bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive young stellar objects in the Local Group spiral galaxy M 33 identified using machine learning
Authors: Kinson David A , Oliveira Joana M , van Loon Jacco Th
Published: September 2022

We present a supervised machine learning classification of stellar populations in the Local Group spiral galaxy M 33. The Probabilistic Random Forest (PRF) methodology, previously applied to populations in NGC 6822, utilizes both near and far-IR classification features. It classifies sources into nine target classes: young stellar objects (YSOs), oxygen, and carbon-rich asymptotic giant branch stars, red giant branch, and red super-giant stars, active galactic nuclei, blue stars (e.g. O-, B-, and A-type main sequence stars), Wolf–Rayet stars, and Galactic foreground stars. Across 100 classification runs the PRF classified 162 746 sources with an average estimated accuracy of ∼86 per cent, based on confusion matrices. We identified 4985 YSOs across the disc of M 33, applying a density-based clustering analysis to identify 68 star forming regions (SFRs) primarily in the galaxy’s spiral arms. SFR counterparts to known H ii regions were recovered with ∼91 per cent of SFRs spatially coincident with giant molecular clouds identified in the literature. Using photometric measurements, as well as SFRs in NGC 6822 with an established evolutionary sequence as a benchmark, we employed a novel approach combining ratios of [Hα]/[24 μm] and [250 μm]/[500 μm] to estimate the relative evolutionary status of all M 33 SFRs. Masses were estimated for each YSO ranging from 6–27M⊙. Using these masses, we estimate star formation rates based on direct YSO counts of 0.63M⊙ yr−1 in M 33’s SFRs, 0.79 ± 0.16M⊙ yr−1 in its centre and 1.42 ± 0.16M⊙ yr−1 globally.
Broad-band spectral analysis of LMXB 2S 0921-63 with Suzaku
Authors: Sharma Prince , Jain Chetana , Dutta Anjan
Published: September 2022

We present the broad-band spectral analysis of the low-mass X-ray binary 2S 0921-63 by using the Suzaku archival data covering the orbital phase between 0.31 and 1.16 during four close observations. It is the first time that a broad-band spectral analysis of 2S 0921-63 has been done up to 25 keV. The 0.5–10 keV XIS count rate varied between ∼1 and ∼5 counts s−1 during the observations. A partial X-ray eclipse and broad post-eclipse intensity dip were observed during the observations. The X-ray emission hardened marginally during the intensity dip. We have modelled the source spectra by simultaneously fitting the XIS and HXD-PIN spectra for each of the four observations. The broad-band spectra of the source can be described by a model comprising a very hot blackbody having temperature, kTBB ≈ 1.66–2.13 keV, a high-energy cut-off power law, and an Fe emission line at Eline ∼ 6.7 keV. A second model, accounting for the Comptonization of the thermal emission from accretion disc along with an Fe emission line, describes the broad-band spectra of 2S 0921-63 equally well.
The survey of planetary nebulae in Andromeda (M31) – IV. Radial oxygen and argon abundance gradients of the thin and thicker disc
Authors: Bhattacharya Souradeep , Arnaboldi Magda , Caldwell Nelson , Gerhard Ortwin , Kobayashi Chiaki , Hartke Johanna , Freeman Kenneth C , McConnachie Alan W , Guhathakurta Puragra
Published: September 2022

We obtain a magnitude-limited sample of Andromeda (M 31) disc PNe with chemical abundance estimated through the direct detection of the [O iii] 4363 Å line. This leads to 205 and 200 PNe with oxygen and argon abundances, respectively. We find that high- and low-extinction M 31 disc PNe have statistically distinct argon and oxygen abundance distributions. In the radial range of 2−30 kpc, the older low-extinction disc PNe are metal-poorer on average with a slightly positive radial oxygen abundance gradient (0.006 ± 0.003 dex kpc−1) and slightly negative for argon (−0.005 ± 0.003 dex kpc−1), while the younger high-extinction disc PNe are metal-richer on average with steeper radial abundance gradients for both oxygen (−0.013 ± 0.006 dex kpc−1) and argon (−0.018 ± 0.006 dex kpc−1), similar to the gradients computed for the M 31 H ii regions. The M 31 disc abundance gradients are consistent with values computed from major merger simulations, with the majority of the low-extinction PNe being the older pre-merger disc stars in the thicker disc, and the majority of the high-extinction PNe being younger stars in the thin disc, formed during and after the merger event. The chemical abundance of the M 31 thicker disc has been radially homogenized because of the major merger. Accounting for disc scale lengths, the positive radial oxygen abundance gradient of the M 31 thicker disc is in sharp contrast to the negative one of the MW thick disc. However, the thin discs of the MW and M 31 have remarkably similar negative oxygen abundance gradients.
Galaxy source counts at 7.7, 10, and 15 μm with the James Webb Space Telescope
Authors: Ling Chih-Teng , Kim Seong Jin , Wu Cossas K-W , Goto Tomotsugu , Kilerci Ece , Hashimoto Tetsuya , Lin Yu-Wei , Wang Po-Ya , Ho Simon C-C , Hsiao Tiger Yu-Yang
Published: September 2022

We present mid-infrared (IR) galaxy number counts based on the Early Release Observations obtained by the James Webb Space Telescope (JWST) at 7.7-, 10-, and 15-μm (F770W, F1000W, and F1500W, respectively) bands of the Mid-Infrared Instrument (MIRI). Due to the superior sensitivity of JWST, the 80-per cent completeness limits reach 0.32, 0.79, and 2.0 μJy in F770W, F1000W, and F1500W filters, respectively, i.e. ∼100 times deeper than previous space IR telescopes such as Spitzer or AKARI. The number counts reach much deeper than the broad bump around 0.05∼0.5 mJy due to polycyclic aromatic hydrocarbon (PAH) emissions. An extrapolation towards fainter flux from the evolutionary models in the literature agrees amazingly well with the new data, where the extrapolated faint-end of IR luminosity functions combined with the cosmic star-formation history to higher redshifts can reproduce the deeper number counts by JWST. Our understanding of the faint IR sources has been confirmed by the observed data due to the superb sensitivity of JWST.
The globular clusters and star formation history of the isolated, quiescent ultra-diffuse galaxy DGSAT I
Authors: Janssens Steven R , Romanowsky Aaron J , Abraham Roberto , Brodie Jean P , Couch Warrick J , Forbes Duncan A , Laine Seppo , Martínez-Delgado David , van Dokkum Pieter G
Published: September 2022

We investigate the isolated, quiescent ultra-diffuse galaxy (UDG) DGSAT I and its globular cluster (GC) system using two orbits of Hubble Space Telescope Advanced Camera for Surveys imaging in the F606W and F814W filters. This is the first study of GCs around a UDG in a low-density environment. DGSAT I was previously found to host an irregular blue low surface brightness clump, which we confirm as very likely belonging to the galaxy rather than being a chance projection, and represents a recent episode of star formation (∼500 Myr) that challenges some UDG formation scenarios. We select GC candidates based on colours and magnitudes, and construct a self-consistent model of the GC radial surface density profile along with the background. We find a half-number radius of RGC = 2.7 ± 0.1 kpc (more compact than the diffuse starlight) and a total of 12 ± 2 GCs. The total mass fraction in GCs is relatively high, supporting an overmassive dark matter halo as also implied by the high velocity dispersion previously measured. The GCs extend to higher luminosities than expected, and have colours that are unusually similar to their host galaxy colour, with a very narrow spread, all of which suggest an early, intense burst of cluster formation. The nature and origin of this galaxy remain puzzling, but the most likely scenario is a ‘failed galaxy’ that formed relatively few stars for its halo mass, and could be related to cluster UDGs whose size and quiescence pre-date their infall.
Modelling the flare in NGC 1097 from 1991 to 2004 as a tidal disruption event
Authors: Zhang Xue-Guang
Published: September 2022

In the letter, interesting evidence is reported to support a central tidal disruption event (TDE) in the known AGN NGC 1097. Considering the motivations of TDE as one probable origination of emission materials of double-peaked broad emission lines and also as one probable explanation to changing-look AGN, it is interesting to check whether there are clues to support a TDE in NGC 1097, not only a changing-look AGN but also an AGN with double-peaked broad emission lines. Under the assumption that the onset of broad Hα emission was due to a TDE, the 13 yr-long (1991–2004) variability of double-peaked broad Hα line flux in NGC 1097 can be well predicted by theoretical TDE model, with a (1 − 1.5) M⊙ main-sequence star tidally disrupted by the central BH with TDE model determined mass about (5 − 8) × 107 M⊙. The results provide interesting evidence to not only support TDE-related origin of double-peaked broad line emission materials but also support TDE as an accepted physical explanation to physical properties of changing-look AGN.
The pattern speeds of vertical breathing waves
Authors: Khachaturyants Tigran , Debattista Victor P , Ghosh Soumavo , Beraldo e Silva Leandro , Daniel Kathryne J
Published: September 2022

We measure and compare the pattern speeds of vertical breathing, vertical bending, and spiral density waves in two isolated N-body+SPH simulations, using windowed Fourier transforms over $1 \mbox{$\:{\rm Gyr}$}$ time intervals. We show that the pattern speeds of the breathing waves match those of the spirals but are different from those of the bending waves. We also observe matching pattern speeds between the bar and breathing waves. Our results not only strengthen the case that, throughout the disc, breathing motions are driven by spirals but indeed that the breathing motions are part and parcel of the spirals.
Topological materials for full-vector elastic waves
Authors: Wu Ying , Lu Jiuyang , Huang Xueqin , Yang Yating , Luo Li , Yang Linyun , Li Feng , Deng Weiyin , Liu Zhengyou
Published: September 2022

Elastic wave manipulation is important in a wide variety of applications, including information processing in small elastic devices and noise control in large solid structures. The recent emergence of topological materials has opened new avenues for modulating elastic waves in solids. However, because of the full-vector feature and the complicated couplings of the longitudinal and transverse components of elastic waves, manipulating elastic waves is generally difficult compared with manipulating acoustic waves (scalar waves) and electromagnetic waves (vectorial waves but transverse only). To date, topological materials, including insulators and semimetals, have been used for acoustic and electromagnetic waves. Although topological materials with elastic waves have also been reported, the observed topological edge modes lie on the domain wall. A natural question arises: Is there an elastic metamaterial with topological edge modes on its own boundary? Here, we report a 3D metal-printed bilayer metamaterial that topologically insulates elastic waves. By introducing chiral interlayer couplings, the spin–orbit couplings for elastic waves are induced, which give rise to nontrivial topological properties. Helical edge states with vortex features were demonstrated on the boundary of the single topological phase. We further show a heterostructure of the metamaterial that exhibits tunable edge transport. Our findings could be used in devices based on elastic waves in solids.
Incidence of Invasive Fungal Infections in Patients With Previously Untreated Acute Myeloid Leukemia Receiving Venetoclax and Azacitidine
Authors: Zhang Alexander , Johnson Tanner , Abbott Diana , Phupitakphol Tanit , Gutman Jonathan A , Pollyea Daniel A , Koullias Yiannis
Published: September 2022

Background

Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with comorbidities. Combining azacitidine (AZA) with BCL-2 inhibitor venetoclax (VEN) demonstrated significant improvement in outcomes for newly-diagnosed AML patients compared to AZA alone. However, this regimen is myelosuppressive, and the incidence of invasive fungal infections (IFIs) and impact of antifungal prophylaxis are not well defined.

Methods

This retrospective cohort study evaluated newly-diagnosed AML patients treated with VEN/AZA at the University of Colorado Hospital from January 2014 to August 2020. Patients with history of prior IFI were excluded. Primary outcome was IFI incidence during VEN/AZA therapy. χ2 and Fisher exact tests assessed the impact of patient demographics, AML-specific risk factors, and receipt of antifungal prophylaxis on IFI incidence.

Results

144 VEN/AZA-treated AML patients were included in the study. 25 (17%) patients developed IFI: 8% (n = 2) “proven,” 24% (n = 6) “probable,” and 68% (n = 17) “possible” per European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium criteria. There was no statistically significant association between IFI incidence with age, sex, or European LeukemiaNet classification. 10 patients received antifungal prophylaxis; none developed IFI. IFI incidence rate per 1000 patient-days was greatest 0–9 days after starting VEN/AZA, at 8.39.

Conclusions

Incidence of “proven” and “probable” IFI in our VEN/AZA-treated AML cohort was 5.6%, in-line with incidence rates reported by recent similar studies. Furthermore, IFI incidence decreased as days from starting VEN/AZA therapy increased.
Green Lungs and Green Liberty: The Modern City Park and Public Health in an Urban Metabolic Landscape
Authors: Jones Karen R
Published: September 2022

This paper explores processes of urban park creation from the mid-1800s to show how ‘green lungs’ and ‘green liberty’ shaped the health geography of the modern city. Tracking this story across a transatlantic canvas (using examples from London, Paris, New York and Montreal), it looks at how ideas around fresh air, exercise and greenery sat within municipal designs for a functional metabolic landscape, what I call somatic urbanism. Plotting the historical contours of the park as a landscape of health has two main uses. First, it usefully connects the worlds of medicine and environment to show how debates about industrialism, modernity, sanitation and social reform found common ground. Second, in a contemporary world where ventilation issues have been highlighted by the coronavirus pandemic and municipal authorities grapple with anthropogenic challenges, it argues that historical studies of health and environment assume a vital importance in shaping the future of sustainable cities.
Performing 2-Stage Circumferential Fusion in an Adolescent With High-Grade Spondylolisthesis
Authors: Salmons Harold I. , Pinter Zachariah W. , Streufert Benjamin , Sebastian Arjun S. , Nassr Ahmad ,   Investigation Performed at the Mayo Clinic, Rochester, MN
Published: September 2022

The surgical approach to high-grade spondylolisthesis at the lumbosacral junction remains controversial. Appropriate surgical techniques can be challenging with the potential for high complication rates, particularly with reduction. Multiple techniques have been described including posterior only reduction and instrumentation, posterior only instrumentation with in situ arthrodesis, and anterior-posterior reduction and instrumentation. Regardless of technique, the operative goals are to provide sufficient stability and biological support to promote bony fusion, maintain global balance, and decompress the neural elements while avoiding neurological complications. During instrumentation of a high-grade spondylolisthesis at the lumbosacral junction, it can be difficult to obtain access to the L5–S1 disc space for interbody insertion. We present a novel technique for improving access to the L5–S1 disc space through an osteotomy of the anterior-inferior aspect of the L5 vertebral body as part of a 2-stage circumferential fusion in the treatment of high-grade spondylolisthesis in an adolescent.
Clinical management of brain tumors in pregnancy
Authors: Karbhari Nishika , Thomas Alissa A.
Published: September 2022

Purpose of review

We review the diagnostic tools, treatment options, and clinical management for brain tumors diagnosed in pregnancy with consideration for management approaches that are best suited to preserve maternal and fetal health.

Recent findings

Women of child-bearing age are at risk of developing brain tumors and are at increased risk compared with male counterparts for tumors that are hormonally driven. Brain tumors are rare neoplasms, and diagnosis of brain tumors in pregnancy is uncommon, such that management guidelines and treatment recommendations are lacking for most tumor types. We discuss the standard treatment options for brain tumors and the relative risks and safety when these treatments are considered during pregnancy. We review the neoplasms most commonly affecting pregnant women and the existing literature and guidelines.

Pregnancy is a unique phase of life in which hormonal, immunologic, and vascular changes may impact tumor growth and presentation. Treatment decisions should consider the symptoms and stability of the pregnant patients, the gestational age and health of the fetus, and the location and behavior of the neoplasm.
Development and Validation of an Efficient and Highly Sensitive Enzyme-Linked Immunosorbent Assay for Alemtuzumab Quantification in Human Serum and Plasma
Authors: Achini-Gutzwiller Federica R. , Jol-van der Zijde Cornelia M. , Jansen-Hoogendijk Anja M. , Lankester Arjan C. , Bredius Robbert G. M. , van Tol Maarten J. D. , Moes Dirk Jan A. R. , Schilham Marco W.
Published: September 2022

Background:

Alemtuzumab is a humanized monoclonal antibody that targets the CD52 glycoprotein expressed on most lymphocytes, subsequently inducing complement-mediated and antibody-mediated cytotoxicity. Owing to its ability to induce profound immune depletion, alemtuzumab is frequently used in patients before allogeneic hematopoietic stem cell transplantation to prevent graft rejection and acute graft-versus-host disease. In this clinical context, a stable immunoassay with high sensitivity and specificity to determine alemtuzumab levels is essential for performing pharmacokinetic and pharmacodynamic analyses; however, the available methods have several limitations. Here, we report the successful development and validation of an efficient and highly sensitive enzyme-linked immunosorbent assay technique based on commercially available reagents to quantify alemtuzumab in human serum or plasma.

Methods:

This enzyme-linked immunosorbent assay technique was developed and validated in accordance with the European Medicines Agency guidelines on bioanalytical method validation.

Results:

The assay sensitivity (lower limit of quantification) is 0.5 ng·mL−1, and the dynamic range is 0.78–25 ng·mL−1. To accommodate quantification of peak concentration and concentrations below the lympholytic level (<0.1 mcg·mL−1), patients' serum samples were prediluted 20–400 times according to the expected alemtuzumab concentration. The overall within-run accuracy was between 96% and 105%, whereas overall within-run precision (coefficient of variation) was between 3% and 9%. The between-run assessment provided an overall accuracy between 86% and 95% and an overall coefficient of variation between 5% and 14%.

Conclusions:

The developed assay provides accurate insight into alemtuzumab exposure and its effects on the clinical response to treatment, which is key to optimizing treatment strategies.
Associations among Plasma Concentrations of Edoxaban and M-4, Prothrombin Time, and the SLCO1B1*15 Haplotype in Patients With Nonvalvular Atrial Fibrillation
Authors: Nakagawa Junichi , Kinjo Takahiko , Aiuchi Naoya , Ueno Kayo , Tomita Hirofumi , Niioka Takenori
Published: September 2022

Introduction:

The authors aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, the hepatic uptake transporter organic anion transporter protein 1B1, cytochrome P450 (CYP) 3A5, and carboxylesterase-1 (CES1) on the steady-state dose-adjusted trough concentrations of edoxaban (CEdo/D) and M-4 (CM-4/D). They also investigated whether CM-4 and CEdo affect prothrombin time (PT).

Methods:

The analyses included 152 patients with nonvalvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3; CES1 c.1168-33A>C, c.257+885T>C; SLCO1B1 c.388A>G, c.521T>C; and ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T genotypes were determined.

Results:

Stepwise selection multiple linear regression analyses demonstrated that creatinine clearance (Ccr), concomitant use of amiodarone, and SLCO1B1*15 haplotype status were independent factors influencing CM-4/D (partial R
2 = 0.189, 0.098, 0.067, respectively, all P values < 0.005). Ccr and concomitant use of amiodarone were independent factors influencing CEdo/D (partial R
2 = 0.260, 0.117, respectively, both P value < 0.001). CEdo and CM-4 showed a weak correlation with PT (ρ = 0.369 and 0.315, both P values < 0.001).

Conclusions:

Although information concerning Ccr, concomitant use of amiodarone, and SLCO1B1*15 haplotype may be useful in assessing the pharmacokinetics of edoxaban, further studies are needed to clarify the requirement of PT monitoring at the trough level for dose adjustment of edoxaban in patients with NVAF.
BinDel: detecting clinically relevant fetal genomic microdeletions using low-coverage whole-genome sequencing-based NIPT
Authors: Paluoja Priit , Jatsenko Tatjana , Teder Hindrek , Krjutškov Kaarel , Vermeesch Joris Robert , Salumets Andres , Palta Priit
Published: September 2022

Background

Clinically pathogenic chromosomal microdeletions (MDs) cause severe fetal genetic disorders such as DiGeorge and Prader-Willi/Angelman syndromes. Motivated by the absence of reliable blood and/or ultrasound screening biomarkers for detecting microdeletion risk during the first-trimester screening, we developed and validated BinDel, a software package to evaluate the risk of clinically pathogenic microdeletions from low-coverage whole-genome-sequencing (WGS)-based NIPT data.

Results

We used 584 NIPT samples, including 34 clinically pre- and postnatally confirmed microdeletions, to perform a blind evaluation of the BinDel software. In a combined analysis of 34 microdeletion and 50 euploid fetal samples, BinDel correctly identified 25 samples with microdeletions in the ‘blind’ analysis. BinDel had 15 false-positive microdeletion calls, whereas the majority of them were concentrated in a few challenging regions, like NF1 microdeletion region. As a comparison, WisecondorX identified 16 correct microdeletion calls with no false-positive calls. After improving BinDel, 30 microdeletion samples were correctly determined, with a total of three false-positive microdeletion calls. Using simulated fetal microdeletions, we investigated the impact of fetal DNA fraction (FF) and microdeletion region length on BinDel’s microdeletion risk detection accuracy in 12 clinically pathogenic microdeletion regions and determined that high FF is one of the most important factors for correct MD risk detection, followed by the observation, particularly in samples with lower FF, that longer microdeletion regions exhibit higher MD risk detection sensitivity.

Conclusions

We confirmed BinDel feasibility for fetal microdeletion risk detection in NIPT. Remarkably, the final BinDel tool correctly identified 88.2% (30 out of 34) MD cases, opening the possibility to integrate microdeletion analysis successfully into routine NIPT protocol. Additionally, we demonstrated that high FF is one of the most important factors for correct microdeletion risk estimation and that longer microdeletion regions display higher MD calling sensitivity. This work stands as a unique contribution to prenatal microdeletion screening, exhibiting a novel software simultaneously validated with a large microdeletion sample set, positioning it as the first of its kind in the field. BinDel is available athttps://github.com/seqinfo/BinDel.
Force Sensor Reduces Measurement Error during Sit-to-Stand Assessment of Cerebral Autoregulation
Authors: Whitaker Alicen A. , Vidoni Eric D. , Montgomery Robert N. , Carter Kailee , Struckle Katelyn , Billinger Sandra A.
Published: September 2022

Introduction

Novel implementation of a force sensor during a sit-to-stand measure of dynamic cerebral autoregulation (dCA) has been shown to measure the exact moment an individual stands up from a chair, called arise-and-off (AO). Traditional measures estimate time delay (TD) before the onset of the dCA response from the verbal command to stand. We hypothesized that using a force sensor to measure AO would significantly improve the accuracy of the TD measure compared to estimating from verbal command.

Methods

Middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) were measured simultaneously during three sit-to-stand measures of dCA. Participants were seated for 60 seconds, then performed a sit-to-stand and the force sensor detected AO. TD was calculated as the time from AO until an increase in cerebrovascular conductance (CVC = MCAv/MAP). TD was also calculated from verbal command to stand.

Results

Sixty-five participants completed the study: twenty-five young adults (age 25±2 years), twenty older adults (age 61±13 years), and twenty individuals with stroke (age 60±13 years). There was a significant difference in TD when using AO compared to estimating (F-value=49.9, p<0.001). Estimated TD introduced ∼17% measurement error. Average TD measurement error was not related to age (r =-0.04, p=0.76) or history of stroke (r=0.01, p=0.96).

Discussion

The addition of a force sensor to detect AO during a sit-to-stand procedure showed a significant difference in the TD dCA measurement. Our data support the implementation of a force sensor during sit-to-stand dCA measures in healthy adults across all ages and after stroke.
Tailored magnetic resonance fingerprinting of post-operative pediatric brain tumor patients
Authors: Poojar Pavan , Qian Enlin , Jin Zhezhen , Fung Maggie , Maddocks Alexis B , Geethanath Sairam
Published: September 2022

Purpose

Brain and spinal cord tumors are the second most common cancer in children and account for one out of four cancers diagnosed. However, the long acquisition times associated with acquiring both data types prohibit using quantitative MR (qMR) in pediatric imaging protocols. This study aims to demonstrate the tailored magnetic resonance fingerprinting’s (TMRF) ability to simultaneously provide quantitative maps (T1, T2) and multi-contrast qualitative images (T1weighted, T1FLAIR, T2weighted) rapidly in pediatric brain tumor patients.

Methods

In this work, we imaged five pediatric patients with brain tumors (resected/residual) using TMRF at 3T. We compared the TMRF-derived T2weighted images with those from the vendor-supplied sequence (as the gold standard, GS) for healthy and pathological tissue signal intensities. The relaxometric maps from TMRF were subjected to a region of interest (ROI) analysis to differentiate between healthy and pathological tissues. We performed the Wilcoxon rank sum test to check for significant differences between the two tissue types.

Results

We found significant differences (P < 0.05) in both T1and T2ROI values between the two tissue types. A strong correlation was found between the TMRF-based T2weighted and GS signal intensities for the healthy (correlation coefficient, r = 0.99) and pathological tissues (r = 0.88).

Conclusion

The TMRF implementation provides the two relaxometric maps and can potentially save ∼2 minutes if it replaces the T2-weighted imaging in the current protocol.
How do the activities of daily living decline in people living with rarer dementias? A systematic review
Authors: Taylor Beatrice , Mohamud Suraya , Brotherhood Emilie V , Harding Emma , Waddington Claire , Camic Paul M , Alexander Daniel C , Crutch Sebastian J , Stott Joshua , Hardy Chris , Oxtoby Neil P
Published: September 2022

Objective

To study how activities of daily living (ADLs) decline over the progressive course of rarer dementias (prevalence below 10%), in a systematic review of the literature.

Methods Relevant studies were identified by searching Medline, Embase, Emcare, PsycINFO and Cinahl. The databases were searched for terms relating to (rarer dementias) AND (activities of daily living) AND (longitudinal OR cross-sectional studies), using a pre-established protocol registered with the international prospective register of systematic reviews (registration: CRD42021283302).

Results

A total of 579 articles were screened for relevant content, of which 20 full-text publications were included in the analysis. Nineteen studies were about rarer dementias on the frontotemporal dementia/primary progressive aphasia spectrum, and one was about posterior cortical atrophy. Long term description of decline was limited to just seven studies following patients for longer than five years. The rate of decline, sequence of symptom onset, and symptom duration were also highlighted.

Conclusion

Descriptions of ADL progression were inadequately long term, covering an average of 3.5 years from symptom onset, and lacked phenotypic specificity. The literature disproportionately studied dementias on the frontotemporal dementia spectrum. To facilitate better care, more longitudinal data, quantitative analyses, and development of rarer dementia-specific ADL scales is needed. Given the low prevalence of rarer dementias, big data analyses may never be applicable and so personalised medicine approaches should be pursued, including innovative possibilities in digital biomarkers such as from wearable technology.
Commercial immunoglobulin products now contain neutralising antibodies against SARS-CoV-2 spike protein which are detectable in patient serum
Authors: Upasani Vinit , O’Sullivan Mary , Moreira Fernando , Workman Sarita , Symes Andrew , Burns Siobhan O , Tadros Susan , McCoy Laura , Lowe David M
Published: September 2022

Antibody-deficient patients respond poorly to COVID-19 vaccination and are at risk of severe or prolonged infection. Prophylaxis with anti-SARS-CoV-2 monoclonal antibodies has been considered. We here demonstrate that many immunoglobulin preparations now contain neutralising anti-SARS-CoV-2 antibodies which are transmitted to patients in good concentrations, albeit with significant differences between products.
Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic
Authors: Boehm Alexandria B. , Hughes Bridgette , Duong Dorothea , Chan-Herur Vikram , Buchman Anna , Wolfe Marlene K. , White Bradley J.
Published: September 2022

Background

Respiratory disease is a major cause of morbidity and mortality; however, current surveillance for circulating respiratory viruses is passive and biased. Seasonal circulation of respiratory viruses changed dramatically during the COVID-19 pandemic. More active methods for understanding respiratory disease dynamics are needed to better inform public health response and to guide clinical decision making. Wastewater-based epidemiology has been used to understand COVID-19, influenza A, and RSV infection rates at a community level, but has not been used to investigate other respiratory viruses.

Methods

We measured concentrations of influenza A and B, RSV A and B, human parainfluenza (1-4), rhinovirus, seasonal human coronaviruses, and human metapneumovirus RNA in wastewater solids three times per week for 17 months spanning the COVID-19 pandemic at a wastewater treatment plant in California, USA. Novel probe-based assays were developed and validated for non-influenza viral targets. We compared viral concentrations to positivity rates for viral infections from clinical specimens submitted to sentinel laboratories.

Findings

We detected RNA from all target viruses in wastewater solids. Human rhinovirus and seasonal coronaviruses were found at highest concentrations. Concentrations of viruses correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories. Measurements from wastewater indicated limited circulation of RSV A and influenza B, and human coronavirus OC43 dominated the seasonal human coronavirus infections while human parainfluenza 1 and 4A dominated among parainfluenza infections.

Interpretation

Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 hours of sample collection, allowing real time information to inform public health response, clinical decision making, and individual behavior modifications.
Reduction of pro-inflammatory effector functions through remodeling of fatty acid metabolism in CD8+ T-cells from Rheumatoid Arthritis patients
Authors: Kraus Franziska V. , Keck Simon , Klika Karel D. , Graf Jürgen , Carvalho Rui A. , Lorenz Hanns-Martin , Souto-Carneiro M Margarida
Published: September 2022

Objectives

RA CD8+ T-cells (CD8) maintain their effector pro-inflammatory phenotype by changing their metabolism towards aerobic glycolysis. However, their massive energetic and biosynthetic needs may require additional substrates to furnish this high demand. Since systemic alterations in lipid metabolism have been reported in RA patients, we explored the role of fatty acid (FA) metabolism in CD8 to identify potential targets to curb their pro-inflammatory potential.

Methods

The expression of FA metabolism-related genes was analyzed for total and CD8-subsets from RA patients and healthy controls (CNT). Peripheral-blood CD8 were isolated from RA, PsA, SpA patients under different therapies (DMARD, biologicals, JAK-inhibitors) and CNT and were TCR-stimulated with or without FA metabolism inhibitors. We quantified the expression of the main FA transporters, lipid uptake, intracellular content of (un-)saturated FA, cytokine production, activation, proliferation, and capacity to inhibit tumor cell growth.

Results

The CD8 gene expression profile of FA metabolism-related genes was significantly different between untreated RA patients and CNT. RA patients with a good clinical response after 6 months MTX therapy significantly increased the expression of FA metabolism-related genes. Cell-surface expression of FA transporters FABP4 and GPR84 and FA-uptake was higher in effector and memory CD8 of RA patients than for CNT. In vitro blockade of FA metabolism significantly impaired CD8 effector functions.

Conclusions

RA CD8 present an altered FA-metabolism which can be potential therapeutic targets to control their pro-inflammatory profile, especially by targeting the transport and oxidation of free FAs which are abundant in the serum and synovial fluid of patients.
Mapping associations of polygenic scores with autism and ADHD traits in a single city region
Authors: Reed Zoe E. , Thomas Richard , Boyd Andy , Griffith Gareth J. , Morris Tim T. , Rai Dheeraj , Manley David , Smith George Davey , Davis Oliver S.P.
Published: September 2022

Background

The genetic and environmental aetiology of autistic and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary spatially, but does this translate into variation in the association of specific common genetic variants?

Methods

We mapped associations between polygenic scores for autism and ADHD and their respective traits in the Avon Longitudinal Study of Parents and Children (N=4,255 to 6,165) across the area surrounding Bristol, UK, and compared them to maps of environments associated with the prevalence of autism and ADHD.

Results

Our maps suggest genetic associations vary spatially, with consistent patterns for autistic traits across polygenic scores constructed at different p-value thresholds. Patterns for ADHD traits were more variable across thresholds. We found that the spatial distributions often correlated with known environmental influences.

Conclusions

These findings shed light on the factors that contribute to the complex interplay between the environment and genetic influences in autism and ADHD traits.

Key points

The prevalence of autism and ADHD vary spatially.

Our study highlights that genetic influences based on PGS also vary spatially.

This spatial variation correlates with spatial variation in environmental characteristics as well, which would be interesting to examine further.

Our findings have implications for future research in this area examining the factors that contribute to the complex interplay between the environment and genetic influences on autistic and ADHD traits.
Large-Scale Application of Named Entity Recognition to Biomedicine and Epidemiology
Authors: Raza Shaina , Reji Deepak John , Shajan Femi , Bashir Syed Raza
Published: September 2022

Background

Despite significant advancements in biomedical named entity recognition methods, the clinical application of these systems continues to face many challenges: (1) most of the methods are trained on a limited set of clinical entities; (2) these methods are heavily reliant on a large amount of data for both pretraining and prediction, making their use in production impractical; (3) they do not consider non-clinical entities, which are also related to patient’s health, such as social, economic or demographic factors.

Methods

In this paper, we develop Bio-Epidemiology-NER (https://pypi.org/project/Bio-Epidemiology-NER/) an open-source Python package for detecting biomedical named entities from the text. This approach is based on Transformer-based approach and trained on a dataset that is annotated with many named entities (medical, clinical, biomedical and epidemiological). This approach improves on previous efforts in three ways: (1) it recognizes many clinical entity types, such as medical risk factors, vital signs, drugs, and biological functions; (2) it is easily configurable, reusable and can scale up for training and inference; (3) it also considers non-clinical factors (age and gender, race and social history and so) that influence health outcomes. At a high level, it consists of the phases: preprocessing, data parsing, named entity recognition and named entities enhancement.

Results

Experimental results show that our pipeline outperforms other methods on three benchmark datasets with macro-and micro average F1 scores around 90 percent and above.

Conclusion

This package is made publicly available for use by researchers, doctors, clinicians and anyone to extract biomedical named entities from unstructured biomedical texts.

Author Summary

This paper introduces and presents a python packagehttps://pypi.org/project/Bio-Epidemiology-NER/that can extract named entities from the biomedical texts. Different from previous works, this package extracts not only clinical entities, such as disease, signs, symptoms but also demographics of the patients from the texts. This package can be used with least code requirements and can be used by epidemiologists, doctors, practitioners or others in the field to see the named entities from texts. The knowledge gained from the named entities help the end users to see the statistics or spread of infectious disease in least time and while parsing a large amount of free texts.
Intestinal helminth infection impairs oral and parenteral vaccine efficacy
Authors: Hardy LaKeya C. , Kapita Camille M. , Campbell Evelyn , Hall Jason A. , Urban Joseph F. , Belkaid Yasmine , Nagler Cathryn R. , Iweala Onyinye I.
Published: September 2022

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminthHeligmosomoides polygyrus bakerialters antigen-specific antibody and cellular immune responses to oral and parenteral vaccination in mice. We found that oral vaccination of mice with a clinically relevant, live, attenuated, recombinantSalmonellavaccine that expresses chicken egg ovalbumin (Salmonella-OVA) disrupts ovalbumin-specific regulatory T cell networks in the gut associated lymphoid tissue and promotes T-effector responses to OVA. Chronic intestinal helminth infection significantly reduced Th1-skewed antibody responses to oral vaccination withSalmonella-OVA. Activated, adoptively-transferred, OVA-specific CD4+T cells accumulated in draining mesenteric lymph nodes (MLN) of vaccinated mice, irrespective of their helminth-infection status. However, helminth infection increased the frequencies of adoptively-transferred OVA-specific CD4+T cells producing IL-4 and IL-10 in the MLN. Chronic intestinal helminth infection also significantly reduced Th2-skewed antibody responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest helminth-induced impairment of vaccine antibody responses may be driven by the development of IL-10-secreting CD4+T regulatory cells. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas.
Comprehensive evaluation of harmonization on functional brain imaging for multisite data-fusion
Authors: Wang Yu-Wei , Chen Xiao , Yan Chao-Gan
Published: September 2022

To embrace big-data neuroimaging, harmonization of site effect in resting-state functional magnetic resonance imaging (R-fMRI) data fusion is a fundamental challenge. Comprehensive evaluation of potentially effective harmonization strategies, particularly with specifically collected data has been rare, especially for R-fMRI metrics. Here, we comprehensively assess harmonization strategies from multiple perspectives, including efficiency, individual identification, test-retest reliability and replicability of group-level statistical results, on widely used R-fMRI metrics across multiple datasets including data obtained from the same participants scanned at several sites. For individual identifiability (i.e., whether the same subject could be identified across R-fMRI data scanned across different sites), we found that, while most methods decreased site effects, the Subsampling Maximum-mean-distance based distribution shift correction Algorithm (SMA) outperformed linear regression models, linear mixed models, ComBat series and invariant conditional variational auto-encoder. Test-retest reliability was better for SMA and adjusted ComBat series than alternatives, while SMA was superior to the latter in replicability, both in terms of Dice coefficient and the scale of brain areas showing sex differences reproducibly observed across datasets. Moreover, we examined test-retest datasets to identify the best target site features to optimize SMA identifiability and test-retest reliability. We noted that both sample size and distribution of the target site matter and introduced a heuristic target site selection formula. In addition to providing practical guidelines, this work can inform continuing improvements and innovations in harmonizing methodologies for big R-fMRI data.
A role for myeloid miR-155 in regulating hypoxia induced seizures in neonatal C57BL/J6 mice
Authors: Dahiya Devika , Smith Jonathan , Strickland Tammy , Morris Delphi , Reschke Cristina , Engel Tobias , Henshall David , McCoy Claire E , Dowling Jennifer K
Published: September 2022

Hypoxic ischaemic injury (HIE) in the neonatal brain has significant consequences on neurodevelopment and increases the occurrence of neurological deficits in infants. HIE is also a leading cause of neonatal seizures. Therapeutic options for the treatment of HIE are very limited. Hypoxia-ischemia directly damages brain tissue in a primary-wave of injury which activates a cascade of events triggering local and systemic inflammatory responses, driven by the innate immune system, which contribute to a significant secondary-wave of injury taking place as early as 6 hours post-hypoxia-ischaemia. Levels of the well documented inflammatory microRNA, miR-155 are elevated in rodent seizure and epilepsy models. Here, we assessed the impact of, miR-155 deletion in myeloid cells, on regulating inflammation and seizure severity in a preclinical model of neonatal hypoxia-induced seizures (Hypoxia-Sz). Wildtype miR-155 (miR-155+/+LysMCre) mice were compared to a mouse line in which miR-155 was deleted in myeloid cells (miR-155fl/flLysMCre). We demonstrate significant upregulation of miR-155 target genes, brain-derived neurotrophic factor (bdnf), arginase-2 (arg-2),ship-1andsocs-1in miR-155fl/flLysMCre mice compared to controls at various time points following Hypoxia-Sz. Conversely, we report decreased mRNA levels of pro-inflammatory cytokines IL-1β and IL-6 and lower protein levels of IL-1β in miR-155fl/flLysMCre mice as compared to WTs. Myeloid miR-155 deletion significantly reduced behavioural seizure severity score, reduced electrographically (EEG) measured seizure frequency and seizure burden as compared to mice to wildtypes, suggesting miR-155 regulation of seizure occurrence in this model. Behavioural tests for motor functions at 5 weeks post Hypoxia-Sz demonstrated differences between genotypes. Excitingly this work highlights that inhibition of miR-155, specifically in myeloid cells, may hold therapeutic benefit for both seizures and comorbidities associated with hypoxic brain injury.
Validity of fecal sampling for characterizing temporal variation in threespine stickleback’s gut microbiota
Authors: Härer Andreas , Rennison Diana J.
Published: September 2022

Diverse microbial communities associated with the guts of their hosts are crucial for many aspects of their hosts’ physiology, ecology, and evolution. The gut microbiota has been characterized for a broad range of species across the animal kingdom. Yet, for many host species we still don’t have a good understanding of whether non-lethal sampling (e.g., fecal matter) can accurately capture the diversity of gut-associated bacterial communities, as estimated from lethal sampling of intestinal tissue. We further lack knowledge on whether such non-lethal sampling methods are suitable for studying temporal gut microbiota dynamics. Here, we addressed these questions in threespine stickleback fish, a model system in evolutionary ecology, by comparing bacterial communities based on 16S rRNA gene sequencing from intestinal tissue and feces. Despite some differences in community composition between the two sample types, we show that bacterial communities of feces and intestinal tissue largely overlap. Further, we were able to detect consistent and significant changes of fecal bacterial communities associated with an experimental diet shift. These results suggest that fecal sampling represents an adequate non-lethal method to characterize the gut microbiota of threespine stickleback. This allows for studying temporal gut microbiota dynamics at the individual level, which increases opportunities for future experimental gut microbiota research.