bluuebunny/crossref_metadata_2025 huggingface dataset:
A228 WHEN ASCITES & VARICEAL BLEEDING ARE NOT FROM CIRRHOSIS: A CASE OF MUTIPLE ARTERIOPORTAL FISTULAE CAUSING PORTAL HYPERTENSION
Authors: Leung K , Jaberi A , Kachura J , Duan K , Wong D
Published: March 2021

Background

Portal hypertension is usually due to increased resistance from cirrhosis. However, pressures can also be elevated due to increased flow.

Aims

To describe a peculiar case of non-cirrhotic portal hypertension.

Methods

A case report and literature review was performed.

Results

A 47-year-old previously well man presented with a 6 month history of rapidly progressive weight loss, ascites and variceal bleed. Workup ruled out common causes of primary liver disease. Initial imaging demonstrated a heterogenous liver, splenomegaly, ascites, patent hepatic/portal veins and multiple poorly defined low-density hepatic lesions with the largest measuring 2.1 cm. Transient elastography was 7.3 kPa (F1-mild fibrosis). At transjugular liver biopsy, hepatic venogram ruled out Budd-Chiari and hepatic vein pressure gradient was normal at 3–4 mmHg. Histology unfortunately showed hemangioma. A percutaneous liver biopsy suggested nodular regenerative hyperplasia, minimal fibrosis and mild cholestasis. Given worsening ascites, hyponatremia and 7 months of rapidly progressive decline, transjugular intrahepatic portosystemic shunt (TIPSS) was inserted. Intra-procedure, portal vein pressure was noted to be 51 mmHg, with a portosystemic gradient of 42 mmHg. Although numerous abdominal CT and MRI did not show AV shunting, ultrasound post-TIPSS showed hepatic pseudoaneurysms & arterioportal fistulae (APF). Direct angiogram showed numerous hepatic pseudoaneurysms and intrahepatic fistulae making embolization impossible. CT showed no evidence of pseudoaneurysms or fistulae outside of the liver. Workup for autoimmune rheumatological diseases and congenital telangiectatic syndromes were negative. Given the high pressures being directed through the new TIPSS, right heart failure is an ongoing concern.

APF are rarely encountered causes of presinusoidal portal hypertension, with communications most commonly arising from the hepatic (65%) & splenic arteries (11%) & the portal vein. Causes include traumatic (28%), iatrogenic (16%), vascular/telangiectatic malformations (15%), tumors (15%), aneurysms (14%) & congenital disease. Endovascular embolization can be used to treat single lesions. In complex cases with mulitple APF, surgery and/or liver transplantation may be required.

Conclusions

We report a rare case of non-cirrhotic portal hypertension due to increased flow rather than increased resistance secondary to APF.

Funding Agencies

None
A235 EFFECTS OF SACRAL PHOTOBIOMODULATION ON THE AUTONOMIC NERVOUS SYSTEM IN PATIENTS WITH COLONIC DYSMOTILITY
Authors: Chen J , Liu L , Ali M , Huizinga J D
Published: March 2021

Background

Patients with chronic refractory constipation show colon dysmotility, including impaired coordination of descending colon-sigmoid colon-rectum-anal sphincter motor functions; this may involve slow colonic transit and colo-anal dyssynergia. Impaired neuronal communication between the sacral defecation center and the distal colon may be causative. In addition, patients with lumbosacral neurological conditions (with lower back pain) may not be able to evoke an effective defecation reflex.

Aims

To evaluate if a single therapeutic session of sacral low-level laser therapy (LLLT) would affect the autonomic activity in patients with chronic constipation as revealed by changes in heart rate variability, and to report a multi-session treatment case study.

Methods

In 41 patients with chronic constipation, one session of LLLT was executed, using red LED light at a wavelength of 660 nm for 10 minutes and infrared LED light at wavelength of 840 nm for 10 minutes followed by infrared laser light with wavelength of 825 nm for 20 minutes, while measuring the electrocardiogram. One patient received this treatment 8x over 3 weeks.

Results

The lumbar-sacral light array treatment showed a significant decrease in parasympathetic activity (RSA & RMSSD) whereas pure sacral laser light treatment showed a significant increase in parasympathetic activity (RSA & RMSSD) as well as a reduction in sympathetic activity (Baevsky’s stress index: SI) (table). A single session of LLLT was also executed during HRCM in 8 patients with some but not all showing evoked colonic motility. Before COVID-19 shutdown, one patient was successfully treated. With a history of chronic constipation without ability to have spontaneous bowel movements for 5 years, symptoms improved from 13 to 8 (on a 20 scale) and quality of life improved from 1.5 to 2.5 (on a 0–4 scale) after 8 sessions. Sympathetic reactivity from supine to standing markedly reduced, from highly elevated measured as the Baevsky index from 55 to 153 s-2 it improved from 42 to 75 s-2 upon standing after 4 sessions. Parasympathetic reactivity did not change.

Conclusions

A single session of sacral LLLT markedly affected autonomic nervous activity reflected in changes in HRV. The LLLT is likely affecting the sacral defecation center through peripheral nerves entering and exiting the spinal cord including the dorsal root ganglia. LLLT treatment of a patient with inability to generate spontaneous bowel movements, resulted in ability to have complete evacuations associated with marked reduction in sympathetic reactivity during the supine-standing test, after 4 LLLT sessions.

Funding Agencies

CIHRFarncombe Family Digestive Health Research Institute
A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE
Authors: Kraimi N , De Palma G , Lu J , Bowdish D , Verdu E , Sibille E , Prevot T , Collins S M , Bercik P
Published: March 2021

Background

Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown.

Aims

Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota.

Methods

We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test.

Results

GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p < 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p > 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13).

Conclusions

We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging.

Funding Agencies

CIHRBalsam Family Foundation
A241 A REVIEW OF 101 CHILDREN WITH GASTRO-JEJUNAL FEEDING TUBES INCLUDING THEIR COMPLICATIONS AT BC CHILDREN’S HOSPITAL.
Authors: Avinashi V , Hoang T , Lee E , Dewan T , Heran M , Maroo S
Published: March 2021

Background

The use of GastroJejunal Tubes (GJTs) is an increasingly common method for providing post-pyloric enteral nutrition in pediatric patients.

Aims

To describe the patients with GJT including the indication, comorbidities including by system, as well as tube related complications.

Methods

The charts of 101 patients who had a GJT over a one-year period (2019–20) were retrospectively reviewed including demographics, medical diagnoses, information about tube placement, maintenance, and complications including malposition, balloon failure, blockages, and leakages / breaks.

Results

The top indications for GJT are aspiration and GERD. 73.3% have >3 system comorbidities (ie CNS, GI, Resp). Mean age of GJT placement was 43 months. 78% remain on a PPI and 24% are on a prokinetic. 24% continue to eat some amount orally. Over this one-year period, 92% continue with a GJT (mean duration 4 years, max 15), 4% have reverted back to a G-tube, 1% had a surgical J tube placed, and 3% died (not due to the GJT). Following initial placement, these 101 patients underwent 1194 GJT related procedures, (417 urgent changes, 777 routine changes) with 98.3% technical success. Patients needed an average of one urgent repair per year (3.2/1000 GJT days) and the majority of patients required >1 emergency visit. Those with routine GJT changes seem to have fewer urgent repairs (Figure 1).

Conclusions

Children with GJT represent a growing complex patient population. GJT are being used for the longer term. Routine maintenance seems supported by our data although doesn’t prevent the need for urgent repairs or other complications. Frameworks and guidelines are needed for this essential technology to improve clinical care.

Funding Agencies

None
A246 THE GLOBAL INCIDENCE OF ACUTE PANCREATITIS IS INCREASING OVER TIME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Iannuzzi J , Leong J H , Quan J , King J A , Windsor J W , Tanyingoh D , Coward S , Forbes N , Heitman S , Buie M , Underwood F , Kaplan G G
Published: March 2021

Background

Acute pancreatitis is a common disease with significant associated morbidity and mortality. Historically, acute pancreatitis has been considered a disease with multiple etiologies and risk factors but is driven by alcohol and biliary disease. Multiple studies have shown that the incidence of acute pancreatitis is increasing globally among both adults and children.

Aims

The purpose of this study was to assess temporal trends in incidence of acute pancreatitis globally.

Methods

We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were independently assessed in duplicate to identify applicable papers for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CI). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map to illustrate global differences.

Results

Forty-five studies reported the temporal incidence of acute pancreatitis (static map provided, online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC = 2.89%; 95% CI: 2.26, 3.52; n=41). Increasing incidence was observed in North America (AAPC = 2.71%; 95% CI: 1.93, 3.50; n=10) and Europe (AAPC = 2.79%; 95% CI: 1.95, 3.63; n=24). The incidence of acute pancreatitis was stable in Asia (AAPC = −0.28%; 95% CI: −5.03, 4.47; n=2).

Conclusions

This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last five decades and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa and Latin America.

Funding Agencies

None
Neutral model-based interfacing of 3D design to support collaborative project management in the process plant industry
Authors: Lee Hyunoh , Noh Chiho , Kim Seyun , Kim Byung Chul , Park Jinpyo , Mun Duhwan , Han Soonhung
Published: March 2021

The three-dimensional (3D) design data employed in a process plant construction project are generated during both the basic design and detailed design stages and are used for various purposes throughout the life cycle of the project. After the design stage, 3D design data are converted to a lightweight 3D format and utilized to support procurement, construction, and audit work in a collaborative project management system. However, significant time and cost are incurred when separate interfaces to convert design data are developed for each plant 3D computer-aided design (CAD) system. As an alternative, a method exists to integrate an interface using a neutral model. After translating the 3D input design data for the plant 3D CAD system to a neutral format, this study proposes an interface for use in collaborative project management by converting the data into a lightweight 3D model. In addition, detailed techniques for implementing the proposed interface are described. To verify the validity of the proposed neutral model-based 3D design data interface, translation, inspection, and lightweighting experiments are performed using 3D design data for a synthesized natural gas production plant project.
Preoperative psychogenic fever: to operate or not to operate
Authors: Koren Sondre F , Engel Lilan E , Møller Michael P
Published: March 2021

Postponing elective surgery because of fever on the morning of the operation is frustrating for patients as well as doctors. It is also not cost effective and the unused operation capacity could have been used on other patients. On the other hand, surgery and general anaesthesia will put unwanted physiological strain on a patient fighting an on-going infection. Preoperative fever therefore poses a dilemma; to proceed with-, or to postpone the scheduled operation.

We report a case where a 58-year-old woman, scheduled for prophylactic bilateral mastectomy and primary implant-based reconstruction, was postponed because of a temperature of 37.9°C. The morning of her new operation date, she developed a fever of 39.2°C which fell to 38.2°C shortly after administration of 0.25 mg triazolam. She was diagnosed with psychogenic fever, and we went through with the operation, even though the patient was febrile. The operation was successful, and she had no post-operative complications.
Using MALDI-ToF mass spectrometry to identify mushroom species: Proof of concept analysis ofAmanitagenus specimens
Authors: Piarroux Raphael , Gabriel Frédéric , Grenouillet Frédéric , Collombon Patrick , Louasse Philippe , Piarroux Martine , Normand Anne-Cécile
Published: March 2021

Food poisoning caused by toxic mushrooms, such as species in the Amanita genus, occurs frequently around the world. To properly treat these patients, it is important to rapidly and accurately identify the causal species. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry is a rapid technique that has been used in medical laboratories for the past three decades to identify bacteria, yeasts, and filamentous fungi.

Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-Tof MS) is a rapid method used for the past three decades to identify microorganisms. In this study, we created and internally validated a MALDI-Tof MS reference database comprising 15 Amanita species frequently encountered in France, and we challenged this database with 38 Amanita specimens from four French locations, using a free online application for MALDI-ToF spectra identifications.

Assessment of the database showed that mass spectra can be obtained by analyzing any portion of a carpophore and that all portions enabled identification of the carpophore at the species level. Most carpophores were correctly identified using our database, with the exception of specimens from the Vaginatae section. Decay tests also demonstrated that decayed portions (like those found in the kitchen garbage can) of Amanita phalloides mushrooms could be properly identified using MALDI-ToF MS.

Our findings provide important insight for toxicology laboratories that often rely on DNA sequencing to identify meal leftovers implicated in food poisoning. In future developments, this technique could also be used to detect counterfeit mushrooms by including other genera in the reference database.

Lay Summary

MALDI-ToF MS is a powerful identification tool for microorganisms. We demonstrate that the technique can be applied to Amanita specimens. This will prevent food intoxications as a rapid and definite identification can be obtained, and it can also be used for food remnants.
Modelling the M*–SFR relation at high redshift: untangling factors driving biases in the intrinsic scatter measurement
Authors: Curtis-Lake E , Chevallard J , Charlot S , Sandles L
Published: March 2021

We present a method to self-consistently propagate stellar-mass [$\hbox{$\hbox{${\rm M}$}_{\star }$}=\log (\hbox{${\rm M}$}/\hbox{${\rm M}_{\odot }$})$] and star-formation-rate [$\hbox{${\Psi }$}=\log (\hbox{${\psi }$}/\hbox{${\rm M}_{\odot }$}\, {\rm yr}^{-1}$)] uncertainties on to intercept (α), slope (β), and intrinsic-scatter (σ) estimates for a simple model of the main sequence of star-forming galaxies, where $\hbox{${\Psi }$}= \alpha + \beta \hbox{$\hbox{${\rm M}$}_{\star }$}+ \mathcal {N}(0,\sigma)$. To test this method and compare it with other published methods, we construct mock photometric samples of galaxies at z ∼ 5 based on idealized models combined with broad- and medium-band filters at wavelengths 0.8–5 μm. Adopting simple Ψ estimates based on dust-corrected ultraviolet luminosity can underestimate σ. We find that broad-band fluxes alone cannot constrain the contribution from emission lines, implying that strong priors on the emission-line contribution are required if no medium-band constraints are available. Therefore, at high redshifts, where emission lines contribute a higher fraction of the broad-band flux, photometric fitting is sensitive to Ψ variations on short (∼10 Myr) time-scales. Priors on age imposed with a constant (or rising) star formation history (SFH) do not allow one to investigate a possible dependence of σ on $\hbox{${\rm M}$}_{\star }$ at high redshifts. Delayed exponential SFHs have less constrained priors, but do not account for Ψ variations on short time-scales, a problem if σ increases due to stochasticity of star formation. A simple SFH with current star formation decoupled from the previous history is appropriate. We show that, for simple exposure-time calculations assuming point sources, with low levels of dust, we should be able to obtain unbiased estimates of the main sequence down to $\mathrm{ log}(\hbox{${\rm M}$}/\hbox{${\rm M}_{\odot }$})\sim 8$ at z ∼ 5 with the James Webb Space Telescope while allowing for stochasticity of star formation.
Galactic seismology: the evolving ‘phase spiral’ after the Sagittarius dwarf impact
Authors: Bland-Hawthorn Joss , Tepper-García Thor
Published: March 2021

In 2018, the ESA Gaia satellite discovered a remarkable spiral pattern (‘phase spiral’) in the z − Vz phase plane throughout the solar neighbourhood, where z and Vz are the displacement and velocity of a star perpendicular to the Galactic disc. In response to Binney & Schönrich’s analytic model of a disc-crossing satellite to explain the Gaia data, we carry out a high-resolution, N-body simulation (N  ≈ 108 particles) of an impulsive mass (2 × 1010 M⊙) that interacts with a cold stellar disc at a single transit point. The disc response is complex since the impulse triggers a superposition of two distinct bisymmetric (m = 2) modes − a density wave and a corrugated bending wave − that wrap up at different rates. Stars in the faster density wave wrap up with time T according to ϕD(R, T) = (ΩD(R) + Ωo) T, where ϕD describes the spiral pattern and ΩD = Ω(R) − κ(R)/2, where κ is the epicyclic frequency. While the pattern speed Ωo is small, it is non-zero. The slower bending wave wraps up according to ΩB ≈ ΩD/2 producing a corrugated wave. The bunching effect of the density wave triggers the phase spiral as it rolls up and down on the corrugated wave (‘roller coaster’ model). The phase spiral emerges slowly about ΔT ≈ 400 Myr after impact. It appears to be a long-lived, disc-wide phenomenon that continues to evolve over most of the 2 Gyr simulation. Thus, given Sagittarius’ (Sgr) low total mass today (Mtot ∼ 3 × 108 M⊙ within 10 kpc diameter), we believe that the phase spiral was excited by the disc-crossing dwarf some 1–2 Gyr before the recent transit. For this to be true, Sgr must be losing mass at 0.5–1 dex per orbit loop.
Linear systematics mitigation in galaxy clustering in the Dark Energy Survey Year 1 Data
Authors: Wagoner Erika L , Rozo Eduardo , Fang Xiao , Crocce Martín , Elvin-Poole Jack , Weaverdyck Noah ,   (DES Collaboration)
Published: March 2021

We implement a linear model for mitigating the effect of observing conditions and other sources of contamination in galaxy clustering analyses. Our treatment improves upon the fiducial systematics treatment of the Dark Energy Survey (DES) Year 1 (Y1) cosmology analysis in four crucial ways. Specifically, our treatment (1) does not require decisions as to which observable systematics are significant and which are not, allowing for the possibility of multiple maps adding coherently to give rise to significant bias even if no single map leads to a significant bias by itself, (2) characterizes both the statistical and systematic uncertainty in our mitigation procedure, allowing us to propagate said uncertainties into the reported cosmological constraints, (3) explicitly exploits the full spatial structure of the galaxy density field to differentiate between cosmology-sourced and systematics-sourced fluctuations within the galaxy density field, and (4) is fully automated, and can therefore be trivially applied to any data set. The updated correlation function for the DES Y1 redMaGiC catalogue minimally impacts the cosmological posteriors from that analysis. Encouragingly, our analysis does improve the goodness-of-fit statistic of the DES Y1 3 × 2pt data set (Δχ2 = −6.5 with no additional parameters). This improvement is due in nearly equal parts to both the change in the correlation function and the added statistical and systematic uncertainties associated with our method. We expect the difference in mitigation techniques to become more important in future work as the size of cosmological data sets grows.
Computational meta-analysis of ribosomal RNA fragments: potential targets and interaction mechanisms
Authors: Guan Lingyu , Grigoriev Andrey
Published: March 2021

The most abundant cellular RNA species, ribosomal RNA (rRNA), appears to be a source of massive amounts of non-randomly generated fragments. We found rRNA fragments (rRFs) in immunoprecipitated Argonaute (Ago-IP) complexes in human and mouse cells and in small RNA sequencing datasets. In human Ago1-IP, guanine-rich rRFs were preferentially cut in single-stranded regions of mature rRNAs between pyrimidines and adenosine, and non-randomly paired with cellular transcripts in crosslinked chimeras. Numerous identical rRFs were found in the cytoplasm and nucleus in mouse Ago2-IP. We report specific interaction motifs enriched in rRF-target pairs. Locations of such motifs on rRFs were compatible with the Ago structural features and patterns of the Ago-RNA crosslinking in both species. Strikingly, many of these motifs may bind to double-stranded regions on target RNAs, suggesting a potential pathway for regulating translation by unwinding mRNAs. Occurring on either end of rRFs and matching intronic, untranslated or coding regions in targets, such interaction sites extend the concept of microRNA seed regions. Targeting both borders of certain short introns, rRFs may be involved in their biogenesis or function, facilitated by Ago. Frequently dismissed as noise, rRFs are poised to greatly enrich the known functional spectrum of small RNA regulation.
Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study
Authors: Khandelwal Priyank , Al-Mufti Fawaz , Tiwari Ambooj , Singla Amit , Dmytriw Adam A , Piano Mariangela , Quilici Luca , Pero Guglielmo , Renieri Leonardo , Limbucci Nicola , Martínez-Galdámez Mario , Schüller-Arteaga Miguel , Galván Jorge , Arenillas-Lara Juan Francisco , Hashim Zafar , Nayak Sanjeev , Desousa Keith , Sun Hai , Agarwalla Pankaj K , Nanda Anil , Roychowdhury J Sudipta , Nourollahzadeh Emad , Prakash Tannavi , Gandhi Chirag D , Xavier Andrew R , Lozano J Diego , Gupta Gaurav , Yavagal Dileep R
Published: March 2021

BACKGROUND

While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear.

OBJECTIVE

To attempt to establish incidence of AIS in COVID-19 patients in an international cohort.

METHODS

A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers.

RESULTS

Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities.

CONCLUSION

LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.
Recoverability and Expectations-Driven Fluctuations
Authors: Chahrour Ryan , Jurado Kyle
Published: March 2021

Time series methods for identifying structural economic disturbances often require disturbances to satisfy technical conditions that can be inconsistent with economic theory. We propose replacing these conditions with a less restrictive condition called recoverability, which only requires that the disturbances can be inferred from the observable variables. As an application, we show how shifting attention to recoverability makes it possible to construct new identifying restrictions for technological and expectational disturbances. In a vector autoregressive example using post-war U.S. data, these restrictions imply that independent disturbances to expectations about future technology are a major driver of business cycles.
Extracutaneous involvement is common and associated with prolonged disease activity and greater impact in juvenile localized scleroderma
Authors: Li Suzanne C , Higgins Gloria C , Chen Mallory , Torok Kathryn S , Rabinovich C Egla , Stewart Katie  , Laxer Ronald M , Pope Elena , Haines Kathleen A , Punaro Marilynn , O’Neil Kathleen M
Published: March 2021

Objective

The aim of this study was to evaluate factors associated with extracutaneous involvement (ECI) in juvenile localized scleroderma (jLS).

Methods

A prospective, multicentre, 6-month observational study was performed. The data collected included disease features, global assessments, and subject symptoms. Bivariate and linear multilevel regression analyses were performed.

Results

A total of 86 jLS subjects (80% female, 80% Caucasian), median age of disease onset 7.7 years, were evaluated. Most had linear scleroderma or mixed morphea. Of the 86 subjects, 49 (57%) had 125 extracutaneous problems {median 2 [interquartile range (IQR) 1, 3] per subject} from nine organ systems. Most of these subjects had multiple musculoskeletal problems. ECI was associated with more extensive cutaneous involvement, higher number of symptoms, family history of autoimmunity, and ANA and RF positivity. Subjects with ECI had higher scores for physician global assessment of damage (PGA-D), and parental global assessment of disease impact, but not baseline physician global assessment of disease activity (PGA-A). Although subjects with ECI received more MTX and glucocorticoid treatment, they had a slower reduction in PGA-A scores and symptoms over time, suggesting a poorer response to treatment. In logistic regression modelling, female sex had the largest effect on parental impact scores.

Conclusion

ECI occurred in the majority of subjects with jLS, and was associated with more medication use, longer treatment duration, higher PGA-D scores, and higher parental assessment of disease impact. Our findings suggest that jLS subjects with ECI have greater overall disease burden, both cutaneous and extracutaneous, and poorer response to treatment. More study of the treatment needs of this population is warranted.
Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis
Authors: Silva Catherine F , Nardelli Mateus J , Barbosa Fernanda A , Galizzi Humberto O , Cal Tereza C M F , Ferrari Teresa C A , Faria Luciana C , Couto Claudia A
Published: March 2021

Background

Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS.

Method

A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol.

Results

HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504).

Conclusion

TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.
Beliefs about Mask Efficacy and the Effect of Social Norms on Mask Wearing Intentions for COVID-19 Risk Reduction
Authors: Bokemper Scott E. , Cucciniello Maria , Rotesi Tiziano , Pin Paolo , Malik Amyn A. , Willebrand Kathryn , Paintsil Elliott E. , Omer Saad B. , Huber Gregory A. , Melegaro Alessia
Published: March 2021

In the absence of widespread vaccination for COVID-19, governments and public health officials have advocated for the public to wear masks during the pandemic. The decision to wear a mask in public is likely affected by both beliefs about its efficacy and the prevalence of the behavior. Greater mask use in the community may encourage others to follow this norm, but it also creates an incentive for individuals to free ride on the protection afforded to them by others. We report the results of two vignette-based experiments conducted in the United States and Italy to examine the causal relationship between beliefs, social norms, and reported intentions to engage in mask promoting behavior. We find that providing factual information about how masks protect others increases the likelihood that someone would wear a mask or encourage others to do so in the United States, but not in Italy. There is no effect of providing information about how masks protect the wearer in either country. Additionally, greater mask use increases intentions to wear a mask and encourage someone else to wear theirs properly in both the United States and Italy. Thus, community mask use may be self-reinforcing.
Apparent growth paradox ofStaphylococcus epidermidisin response to extremely low frequency electromagnetic radiation exposure
Authors: Malik Dyaan , Pineda Esmeralda , Zambrana Deyvis Mejia
Published: March 2021

Staphylococcus epidermidisis a normal part of the human microbiome; however, it is an opportunistic pathogen and can cause infections when the delicate balance of this microbiome is disrupted. Furthermore, infections caused by this bacterium can be hard to treat as a result of antibiotic resistance and biofilm production. This experiment aimed to determine whether electromagnetic field radiation (ELF-EMF) could be a deterrent of bacterial growth, as an alternative treatment to antibiotics. A non-pathogenic strain ofS. epidermidiswas used for experimentation, which took place in a school laboratory setting. The experimental group was exposed to ELF-EMF, while the control group did not receive the ELF-EMF treatment. The number of bacterial colonies, represented as colony forming units (CFUs) and area of random colonies were calculated to determine the effect of this treatment. There was no dramatic difference of colony formation on days 0, 1, and 2 of the four day period of ELF-EMF exposure. However, colony formation for days 3 and 4 showed a significant difference between the control and the experimental groups, as the experimental group had a significantly higher CFU count than the control. The average CFU count for day 3 in the control group was 420.6 and 1,097.4 for the experimental group (p<0.0001, t=12.9803). On the final day of the experimentation (Day 4) the average CFU count for the control group was 424.6 and 896.4 for the experimental group (p<0.0001, t=5.8926). The area for five randomly chosen colonies from each petri dish was calculated on the fourth day of experimentation. The area for the experimental group was significantly lower than that control (p<0.0001, with t=6.8659). The average area for the control group was 1.3249 mm2and a lower average of 0.6375mm2for the experimental group. These results demonstrate that the ELF-EMF treatment had an inhibitory effect on the area growth ofS. epidermidis, but not on the colony-forming ability of S. epidermidis. This suggests that ELF-EMF influences the means by which the bacteriumS. epidermidisgrows.
A Comparative Analysis of Clinical Stage 3 COVID-19 Vaccines using Knowledge Representation
Authors: Burgos-Salcedo Javier
Published: March 2021

The emergence of a novel SARS-CoV-2 coronavirus at the end of 2019 and its accelerated spread worldwide to become a pandemic has had, from the medical biotechnology point of view, an unprecedented global response, to the point that there are currently 176 vaccine candidates in preclinical stage, 66 in clinical stage, of which 19 are in phase 3, and 5 of these are massively applied worldwide. The purpose of the present work is to elaborate a hierarchical landscape of the current status of phase 3 vaccines, taking into account their attributes of technological platform, safety and efficacy. The methodology used was that of conceptual knowledge representation, resulting in, firstly, an appropriate classification of stage 3 vaccines, The Conceptual Lattice for COVID-19 vaccines, constructed according to how they relate to each other with respect to the set of their attributes. Secondly, the approach used allows proposing rational strategies for the design of heterologous vaccination schemes, which are urgently needed to control the pandemic.
Role of IL-23 neutralization in psoriasis – insights from a mechanistic PK/PD model and meta-analysis of clinical data
Authors: Kapitanov Georgi I.
Published: March 2021

Blocking of IL-23 has shown a profound effect on patient outcomes in psoriasis. The current IL-23 binding monoclonal antibodies show differences in dosing regimens, pharmacokinetics, affinity for the target, and efficacy outcomes in the clinic. The goal of the current work is to use a mechanistic pharmacokinetics/pharmacodynamics mathematical model to estimate projected free IL-23 neutralization for the different therapeutic molecules and connect it to clinical efficacy outcomes. The meta-analysis indicates a sigmoid-like relationship and suggests that the best current anti-IL23 antibodies are close to saturating the efficacy that can be achieved by this pathway in psoriasis.
Predicting vaccine hesitancy from area-level indicators: A machine learning approach
Authors: Carrieri Vincenzo , Lagravinese Raffele , Resce Giuliano
Published: March 2021

Vaccine hesitancy (VH) might represent a serious threat to the next COVID-19 mass immunization campaign. We use machine-learning algorithms to predict communities at a high risk of VH relying on area-level indicators easily available to policymakers. We illustrate our approach on data from child immunization campaigns for seven non-mandatory vaccines carried out in 6408 Italian municipalities in 2016. A battery of machine learning models is compared in terms of area under the Receiver Operating Characteristics (ROC) curve. We find that the Random Forest algorithm best predicts areas with a high risk of VH improving the unpredictable baseline level by 24% in terms of accuracy. Among the area-level indicators, the proportion of waste recycling and the employment rate are found to be the most powerful predictors of high VH. This can support policy makers to target area-level provaccine awareness campaigns.
Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations
Authors: Singh Uday , Saito Kenji , Toth Brandon A. , Dickey Jacob E. , Rodeghiero Samuel R. , Deng Yue , Deng Guorui , Xue Baojian , Zhu Zhiyong , Jiang Jingwei , Zingman Leonid V. , Cui Huxing
Published: March 2021

Objective

The paraventricular nucleus of hypothalamus (PVN) is an integrative center in the brain orchestrating a wide range of physiological and behavioral responses. While the PVN melanocortin 4 receptor (MC4R) signaling (PVNMC4R+) is undoubtedly involved in feeding regulation, the neuroanatomical organization of PVNMC4R+pathway and its role in diverse physiological and behavioral regulations have not been fully understood. Here we aimed to better characterize the input-output organization of PVNMC4R+neurons and further test their potential functional roles beyond feeding.

Methods

Using a combination of viral tools, we performed a comprehensive mapping of PVNMC4R+circuits and tested the effects of chemogenetic activation of PVNMC4R+neurons on thermogenesis, cardiovascular control and other behavioral regulations beyond feeding.

Results

We found that PVNMC4R+neurons broadly innervate many different brain regions known to be important not only for feeding but also for neuroendocrine and autonomic control of thermogenesis and cardiovascular function, including but not limited to preoptic area, median eminence, parabrachial nucleus, locus coeruleus, nucleus of solitary tract, ventrolateral medulla and thoracic spinal cord. Contrary to broad efferent projections, PVNMC4R+neurons receive monosynaptic inputs from limited brain regions, including medial preoptic nucleus, arcuate and dorsomedial hypothalamic nuclei, and supraoptic nucleus. Consistent with broad efferent projections, chemogenetic activation of PVNMC4R+neurons not only suppressed feeding but also led to an apparent increase in heart rate, blood pressure and brown adipose tissue thermogenesis. Strikingly, these physiological changes accompanied an unexpected repetitive bedding-removing behavior followed by hypoactivity and resting-like behavior.

Conclusions

Our results clarify the neuroanatomical organization of PVNMC4R+circuits and shed new light on the roles of PVNMC4R+pathways in autonomic control of thermogenesis, cardiovascular function and other behavioral regulations.
Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistantS. pseudintermedius
Authors: O’Neill Alan M. , Worthing Kate A. , Kulkarni Nikhil , Li Fengwu , Nakatsuji Teruaki , Mills Robert H. , Cheng Joyce Y. , Gonzalez David J. , Norris Jacqueline M. , Gallo Richard L.
Published: March 2021

Methicillin-resistantStaphylococcus pseudintermedius(MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felisC4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Competition experiments in mice showed thatS. felissignificantly reduced MRSP skin colonization and an antimicrobial extract fromS. felissignificantly reduced necrotic skin injury from MRSP infection. Fluorescence and electron microscopy revealed thatS. felisantimicrobials disrupted bacterial but not eukaryotic cell membranes. LC/MS identified severalS. felisphenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.
Self-healing codes: how stable neural populations can track continually reconfiguring neural representations
Authors: Rule M. E. , O’Leary T.
Published: March 2021

As an adaptive system, the brain must retain a faithful representation of the world while continuously integrating new information. Recent experiments have measured population activity in cortical and hippocampal circuits over many days, and found that patterns of neural activity associated with fixed behavioral variables and percepts change dramatically over time. Such “representational drift” raises the question of how malleable population codes can interact coherently with stable long-term representations that are found in other circuits, and with relatively rigid topographic mappings of peripheral sensory and motor signals. We explore how known plasticity mechanisms can allow single neurons to reliably read out an evolving population code without external error feedback. We find that interactions between Hebbian learning and single-cell homeostasis can exploit redundancy in a distributed population code to compensate for gradual changes in tuning. Recurrent feedback of partially stabilized readouts could allow a pool of readout cells to further correct inconsistencies introduced by representational drift. This shows how relatively simple, known mechanisms can stabilize neural tuning in the short term, and provides a plausible explanation for how plastic neural codes remain integrated with consolidated, long-term representations.

Significance

The brain is capable of adapting while maintaining stable long-term memories and learned skills. Recent experiments show that neural responses are highly plastic in some circuits, while other circuits maintain consistent responses over time, raising the question of how these circuits interact coherently. We show how simple, biologically motivated Hebbian and homeostatic mechanisms in single neurons can allow circuits with fixed responses to continuously track a plastic, changing representation without reference to an external learning signal.
Laminar-specific interhemispheric connectivity mapping with bilateral line-scanning fMRI
Authors: Choi Sangcheon , Chen Yi , Zeng Hang , Biswal Bharat , Yu Xin
Published: March 2021

Despite extensive studies detecting blood-oxygen-level-dependent (BOLD) fMRI signals across two hemispheres to present cognitive processes in normal and diseased brains, the role of corpus callosum (CC) to mediate interhemispheric functional connectivity remains controversial. Several studies show maintaining low-frequency fluctuation of resting-state (rs)-fMRI signals in homotopic brain areas of acallosal humans and post-callosotomy animals, raising the question: how can we specify the circuit-specific rs-fMRI signal fluctuation from other sources? To address this question, we have developed a bilateral line-scanning fMRI (BiLS) method to detect bilateral laminar BOLD fMRI signals from symmetric cortical regions with high spatial (100 μm) and temporal (100 ms) resolution in rodents under anesthesia. In addition to ultra-slow oscillation (0.01-0.02 Hz) patterns across all cortical layers, a layer-specific bilateral coherence pattern was observed with a peak at Layer (L)2/3, where callosal projection neurons are primarily located and reciprocal transcallosal projections are received. In particular, the L2/3-specific coherence pattern showed a peak at 0.05 Hz based on the stimulation paradigm, depending on the interhemispheric CC activation. Meanwhile, the L2/3-specific rs-fMRI coherence was peaked at 0.08-0.1Hz which was independent of the varied ultra-slow oscillation patterns (0.01-0.02 Hz) presumably involved with global neuromodulation. This work provides a unique laminar fMRI mapping scheme to characterize the CC-mediated evoked fMRI and frequency-dependent rs-fMRI responses, presenting crucial evidence to distinguish the circuit-specific fMRI signal fluctuations across two hemispheres.

Significance statement

Laminar fMRI is a promising method to better understand neuronal circuit contribution to functional connectivity (FC) across cortical layers. Here, we developed a bilateral line-scanning fMRI method, allowing the detection of laminar-specific BOLD-fMRI signals from homologous cortical regions in rodents with high spatial and temporal resolution. Laminar coherence patterns of both evoked and rs-fMRI signals revealed that CC-dependent interhemispheric FC is significantly strong at Layer 2/3, where callosal projection neurons are primarily located. The Layer 2/3-specific rs-fMRI coherence is independent of ultra-slow oscillation based on global neuromodulation, distinguishing the circuit-specific rs-fMRI signal fluctuation from different regulatory sources.