bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and microbiological effects in high-risk beef calves administered intranasal or parenteral modified-live virus vaccines
Authors: Powledge Sherri A , McAtee Taylor B , Woolums Amelia R , Robin Falkner T , Groves John T , Thoresen Merilee , Valeris-Chacin Robert , Richeson John T
Published: August 2022

Experimental bovine respiratory syncytial virus (BRSV) infection can enhance Histophilus somni (Hs) disease in calves; we thus hypothesized that modified-live virus (MLV) vaccines containing BRSV may alter Hs carriage. Our objective was to determine the effects of an intranasal (IN) trivalent (infectious bovine rhinotracheitis virus [IBRV], parainfluenza-3 virus [PI3V], and BRSV) respiratory vaccine with parenteral (PT) bivalent bovine viral diarrhea virus (BVDV) type I + II vaccine, or a PT pentavalent (BVDV type I and II, IBRV, BRSV, and PI3V) respiratory vaccine, on health, growth, immunity, and nasal pathogen colonization in high-risk beef calves. Calves (n = 525) were received in five truckload blocks and stratified by body weight (213 ± 18.4 kg), sex, and presence of a pre-existing ear-tag. Pens were spatially arranged in sets of three within a block and randomly assigned to treatment with an empty pen between treatment groups consisting of: 1) no MLV respiratory vaccination (CON), 2) IN trivalent MLV respiratory vaccine with PT BVDV type I + II vaccine (INT), or 3) PT pentavalent, MLV respiratory vaccine (INJ). The pen was the experimental unit, with 15 pens/treatment and 11 to 12 calves/pen in this 70-d receiving study. Health, performance, and BRSV, Hs, Mycoplasma bovis (Mb), Mannheimia haemolytica (Mh), and Pasteurella multocida (Pm) level in nasal swabs via rtPCR was determined on days 0, 7, 14, and 28, and BRSV-specific serum neutralizing antibody titer, and serum IFN-γ concentration via ELISA, were evaluated on days 0, 14, 28, 42, 56, and 70. Morbidity (P = 0.83), mortality (P = 0.68) and average daily gain (P ≥ 0.82) did not differ. Serum antibodies against BRSV increased with time (P < 0.01). There was a treatment × time interaction (P < 0.01) for Hs detection; on days 14 and 28, INT (21.1% and 57.1%) were more frequently (P < 0.01) Hs positive than CON (3.6% and 25.3%) or INJ (3.4 % and 8.4%). Also, INT had reduced (P = 0.03) cycle time of Hs positive samples on day 28. No difference (P ≥ 0.17) was found for IFN-γ concentration and Mb, Mh, or Pm detection. The proportion of Mh positive culture from lung specimens differed (P < 0.01); INT had fewer (0.0%; 0 of 9) Mh positive lungs than INJ (45.5%; 6 of 13) or CON (74.0%; 14 of 19). Vaccination of high-risk calves with MLV did not clearly impact health or growth during the receiving period. However, INT was associated with an altered upper respiratory microbial community in cattle resulting in increased detection and level of Hs.
Effects of dietary cholesterol and phospholipid levels on growth performance, antioxidant capacity, and tissue fatty acid in the juvenile mud crab Scylla paramamosain Estampador, 1950 (Decapoda: Brachyura: Portunidae)
Authors: Chen Cuiying , Nie Xiaofeng , Cheng Yu , Shen Jiajian , Zhang Pengyuan , Zhong Wenjie , Wang Shuqi , You Cuihong , Li Yuanyou
Published: August 2022

To investigate whether an interaction between the levels of dietary cholesterol (CHOL) and phospholipid (PL) exists in the growth performance, antioxidant, and immune parameters of juvenile Scylla paramamosainEstampador, 1950, a 3 × 3 factorial feeding trial was conducted in polypropylene tanks with nine diets containing three CHOL levels (0.5%, 1.0%, 1.5% of dry weight) and three PL levels (0.5%, 1.0%, 1.5% of dry weight). After the eight-week feeding trial, crabs fed the diets with 0.5% CHOL and 1.0 or 1.5% PL achieved the best growth performance with a relatively higher survival rate. Hemolymph CHOL, low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol (HDLC) increased with the increasing dietary CHOL levels, whereas decreased LDLC levels were observed as dietary PL levels increased. With the increasing dietary levels of PL, the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were markedly enhanced in crabs fed the basal diets with 0.5 or 1.0% CHOL and PL. Tissue fatty acid composition reflected dietary fatty acids. Increasing dietary PL levels resulted in rising contents of total n-6 polyunsaturated fatty acids (PUFA) in the hepatopancreas and muscle. A synergistic effect between CHOL and PL was not observed on growth performance but such effect was found instead in the biochemical indices of hemolymphs and the antioxidant capacity of the hepatopancreas. These results suggest that proper dietary levels of 0.5% CHOL and 1.0–1.5% PL could maintain solid growth performance and antioxidant capacity of juvenile S. paramamosain.
Non-solar abundance ratios trends of dEs in the Fornax Cluster using newly defined high-resolution indices
Authors: Şen Şeyda , Peletier Reynier F , Vazdekis Alexandre
Published: August 2022

We perform a detailed study of the stellar populations in a sample of massive Fornax dwarf galaxies using a set of newly defined line indices. Using data from the Integral Field Spectroscopic data, we study abundance ratios of eight dEs with stellar mass ranging from 108 to 109.5 M⊙ in the Fornax Cluster. We present the definitions of a new set of high-resolution Lick-style indices to be used for stellar population studies of unresolved small stellar systems. We identify 23 absorption features and continuum regions, mainly dominated by 12 elements (Na, Ca, Sc, Ti, V, Cr, Mn, Fe, Ni, Y, Ba, and Nd) in the wavelength range 4700–5400 Å and characterize them as a function of age, metallicity, and alpha element abundance ratios. We analyse eight dEs and interpret the line strengths, measured in our new high-resolution system of indices, with the aid of stellar population models with high enough spectral resolution. We obtain abundance ratio proxies for a number of elements that have never been studied before for dwarf ellipticals outside the Local Group. These proxies represent relative deviations from predicted index strengths of base stellar population models built-up following the abundance pattern of The Galaxy. The abundance proxy trend results are compared to abundance ratios from resolved stars in the Local Group, and indices from integrated light of larger early-type galaxies. We find that all our dwarfs show a pattern of abundance ratios consistent with the disc of the Milky Way, indicative of slow formation in comparison to their high-mass counterparts.
Spectroscopic characterization of the Gefion Asteroid Family: implications for L-chondrite Link
Authors: McGraw Allison M , Reddy Vishnu , Sanchez Juan A
Published: August 2022

Asteroid families are cosmic puzzles that help us understand the true nature of their original parent body. Ordinary chondrites are the most common types of meteorites that arrive to Earth and are composed of three subtypes: H, L, and LL chondrites. The Gefion Asteroid Family (GAF) has been proposed to be the source asteroids for the L chondrites. In this work, we present the results of a spectroscopic campaign of six dynamically defined members of the GAF to test the hypothesis if L chondrites come from this family. Our compositional analysis of these six asteroids shows a range of meteorite analogues from L- to LL chondrites. Combining these results with our previous work, we note that GAF asteroids span the entire ordinary chondrite range of H-, L-, and LL. The observed compositional heterogeneity in the GAF is likely due to largest members of the GAF consisting of interlopers. A more detailed spectroscopic survey of a large subset of asteroids in the GAF region is needed to further isolate true family members.
Signatures of Light Massive Relics on non-linear structure formation
Authors: Banerjee Arka , Das Subinoy , Maharana Anshuman , Sharma Ravi Kumar
Published: August 2022

Cosmologies with Light Massive Relics (LiMRs) as a subdominant component of the dark sector are well-motivated from a particle physics perspective, and can also have implications for the σ8 tension between early and late time probes of clustering. The effects of LiMRs on the cosmic microwave background (CMB) and structure formation on large (linear) scales have been investigated extensively. In this paper, we initiate a systematic study of the effects of LiMRs on smaller, non-linear scales using cosmological N-body simulations; focusing on quantities relevant for photometric galaxy surveys. For most of our study, we use a particular model of non-thermal LiMRs but the methods developed generalizing to a large class of LiMR models – we explicitly demonstrate this by considering the Dodelson–Widrow velocity distribution. We find that, in general, the effects of LiMR on small scales are distinct from those of a ΛCDM universe, even when the value of σ8 is matched between the models. We show that weak lensing measurements around massive clusters, between ∼0.1 h−1Mpc and ∼10 h−1Mpc, should have sufficient signal-to-noise in future surveys to distinguish between ΛCDM and LiMR models that are tuned to fit both CMB data and linear scale clustering data at late times. Furthermore, we find that different LiMR cosmologies indistinguishable by conventional linear probes can be distinguished by non-linear probes if their velocity distributions are sufficiently different. LiMR models can, therefore, be best tested by jointly analyzing the CMB and late-time structure formation on both large and small scales.
Quantifying the role of ram-pressure stripping of galaxies within galaxy groups
Authors: Kolcu Tutku , Crossett Jacob P , Bellhouse Callum , McGee Sean
Published: August 2022

It is often stated that the removal of gas by ram-pressure stripping of a galaxy disc is not a common process in galaxy groups. In this study, with the aid of an observational classification of galaxies and a simple physical model, we show that this may not be true. We examined and identified 45 ram-pressure-stripped galaxy candidates from a sample of 1311 galaxy group members within 125 spectroscopically selected galaxy groups. Of these, 13 galaxies are the most secure candidates with multiple distinct features. These candidate ram-pressure-stripped galaxies have similar properties to those found in clusters – they occur at a range of stellar masses, are largely blue and star-forming, and have phase-space distributions consistent with being first infallers into their groups. The only stand-out feature of these candidates is they exist not in clusters, but in groups, with a median halo mass of 1013.5 M⊙. Although this may seem surprising, we employ an analytic model of the expected ram-pressure stripping force in groups and find that reasonable estimates of the relevant infall speeds and intragroup medium content would result in ram-pressure-stripped galaxies at these halo masses. Finally, given the considerable uncertainty on the lifetime of the ram-pressure phase, this physical mechanism could be the dominant quenching mechanism in galaxy groups, if our ram-pressure-stripped candidates can be confirmed.
Maximal X-ray feedback in the pre-reionization Universe
Authors: Jeon Junehyoung , Bromm Volker , Finkelstein Steven L
Published: August 2022

X-ray feedback in the pre-reionization Universe provided one of the major energy sources for reionization and the thermal evolution of the early intergalactic medium. However, X-ray sources at high redshift have remained largely inaccessible to observations. One alternative approach to study the overall effects of X-ray feedback in the early Universe is a full cosmological simulation. Towards this goal, in this paper we create an analytic model of X-ray feedback from accretion on to supermassive black holes (SMBHs), to be used as a sub-grid model in future cosmological simulations. Our analytic model provides a relation between the mass of a dark matter halo and the SMBH it hosts, where the efficiency is governed by an energy balance argument between thermal feedback and the confining gravitational potential of the halo. To calibrate the model, we couple the halo-level recipe with the Press–Schechter halo mass function and derive global mass and energy densities. We then compare our model to various observational constraints, such as the resulting soft X-ray and IR cosmic radiation backgrounds, to test our choice of model parameters. We in particular derive model parameters that do not violate any constraints, while providing maximal X-ray feedback prior to reionization. In addition, we consider the contribution of SMBH X-ray sources to reionization and the global 21 cm absorption signal.
The convergent xenogeneic silencer MucR predisposes α-proteobacteria to integrate AT-rich symbiosis genes
Authors: Shi Wen-Tao , Zhang Biliang , Li Meng-Lin , Liu Ke-Han , Jiao Jian , Tian Chang-Fu
Published: August 2022

Bacterial adaptation is largely shaped by horizontal gene transfer, xenogeneic silencing mediated by lineage-specific DNA bridgers (H-NS, Lsr2, MvaT and Rok), and various anti-silencing mechanisms. No xenogeneic silencing DNA bridger is known for α-proteobacteria, from which mitochondria evolved. By investigating α-proteobacterium Sinorhizobium fredii, a facultative legume microsymbiont, here we report the conserved zinc-finger bearing MucR as a novel xenogeneic silencing DNA bridger. Self-association mediated by its N-terminal domain (NTD) is required for DNA–MucR–DNA bridging complex formation, maximizing MucR stability, transcriptional silencing, and efficient symbiosis in legume nodules. Essential roles of NTD, CTD (C-terminal DNA-binding domain), or full-length MucR in symbiosis can be replaced by non-homologous NTD, CTD, or full-length protein of H-NS from γ-proteobacterium Escherichia coli, while NTD rather than CTD of Lsr2 from Gram-positive Mycobacterium tuberculosis can replace the corresponding domain of MucR in symbiosis. Chromatin immunoprecipitation sequencing reveals similar recruitment profiles of H-NS, MucR and various functional chimeric xenogeneic silencers across the multipartite genome of S. fredii, i.e. preferring AT-rich genomic islands and symbiosis plasmid with key symbiosis genes as shared targets. Collectively, the convergently evolved DNA bridger MucR predisposed α-proteobacteria to integrate AT-rich foreign DNA including symbiosis genes, horizontal transfer of which is strongly selected in nature.
Early volumetric, perfusion, and diffusion MRI changes after mutant isocitrate dehydrogenase (IDH) inhibitor treatment in IDH1-mutant gliomas
Authors: Cho Nicholas S , Hagiwara Akifumi , Eldred Blaine S C , Raymond Catalina , Wang Chencai , Sanvito Francesco , Lai Albert , Nghiemphu Phioanh , Salamon Noriko , Steelman Lori , Hassan Islam , Cloughesy Timothy F , Ellingson Benjamin M
Published: August 2022

Background

Inhibition of the isocitrate dehydrogenase (IDH)-mutant enzyme is a novel therapeutic target in IDH-mutant gliomas. Imaging biomarkers of IDH inhibitor treatment efficacy in human IDH-mutant gliomas are largely unknown. This study investigated early volumetric, perfusion, and diffusion MRI changes in IDH1-mutant gliomas during IDH inhibitor treatment.

Methods

Twenty-nine IDH1-mutant glioma patients who received IDH inhibitor and obtained anatomical, perfusion, and diffusion MRI pretreatment at 3–6 weeks (n = 23) and/or 2–4 months (n = 14) of treatment were retrospectively studied. Normalized relative cerebral blood volume (nrCBV), apparent diffusion coefficient (ADC), and fluid-attenuated inversion recovery (FLAIR) hyperintensity volume were analyzed.

Results

After 3–6 weeks of treatment, nrCBV was significantly increased (P = .004; mean %change = 24.15%) but not FLAIR volume (P = .23; mean %change = 11.05%) or ADC (P = .52; mean %change = -1.77%). Associations between shorter progression-free survival (PFS) with posttreatment nrCBV > 1.55 (P = .05; median PFS, 240 vs 55 days) and increased FLAIR volume > 4 cm3 (P = .06; 227 vs 29 days) trended toward significance. After 2–4 months, nrCBV, FLAIR volume, and ADC were not significantly different from baseline, but an nrCBV increase > 0% (P = .002; 1121 vs 257 days), posttreatment nrCBV > 1.8 (P = .01; 1121 vs. 270 days), posttreatment ADC < 1.15 μm2/ms (P = .02; 421 vs 215 days), median nrCBV/ADC ratio increase > 0% (P = .02; 1121 vs 270 days), and FLAIR volume change > 4 cm3 (P = .03; 421 vs 226.5 days) were associated with shorter PFS.

Conclusions

Increased nrCBV at 3–6 weeks of treatment may reflect transient therapeutic and/or tumor growth changes, whereas nrCBV, ADC, and FLAIR volume changes occurring at 2–4 months of treatment may more accurately reflect antitumor response to IDH inhibition.
Association Between Smoking Behavior and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis
Authors: Zeng Xiangxia , Ren Yingying , Wu Kang , Yang Qifeng , Zhang Sun , Wang Donghao , Luo Yateng , Zhang Nuofu
Published: August 2022

Introduction

To systematically review the association between smoking behavior and obstructive sleep apnea (OSA).

Aims and Methods

PubMed, Medline, the Cochrane Library, EMBASE, and Scopus databases were used to conduct this review. The two researchers independently screened the literatures, conducted the quality assessment, and data extraction according to the inclusion and exclusion criteria. The RevMan 5.3 was used to analysis the apnea hypopnea index (AHI) index, min saturation of oxyhemoglobin (SaO2), Epworth Sleepiness Scale (ESS) score, and oxygen desaturation index (DOI) and publication bias analysis to assess the effect of smoking on OSA patients. Furthermore, we performed subgroup of the severity of OSA, different countries of sample origin (western countries or eastern countries), and pack-years (PYs < 10 or PYs ≥ 20) to analyze the heterogeneity.

Results

Thirteen studies were included in this analysis that conformed to inclusion criteria and exclusion criteria. Totally 3654 smokers and 9796 non-smokers have participated. The meta-analysis of 13 studies demonstrated that AHI levels were significantly higher in smoker group compared with non-smoker, ESS scores were also significantly higher in smoker group compared with non-smoker, min SaO2 levels were obviously lower in smoker group compared with non-smoker, however, DOI levels hadn’t significantly different between two groups. The subgroup analysis showed that there was an association between severe OSA, eastern countries, pack-years, and smoking.

Conclusions

Smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significantly association with smoking compared with patients with mild or moderate OSA.

Implications

The relationship between smoking and OSA was controversial, especially, whether smoking increase or aggravate the risk of OSA. In our review and meta-analysis, we demonstrated that smoking behavior is a significant association with OSA. Heavy smokers with histories of more than 20 PYs were at a higher risk of OSA. Moreover, patient with severe OSA exhibited a significant association with smoking compared with patients with mild or moderate OSA. More prospective long-term follow-up studies about effect of quit smoking on OSA are recommended to establish the further relationship.
An Expert, Multidisciplinary Perspective on Best Practices in Biomarker Testing in Intrahepatic Cholangiocarcinoma
Authors: Madoff David C , Abi-Jaoudeh Nadine , Braxton David , Goyal Lipika , Jain Dhanpat , Odisio Bruno C , Salem Riad , Schattner Mark , Sheth Rahul , Li Daneng
Published: August 2022

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy that arises from the intrahepatic biliary tree and is associated with a poor prognosis. Until recently, the treatment landscape of advanced/metastatic iCCA has been limited primarily to chemotherapy. In recent years, the advent of biomarker testing has identified actionable genetic alterations in 40%-50% of patients with iCCA, heralding an era of precision medicine for these patients. Biomarker testing using next-generation sequencing (NGS) has since become increasingly relevant in iCCA; however, several challenges and gaps in standard image-guided liver biopsy and processing have been identified. These include variability in tissue acquisition relating to the imaging modality used for biopsy guidance, the biopsy method used, number of passes, needle choice, specimen preparation methods, the desmoplastic nature of the tumor, as well as the lack of communication among the multidisciplinary team. Recognizing these challenges and the lack of evidence-based guidelines for biomarker testing in iCCA, a multidisciplinary team of experts including interventional oncologists, a gastroenterologist, medical oncologists, and pathologists suggest best practices for optimizing tissue collection and biomarker testing in iCCA.
The Shallow Magmatic Plumbing System of the Deccan Traps, Evidence from Plagioclase Megacrysts and Their Host Lavas
Authors: Marzoli Andrea , Renne Paul R , Andreasen Rasmus , Spiess Richard , Chiaradia Massimo , Ruth Dawn C S , Tholt Andrew J , Pande Kanchan , Costa Fidel
Published: August 2022

We investigate the shallow plumbing system of the Deccan Traps Large Igneous Province using rock and mineral data from Giant Plagioclase Basalt (GPB) lava flows from around the entire province, but with a focus on the Saurashtra Peninsula, the Malwa Plateau, and the base and top of the Western Ghats (WG) lava pile. GPB lavas in the WG typically occur at the transition between chemically distinct basalt formations. Most GPB samples are evolved basalts, with high Fe and Ti contents, and show major and trace elements and Sr-Nd-Pb isotopic compositions generally similar to those of previously studied Deccan basalts. Major element modeling suggests that high-Fe, evolved melts typical of GPB basalts may derive from less evolved Deccan basalts by low-pressure fractional crystallization in a generally dry magmatic plumbing system. The basalts are strongly porphyritic, with 6–25% of mm- to cm-sized plagioclase megacrysts, frequently occurring as crystal clots, plus relatively rare olivine and clinopyroxene. The plagioclase crystals are mostly labradoritic, but some show bytownitic cores (general range of anorthite mol%: 78–55). A common feature is a strong Fe enrichment at the plagioclase rims, indicating interaction with an Fe-rich melt similar to that represented by the matrix compositions (FeOt up to 16–17 wt%). Plagioclase minor and trace elements and Sr isotopic compositions analyzed by laser ablation inductively coupled plasma mass spectrometry show evidence of a hybrid and magma mixing origin. In particular, several plagioclase crystals show variable 87Sr/86Sri, which only partially overlaps with the 87Sr/86Sri of the surrounding matrix. Diffusion modeling suggests residence times of decades to centuries for most plagioclase megacrysts. Notably, some plagioclase crystal clots show textural evidence of deformation as recorded by electron back-scatter diffraction analyses and chemical maps, which suggest that the plagioclase megacrysts were deformed in a crystal-rich environment in the presence of melt. We interpret the plagioclase megacrysts as remnants of a crystal mush originally formed in the shallow plumbing system of the Deccan basalts. In this environment, plagioclase acquired a zoned composition due to the arrival of chemically distinct basaltic magmas. Prior to eruption, a rapidly rising but dense Fe-rich magma was capable of disrupting the shallow level crystal mush, remobilizing part of it and carrying a cargo of buoyant plagioclase megacrysts. Our findings suggest that basaltic magmas from the Deccan Traps, and possibly from LIPs in general, are produced within complex transcrustal magmatic plumbing systems with widespread crystal mushes developed in the shallow crust.
Roads and Loans
Authors: Agarwal Sumit , Mukherjee Abhiroop , Naaraayanan S Lakshmi
Published: August 2022

Does financing respond to changes in productive opportunities, even for the world’s poor? We answer this question by examining the response of private bank financing to an infrastructure program that brought road access to unconnected Indian villages. This program prioritized roads for villages above specific population thresholds, allowing us to exploit the resultant discontinuities for identification. Using detailed data from a large bank, we find that 75$\%$ more villagers get loans, and the average amount lent to them is 30$\%$–35$\%$ higher, in villages just above these thresholds. District-level analyses further suggest that roads and loans are complements in the growth process.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Influences on the Genetic Relationship Between Cannabis Use and Schizophrenia: The Role of the Externalizing Spectrum
Authors: Wormington Briar , Thorp Jackson G , Scott James G , Derks Eske M
Published: August 2022

Background and Hypothesis

The nature of the robust association between cannabis use and schizophrenia remains undetermined. Plausible hypotheses explaining this relationship include the premise that cannabis use causes schizophrenia, increased liability for schizophrenia increases the risk of cannabis use initiation (eg, self-medication), or the bidirectional causal hypothesis where both factors play a role in the development of the other. Alternatively, factors that confound the relationship between schizophrenia and cannabis use may explain their association. Externalizing behaviors are related to both schizophrenia and cannabis use and may influence their relationship.

Study Design

This study aimed to evaluate whether externalizing behaviors influence the genetic relationship between cannabis use and schizophrenia. We conducted a multivariate genome-wide association analysis of 6 externalizing behaviors in order to construct a genetic latent factor of the externalizing spectrum. Genomic structural equation modeling was used to evaluate the influence of externalizing behaviors on the genetic relationship between cannabis use and schizophrenia.

Results

We found that externalizing behaviors partially explained the association between cannabis use and schizophrenia by up to 42%.

Conclusions

This partial explanation of the association by externalizing behaviors suggests that there may be other unidentified confounding factors, alongside a possible direct association between schizophrenia and cannabis use. Future studies should aim to identify further confounding factors to accurately explain the relationship between cannabis use and schizophrenia.
Childhood Drownings: An Opportunity for Injury Prevention in a Resource-Limited Setting
Authors: Akinkuotu Adesola C , Purcell Laura N , Varela Carlos , Hayes Andrea , Charles Anthony
Published: August 2022

Introduction

Drowning is a public health problem that is under-reported in Africa. We sought to evaluate the epidemiology and risk factors for drownings in Malawi.

Methods

We performed a retrospective review of all pediatric (≤15 years old) patients who presented following a drowning incident to Kamuzu Central Hospital in Lilongwe, Malawi, from 2009–19. Demographics and outcomes were compared between survivors and non-survivors. Logistic multivariate regression analysis was used to identify factors associated with increased odds of mortality.

Results

There were 156 pediatric drowning victims during the study period. The median age at presentation was 3 (IQR: 2–7 years). Survivors were younger [median age: 2 years (IQR: 2–5) vs. 5 years (IQR: 2–10), p = 0.004], with a higher proportion of drownings occurring at home (85.6% vs. 58.3%, p = 0.001) compared to non-survivors. Patients who had a drowning event at a public space had increased odds of mortality (OR 8.17, 95% CI 2.34–28.6). Patients who were transferred (OR 0.03, 95% CI 0.003–0.25) and had other injuries (OR 0.20, 95% CI 0.06–0.70) had decreased odds of mortality following drowning.

Conclusion

Over half of pediatric drowning victims at a tertiary-care facility in Malawi survived. Drowning survivors were significantly younger, more likely to have drowned at home, and transported by private vehicles and minibus than non-survivors. There is a need for scalable, cost-effective drowning prevention strategies that focus on water safety education and training community members and police officers in basic life support and resuscitation.
Safety of Booster Doses of Coronavirus Disease 2019 (COVID-19) Vaccine in Pregnancy in the Vaccine Adverse Event Reporting System
Authors: Moro Pedro L. , Olson Christine K. , Zhang Bicheng , Marquez Paige , Strid Penelope
Published: August 2022

OBJECTIVE:

To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, in pregnant people who received a booster dose of mRNA coronavirus disease 2019 (COVID-19) vaccine.

METHODS:

We searched VAERS for U.S. reports of adverse events in pregnant people who received a booster dose of an mRNA COVID-19 vaccine from September 22, 2021, to March 24, 2022. Clinicians reviewed reports and available medical records.

RESULTS:

The Vaccine Adverse Event Reporting System received 323 reports of adverse events in pregnant people who received a booster dose of COVID-19 vaccine; 178 (55.1%) after BNT162b2 from Pfizer–BioNTech and 145 (44.9%) after mRNA-1273 from Moderna. Seventy-two (22.3%) reports were coded as serious. One neonatal death was reported, but no maternal deaths occurred. Pregnancy-specific outcomes included 56 (17.3%) spontaneous abortions (before 20 weeks of gestation), eight (2.5%) episodes of vaginal bleeding, five (1.5%) stillbirths (at or after 20 weeks of gestation), four (1.2%) episodes of preeclampsia, and two (0.6%) preterm deliveries. Reporting rates for stillbirth and preterm delivery were below background rates. Ten instances of adverse events in neonates were reported, which included two reports of birth defects. Non–pregnancy-specific adverse events (n=207; 64.1%) were mostly systemic (eg, headache, fatigue) and local reactions and occurred in proportions comparable with those seen in pregnant people who received the primary COVID-19 vaccination series and reported to VAERS during the same period.

CONCLUSION:

Review of reports after a booster dose of mRNA COVID-19 vaccine in pregnant people in VAERS found their safety profile was comparable with that of published reports after primary COVID-19 vaccination in pregnant people.
Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis
Authors: Andia Isabel , Atilano Leire , Maffulli Nicola
Published: August 2022

Knee osteoarthritis (OA) is a common condition, prevalent in middle-agedness, associated with chronic pain and impaired quality of life. Two interrelated biological processes fuel early OA progression: inflammation and structural tissues catabolism. Procatabolic and proinflammatory mediators are interconnected and form part of a self-perpetuating loop. They leverage OA research complexity because of the impossibility to discern certain spatiotemporal tissues’ changes from others. Both are shared targets of versatile regenerative multimolecular therapies. In particular, platelet-rich plasma can interfere with inflammation and inflammatory pain. The therapeutic approach is to alter the vicious inflammatory loop by modifying the molecular composition of the synovial fluid, thereby paracrine cellular cross talk. Intra-articular injections of platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors, targeting macrophage dysfunction and modulating immune mechanisms within the knee.
A unique global metabolic trait of Pseudomonas bharatica CSV86T: metabolism of aromatics over simple carbon sources and co-metabolism with organic acids
Authors: Dhamale Tushar , Saha Braja Kishor , Papade Sandesh E. , Singh Srushti , Phale Prashant S.
Published: August 2022

Hierarchical utilization of substrate by microbes (utilization of simple carbon sources prior to complex ones) poses a major limitation to the efficient remediation of aromatic pollutants. Aromatic compounds, being complex and reduced in nature, appear to be a deferred choice as the carbon source in the presence of a plethora of simple organic compounds in the environment. The soil bacterium Pseudomonas bharatica CSV86T displays a unique carbon source utilization hierarchy. It preferentially utilizes aromatics over glucose and co-metabolizes them with succinate or pyruvate (Basu et al., 2006, Applied and Environmental Microbiology, 72 : 22226–2230). In the present study, the substrate utilization hierarchy for strain CSV86T was tested for additional simple carbon sources such as glycerol, acetate, and tri-carboxylic acid (TCA) cycle intermediates like α-ketoglutarate and fumarate. When grown on a mixture of aromatics (benzoate or naphthalene) plus glycerol, the strain displayed a diauxic growth profile with significantly high activity of aromatic utilization enzymes (catechol 1,2- or 2,3-dioxygenase, respectively) in the first-log phase. This suggests utilization of aromatics in the first-log phase followed by glycerol in the second-log phase. On a mixture of an aromatic plus organic acid (acetate, α-ketoglutarate or fumarate), the strain displayed a monoauxic growth profile, indicating co-metabolism. Interestingly, the presence of glycerol, acetate, α-ketoglutarate or fumarate does not repress metabolism/utilization of the aromatic. Thus, the substrate utilization hierarchy of strain CSV86T is aromatics=organic acids>glucose/glycerol, which is unique as compared to other

Pseudomonas

species, where degradation of aromatics is repressed by glycerol, glucose, acetate or organic acids, including TCA cycle intermediates. This novel substrate utilization hierarchy appears to be a global metabolic phenomenon in strain CSV86T, thus implying it to be an ideal host for metabolic engineering as well as for its potential application in bioremediation.
MUC5AC genetic variation is associated with tuberculosis meningitis CSF cytokine responses and mortality
Authors: Sabo Michelle C. , Thuong Nguyen T.T. , Chang Xuling , Ardiansyah Edwin , Tram Trinh T.B. , Hai Hoang T. , Nghia Ho D.T. , Bang Nguyen D. , Dian Sofiati , Ganiem A. Rizal , Kumar Vinod , Li Zheng , Hibberd Martin , Khor Chiea Chuen , Thwaites Guy E. , Heemskerk Dorothee , van Laarhoven Arjan , van Crevel Reinout , Dunstan Sarah J. , Shah Javeed A.
Published: August 2022

Rationale

Lung mucins are an understudied component of the mucosal immune response and may influence tuberculosis pathogenesis and outcomes.

Objectives

To assess if variants in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis immune responses, susceptibility, and outcomes.

Methods

We characterized four haplotype tagging single nucleotide polymorphisms (SNPs) in MUC5B and MUC5AC for association with log2 TNF concentrations in cerebral spinal fluid (CSF) from TBM patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal TB susceptibility and TBM mortality.

Measurements and Main Results

MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF(p=1.8*10−8) and IFNγ(p=2.3*10−6), and higher TBM, but not pulmonary TB, susceptibility (OR 1.24, 95% confidence interval 1.03, 1.49; p=0.021). Mortality from TBM was higher among participants with the rs28737416 T/T and T/C genotype (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank p=0.005) in a Vietnamese cohort (N=211). This finding was confirmed in an independent Vietnamese validation cohort (N=87; 9/87, 19.1% vs 1/20, 2.5%; log-rank p=0.02) and an Indonesian validation cohort (N=468, 127/287, 44.3% vs 65/181, 35.9%, log-rank p=0.06).

Conclusions

The MUC5AC rs28737416 T/T and T/C genotypes were associated with higher susceptibility and mortality from TBM and lower CSF concentrations of TNF and IFNγ compared to the C/C genotype, suggesting that MUC5AC contributes to immune changes that influence TBM outcomes.
Completeness and consistency of ethnicity categorisations in administrative data: A comparison between linked health and education datasets
Authors: Wickersham Alice , Das-Munshi Jayati , Ford Tamsin , Stewart Robert , Downs Johnny
Published: August 2022

Background

Ethnicity data are critical for identifying inequalities in the population, but previous studies suggest that it is not consistently recorded between different administrative datasets. With researchers increasingly leveraging cross-domain data linkages, we aimed to investigate the completeness and consistency of ethnicity data in two linked health and education datasets.

Methods

We used an existing individual-level data linkage between South London and Maudsley NHS Foundation Trust de-identified electronic health records, accessed via the Clinical Record Interactive Search (CRIS), and the National Pupil Database (NPD) (2007-2013). For a cohort of children and adolescents referred to Child and Adolescent Mental Health Services, we used descriptive statistics to summarise the availability of ethnicity data from each source and explore how aggregate ethnicity (White, Black, Asian, Mixed and Other) compared between the sources. We also conducted unadjusted logistic regression analyses to estimate how ethnicity was associated with two key educational and clinical outcomes (educational attainment and neurodevelopmental disorder) when coding ethnicity from each source.

Results

Of the n=30,426 available linked records, ethnicity data was available for 79.3% from the NPD, 87.0% from CRIS, 97.3% from either source and 69.0% from both sources. Among those who had ethnicity data from both, the two data sources agreed on 87.0% of aggregate ethnicity categorisations overall, but with high levels of disagreement in Mixed and Other ethnic groups. Strength of the associations between ethnicity, educational attainment and neurodevelopmental disorder varied according to which data source was used to code ethnicity. For example, as compared to White pupils, a significantly higher proportion of Asian pupils achieved expected educational attainment thresholds only if ethnicity was coded from the NPD (OR=1.85, 95% CI=1.48 to 2.31, p<0.001), not if ethnicity was coded from CRIS (OR=1.18, 95% CI=0.97 to 1.44, p=0.099).

Conclusions

Data linkage has the potential to minimise missing ethnicity data, and overlap in ethnicity categorisations between CRIS and the NPD was generally high. However, choosing which data source to primarily code ethnicity from can have implications for analyses of ethnicity, mental health, and educational outcomes. Users of linked data should exercise caution in combining and comparing ethnicity between different data sources.
Selective Androgen Receptor Modulator Microparticle Formulation Reverses Muscle Hyperalgesia in Mouse Model of Widespread Muscle Pain
Authors: Lesnak Joseph B. , Nakhla David S. , Plumb Ashley N. , McMillan Alexandra , Saha Sanjib , Gupta Nikesh , Xu Yan , Phruttiwanichakun Pornpoj , Rasmussen Lynn , Meyerholz David K. , Salem Aliasger K. , Sluka Kathleen A.
Published: August 2022

Currently, there is a need for the generation of non-opioid analgesics for treating chronic pain. Preclinical and clinical studies demonstrate the analgesic effects of testosterone. However, treatment with testosterone is not feasible due to adverse effects. Selective androgen receptor modulators (SARMs) were developed to overcome these limitations by minimizing activation of androgenic side effects. First, we demonstrate SARM administration alleviates widespread muscle pain in male and female mice. We then developed a SARM-loaded PLGA microparticle formulation that reverses widespread muscle pain in two injections. In vitro and in vivo release kinetics demonstrate the microparticle formulation had sustained SARM release for 4 weeks. Antagonism of androgen receptors blocked the analgesic effects of the SARM microparticles. SARM treatment had no effect on cardiac or liver enzymes, cardiac histology, and did not produce rewarding behavior. These studies demonstrate SARM microparticles as a potential therapeutic for chronic muscle pain.

One Sentence Summary

A selective androgen receptor modulator microparticle formulation alleviates widespread muscle pain in male and female mice while being non-toxic.
Regulation of Auditory Sensory Neuron Diversity by Runx1
Authors: Shrestha Brikha R , Wu Lorna , Goodrich Lisa V
Published: August 2022

Functional heterogeneity among sensory neurons is a cardinal property of the vertebrate auditory system, yet it is not known how this heterogeneity is established to ensure proper encoding of sound. Here, we show that the transcription factor Runx1 controls the composition of molecularly and physiologically diverse sensory neurons (Ia, Ib, Ic) in the murine cochlea, which collectively encode a wide range of sound intensities. Runx1 is enriched in Ib and Ic spiral ganglion neuron (SGN) precursors by late embryogenesis. Loss of Runx1 from embryonic SGNs (Runx1CKO) shifted the balance of subtype identities without affecting neuron number, with more SGNs taking on Ia identities at the expense of Ib/Ic identities, as shown by single cell RNA-sequencing. This conversion was more complete for genes linked to neuronal function than for those related to connectivity. Accordingly, although synaptic position did not change, synapses in the Ib/Ic location took on Ia-like properties. Suprathreshold responses to sound were enhanced in the auditory nerve of Runx1CKO mice, confirming an expansion of neurons behaving functionally like Ia SGNs. Fate-mapping experiments further showed that deletion of Runx1 shortly after birth also redirected Ib and Ic SGNs towards Ia identity, indicating that SGN subtype identities remain plastic postnatally. Altogether, these findings show that diverse neuronal identities essential for normal auditory stimulus coding arise in a hierarchical fashion that remains malleable during postnatal development.
Amygdala hyperactivation relates to eating behavior: a potential indicator of food addiction in Prader-Willi syndrome
Authors: Strelnikov Kuzma , Debladis Jimmy , Salles Juliette , Valette Marion , Cortadellas Julie , Tauber Maithé , Barone Pascal
Published: August 2022

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder involving nutritional, endocrine /metabolic, emotional and behavior dimensions. There is evidence for impaired hypothalamic development and function in PWS, involving oxytocin and ghrelin, which can account for the typical PWS phenotype. Hyperphagia with addiction-like behavior is one of the common features of PWS and is a consequence of the hypothalamic dysfunction. In this study, we hypothesized that brain regions associated with compulsive eating behavior would be abnormally activated by food-related odors in PWS, as these can stimulate the appetite and induce hunger-related behavior.

Methods

We used a classic olfactory discrimination test to verify that olfaction was normal in patients with PWS. In an fMRI scanner, we presented two odors, a tulip and a caramel odor, which have a different hedonic valence and a different capacity to arouse hunger-related behavior.

Results

There was a five-fold higher activation in the right amygdala for the caramel odor compared with the tulip odor in patients with PWS (n=14). No such hyperactivation was found in age-matched controls (n=11). Cluster analysis of clinical hyperphagia scores in patients with PWS revealed a link with the right amygdala hyperactivation.

Conclusions

Our study provides evidence for functional alteration of the right amygdala in PWS, which is part of the brain reward network involved in food addiction. This finding may relate to dysfunction of the ghrelin and oxytocin systems in PWS, as these are involved in addictive behavior, appetite, and olfactory bulb regulation.
Current state of prevention of mother-to-child transmission of HIV in informal health centers in Douala and Ebolowa, Cameroon
Authors: Amboua-Schouamé Lydie Audrey , Bigna Jean Joel , Schouamé Isacar Lucel , Nolna Sylvie Kwedi , Socpa Antoine
Published: August 2022

Background

Informal health care providers are key actors for health care provision in developing countries for poor populations. Thus, in Cameroon, in 2017, there were more than 3,000 Informal Health facilities. In a context of elimination of mother-to-child transmission of HIV, we describe the offer of Prevention of Mother to Child Transmission of HIV (PMTCT) in informal health centers.

Methods

This two-phase cross-sectional study was carried out in two cities in Cameroon notably Douala and Ebolowa. The first step was conducted from March 2019 to July 2019 in 110 informal health centers and the second from August 2019 to January 2020 with 183 Health Providers in these informal health centers. Standardized questionnaires were administered. Data collected were entered in kobo Collect software. Descriptive statistics and logistic regression at a level of significance of 5% were used.

Results

Of the 110 informal health centers, 109 integrated HIV testing into the antenatal check-up package. Among them, 43% (47/109) reported giving antiretroviral treatment to HIV infected pregnant women, while the remaining referred them to formal HIV care centers. Regarding delivery services, 52% (53/101) of those who offered them referred HIV exposed newborn for further PMTCT care. Knowledge of PMTCT was insufficient among 51% (94/183) of health providers and 90% (165/183) had insufficient PMTCT practices. Health providers with no PMTCT experience were more likely to have insufficient knowledge of PMTCT (aOR= 32.04, 95%CI: 6.29 to 163.10, p<0.001) whereas, those without any formal PMTCT training were more at risk of having insufficient knowledge (aOR= 3.02, 95%CI: 1.06 to 8.64, p=0.03) and insufficient practices (OR= 4.35, 95%CI: 1.44 to 13.09, p=0.009) towards PMTCT.

Conclusion

Given their proximity to the populations and the PMTCT activities they conduct most often; particular attention should be paid to PMTCT in informal health centers.
Rationally designed Gla-domainless FXa as TFPI bait in hemophilia
Authors: Dagher Marie-Claire , Ersayin Atanur , Seyve Landry , Castellan Mathieu , Moreau Cyril , Choisnard Luc , Thielens Nicole , Marlu Raphaël , Polack Benoît , Thomas Aline
Published: August 2022

Gla-domainless factor Xa (GD-FXa) was proposed as a trap to the endogenous anticoagulant Tissue Factor Pathway Inhibitor (TFPI) to restore thrombin generation in hemophilia. Using computational chemistry and experimental approaches, we previously showed that S195A GD-FXa also binds TFPI and restores ex vivo coagulation in hemophilia plasmas.

To design a GD-FXa variant with improved anti-TFPI activity and identify suitable sites for mutagenesis, we performed molecular dynamics simulations. The calculations identified residues R150FXa and K96FXa as cold-spots of interaction between GD-FXa and the K2 domain of TFPI. In the three-dimensional model, both residues are facing TFPI hydrophobic residues and are thus potential candidates for mutagenesis into hydrophobic residues to favor an improved protein-protein interaction.

Catalytically inactive GD-FXa variants containing the S195A mutation and additional mutations as K96Y, R150I, R150G and R150F were produced to experimentally confirm these computational hypotheses. Among these mutants, the R150FFXA showed increased affinity for TFPI as theoretically predicted, and was also more effective than S195A GD-FXa in restoring coagulation in FVIII deficient plasmas. Moreover, the R150 mutants lost interaction with antithrombin, which is favorable to extend their half-life.