one dose of either MVC-COV1901 (N=341) or placebo (N=58). Of these, 334 and 46 participants went on to receive two doses of either MVC-COV1901 or placebo, respectively, and were included in the per protocol set (PPS) for immunogenicity analysis. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups. The most commonly reported adverse events were pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups.

Conclusions

The safety and immunogenicity data presented here showed that MVC-COV1901 has similar safety profile and non-inferior immunogenicity in adolescents compared to young adults.

ClinicalTrials.gov registration

NCT04951388.
Functional architecture of cerebral cortex during naturalistic movie-watching
Authors: Rajimehr Reza , Xu Haoran , Farahani Asa , Kornblith Simon , Duncan John , Desimone Robert
Published: March 2022

Characterizing the functional organization of cerebral cortex is a fundamental step in understanding how different kinds of information are processed in the brain. Neuroimaging studies over the past decades have uncovered the function of many cortical areas in response to selected stimulus categories. However, it is still unclear how cortical areas are organized during naturalistic visual and auditory stimulation. Here we used high-resolution functional MRI data from 176 human subjects to map the macro-architecture of the entire cerebral cortex based on responses to a 60-minute audiovisual movie stimulus. A data-driven clustering approach revealed a map of 24 functional areas/networks, each related to a specific aspect of sensory or cognitive processing. The map included three distinct executive control (domain-general) networks which showed a strong push-pull interaction with domain-specific regions in visual, auditory, and language cortex. The cortical parcellation scheme presented here provides a comprehensive and unified map of functionally defined areas, which could replace a large set of functional localizer maps.
Zfp281 inhibits the pluripotent-to-totipotent state transition in mouse embryonic stem cells
Authors: Wen Xinpeng , Lin Zesong , Wu Hao , Fu Xudong
Published: March 2022

The cell-fate transition between pluripotent and totipotent states determines embryonic development and the first cell-lineage segregation. However, limited by the scarcity of totipotent embryos, regulators on this transition remain largely elusive. A novel model to study the transition has been recently established, named the 2-cell-like (2C-like) model. The 2C-like cells are rare totipotent-like cells in the mouse embryonic stem cell (mESC) culture. Pluripotent mESCs can spontaneously transit into and out of the 2C-like state. We previously dissected the transcriptional roadmap of the transition. In this study, we revealed that Zfp281 is a novel regulator for the pluripotent-to-totipotent transition in mESCs. Zfp281 is a transcriptional factor involved in the cell-fate transition. Our study shows that Zfp281 represses transcripts upregulated during the 2C-like transition via Tet1 and consequentially inhibits mESCs from transiting into the 2C-like state. Interestingly, we found that the inhibitory effect of Zfp281 on the 2C-like transition leads to an impaired 2C-like-transition ability in primed-state mESCs. Altogether, our study reveals a novel mediator for the pluripotent-to-totipotent state transition in mESCs and provides insights into the dynamic transcriptional control of the transition.
Dual spatially resolved transcriptomics for SARS-CoV-2 host-pathogen colocalization studies in humans
Authors: Sounart Hailey , Lázár Enikő , Masarapu Yuvarani , Wu Jian , Várkonyi Tibor , Glasz Tibor , Kiss András , Borgström Erik , Hill Andrew , Jurek Aleksandra , Niesnerová Anezka , Druid Henrik , Bergmann Olaf , Giacomello Stefania
Published: March 2022

To advance our understanding of cellular host-pathogen interactions, technologies that facilitate the co-capture of both host and pathogen spatial transcriptome information are needed. Here, we present an approach to simultaneously capture host and pathogen spatial gene expression information from the same formalin-fixed paraffin embedded (FFPE) tissue section using the spatial transcriptomics technology. We applied the method to COVID-19 patient lung samples and enabled the dual detection of human and SARS-CoV-2 transcriptomes at 55 μm resolution. We validated our spatial detection of SARS-CoV-2 and identified an average specificity of 94.92% in comparison to RNAScope and 82.20% in comparison toin situsequencing (ISS). COVID-19 tissues showed an upregulation of host immune response, such as increased expression of inflammatory cytokines, lymphocyte and fibroblast markers. Our colocalization analysis revealed that SARS-CoV-2+spots presented shifts in host RNA metabolism, autophagy, NFκB, and interferon response pathways. Future applications of our approach will enable new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes.
Genomes of Two Flying Squid Species Provide Novel Sights into Adaptations of Cephalopods to Pelagic Life
Authors: Li Min , Wu Baosheng , Zhang Peng , Li Ye , Xu Wenjie , Wang Kun , Qiu Qiang , Zhang Jun , Li Jie , Zhang Chi , Fan Jiangtao , Feng Chenguang , Chen Zuozhi
Published: March 2022

Pelagic cephalopods have evolved a series of fascinating traits, such as excellent visual acuity, high-speed agility, and photophores for adaptation to open pelagic oceans. However, the genetic mechanisms underpinning these traits are not well understood. Thus, in this study, we obtained high-quality genomes of two purpleback flying squid species (Sthenoteuthis oualaniensis and Sthenoteuthis sp.), with sizes of 5450 and 5651 Mb. Comparative genomic analyses revealed a common expansion of the S-crystallin subfamily SL20-1 associated with visual acuity in the purpleback flying squid lineage and showed that evolution of high-speed agility for the species was accompanied by significant positive selection pressure on genes related to energy metabolism. These molecular signals might have contributed to the evolution of their adaptative predatory and anti-predatory traits. In addition, transcriptomic analysis provided clear indications of the evolution for the photophores of purpleback flying squids, inter alia that recruitment of new genes and energy metabolism genes may have played key functional roles in the process.
The development of efficient communication in the human connectome
Authors: van Blooijs D. , van den Boom M.A. , van der Aar J.F. , Huiskamp G.J.M. , Castegnaro G. , Demuru M. , Zweiphenning W.J.E.M. , van Eijsden P. , Miller K. J. , Leijten F.S.S. , Hermes D.
Published: March 2022

The structure of the human connectome develops from childhood throughout adolescence to middle age, but how this affects the speed of neuronal signaling is not well described. To understand the maturation process of transmission speed across the connectome, we stimulated electrocorticographic (ECoG) electrode pairs in 75 human subjects of 4 to 51 years old. We then measured the latency of cortico-cortical evoked responses in other electrodes. Each year, responses got faster, until transmission speed reached a minimum latency at the age of 29-44 years old. Responses during middle age were about two times faster compared to childhood. These increases in speed were observed in both long- and short-range connections between and within frontal, central, parietal, and temporal areas. These findings indicate that long-range and short-range communication between brain regions increase in efficiency well throughout adolescence.
Regulation of presynaptic Ca2+ channel abundance at active zones through a balance of delivery and turnover
Authors: Cunningham Karen L. , Sauvola Chad W. , Tavana Sara , Littleton J. Troy
Published: March 2022

Abstract

Voltage-gated Ca2+ channels (VGCCs) mediate Ca2+ influx to trigger neurotransmitter release at specialized presynaptic sites termed active zones (AZs). The abundance of VGCCs at AZs regulates neurotransmitter release probability (Pr), a key presynaptic determinant of synaptic strength. Although biosynthesis, delivery and recycling cooperate to establish AZ VGCC abundance, experimentally isolating these distinct regulatory processes has been difficult. Here we describe how the AZ levels of Cacophony (Cac), the sole VGCC mediating synaptic transmission in Drosophila, are determined. We also analyzed the relationship between Cac, the conserved VGCC regulatory subunit α2δ, and the core AZ scaffold protein Bruchpilot (BRP) in establishing a functional AZ. We find Cac and BRP are independently regulated at growing AZs, as Cac is dispensable for AZ formation and structural maturation, and BRP abundance is not limiting for Cac accumulation. Additionally, AZs stop accumulating Cac after an initial growth phase, whereas BRP levels continue to increase given extended developmental time. AZ Cac is also buffered against moderate increases or decreases in biosynthesis, whereas BRP lacks this buffering. To probe mechanisms that determine AZ Cac abundance, intravital FRAP and Cac photoconversion were used to separately measure delivery and turnover at individual AZs over a multi-day period. Cac delivery occurs broadly across the AZ population, correlates with AZ size, and is rate-limited by α2δ. Although Cac does not undergo significant lateral transfer between neighboring AZs over the course of development, Cac removal from AZs does occur and is promoted by new Cac delivery, generating a cap on Cac accumulation at mature AZs. Together these findings reveal how Cac biosynthesis, synaptic delivery, and recycling set the abundance of VGCCs at individual AZs throughout synapse development and maintenance.
Atypical small GTPase RABL3 interacts with RAB11 to regulate early ciliogenesis in human cells
Authors: Kobayashi Tetsuo , Ikeda Tatsuya , Ota Reo , Yasukawa Takafumi , Itoh Hiroshi
Published: March 2022

Primary cilia are near-ubiquitously assembled on cells in the human body and are broadly associated with genetic diseases and cancers. In the early stage of ciliogenesis, the ciliary vesicle (CV) is formed on the mother centriole, which nucleates the primary cilium. However, the regulatory mechanisms underlying CV formation have not yet been fully elucidated. Here, we found that the atypical small GTPase RAB-Like 3 (RABL3) is necessary to assemble primary cilia in human cells. RABL3 directly interacts with RAB11, which is involved in CV formation. RABL3 localizes around the centrosome during early ciliogenesis, reminiscent of RAB11 dynamics. Furthermore, RABL3 positively controls the CV formation like RAB11. These findings suggest that RABL3 plays an important role, in cooperation with RAB11, in CV formation during early ciliogenesis.
Dual targeting ofSaccharomyces cerevisiaePso2 to mitochondria and the nucleus, and its functional relevance in the repair of DNA interstrand crosslinks
Authors: Somashekara Shravanahalli C. , Muniyappa Kalappa
Published: March 2022

Repair of DNA interstrand crosslinks (ICLs) involves a functional interplay among different DNA surveillance and repair pathways. Previous work has shown that ICL- inducing agents cause damage toSaccharomyces cerevisiaenuclear and mitochondrial DNA (mtDNA), and itspso2/snm1mutants exhibit a petite phenotype followed by loss of mtDNA integrity and copy number. Complex as it is, the cause and underlying molecular mechanisms remains elusive. Here, by combining a wide range of approaches within vitroandin vivoanalyses, we assessed the subcellular localization and function of Pso2. We found evidence that the nuclear-encoded Pso2 contains one mitochondrial targeting sequence (MTS) and two nuclear localization signals (NLS1 and NLS2), although NLS1 resides within the MTS. Further analysis revealed that Pso2 is a dual-localized ICL repair protein; it can be imported into both nucleus and mitochondria, and that genotoxic agents enhance its abundance in the latter. While MTS is essential for mitochondrial Pso2 import, either NLS1 or NLS2 is sufficient for its nuclear import; this implies that the two NLS motifs are functionally redundant. Ablation of MTS abrogated mitochondrial Pso2 import, and concomitantly, raised its levels in the nucleus. Strikingly, mutational disruption of both NLS motifs blocked the nuclear Pso2 import; at the same time, they enhanced its translocation into the mitochondria, consistent with the notion that the relationship between MTS and NLS motifs is competitive. However, the nuclease activity of import-deficient species of Pso2 was not impaired. The potential relevance of dual-targeting of Pso2 into two DNA-bearing organelles is discussed.
Long-term survival analysis of HIV patients on antiretroviral therapy in Congo: a 14 years retrospective cohort analysis, 2003-2017
Authors: Ndziessi Gilbert , Niama Ange Clauvel , Nkodia Arkadit Jeandria , Diafouka Merlin
Published: March 2022

Background

The long-term survival of patients on antiretroviral treatment in Congo remains less documented. Our study aimed to analyze the long-term survival of adults living with HIV on ART (Antiretroviral Therapy).

Methods

We conducted a historical cohort study on 2,309 adult PLHIV (People Living with HIV) followed between January 1, 2003 and December 31, 2017 whose viral load and date of initiation of ART were known. The Kaplan Meier method was used to estimate the probability of survival and the Cox regression model to identify factors associated with death.

Results

The median age was 49 years; the female sex was predominant with 68.56%. The probability of survival at 14 years was 83%, (95% CI (Confidence Interval) [78-87]). On the other hand, when the lost to follow-up died, it was 66% (95% CI [62-70]) in the worst scenario. Stratified cox regression analysis showed that: being male, AHR (Adjusted Hazard Ratio) = 1.65 (95% CI [1.26-2.17]) was significantly associated with death, p-value <0.0001. Furthermore, having a viral load> 1000 copies / ml, AHR = 2.56 (95% CI [1.93-3.40]), be in the advanced WHO clinical stage, in particular: stage II, AHR = 4.07 (95% CI [2.36-7.01]); stage III, AHR = 13.49 (95% CI [8.99-20.27]) and stage IV, AHR = 34.45 (95% CI [23.74-50]) were also significantly associated with death; p-value <0.0001.

Conclusion

The long-term survival of PLHIV is worrying despite the offer of ARVs.