bluuebunny/crossref_metadata_2025 huggingface dataset:
A Task-Specific Algorithm to Estimate Occupational (1→3)-β-D-glucan Exposure for Farmers in the Biomarkers of Exposure and Effect in Agriculture Study
Authors: Friesen Melissa C , Hung Felicia , Xie Shuai , Viet Susan M , Deziel Nicole C , Locke Sarah J , Josse Pabitra R , Sauvé Jean-François , Andreotti Gabriella , Thorne Peter S , Beane-Freeman Laura E , Hofmann Jonathan N
Published: June 2022

Objectives

Farmers may be exposed to glucans (a cell component of molds) through a variety of tasks. The magnitude of exposure depends on each farmer’s activities and their duration. We developed a task-specific algorithm to estimate glucan exposure that combines measurements of (1→3)-β-D-glucan with questionnaire responses from farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study.

Methods

To develop the algorithm, we first derived task-based geometric means (GMs) of glucan exposure for farming tasks using inhalable personal air sampling data from a prior air monitoring study in a subset of 32 BEEA farmers. Next, these task-specific GMs were multiplied by subject-reported activity frequencies for three time windows (the past 30 days, past 7 days, and past 1 day) to obtain subject-, task-, and time window-specific glucan scores. These were summed together to obtain a total glucan score for each subject and time window. We examined the within- and between-task correlation in glucan scores for different time frames. Additionally, we assessed the algorithm for the ‘past 1 day’ time window using full-shift concentrations from the 32 farmers who participated in air monitoring the day prior to an interview using multilevel statistical models to compare the measured glucan concentration with algorithm glucan scores.

Results

We focused on the five highest exposed tasks: poultry confinement (300 ng/m3), swine confinement (300 ng/m3), clean grain bins (200 ng/m3), grind feed (100 ng/m3), and stored seed or grain (50 ng/m3); the remaining tasks were <50 ng/m3 and had similar concentrations to each other. Overall, 67% of the participants reported at least one of these tasks. The most prevalent task was stored seed or grain (64%). The highest median glucan scores were observed for poultry confinement and swine confinement; these tasks were reported by 2% and 8% of the participants, respectively. The correlation between scores for the same task but different time windows was high for swine confinement and poultry confinement, but low for clean grain bins. Task-specific scores had low correlation with other tasks. Prior day glucan concentration was associated with the total glucan ‘past 1 day’ score and with swine confinement and clean grain bin task scores.

Conclusions

This study provides insight into the variability and key sources of glucan exposure in a US farming population. It also provides a framework for better glucan exposure assessment in epidemiologic studies and is a crucial starting point for evaluating health risks associated with glucans in future epidemiologic evaluations of this population.
Characterization of carbohydrate metabolism in in vivo- and in vitro-grown and matured mouse antral follicles
Authors: Herta Anamaria-Cristina , von Mengden Lucia , Akin Nazli , Billooye Katy , Coucke Wim , van Leersum Julia , Cava-Cami Berta , Saucedo-Cuevas Laura , Klamt Fábio , Smitz Johan , Anckaert Ellen
Published: June 2022

Establishing an ideal human follicle culture system for oncofertility patients relies mainly on animal models since donor tissue is scarce and often of suboptimal quality. The in vitro system developed in our laboratory supports the growth of prepubertal mouse secondary follicles up to mature oocytes. Given the importance of glucose in preparing the oocyte for proper maturation, a baseline characterization of follicle metabolism both in the culture system and in vivo was carried out. Markers of glucose-related pathways (glycolysis, tricarboxylic acid [TCA] cycle, pentose phosphate pathway [PPP], polyol pathway, and hexosamine biosynthetic pathway), as well as the antioxidant capacity, were measured in the different follicle cell types by both enzymatic activities (spectrophotometric detection) and gene expression (qPCR). This study confirmed that in vivo the somatic cells, mainly granulosa, exhibit intense glycolytic activity, while oocytes perform PPP. Throughout the final maturation step, oocytes in vivo and in vitro showed steady levels for all the key enzymes and metabolites. On the other hand, ovulation triggers a boost of pyruvate and lactate uptake in cumulus cells in vivo, consumes reduced nicotinamide adenine dinucleotide phosphate, and increases TCA cycle and small molecules antioxidant capacity activities, while in vitro, the metabolic upregulation in all the studied pathways is limited. This altered metabolic pattern might be a consequence of cell exhaustion because of culture conditions, impeding cumulus cells to fulfill their role in providing proper support for acquiring oocyte competence.
From self-help to self-advocacy for people with disadvantages: narrating problems through Japanese community radio
Authors: Ogawa Akiko
Published: June 2022

This study explores an alternative way for tojisha—a Japanese term that usually translates to ‘the parties concerned’ and ‘who face challenges’—to represent themselves. Specifically, it investigates how tojisha can develop self-advocacy skills using the narrative method that facilitates storytelling and community broadcasting. To this end, we scheduled community radio programmes with the aid of a local social worker, five individuals involved in self-help activities, and their supporters. The structured format of the broadcast enabled the tojisha to talk about their difficulties, desires, and ambitions. Data acquired through pre- and post-activity interviews were analysed to understand how storytelling and community radio help tojisha acquire self-advocacy skills. First, we found that the narrative method enabled the participants to bridge their past and future and contemplate the significance of their difficult experiences. Second, the ‘public’ experience of broadcasting helped the participants gain social awareness, particularly regarding the significance of how their storytelling can initiate social change. The broadcast format developed for this study will be useful to other disadvantaged groups considering the use of media for self-advocacy.
Population Immunity to Pre-Omicron and Omicron Severe Acute Respiratory Syndrome Coronavirus 2 Variants in US States and Counties Through 1 December 2021
Authors: Klaassen Fayette , Chitwood Melanie H , Cohen Ted , Pitzer Virginia E , Russi Marcus , Swartwood Nicole A , Salomon Joshua A , Menzies Nicolas A
Published: June 2022

Background

Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination contribute to population-level immunity against SARS-CoV-2. This study estimated the immunological exposure and effective protection against future SARS-CoV-2 infection in each US state and county over 2020–2021 and how this changed with the introduction of the Omicron variant.

Methods

We used a Bayesian model to synthesize estimates of daily SARS-CoV-2 infections, vaccination data and estimates of the relative rates of vaccination conditional on infection status to estimate the fraction of the population with (1) immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received ≥1 doses of a COVID-19 vaccine), (2) effective protection against infection, and (3) effective protection against severe disease, for each US state and county from 1 January 2020 to 1 December 2021.

Results

The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination as of 1 December 2021 was 88.2% (95% credible interval [CrI], 83.6%–93.5%). Accounting for waning and immune escape, effective protection against the Omicron variant on 1 December 2021 was 21.8% (95% CrI, 20.7%–23.4%) nationally and ranged between 14.4% (13.2%–15.8%; West Virginia) and 26.4% (25.3%–27.8%; Colorado). Effective protection against severe disease from Omicron was 61.2% (95% CrI, 59.1%–64.0%) nationally and ranged between 53.0% (47.3%–60.0%; Vermont) and 65.8% (64.9%–66.7%; Colorado).

Conclusions

While more than four-fifths of the US population had prior immunological exposure to SARS-CoV-2 via vaccination or infection on 1 December 2021, only a fifth of the population was estimated to have effective protection against infection with the immune-evading Omicron variant.
Tuberculosis Molecular Bacterial Load Assay Reveals Early Delayed Bacterial Killing in Patients With Relapse
Authors: Ntinginya Nyanda Elias , Bakuli Abhishek , Mapamba Daniel , Sabiiti Wilber , Kibiki Gibson , Minja Lilian Tina , Kuchaka Davis , Reither Klaus , Phillips Patrick Peter John , Boeree Martin Johan , Gillespie Stephen H , Hoelscher Michael , Heinrich Norbert ,   for the Pan African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) Consortium
Published: June 2022

Bacterial killing in patients with tuberculosis (TB) relapse was compared to that in patients achieving cure, measured by TB molecular bacterial load assay (TB-MBLA) or mycobacteria growth indicator tube (MGIT) time to positivity (TTP). TB-MBLA in 4 relapsed patients was significantly different compared to 132 cured patients after 2 weeks of treatment; MGIT TTP showed a significant difference from week 8.
TheStaphylococcus aureusNetwork Adaptive Platform Trial Protocol: New Tools for an Old Foe
Authors: Tong Steven Y C , Mora Jocelyn , Bowen Asha C , Cheng Matthew P , Daneman Nick , Goodman Anna L , Heriot George S , Lee Todd C , Lewis Roger J , Lye David C , Mahar Robert K , Marsh Julie , McGlothlin Anna , McQuilten Zoe , Morpeth Susan C , Paterson David L , Price David J , Roberts Jason A , Robinson J Owen , van Hal Sebastiaan J , Walls Genevieve , Webb Steve A , Whiteway Lyn , Yahav Dafna , Davis Joshua S ,   for the Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group, Anagnostou Nick , Archuleta Sophia , Athan Eugene , Barina Lauren , Best Emma , Bloomfield Max , Bostock Jennifer , Botheras Carly , Bowen Asha , Britton Philip , Burden Hannah , Campbell Anita , Carter Hannah , Cheng Matthew , Chew Ka Lip , Chong Russel Lee Ming , Coombs Geoff , Daley Peter , Daneman Nick , Davies Jane , Davis Joshua , Dishon Yael , Dotel Ravindra , Dunlop Adrian , Flack Felicity , Flanagan Katie , Foo Hong , Ghanem-Zoubi Nesrin , Giulieri Stefano , Goodman Anna , Grant Jennifer , Gregson Dan , Guy Stephen , Gwee Amanda , Hardy Erica , Henderson Andrew , Heriot George , Howden Benjamin , Hudson Fleur , Johnstone Jennie , Kalimuddin Shirin , Kretser Dana de , Kwa Andrea , Lee Todd , Legg Amy , Lewis Roger , Llewelyn Martin , Lumley Thomas , Lye David , MacFadden Derek , Mahar Robert , Malhamé Isabelle , Marks Michael , Marsh Julie , Martinello Marianne , Matthews Gail , McArthur Colin , McGlothlin Anna , McKew Genevieve , McMullan Brendan , McQuilten Zoe , Milliken Eliza , Mora Jocelyn , Morpeth Susan , Murthy Srinivas , Nourse Clare , O'Sullivan Matthew , Paterson David , Paul Mical , Petersiel Neta , Petrella Lina , Pett Sarah , Price David , Roberts Jason , Robinson Owen , Rogers Ben , Saville Benjamin , Scarborough Matthew , Scheetz Marc , Scheuerman Oded , Schwartz Kevin , Smith Simon , Snelling Tom , Soares Marta , Sommerville Christine , Stewardson Andrew , Stone Neil , Sud Archana , Tilley Robert , Tong Steven , Turner Rebecca , Underwood Jonathan , Hal Sebastiaan van , Voss Lesley , Walls Genevieve , Webb Rachel , Webb Steve , Whiteway Lynda , Wilson Heather , Wuerz Terry , Yahav Dafna
Published: June 2022

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.
Coronavirus Disease 2019 (COVID-19) Severity Among Women of Reproductive Age With Symptomatic Laboratory-Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Pregnancy Status—United States, 1 January 2020–25 December 2021
Authors: Strid Penelope , Zapata Lauren B , Tong Van T , Zambrano Laura D , Woodworth Kate R , Riser Aspen P , Galang Romeo R , Gilboa Suzanne M , Ellington Sascha R
Published: June 2022

Background

Information on the severity of coronavirus disease 2019 (COVID-19) attributable to the Delta variant in the United States among pregnant people is limited. We assessed the risk for severe COVID-19 by pregnancy status in the period of Delta variant predominance compared with the pre-Delta period.

Methods

Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among symptomatic women of reproductive age (WRA) were assessed. We calculated adjusted risk ratios for severe disease including intensive care unit (ICU) admission, receipt of invasive ventilation or extracorporeal membrane oxygenation (ECMO), and death comparing the pre-Delta period (1 January 2020–26 June 2021) and the Delta period (27 June 2021–25 December 2021) for pregnant and nonpregnant WRA.

Results

Compared with the pre-Delta period, the risk of ICU admission during the Delta period was 41% higher (adjusted risk ratio [aRR], 1.41 [95% confidence interval {CI}, 1.17–1.69]) for pregnant WRA and 9% higher (aRR, 1.09 [95% CI, 1.00–1.18]) for nonpregnant WRA. The risk of invasive ventilation or ECMO was higher for pregnant (aRR, 1.83 [95% CI, 1.26–2.65]) and nonpregnant (aRR, 1.34 [95% CI, 1.17–1.54]) WRA in the Delta period. During the Delta period, the risk of death was 3.33 (95% CI, 2.48–4.46) times the risk in the pre-Delta period among pregnant WRA and 1.62 (95% CI, 1.49–1.77) among nonpregnant WRA.

Conclusions

Compared with the pre-Delta period, pregnant and nonpregnant WRA were at increased risk for severe COVID-19 in the Delta period.
Kinetics of Maternally Derived Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Infants in Relation to the Timing of Antenatal Vaccination
Authors: Rottenstreich Amihai , Zarbiv Gila , Oiknine-Djian Esther , Vorontsov Olesya , Zigron Roy , Kleinstern Geffen , Porat Shay , Wolf Dana G
Published: June 2022

Background

SARS-CoV-2 infection during early infancy can result in severe disease. We evaluated the durability of maternally-derived anti-SARS-CoV-2 antibodies in infants and its relation to antenatal vaccination timing.

Methods

Sera were prospectively collected at birth and 3 months after delivery from mother-infant pairs following antenatal BNT162b2 vaccination. SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels and neutralizing activity were evaluated.

Results

56 mother-infant pairs were included: 15 (26.8%) were vaccinated in the first trimester, 16 (28.6%) in the second trimester, and 25 (44.6%) in the third trimester.

At the time of delivery, all neonates were positive for anti-RBD-specific IgG with a median concentration of 4046 [IQR 2446–7896] AU/mL, with the highest concentration found after third trimester vaccination (median 6763 [IQR 3857–12561] AU/mL). At 3 months after delivery, anti RBD-specific IgG levels in infants significantly waned with a median concentration of 545 [IQR 344–810] AU/mL (P < .001). The half-life of anti-RBD-specific IgG was 66 days among mothers and 30 days among infants. While at the time of delivery, all neonates had detectable neutralizing activity regardless of gestational age at vaccination, at 3-months of age, a higher proportion of infants born to mothers vaccinated in third trimester had persistent neutralizing activity as compared to those born to mothers vaccinated in second trimester.

Conclusions

Maternal vaccination leads to efficient transplacental antibody transfer, with persistent anti-SARS-CoV-2 antibodies detected at 3 months of age in all infants. The observed effect of antenatal immunization timing on the kinetics of maternally-derived antibodies may have implications for SARS-CoV-2 vaccination strategies.
Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study)
Authors: Lilleri Daniele , Tassis Beatrice , Pugni Lorenza , Ronchi Andrea , Pietrasanta Carlo , Spinillo Arsenio , Arossa Alessia , Achille Cristian , Vergani Patrizia , Ornaghi Sara , Riboni Silvia , Cavoretto Paolo , Candiani Massimo , Gaeta Gerarda , Prefumo Federico , Fratelli Nicola , Fichera Anna , Vignali Michele , Barbasetti Di Prun Allegra , Fabbri Elisa , Cetin Irene , Locatelli Anna , Consonni Sara , Rutolo Simona , Miotto Elena , Savasi Valeria , Di Giminiani Maria , Cromi Antonella , Binda Sandro , Fiorina Loretta , Furione Milena , Cassinelli Gabriela , Klersy Catherine ,   for the CHILd Study Group, Piccini Stefania , Marrazzi Valentina , Muscettola Giulia , Zelini Paola , d’Angelo Piera , De Cicco Marica , Cirasola Daniela , Zavaglio Federica , Testa Lea , Ballerini Claudia , Stachetti Rebecca , Fondazione Marta Ruggiero , De Liso Federica , Cavallero Annalisa , Tessitore Isadora Vaglio , Ventura Maria Luisa , Pozzoni Mirko , Merlo Camilla , Rivetti Giulia , Spinoni Vania , Belloni Gaia , Querzola Camilla , Pessina Marta , Ligato Elisa , Zavatta Alice , Balconi Marta , Mussi Serena , Biraghi Patrizia , Cammarata Selene , Ghezzi Fabio , Agosti Massimo , Pellegrinelli Laura , Galli Cristina , Primache Valeria
Published: June 2022

Background

Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population.

Methods

The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing.

Results

Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11–.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7–32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5–10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled.

Conclusions

Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV.

Clinical trials registration

www.clinicaltrials.gov (NCT03973359).
Integration of Sequencing and Epidemiologic Data for Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections in a Tertiary-Care Hospital
Authors: Czech-Sioli Manja , Günther Thomas , Robitaille Alexis , Roggenkamp Hannes , Büttner Henning , Indenbirken Daniela , Christner Martin , Lütgehetmann Marc , Knobloch Johannes , Aepfelbacher Martin , Grundhoff Adam , Fischer Nicole
Published: June 2022

Background

The ongoing coronavirus disease 2019 pandemic significantly burdens hospitals and other healthcare facilities. Therefore, understanding the entry and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for effective prevention and preparedness measures. We performed surveillance and analysis of testing and transmission of SARS-CoV-2 infections in a tertiary-care hospital in Germany during the second and third pandemic waves in fall/winter 2020.

Methods

Between calendar week 41 in 2020 and calendar week 1 in 2021, 40%, of all positive patient and staff samples (284 total) were subjected to full-length viral genome sequencing. Clusters were defined based on similar genotypes indicating common sources of infection. We integrated phylogenetic, spatial, and temporal metadata to detect nosocomial infections and outbreaks, uncover transmission chains, and evaluate containment measures’ effectiveness.

Results

Epidemiologic data and contact tracing readily recognize most healthcare-associated (HA) patient infections. However, sequencing data reveal that temporally preceding index cases and transmission routes can be missed using epidemiologic methods, resulting in delayed interventions and serially linked outbreaks being counted as independent events. While hospital-associated transmissions were significantly elevated at a moderate rate of community transmission during the second wave, systematic testing and high vaccination rates among staff have led to a substantial decrease in HA infections at the end of the second/beginning of the third wave despite high community transmissions.

Conclusions

While epidemiologic analysis is critical for immediate containment of HA SARS-CoV-2 outbreaks, integration of genomic surveillance revealed weaknesses in identifying staff contacts. Our study underscores the importance of high testing frequency and genomic surveillance to detect, contain and prevent SARS-CoV-2–associated infections in healthcare settings.
Association Between Increased Linezolid Plasma Concentrations and the Development of Severe Toxicity in Multidrug-Resistant Tuberculosis Treatment
Authors: Eimer Johannes , Fréchet-Jachym Mathilde , Le Dû Damien , Caumes Eric , El-Helali Najoua , Marigot-Outtandy Dhiba , Mechai Frédéric , Peytavin Gilles , Pourcher Valérie , Rioux Christophe , Yazdanpanah Yazdan , Robert Jérôme , Guglielmetti Lorenzo ,   for the LZDM group, Aubry Alexandra , Bonnet Isabelle , Morel Florence , Veziris Nicolas , Lecorché Emmanuel , Mougari Faiza , Andrejak Claire , Bourgarit Anne , Klement Elise , Rivoire Bénédicte , Thouvenin Guillaume , Tunesi Simone , Wicky Marie , Jaspard Marie , Alauzet Corentine , Escaut Lelia , Ellis-Corbet Sophie , Bernard Christine , Roux Anne-Laure
Published: June 2022

Background

Treatment of multidrug-resistant (MDR) tuberculosis with linezolid is characterized by high rates of adverse events. Evidence on therapeutic drug monitoring to predict drug toxicity is scarce. This study aimed to evaluate the association of linezolid trough concentrations with severe toxicity.

Methods

We retrospectively assessed consecutive patients started on linezolid for MDR tuberculosis between 2011 and 2017. The primary outcome was severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation. The impact of plasma linezolid trough concentrations >2 mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates.

Results

SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95% confidence interval, .30–.49). A maximum linezolid trough concentration >2 mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2 mg/L in 22 (15%). The adjusted hazard ratio for SMT was 2.35 (95% confidence interval, 1.26–4.38; P = .01) in patients with a mean trough concentration >2 mg/L and 2.63 (1.55–4.47; P < .01) for SMT after the first detection of a trough concentration >2 mg/L. In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering elevated trough concentrations did not restore baseline risk.

Conclusions

Linezolid trough concentrations >2 mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR tuberculosis. Pending further prospective evidence, an individual risk-benefit assessment on the continuation of linezolid treatment is warranted in any patient with trough concentrations >2 mg/L.
Reported Exposures Among In-Person Workers With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in 6 States, September 2020–June 2021
Authors: Free Hannah , Luckhaupt Sara E , Billock Rachael M , Groenewold Matthew R , Burrer Sherry , Sweeney Marie Haring , Wong Jessie , Gibb Kathryn , Rodriguez Andrea , Vergara Ximena P , Cummings Kristin J , Lavender Antionette , Argueta Gabriel , Crawford Hannah Leigh , Erukunuakpor Kimberly , Karlsson Nicole D , Armenti Karla , Thomas Hannah , Gaetz Kim , Dang Gialana , Harduar-Morano Laurel , Modji Komi
Published: June 2022

Background

Surveillance systems lack detailed occupational exposure information from workers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The National Institute for Occupational Safety and Health partnered with 6 states to collect information from adults diagnosed with SARS-CoV-2 infection who worked in person (outside the home) in non-healthcare settings during the 2 weeks prior to illness onset.

Methods

The survey captured demographic, medical, and occupational characteristics and work- and non–work-related risk factors for SARS-CoV-2 infection. Reported close contact with a person known or suspected to have SARS-CoV-2 infection was categorized by setting as exposure at work, exposure outside of work only, or no known exposure/did not know. Frequencies and percentages of exposure types are compared by respondent characteristics and risk factors.

Results

Of 1111 respondents, 19.4% reported exposure at work, 23.4% reported exposure outside of work only, and 57.2% reported no known exposure/did not know. Workers in protective service occupations (48.8%) and public administration industries (35.6%) reported exposure at work most often. More than one third (33.7%) of respondents who experienced close contact with ≥10 coworkers per day and 28.8% of respondents who experienced close contact with ≥10 customers/clients per day reported exposures at work.

Conclusions

Exposure to occupational SARS-CoV-2 was common among respondents. Examining differences in exposures among different worker groups can help identify populations with the greatest need for prevention interventions. The benefits of recording employment characteristics as standard demographic information will remain relevant as new and reemerging public health issues occur.
Vaccine Effectiveness of CanSino (Adv5-nCoV) Coronavirus Disease 2019 (COVID-19) Vaccine Among Childcare Workers—Mexico, March–December 2021
Authors: Richardson Vesta L , Camacho Franco Martín Alejandro , Bautista Márquez Aurora , Martínez Valdez Libny , Castro Ceronio Luis Enrique , Cruz Cruz Vicente , Gharpure Radhika , Lafond Kathryn E , Yau Tat S , Azziz-Baumgartner Eduardo , Hernández Ávila Mauricio
Published: June 2022

Background

Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) coronavirus disease 2019 (COVID-19) vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE).

Methods

We evaluated CanSino VE within a childcare worker cohort that included 1408 childcare facilities. Participants were followed during March–December 2021 and tested through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% × (1 − hazard ratio for SARS-CoV-2 infection in fully vaccinated vs unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation.

Results

The cohort included 43 925 persons who were mostly (96%) female with a median age of 32 years; 37 646 (86%) were vaccinated with CanSino. During March–December 2021, 2250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% confidence interval [CI], 10%–29%) against illness, 76% (95% CI, 42%–90%) against hospitalization, and 94% (95% CI, 66%–99%) against death. VE against illness declined from 48% (95% CI, 33%–61%) after 14–60 days following full vaccination to 20% (95% CI, 9%–31%) after 61–120 days.

Conclusions

CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes.
Increased Deaths From Fungal Infections During the Coronavirus Disease 2019 Pandemic—National Vital Statistics System, United States, January 2020–December 2021
Authors: Gold Jeremy A W , Ahmad Farida B , Cisewski Jodi A , Rossen Lauren M , Montero Alejandro J , Benedict Kaitlin , Jackson Brendan R , Toda Mitsuru
Published: June 2022

Background

Coronavirus disease 2019 (COVID-19)–associated fungal infections cause severe illness, but comprehensive data on disease burden are lacking. We analyzed US National Vital Statistics System (NVSS) data to characterize disease burden, temporal trends, and demographic characteristics of persons dying of fungal infections during the COVID-19 pandemic.

Methods

Using NVSS’s January 2018–December 2021 Multiple Cause of Death Database, we examined numbers and age-adjusted rates (per 100 000 population) of deaths due to fungal infection by fungal pathogen, COVID-19 association, demographic characteristics, and year.

Results

Numbers and age-adjusted rates of deaths due to fungal infection increased from 2019 (n = 4833; rate, 1.2 [95% confidence interval, 1.2–1.3]) to 2021 (n = 7199; rate, 1.8 [1.8–1.8] per 100 000); of 13 121 such deaths during 2020–2021, 2868 (21.9%) were COVID-19 associated. Compared with non–COVID-19–associated deaths (n = 10 253), COVID-19–associated deaths more frequently involved Candida (n = 776 [27.1%] vs n = 2432 [23.7%], respectively) and Aspergillus (n = 668 [23.3%] vs n = 1486 [14.5%]) and less frequently involved other specific fungal pathogens. Rates of death due to fungal infection were generally highest in nonwhite and non-Asian populations. Death rates from Aspergillus infections were approximately 2 times higher in the Pacific US census division compared with most other divisions.

Conclusions

Deaths from fungal infection increased during 2020–2021 compared with previous years, primarily driven by COVID-19–associated deaths, particularly those involving Aspergillus and Candida. Our findings may inform efforts to prevent, identify, and treat severe fungal infections in patients with COVID-19, especially in certain racial/ethnic groups and geographic areas.
Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants
Authors: Junker Daniel , Becker Matthias , Wagner Teresa R , Kaiser Philipp D , Maier Sandra , Grimm Tanja M , Griesbaum Johanna , Marsall Patrick , Gruber Jens , Traenkle Bjoern , Heinzel Constanze , Pinilla Yudi T , Held Jana , Fendel Rolf , Kreidenweiss Andrea , Nelde Annika , Maringer Yacine , Schroeder Sarah , Walz Juliane S , Althaus Karina , Uzun Gunalp , Mikus Marco , Bakchoul Tamam , Schenke-Layland Katja , Bunk Stefanie , Haeberle Helene , Göpel Siri , Bitzer Michael , Renk Hanna , Remppis Jonathan , Engel Corinna , Franz Axel R , Harries Manuela , Kessel Barbora , Lange Berit , Strengert Monika , Krause Gerard , Zeck Anne , Rothbauer Ulrich , Dulovic Alex , Schneiderhan-Marra Nicole
Published: June 2022

Background

The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction.

Methods

We assessed antibody (immunoglobulin G [IgG]) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals.

Results

While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose.

Conclusions

Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.
Rare germline deleterious variants increase susceptibility for lung cancer
Authors: Sang Jian , Zhang Tongwu , Kim Jung , Li Mengying , Pesatori Angela C , Consonni Dario , Song Lei , Liu Jia , Zhao Wei , Hoang Phuc H , Campbell Dave S , Feng James , D’Arcy Monica E , Synnott Naoise , Chen Yingxi , Wu Zeni , Zhu Bin , Yang Xiaohong R , Brown Kevin M , Choi Jiyeon , Shi Jianxin , Landi Maria Teresa
Published: June 2022

Although multiple common susceptibility loci for lung cancer (LC) have been identified by genome-wide association studies, they can explain only a small portion of heritability. The etiological contribution of rare deleterious variants (RDVs) to LC risk is not fully characterized and may account for part of the missing heritability. Here, we sequenced the whole exomes of 2777 participants from the Environment and Genetics in Lung cancer Etiology study, a homogenous population including 1461 LC cases and 1316 controls. In single-variant analyses, we identified a new RDV, rs77187983 [EHBP1, odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.34–7.30, P = 0.008] and replicated two previously reported RDVs, rs11571833 (BRCA2, OR = 2.18; 95% CI = 1.25–3.81, P = 0.006) and rs752672077 (MPZL2, OR = 3.70, 95% CI = 1.04–13.15, P = 0.044). In gene-based analyses, we confirmed BRCA2 (P = 0.007) and ATM (P = 0.014) associations with LC risk and identified TRIB3 (P = 0.009), involved in maintaining genome stability and DNA repair, as a new candidate susceptibility gene. Furthermore, cases were enriched with RDVs in homologous recombination repair [carrier frequency (CF) = 22.9% versus 19.5%, P = 0.017] and Fanconi anemia (CF = 12.5% versus 10.2%, P = 0.036) pathways. Our results were not significant after multiple testing corrections but were enriched in cases versus controls from large scale public biobank resources, including The Cancer Genome Atlas, FinnGen and UK Biobank. Our study identifies novel candidate genes and highlights the importance of RDVs in DNA repair-related genes for LC susceptibility. These findings improve our understanding of LC heritability and may contribute to the development of risk stratification and prevention strategies.
De novo non-synonymous CTR9 variants are associated with motor delay and macrocephaly: human genetic and zebrafish experimental evidence
Authors: Suzuki Hisato , Aoki Kana , Kurosawa Kenji , Imagawa Kazuo , Ohto Tatsuyuki , Yamada Mamiko , Takenouchi Toshiki , Kosaki Kenjiro , Ishitani Tohru
Published: June 2022

CTR9 is one of five genes that form the PAF1 complex, which binds to RNA polymerase II and plays critical roles in transcriptional elongation and transcription-coupled histone modifications including histones H3K4me3 and H3K36me3. In this study, de novo CTR9 non-synonymous variants (p.(Glu15Asp) and p.(Pro25Arg)) were detected in two unrelated patients with macrocephaly, motor delay, and intellectual disability. A pull-down assay showed that the mutant CTR9 proteins had stronger affinities to the PAF1 protein than the wild-type protein. Functional analyses using zebrafish showed that the knockout of the ctr9 gene caused motor defects and enlargement of the telencephalon, which is homologous to the mammalian cerebrum. The rescue experiment, in which the human CTR9 mutants were introduced into ctr9-knockout zebrafish, failed to maintain the swimming posture of the ctr9-knockout fish, suggesting that the human CTR9 mutant proteins do not function normally in vivo. In addition, the overexpression of human CTR9 mutant mRNA caused telencephalon enlargement in zebrafish larvae, suggesting that the human CTR9 mutant proteins interfered with normal endogenous CTR9 function. We concluded that the two missense variants in CTR9 (p.(Glu15Asp) and p.(Pro25Arg)) cause a new syndrome involving macrocephaly, motor delay and intellectual disability through the loss of the normal function of CTR9 and the inhibition of the normal intrinsic CTR9 function of the contralateral allele.
Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia
Authors: Xu Keren , Li Shaobo , Pandey Priyatama , Kang Alice Y , Morimoto Libby M , Mancuso Nicholas , Ma Xiaomei , Metayer Catherine , Wiemels Joseph L , de Smith Adam J
Published: June 2022

Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest that epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes. Here, we investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL. We performed an epigenome-wide association study (EWAS) including 808 childhood ALL cases and 919 controls from California-based studies using neonatal blood DNA. For differentially methylated CpG positions (DMPs), we next conducted association analysis with 23 known ALL risk SNPs followed by causal mediation analyses addressing the significant SNP-DMP pairs. DNA methylation at CpG cg01139861, in the promoter region of IKZF1, mediated the effects of the intronic IKZF1 risk SNP rs78396808, with the average causal mediation effect (ACME) explaining ~30% of the total effect (ACME P = 0.0031). In analyses stratified by self-reported race/ethnicity, the mediation effect was only significant in Latinos, explaining ~41% of the total effect of rs78396808 on ALL risk (ACME P = 0.0037). Conditional analyses confirmed the presence of at least three independent genetic risk loci for childhood ALL at IKZF1, with rs78396808 unique to non-European populations. We also demonstrated that the most significant DMP in the EWAS, CpG cg13344587 at gene ARID5B (P = 8.61 × 10−10), was entirely confounded by the ARID5B ALL risk SNP rs7090445. Our findings provide new insights into the functional pathways of ALL risk SNPs and the DNA methylation differences associated with risk of childhood ALL.
Embryo cryopreservation leads to sex-specific DNA methylation perturbations in both human and mouse placentas
Authors: Mani Sneha , Ghosh Jayashri , Rhon-Calderon Eric A , Lan Yemin , Ord Teri , Kalliora Charikleia , Chan Joe , Schultz Bryant , Vaughan-Williams Elaine , Coutifaris Christos , Sapienza Carmen , Senapati Suneeta , Bartolomei Marisa S , Mainigi Monica
Published: June 2022

In vitro fertilization (IVF) is associated with DNA methylation abnormalities and a higher incidence of adverse pregnancy outcomes. However, which exposure(s), among the many IVF interventions, contributes to these outcomes remains unknown. Frozen embryo transfer (ET) is increasingly utilized as an alternative to fresh ET, but reports suggest a higher incidence of pre-eclampsia and large for gestational age infants. This study examines DNA methylation in human placentas using the 850K Infinium MethylationEPIC BeadChip array obtained after 65 programmed frozen ET cycles, 82 fresh ET cycles and 45 unassisted conceptions. Nine patients provided placentas following frozen and fresh ET from consecutive pregnancies for a paired subgroup analysis. In parallel, eight mouse placentas from fresh and frozen ET were analyzed using the Infinium Mouse Methylation BeadChip array. Human and mouse placentas were significantly hypermethylated after frozen ET compared with fresh. Paired analysis showed similar trends. Sex-specific analysis revealed that these changes were driven by male placentas in humans and mice. Frozen and fresh ET placentas were significantly different from controls, with frozen samples hypermethylated compared with controls driven by males and fresh samples being hypomethylated compared with controls, driven by females. Sexually dimorphic epigenetic changes could indicate differential susceptibility to IVF-associated perturbations, which highlights the importance of sex-specific evaluation of adverse outcomes. Similarities between changes in mice and humans underscore the suitability of the mouse model in evaluating how IVF impacts the epigenetic landscape, which is valuable given limited access to human tissue and the ability to isolate specific interventions in mice.
Acute appendicitis following the COVID-19 vaccine
Authors: Oganesyan Ani , Schäfer Michal , Lesh Caitlyn
Published: June 2022

We report the case of a previously healthy 69-year-old female who developed appendicitis after receiving the third dose of the Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) vaccine; no other triggers were identified. We speculate that an association exists which may be mediated by colonic lymphoid hyperplasia, a condition that might be indicative of an enhanced immunological mucosal response to antigenic stimulation. As widespread vaccination coverage continues, it is crucial to monitor and accurately report the adverse reactions that may otherwise remain unidentified in vaccination trials. Therefore, we suggest that adults experiencing spontaneous, severe abdominal pain following COVID-19 vaccination may benefit from seeking emergent medical care. Likewise, providers should have a low threshold to consider and evaluate patients for appendicitis. If a true causal link is identified, the risk must also be deliberated in context with the millions of patients who have been safely vaccinated and the known morbidity and mortality from COVID-19 infection.
Utilization of Machine Learning Approaches to Predict Mortality in Pediatric Warzone Casualties
Authors: Lammers Daniel , Williams James , Conner Jeff , Francis Andrew , Prey Beau , Marenco Christopher , Morte Kaitlin , Horton John , Barlow Meade , Escobar Mauricio , Bingham Jason , Eckert Matthew
Published: June 2022

Background

Identification of pediatric trauma patients at the highest risk for death may promote optimization of care. This becomes increasingly important in austere settings with constrained medical capabilities. This study aimed to develop and validate predictive models using supervised machine learning (ML) techniques to identify pediatric warzone trauma patients at the highest risk for mortality.

Methods

Supervised learning approaches using logistic regression (LR), support vector machine (SVM), neural network (NN), and random forest (RF) models were generated from the Department of Defense Trauma Registry, 2008-2016. Models were tested and compared to determine the optimal algorithm for mortality.

Results

A total of 2,007 patients (79% male, median age range 7-12 years old, 62.5% sustaining penetrating injury) met the inclusion criteria. Severe injury (Injury Severity Score > 15) was noted in 32.4% of patients, while overall mortality was 7.13%. The RF and SVM models displayed recall values of .9507 and .9150, while LR and NN displayed values of .8912 and .8895, respectively. Random forest (RF) outperformed LR, SVM, and NN on receiver operating curve (ROC) analysis demonstrating an area under the ROC of .9752 versus .9252, .9383, and .8748, respectively.

Conclusion

Machine learning (ML) techniques may prove useful in identifying those at the highest risk for mortality within pediatric trauma patients from combat zones. Incorporation of advanced computational algorithms should be further explored to optimize and supplement the diagnostic and therapeutic decision-making process.
Abstract Concepts and the Embodied Mind
Authors: Dove Guy
Published: June 2022

Our thoughts depend on knowledge about objects, people, properties, and events. In order to think about where we left our keys, what we are going to make for dinner, when we last fed the dogs, and how we are going to survive our next visit with our family, we need to know something about locations, keys, cooking, dogs, survival, families, and so on. Researchers have sought to explain how our brains can store and access such general knowledge. A growing body of evidence suggests that many of our concepts are grounded in action, emotion, and perception systems. We appear to think about the world by means of the same mechanisms that we use to experience it. Abstract concepts like “democracy,” “fermion,” “piety,” “truth,” and “zero” represent a clear challenge to this idea. Given that they represent a uniquely human cognitive achievement, answering the question of how we acquire and use them is central to our ability to understand ourselves. In Abstract Concepts and the Embodied Mind, Guy Dove contends that abstract concepts are heterogeneous and pose three important challenges to embodied cognition. They force us to ask these questions: How do we generalize beyond the specifics of our experience? How do we think about things that we do not experience directly? How do we adapt our thoughts to specific contexts and tasks? He argues that a successful theory of grounding must embrace multimodal representations, hierarchical architecture, and linguistic scaffolding. Abstract concepts are the product of an elastic mind.
The Influence of Reuse on Architectural Practices in Late Imperial Rome
Authors: Ann Dumser Elisha
Published: June 2022

Much of what is known about Roman building practices derives from the study of structures built between the 2nd century bce and the 2nd century ce. Shifting our focus to the late Roman Empire reveals very different practices at work. In the 3rd and 4th centuries ce there are far fewer of the freshly quarried and custom requisitioned architectural marbles that had dominated imperial building a century earlier. In their place, reuse emerges as a normative architectural practice, even for the most prestigious imperial commissions. Carved architectural elements and relief sculpture appear in secondary contexts as a matter of course, and architectural designs adapt in response to reused materials. Yet reuse in late imperial Rome also extends to the building sites themselves: by the Tetrarchal period, almost every major imperial commission is built atop or adjoining another structure. Using late 3rd- and early 4th-century imperial commissions in Rome as a case study, the chapter outlines the evidence for this shift in architectural practice and argues for a new appreciation of the complexities of designing and building in a city that had seen over 1,000 years of continuous habitation and four centuries of dense urban construction in concrete.