bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection by vaccines and previous infection against the Omicron variant of SARS-CoV-2
Authors: Šmíd Martin , Berec Luděk , Májek Ondřej , Pavlík Tomáš , Jarkovský Jiří , Weiner Jakub , Přibylová Lenka , Barusová Tamara , Trnka Jan
Published: February 2022

The Omicron variant of the SARS-CoV-2 virus carries mutations, which enable it to evade immunity conferred by vaccines and previous infections. We used a Cox proportional hazards model and a logistic regression model on individual-level data on all laboratory-confirmed SARS-CoV-2 infections in the Czech Republic to estimate the relative risk of infection, hospitalization, including severe states, for Delta and Omicron variants, adjusting for sex, age, previous infection, vaccine type and vaccination status. A recent (<2 months) two-dose vaccination reached VE 43% (95% CI: 42-44) against infection by Omicron compared to 73% (95% CI: 72-74) against Delta. A recent booster increased VE to 56% (95% CI: 55-56) against Omicron infection compared to 90% (95% CI: 90-91) for Delta. The VE against Omicron hospitalization of a recent two-dose vaccination was 45% (95% CI: 29-57), with a recent booster 87% (95% CI: 84-88). The VE against the need for oxygen therapy due to Omicron was 57% (95% CI: 32-72) for recent vaccination, 90% (95% CI: 87-92) for a recent booster. Post-infection protection against Omicron hospitalization declined from 68% (95% CI: 68-69) at <6 months to 13% (95% CI: 11-14) at >6 months after a previous infection. A recent combination of a previous infection and vaccination was more protective then either alone with a slight benefit from a vaccination preceding an infection. Once infected, the OR for Omicron relative to Delta was 0.36 (95% CI: 0.34-0.38) for hospitalization, 0.24 (95% CI: 0.22-0.26) for oxygen therapy, and 0.24 (95% CI: 0.21-0.28) for ICU admission.

Significance Statement

A nation-wide study shows that the protection of a previous infection or vaccination is lower against Omicron compared to Delta variant of SARS-CoV-2 and further declines with time. A booster dose or a combination of post-infection immunity with a vaccine conferred significant benefit to individuals in the Omicron wave in the Czech Republic, which further strengthens the importance of vaccination as an effective public health measure.
Prevalence of central obesity and its associated risk factors among adults in Southeast Ethiopia: a community-based cross-sectional study
Authors: Tekalegn Yohannes , Solomon Damtew , Sahiledengle Biniyam , Assefa Tesfaye , Negash Wegene , Tahir Anwar , Regassa Tadele , Mamo Ayele , Gezahegn Habtamu , Bekele Kebebe , Zenbaba Demisu , Tasew Alelign , Desta Fikreab , Atilaw Daniel , Regassa Zegeye , Nugusu Fikadu , Engida Zinash Teferu , Tesfaye Degefa Gomora , Kene Chala , Nigussie Wondu Shiferaw , Chala Dereje , Abdi Adisu Gemechu , Beressa Girma , Woldeyohannes Demelash , Rogers Heather L. , Mwanri Lillian
Published: February 2022

Background

Obesity and overweight are known are public health scourge challenges affecting populations across the world. These conditions have been associated with a wide range of chronic diseases including type 2 diabetes mellitus, cardiovascular disease, and cancers. In Ethiopia, literature regarding the burden of central (abdominal) obesity is scarce. This study aimed to fill this gap by assessing the prevalence and risk factors associated with central obesity among adults in Ethiopia.

Methods

From May to July 2021, a community-based cross-sectional survey was conducted on a sample of 694 adults aged ≥18 years in administrative towns of Bale zone, Southeast Ethiopia. Multi-stage sampling followed by systematic random sampling was employed to identify study participants. Waist and hip circumferences were measured using standard protocols. The World Health Organization STEPS wise tool was used to assess risk factors associated with central obesity. Bi-variable and multi-variable binary logistic regression were used to identify factors associated with central obesity. Adjusted odds ratios (AOR) and their corresponding 95% confidence intervals (CI) were reported to estimate the strength of associations.

Results

The overall prevalence of central obesity using waist circumference was 39.01% (15.44% for men and 53.12% for women). Multi-variable binary logistic regression analysis revealed that female sex (AOR=12.93, 95% CI: 6.74-24.79), Age groups: 30-39 years old (AOR=2.8, 95% CI: 1.59-4.94), 40-49 years (AOR=7.66, 95% CI: 3.87-15.15), 50-59 years (AOR=4.65, 95% CI: 2.19-9.89), ≥60 years (AOR=12.67, 95% CI: 5.46-29.39), occupational status like: housewives (AOR=5.21, 95% CI: 1.85-14.62), self-employed workers (AOR=4.63, 95% CI: 1.62-13.24), government/private/non-government employees (AOR=4.68, 95% CI: 1.47-14.88) and skipping breakfast (AOR=0.46, 95% CI: 0.23-0.9) were significantly associated with central obesity.

Conclusions

Abdominal obesity has become an epidemic in towns of southeast Ethiopia, and the prevalence is higher among women. Female sex, older age group, being employed, not skipping breakfast were significantly associated with central obesity.
Saliva metabolome alterations after acute stress
Authors: Morgan Liat , Dupont Birkler Rune Isak , Shaham-Niv Shira , Dong Yonghui , Wachsman Tal , Carmi Lior , Yakobson Boris , Adler-Abramovich Lihi , Cohen Hagit , Zohar Joseph , Bateson Melissa , Gazit Ehud
Published: February 2022

Major stress has systemic effects on the body that can have adverse consequences for physical and mental health. However, the molecular basis of these damaging effects remains incompletely understood. Here we use a longitudinal approach to characterise the acute systemic impact of major psychological stress in a pig model. We perform untargeted metabolomics on non-invasively-obtained saliva samples from pigs before and 24-hours after transfer to the novel physical and social environment of a slaughterhouse. The main molecular changes occurring include decreases in amino acids, B-vitamins, and amino acid-derived metabolites synthesized in B-vitamin-dependent reactions, as well as yet-unidentified metabolite features. Decreased levels of several of the identified metabolites are implicated in the pathology of human psychological disorders and neurodegenerative disease, suggesting a possible neuroprotective function. Our results provide a fingerprint of the acute effect of psychological stress on the metabolome and suggest candidate biomarkers with potential roles in stress-related disorders.

One Sentence Summary

Identification of metabolites decreased under acute psychological stress may lead to future discoveries for the prevention and treatment of stress-related disorders.
Screening and Identification of Azo Dye Decolourizers from Mangrove Rhizospheric soil
Authors: Modi Akhilesh , Singh Sunita , Patki Jyoti , Padmadas Naveen
Published: February 2022

Removal of synthetic textile dye poses a challenge to the textile industry and a threat to environment flora and fauna. These dyes are marginally degradable and recalcitrant, hence alternatives to physical and chemical techniques like various bioremediation studies involving plants, plant roots, single or consortium of microbes have been used as environment friendly methods for the removal of textile dye. In the present study potent bacteria for dye decolourization were isolated from rhizospheric soil collected from Kamothe, Navi Mumbai, India. Of the 20 isolates obtained after enrichment, seven isolates were used for further screening of efficient decolourization ability in MBM media containing 10% glucose, 2.5 % trace metal solution and 0.1% of MO dye concentration. Physiological parameters to optimize the decolourization of dye at optimum pH, temperature and incubation time was studied for all the seven isolates. UV-vis and Fourier Transform Infrared spectroscopy were used to investigate dye decolorization. The seven isolates were characterized morphologically, biochemically, and molecular identification of these strains were performed by 16S rRNA sequence analysis. The isolates were identified asBacillus paramycoides, Pseudomonas taiwanensis, Citrobacter murliniae, Acinetobacter pitti, Exiguobacterium acetylicum, Psychrobacter celer, andAeromonas taiwanensis. Out of theseAeromonas taiwanensishas shown exceptional capacity by 100% decolorization of azo dye in minimum time.

1.

Graphical Abstract

Highlights of the study

Collection of soil samples from rhizospheric and non-rhizospheric region of the mangroves plant.

Enrichment of soil sample in media containing azo dye for dye decolourization.

Screening and isolation of potential dye decolourizers.

Optimize the condition for dye decolourization.

FTIR analysis and application based studies.

Identification of microbes using 16SrRNA.
Brain structure, phenotypic and genetic correlates of reading abilities
Authors: Carrión-Castillo Amaia , Paz-Alonso Pedro M. , Carreiras Manuel
Published: February 2022

Reading is an evolutionary new development that recruits and tunes brain circuitry connecting visual- and language-processing regions. We investigated the structural correlates of reading and whether genetics influence brain-reading associations. First, we identified left hemisphere cortical surface area (CSA) and cortical thickness (CT) correlates of reading in the large ABCD dataset (N=9,013) of 9-to-10-year-olds. Next, the heritability of cognitive and brain measures of interest was examined through complementary approaches. Last, shared genetic effects between reading, reading-related cognitive traits and reading-associated brain measures were examined by computing genetic correlations and polygenic score analyses, and through mediation analyses. Our results support that morphometric brain measures are related to reading abilities, and that the total left CSA in general, and left superior temporal gyrus CSA in particular, contribute to reading partially through genetic factors.
A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein
Authors: Huang Jiachen , Miller Rose , Mousa Jarrod
Published: February 2022

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and negative-stain EM analysis demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. BALB/c mice immunized with RHMS-1 had serum binding and neutralizing antibodies to both viruses. RHMS-1 vaccinated mice challenged with RSV or hMPV had undetectable virus in lung homogenates for both viruses, in contrast to RSV F or hMPV F vaccinated mice, which had detectable virus for hMPV and RSV, respectively. Overall, this study demonstrates protection against two viruses with a single antigen and supports further testing of RHMS-1 in additional pre-clinical animal models.

Significance

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two Pneumoviruses that cause substantial respiratory tract infections in young children, the elderly, and immunocompromised adults. Yet vaccines against either of them are still unavailable. Multiple promising vaccine designs based on the fusion proteins of RSV and hMPV have been tested, but none of them can induce cross-protective antibody responses despite their similar structures and closely related amino acid sequence identity. Here, we report a vaccine candidate, RHMS-1, which combines the immunodominant epitopes of the RSV and hMPV fusion proteins into a single antigen. RHMS-1 maintains the immunological features of both RSV F and hMPV F, which can be recognized by epitope-specific mAbs and human B cells pre-exposed to RSV or hMPV. Furthermore, this is the first immunogen that induced potent cross-neutralizing antibodies and protected mice from RSV and hMPV challenge. Our results suggest RHMS-1 is a promising Pan-Pneumovirus vaccine.
TraB is a novel component of the ER-Mitochondria contact site (EMCS) with dual roles in ER-Mitochondrial tethering and mitophagy
Authors: Li Chengyang , Duckney Patrick , Zhang Tong , Fu Yanshu , Li Xin , Kroon Johan , De Jaeger Geert , Cheng Yunjiang , Hussey Patrick J , Wang Pengwei
Published: February 2022

ER-mitochondria contact sites (EMCSs) are important for mitochondrial function. Here, we have identified a novel eukaryotic EMCS complex, comprising a family of uncharacterised mitochondrial outer-membrane proteins, TraB1 and the ER protein, VAP27-1. In Arabidopsis, there are two TraB1 isoforms and thetrab1a/trab1bdouble mutant exhibits abnormal mitochondrial morphology, strong starch accumulation and impaired energy metabolism, indicating that these proteins are essential for normal mitochondrial function. Moreover, TraB1 proteins also interact with ATG8 in order to regulate mitochondrial degradation (mitophagy). The turnover of depolarised mitochondria is significantly reduced in bothtrab1a/band VAP27 mutants (vap27-1/3/4/6)under mitochondrial stress conditions, with an increased population of dysfunctional mitochondria present in the cytoplasm. Consequently, plant recovery after stress is significantly perturbed. A similar phenotype is found in both autophagy mutants (atg5andatg7), suggesting that TraB1 regulated mitophagy and ER-mitochondrial tethering are two closely related processes, necessary for normal mitochondrial function. Taken together, we ascribe a dual role to TraB1 which is a novel component of the EMCS complex in eukaryotes, regulating both tethering of the mitochondria to the ER and mitophagy.
Evaluating a mindfulness-based group intervention for adults with intellectual disabilities
Authors: Power Niall , Rawlings Gregg H. , Bennett Claire
Published: February 2022

Purpose

There is growing evidence examining mindfulness-based interventions (MI) for people with intellectual disabilities (IDs). As discussed in this paper, MI may be particularly suited for people with ID given high rates of difficulties in identifying and regulating emotions and as this approach may rely less on cognitive ability compared to other therapies. This study aims to assess the acceptability and preliminary effectiveness of a six-session MI group [the Coping Well Group (CWG)] delivered within routine clinical practice.

Design/methodology/approach

Six separate cohorts (n = 25) of adults with ID attended CWG. Quantitative data were collected from service users, including a pre- and post-quality of life (QoL) measure and qualitative data from group facilitators.

Findings

Roughly one-half (53%) of service users invited to the group attended at least one session, with low levels of dropout observed among group attendees. A significant improvement in QoL was reported demonstrating a small effect (d = 0.46, p = 0.022) after attending the group. Most service users (72%) were referred to the CWG for help managing difficult emotions. One-half (44%) of attendees required individual therapy after attending the group. Limitations of the evaluation and potential future research are discussed.

Originality/value

The current evaluation contributes a practice-based service evaluation of an MI group for people with ID and mental health difficulties to the currently limited evidence base. To the best of the authors’ knowledge, this is one of the first studies to investigate the impact of group psychological interventions collecting data across cohorts and assessing QoL, a more general measure of well-being than has been used previously.
Pluchea indica tea-leaf extracts exert anti-cancer activity by inducing ROS-mediated cytotoxicity on breast and cervical cancer cells
Authors: Iawsipo Panata , Poonbud Rotsukon , Somtragool Natcha , Mutapat Photsathorn , Meejom Anan
Published: February 2022

Purpose

The study aimed to disclose the anti-cancer activity of Pluchea indica tea leaves by evaluating the cytotoxicity on breast and cervical cancer cells, compared with non-cancer cells.

Design/methodology/approach

Two P. indica extracts were prepared using two solvents, namely hot water (PA) and ethanol (PE). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and clonogenic assays were applied to determine cytotoxic effect of both extracts toward cancer cells from human breast (MDA-MB-231 and MCF7) and cervix (SiHa, HeLa and C-33A) and also non-cancer Vero cells. Dichlorofluorescein diacetate (DCFDA)-staining assay was used to quantify the intracellular level of the reactive oxygen species (ROS). Correlation between the quantity of compounds present and the cytotoxicity of the extracts was analyzed by Pearson's method and a possible class of bioactive compounds was proposed based on the highest correlation coefficient (r).

Findings

Significant reduction in cell viability and proliferation capability was observed in all cancer cells after treatment with either PA or PE extract albeit PE was more effective. Lower toxicity was detected in Vero cells, indicating the selectivity and safety of extracts. The intracellular ROS level was augmented in treated cancer cells which were inversely correlated to cell viability, suggesting the cancer toxicity was likely induced by intracellular oxidative stress. As flavonoids were found abundantly in the extracts and flavonoids' content was the most related to the activity (r = 0.815), it was hypothesized that the flavonoids might play crucial roles in cancer cytotoxicity.

Originality/value

P. indica tea-leaf extracts can be a good source of promising anti-cancer agents with reduced side effects for breast and cervical cancer treatment.
Production of antimicrobial, natural, and reusable material for stitching eco-friendly, extra-protective face masks
Authors: Sadaf Shama , Hassan Komal , Saeed Ayesha , Ahmad Zeeshan , Abdus Samad Hodaa Usama
Published: February 2022

Purpose

The COVID-19 pandemic has popularized wearing face masks for personal protection. However, the protection afforded by a mask is decreased if an individual accidently touches the outer surface of the mask and then touches other parts of their face. To overcome this problem, antimicrobial masks have become commercially available. However, many are disposable and/or made from synthetic antimicrobial agents which have a negative impact on the environment. The purpose of this study was to create material for stitching antimicrobial masks that are reusable and natural.

Design/methodology/approach

The authors developed natural antimicrobial finishes from Azadirachata indica, Butea monosperma and Litchi chinensis leaves. The authors used biodegradable polyurethane binder and pad-dry-cure method to apply them on 100% cotton fabric. The authors used Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) to confirm the application and ASTM E2149 to assess the efficacy and wash-resistance of the finish.

Findings

Fabric treated with leaves of A. indica, B. monosperma and L. chinensis showed 80%, 100 and 100% antimicrobial activity, respectively. All fabrics were washed 25 times in home laundry cycles and maintained 100% of their antimicrobial effect.

Originality/value

These findings highlight that B. monosperma and L. chinensis finishes on cotton fabric can be a used as a material for stitching antimicrobial, natural and reusable masks that provide more protection than traditional masks but do not pose the environmental concerns of disposable masks or synthetic finishes. This study can be furthered by performing more laundry cycles to determine if the finishes remain 100% effective beyond 25 cycles.
Manager and vendor perceptions of farmers’ markets’ impacts on communities: evidence from Michigan
Authors: Warsaw Phillip , Wentworth Chelsea , Lewis Arena , Isaacs Krista , Traore Abou
Published: February 2022

Purpose

The purposes of this paper are to: (1) characterize farmers’ market manager and vendor perceptions of the economic, social and environmental impact markets have on their local communities; and (2) how those impacts are tracked and communicated to market actors and the local community.

Design/methodology/approach

Twenty-nine semistructured interviews were conducted with market managers and vendors across four farmers’ markets within Michigan. The interviews were coded and analyzed using thematic analysis.

Findings

Managers and vendors report economic and social and environmental benefits associated with the presence of a farmers' market, consistent with the existing literature. Metrics are tracked to estimate market impact, particularly economic and social benefits. Market managers reported uncertainty about how best to use data internally, and there are gaps in communicating market impacts with vendors. Most data are used for external reporting, to statewide organizations or for grant evaluation. Respondents reported data fatigue and unwillingness among vendors to share personal business information due to concerns about privacy relative to the perceived benefits of sharing data.

Practical implications

Additional resources are needed for markets, specifically market managers, to better utilize the data they collect for internal versus external purposes.

Originality/value

Metric collection and reporting are a nascent development among markets. Understanding how market actors are utilizing these tools will provide guidance to improve future efforts at impact measurement.
The changing face of the automotive robotics industry
Authors: Bogue Robert
Published: February 2022

Purpose

This study aims to provide an insight into recent technological developments and applications that are driving growth and change in the automotive robotics sector.

Design/methodology/approach

Following a short introduction which provides a commercial perspective, this study discusses the role of collaborative robots and provides examples of applications. It then considers robotic three-dimensional (3D) printing and artificial intelligence (AI)-enabled robots. This is followed by a discussion of the impact of the burgeoning electric vehicle sector. Finally, brief conclusions are drawn.

Findings

This study shows that the automotive robotics sector is growing more rapidly than vehicle production volumes due to factors which include the move to vehicle electrification, the growing use of cobots, 3D printing, which is moving from specialist and low volume to high volume component production, and the advent of AI-enabled robots.

Originality/value

This study provides details of the factors driving the automotive robotics market by discussing a selection of emerging applications and developments.
Review: Phytogeography and history of Japanese beech forests: Recent advances and implications for vegetation ecology
Authors: Hara Masatoshi
Published: February 2022

In this review, the phytogeography and history of Japanese beech (Fagus crenata Blume and F. japonica Maxim.) forests are re‐examined in light of recent phytogeographical and palaeobotanical research advances. I explain the floristics and the climatic and geological contrasts between Japanese beech forests on the Sea of Japan side and the Pacific side of the Japanese archipelago. We also review recent studies on the origin of dwarf evergreen shrub species occurring along the Sea of Japan. The old scenario that these dwarf evergreen shrub species diverged directly from counterpart species occurring on the Pacific coast of Japan is no longer supported. We propose more intricate speciation processes, including phylogenetic relations to extant Chinese species and inter‐species hybridization. We also review the results of recent palaeobotanical studies of forests on the Japanese islands in the Quaternary. The long persistence of beech forests through glacial/interglacial cycles of the Quaternary—with repeated spread and contraction of the geographical range—is confirmed. In addition, we briefly explain the phytosociological classification system of the Japanese beech forest and the geographical ranges of each vegetation type. We review studies of the geographic distribution of F. crenata and F. japonica at the population level, highlighting the need for further ecological and genetic studies of population dynamics near the range limits to understand historic migration processes better.
The development of the Australian Unemployed Workers Union Rating Scale (AUWURS) of employment service providers
Authors: O'Halloran David , Farnworth Louise , Thomacos Nikos
Published: February 2022

This article reports on the ongoing development of the Australian Unemployed Workers Union Rating Scale (AUWURS), which allows unemployed workers to rate their experiences of employment services to allow the evaluation and improvement of service delivery, as well as an aid to the selection of a service provider. The seven subscales comprising the AUWURS (‘Useful’, ‘Client Centred’, ‘Fair’, ‘Trustworthy’, ‘Responsive to Feedback’, ‘Friendly’, and ‘Realistic’) reflect the multifaceted nature of unemployed workers’ experiences of employment services and it offers a way for employment services to be held accountable to a significant stakeholder group whom they aim to serve—unemployed workers.
Research priority setting with parents of students with learning exceptionalities and disabilities
Authors: Baumbusch Jennifer , Lloyd Jennifer E. V.
Published: February 2022

With an increasing focus on knowledge mobilisation, there is a concomitant shift in how stakeholders, such as parents, ought to be engaged in the research process. The purpose of this study was to explore the research priorities of parents of Kindergarten to Grade 12 students with learning exceptionalities and disabilities in British Columbia, Canada. A cross‐sectional survey design was employed. A convenience sample of 130 parents completed the survey. From a list of pre‐selected variables, parents identified time to initial designation, high school graduation, and home‐schooling/independent schooling as the three most important research priorities, with learning disabilities, autism spectrum disorder, and moderate behaviour support/mental illness as the three most important designations. In an open‐ended response, parents recommended further areas for inquiry, including the effectiveness of inclusive education and school exclusion. Research priority setting can help create research agendas that align with the needs and interests of stakeholders.
Consent to Treatment for Transgender Youth: The Next Chapter – Bell & Anor v The Tavistock and Portman NHS Foundation Trust & Ors
Authors: Chua Hillary
Published: February 2022

In September 2021, the Court of Appeal reversed the controversial decision of Quincy Bell v Tavistock and Portman NHS Trust in a victory for transgender rights. At first instance, the Divisional Court had set a high legal threshold for transgender children to attain Gillick competence to consent to treatment with puberty blockers – effectively restricting access to treatment for many. On appeal, the Court of Appeal held that children are capable in law of giving valid consent to treatment for gender dysphoria, and court authorisation would not be routinely required before children could access such treatment. This note considers the implications of the Court of Appeal decision for the law on minors and consent to medical treatment in the transgender health context.
Trends and determinants of retail prescription drug costs
Authors: Teasdale Ben , Nguyen Amanda , van Meijgaard Jeroen , Schulman Kevin A.
Published: February 2022

Objective

To characterize price trends and variation for US generic and branded drugs at the retail level as they relate to pharmacy acquisition costs and local market factors.

Data Sources

Drug pricing data consisting of US pharmacy claims from 2014 to 2019 collected and licensed by GoodRx, an online tool for comparing drug prices.

Study Design

Time trends of median drug prices and coefficients of variation were measured for generic and branded drugs, including subgroups based on clinical condition (i.e., diabetes and cancer). Pharmacy competition was measured using the Herfindahl–Hirschman Index (HHI) at the zip‐code level. Multivariable linear regression analysis assessed the impact of local market‐level factors on drug prices and variation.

Data Collection

US drug pricing data consisting of claims filled through a mix of public and private insurance at 58,332 chain and independent pharmacies across 14,421 zip codes in all 50 states.

Principal Findings

From 2014 to 2019, pharmacy retail markets trended towards greater competition: average HHI by zip code decreased by 15.0% (p < 0.001). Median cash price increased significantly for both generic (6.58%, p < 0.001) and branded (84.10%, p < 0.001) drugs. When normalized to acquisition costs, cash prices for generic drugs rose 22.03% (p < 0.001) while those of branded drugs decreased by 2.31% (p < 0.001). Diabetes drugs showed higher baseline overall markup of cash prices relative to acquisition costs (10.54, Interquartile range (IQR) 3.28–18.43) than cancer drugs (1.88, IQR 1.36–3.08). Neither local pharmacy competition nor median income significantly predicted drug price or variation.

Conclusion

Measures of generic drug price and price variation are high despite decreased costs earlier in the pharmaceutical supply chain, defying expectations of what would happen in a competitive market. Efforts to bypass the pharmacy benefit model for generic drugs may offer consumers an opportunity for substantial savings.
How price and quantity factors drive spending in nongroup and employer health plans
Authors: Pelech Daria , Stockley Karen
Published: February 2022

Objectives

To describe how spending in private, nongroup health insurance plans compared to spending in employer plans and to attribute those spending differences to components related to provider prices and quantity of care.

Data Sources

The 2016 commercial claims and enrollment data of three large, national insurers from the Health Care Cost Institute.

Study Design

We compared per member per month spending across three employer and three nongroup market segments, including on‐exchange, off‐exchange, and short‐term plans, to average commercial spending. We constructed price indices in each market segment and then decomposed spending differences into those attributable to differences in prices, health risk, plan generosity, and other factors.

Data Collection/Extraction Methods

We selected all medical claims for enrollees in commercial plans. We excluded enrollees with Medicare Advantage coverage or those for whom the majority of claims were covered by a secondary payer.

Results

Provider prices were 4.1% lower in on‐exchange plans (p < 0.001) and 1.4% lower in off‐exchange plans (p < 0.001), compared to average prices in the same geographic area. In contrast, prices in employer plans were within roughly a percentage point of those averages. Differences in average spending were much larger than price differences. Off‐exchange enrollees spent 20% less than the sample average (p < 0.001), whereas on‐exchange enrollees spent 12% more (p < 0.001). Those differences were driven largely by variation in health risk, with variation in prices, plan generosity, and other factors contributing smaller amounts.

Conclusions

Our results indicate that provider prices in nongroup plans are much closer to the prices paid by employer plans than to the substantially lower prices paid by public payers. In addition, health risk was the largest contributor to differences in spending. Lowering provider prices and attracting healthier enrollees in nongroup plans may be crucial for lowering premiums.
Analysis of sysdiagnose in iOS 15 to identify the sending phone number of AirDrop data
Authors: Epstein Brandon , Klein Benjamin , Feuerstein Derek
Published: February 2022

Modern cell phones allow for easy communication and transfer of data between devices. Unfortunately, some of the data transferred can be of unwelcomed, illicit, or threatening imagery and other files; digital forensic examiners are often asked to identify the source of these files. In this project, we developed a method to gain insights into the device used to send a file via Apple AirDrop. Our method brute forces the partial SHA256 hash entries found in the receiving Apple device's sysdiagnose logs to reveal the sender's phone number, even if that phone number was not known by the receiving device. This research publishes a method to generate permutations of the partial hash values using potential US area codes to identify the complete phone number of the sending device. In this research project, exemplar photographs were transmitted via AirDrop between Apple devices running iOS 15. A sysdiagnose was then generated on the receiving phone and exported by AirDrop to a MacBook Air for analysis. The analysis of the generated sysdiagnose archive found a partial SHA‐256 hash of the sending device's phone number. This research identified a method to generate permutations of the partial SHA‐256 hashes using a possible country and area code for the sending device in order to successfully identify the sending device's phone number. As a result, it was found that the sender of an unknown AirDrop file's phone number can be identified from the receiving device's sysdiagnose log files.
Redirection of acyl donor metabolic flux for lipopeptide A40926B0 biosynthesis
Authors: Xia Tian‐Yu , Chen Xin‐Ai , Liu Yan‐Qiu , Scharf Daniel H. , Zhao Qing‐Wei , Li Yong‐Quan
Published: February 2022

The metabolic flux of fatty acyl‐CoAs determines lipopeptide biosynthesis efficiency, because acyl donor competition often occurs from polyketide biosynthesis and homologous pathways. We used A40926B0 as a model to investigate this mechanism. The lipopeptide A40926B0 with a fatty acyl group is the active precursor of dalbavancin, which is considered as a new lipoglycopeptide antibiotic. The biosynthetic pathway of fatty acyl‐CoAs in the A40926B0 producer Nonomuraea gerenzanensis L70 was efficiently engineered using endogenous replicon CRISPR (erCRISPR). A polyketide pathway and straight‐chain fatty acid biosynthesis were identified as major competitors in the malonyl‐CoA pool. Therefore, we modified both pathways to concentrate acyl donors for the production of the desired compound. Combined with multiple engineering approaches, including blockage of an acetylation side reaction, overexpression of acetyl‐CoA carboxylase, duplication of the dbv gene cluster and optimization of the fermentation parameters, the final strain produced 702.4 mg l‐1 of A40926B0, a 2.66‐fold increase, and the ratio was increased from 36.2% to 81.5%. Additionally, an efficient erCRISPR‐Cas9 editing system based on an endogenous replicon was specifically developed for L70, which increased conjugation efficiency by 660% and gene‐editing efficiency was up to 90%. Our strategy of redirecting acyl donor metabolic flux can be widely adopted for the metabolic engineering of lipopeptide biosynthesis.
GalR, GalX and AraR co‐regulate d‐galactose and l‐arabinose utilization in Aspergillus nidulans
Authors: Meng Jiali , Németh Zoltán , Peng Mao , Fekete Erzsébet , Garrigues Sandra , Lipzen Anna , Ng Vivian , Savage Emily , Zhang Yu , Grigoriev Igor V. , Mäkelä Miia R. , Karaffa Levente , de Vries Ronald P.
Published: February 2022

Filamentous fungi produce a wide variety of enzymes in order to efficiently degrade plant cell wall polysaccharides. The production of these enzymes is controlled by transcriptional regulators, which also control the catabolic pathways that convert the released monosaccharides. Two transcriptional regulators, GalX and GalR, control d‐galactose utilization in the model filamentous fungus Aspergillus nidulans, while the arabinanolytic regulator AraR regulates l‐arabinose catabolism. d‐Galactose and l‐arabinose are commonly found together in polysaccharides, such as arabinogalactan, xylan and rhamnogalacturonan I. Therefore, the catabolic pathways that convert d‐galactose and l‐arabinose are often also likely to be active simultaneously. In this study, we investigated the interaction between GalX, GalR and AraR in d‐galactose and l‐arabinose catabolism. For this, we generated single, double and triple mutants of the three regulators, and analysed their growth and enzyme and gene expression profiles. Our results clearly demonstrated that GalX, GalR and AraR co‐regulate d‐galactose catabolism in A. nidulans. GalX has a prominent role on the regulation of genes of d‐galactose oxido‐reductive pathway, while AraR can compensate for the absence of GalR and/or GalX.
In‐field genetic stock identification of overwintering coho salmon in the Gulf of Alaska: Evaluation of Nanopore sequencing for remote real‐time deployment
Authors: Deeg Christoph M. , Sutherland Ben J. G. , Ming Tobi J. , Wallace Colin , Jonsen Kim , Flynn Kelsey L. , Rondeau Eric B. , Beacham Terry D. , Miller Kristina M.
Published: February 2022

Genetic stock identification (GSI) from genotyping‐by‐sequencing of single nucleotide polymorphism (SNP) loci has become the gold standard for stock of origin identification in Pacific salmon. The sequencing platforms currently applied require large batch sizes and multiday processing in specialized facilities to perform genotyping by the thousands. However, recent advances in third‐generation single‐molecule sequencing platforms, such as the Oxford Nanopore minION, provide base calling on portable, pocket‐sized sequencers and promise real‐time, in‐field stock identification of variable batch sizes. Here we evaluate utility and comparability to established GSI platforms of at‐sea stock identification of coho salmon (Oncorhynchus kisutch) using targeted SNP amplicon sequencing on the minION platform during a high‐sea winter expedition to the Gulf of Alaska. As long read sequencers are not optimized for short amplicons, we concatenate amplicons to increase coverage and throughput. Nanopore sequencing at‐sea yielded data sufficient for stock assignment for 50 out of 80 individuals. Nanopore‐based SNP calls agreed with Ion Torrent‐based genotypes in 83.25%, but assignment of individuals to stock of origin only agreed in 61.5% of individuals, highlighting inherent challenges of Nanopore sequencing, such as resolution of homopolymer tracts and indels. However, poor representation of assayed salmon in the queried baseline data set contributed to poor assignment confidence on both platforms. Future improvements will focus on lowering turnaround time and cost, increasing accuracy and throughput, as well as augmentation of the existing baselines. If successfully implemented, Nanopore sequencing will provide an alternative method to the large‐scale laboratory approach by providing mobile small batch genotyping to diverse stakeholders.
Confounding and bias in observational studies in inflammatory bowel disease: a meta‐epidemiological study
Authors: Piovani Daniele , Pansieri Claudia , Peyrin‐Biroulet Laurent , Danese Silvio , Bonovas Stefanos
Published: February 2022

Background

Observational research concerning inflammatory bowel disease (IBD) is highly susceptible to spurious findings because of confounding and bias.

Aim

To investigate how these issues were reported in this research field.

Methods

We identified and appraised a random sample of 160 observational studies concerning IBD published in high‐impact gastroenterology journals and the most respected specialty journals of the condition. We applied a standardised methodology to assess how confounding and bias were reported and discussed, and investigated the association between yearly citations and study characteristics using mixed‐effect multivariable regression analysis.

Results

The authors of 67 out of 160 articles (41.9%) mentioned confounding, and in 89 cases (55.6%) reported any bias. Although most authors applied strategies to minimise confounding or bias (n = 139; 86.9%) and acknowledged at least one unadjusted confounder (n = 116; 72.5%), a minority commented about whether the main findings could have been affected (n = 60; 37.5%). Very few authors (n = 7; 4.4%) called for caution in interpreting the results in the discussion. Reporting of confounding and bias was particularly lacking for case‐control studies, those not using routinely collected data, those employing laboratory analyses as the primary method of assessment and studies investigating non‐modifiable exposures. In adjusted analyses, mentioning or alluding to confounding was positively associated with yearly citations (P = 0.010), whereas calling for a cautious interpretation of the findings was not.

Conclusions

Reporting of confounding is inadequate and its acknowledgement is often neglected in interpreting high‐impact observational research in IBD. These results encourage a more careful evaluation of the consequences of confounding and bias.
The occurrence of a palaeo‐lithification front in an overpressured basin (Chalk Group)—Timing from clumped isotopes and seismic stratigraphic analysis
Authors: Smit F. W. H. , Stemmerik L. , Smith M. E. , Staudigel P. T. , Lüthje M. , Mathiesen A. , van Buchem F. S. P. , Swart P. K.
Published: February 2022

This study proposes a unique workflow to unravel complex burial diagenetic histories of overpressured basins based on the integration of seismic and well log data, biostratigraphy, petrography, clumped isotope analyses and basin modelling. This approach is demonstrated with an example from the Chalk Group in the Danish Central Graben, where a seismic‐scale palaeo‐lithification front has been observed and studied in detail to elucidate the timing of the establishment of overpressured conditions and its relation to changing diagenetic activity. The palaeo‐lithification front separates high‐porosity chalks above, that dominantly underwent mechanical compaction and contact cementation, from low‐porosity chalk below, that dominantly underwent severe pressure dissolution and pore‐filling cementation. Analysis of chalk buried under hydrostatic conditions shows a strikingly similar lithification front between 1000 and 1200 m burial, much shallower than the lithification front in the Danish Central Graben at a current depth between 2100 and 2400 m below seafloor. The discrepancy of 1200 m is due to the establishment of overpressured conditions that limited the increase in effective stress as burial continued, finally halting burial compaction when formation fluids started to carry the lithostatic weight. Basin modelling data indicate that this occurred at the end of the Oligocene for large parts of the Danish Central Graben, which is much earlier than the Middle Miocene timing that is currently assumed. The results imply a regional occurrence of a relict lithification front in the North Sea Basin, its position guided by stratigraphy, but mainly dependent on the maximum effective stress experienced during its burial history. The study shows that the porosity bipartition is a remnant of the past and not from ongoing compaction as has previously been suggested. Since it was established before the thermal maturity of the main source rocks, chalk below the lithification front must have formed a sealing unit during hydrocarbon migration. The recognition of the lithification front is also of importance to velocity modelling and depth‐conversion since a non‐linear increase between velocity and depth is expected across this boundary. The methodology may be applied in other overpressured basins where the diagenetic state of reservoir rocks at the end of hydrostatic conditions must be constrained.
Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer
Authors: Macmillan Mark T. , Hopkins Michael E. , Gomati Anas , Subedi Deepak , Reid Helen , Bruce Lorna , Murchison John T. , Nixon Iain J.
Published: February 2022

Background

This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC).

Methods

Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow‐up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients.

Results

About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively).

Conclusion

Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.
1020. CYNORKIS MAMMUTHUS: Orchidaceae
Authors: Hermans Johan , Rajaovelona Landy , Sieder Anton , Pertl Margareta , Brown Andrew
Published: February 2022

Cynorkis mammuthus Hermans & P.J.Cribb from Madagascar was formally described in 2017 from an unidentified herbarium specimen and was thought to be extinct until it was recently found flourishing in northern Madagascar. It is illustrated here and a full description, history and conservation assessment are provided. It is compared with similar species from the region, especially Cynorkis elephantina.
The effect of payment medium on effort
Authors: Incekara‐Hafalir Elif , Kumar Raymond , Silva‐Goncalves Juliana
Published: February 2022

Employers reward workers and researchers pay human subjects using different payment mediums. These payment mediums can have various psychological effects on workers/research participants, and thereby influence their effort provision. In this paper, we investigate the effect of payment medium on participants' effort in a lab experiment. We find evidence that payment mediums affect participants' productivity when a fixed payment scheme is used, but not under a performance‐based payment scheme.