bluuebunny/crossref_metadata_2025 huggingface dataset:
Kolakhar – a traditionally prepared biochar revealed potentiality in ameliorating soil acidity stress in rice
Authors: Shandilya Zina Moni , Tanti Bhaben
Published: May 2022

Context Acidic soil stress is a silent threat to the plant biome including rice. Aim To develop a feasible method for ameliorating acidic soil stress that neutralises the acidity and benefits the plants to restore the necessary nutrients in the soil environment in an eco-friendly approach. Methods A traditionally prepared organic biochar from stem, peel and suckers of banana, i.e. kolakhar was used individually and also in a combination with commercial biochar (biokhar) to evaluate the growth of five traditional rice varieties with contrasting characters for tolerability of Al toxicity and P deficiency. Key Results The rice seedlings treated with kolakhar showed better responses in biomass, photosynthetic efficiency and antioxidant protection mechanisms. Enhanced production of ascorbate peroxidase, guaiacol peroxidase etc. in seedlings growing under kolakhar treated soil reveals their possible mechanism developed to cope with the stress. The final pH of all the treated soils with ameliorants was found to change to ∼6.0, nearly similar to normal soil from 4.2 to 4.5. The amount of phosphorous was highest in soil treated with kolakhar 250 mg kg−1. Kolakhar showed the highest reduction of available Al from 2.107 to 0.018 mg kg−1 after 30 days of treatment. Above all, the histochemical staining elucidated that the Al uptake was more profound in the controls. In contrast, much reduced Al uptake was observed in roots under treatment with ameliorants, which could be because of the decreased Al content in the soil as determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis. Conclusions These findings have paved the way to overcome the severe issues of acidic soil stress, associated hazards of Al accumulation and other stresses. Implications Kolakhar could be exploited for ameliorating soil acidity through low cost and eco-friendly way.
Processing clause-internal discourse relations in a second language
Authors: Wetzel Mathis , Crible Ludivine , Zufferey Sandrine
Published: May 2022

Coherence relations are expressed differently across languages, often leading to language learners misusing
discourse connectives. We argue that the ability to detect these errors crucially depends on the coherence relation under
scrutiny, as errors may remain unnoticed when the relation is clause-internal and marked with a highly optional connective. We
focus, therefore, on specifications, a relation that German-speaking learners sometimes struggle to correctly indicate when
writing in French. We assessed whether non-native readers detect this error and show preferences for either explicit or implicit
marking of specifications. Findings show that non-native speakers were generally able to detect the error in a sentence-evaluation
task but did not react to it in a self-paced-reading task, contrary to native speakers. They also judged implicit specifications
as more correct than explicitly marked specifications. We conclude that non-native speakers do not always benefit from connectives
during text processing, especially when they are highly optional.
Metonymy, reflexive hyperbole and broadly reflexive relationships
Authors: Barnden John A.
Published: May 2022

I explore some relationships between metonymy and a special type of hyperbole that I call reflexive
hyperbole. Reflexive hyperbole provides a unified, simple explanation of certain natural meanings of statements such
as the following: Sailing is Mary’s life, The undersea sculptures became the ocean, When Sally watched the film she became
James Bond, I am Charlie Hebdo, John is Hitler, The internet is cocaine and I am Amsterdam. The
meanings, while of seemingly disparate types, are deeply united: they are all hyperbolic about some contextually salient
relationship that has a special property that I call “broad reflexivity.” Although a few of the types of meaning of interest have
metonymic aspects (or metaphorical aspects), reflexive hyperbole cannot just be explained by a straightforward application of
metonymy theory (or metaphor theory). Indeed, I argue instead for a dependency in the converse direction: that much and perhaps
even all metonymy is rooted – if sometimes slightly indirectly – in broadly reflexive relationships, though not usually in a
hyperbolic way.
Field-effect conductivity scaling for two-dimensional materials with tunable impurity density
Authors: Wang Chulin , Peng Lintao , Wells Spencer A , Cain Jeffrey D , Huang Yi-Kai , Rhoads Lawrence A , Dravid Vinayak P , Hersam Mark C , Grayson Matthew A
Published: May 2022

A scaling law is demonstrated in the conductivity of gated two-dimensional (2D) materials with tunable concentrations of ionized impurity scatterers. Experimental data is shown to collapse onto a single 2D conductivity scaling (2DCS) curve when the mobility is scaled by r, the relative impurity-induced scattering, and the gate voltage is shifted by

V

s

, a consequence of impurity-induced doping. This 2DCS analysis is demonstrated first in an encapsulated 2D black phosphorus multilayer at

T
=
100

K

with charge trap densities programmed by a gate bias upon cooldown, and next in a Bi2Se3 2D monolayer at room temperature exposed to varying concentrations of gas adsorbates. The observed scaling can be explained using a conductivity model with screened ionized impurity scatterers. The slope of the r vs. 

V

s

plot defines a disorder-charge specific scattering rate

Γ
q

=

d

r

/

d

V

s

equivalent to a scattering strength per unit impurity charge density:

Γ
q

>
0

indicates a preponderance of positively charged impurities with

Γ
q

<
0

for negatively charged. This 2DCS analysis is expected to be applicable in arbitrary 2D materials systems with tunable impurity density, which will advance 2D materials characterization and improve performance of 2D sensors and transistors.
Partial substitution of feldspar by alkaline-rich materials in the electrical porcelain insulator for reduction of processing temperature
Authors: Beyene Eaba , Tiruneh Sintayehu Nibret , Andoshe Dinsefa Mensur , Abebe Adane Muche , Tullu Andualem Merga
Published: May 2022

Porcelain is the most widely used overhead power-line insulator. The demands for porcelain insulators have increased dramatically owing to a sharp increase in the electric power demand and supply. Usually, porcelain production demands high sintering temperatures. Herein, an electrical porcelain insulator was produced from Bombowha clay and Arero quartz and partially replaced feldspar with sodium carbonate at a reduced processing temperature. The porcelain samples were prepared by fixing the clay and quartz amount 45 and 10 wt%, respectively, and the portion of feldspar was replaced by 5, 7.5, and 10 wt% of alkaline-rich sodium carbonate. The desired composition was milled, shaped, and finally sintered at 1000, 1100, and 1200 °C. The XRD and SEM results show the early formation of quartz and mullite phases at 1000 °C, which determine the mechanical and dielectric strengths of the porcelains. The dielectric strength of the samples increases with increasing the alkaline-rich sodium carbonate content owing to the vitrification and needle-shaped mullite formation. The porcelain sample with 10 wt% of Na2CO3 content and a sintering temperature of 1200 °C has an optimum dielectric strength of 7.60 kV mm−1.
Gagliardo-Nirenberg type inequalities on Lorentz, Marcinkiewicz and weak-𝐿^{∞} spaces
Authors: Dao Anh , Lam Nguyen , Lu Guozhen
Published: May 2022

We establish the Gagliardo-Nirenberg inequality, Trudinger-Moser inequality and John-Nirenberg inequality using the Lorentz spaces

L

p
,
α

L^{p,\alpha }

, the Marcinkiewicz space

L

q
,
∞

L^{q,\infty }

and the weak-

L

∞

L^{\infty }

space

W
W

introduced by Bennett, DeVore and Sharpley [Ann. of Math. (2) 113 (1981), pp. 601–611]. As consequences, we obtain the Gagliardo-Nirenberg type inequality with weak-

L

∞

L^{\infty }

norm and BMO norm, Trudinger-Moser type inequality and John-Nirenberg type estimate with

B
M
O

BMO

norm and weak-

L

1

L^{1}

norm.
Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Neutralization After Antenatal Messenger RNA Vaccination
Authors: Rottenstreich Amihai , Vorontsov Olesya , Alfi Or , Zarbiv Gila , Oiknine-Djian Esther , Zigron Roy , Kleinstern Geffen , Mandelboim Michal , Porat Shay , Wolf Dana G
Published: May 2022

We evaluated the neutralization efficiency against SARS-CoV-2 Omicron variant in maternal and cord blood sera after antenatal BNT162b2 vaccination. Neutralizing antibodies against Omicron were lacking at the time of delivery after 2-dose vaccination. A third booster dose was essential in building neutralizing antibody capacity against Omicron among mothers and neonates.
Performance assessment of solar chimney power plants with natural thermal energy storage materials on ground: CFD analysis with experimental validation
Authors: Cuce Erdem , Saxena Abhishek , Cuce Pinar Mert , Sen Harun , Eroglu Hasan , Selvanathan Shanmuga Priya , Sudhakar Kumarasamy , Hasanuzzaman Md
Published: May 2022

This study interprets the effect of using sand or gravel as energy storage unit in solar chimney power plants. The effect of using low-cost materials is evaluated. Based on the Manzanares pilot plant, a 3D CFD model is created. Geometric parameters are kept constant in simulations performed with ANSYS FLUENT engineering commercial software. By simultaneously solving DO (discrete ordinates) solar ray tracing algorithm and RNG k-ε turbulence model, the outputs of the system are examined at 290 and 300 K temperatures. The temperature distribution and power outputs of the use of sand and gravel as soil material at different temperatures and solar radiation are compared. It is understood that the use of both materials does not significantly affect the performance of the system and can be used economically instead of each other. It is seen that the system will give a power output of approximately 41.636 kW with both storage materials at a radiation intensity of 800 W/m2 and an ambient temperature of 300 K. It is seen that the ambient temperature affects the temperature increase in the system, and the temperature increase is higher at 290 K.
Inhaled open safety pin: a challenging case
Authors: Sedhai Milan , Tripathi Prashant
Published: May 2022

Foreign body aspiration in children, specifically sharp and metallic type, imposes a serious morbidity and mortality risk if intervention is delayed. The bronchoscopic removal of sharp metallic foreign bodies is technically challenging for the operating surgeon. We present a case of an 8-year-old girl who presented with an alleged history of aspiration of metallic, sharp and open safety pin 8 hours prior to presentation following which she developed throat pain and painful swallowing. X-ray of soft tissue neck showed a radio-opaque foreign body being lodged in the supraglottic area. She underwent emergency direct laryngoscopy-guided foreign body removal under general anesthesia. There was an open metallic sharp safety pin hinged over the inter-arytenoid region with its one end reaching sub-glottis and other end toward the hypopharynx. No post-operative complications occurred and patient was discharged on the third post-operative day.
Feasibility analysis of super-speed rail based on improved value function
Authors: Hu Qizhou , Wu Yikai
Published: May 2022

Super-speed rail (SSR) is a kind of train design based on the theory of vacuum pipeline transportation, having the advantages of super speed, high safety, low energy consumption, low noise, no vibration and no pollution. SSR may be a new generation of trains after cars, ships, trains and aeroplanes. The SSR system includes two parts, namely vacuum pipe technology and magnetic levitation technology. Based on the definition of SSR, the present paper analyses the operation principle of SSR. According to distribution characteristics of SSR, the evaluation index system of SSR was set up. In analysing the main characteristics of SSR, this paper builds the evaluation model by improved value function. The application results validate the feasibility of the new method in comprehensive evaluation for SSR. It is consistent with the results of other methods. The result reveals that SSR is completely feasible from a theoretical point of view and it is impossible to build SSR in a short time from the application perspective. The evaluation results can reflect the actual situation. The comprehensive evaluation model is scientific and the process is simple.
Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19*
Authors: Rocheleau Genevieve L. Y. , Lee Terry , Mohammed Yassene , Goodlett David , Burns Kevin , Cheng Matthew P. , Tran Karen , Sweet David , Marshall John , Slutsky Arthur S. , Murthy Srinivas , Singer Joel , Patrick David M. , Du Bin , Peng Zhiyong , Lee Todd C. , Boyd John H. , Walley Keith R. , Lamontagne Francois , Fowler Robert , Winston Brent W. , Haljan Greg , Vinh Donald C. , McGeer Alison , Maslove David , Patrigeon Santiago Perez , Mann Puneet , Donohoe Kathryn , Hernandez Geraldine , Russell James A. ,   for ARBs CORONA I Investigators
Published: May 2022

OBJECTIVES:

To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components.

DESIGN:

Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), comparing males with females.

SETTING:

ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces.

PATIENTS:

One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation (p = 0.006) and vasopressors (p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females.

CONCLUSIONS:

ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.
Review of Delayed Reactions to 15 Hyaluronic Acid Fillers
Authors: Kokoska Ryan E. , Lima Amanda M. , Kingsley Melanie M.
Published: May 2022

BACKGROUND

Delayed-onset reactions are increasingly relevant given the growing use of hyaluronic acid dermal fillers. There is poor understanding of the phenomenon's etiology and incidence.

OBJECTIVE

To highlight differences between the dermal filler products with an emphasis on delayed-onset reaction incidence, pathogenesis, prevention, and treatment.

METHODS

A literature review was performed for delayed-onset reactions following hyaluronic acid dermal filler injection using PubMeb and Embase. Articles were included based on relevance, quality, and the predetermined definition of “delayed-onset reaction” (>30 days post injection). A total of 28 studies were included in the data analysis.

RESULTS

A total of 13,136 subjects from 28 studies treated with 15 filler types were included in the analysis. VYC-15L dermal filler injections carried the highest risk of delayed reaction with a mean incidence of 3.83% (n = 46/1,202), followed by VYC-20L (0.92%) and VYC-17.5L (0.88%). The mean incidence of delayed reactions among all filler types was 1.13%.

CONCLUSION

Incidence of delayed reaction to hyaluronic fillers ranges from 0% to 3.83% (mean = 1.13%) and varies by filler type. The exact etiology of these delayed reactions remains disputed. Future studies should report reaction description, precise timeline, and posttreatment immunologic history to better delineate the incidence of delayed-onset hypersensitivity reactions.
Uninterrupted Actigraphy Recording to Quantify Physical Activity and Sedentary Behaviors in Mechanically Ventilated Adults
Authors: González-Seguel Felipe , Camus-Molina Agustín , Leiva-Corvalán Macarena , Mayer Kirby P. , Leppe Jaime
Published: May 2022

Purpose:

We evaluated the feasibility of quantification of physical activity (PA) and sedentary behaviors (SB) using actigraphy during an entire intensive care unit (ICU) length of stay.

Methods:

A prospective study was performed in a 12-bed ICU. Triaxial accelerometers were fitted on the right ankle of mechanically ventilated adults. Twenty accelerometers were available to guarantee uninterrupted actigraphy recording 24 hours/day. Data were analyzed: (1) between awakening and ICU discharge to quantify daytime PA/SB and (2) between admission and ICU discharge to quantify day/nighttime inactivity. Secondarily, we assessed the relationship between inactivity/SB and clinical variables.

Results:

Thirty patients were enrolled, obtaining 5477 recording hours. No patient reported discomfort or injury. The median (min-max) delay time between admission and accelerometer installation was 2.1 (0.0-11.9) hours. Actigraphy recording duration was 5.4 (2.2-34.4) days. The time spent in SB and PA (percentage of minutes per hour) was 94.7% and 5.3%, respectively. PA was stratified by light, moderate, and vigorous levels equating to 91.8%, 7.7%, and 0.5%, respectively. Inactivity time (r = 0.991, P ≤ .001) and SB (r = 0.859, P ≤ .001) were strongly correlated with ICU length of stay.

Conclusions:

Quantifying PA levels with continuous monitoring through actigraphy is feasible, demonstrating prolonged periods of inactivity/SB. This study highlights that uninterrupted actigraphy could contribute to pursuing the optimal dose and the intervention fidelity of the ICU mobilization in the subsequent clinical trials.
Impact of Temporary Preoperative Mechanical Support on Heart Transplant Outcomes
Authors: Ganapathi Asvin M. , Benissan-Messan Dathe Z. , Mokadam Nahush A. , Henn Matthew C. , Lampert Brent C. , Hasan Ayesha , Emani Sitaramesh , Whitson Bryan A.
Published: May 2022

We sought to assess the impact of temporary preoperative mechanical circulatory support (TPMCS) on heart transplantation outcomes. A total of 4,060 adult heart transplants from June 1, 2006, to December 31, 2019, were identified in the Scientific Registry of Transplant Recipients database as having TPMCS. Recipients were divided into groups based on their type of TPMCS: intra-aortic balloon pump (IABP), temporary ventricular assist device (VAD), biventricular assist device (BIVAD), and extracorporeal membrane oxygenation (ECMO). Perioperative outcomes and survival were compared among groups. Recipients with IABP were associated with older age, a smoking history, and a significantly shorter wait list time (p < 0.01). Recipients with ECMO had a significantly increased in-hospital mortality as well as an increased incidence of dialysis (p < 0.01). Kaplan-Meier analysis revealed worse 1 and 5 year survival for recipients with ECMO. Cox model demonstrated a significantly increased risk of mortality with BIVAD (hazard ratio [HR], 1.33; 95% CI, 1.12–1.57; p < 0.01) and ECMO (HR, 1.64; 95% CI, 1.33–2.03; p < 0.01). While patients with IABP have a survival comparable to patients without TPMCS or durable left VAD, outcomes for BIVADs and ECMO are not as favorable. Transplantation centers must continue to make careful choices about the type of TPMCS utilized before heart transplant.
Utility of D-dimers in COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation
Authors: Shakoor Aqsa , Chen Stacey , Hyde Jonathan , Wu Brendan , Toy Bridget , Chang Stephanie , Kon Zachary , Piper Greta , Smith Deane
Published: May 2022

A retrospective study was performed examining the trend of inflammatory markers, including D-dimers, in 29 COVID-19 patients requiring veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support. We observed that COVID-19 patients with pre-cannulation D-dimer levels >3,000 ng/mL had a significantly shorter time from admission to cannulation (4.78 vs. 8.44 days, p = 0.049) compared to those with D-dimer <3,000 ng/mL. Furthermore, patients with D-dimer >3,000 ng/mL had a trend of lower pH (7.24 vs. 7.33), higher pCO2 (61.33 vs. 50.69), and higher vasoactive inotropic score (7.23 vs. 3.97) at time of cannulation, however, these were not statistically significant. This cohort of patients also required a longer duration of ECMO support (51.44 vs. 31.25 days). However, 13 patients required at least one ECMO-circuit exchange and 16 patients did not require any exchanges. There was a consistent drop in D-dimer values after every circuit exchange, which was not observed in any of the other examined inflammatory markers, including ferritin, lactate dehydrogenase, or C-reactive protein. We propose that elevated D-dimer levels (>3,000 ng/mL) reflect increased disease severity in COVID-19, and predict a longer ECMO course. Once on ECMO, however, the D-Dimer level consistently decreased with every circuit exchange, which may reflect thrombus within the oxygenator rather than just disease severity.
Successful Provision of Long-Acting Reversible Contraception in a Sexual Health Clinic
Authors: Obafemi Oluyomi A. , Leichliter Jami S. , Maravi Moises , Alfonsi Grace A. , Shlay Judith C. , Wendel Karen A. , Rietmeijer Cornelis A.
Published: May 2022

Background

Women who attend sexual health clinics are at high risk for sexually transmitted infections and unintended pregnancy. Long-acting reversible contraceptives (LARC) are very effective contraceptive methods, but the provision of LARC in such clinics is not well described in the literature.

Methods

We conducted a retrospective chart review of women who presented to Denver Sexual Health Clinic for any reason and received family planning services between April 1, 2016, and October 31, 2018. We assessed demographic and clinical factors associated with contraceptive method received and conducted a subanalysis of those with intrauterine device (IUD) insertions on the same-day versus delayed insertion. Among those who received an IUD, we assessed rates of pelvic inflammatory disease (PID) 30 days after insertion.

Results

Of the 5064 women who received family planning services in our clinic, 1167 (23%) were using a LARC method at the time of their visit. Of the 3897 who were not using a LARC, fewer women, 12.6%, chose LARC (IUD and progestin implant), compared with 33.3% who chose new short-acting reversible contraceptives. Further analysis of the 270 IUD initiators revealed 202 (74.8%) received the IUD on the same day, whereas 68 (25.2%) had delayed IUD insertion. There were 9 incident cases of gonorrhea or chlamydia in those who received same-day IUD and 1 incident case among those who had delayed IUD insertion. There were no cases of PID at 30 days after insertion in either group.

Conclusions

Study findings support IUD provision in a sexual health clinic on the day of initial visit without increased risk of PID.
Evaluating Provider Documentation of Suicide Risk Factors Among Youth Screening Positive for Suicide Risk in a Pediatric Emergency Department
Authors: Cafferty Rachel , Ambroggio Lilliam , Leonard Jan , Schmidt Sarah , Haasz Maya
Published: May 2022

Objective

Screening for suicidal ideation in the pediatric emergency department (ED) enhances recognition of suicidality among patients presenting with a nonmental health complaint. Little is known about the assessment of suicide risk factors and disposition among these patients. This study aimed to evaluate pediatric ED providers' documentation of suicide risk factors in this population.

Methods

We performed a retrospective cohort study of patients screening at risk for suicide on the Ask Suicide-Screening Questions tool. Demographic variables and risk factors for youth suicide were extracted from the electronic health record for eligible patients each month from January 1, 2019, to December 31, 2019. We compared risk factors using χ
2 or Fisher exact test.

Results

In 2019, of the 7484 patients screened for suicide, 524 (7%) had a positive screen. Of 220 patient charts reviewed, no suicide risk factors were documented in 53.6% of encounters, and only 1 risk factor was documented in 18.2% of encounters. Substance use was the most frequently discussed risk factor, documented in 33.6% of encounters. History of nonsuicidal self-injury was documented in 11.8% of visits. Other risk factors were documented in fewer than 10% of at-risk patients.

Conclusion

Pediatric ED providers do not routinely document risk factors for suicide in medical patients screening at risk. Although the Ask Suicide-Screening Questions is an important initial screen, a standardized secondary risk factor assessment is necessary for a more complete risk stratification for patients with suicidal ideation.
Not like night and day: the nocturnal letter-winged kite does not differ from diurnal congeners in orbit or endocast morphology
Authors: Keirnan Aubrey , Worthy Trevor H. , Smaers Jeroen B. , Mardon Karine , Iwaniuk Andrew N. , Weisbecker Vera
Published: May 2022

Nocturnal birds display diverse adaptations of the visual system to low-light conditions. The skulls of birds reflect many of these and are used increasingly to infer nocturnality in extinct species. However, it is unclear how reliable such assessments are, particularly in cases of recent evolutionary transitions to nocturnality. Here, we investigate a case of recently evolved nocturnality in the world's only nocturnal hawk, the letter-winged kiteElanus scriptus. We employed phylogenetically informed analyses of orbit, optic foramen and endocast measurements from three-dimensional reconstructions of micro-computed tomography scanned skulls of the letter-winged kite, two congeners, and 13 other accipitrid and falconid raptors. Contrary to earlier suggestions, the letter-winged kite was not unique in any of our metrics. However, all species ofElanushave significantly higher ratios of orbit versus optic foramen diameter, suggesting high visual sensitivity at the expense of acuity. In addition, visual system morphology varies greatly across accipitrid species, likely reflecting hunting styles. Overall, our results suggest that the transition to nocturnality can occur rapidly and without changes to key hard-tissue indicators of vision, but also that hard-tissue anatomy of the visual system may provide a means of inferring a range of raptor behaviours, well beyond nocturnality.
ALTERNATING HEMIPLEGIA OF CHILDHOOD: AN ELECTROCLINICAL STUDY OF SLEEP AND HEMIPLEGIA
Authors: Poole Josephine , Zagaglia Sara , Demurtas Rita , Farrell Fiona , Walker Matthew C. , Sisodiya Sanjay M. , Balestrini Simona , Vivekananda Umesh
Published: May 2022

Objective

Alternating Hemiplegia of Childhood (AHC) is characterised by paroxysmal hemiplegic episodes and seizures. Remission of hemiplegia upon sleep is a clinical diagnostic feature of AHC. We investigated whether: 1) Hemiplegic events are associated with spectral EEG changes 2) Sleep in AHC is associated with clinical or EEG spectral features that may explain its restorative effect.

Methods

We retrospectively performed EEG spectral analysis in five adults with AHC and twelve age-/gender-matched epilepsy controls. Five-minute epochs of hemiplegic episodes and ten-minute epochs of four sleep stages were selected from video-EEGs. Arousals were counted per hour of sleep.

Results

We found 1) hemispheric differences in pre-ictal and ictal spectral power (p=0.034), during AHC hemiplegic episodes 2) 22% reduced beta power (p=0.017) and 26% increased delta power (p=0.025) during wakefulness in AHC versus controls. There were 98% more arousals in the AHC group versus controls (p=0.0003).

Conclusions

There are hemispheric differences in spectral power preceding hemiplegic episodes in adults with AHC, and sleep is disrupted.

Significance

Spectral EEG changes may be a potential predictive tool for AHC hemiplegic episodes. Significantly disrupted sleep is a feature of AHC and is of particular importance when considering risk of sudden unexpected death in epilepsy (SUDEP).
Secure and federated linear mixed model association tests
Authors: Chen Jeffrey , Edupalli Manaswitha , Berger Bonnie , Cho Hyunghoon
Published: May 2022

Privacy-preserving algorithms for genome-wide association studies (GWAS) promise to facilitate data sharing across silos to accelerate new discoveries. However, existing approaches do not support an important, prevalent class of methods known as linear mixed model (LMM) association tests or would provide limited privacy protection, due to the high computational burden of LMMs under existing secure computation frameworks. Here we introduce SafeGENIE, an efficient and provably secure algorithm for LMM-based association studies, which allows multiple entities to securely share their data to jointly compute association statistics without leaking any intermediary results. We overcome the computational burden of LMMs by leveraging recent advances in LMMs and secure computation, as well as a novel scalable dimensionality reduction technique. Our results show that SafeGENIE obtains accurate association test results comparable to a state-of-the-art centralized algorithm (REGENIE), and achieves practical runtimes even for large datasets of up to 100K individuals. Our work unlocks the promise of secure and distributed algorithms for collaborative genomic studies.1
Patient satisfaction with telemedicine in the Philippines during the COVID-19 pandemic
Authors: Noceda Alicia Victoria G. , Acierto Lianne Margot M. , Bertiz Morvenn Chaimek C. , Dionisio David Emmanuel H. , Laurito Chelsea Beatrice L. , Sanchez Girrard Alphonse T. , Amit Arianna Maever L.
Published: May 2022

Introduction

The capacity to deliver essential health services has been negatively impacted by the COVID-19 pandemic particularly due to lockdown restrictions. Telemedicine provides a safe, efficient, and effective solution that addresses the needs of patients and the health system. However, there remain implementation challenges and barriers to patient adoption in resource-limited settings as in the Philippines. This study thus aimed to describe patient perspectives and experiences with telemedicine services, and explore the factors that influence telemedicine use and satisfaction.

Methods

This study used a mixed-methods design through online surveys and in-depth interviews. An online survey using Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group Adult Visit Survey 4.0 (beta) and Telehealth Usability Questionnaire (TUQ) was accomplished by 200 participants aged 18 to 65 years. A subsample of 16 participants was interviewed to provide insights to the quantitative data. We used descriptive statistics to analyze survey data and grounded theory to analyze data from interviews.

Results

Participants were generally satisfied with telemedicine services, with most reporting that this was an efficient and convenient alternative to face-to-face consultations. However, only 2 in 5 perceived telemedicine as affordable. Our quantitative findings suggest that participants preferred telemedicine services rather than in-person consultations, especially in cases where they feel that their condition is not urgent and does not need extensive physical examination. Safety against COVID-19, and the availability of multiple communication platforms contributed to patient satisfaction with telemedicine. Negative perceptions of patients on their telemedicine provider, perceived higher costs, poor connectivity and other technological issues were found to be barriers to patient satisfaction.

Discussion

Telemedicine is viewed as a safe and efficient alternative to receiving care. Continued adoption of telemedicine will require improvements in technology and better patient communication related to their telemedicine provider and the associated costs.
Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Authors: Brugarolas Pedro , Wilks Moses Q. , Noel Jacqueline , Kaiser Julia-Ann , Vesper Danielle R. , Ramos-Torres Karla M. , Guehl Nicolas J. , Macdonald-Soccorso Marina T. , Rice Peter A. , Yokell Daniel L. , Lim Ruth , Normandin Marc D. , Fakhri Georges El
Published: May 2022

Purpose

[18F]3F4AP is a novel PET radiotracer that targets voltage-gated potassium (K+) channels and has shown promise for imaging demyelinated lesions in animal models of neurological diseases. This study aimed to evaluate the biodistribution, safety and radiation dosimetry of [18F]3F4AP in healthy human volunteers.

Methods

Four healthy volunteers (2 female) underwent a 4-hour dynamic PET scan from cranial vertex to mid-thigh using multiple bed positions after administration of 368 ± 17.9 MBq (9.94 ± 0.48 mCi) of [18F]3F4AP was produced in a cGMP laboratory under IND authorization from the FDA. Volumes of interest for relevant organs were manually drawn guided by the CT and PET images and time-activity curves (TACs) were extracted. Radiation dosimetry was estimated from the integrated TACs using OLINDA software. Safety assessments included measuring vital signs immediately before and after the scan, monitoring for adverse events, as well as obtaining a comprehensive metabolic panel (CMP) and electrocardiogram (ECG) within 30 days before and after the scan. The study was approved by the institutional review board (IRB) and registered at clinicaltrials.gov (NCT04710550) before commencement.

Results

[18F]3F4AP distributed throughout the body with the highest levels of activity in the kidneys, urinary bladder, stomach, liver, spleen and brain and with low accumulation in muscle and fat. The tracer cleared quickly from circulation and from most organs. The clearance of the tracer was noticeably faster than previously reported clearance in nonhuman primates (NHPs). The average effective dose (ED) across all subjects was 12.1 ± 2.2 µSv/MBq, which is lower than the estimated ED from the NHP studies (21.6 ± 0.6 µSv/MBq) as well as the ED of other fluorine-18 radiotracers such as [18F]FDG (∼20 µSv/MBq). No differences in ED between males and females were observed. No substantial changes in safety assessments or adverse events were recorded.

Conclusion

The biodistribution and radiation dosimetry of [18F]3F4AP in humans is reported for the first time. The average total ED across four subjects was lower than most 18F-labeled PET tracers. The tracer and study procedures were well tolerated and no adverse events occurred.
Using a reverse genetics system to generate recombinant SARS-CoV-2 expressing robust levels of reporter genes
Authors: Ye Chengjin , Martinez-Sobrido Luis
Published: May 2022

Reporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the still ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) to study the contribution of viral proteins in viral pathogenesis. In addition, we have also engineered reporter-expressing recombinant viruses in which we place the reporter genes upstream of the viral nucleocapsid (N) gene to promote high levels of reporter gene expression that facilitates the study of SARS-CoV-2 in vitro and in vivo. Although successful, the genetic manipulation of the BAC containing the entire SARS-CoV-2 genome of ∼30,000 nucleotides, is challenging. Herein, we depict the technical details to engineer rSARS-CoV-2 expressing reporter genes using the BAC-based RG approach. We describe i) assembly of the full-length (FL) SARS-CoV-2 genome sequences into the empty pBeloBAC, ii) verification of the pBeloBAC-FL, iii) cloning of a Venus reporter gene into the pBeloBAC-FL, and iv) recovery of the Venus-expressing rSARS-CoV-2. By following this protocol, researchers with basic molecular biology and gene engineering techniques knowledge will be able to generate wild-type and reporter-expressing rSARS-CoV-2.
Alzheimer’s disease rewires gene coexpression networks coupling different brain regions
Authors: Mitra Sanga , B P Kailash , C R Srivatsan , Saikumar Naga Venkata , Philip Philge , Narayanan Manikandan
Published: May 2022

Connectome studies have revealed how neurodegenerative diseases like Alzheimer’s disease (AD) disrupt functional and structural connectivity among brain regions, but the molecular basis of such disruptions is less studied, with most genomic studies focusing on within-brain-region molecular analyses. We performed an inter-brain-region differential correlation (DC) analysis of postmortem human brain RNA-seq data available for four brain regions – frontal pole, superior temporal gyrus, parahippocampal gyrus, and inferior frontal gyrus – from Mount Sinai Brain Bank for hundreds of AD vs. control samples. For any two brain regions, our DC analysis identifies all pairs of genes across these regions whose coexpression/correlation strength in the AD group differs significantly from that in the Control group, after adjusting for cell type compositional effects to better capture cell-intrinsic changes. Such DC gene pairs provided information complementary to known differentially expressed genes in AD, and highlighted extensive rewiring of the network of cross-region coexpression-based couplings among genes. The most vulnerable region in AD, parahippocampal gyrus, showed the most rewiring in its coupling with other brain regions. Decomposing the DC network into bipartite (region-region) gene modules revealed enrichment for synaptic signaling and ion transport pathways in several modules, revealing the dominance of five genes (BSN, CACNA1B, GRIN1, IQSEC2, and SYNGAP1). AD cerebrospinal fluid biomarkers (AD-CSF), neurotransmitters, secretory proteins, ligand and receptors were found to be part of the DC network, suggesting how pathways comprising such signaling molecules could mediate region-region communication. A module enriched for AD GWAS (Genome-wide Association Studies) signals is also enriched for NF-κβ signaling pathway, a key mediator of brain inflammation in AD. Beyond modules, we also identified individual genes that act as hubs of AD dysregulation across regions, such as ZKSCAN1 (Zinc Finger with KRAB And SCAN Domains) – this gene is known to be linked to AD in GWAS studies but via unknown mechanisms, and the specific DC interactions of ZKSCAN1 found in this study can be used to dissect these mechanisms. Thus, our inter-region DC framework provides a valuable new perspective to comprehend AD aetiology.
Brain Serotonergic Fibers Suggest Anomalous Diffusion-Based Dropout in Artificial Neural Networks
Authors: Lee Christian , Zhang Zheng , Janušonis Skirmantas
Published: May 2022

Random dropout has become a standard regularization technique in artificial neural networks (ANNs), but it is currently unknown whether an analogous mechanism exists in biological neural networks (BioNNs). If it does, its structure is likely to be optimized by hundreds of millions of years of evolution, which may suggest novel dropout strategies in large-scale ANNs. We propose that the brain serotonergic fibers meet some of the expected criteria because of their ubiquitous presence, stochastic structure, and ability to grow throughout the individual’s lifespan. Since the trajectories of serotonergic fibers can be modeled as paths of anomalous diffusion processes, in this proof-of-concept study we investigated a dropout algorithm based on the superdiffusive fractional Brownian motion (FBM). This research contributes to biologically-inspired regularization in ANNs.
Benchmarking de novo assembly methods on metagenomic sequencing data
Authors: Zhang Zhenmiao , Yang Chao , Fang Xiaodong , Zhang Lu
Published: May 2022

Metagenome assembly is an efficient approach to deciphering the “microbial dark matter” in the microbiota based on metagenomic sequencing, due to the technical challenges involved in isolating and culturing all microbes in vitro. Although short-read sequencing has been widely used for metagenome assembly, linked- and long-read sequencing have shown their advancements by providing long-range DNA connectedness in assembly. Many metagenome assembly tools use dedicated algorithms to simplify the assembly graphs and resolve the repetitive sequences in microbial genomes. However, there remains no comprehensive evaluation of the pros and cons of various metagenomic sequencing technologies in metagenome assembly, and there is a lack of practical guidance on selecting the appropriate metagenome assembly tools. Therefore, this paper presents a comprehensive benchmark of 15 de novo assembly tools applied to 32 metagenomic sequencing datasets obtained from simulation, mock communities, or human stool samples. These datasets were generated using mainstream sequencing platforms, such as Illumina and BGISEQ short-read sequencing, 10x Genomics linked-read sequencing, and PacBio and Oxford Nanopore long-read sequencing. The assembly tools were extensively evaluated against many criteria, which revealed that compared with the other sequencing technologies, long-read assemblers generated the highest contig continuity but failed to reveal some medium- and high-quality metagenome-assembled genomes (MAGs). In addition, hybrid assemblers using both short- and long-read sequencing were promising tools to both improve contig continuity and increase the number of near-complete MAGs. This paper also discussed the running time and peak memory consumption of these tools and provided practical guidance on selecting them.
Regression Based Accuracy Estimation for Multiple Sequence Alignment
Authors: Cedillo Luis , Ruiz Hector Richart , DeBlasio Dan
Published: May 2022

Multiple sequence alignment plays an important role in many important analyses. However, aligning multiple biological sequences is a complex task, thus many tools have been developed to align sequences under a biologically-inspired objective function. But these tools require a user-defined parameter vector, which if chosen incorrectly, can greatly impact down-stream analysis. Parameter Advising addresses this challenge of selecting input-specific parameter vectors by comparing alignments produced by a carefully constructed set of parameter configurations. In an ideal scenario, we would rank alignments based on their accuracy. However, in practice, we do not have a reference from which to calculate accuracy. Therefore, it becomes necessary toestimatethe accuracy to rank the alignments. One solution involves the use of estimators such asFacet. The accuracy estimatorFacetcomputes an estimate of accuracy as a linear combination of efficiently-computable feature functions. In this work we introduce two new estimators calledLead(short forLearnedaccuracyestimator from largedatasets) which use the same underlying feature functions asFacetbut are built on top of highly efficient machine learning protocols, allowing us to take advantage of a larger training corpus.

Note about previous versions

A previous version of this paper was released on bioRxiv and presented the results of our previous study (Facet) with an error. This error has been corrected, and the conclusions made have been updated based on this new data. This corrected version stands as reference for anyone who may have encountered the versions with inaccuracies.
Resilient anatomy and local microplasticity of naïve and stress hematopoiesis
Authors: Wu Qingqing , Zhang Jizhou , Johnson Courtney B. , Slaughter Anastasiya , Weinhaus Benjamin , McKnight Morgan , Sherman Bryan E. , Shao Tzu-Yu , Song Baobao , Filippi Marie Dominique , Grimes H. Leighton , Way Sing Sing , Kofron J. Matthew , Lucas Daniel
Published: May 2022

The bone marrow has an extraordinary capacity to adjust blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses is largely unknown due to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent hematopoiesis, megakaryopoiesis, erythropoiesis, and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of hematopoiesis in homeostasis, after acute insults, and during geriatric age. Blood production takes place via long-range migration of multipotent progenitors away from stem cells. Lineage-committed progenitors are then serially recruited to blood vessels where they contribute to lineage-specific microanatomical structures, composed of progenitors and immature cells, which function as production lines for mature blood cells. This anatomy is durable and resilient to insults as it was maintained after hemorrhage, acute bacterial infection, and with aging. Production lines enable hematopoietic plasticity as they differentially -and selectively-modulate their numbers and output in response to acute insults and then return to homeostasis. In geriatric mice the number of production lines is maintained, but their microanatomy becomes permanently remodeled in a cell- and lineage-specific manner indicating chronic anatomical adaptations to hematopoietic aging. Our studies uncover the sophisticated and durable anatomy of blood production -defined by distinct migratory behaviors depending on the maturation stage- and identify discrete microanatomical production lines that confer plasticity to hematopoiesis.
PEG-Free Polyion Complex Nanocarriers for Brain Derived Neurotrophic Factor
Authors: Fay James M. , Lim Chaemin , Finkelstein Anna , Batrakova Elena , Kabanov Alexander V.
Published: May 2022

Many therapeutic formulations incorporate poly(ethylene glycol) (PEG) as a stealth component to minimize early clearance. However, PEG is immunogenic and susceptible to accelerated clearance after multiple administrations. Here, we present two novel reformulations of a polyion complex (PIC), originally comprised of poly(ethylene glycol)113-b-poly(glutamic acid)50 (PEG-PLE) and brain derived neurotrophic factor (BDNF), termed Nano-BDNF (Nano-BDNF PEG-PLE). We replace the PEG based block copolymer with two new polymers, poly(sarcosine)127-b-poly(glutamic acid)50 (PSR-PLE) and poly(methyl-2-oxazolines)38-b-poly(oxazolepropanoic acid)27-b-(poly(methyl-2-oxazoline)38 (PMeOx-PPaOx-PMeOx) which are driven to association with BDNF via electrostatic interactions and hydrogen bonding to form a PIC. Formulation using a microfluidic mixer yields small and narrowly disperse nanoparticles which associate following similar principles. Additionally, we demonstrate that encapsulation does not inhibit access by the receptor kinase, which effects BDNF’s physiologic benefits. Finally, we investigate the formation of nascent nanoparticles through a series of characterization experiments and isothermal titration experiments which show the effects of pH in the context of particle self-assembly. Our findings indicate that thoughtful reformulation of PEG based, therapeutic PICs with non-PEG alternatives can be accomplished without compromising the self-assembly of the PIC.