bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonpharmacological treatment for coping with pain
Authors: Torres-Ortuño Ana
Published: May 2023

Pain is one of the most common reasons for consultation and one of the most difficult tasks to handle for doctors. If it is chronic, the frequency of disorders increases associates that we cannot exclude from the treatment, and further complicates your treatment. The Asociation International Association for the Study of Pain (IAPS)1 defines the pain as “a sensory and emotional experience unpleasant associated with actual or potential tissue damage, or described in terms of such damage”. So the pain is not only a nociceptive experience, but also involves emotional and subjective components, considering that It can even occur without a somatic cause justify. Its nature is complex, including factors biological and others such as subjective experience, education and emotion. Therefore pain is a personal, multidimensional problem, unique experience and non-transferable of the person who suffers it. Being a pharmacological and non-pharmacological approach is necessary for its management
Interferon regulatory factor-8-dependent innate immune alarm senses GATA2 deficiency to alter hematopoietic differentiation and function
Authors: Johnson Kirby D. , Jung Mabel M. , Tran Vu L. , Bresnick Emery H.
Published: May 2023

Purpose of review

Recent discoveries have provided evidence for mechanistic links between the master regulator of hematopoiesis GATA2 and the key component of interferon and innate immunity signaling pathways, interferon-regulatory factor-8 (IRF8). These links have important implications for the control of myeloid differentiation in physiological and pathological states.

Recent findings

GATA2 deficiency resulting from loss of the Gata2 −77 enhancer in progenitors triggers an alarm that instigates the transcriptional induction of innate immune signaling and distorts a myeloid differentiation program. This pathological alteration renders progenitors hyperresponsive to interferon γ, toll-like receptor and interleukin-6 signaling and impaired in granulocyte-macrophage colony-stimulating factor signaling. IRF8 upregulation in −77−/− progenitors promotes monocyte and dendritic cell differentiation while suppressing granulocytic differentiation. As PU.1 promotes transcription of Irf8 and other myeloid and B-lineage genes, GATA2-mediated repression of these genes opposes the PU.1-dependent activating mechanism.

As GATA2 deficiency syndrome is an immunodeficiency disorder often involving myelodysplastic syndromes and acute myeloid leukemia, elucidating how GATA2 commissions and decommissions genome activity and developmental regulatory programs will unveil mechanisms that go awry when GATA2 levels and/or activities are disrupted.
Chediak-Higashi syndrome
Authors: Talbert Mackenzie L. , Malicdan May Christine V. , Introne Wendy J.
Published: May 2023

Purpose of review

Chediak-Higashi syndrome is a rare autosomal recessive disorder characterized by congenital immunodeficiency, bleeding diathesis, pyogenic infection, partial oculocutaneous albinism, and progressive neurodegeneration. Treatment is hematopoietic stem cell transplantation or bone marrow transplantation; however, this does not treat the neurologic aspect of the disease. Mutations in the lysosomal trafficking regulator (LYST) gene were identified to be causative of Chediak-Higashi, but despite many analyses, there is little functional information about theLYSTprotein. This review serves to provide an update on the clinical manifestations and cellular defects of Chediak-Higashi syndrome.

Recent findings

More recent papers expand the neurological spectrum of disease in CHS, to include hereditary spastic paraplegia and parkinsonism. Granule size and distribution in NK cells have been investigated in relation to the location of mutations in LYST. Patients with mutations in the ARM/HEAT domain had markedly enlarged granules, but fewer in number. By contrast, patients with mutations in the BEACH domain had more numerous granules that were normal in size to slightly enlarged, but demonstrated markedly impaired polarization. The role of LYST in autophagosome formation has been highlighted in recent studies; LYST was defined to have a prominent role in autophagosome lysosome reformation for the maintenance of lysosomal homeostasis in neurons, while in retinal pigment epithelium cells, LYST deficiency was shown to lead to phagosome accumulation.

Despite CHS being a rare disease, investigation into LYST provides an understanding of basic vesicular fusion and fission. Understanding of these mechanisms may provide further insight into the function of LYST.
Crosstalk between terminal erythropoiesis and granulopoiesis within their common niche: the erythromyeloblastic island
Authors: Romano Laurel , Seu Katie G. , Blanc Lionel , Kalfa Theodosia A.
Published: May 2023

Purpose of review

The identity of the erythroblastic island (EBI) macrophage (Mϕ) has been under investigation for decades since it was recognized as the first hematopoietic niche ‘nursing’ terminal erythropoiesis. This review will focus on the current insights to the characteristics and the role of the EBI Mϕ balancing terminal erythropoiesis and granulopoiesis.

Recent findings

While the EBI has long been known as the niche for erythroid precursors, significant advancements in biology research technologies, including optimization of EBI enrichment protocols, single-cell ribonucleic acid sequencing, and imaging flow cytometry, have recently revealed that granulocytic precursors co-exist in this niche, termed erythromyeloblastic island (EMBI). More importantly, the balance noted at baseline between terminal granulopoiesis and erythropoiesis within EBIs/EMBIs is altered with diseases affecting hematopoiesis, such as stress erythropoiesis and inflammatory conditions causing anemia of inflammation. The role of the EMBI niche has yet to be fully investigated mechanistically, however, a notable degree of transcriptional and cell surface marker heterogeneity has been identified for the EMBI Mϕ, implicating its plasticity and diverse function.

Terminal erythropoiesis and granulopoiesis are regulated within the EMBI. Investigations of their balance within this niche in health and disease may reveal new targets for treatment of diseases of terminal hematopoiesis.
Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition
Authors: Norsa Lorenzo , Goulet Olivier , Alberti Daniele , DeKooning Barbara , Domellöf Magnus , Haiden Nadja , Hill Susan , Indrio Flavia , Kӧglmeier Jutta , Lapillonne Alexandre , Luque Veronica , Moltu Sissel J. , Saenz De Pipaon Miguel , Savino Francesco , Verduci Elvira , Bronsky Jiri
Published: May 2023

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.
Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure
Authors: Chapin Catherine A. , Diamond Tamir , Harris Rebecca M. , Vaccaro Olivia , Loomes Kathleen M. , Alonso Estella M. , Behrens Edward M.
Published: May 2023

There has been a recent surge in cases of pediatric acute hepatitis and pediatric acute liver failure (PALF) of unknown cause. Several reports have described clusters of these children who were positive for adenovirus (AdV) DNA, primarily in peripheral blood but some in liver tissue. We tested archived liver tissue specimens from a historical cohort of 44 children with PALF who were enrolled in a multicenter biorepository between 2007 and 2014 for AdV 40/41 using quantitative polymerase chain reaction. Most children had final diagnosis indeterminate. All samples were negative. Our findings suggest that AdV was unlikely to be an unidentified cause of indeterminate PALF during this past era. The significance of AdV viremia in contemporary cohorts of children with PALF remains unknown and requires further study.
Use of Elastomeric Half-Mask Respirator in the Clinical Care Environment
Authors: Bryant Ruth A. , Smith Justin M. , Tervola Ned K. , Smith Claire , Hoyt Cecely , Dawud Barite , Dugan Siobhán , St. Hill Catherine A.
Published: May 2023

Background:

Elastomeric half-mask respirators (EHMR) reduce health care workers' exposure to airborne hazards including bioaerosols but have primarily been used in the industrial setting.

Purpose:

To assess health care workers' perceptions, attitudes, and experiences wearing EHMRs in a clinical environment.

Methods:

Employees within a single health care system who wore the EHMR continuously during their shift completed an investigator developed survey. Descriptive statistics and thematic analysis were used.

Results:

Of the 8273 EHMR “fit-tested” eligible employees, 1478 met inclusion criteria and participated. Respondents reported that they felt well protected with the EHMR and confident in their care and maintenance of the EHMR. Although skin changes developed, they were primarily managed by adjusting the straps. Clarity of communication was a concern across all respondents and disciplines.

Conclusions:

The EHMR was preferred over reusing the N95 although clarity in communication was challenging.
Preferences for Rectal STI Sample Collection and Sexual Behaviors Among Adolescent and Young Adult Women Accessing Primary Care Services
Authors: Woods Hannah E. , Schuh Aaron M. , Gaydos Charlotte A. , Fenchel Matthew , Kowalczyk Mullins Tanya L. , Conard Lee Ann E. , Manabe Yukari C. , Widdice Lea E
Published: May 2023

Background

High prevalence of asymptomatic rectal chlamydia and gonorrhea (CT/NG) among women is increasingly recognized. Screening is controversial due to lack of natural history data. Barriers to screening may include reluctance to discuss anal sex and collect rectal samples. This study describes the prevalence of sexual contact exposing adolescent and young adult (AYA) women to extragenital STIs and acceptability of self- and clinician-collection of rectal samples, preference for self- versus clinician-collected rectal samples and preference for home or doctor’s office for sample collection.

Methods

Participants were recruited from a primary care office and completed structured interviews assessing types of sexual contact and attitudes about rectal sampling. Differences were tested using chi-square and two-sided Fisher’s exact test.

Results

Of 110 cisgender women (aged 14-22 years) enrolled, the average age was 18.4 years (SD 1.7); 83% reported a history of extragenital contact; 22% reported history of receptive anal intercourse. A majority of participants reported self- and clinician-collected rectal samples to be acceptable (86% and 73%, respectively), with preferences for self-collection (71%) over clinician-collection (29%, p < 0.001) and collection at the doctor’s office (85%) over home (15%, p < 0.001).

Conclusions

AYA women engage in behaviors that increase risk for rectal STI. Self- and clinician-collected rectal samples were acceptable. A majority of AYA women preferred to collect rectal samples in the doctor’s office rather than at home. This may reduce adolescents’ access to direct-to-consumer STI services. Offering in-clinic, self-collected rectal samples may improve uptake of rectal STI screening in adolescent females.
Herpes Zoster after Botulinum Toxin Combined with Hyaluronic Acid Injection
Authors: Zhuang Jun , Liu Tun , Hu Jintian
Published: May 2023

Botulinum toxin and hyaluronic acid injections are commonly used in plastic surgery. However, these treatment methods can also cause adverse events. This article reports a case of herpes zoster that occurred several days after botulinum toxin and hyaluronic acid injections. Antiviral treatment of herpes zoster virus proved successful in managing this complication. Furthermore, several articles concerning injection therapy-induced herpes zoster are reviewed. It is suggested that clinicians should consider herpes zoster in the differential diagnosis of unilateral erythema and papules, following injection therapy, in order to provide timely treatment.
Application of a Single T-Shaped Porous High-Density Polyethylene in Oriental Nasal Tip-Plasty
Authors: Peng Su , Huang Xin , Gu Tianya , Liang Yan , Yu Lei , Wu Jie , Guo Zongke , Lin Jinde
Published: May 2023

Porous high-density polyethylene (pHDPE) is an alternative material for septal extension grafts. This study investigated the clinical application of a single T-shaped pHDPE graft combined with auricular cartilage in oriental nasal tip-plasty. A retrospective analysis was conducted of 66 patients who underwent septal extension graft with a T-shaped pHDPE and auricular cartilage graft from December 2018 to November 2021. All patients were female from 19 to 51 years old (average: 28.9 years). Patients were followed up for 5 to 40 months with an average of 23.8 months. The postoperative nasal length (39.8±3.7 mm) was significantly improved (35.6±5.7 mm preoperatively, P<0.0001) with the tip projection increasing from 23.9±2.3 mm preoperatively to 25.3±2.4 mm postoperatively (P=0.0005). There was a significant difference in the nasolabial angle (96.8±14.1 degrees preoperatively versus 101.8±7.2 degrees postoperatively, P=0.0105) but no significant change in the nasofrontal angle (143.3±9.5 degrees preoperatively versus 143.7±5.5 degrees postoperatively, P=0.7546), with an improved tip projection achieved in 93.9% of patients. One patient had an abscess in the nasal septum and a tip graft was performed using auricular cartilage in another patient because of an insufficient postoperative tip projection. There was a slight tip deviation in 2 patients, 1 case of a deviated nasal tip was corrected with a pHDPE sheet graft, while the other was left intact. Two patients had excess cartilaginous graft protruding to the nasal cavity that did not affect nasal ventilation and the shape of the nasal tip was relatively good, so the prominent cartilaginous graft was not addressed. In conclusion, this technique not only improved the bulbous nasal tip, lengthened the short nose, and increase the tip projection, but also prevented absorption of the existing septal cartilage and reduced infection or extrusion of the pHDPE.
Correlations between oxidative DNA damage and formation of hepatic tumours in two flatfish species from contaminated environments
Authors: Baines Ciara , Meitern Richard , Kreitsberg Randel , Fort Jérôme , Scharsack Jörn Peter , Nogueira Pedro , Giraudeau Mathieu , Sepp Tuul
Published: May 2023

Many species in aquatic environments face increased exposure to oncogenic pollution due to anthropogenic environmental change which can lead to higher cancer prevalence. The mechanistic relationship connecting environmental pollution and cancer is multi-factorial and poorly understood, and the specific mechanisms are so far still uncharacterized. One potential mediator between pollutant exposure and cancer is oxidative damage to DNA. We conducted a study in the field with two flatfish species, European flounder (
Platichthys flesus
L.) and common dab (
Limanda limanda L.
) with overlapping distribution and similar ecological niche, to investigate if the link between oncogenic pollutants and cancer described in ecotoxicological literature could be mediated by oxidative DNA damage. This was not the case for flounders as neither polycyclic aromatic hydrocarbon (PAH) bile metabolites nor metallic trace element concentrations were related to oxidative DNA damage measurements. However, dabs with higher PAH concentrations did exhibit increased oxidative damage. High oxidative DNA damage also did not predict neoplasm occurrence, rather, healthy individuals tended to have higher oxidative damage measurements compared to fishes with pre-neoplastic tumours. Our analyses showed that flounders had lower concentrations of PAH bile metabolites, suggesting that compared to dab this species is less exposed or better at eliminating these contaminants.
Multi-scale dissection of wing transparency in the clearwing butterfly
Phanus vitreus
Authors: Finet Cédric , Ruan Qifeng , Bei Yi Yang , You En Chan John , Saranathan Vinodkumar , Yang Joel K. W. , Monteiro Antónia
Published: May 2023

Optical transparency is rare in terrestrial organisms, and often originates through loss of pigmentation and reduction in scattering. The coloured wings of some butterflies and moths have repeatedly evolved transparency, offering examples of how they function optically and biologically. Because pigments are primarily localized in the scales that cover a colourless wing membrane, transparency has often evolved through the complete loss of scales or radical modification of their shape. Whereas bristle-like scales have been well documented in glasswing butterflies, other scale modifications resulting in transparency remain understudied. The butterfly
Phanus vitreus
achieves transparency while retaining its scales and exhibiting blue/cyan transparent zones. Here, we investigate the mechanism of wing transparency in
P. vitreus
by light microscopy, focused ion beam milling, microspectrophotometry and optical modelling. We show that transparency is achieved via loss of pigments and vertical orientation in normal paddle-like scales. These alterations are combined with an anti-reflective nipple array on portions of the wing membrane being more exposed to light. The blueish coloration of the
P. vitreus
transparent regions is due to the properties of the wing membrane, and local scale nanostructures. We show that scale retention in the transparent patches might be explained by these perpendicular scales having hydrophobic properties.
Thermomonas mangrovi sp. nov., isolated from soil of a mangrove nature reserve
Authors: Xu Shanshan , Chen Junpeng , Chen Si , Lai Qiliang , Liu Zengzhi , Xu Ying
Published: May 2023

A Gram-stain-negative, non-motile, aerobic and ovoid-rod-shaped bacterial strain, designated as 2C3345T, was isolated from soil of a mangrove nature reserve in Shenzhen, PR China and its taxonomic position was investigated. The 16S rRNA gene sequence of strain 2C3345T exhibited the highest similarity value to that of the type strains

Thermomonas aquatica

NBRC 113114T (98.4 %),

Thermomonas carbonis

KCTC 42013T (98.1 %),

Thermomonas brevis

DSM 15422T (98.0 %) and

Thermomonas haemolytica

DSM 13605T (97.9 %). Strain 2C3345T grew optimally at 28–30 °C, pH 7.0 and without NaCl. The predominant ubiquinone in 2C3345T was identified as Q-8. The major fatty acids of 2C3345T were iso-C15 : 0, iso-C16 : 0 and summed feature 9 (is0-C17:1ω9c and/or 10-methyl C16:0). The major polar lipids of 2C3345T were phosphatidylcholine (PC), phosphatidylglycerol (PG), diphosphatidglycerol (DPG), phosphatidylethanolamine (PE), an unidentified phospholipid, an unidentified aminolipid and two unidentified lipids. The DNA G+C content of strain 2C3345T was 69.9 %. The draft genome sequence of 2C3345T included 2 888 645 bp in total (N50
=310 730 bp) with a medium read coverage of 388.6×and 21 scaffolds. In silico DNA–DNA hybridisation with type strains of species of the genus

Thermomonas

showed 24.4, 22.4, 24.1 and 23.2% relatedness to

T. aquatica

NBRC 113114T,

T. carbonis

KCTC 42013T,

T. brevis

DSM 15422T and

T. haemolytica

DSM 13605T, respectively. And the average nucleotide identity by blast (ANIb) values between 2C3345T and these four reference strains were 81.9, 80.0, 81.2 and 80.6 %, respectively, lower than the 95–96% threshold value for dividing prokaryotic species. On the basis of its phenotypic, chemotaxonomic, phylogenetic and phylogenomic properties, strain 2C3345T is considered to represent a novel species within the genus

Thermomonas

, for which the name Thermomonas mangrovi sp. nov. is proposed. The type strain is 2C3345T (=KCTC 92730T =MCCC 1K08335T).
Streptomyces cylindrosporus sp. nov. and Streptomyces spinosisporus sp. nov.: two new endophytic actinobacteria isolated from the roots of Barleria lupulina Lindl.
Authors: Kanchanasin Pawina , Sripreechasak Paranee , Suriyachadkun Chanwit , Rueangsawang Kanokorn , Tanasupawat Somboon , Phongsopitanun Wongsakorn
Published: May 2023

Two endophytic actinobacteria, designated as strains 7R015T and 7R016T, were isolated from the roots of Barleria lupulina collected in Thailand. The morphological characteristics and results of chemotaxonomic studies and 16S rRNA gene analysis indicated that both strains represented members of the genus

Streptomyces

. They contained ll-diaminopimelic acid in the peptidoglycan. Ribose and glucose were detected as the whole-cell sugars. MK-9(H4), MK-9(H6) and MK-9(H8), were found as the membrane menaquinone. The predominant cellular fatty acids detected were iso-C16 : 0 and anteiso-C15 : 0. The genomes of both strains harboured biosynthetic gene clusters for melanin, terpene, lanthipeptide, polyketides, non-ribosomal peptide synthetase, siderophore and ectoine. The 16S rRNA gene sequence of 7R015T showed the highest similarity to that of

Streptomyces pseudovenezuelae

DSM 40212T (98.6 %),

Streptomyces cyaneus

NRRL B2296T (98.6 %) and

Streptomyces curacoi

DSM 40107T (98.6 %). Strain 7R016T showed the highest 16S rRNA gene sequence similarity to

Streptomyces gilvifuscus

NBRC 110904T (98.2 %), which is lower than the threshold value for 16S rRNA gene sequence similarity for differentiation at the species level (98.65 %). Comparative genome analysis revealed that the genomes of 7R015T, 7R016T and the closely related type strains had an average nucleotide identity (ANI) of less than 95 % and a digital DNA–DNA hybridisation (dDDH) of less than 70 %, the thresholds for species demarcation. On the basis of the results of the polyphasic study, strains 7R015T and 7R016T represent novel species of the genus

Streptomyces

and are named herein as Streptomyces cylindrosporus sp. nov. (=NBRC 115200T = TBRC 14542T) for strain 7R015T and Streptomyces spinosisporus sp. nov. (=NBRC 115201T = TBRC 14543T) for strain 7R016T.
Characterisation of populations at risk of sub-optimal dosing of artemisinin-based combination therapy in Africa
Authors: Takyi Abena , Carrara Verena I. , Dahal Prabin , Przybylska Marianna , Harriss Eli , Insaidoo Genevieve , Barnes Karen I. , Guerin Philippe J , Stepniewska Kasia
Published: May 2023

Introduction

Selection of resistant malaria strains occurs when parasites are exposed to inadequate antimalarial drug concentrations. The proportion of uncomplicatedfalciparummalaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown. This study aims to estimate this proportion and the excess number of treatment failures (recrudescences) associated with sub-optimal dosing in Sub-Saharan Africa.

Methods

Sub-populations at risk of sub-optimal dosing include wasted children <5 years of age; patients with hyperparasitaemia; pregnant women; people living with HIV; and overweight adults. Country-level data on population structure were extracted from openly accessible data sources. Pooled adjusted Hazard Ratios for PCR-confirmed recrudescence were estimated for each risk group from published meta-analyses using fixed-effect meta-analysis.

Results

In 2020, of 153.1 million uncomplicatedP. falciparummalaria patients in Africa, the largest risk groups were the hyperparasitaemic patients (13.2 million, 8.6% of uncomplicated malaria cases) and overweight adults (10.3 million, 6.7% of uncomplicated cases). The excess total number of treatment failures ranged from 323,247 for a 98% baseline ACT efficacy to 1,292,987 for a 92% baseline ACT efficacy.

Conclusion

An estimated 1 in nearly 4 people with uncomplicated confirmedP. falciparummalaria in Africa are at risk of receiving a sub-optimal antimalarial drug dosing. This increases the risk of antimalarial drug resistance and poses a serious threat to malaria control and elimination efforts. Changes in antimalarial dosing or treatment duration of current antimalarials may be needed and new antimalarials development should ensure sufficient drug concentration levels in these sub-populations that carry a high malaria burden.
Infection by SARS-CoV-2 with alternate frequencies of mRNA vaccine boosting for patients undergoing antineoplastic treatment for cancer
Authors: Townsend Jeffrey P. , Hassler Hayley B. , Emu Brinda , Dornburg Alex
Published: May 2023

Patients undergoing antineoplastic therapies often exhibit reduced immune response to COVID-19 vaccination, necessitating assessment of alternate boosting frequencies for these patients. However, data on reinfection risks to guide clinical decision-making is limited. We quantified reinfection risks of SARS-CoV-2 at different mRNA boosting frequencies of patients on antineoplastic therapies. Antibody levels following Pfizer-BioNTech BNT162b2 vaccination were analyzed for patients without cancer, with cancer undergoing various treatments, and treated with different antineoplastic therapeutics. Using long-term antibody data from other coronaviruses in an evolutionary framework, we estimated infection probabilities based on antibody levels and projected waning. We calculated cumulative probabilities of breakthrough infection for alternate booster schedules over two years. Annual boosting reduced risks for targeted or hormonal treatments, immunotherapy, and chemotherapy-immunotherapy combinations similarly to the general population. Patients receiving no treatment or chemotherapy exhibited higher risks, suggesting that accelerated vaccination schedules should be considered. Patients treated with rituximab therapy posed the highest infection risk, suggesting that a combination of frequent boosting and additional interventions may be warranted for mitigating SARS-CoV-2 infection in these patients.
Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study
Authors: Rogers Julia H. , Cox Sarah N. , Link Amy C. , Nwanne Gift , Han Peter D. , Pfau Brian , Chow Eric J. , Wolf Caitlin R. , Boeckh Michael , Hughes James P. , Halloran Elizabeth , Uyeki Timothy M. , Shim Mia , Duchin Jeffrey , Englund Janet A. , Mosites Emily , Rolfes Melissa A. , Starita Lea A. , Chu Helen Y.
Published: May 2023

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1/1/2020-5/31/2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00 – 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12 – 5.91; staff: 3.86, 95% CI 2.43 – 5.79). Most infections were asymptomatic at time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.
Antiviral activities of sotrovimab against BQ.1.1 and XBB.1.5 in sera of treated patients
Authors: Bruel Timothée , Vrignaud Lou-Léna , Porrot Françoise , Staropoli Isabelle , Planas Delphine , Guivel-Benhassine Florence , Puech Julien , Prot Matthieu , Munier Sandie , Henry-Bolland William , Soulié Cathia , Zafilaza Karen , Lusivika-Nzinga Clovis , Meledge Marie-Laure , Dorival Céline , Molino Diana , Péré Hélène , Yordanov Youri , Simon-Lorière Etienne , Veyer David , Carrat Fabrice , Schwartz Olivier , Marcelin Anne-Geneviève , Martin-Blondel Guillaume ,   the ANRS 0003S CoCoPrev Study Group
Published: May 2023

Background

Monoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.1 and XBB.1.5 evade neutralization of therapeutic mAbs, leading to recommendations against their use. Yet, the antiviral activities of mAbs in treated patients remain ill-defined.

Methods

We investigated neutralization and antibody-dependent cellular cytotoxicity (ADCC) of D614G, BQ.1.1 and XBB.1.5 in 320 sera from 80 immunocompromised patients with mild-to-moderate COVID-19 prospectively treated with mAbs (sotrovimab, n=29; imdevimab/casirivimab, n=34; cilgavimab/tixagevimab, n=4) or anti-protease (nirmatrelvir/ritonavir, n=13). We measured live-virus neutralization titers and quantified ADCC with a reporter assay.

Findings

Only Sotrovimab elicits serum neutralization and ADCC against BQ.1.1 and XBB.1.5. As compared to D614G, sotrovimab neutralization titers of BQ.1.1 and XBB.1.5 are reduced (71- and 58-fold, respectively), but ADCC levels are only slightly decreased (1.4- and 1-fold, for BQ.1.1 and XBB.1.5, respectively).

Interpretation

Our results show that sotrovimab is active against BQ.1.1 and XBB.1.5 in treated individuals, suggesting that it may be a valuable therapeutic option.
Convolutional neural network reveals frequency content of medio-lateral COM body sway to be highly predictive of Parkinson’s disease
Authors: Engel David , Greulich R. Stefan , Parola Alberto , Vinehout Kaleb , Dowiasch Stefan , Waldthaler Josefine , Timmermann Lars , Rothkopf Constantin A. , Bremmer Frank
Published: May 2023

Postural instability as a symptom of progressing Parkinson’s disease (PD) greatly reduces quality of life. Hence, early detection of postural impairments is crucial to facilitate interventions. Our aim was to use a convolutional neural network (CNN) to differentiate people with early to mid-stage PD from healthy age-matched individuals based on spectrogram images obtained from their body movement. We hypothesized the time-frequency content of body sway to be predictive of PD, even when impairments are not yet manifested in day-to-day postural control. We tracked their center of pressure (COP) using a Wii Balance Board and their full-body motion using a Microsoft Kinect, out of which we calculated the trajectory of their center of mass (COM). We used 30 s-snippets of motion data from which we acquired wavelet-based time-frequency spectrograms that were fed into a custom-built CNN as labeled images. We used binary classification to have the network differentiate between individuals with PD and controls (n=15, respectively). Classification performance was best when the medio-lateral motion of the COM was considered. Here, our network reached an average predictive accuracy of 98.45 % with a receiver operating characteristic area under the curve of 1.0. Moreover, an explainable AI approach revealed high frequencies in the postural sway data to be most distinct between both groups. Our findings suggest a CNN classifier based on cost-effective and conveniently obtainable posturographic data to be a promising approach to detect postural impairments in early to mid-stage PD and to gain novel insight into the subtle characteristics of impairments at this stage of the disease.
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C)
Authors: Bodansky Aaron , Sabatino Joseph J. , Vazquez Sara E. , Chou Janet , Novak Tanya , Moffitt Kristin L. , Miller Haleigh S. , Kung Andrew F. , Rackaityte Elze , Zamecnik Colin R. , Rajan Jayant V. , Kortbawi Hannah , Mandel-Brehm Caleigh , Mitchell Anthea , Wang Chung-Yu , Saxena Aditi , Zorn Kelsey , Yu David J.L. , Asaki James , Pluvinage John V. , Wilson Michael R. , Loftis Laura L. , Hobbs Charlotte V. , Tarquinio Keiko M. , Kong Michele , Fitzgerald Julie C. , Espinal Paula S. , Walker Tracie C. , Schwartz Stephanie P. , Crandall Hillary , Irby Katherine , Staat Mary Allen , Rowan Courtney M. , Schuster Jennifer E. , Halasa Natasha B. , Gertz Shira J. , Mack Elizabeth H. , Maddux Aline B. , Cvijanovich Natalie Z. , Zinter Matt S. , Zambrano Laura D. , Campbell Angela P. , Randolph Adrienne G. , Anderson Mark S. , DeRisi Joseph L. ,   the Overcoming COVID-19 Network Study Group Investigators
Published: May 2023

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome.
Identification and quantification of transposable element transcripts using Long-Read RNA-seq inDrosophilagermline tissues
Authors: Rebollo Rita , Gerenton Pierre , Cumunel Eric , Mary Arnaud , Sabot François , Burlet Nelly , Gillet Benjamin , Hughes Sandrine , Oliveira Daniel S. , Goubert Clément , Fablet Marie , Vieira Cristina , Lacroix Vincent
Published: May 2023

Transposable elements (TEs) are repeated DNA sequences potentially able to move throughout the genome. In addition to their inherent mutagenic effects, TEs can disrupt nearby genes by donating their intrinsic regulatory sequences, for instance, promoting the ectopic expression of a cellular gene. TE transcription is therefore not only necessary for TE transpositionper sebut can also be associated with TE-gene fusion transcripts, and in some cases, be the product of pervasive transcription. Hence, correctly determining the transcription state of a TE copy is essential to apprehend the impact of the TE in the host genome. Methods to identify and quantify TE transcription have mostly relied on short RNA-seq reads to estimate TE expression at the family level while using specific algorithms to discriminate copy-specific transcription. However, assigning short reads to their correct genomic location, and genomic feature is not trivial. Here we retrieved full-length cDNA (TeloPrime, Lexogen) ofDrosophila melanogastergonads and sequenced them using Oxford Nanopore Technologies. We show that long-read RNA-seq can be used to identify and quantify transcribed TEs at the copy level. In particular, TE insertions overlapping annotated genes are better estimated using long reads than short reads. Nevertheless, long TE transcripts (> 4.5 kb) are not well captured. Most expressed TE insertions correspond to copies that have lost their ability to transpose, and within a family, only a few copies are indeed expressed. Long-read sequencing also allowed the identification of spliced transcripts for around 107 TE copies. Overall, this first comparison of TEs between testes and ovaries uncovers differences in their transcriptional landscape, at the subclass and insertion level.
Chemogenetic approaches reveal dual functions of microglia in epilepsy
Authors: Dheer Aastha , Bosco Dale B. , Zheng Jiaying , Wang Lingxiao , Zhao Shunyi , Haruwaka Koichiro , Yi Min-Hee , Barath Abhijeet , Tian Dai-Shi , Wu Long-Jun
Published: May 2023

Microglia are key players in maintaining brain homeostasis and exhibit phenotypic alterations in response to epileptic stimuli. However, it is still relatively unknown if these alterations are pro- or anti-epileptic. To unravel this dilemma, we employed chemogenetic manipulation of microglia via of the artificial Gi-Dreadd receptor within a kainic acid (KA) induced murine seizure model. Our results indicate that Gi-Dreadd activation can reduce seizure severity. Additionally, we observed increased interaction between microglia and neuronal soma, which correlated with reduced neuronal hyperactivity. Interestingly, prolonged activation of microglial Gi-Dreadds by repeated doses over 3 days, arrested microglia in a less active, homeostatic-like state, which associated with increased neuronal loss after KA induced seizures. RNAseq analysis revealed that prolonged activation of Gi-Dreadd interferes with interferon β signaling and microglia proliferation. Thus, our findings highlight the importance of microglial activation not only duringstatus epilepticus(SE) but also within later seizure induced pathology.
Are fungi capacitors?
Authors: Szaciłowski Konrad , Beasley Alexander E. , Mech Krzysztof , Adamatzky Andrew
Published: May 2023

The emerging field of living technologies aims to create new functional hybrid materials in which living systems interface and interact with inanimate ones. Combining research into living technologies with emerging developments in computing architecture has enabled the generation of organic electronics from plants and slime mould. Here, we expand on this work by studying capacitive properties of a substrate colonised by mycelium of grey oyster fungi,Pleurotus ostreatus. Capacitors play a fundamental role in traditional analogue and digital electronic systems and have a range of uses including sensing, energy storage and filter circuits. Mycelium has the potential to be used as an organic replacement for traditional capacitor technology. Here, were show that the capacitance of mycelium is in the order of hundreds of picofarads and at the same time a voltage-dependent pseudocapacitance of the order of hundreds of microfarads. We also demonstrate that the charge density of the mycelium ‘dielectric’ decays rapidly with increasing distance from the source probes. This is important as it indicates that small cells of mycelium could be used as a charge carrier or storage medium, when employed as part of an array with reasonable density.
Dynamics of Gut Metabolome and Microbiome Maturation during Early Life
Authors: Aatsinki Anna-Katariina , Lamichhane Santosh , Isokääntä Heidi , Sen Partho , Kråkström Matilda , Alves Marina Amaral , Keskitalo Anniina , Munukka Eveliina , Karlsson Hasse , Perasto Laura , Lukkarinen Minna , Oresic Matej , Kailanto Henna-Maria , Karlsson Linnea , Lahti Leo , Dickens Alex M
Published: May 2023

Early-life gut microbiome-metabolome crosstalk has a pivotal role in the maintenance of host physiology. However, our understanding on early-life gut microbiome-metabolome maturation trajectories in humans remains limited. This study aims to explore the longitudinal patterns of gut metabolites during early life, and how they are related to gut microbiota composition in birth cohort samples of n = 670 children collected at 2.5 (n=272), 6 (n=232), 14 (n=289), and 30 months (n=157) of age.

Factor analysis showed that breastfeeding has an effect on several metabolites including secondary bile acids. We found that the prevalent gut microbial abundances were associated with metabolite levels, especially in the 2.5 months-olds. We also demonstrated that the prevalent early colonizersBacteroides, EscherichiaandBifidobacteriumabundances associated with microbial metabolites bile acids especially in the breastfed infants.

Taken together, our results suggests that as the microbiome matures during the early-life there is an association with the metabolome composition in an analogous fashion to how the genome information mature during early life.
Snow flies self-amputate freezing limbs to sustain behavior at sub-zero temperatures
Authors: Golding Dominic , Rupp Katie , Sustar Anne , Pratt Brandon , Tuthill John C.
Published: May 2023

All living things are profoundly affected by temperature. In spite of the thermodynamic constraints on biology, some animals have evolved to live and move in extremely cold environments. Here, we investigate behavioral mechanisms of cold tolerance in the snow fly (Chioneaspp.), a flightless crane fly that is active throughout the winter in boreal and alpine environments of the northern hemisphere. Using thermal imaging, we show that adult snow flies maintain the ability to walk down to an average body temperature of -7 °C. At this supercooling limit, ice crystallization occurs within the snow fly’s hemolymph and rapidly spreads throughout the body, resulting in death. However, we discovered that snow flies frequently survive freezing by rapidly amputating legs before ice crystallization can spread to their vital organs. Self-amputation of freezing limbs is a last-ditch tactic to prolong survival in frigid conditions that few animals can endure. Understanding the extreme physiology and behavior of snow insects is urgently important, as the alpine ecosystems they inhabit are being disproportionately altered by anthropogenic climate change.
A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactionsin vivo
Authors: Michael Cassia , Di Cristofano Antonio , de Oliveira Sofia
Published: May 2023

Anaplastic thyroid cancer (ATC) is a rare malignant subtype of thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643) derived fluorescently labeled ATC cell lines we show these cell lines display different engraftment rates, mass volume, proliferation, and angiogenic potential. Next, using a PIP-FUCCI reporter to track proliferationin-vivowe observed cells in each phase of the cell cycle. Additionally, we performed long-term non-invasive intravital microscopy over 48 hours to understand cellular dynamics in the tumor microenvironment at the single cell level. Lastly, we tested a well-known mTOR inhibitor to show our model could be used as an effective screening platform for new therapeutic compounds. Altogether, we show that zebrafish xenotransplants make a great model to study thyroid carcinogenesis and the tumor microenvironment, while also being a suitable model to test new therapeuticsin vivo.

SUMMARY STATEMENT

Anaplastic thyroid cancer xenotransplant model in zebrafish larvae to study thyroid cancer tumorigenesis and tumor microenvironment. Using confocal microscopy to understand cell cycle progression, interactions with the innate immune system, and test therapeutic compounds in vivo.
Gene expression QTL mapping in stimulated iPSC-derived macrophages provides insights into common complex diseases
Authors: Panousis Nikolaos I , Garwany Omar El , Knights Andrew , Rop Jesse Cheruiyot , Kumasaka Natsuhiko , Imaz Maria , Vilarino Lorena Boquete , Tsingene Anthi , Barnett Alice , Gomez Celine , Anderson Carl A. , Gaffney Daniel J.
Published: May 2023

Many disease-associated variants are thought to be regulatory but are not present in existing catalogues of expression quantitative trait loci (eQTL). We hypothesise that these variants may regulate expression in specific biological contexts, such as stimulated immune cells. Here, we used human iPSC-derived macrophages to map eQTLs across 24 cellular conditions. We found that 76% of eQTLs detected in at least one stimulated condition were also found in naive cells. The percentage of response eQTLs (reQTLs) varied widely across conditions (3.7% - 28.4%), with reQTLs specific to a single condition being rare (1.11%). Despite their relative rarity, reQTLs were overrepresented among disease-colocalizing eQTLs. We nominated an additional 21.7% of disease effector genes at GWAS loci via colocalization of reQTLs, with 38.6% of these not found in the Genotype–Tissue Expression (GTEx) catalogue. Our study highlights the diversity of genetic effects on expression and demonstrates how condition-specific regulatory variation can enhance our understanding of common disease risk alleles.
Genetic identification of novel medullary neurons underlying congenital central hypoventilation syndrome
Authors: Cui Ke , Xia Yiling , Patnaik Abhisarika , Lowenstein Elijah D. , Isik Eser Göksu , Knorz Adrian L. , Airaghi Laura , Crotti Michela , Studer Michèle , Rijli Filippo M. , Nothwang Hans G. , Hernandez-Miranda Luis R.
Published: May 2023

Congenital Central Hypoventilation Syndrome (CCHS) is a rare, but life-threatening, respiratory disorder that is classically diagnosed in children. This disease is characterized by pronounced alveolar hypoventilation and diminished chemoreflexes, particularly to abnormally high levels of arterial pCO2. Mutations in the transcription factorsPHOX2BandLBX1have been identified in CCHS patients, but the dysfunctional circuit responsible for this disease remains unknown. Here, we show that distinct sets of medullary neurons co-expressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in CCHS. By combining murine intersectional chemogenetics, intersectional labeling, and the selective targeting of the CCHS disease-causingLbx1FSmutation to specific subgroups of dB2 neurons, we uncovered novel sets of these cells key for i) respiratory tidal volumes and the hypercarbic reflex, ii) neonatal respiratory stability and iii) neonatal survival. These data provide functional evidence for the essential role of dB2 neurons in neonatal respiratory physiology and will be instrumental for the development of therapeutic strategies for the management of CCHS. In summary, our work uncovers new neural components of the central circuit regulating breathing and establishes dB2 neuron dysfunction to be causative of CCHS.