bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment
Authors: Jabba Sairam V , Erythropel Hanno C , Torres Deyri Garcia , Delgado Lauren A , Woodrow Jackson G , Anastas Paul T , Zimmerman Julie B , Jordt Sven-Eric
Published: February 2022

Introduction

Menthol, through its cooling and pleasant sensory effects, facilitates smoking and tobacco product initiation, resulting in the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited.

Aims and Methods

E-liquid vendor sites were searched with the terms “koolada”, “kool/cool”, “ice”, or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. “Ice” flavor varieties of Puffbar, the most popular disposable E-cigarette brand, were compared with non-“Ice” varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use.

Results

WS-3 was detected in 24/25 refill E-liquids analyzed. All Puffbar flavor varieties contained either WS-23 (13/14) or WS-3 (5/14), in both “Ice”- and non-“Ice” flavors. Modeling consumption of WS-3 from vaped E-liquids, resulted in MOEs below the safe margin of 100 for most daily use scenarios. MOEs for WS-23 were <100 for 10/13 Puffbar flavors in all use scenarios. Puffbar power specifications are identical to Juul devices.

Conclusions

Synthetic cooling agents (WS-3/WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic coolants are not only found in mint- or menthol-flavored products but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar.

Implications

Synthetic cooling agents are widely used in “kool/cool”- and “ice”-flavored E-liquids and in E-liquids without these labels, both as a potential replacement for menthol or to add cooling “notes” to nonmenthol flavors. These agents may be used to bypass current and future regulatory limits on menthol content in tobacco products, and not just E-cigarettes. Because synthetic cooling agents are odorless, they may not fall under the category of “characterizing flavor”, potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents.
Is replacing red meat with other protein sources associated with lower risks of coronary heart disease and all-cause mortality? A meta-analysis of prospective studies
Authors: Hidayat Khemayanto , Chen Jing-Si , Wang Hai-Peng , Wang Tian-Ci , Liu Yu-Jie , Zhang Xue-Ying , Rao Chun-Ping , Zhang Jian-Wei , Qin Li-Qiang
Published: February 2022

Context

A high amount of red meat consumption has been associated with higher risks of coronary heart disease (CHD) and all-cause mortality in a single food-exposure model. However, this model may overlook the potentially differential influence of red meat on these outcomes depending on the foods replaced by red meat.

Objective

A PRISMA-compliant meta-analysis of prospective observational studies was performed to quantify the risks of CHD and all-cause mortality associated with the replacement of total, unprocessed, or processed red meat with fish/seafood, poultry, dairy, eggs, nuts, and legumes.

Data sources

The PubMed and Web of Science databases were searched to identify relevant articles published in any language from database inception to October 30, 2021.

Data extraction

The prospective observational studies were considered relevant if they reported relative risks (RRs) and 95%CIs for the associations of interest.

Data analysis

Thirteen articles were included. A random-effects model was used to estimate the summary RRs and 95%CIs for the associations of interest. Replacing total red meat with poultry (RR, 0.88, 95%CI, 0.82–0.96; I2 = 0%), dairy (RR, 0.90, 95%CI, 0.88–0.92; I2 = 0%), eggs (RR, 0.86, 95%CI, 0.79–0.94; I2 = 7.1%), nuts (RR, 0.84, 95%CI, 0.74–0.95; I2 = 66.8%), or legumes (RR, 0.84, 95%CI, 0.74–0.95; I2 = 7.3%) was associated with a lower risk of CHD, whereas substituting fish/seafood (RR, 0.91, 95%CI, 0.79–1.04; I2 = 69.5%) for total red meat was not associated with the risk of CHD. The replacement of total red meat with fish/seafood (RR, 0.92, 95%CI, 0.89–0.96; I2 = 86.9%), poultry (RR, 0.92, 95%CI, 0.90–0.95; I2 = 61.6%), eggs (RR, 0.91, 95%CI, 0.87–0.95; I2 = 33.8%), or nuts (RR, 0.92, 95%CI, 0.87–0.97; I2 = 81.9%) was associated with a lower risk of all-cause mortality, whereas the substitution of dairy (RR, 0.97, 95%CI, 0.93–1.01; I2 = 33.9%) or legumes (RR, 0.97, 95%CI, 0.93–1.01; I2 = 53.5%) for total red meat was not associated with the risk of all-cause mortality. Lower risks of CHD and all-cause mortality were more consistently observed for processed red meat replacements than for unprocessed red meat replacements. The results did not materially change when the analyses of total, processed, and unprocessed red meat were restricted to the studies that used a uniform substitution amount per unit of 1 serving/d.

Conclusion

Keeping red meat, particularly processed red meat, consumption to a minimum along with increasing healthier alternative protein sources to replace red meat in the diet may contribute to the prevention of CHD and premature death.

Systematic review registration

PROSPERO registration no. CRD42021259446.
Neural Stem Cell-Derived Exosomal Netrin1 Contributes to Neuron Differentiation of Mesenchymal Stem Cells in Therapy of Spinal Bifida Aperta
Authors: Ma Ling , Wei Xiaowei , Ma Wei , Liu Yusi , Wang Yanfu , He Yiwen , Jia Shanshan , Wang Yu , Luo Wenting , Liu Dan , Huang Tianchu , Yan Jiayu , Gu Hui , Bai Yuzuo , Yuan Zhengwei
Published: February 2022

Spinal bifida aperta (SBA) is a congenital malformation with a high incidence. Bone marrow mesenchymal stem cell (BMSC) transplantation has the potential to repair the structure of damaged tissues and restore their functions. This is an optional treatment that can be used as a supplement to surgery in the treatment of SBA. However, the application of BMSCs is limited, as the neuronal differentiation rate of BMSCs is not satisfactory when used in treating severe SBA. Thus, we aimed to assess the effect of neural stem cell (NSC)-derived exosomes on BMSC neuronal differentiation and observe the therapeutic effect in an ex vivo rat SBA embryo model. We found that NSC-derived exosomes increased the neuronal differentiation rate of BMSCs in vitro and in the SBA embryo model ex vivo. Proteomic analysis showed that NSC-derived exosomes were enriched in Netrin1, which positively regulated neuronal differentiation. Netrin1 increased the neuronal differentiation rate of BMSCs and NSCs and upregulated the expression of the neuronal markers, microtubule-associated protein (Map2), neurofilament, and β3-tubulin. Bioinformatic analysis revealed that Netrin1 treatment increased the expression of the transcription factors Hand2 and Phox2b, related to neuronal differentiation. Furthermore, the Netrin1-induced NSC neuronal differentiation was significantly blocked by Phox2b knockdown. We suggest that NSC-derived exosomal Netrin1 induces neuronal differentiation via the Hand2/Phox2b axis by upregulating the expression of Hand2 and Phox2b. Therefore, NSC-derived exosomes are a critical inducer of BMSC neuronal differentiation and represent a potential treatment agent that can benefit BMSC treatment in SBA.
Characteristics of allergen profile, sensitization patterns and Allergic Rhinitis in SouthEast Asia
Authors: Pham Duy Le , Trinh Tu Hoang Kim , Le Kieu_Minh , Pawankar Ruby
Published: February 2022

Purpose of review

To highlight the characteristics of allergic rhinitis, local allergic rhinitis (LAR), and importance of allergens in Southeast Asian countries.

Recent findings

The Asia-Pacific region is very diverse with disparities in the epidemiological data between countries as well as in the unmet needs. The prevalence of allergic rhinitis has markedly increased in the past decades, with a high variation between countries, ranging from 4.5--80.3%. In terms of LAR, the reported prevalence in Southeast Asia is similar to that of other Asian countries (3.7–24.9%) but lower than that in western countries. House dust mites, cockroach, pollens, and molds are major allergens that are known triggers for of allergic rhinitis in this region, whereas the association with helminth infection requires further investigation.

There are gaps and high variation between countries in Southeast Asia regarding the prevalence of allergic rhinitis and LAR. Further studies are needed to fully elucidate the association between allergens and allergic rhinitis in Southeast Asia.
Atopic dermatitis endotypes: knowledge for personalized medicine
Authors: Kim Jihyun , Ahn Kangmo
Published: February 2022

Purpose of review

Endotypes are clinically relevant phenotypes that can be explained by molecular mechanisms, and are defined to predict the development, progression, prognosis and responses to treatment on the individual level. This review summarizes atopic dermatitis phenotypes, endotypes and their potential application for personalized medicine.

Recent findings

Atopic dermatitis can be classified into several phenotypes according to disease courses that likely have common pathophysiology. The genotype is important to define endotypes, but the value of genotype alone remains somewhat limited in most atopic dermatitis patients. Recent studies have demonstrated that atopic dermatitis phenotypes according to ethnicity or age can be classified into endotypes based on the dominant immunologic markers, that is TH1/TH2/TH17/TH22 cells. Newly developed biologic agents targeting specific cytokines show therapeutic potential in a personalized medicine approach.

Cytokine-based endotypes in different age groups or ethnic groups have contributed to expanding our understanding of atopic dermatitis. Recent biologics or small molecules can be used for more personalized treatment of atopic dermatitis. Further research using integrated multiomic analysis is needed to define a more detailed classification of endotypes and provide endotype-driven targeted therapies for personalized medicine.
Drug allergy desensitization is not a unique recipe
Authors: Madrigal-Burgaleta Ricardo , Guzman-Melendez Maria Antonieta , Alvarez-Cuesta Emilio
Published: February 2022

Purpose of review

Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field.

Recent findings

Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics.

Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres.
Uveal melanoma metastatic at initial diagnosis: a case series
Authors: Steckler Alexa M. , Francis Jasmine H. , Shoushtari Alexander N. , Abramson David H. , Barker Christopher A.
Published: February 2022

Detectable metastasis at the time of initial diagnosis of uveal melanoma (UM) is rare. The purpose of this investigation was to evaluate the characteristics and outcomes in patients with metastatic UM (MUM) at initial diagnosis. An institutional review board-approved retrospective case series analysis was performed in 21 patients that presented for management of MUM at initial diagnosis. Patient, tumor and treatment parameters were recorded, and ophthalmic symptoms, metastasis response and overall survival were assessed. Among 21 patients, median tumor diameter was 18 mm (range, 9.1–35 mm), with 76% classified as a Collaborative Ocular Melanoma Study (COMS) large size. Sites of metastasis included liver (95%), bone (29%) and lung (29%), among others, and were confirmed by biopsy in 95% of patients studied. Symptomatic primary tumors were present in 81%, causing pain (24%) or vision loss (57%). Primary tumor therapy (PTT) was provided upfront for 52% of patients with enucleation (24%) and brachytherapy (29%). Eye pain developed 3–6 months after diagnosis in four of 10 patients who did not receive upfront PTT, whereas it did not occur in any of the 11 patients who received upfront PTT (P = 0.04). PTT palliated pain in all cases. The median overall survival was 11.9 months (range, 2.5–21.1 months). Patients presenting with MUM at initial diagnosis have high-risk tumors and experience survival like patients who develop metastases metachronously. PTT is not associated with survival but may mitigate ophthalmic symptoms, especially in patients with large tumors at risk for causing symptoms.
Direct Exchange of PerfluoroCarbon Liquid for Silicone Oil: A Surgical Technique to Control Pressure and Avoid Retinal Slippage
Authors: Treacy Maxwell P. , Conway Marcus P. , Hammoud Mohammad Al , Duignan Emma S. , Ahearne Mark , Ezra Eric
Published: February 2022

Background/Purpose:

Perfluorocarbon heavy liquid (PFCL) is used in vitreoretinal surgery to flatten the unsupported detached retina before insertion of silicone oil in cases of giant retinal tear or relaxing retinectomy. Direct exchange of PFCL for silicone oil is recommended to reduce retinal slippage when compared with fluid–air exchange, but it is commonly regarded as a difficult procedure. We describe our technique for direct PFCL–silicone oil exchange using a 20-gauge drainage cannula, reliably avoiding the complications of retinal slippage and high intraoperative intraocular pressure.

Methods:

We present a consecutive case series of patients undergoing PFCL–oil exchange and explain, using Poiseuille's equation for laminar fluid flow through a cannula, the rationale for using a 20-gauge drainage cannula rather than smaller gauges to avoid high intraocular pressure.

Results:

Twenty-six patients underwent PFCL–oil exchange from February 1, 2019, to September 30, 2019. There was no intraoperative retinal slippage or pressure-related complications. Postoperatively 20 patients underwent oil removal. Six suffered retinal redetachment, and 14 remained attached. The vision postoil removal ranged from 6/6 to hand movements.

Conclusion:

We are confident that the PFCL–oil exchange technique described here is reliable and safe. The use of a 20-gauge drainage cannula is recommended regardless of vitrectomy gauge.
OUTCOMES IN PRIMARY UNCOMPLICATED RHEGMATOGENOUS RETINAL DETACHMENT REPAIR USING PARS PLANA VITRECTOMY WITH OR WITHOUT SCLERAL BUCKLE
Authors: Hébert Mélanie , You Eunice , Garneau Jérôme , Qi Susan Ruyu , Bourgault Serge , Caissie Mathieu , Tourville Éric , Dirani Ali
Published: February 2022

Purpose:

To compare outcomes after primary uncomplicated rhegmatogenous retinal detachment repair using pars plana vitrectomy (PPV) or PPV with scleral buckle (PPV-SB).

Methods:

This is a retrospective cohort study with propensity score analysis in a single tertiary care center between 2014 and 2018 comparing patients with primary uncomplicated rhegmatogenous retinal detachment repaired using PPV only or PPV-SB (full cohort: n = 1,516, propensity-matched cohort: n = 908). The primary outcome was single surgery anatomic success, whereas secondary outcomes were 3-month and final pinhole visual acuity in logarithm of the minimum angle of resolution and final retina status.

Results:

In the full cohort, single surgery anatomic success was achieved in 745 (91%) PPV patients versus 623 (89%) PPV-SB patients (P = 0.13). This was 390 (92%) versus 314 (88%) in phakic patients (P = 0.06) compared with 353 (91%) versus 301 (90%) in pseudophakic patients (P = 0.79), respectively. After matching, single surgery anatomic success was achieved in 424 (93%) PPV patients versus 412 (91%) PPV-SB patients (P = 0.14). Median pinhole visual acuity after PPV was better at 3 months (PPV: 20/40 vs. PPV-SB: 20/50; both cohorts: P < 0.001) and final follow-up (PPV: 20/29 vs. PPV-SB: 20/38; full cohort: P < 0.001 and PPV: 20/29 vs. PPV-SB: 20/36; matched cohort: P < 0.001).

Conclusion:

Addition of scleral buckle does not significantly change the rate of single surgery anatomic success compared with PPV only in primary uncomplicated rhegmatogenous retinal detachment. It is also associated with worse pinhole visual acuity at follow-up.
AUTOMATIC DETECTION AND GRADING OF DIABETIC MACULAR EDEMA BASED ON A DEEP NEURAL NETWORK
Authors: Guo Xiaoxin , Lu Xinfeng , Zhang Baoliang , Hu Xiaoying , Che Songtian
Published: February 2022

Purpose:

To solve the problem of automatic grading of macular edema in retinal images in a more stable and reliable way and reduce the workload of ophthalmologists, an automatic detection and grading method of diabetic macular edema based on a deep neural network is proposed.

Methods:

The enhanced green channels of fundus images are input into the YOLO network for training and testing. Diabetic macular edema is graded according to the distance of the macula and hard exudate. We used multiscale feature fusion to form more comprehensive features on different grain images to improve the effect of hard exudate detection. We adopted K-means++ algorithm to cluster anchor box size and use

loss of the original network to guide the regression of hard exudate bounding box and improve the regression accuracy of anchor boxes. We increased the diversity of samples for sample training by data augmentation, including cropping, flipping, and rotating of fundus images, so that each batch of training data can better represent the distribution of samples.

Results:

The detection accuracy of the proposed method can reach 96% on the MESSIDOR data set. The detection rates of hard exudate with high, median, and low probability are 100%, 79.12%, and 60.40%, respectively.

Conclusion:

The proposed method exhibits a very good detection stability on healthy and diseased fundus images.
BACILLARY LAYER DETACHMENT IN A KOREAN COHORT WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kim Jae Hui , Kim Jong Woo , Kim Chul Gu
Published: February 2022

Purpose:

To evaluate the incidence and characteristics of bacillary layer detachment (BALAD) in neovascular age-related macular degeneration.

Methods:

This retrospective study was performed at Kim's Eye Hospital in South Korea. Patients who were diagnosed with neovascular age-related macular degeneration between January 2017 and December 2017 were included. The incidence of BALAD was compared among different types of macular neovascularization (MNV). The best-corrected visual acuity and central retinal thickness at diagnosis were compared between patients showing BALAD at diagnosis and those who did not.

Results:

Among the 442 patients included, BALAD was observed in 20 patients (4.5%). There was a significant difference in the incidence of BALAD between Type 1 MNV (2.7%), Type 2 MNV (12.5%), and Type 3 MNV (0%) (P< 0.001). The best-corrected visual acuity was significantly worse (mean 1.26 ± 0.79 vs. 0.62 ± 0.50,P= 0.001), and the central retinal thickness was significantly greater (mean 648.2 ± 211.1µm vs. 464.0 ± 175.5µm,P< 0.001) in patients with BALAD than in those without it. After antivascular endothelial growth factor therapy, all BALADs resolved.

Conclusion:

This study first reported the incidence of the BALAD in neovascular age-related macular degeneration in a Korean population. The incidence of BALAD was the highest in Type 2 MNVs. Bacillary layer detachment generally develops in eyes with great macular thickness and poor visual acuity.
Personality Organization and Depressive Symptoms Among Psychiatric Outpatients
Authors: Jakšić Nenad , Marčinko Darko , Bjedov Sarah , Mustač Filip , Bilić Vedran
Published: February 2022

Previous research has demonstrated relations between lower level of personality organization (PO) and multiple indices of mental health disturbances. The goal of this research was to examine whether experience of shame would mediate the relationship between PO and depressive symptoms in a sample of 321 Croatian psychiatric outpatients (64% female; mean age, 38.67 years). The total PO level exhibited positive associations with depressive symptoms and with all three subscales of shame (p < 0.01). Characterological, behavioral, and bodily shame showed significant mediating effects in the PO-depression relationship, while controlling for the influence of age and sex. PO level seems to be strongly related to depressive disturbances, with the experience of shame representing one of the underlying mechanisms of this relationship. Given that patients with personality disorders (i.e., low PO level) suffer from poorer treatment outcomes for major mental disorders, more emphasis should be placed on psychotherapeutic management of shame-proneness.
Nursing Communication Skills Training
Authors: Roman Annette , Pineiro Annette V.
Published: February 2022

During times of crisis, communication serves as an essential component of patient care. An educational program, previously created to provide knowledge and skills to master concepts of communication, was reexamined for usefulness during the COVID-19 pandemic. Surveyed in 2020, past program participants stated that combining listening skills and concepts of emotional intelligence improved their perceived team communication. Nursing requires communication and conflict management education for effectively functioning teams, which proved paramount during the global pandemic.
Changing dynamics of COVID-19 deaths during the SARS-CoV2 B.1.617.2 (Delta variant) outbreak in England and Wales: Reduced COVID-19 deaths among the Care Home residents
Authors: Emani Venkata R. , Reddy Raghunath , Emani Shaila R. , Goswami Kartik K. , Maddula Kailash R. , Reddy Nikhila K. , Nakka Abirath S. , Reddy Nidhi K. , Nandanoor Dheeraj , Goswami Sanjeev
Published: February 2022

Objectives

Care Homes faced crisis during the SARS-CoV2 pandemic with increased mortality and various corrective interventions were undertaken. The impact of current SARS-CoV2 B.1.617.2 (Delta variant) outbreak on COVID-19 deaths in Care Homes is not completely known.

Design

Observational study

Setting and Participants

We included nationwide data of deaths from all causes and COVID-19 in England and Wales during March 7, 2020-November 26, 2021.

Methods

Impact of COVID-19 deaths in Care Homes, Hospital and Homes relative to total deaths from all causes was investigated.

Results

During March 7-August 28,2020; 15,414 (29.8%) of the 51,740 COVID-19 deaths occurred in Care Homes. During August 29, 2020-May 28, 2021, there were significant decrease in COVID-19 deaths in Care Homes ([19.2%]; RR 0.64; 95%CI 0.63-0.65;p<0.0001], which significantly declined further ([8.9%]; RR 0.46; 95%CI 0.43-0.48;p<0.0001) during May 29-November 26, 2021. During the March 7-August 28, 2020; 20.0% (15,514/76,906) of all Care Home deaths were caused by COVID-19, which significantly declined to 18.5% (RR 0.92; 95%CI 0.90-0.93; p<0.0001) during August 29, 2020-May 28, 2021 and declined further to 2.5% (RR 0.13; 95% CI 0.12-0.14;p<0.0001) during May 29-November 26, 2021. Increased percentages of COVID-19 deaths occurred in Hospitals ([72.3%]; RR 1.14; 95% CI 1.1-1.15;p<0.0001) and Homes ([6.3%]; RR 1.33; 95% CI 1.27-1.40; p<0.0001) during August 29, 2020-May 28, 2021 and further increases in the Hospitals ([80.8%]; RR 1.11; 95% CI 1.10-1.12; p<0.0001) and Homes ([8.8%]; RR 1.39; 95% CI 1.31-1.47; p<0.0001) during May 29-November 26, 2021.

Conclusions and Implications

There was a significantly lower number of COVID-19 deaths occurred in Care Homes and a significantly lower number of Care Homes deaths caused by COVID-19 during the Delta variant surge in England and Wales than the prior surges. Care Home residents are at highest risk for mortality, continuous monitoring and research on COVID-19 preventive interventions are essential.
Coronavirus Disease 2019 (COVID-19) Vaccine Boosting in Persons Already Protected by Natural or Vaccine-Induced Immunity
Authors: Shrestha Nabin K. , Shrestha Priyanka , Burke Patrick C. , Nowacki Amy S. , Terpeluk Paul , Gordon Steven M.
Published: February 2022

Background

The purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant.

Methods

Employees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate.

Results

Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97).

Conclusions

Administering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.

Among 39 766 Cleveland Clinic employees already protected by prior infection or vaccination, vaccine boosting after 6 months was associated with significantly lower risk of COVID-19. After COVID-19 infection, there was no advantage to more than one dose of vaccine.
ICD-10 based syndromic surveillance enables robust estimation of burden of severe COVID-19 requiring hospitalization and intensive care treatment
Authors: Tolksdorf Kristin , Haas Walter , Schuler Ekkehard , Wieler Lothar H. , Schilling Julia , Hamouda Osamah , Diercke Michaela , Buda Silke
Published: February 2022

Objective

The emergence of coronavirus disease 2019 (COVID-19) required countries to establish COVID-19 surveillance by adapting existing systems, such as mandatory notification and syndromic surveillance systems. We estimated age-specific COVID-19 hospitalization and intensive care unit (ICU) burden from existing severe acute respiratory infections (SARI) surveillance and compared the results to COVID-19 notification data.

Methods

Using data on SARI cases with ICD-10 diagnosis codes for COVID-19 (COVID-SARI) from the ICD-10 based SARI sentinel, we estimated age-specific incidences for COVID-SARI hospitalization and ICU for the first five COVID-19 waves in Germany and compared these to incidences from notification data on COVID-19 cases using relative change Δrat the peak of each wave.

Findings

The COVID-SARI incidence from sentinel data matched the notified COVID-19 hospitalization incidence in the first wave with Δr=6% but was higher during second to fourth wave (Δr=20% to 39%). In the fifth wave, the COVID-SARI incidence was lower than the notified COVID-19 hospitalization incidence (Δr=-39%). For all waves and all age groups, the ICU incidence estimated from COVID-SARI was more than twice the estimation from notification data.

Conclusion

The use of validated SARI sentinel data adds robust and important information for assessing the true disease burden of severe COVID-19. Mandatory notifications of COVID-19 for hospital and ICU admission may underestimate (work overload in local health authorities) or overestimate (hospital admission for other reasons than the laboratory-confirmed SARS-CoV-2 infection) disease burden. Syndromic ICD-10 based SARI surveillance enables sustainable cross-pathogen surveillance for seasonal epidemics and pandemic preparedness of respiratory viral diseases.
Persistence, prevalence, and polymorphism of sequelae after COVID-19 in young adults
Authors: Deuel Jeremy Werner , Lauria Elisa , Lovey Thibault , Zweifel Sandrine , Meier Mara Isabella , Züst Roland , Gültekin Nejla , Stettbacher Andreas , Schlagenhauf Patricia
Published: February 2022

Background

COVID-19 sequelae are poorly defined with an ambiguous pathophysiology. Persistent sequelae could have global, public health and societal ramifications. We aimed to describe sequelae presenting more than six months after COVID-19 in non-hospitalized young adults.

Methods

A prospective, longitudinal cohort study followed-up on young Swiss Armed Forces (SAF) personnel. The comprehensive test battery was administered during a single full day of testing at the University of Zürich. It quantified the impact of SARS-CoV-2 infection on cardiovascular, pulmonary, neurological, renal, ophthalmological, male reproductive, psychological, and general health in addition to laboratory parameters.

Results

We included 501 participants (5.6% females) with a median age of 21 years (range 19-29). Cases of previous COVID -19 (>6 months (mean 10 months) since diagnosis, n=177) were compared with never infected controls (n=248). We also included more recent COVID-19 cases (≤6 months, n=19) and asymptomatically infected individuals (n=49). We found a significant trend towards metabolic disorders, higher Body Mass Index (BMI) (p=0.03), lower aerobic threshold (p=0.007), higher blood cholesterol (p<0.001) and low-density lipoprotein LDL levels (p<0.001) in participants> 6 months post Covid-19 when compared to controls. There were no significant differences in psychosocial questionnaire scores, ophthalmological outcomes, sperm quality or motility between controls and those infected more than 6 months previously with SARS-CoV-2.

Conclusions

Young, previously healthy, individuals largely recover from mild infection and the multi-system impact of the infection is less that seen in older or hospitalized patients. These results may be extrapolated to health-care workers and other young workforce adults. However, the constellation of higher body mass index, dyslipidemia and lower physical endurance 6 months post COVID-19 is suggestive of a higher risk of developing metabolic disorders and possible cardiovascular complications. These findings will guide investigation and follow-up management.
Underdispersion in the reported Covid-19 case and death numbers may suggest data manipulations
Authors: Kobak Dmitry
Published: February 2022

We suggest a statistical test for underdispersion in the reported Covid-19 case and death numbers, compared to the variance expected under the Poisson distribution. Screening all countries in the World Health Organization (WHO) dataset for evidence of underdispersion yields 21 country with statistically significant underdispersion. Most of the countries in this list are known, based on the excess mortality data, to strongly undercount Covid deaths. We argue that Poisson underdispersion provides a simple and useful test to detect reporting anomalies and highlight unreliable data.
Polygenic coronary artery disease association with brain atrophy in the cognitively impaired
Authors: de Silva Eric , Sudre Carole H , Barnes Josephine , Scelsi Marzia A , Altmann André ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

The role cardiac function plays in the predilection for, and progression of, Alzheimer’s disease (AD), is complex and unclear. While a number of low-frequency genetic variants of large effect-size have been shown to underlie both cardiovascular disease and dementia, recent studies have highlighted the importance of common genetic variants of small-effect size, which, in aggregate, are embodied by a polygenic risk score (PRS). In this study we aim to investigate the effect of polygenic risk for coronary artery disease (CAD) on brain atrophy in AD using whole brain volume (WBV) and put our findings in context with the polygenic risk for AD and presumed small vessel disease as quantified by white matter hyperintensities (WMH). We used 730 subjects from the ADNI database to investigate PRS effects (beyond APOE) on whole brain volumes, total and regional WMH and amyloid beta across diagnostic groups. In a subset of these subjects (N=602) we utilise longitudinal changes in whole brain volume over a maximum of 24 months using the boundary shift integral approach. Linear regression and linear mixed effects models were used to investigate the effect of WMH at baseline as well as AD-PRS and CAD-PRS on whole brain atrophy and whole brain atrophy acceleration, respectively. All genetic associations were examined under oligogenic (p=1e-5) and the more variant-inclusive polygenic (p=0.5) scenarios. Our results suggest no evidence for a link between PRS score and markers of AD pathology at baseline (when stratified by diagnostic group). However, both AD-PRS and CAD-PRS were associated with longitudinal decline in WBV (AD PRS t=3.3, PFDR=0.007 over 24 months in healthy controls) and surprisingly, under certain conditions WBV atrophy is statistically more correlated with cardiac PRS than AD PRS (CAD PRS t=2.1, PFDR=0.04 over 24 months in the MCI group). Further, in our regional analysis of WMH, AD PRS beyond APOE is predictive of white matter volume in the occipital lobe in AD subjects in the polygenic regime. Finally, the rate of change of brain volume (or atrophy acceleration) may be sensitive to AD polygenic risk beyond APOE in healthy individuals (t=2, p=0.04). For subjects with mild cognitive impairment (MCI), beyond APOE, a more inclusive polygenic risk score including more variants, shows CAD PRS to be more predictive of WBV atrophy, than an oligogenic approach including fewer larger effect size variants.
Comparing Sexual Network Mean Active Degree Measurement Metrics among Men who have Sex with Men
Authors: Chandra Christina , Morris Martina , Van Meter Connor , Goodreau Steven M. , Sanchez Travis , Janulis Patrick , Birkett Michelle , Jenness Samuel M.
Published: February 2022

Background

Mean active degree is an important proxy measure of cross-sectional network connectivity commonly used in HIV/STI epidemiology research. No current studies have compared measurement methods of mean degree using cross-sectional surveys for men who have sex with men (MSM) in the United States.

Methods

We compared mean degree estimates based on reported ongoing main and casual sexual partnerships (current method) against dates of first and last sex (retrospective method) from 0–12 months prior to survey date in ARTnet, a cross-sectional survey of MSM in the U.S. (2017–2019). ARTnet collected data on the number of sexual partners in the past year but limited reporting on details used for calculating mean degree to the 5 most recent partners. We used linear regression to understand the impact of truncated partnership data on mean degree estimation.

Results

Retrospective method mean degree systematically decreased as the month at which it was calculated increased from 0–12 months prior to survey date. Among participants with >5 partners in the past year compared to those with ≤5, the average change in main degree between 12 and 0 months prior to survey date was −0.05 (95% CI: −0.08, −0.03) after adjusting for race/ethnicity, age, and education. The adjusted average change in casual degree was −0.40 (95% CI: −0.45, −0.35).

Conclusions

The retrospective method underestimates mean degree for MSM in surveys with truncated partnership data, especially for casual partnerships. The current method is less prone to bias from partner truncation when the target population experiences higher cumulative partners per year.

Survey designs can lead to potential bias, such as underestimation, in the measurement of mean active degree in sexual networks of men who have sex with men.
Nerve excitability measured with the TROND protocol in amyotrophic lateral sclerosis: a systematic review and meta-analysis
Authors: Lugg Anna , Schindle Mason , Sivak Allison , Tankisi Hatice , Jones Kelvin E.
Published: February 2022

Objective

This meta-analysis assessed the 30+ nerve excitability indices generated by the TROND protocol to identify potential biomarkers for ALS.

Methods

A comprehensive search was conducted in multiple databases, to identify human studies that tested median motor axons. Forest Plot analyses were performed using a random-effects model to determine the pooled effect (Z-score), heterogeneity (I2), and Cohen’s d for potential biomarker identification.

Results

Out of 2866 studies, 23 studies met the inclusion criteria, incorporating data from 719 controls and 942 ALS patients. Seven indices emerged as potential biomarkers: TEd 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing I/V, and subexcitability (ranked by the magnitude of the difference between patients and controls from largest to smallest). In a sensitivity analysis focusing on patients with larger compound muscle action potentials (CMAP), only four indices were potential biomarkers: TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC.

Conclusion

Among the extensive range of 30+ excitability indices generated by the TROND protocol, we have identified seven indices that effectively differentiate ALS patients from healthy controls. Furthermore, a smaller subset of four indices shows promise as potential biomarkers when the CMAP remains relatively large. However, most studies were considered to be at moderate risk of bias due to case-control designs and absence of sensitivity and specificity calculations, underscoring the need for more prospective diagnostic test-accuracy studies with appropriate disease controls.

NEW & NOTEWORTHY

This meta-analysis uncovers seven potential axonal excitability biomarkers for lower motor neuron pathology in ALS, shedding light on ion channel dysfunction. The identified dysfunction aligns with the primary pathology – protein homeostasis disruption. These biomarkers could fill a gap to detect pre-symptomatic spread of the disease in the spinal cord and monitor treatments targeting protein homeostasis and limiting spread, towards enhancing patient care.
Evaluation of the specificity and accuracy of SARS-CoV-2 rapid antigen self-tests compared to RT-PCR from 1015 asymptomatic volunteers
Authors: Iftner Thomas , Iftner Angelika , Pohle Diana , Martus Peter
Published: February 2022

Objective

Evaluation of the specificity and accuracy of four CE-approved SARS-CoV-2 antigen rapid self-tests (AG-ST) Anbio, Clungene, Hotgene and Mexacare.

Method

1015 asymptomatic volunteers were screened for SARS-CoV-2 by means of an oropharyngeal swab taken by qualified personnel and subsequent RT-PCR testing. Each participant additionally performed nasal self-swabs for two of the four rapid antigen tests at the same day according to the manufacturers’ instructions. Study participants transmitted a photo and own interpretation of their test results to the study center. The results of the two self-tests provided by the participants were correlated with the results of the SARS-CoV-2 RT-PCR and independently assessed and evaluated by the study center.

Results

None of the volunteers tested positive upon RT-PCR, whereas 13 AG-ST showed a false positive test result (0.7 %). The highest false positivity rate was found for the Clungene test (2.1 % compared to 0.2 % for the other tests), while the highest test failure rate (invalid) was found for the Mexacare test (3.7%). The Anbio and Hotgene tests produced the fewest false positive results when evaluated by the participants and also showed the best agreement among themselves.

Conclusion

SARS-CoV-2 Antigen rapid self-tests with higher false positive test rates, such as the Clungene test, or with high rates of invalid test results, such as the Mexacare test, are less suitable for screening purposes of asymptomatic study participants especially in low-prevalence settings. False positive or inadequate test results increase the burden on certified test laboratories due to verification PCR tests and cause a substantial economic loss due to unnecessary quarantine measurements and cause psychological stress in the affected study participants. In addition to earlier defined requirements for sensitivity for SARS-CoV-2 detection, a lower acceptance boundary for the false positivity rate of < 0.3% should be demanded.
Stochastic dynamics of social patch foraging decisions
Authors: Bidari Subekshya , El Hady Ahmed , Davidson Jacob , Kilpatrick Zachary P
Published: February 2022

Animals typically forage in groups. Social foraging can help animals avoid predation and decrease their uncertainty about the richness of food resources. Despite this, theoretical mechanistic models of patch foraging have overwhelmingly focused on the behavior of single foragers. In this study, we develop a mechanistic model that accounts for the behavior of individuals foraging together and departing food patches following an evidence accumulation process. Each individual’s belief about patch quality is represented by a stochastically accumulating variable which is coupled to others’ belief to represent the transfer of information. We consider a cohesive group, and model information sharing by considering both intermittent pulsatile coupling (only communicate decision to leave) and continuous diffusive coupling (communicate throughout the evidence accumulation process). We find that foraging efficiency under pulsatile coupling has a stronger dependence on the coupling strength parameter compared to diffusive. Despite employing minimal information transfer, pulsatile coupling can still provide similar or higher foraging efficiency compared to diffusive coupling. Conversely, since diffusive coupling is more robust to parameter choices, it performs better when individuals have heterogeneous departure criteria and social information weighting. Efficiency is measured by a reward rate function that balances the amount of energy accumulated against the time spent in a patch, computed by solving an ordered first passage time problem for the patch departures of each individual. Using synthetic data we show that we can distinguish between the two modes of communication and identify the model parameters. Our model establishes a social patch foraging framework to parse and identify deliberative decision strategies, to distinguish different forms of social communication, and to allow model fitting to real world animal behavior data.
Micro and Nanoplastics Interactions with Plant Species: Trends, Meta-Analysis, and Perspectives
Authors: Azeem Imran , Adeel Muhammad , Ahmad Muhammad Arslan , Shakoor Noman , Zain Muhammad , Yousef Naglaa , Yinghai Zhao , Azeem Kamran , Zhou Pingfan , White Jason C. , Ming Xu , Rui Yukui
Published: February 2022

The ubiquitous presence of nano plastics (NPx) and micro plastics (MPx) in the environment has been demonstrated, and as such, the exposure scenarios, mechanisms of plant response, and ultimate risk must be determined. However, the current literature reports ambiguous outcomes and provides limited mechanistic insight into critical governing processes. Here, we performed a meta-analysis of the most recent literature investigating the effect of MPx/NPx on plant species under laboratory and field conditions so as to evaluate the current state of knowledge. Toxic effects of MPx/NPx exposure in plants varies as a function of plant species and interestingly, generally non-significant responses are reported in staple crops. NPx (<100 nm) more negatively affected plant development parameters (n=341) (n is total number of observations), photosynthetic pigments (n=80), and biochemical indicators (n=91) than did MPx (>100 nm). Surprisingly, NPx exposure yielded negligible effects on germination rate (n=17), although root morphology (n=45) was negatively affected. Alternatively, MPx negatively affected on germination (n= 27) and generally non-significant affect with regard to root morphology (n=64). The effect of MPx/NPx on plant health decreases with increasing exposure time. No specific trends were evident for the production of biochemical enzymes as related to MPx/NPx concentration or size. Future work should include crop full life cycle studies to highlight the accumulation of MPx/NPx in edible tissues and also to investigate potential trophic transfer of MPx/NPx. Furthermore, we provide a framework for additional investigative work to address these and other knowledge gaps and to enable accurate assessment of the fate and risk of these materials to environmental and human health.

Environmental significance

Accumulation of plastic (MPx and NPx) particles is increasing in environmental compartments, and this might be threatened to agricultural plants.

Graphical Abstract