bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Pediatric Patient Transfers From General Emergency Departments in California From 2005 to 2018
Authors: Lee Moon O. , Wall Jessica , Saynina Olga , Camargo Carlos A. , Wang N. Ewen
Published: November 2022

Objective

Each year, approximately 300,000 pediatric patients are transferred out of emergency departments (EDs). Emergency department transfers may not only provide a higher level of care but also incur increased resource use and cost. Our objective was to identify hospital characteristics and patient demographics and conditions associated with ED transfer as well as the trend of transfers over time.

Methods

This was a retrospective cohort study of pediatric visits to EDs in California using the California Office of Statewide Health Planning and Development ED data set (2005–2018). Hospitals were categorized based on inpatient pediatric capabilities. Patients were characterized by demographics and Clinical Classifications Software diagnostic categories. Regression models were created to analyze likelihood of outcome of transfer compared with admission.

Results

Over the 14-year period, there were 38,117,422 pediatric visits to 364 EDs in California with a transfer rate of 1% to 2%. During this time, the overall proportion of pediatric transfers increased, whereas pediatric admissions decreased for all hospital types. Transfers were more likely in general hospitals without licensed pediatric beds (odds ratio [OR], 16.26; 95% confidence interval [CI], 15.87–16.67) and in general hospitals with licensed pediatric beds (OR, 3.54; 95% CI, 3.46–3.62) than in general hospitals with pediatric intensive care unit beds. Mental illness (OR, 61.00; 95% CI, 57.90–63.20), poisoning (OR, 11.78; 95% CI, 11.30–12.30), diseases of the circulatory system (OR, 6.13; 95% CI, 5.84–6.43), diseases of the nervous system (OR, 4.61; 95% CI, 4.46–4.76), and diseases of the blood and blood-forming organs (OR, 3.21; 95% CI, 3.62; 95% CI, 3.45–3.79) had increased odds of transfer.

Conclusion

Emergency departments in general hospitals without pediatric intensive care units and patients' Clinical Classifications Software category were associated with increased likelihood of transfer. A higher proportion of patients with complex conditions are transferred than those with common conditions. General EDs may benefit from developing transfer processes and protocols for patients with complex medical conditions.
Childhood Lead Poisoning 1970-2022: Charting Progress and Needed Reforms
Authors: Jacobs David E. , Brown Mary Jean
Published: November 2022

Context:

Childhood lead poisoning prevention in the United States was marked by a largely failed medical approach from 1971 to 1990; an emergent (but small) healthy housing primary prevention strategy from 1991 to 2015; and implementation of large-scale proven interventions since then.

Program:

Childhood Lead Poisoning Prevention & Healthy Housing.

Methods:

Historic and recent health and housing data from the National Health and Nutrition Examination Survey (NHANES) and the American Healthy Homes Survey (AHHS) were retrieved to analyze trends and associated policy gaps.

Evaluation:

Approximately 590 000 US children aged 1 through 5 years had elevated blood lead levels of 3.5 μg/dL and greater in 2016, and 4.3 million children resided in homes with lead paint in 2019. Despite large improvements, racial and other disparities remain stubbornly and statistically significant. The NHANES and the AHHS require larger sample sizes. The Centers for Disease Control and Prevention has not published children's blood lead surveillance and NHANES data in several years; the Department of Housing and Urban Development (HUD) has no analogous housing surveillance system; and the Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA) have not updated training, Superfund, and occupational standards in decades.

Discussion:

The nation has been without a plan and an associated budget for more than 2 decades. Congress has not reformed the nation's main lead poisoning prevention laws in more than 30 years. Such reforms include stopping US companies from producing new residential lead paint in other countries; enabling the disclosure law to identify all residential lead hazards; closing loopholes in federally assisted housing regulations and mortgage insurance standards; harnessing tax policy to help homeowners mitigate lead hazards; streamlining training requirements; increasing the size of health and housing surveys and surveillance systems; and updating housing codes, medical guidance, dust lead standards, training, Superfund, and worker exposure limits. Congress and the president should reauthorize a cabinet-level task force (dormant since 2010) to develop a new strategic plan with an interagency budget to implement it. These reforms will scale and optimize markets, subsidies, enforcement, and other proven interventions to end ineffective, costly, harmful, and irrational cost shifting that threatens children, workers, and affordable housing.
Brief Report: Refusal of Daily Oral PrEP: Implementation Considerations and Reported Likelihood of Using Various HIV Prophylaxis Products in a Diverse Sample of MSM
Authors: Mansergh Gordon , Kota Krishna Kiran , Carnes Neal , Gelaude Deborah
Published: November 2022

Background:

An important subgroup of gay, bisexual, and other men who have sex with men (MSM) with behavioral indications refuse daily oral pre-exposure prophylaxis (PrEP) when recommended by a provider. Emerging HIV prophylaxis products (eg, injectable, event-driven) offer more options to MSM who refuse daily PrEP. In this article, we assess reasons for refusal and likelihood to use various products among MSM who refused PrEP.

Methods:

MSM who reported anal sex without condoms or PrEP and refused daily oral PrEP in the past 6 months were recruited through clinics, community venues, and online in Atlanta, Chicago, and Raleigh-Durham. Men were asked their main reason for recently refusing daily PrEP and likelihood of using various PrEP options in the future. Bivariate and multivariable regression models were used to estimate associations.

Results:

MSM (n = 93; 70% Black, 48% age 18–29 years) reported their main reason for refusing daily PrEP were potential side effects (35%), a daily pill regimen (22%), and not having enough information (18%). Reported likelihood of using PrEP products was 58% for penile gel, 54% for event-driven oral, 52% for injectable, and 50% for daily PrEP. MSM who reported daily regimen as the main reason for refusing PrEP had greater odds of likelihood to use an injectable [adjusted odds ratio (AOR) = 5.21, 95% confidence interval (CI): 1.32 to 20.52]. Younger men (18–29 vs 30+ years) had greater odds of likelihood to use condoms (AOR = 3.40, 95% CI: 1.15 to 10.04) and daily PrEP (AOR = 2.76, 95% CI: 1.06 to 7.16); there were no product preference differences by race.

Conclusion:

Most men who refused daily PrEP indicated likelihood of using some form of PrEP in the future.
Obstetric Ultrasonography in Postgraduate Radiology Training
Authors: Emekli Emre , Coşkun Özlem , Budakoğlu Işil İrem , Cerit Mahi Nur
Published: November 2022

There is no study in the literature that reveals the adequacy of obstetric ultrasonography (US) training in Turkey. We aimed to evaluate the adequacy of obstetric US training radiologists had received during their residency and determine how competent they considered themselves to be in this regard.

A survey (27 items for residents, 21 items for specialists) was sent to all the radiology residents and specialists in Turkey through the mail list of the Turkish Society of Radiology.

Ninety-one residents and 217 specialists participated in our study. Sixteen residents (17.6%) had received theoretical courses, 21 residents (23.1%) and 59 specialists (27.2%) had attended in-house obstetric US rotations, and 5 residents (5.5%) and 23 specialists (10.6%) had attended obstetric US rotations in another institution. When questioned separately for each trimester, only 11% to 36.3% of the residents stated that they took care of a sufficient number of patients. In general, 62.6% of the residents and 25.3% of the specialists did not consider themselves to be absolutely competent in obstetric US. The competency sources were specified as residency training by 44 residents (48.6%) and 55 specialists (25.3%), postgraduate training by 2 residents (2.2%) and 78 specialist (35.9%).

In Turkey, current obstetric US training does not provide the experience that will allow physicians with radiology training to easily perform and interpret obstetric US. The main reasons for this situation include the limited number of patients the physicians took care of as a resident, insufficient rotation time, and lack of theoretical courses they attended.
A Study on the Expression of Messenger RNAs and Long Noncoding RNA in Keloid Fibroblasts Based on Gene Expression Omnibus Microarray Data Mining
Authors: Su Zhicheng , Liu Xiangxia , Liu Zheng , Deng Yu , Han Bing , Zhang Yujing , Zhu Zhaowei , Xu Yangbin , Xu Shuqia
Published: November 2022

Objective:

The purpose of this study was to find the coding RNA [messenger RNA (mRNA)] and long noncoding RNA (lncRNA) expressed in keloid through the analysis of Gene Expression Omnibus microarray chip of keloid fibroblasts.

Materials and Methods:

Gene Expression Omnibus database GSE7890 database was downloaded with selection of keloids and normal scar group data. The data were analyzed by R language combined with online database. The log2FC>1,Pvalue <0.01 was chosen as screening criteria, and the differentially expressed mRNAs were screened for GO and KEGG function analysis.

Results:

One hundred fifty-five mRNA expression in the keloid group was significantly different from that in the normal group, including 31 groups with upregulated mRNA expression and 124 groups with down-regulated mRNA expression. Meanwhile, 8 lncRNAs were changed in the keloid group, including 3 upregulated (Rp11-420a23.1, Rp11-522b15.3, and Rp11-706j10.1) and 5 down-regulated (LINC00511, LINC00327, Hoxb-as3, Rp11-385n17.1, and Rp3-428l16.2). Quantitative polymerase chain reaction analysis of DElncRNAs in keloid fibroblasts showed that the expression of all DElncRNAs except for RP11-385N17.1 was increased in the keloid group compared with the control group. Moreover, the differences in LINC00511 and RP11-706J10.1 were statistically significant.

Conclusion:

The noncoding RNA information of Gene Expression Omnibus chip data can be deeply mined through bioinformatics, and the potential epigenomic mechanism affecting keloid formation can be found from the existing database.
MiR-140 promotes the progression of intracranial aneurysms by targeting BCL2L2
Authors: Deng Jun , Ning Kangwen , Liu Danhong , Wu Dahua , Wan Rongwen , Ge Jinwen
Published: November 2022

To investigate the role of miR-140/BCL2L2 axis on the formation of intracranial aneurysms. The expression of miR-140 in the serum of patients with intracranial aneurysms and healthy volunteers was detected. CCK-8 assay and Annexin V-FITC/PI double staining flow cytometry were used to evaluate the effect of miR-140 knockdown on the proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs). Meanwhile, the relationship between miR-140 and BCL2L2 was examined. MiR-140 was found to be upregulation in intracranial aneurysm patients. MiR-140 knock-out significantly inhibited the apoptosis of HBVSMCs and promoted cell proliferation. BCL2L2 was a direct target gene of miR-140 and suppressed its expression. Knockdown of miR-140 alleviates the development of intracranial aneurysms. MiR-140/BCL2L2 axis promotes the progression of intracranial aneurysms by regulating apoptosis of HBVSMCs. Therefore, miR-140 is a potential therapeutic target for intracranial aneurysms.
Re-emergence of cholera in Haiti linked to environmentalV. choleraeO1 Ogawa strains
Authors: Mavian Carla N. , Tagliamonte Massimiliano S. , Alam Meer T. , Sakib S. Nazmus , Cash Melanie N. , Riva Alberto , De Rochars V. Madsen Beau , Rouzier Vanessa , Pape Jean William , Morris J. Glenn , Salemi Marco , Ali Afsar
Published: November 2022

BACKGROUND

On September 25th, 2022, cholera re-emerged in Haiti.

OBJECTIVES/METHODS

ToxigenicVibrio choleraeO1 Ogawa were isolated on October 3rd& 4th, 2022, from cholera case patients in Port-au-Prince. The two new genomes were compared with genomes from 2,129V. choleraeO1 isolated worldwide, including 292 Haitian strains from 2010-2018.

RESULTS

Phylogenies conclusively show the 2022 strains clustering within the Haitian monophyletic clade dating back to the 2010 outbreak. Strains shared a most recent common ancestor with a 2018 Haitian Ogawa strain isolated from the aquatic ecosystem, and cluster with the Ogawa clade that was circulating in 2015-2016.

CONCLUSIONS

Re-emergence of cholera in Haiti is the likely result of a spill-over event at the aquatic-human interface related to persistence ofV. choleraeO1 in the environment.

One-Sentence Summary

We analyzed the full genome of twoV. choleraestrains isolated from Haitian patients infected during the early days of the current 2022 epidemic, with data indicating that they originated from strains that have been circulating undetected at sub-epidemic levels in the aquatic environment.
Implementation of flash glucose monitoring in four paediatric diabetes clinics – controlled before and after study to produce real world evidence of patient benefit. Statistical and health economic analysis plan
Authors: Kandiyali R. , Taylor H.
Published: November 2022

This study seeks to answer two key questions:

Does flash glucose monitoring improve outcomes in children with Type 1 diabetes compared to finger prick testing?

What are the healthcare implications associated with flash monitoring when compared to finger prick testing in terms of staff time, experience and healthcare costs?

We report our combined Statistical and Health Economic Plan (SHEAP) for a controlled before and after study using routinely collected health record data on children who are eligible for flash glucose monitoring (Abbott FreeStyle Libre™) and a control population of children who continue to finger prick test in South West England. Our main analysis includes comparison of glucose control in terms of glycated haemoglobin (HbA1c) and UK health service costs relating to prescribing and loss of control (via record of diabetes related complications).
Monoclonal antibody levels and protection from COVID-19
Authors: Stadler Eva , Burgess Martin T , Schlub Timothy E , Chai Khai Li , McQuilten Zoe K , Wood Erica M , Polizzotto Mark N , Kent Stephen J , Cromer Deborah , Davenport Miles P , Khoury David S
Published: November 2022

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in thein vivoconcentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 54-fold of thein vitroIC50 (95% CI: 16 – 183). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants.

Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination.
Community incidence patterns drive the risk of SARS-CoV-2 outbreaks and alter intervention impacts in a high-risk institutional setting
Authors: Moore Sean M. , España Guido , Perkins T. Alex , Guido Robert M. , Jucaban Joaquin B. , Hall Tara L. , Huhtanen Mark E. , Peel Sheila A. , Modjarrad Kayvon , Hakre Shilpa , Scott Paul T.
Published: November 2022

Optimization of control measures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk institutional settings (e.g., prisons, nursing homes, or military bases) depends on how transmission dynamics in the broader community influence outbreak risk locally. We calibrated an individual-based transmission model of a military training camp to the number of RT-PCR positive trainees throughout 2020 and 2021. The predicted number of infected new arrivals closely followed adjusted national incidence and increased early outbreak risk after accounting for vaccination coverage, masking compliance, and virus variants. Outbreak size was strongly correlated with the predicted number of off-base infections among staff during training camp. In addition, off-base infections reduced the impact of arrival screening and masking, while the number of infectious trainees upon arrival reduced the impact of vaccination and staff testing. Our results highlight the importance of outside incidence patterns for modulating risk and the optimal mixture of control measures in institutional settings.

Disclaimer

The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Strengthening response coordination through public health emergency operations centers in Africa: Lessons learned from 56-week webinar sessions, 2020-2021
Authors: Eteng Womi , Lilay Abrham , Tekeste Senait , Mankoula Wessam , Collard Emily , Waya Chimwemwe , Rosenfeld Emily , Wilton Chuck Menchion , Muita Martin , McGinley Liz , Kawe Yan , Abdullah Ali , Halm Ariane , Li Jian , Lokossou Virgil L , Kanoute Youssouf , Sonko Ibrahima , Aragaw Merawi
Published: November 2022

Background

Following the declaration of coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020, in-person events including trainings were canceled to limit the spread of the pandemic. A virtual learning program was established in May 2020 by Africa Centers for Disease Control and Prevention, the World Health Organization, and other partners to strengthen COVID-19 response coordination through the public health emergency operations centers (PHEOCs). We present a review of the webinar series, the experience, and the lessons learned.

Method

A data extraction tool was developed to retrieve data from the Africa CDC’s webinar data repository. Major findings were synthesized and described per thematic area.

Results

A total of 12,715 (13% of the 95,230 registrants) attended the 56 PHEOC webinar sessions between June 2020 and December 2021 and 47% of the attendees came from 17 countries. Of those who attended, 8,528 (70%) were from Africa. The webinars provided 97 learning hours with an average length of 1.18 hours per session. On average, there were 235 attendees per session. In addition, there was an average of 26 interactions between participants and facilitators per session. A total of 4,084 (44%) of the participants (9,283) responded to the post-session surveys, with over 95% rating the webinar topics as being relevant to their work, contributed to improving their understanding of PHEOC operationalization, and with extensive ease of comprehension.

Conclusion

The virtual training served the intended audience given the high number of participants from African member states, with satisfactory feedback on training relevance. We highlighted a just-in-time, progressively adaptive experience in delivering a PHEOC/PHEM virtual learning in Africa with a consequential global audience at the peak of the COVID-19 pandemic.
Heterogeneity of treatment effect of higher dose dexamethasone by geographic region in patients with COVID-19 and severe hypoxemia - Apost hocevaluation of the COVID STEROID 2 trial
Authors: Tirupakuzhi Vijayaraghavan Bharath Kumar , Granholm Anders , Myatra Sheila N , Jha Vivekanand , Hammond Naomi , Micallef Sharon , Munch Marie Warrer , Kjær Maj-Brit N , Møller Morten Hylander , Lange Theis , Perner Anders , Venkatesh Balasubramanian ,   the COVID-STEROID 2 collaborators
Published: November 2022

Background

The COVID-STEROID 2 trial found high probability of benefit with dexamethasone 12 mg vs. 6 mg daily among patients with COVID-19 and severe hypoxemia. There was suggestion of heterogeneity of treatment effects (HTE)between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE by geographical region for the remaining prespecified patient-important outcomes is unclear.

Methods

We evaluated HTE by geographical region (Europe vs. India) for all secondary outcomes assessed in the trial with analyses adjusted for stratification variables. The results are presented as risk differences (RDs) or mean differences (MDs) with 99% confidence intervals (CIs) and P-values from interaction tests.

Results

We found HTE for mortality at day 28 (RD for Europe -8.3% (99 % CI: -17.7 to 1.0) vs. RD for India 0.1% (99% CI: -10.0 to 10.0)), mortality at day 90 (RD for Europe -7.4% (99% CI: -17.1 to 2.0) vs. RD for India -1.4% (99% CI:-12.8 to 9.8)), mortality at day 180 (RD for Europe -6.7% (99%CI:-16.4 to 2.9) vs. RD for India -1.0% (99%CI:-12.3 to 10.3)), and number of days alive without life support at day 90 (MD for Europe 6.1 days (99% CI:-1.3 to 13.4) vs. MD for India 1.7 days (99% CI:-8.4 to11.8)). For serious adverse reactions, the direction was reversed (RD for Europe -1.0% (99% CI:-7.1 to 5.2) vs. RD for India -5.3% (99% CI: -16.2 to 5.0). For HRQoL outcomes, MD in EQ-5D-5L index values was 0.08(99%CI: -0.01 to 0.16) for Europe and 0.02(99%CI:-0.10 to 0.14) for India. For EQ VAS, MD was 4.4(95%CI:-3.1 to 11.9) for Europe and 2.6(99%CI:-9.0 to 14.2) for India. P values for all tests of interaction were ≥0.12.

Conclusions

In thispost hocexploratory analysis, we found that higher dose dexamethasone may have lower beneficial effects for patients in India as compared with those in Europe without an increase in serious adverse reactions.
Sinonasal disease among patients with primary ciliary dyskinesia – an international study
Authors: Lam Yin Ting , Papon Jean-François , Alexandru Mihaela , Anagiotos Andreas , Armengot Miguel , Boon Mieke , Burgess Andrea , Crowley Suzanne , Dheyauldeen Sinan Ahmed. D. , Emiralioglu Nagehan , Eralp Ela Erdem , van Gogh Christine , Gokdemir Yasemin , Gunaydın Onder , Haarman Eric G. , Harris Amanda , Hayn Isolde , Ismail-Koch Hasnaa , Karadag Bülent , Kempeneers Céline , Kim Sookyung , Latzin Philipp , Lorent Natalie , Ozcelik Ugur , Pioch Charlotte , Poirrier Anne-Lise ML , Reula Ana , Roehmel Jobst , Yiallouros Panayiotis , Goutaki Myrofora
Published: November 2022

Background

Although most patients with primary ciliary dyskinesia (PCD) report sinonasal symptoms, little is known about symptom frequency and severity. We describe sinonasal manifestations among PCD patients using data from the Ear, nose, and throat (ENT) Prospective International Cohort of PCD patients.

Methods

We included data from participants with routine clinical ENT examinations and complete FOLLOW-PCD symptoms questionnaires from the same visit or within 2 weeks. We compared the prevalence, reported symptoms, and clinical findings among children and adults and identified potential factors associated with increased risk of sinonasal disease using ordinal regression.

Results

We included 397 (53% male) participants from 12 centres with median age 15 years (IQR 9– 22). Almost all (352; 89%) reported chronic nasal symptoms. More adults (34; 26%) than children (11; 5%) reported anosmia or hyposmia. Among 140 participants who completed SNOT-22 questionnaires, quality of life was moderately affected by sinonasal symptoms (median score 31; IQR 22–45). We observed nasal polyps among 52 (15%) of 352 participants and hypertrophic inferior nasal turbinates among 129 (34%) of 353 participants; facial pain was recorded among 51 (13%) of 353 participants. More adults than children had nasal polyps, hypertrophic turbinates, deviated septum, and facial pain. We found age 10 and older the only factor associated with increased risk of sinonasal disease.

Conclusions

Our study reinforces the importance of regular sinonasal evaluations for patients of all ages with PCD and the need for developing evidence-based guidelines for sinonasal treatments as part of overall PCD management.
Process Model of Emotion Regulation-Based Digital Intervention for Emotional Problems — A mixed methods feasibility study
Authors: Qu Diyang , Liu Dongyu , Cai Chengxi , Yu Jiaao , Zhang Quan , Liu Kunxu , Zhang Xuan , Wei Ziqian , Tan Jiajia , Cui Zaixu , Zhang Xiaoqian , Chen Runsen
Published: November 2022

The current study explored the feasibility of a newly developed self-guided digital intervention program TEA (Training for Emotional Adaptation) in alleviating depressive and anxiety symptoms, corresponding to the urgent call for remote mental health service. It is one of a few studies which adapted from theoretical models with effective intervention techniques. The first part involved 11 professional mental health practitioners giving feedback on the feasibility; while the second part involved a single-arm study with 32 participants recruited online, who went through the seven intervention sessions. The questionnaires were collected before, after, 14-days after and 30-days after the intervention. Moreover, 10 participants were invited to semi-structured interviews. Practitioners thought the TEA showed high professionalism (8.91/10) and is suitable for treating emotional symptoms (8.09/10). The Generalized estimating equation (GEE) model showed that the TEA significantly reduced their psychological symptoms, while the effects of the intervention were retained for 30-day post intervention (Cohen’s d >1). Thematic analysis revealed three main themes about future improvement, including content improvement, interaction improvement and bug-fixing. Taken together, current study supported the effectiveness of TEA, with the potential to address the urgent need for remote mental health service. Future randomized controlled trials to confirm the effectiveness are required.
Accelerated absorption of regular insulin administered via a vascularizing permeable microchamber implanted subcutaneously in diabeticRattus norvegicus
Authors: Steyn Leah V. , Drew Delaney , Vlachos Demetri , Huey Barry , Cocchi Katie , Price Nicholas D. , Johnson Robert , Putnam Charles W. , Papas Klearchos K.
Published: November 2022

In Type 1 diabetes patients, even ultra-rapid acting insulins injected subcutaneously reach peak concentrations in 45 minutes or longer. The lag time between dosing and peak concentration, as well as intra- and inter-subject variability, render prandial glucose control and dose consistency difficult. We postulated that insulin absorption from subcutaneously implantable vascularizing microchambers would be significantly faster than conventional subcutaneous injection. Male athymic nudeR. norvegicusrendered diabetic with streptozotocin were implanted with vascularizing microchambers (single chamber; 1.5 cm2 surface area per side; nominal volume, 22.5 µL). Plasma insulin was assayed after a single dose (1.5 U/kg) of diluted insulin human (Humulin®R U-100), injected subcutaneously or via microchamber. Microchambers were also implanted in additional animals and retrieved at intervals for histologic assessment of vascularity. Following conventional subcutaneous injection, the mean peak insulin concentration was 22.7 (SD 14.2) minutes. By contrast, when identical doses of insulin were injected via subcutaneous microchamber 28 days after implantation, the mean peak insulin time was shortened to 7.50 (SD 4.52) minutes. Peak insulin concentrations were similar by either route; however, inter-subject variability was reduced when insulin was administered via microchamber. Histologic examination of tissue surrounding microchambers showed mature vascularization on days 21 and 40 post-implantation. Implantable vascularizing microchambers of similar design may prove clinically useful for insulin dosing, either intermittently by needle, or continuously by pump including in “closed loop” systems, such as the artificial pancreas.
Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3 to 4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination
Authors: Assawakosri Suvichada , Kanokudom Sitthichai , Suntronwong Nungruthai , Chansaenroj Jira , Auphimai Chompoonut , Nilyanimit Pornjarim , Vichaiwattana Preeyaporn , Thongmee Thanunrat , Duangchinda Thaneeya , Chantima Warangkana , Pakchotanon Pattarakul , Srimuan Donchida , Thatsanatorn Thaksaporn , Klinfueng Sirapa , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Mongkolsapaya Juthathip , Honsawek Sittisak , Poovorawan Yong
Published: November 2022

Objectives

Several countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine-induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming.

Methods

A total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90– 120 after booster.

Results

A waning of total RBD immunoglobulin (Ig) levels, anti-RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90–120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50% to 75% among all booster vaccine.

Conclusions

The antibody response substantially waned after 90–120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection.

Highlights

The persistence of antibody responses is different among three vaccine platforms.

Highly remained antibody levels were observed with the mRNA and viral vector booster.

The half-dose mRNA-1273 can be used interchangeably with the full-dose mRNA-1273.

The neutralizing activity against BA.5 was lower than wild type and BA.2 subvariant.

A fourth dose is recommended for individuals who received an inactivated booster.
Extracellular disintegration of viral proteins as an innovative strategy for developing broad-spectrum antivirals against coronavirus
Authors: Sun Ke , Ding Zhe , Jia Xiaoying , Cheng Haonan , Li Yingwen , Wu Yan , Li Zhuoyu , Huang Xiaohua , Pu Fangxu , Li Entao , Wang Guiyou , Wang Wei , Ding Yun , Wong Gary , Chiu Sandra , Lan Jiaming , Hu Aiguo
Published: November 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives worldwide, not to mention innumerable losses in the global economy and disruptions in social relationships. Unfortunately, state-of-the-art treatments still lag behind the fast emergence of new variants of concern. The key to resolve this issue is to develop broad-spectrum antivirals with innovative antiviral mechanisms in which coronaviruses are deactivated regardless of their variant development. Herein, we report a new antiviral strategy involving extracellular disintegration of viral proteins that are indispensable for viral infection with hyperanion-grafted enediyne molecules. The sulfate groups ensure low cellular permeability and rather low cytotoxicity of the molecules, while the core enediyne generates reactive radical species and causes significant damage to the spike (S) protein of coronavirus. The enediyne compounds exhibit antiviral activity at micromolar to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronaviruses, including the SARS-CoV-2 omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic.
Genome-wide association study of placental weight in 179,025 children and parents reveals distinct and shared genetic influences between placental and fetal growth
Authors: Beaumont Robin N. , Flatley Christopher , Vaudel Marc , Wu Xiaoping , Chen Jing , Moen Gunn-Helen , Skotte Line , Helgeland Øyvind , Sole-Navais Pol , Banasik Karina , Albiñana Clara , Ronkainen Justiina , Fadista João , Stinson Sara Elizabeth , Trajanoska Katerina , Wang Carol A , Westergaard David , Srinivasan Sundararajan , Sánchez-Soriano Carlos , Bilbao Jose Ramon , Allard Catherine , Groleau Marika , Kuulasmaa Teemu , Leirer Daniel J. , White Frédérique , Jacques Pierre-Étienne , Cheng Haoxiang , Hao Ke , Andreassen Ole A. , Åsvold Bjørn Olav , Atalay Mustafa , Bhatta Laxmi , Bouchard Luigi , Brumpton Ben Michael , Brunak Søren , Bybjerg-Grauholm Jonas , Ebbing Cathrine , Elliott Paul , Engelbrechtsen Line , Erikstrup Christian , Estarlich Marisa , Franks Steve , Gaillard Romy , Geller Frank , Grove Jakob , Hougaard David M , Kajantie Eero , Morgen Camilla S. , Nohr Ellen A , Nyegaard Mette , Palmer Colin NA , Pedersen Ole Birger ,   The Early Growth Genetics (EGG) Consortium, Rivadeneira Fernando , Sebert Sylvain , Shields Beverley M. , Stoltenberg Camilla , Surakka Ida , Thørner Lise Wegner , Ullum Henrik , Vaarasmaki Marja , Vilhjalmsson Bjarni J , Willer Cristen J. , Lakka Timo A. , Gybel-Brask Dorte Jensen , Bustamante Mariona , Hansen Torben , Pearson Ewan R , Reynolds Rebecca , Ostrowski Sisse R. , Pennell Craig E , Jaddoe Vincent W. V. , Felix Janine F , Hattersley Andrew T. , Melbye Mads , Lawlor Deborah A. , Hveem Kristian , Werge Thomas , Nielsen Henriette Svarre , Magnus Per , Evans David M , Jacobsson Bo , Järvelin Marjo-Riitta , Zhang Ge , Hivert Marie-France , Johansson Stefan , Freathy Rachel M. , Feenstra Bjarke , Njølstad Pål R.
Published: November 2022

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight after term delivery as a proxy for placental growth, we report genome-wide association analyses in the fetal (n= 65,405), maternal (n= 61,228), and paternal (n= 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are confidently classified as fetal only, four maternal only, and three fetal and maternal. A maternal parent-of-origin effect is seen nearKCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but twelve loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with risk of preeclampsia or shorter gestational duration. Moreover, these analyses support a role for insulin produced by the fetus in regulating the growth of the placenta, providing a key link between fetal and placental growth.
Enhanced cholera surveillance as a tool for improving vaccination campaign efficiency
Authors: Xu Hanmeng , Zou Kaiyue , Dent Juan , Wiens Kirsten E. , Bwenge Espoir Malembaka , Hampton Lee M. , Azman Andrew S. , Lee Elizabeth C.
Published: November 2022

Systematic testing forVibrio cholerae O1is rare, which means that the world’s limited supply of oral cholera vaccines may not be delivered to areas with the highest true cholera burden. We modeled how expandingV. choleraetesting affected vaccine impact and cost-effectiveness across different bacteriological confirmation and vaccine targeting assumptions. Systematic testing yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. With a 10 per 10,000 incidence rate targeting threshold, testing and status quo scenarios averted 10.3 (95% PI: 8.3-13.0) and 5.6 (95% PI: 4.6-6.7) cases per 1,000 FVPs, respectively. Comparing these scenarios, testing costs increased by $37 (95% PI: 29-52) while vaccination costs reduced by $376 (95% PI: 275-556) per averted case. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.
The network structure of hematopoietic cancers
Authors: Nakamura-García Arturo Kenzuke , Espinal-Enríquez Jesús
Published: November 2022

Hematopoietic cancers (HCs) are a heterogeneous group of malignancies that affect blood, bone marrow and lymphatic system. Here, by analyzing 1,960 RNA-Seq samples from three independent datasets, we explored the co-expression landscape in HCs, by inferring gene co-expression networks (GCNs) with four cancer phenotypes (B and T-cell acute leukemia -BALL, TALL-, acute myeloid leukemia -AML-, and multiple myeloma -MM-) as well as non-cancer bone marrow. We characterized their structure (topological features) and function (enrichment analyses). We found that, as in other types of cancer, the highest co-expression interactions are intra-chromosomal, which is not the case for control GCNs. We also detected a highly co-expressed group of overexpressed pseudogenes in HC networks. The four GCNs present only a small fraction of common interactions, related to canonical functions, like immune response or erythrocyte differentiation. With this approach, we were able to reveal cancer-specific features useful for detection of disease manifestations.

Significance

We demonstrate that gene co-expression is deregulated in four HC, observed by an elevated proportion of intrachromosome interactions in their GCNs with respect to their normal counterparts, and increased interactions between pseudogenes (more evident in AML). This deregulation might be associated with the age of the patients.
GlobalUsefulNativeTrees, a database of 14,014 tree species and their uses, supports synergies between biodiversity recovery and local livelihoods in landscape restoration
Authors: Kindt Roeland , Graudal Lars , Lilleso Jens-Peter , Pedercini Fabio , Smith Paul , Jamnadass Ramni
Published: November 2022

Tree planting has the potential to improve the livelihoods of millions of people as well as to support environmental services such as biodiversity preservation. Planting however needs to be executed wisely if benefits are to be achieved. We have developed the GlobalUsefulNativeTrees (GlobUNT) database to directly support the principles advocated by the ‘golden rules for reforestation’, including planting tree mixtures that maximize the benefits to local livelihoods and the diversity of native trees. Developed primarily by combining data from GlobalTreeSearch with the World Checklist of Useful Plant Species, GlobUNT includes 14,014 tree species that can be filtered for ten major use categories, across 242 countries and territories. In a subcontinental comparison GlobUNT revealed that Malesia had the highest useful tree species richness (3,349) and was also richest for materials (2,723), medicines (1,533), human food (958), fuel (734), environmental uses (632), social uses (614), animal food (443), poisons (322) and invertebrate food (266).
Is the health system ready for future crises? A qualitative study protocol
Authors: Rahimi-Ardabili Hania , Magrabi Farah , Coiera Enrico
Published: November 2022

The COVID-19 pandemic serves as a clarion call to ensure health systems are better prepared to meet future emergencies. Digital Health could play a significant role in preparing health systems to bend and stretch their resources and cope with various shocks by facilitating tasks such as disease monitoring and care delivery. However, the health system’s needs during the crises have not been thoroughly examined from the perspective of health professionals in general and in the Australian health setting in particular. Here we describe the protocol of a qualitative design to learn from frontline healthcare workers’ experiences of the pandemic response that can guide preparation for future crises using digital health.
Testing for bi-directional rejection thresholds to sweetness and their links to sugar intake and sweet-taste drink consumption
Authors: Peng Mei , Ginieis Rachel , Abeywickrema Sashie , McCormack Jessica , Prescott John
Published: November 2022

Background and Aims

Sugar intake has been linked to obesity, however, the relationship between individual sugar perception and dietary choice remains unclear. The current study aims to measure individual bi-directional rejection thresholds and compare these measures to sugar intake and consumption patterns of sweet-taste beverages.

Methods

A cross-section design will be used to analyse the relationship between sweetness perception, sucrose liking, and dietary intake. Participants will attend laboratory sessions to assess sucrose liking, ascending and descending rejection thresholds, and detection thresholds, and complete a 4-day weighed food-diary to assess dietary intake. ANCOVA will be used to test for differences in detection threshold and hedonic VAS ratings between the liking and disliking group, with age, gender, and BMI as covariates. A generalised linear mixed-models will be applied to test for differences in individual ascending versus descending rejection threshold across the two sweet liker status groups. Regression models will be used to test the role of ascending versus descending rejection thresholds on predicting sugar and sweet-taste beverage consumption.

Discussion

More research focusing on links between individual sweetness perception and sugar intake will be important for elucidating the mechanism underpinning sensory effects on dietary behaviour.
RBPMS promotes contractile smooth muscle splicing and alters phenotypic behaviour of human embryonic stem cell derived vascular smooth muscle cells
Authors: Jacob Aishwarya G , Moutsopoulous Ilias , Petchey Alex , Mohorianu Irina , Sinha Sanjay , Smith Christopher WJ
Published: November 2022

Differentiated Vascular Smooth Muscle Cells (VSMCs) express a unique network of splice isoforms (smooth muscle specific alternative splicing - SM-AS) in functionally critical genes including those comprising the contractile machinery. We previously described RNA Binding Protein Multiple Splicing (RBPMS) as a potent driver of contractile, aortic tissue like SM-AS in VSMCs using rodent models. What is unknown is how RBPMS affects VSMC phenotype and behaviour. Here, we use human embryonic stem cell-derived VSMCs (hES-VSMCs) to dissect the role of RBPMS in SM-AS in human cells and determine the impact on VSMC phenotypic properties. hES-VSMCs are inherently immature and display only partially differentiated SM-AS patterns while RBPMS levels are undetectable endogenously. Hence, we used an over-expression system and found that RBPMS induces SM-AS patterns in hES-VSMCs akin to the contractile tissue VSMC splicing patterns in multiple events. We presentin silicoand experimental findings that support RBPMS’ splicing activity as mediated through direct binding and via functional cooperativity with splicing factor RBFOX2 on a significant subset of targets. Finally, we demonstrate that RBPMS is capable of altering the motility and the proliferative properties of hES-VSMCs to mimic a more differentiated state. Overall, this study emphasizes a critical splicing regulatory role for RBPMS in human VSMCs and provides evidence of phenotypic modulation by RBPMS.
Hypoxic tumors are sensitive to FLASH radiotherapy
Authors: Leavitt Ron J. , Almeida Aymeric , Grilj Veljko , Montay-Gruel Pierre , Godfroid Céline , Petit Benoit , Bailat Claude , Limoli Charles L. , Vozenin Marie-Catherine
Published: November 2022

Tumor hypoxia is a major cause of resistance to cancer treatments and especially to radiotherapy (RT) and we wanted to assess whether ultra-high dose rate FLASH RT could overcome this resistance. We engrafted tumor cells of various origins subcutaneously in mice to provide a reliable and rigorous way to modulate oxygen supply via vascular clamping or carbogen breathing. We irradiated tumors using a single 20 Gy fraction at either conventional (CONV) or FLASH dose-rate. Using multiple different subcutaneous tumor models, and in contrast CONV-RT, FLASH-RT retained anti-tumor efficacy under extreme hypoxia. These findings demonstrate that in addition to normal tissue sparing, FLASH-RT overcomes hypoxia-mediated tumor resistance. Follow-up molecular analysis using RNAseq profiling uncovered FLASH-specific inhibition of cell proliferation and translation as well as metabolic shifts that discriminated FLASH-RT from CONV-RT. These data provide new and specific insights into the mechanism of action and identify novel targets for intervention.
Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses
Authors: Kahraman Sevim , Shibue Kimitaka , De Jesus Dario F. , Hu Jiang , Manna Debasish , Wagner Bridget K. , Choudhary Amit , Kulkarni Rohit N.
Published: November 2022

Pancreatic α-cells secrete glucagon, an insulin counter-regulatory peptide hormone critical for the maintenance of glucose homeostasis. Investigation of the function of human α-cells remains a challenge due to the lack of cost-effective purification methods to isolate high-quality α-cells from islets. Here, we use the reaction-based probe diacetylated Zinpyr1 (DA-ZP1) to introduce a novel and simple method for enriching live α-cells from dissociated human islet cells with > 97% purity. The α-cells, confirmed by sorting and immunostaining for glucagon, were cultured up to 10 days to form α-pseudoislets. The α-pseudoislets could be maintained in culture without significant loss of viability, and responded to glucose challenge by secreting appropriate levels of glucagon. RNA-sequencing analyses (RNA-seq) revealed that expression levels of key α-cell identity genes were sustained in culture while some of the genes such asDLK1, GSN, SMIM24were altered in α-pseudoislets in a time-dependent manner. In conclusion, we report a method to sort human primary α-cells with high purity that can be used for downstream analyses such as functional and transcriptional studies.