bluuebunny/crossref_metadata_2025 huggingface dataset:
815 Translational Research in Skin of Color Spontaneous Repigmentation of Post-Chemical Burn Leucoderma
Authors: Paiva Marcelo L , Miot Helio A , Beltrame Flavio L , Justo Aline S , Harrington David T , Hunter Mary A , Wambier Carlos G
Published: March 2022

Introduction

After facial burn injuries to skin of color (SOC) patients, repigmentation plays a critical role in post-burn quality of life, given the acquired contrast between preserved skin and achromic scars, and that daily concealment may be difficult. While leucoderma is a well-known side-effect of deep chemabrasion with phenol, phenol-croton oil, and high concentration trichloroacetic acid, mechanisms of repigmentation are still not fully understood, and the observation of spontaneous repigmentation of a deep chemical injury in SOC has not previously been described in the literature. In our study, we present the dynamics of long-term spontaneous facial repigmentation of a Fitzpatrick V chemical burn patient, with microscopic findings of a deep chemical peel SOC animal model.

Methods

We demonstrate spontaneous repigmentation in a 37-year-old female who initially presented with depigmented areas, erosions and eschars on the face, 7 days after accidental deep chemical burn, due to self-application of 70% glycolic acid to improve acne. This is juxtaposed with a SOC porcine experiment, performed with 35% phenol, 1.6% croton-oil, to evaluate depth-of-injury, neocollagenesis band thickness in 21 days, and skin pigmentary safety. A 6mm punch biopsy taken at 21 days underwent Herovici staining to reveal the thickness of collagen type III neocollagenesis, confirm the presence of melanin in the epidermis, and evaluate the presence of melanophages.

Results

On patient presentation, epidermolysis and areas of deep dermal burns were observed over the forehead and cheeks. At 14 days, multiple leucoderma scars persisted and initial perifollicular repigmentation was noticeable. At 28 days, most of the skin was repigmented; however, many areas had only perifollicular repigmentation and still very severe leucoderma. At 6 months, the skin still had small areas of leucoderma with folicular repigmentation. At 11 months the skin color was fully recovered, with minimal post-inflammatory hyperpigmentation (PIH) over the cheeks.

As for the SOC animal model, at 7 days the eschar was detached, and the skin was achromic. At 21 days, skin pigmentation was completely restored without macroscopic signs of PIH. Dermatopathology evaluation revealed microscopic areas of melanophages, a fully recovered epidermal melanin, and a band of over 500 micra of collagen type III.

Overall, on follicle-dense areas after chemical burn, we observed progressive full repigmentation over the course of 11 months on the patient, and by day 21 in the porcine SOC model.

Conclusions

Spontaneous repigmentation occurred both after accidental deep chemical ablation to the face of a SOC patient, and on the porcine SOC model after deep chemical peel formula application.
Patient Experiences in the Management of Inflammatory Bowel Disease: A Qualitative Study
Authors: Mirza Raza M , MacKean Gail , Shaffer Seth R , Sewitch Maida J , Heisler Courtney , McLeod Justine , Habashi Peter , MacDonald Karen V , Barker Karis , Nguyen Geoffrey C , Marshall Deborah A
Published: March 2022

Background

Inflammatory bowel disease (IBD) can lead to substantial impairments of quality-of-life. Clinical guidelines and quality indicators aid physicians in practice but may not reflect the perspectives and experiences of patients with IBD. To address this, the objectives of this study were to understand patient experiences with IBD care and to explore priorities.

Methods

Based on a convenience sample of 36 participants, five focus groups were completed at four sites across Canada. Data were analyzed using a deductive thematic analysis approach to assess emergent themes and variability in participants’ experiences.

Results

Our results are organized by themes of structure, process and outcomes to illustrate common issues with respect to how care is organized in the healthcare system, how patients receive and experience care and how patients perceive the outcomes of their care. Our results frame a health systems quality approach that signal needed improvements in access to care, the need for innovation with respect to virtual medicine, the potential expansion of multidisciplinary team-based care and the importance of addressing the psychosocial dimensions for patients with IBD and their caregivers in order to better deliver patient-centred care.

Conclusions

The issues identified have the potential to impact priority areas in the system, IBD care delivery, and how outcomes can be improved by focusing on ‘lived experience’ and patient-centred care. The differing values and perspectives of all those involved in caring for patients with IBD underscore the importance of good communication with patients, caregivers and family members, as well as staying responsive to evolving needs.
International transport costs: new findings from modeling additive costs
Authors: Daudin Guillaume , Héricourt Jérôme , Patureau Lise
Published: March 2022

International transport costs do have an additive part. How large is it? Does it matter? This article provides new answers to these questions. Using information contained in the US imports flows from 1974 to 2019, we develop an empirical model that disentangles the ad-valorem and the additive components of international transport costs. The per-unit component of transport costs represents a sizeable share of total transport costs, between 30% and 45% depending on the year and the transport mode considered. We then investigate the important consequences of additive costs, under two different perspectives. First, modeling varying additive costs modifies the decomposition of transport costs time trend between the reduction in ‘pure’ transport costs and trade composition effects, the latter playing a minor role. Second, we revisit the welfare gains of the transport cost reduction in presence of additive costs. In this regard, we shed light on the welfare variations induced by the international trade acceleration and the ‘hyper-globalization’, as well as the key role of additive transport costs in determining those welfare variations. Neglecting the additive component substantially underestimates the welfare gains of the transport cost decrease.
‘Faith in God and the last day’ in Ghazālī: What Faith for What People?
Authors: Leites Adrien
Published: March 2022

This article considers the use of the traditional phrase ‘faith in God and the last day’ in five shorter works of Abū Ḥāmid al-Ghazālī. It looks into Ghazālī’s understanding of the ‘minimal faith’ specified by this phrase, and makes three main points. Ghazālī regards minimal faith as having a synthetic object, which may be called ‘a retributory God’ or simply ‘otherworldly retribution’. Minimal faith as understood by Ghazālī is useful to bring deficient Muslims back to observance. Ghazālī also regards minimal faith as useful to make non-Muslims shift to Islam, but does not regard this faith as shared specifically by Jews and Christians. The rhetorical and polemical trend of Ghazālī, on the other hand, is presented in the course of the article. Ghazālī’s concern with persuading or discrediting, I eventually argue, might outweigh his involvement in ‘doctrine’.
Changing Norms in Practice: Noninterference in the UN and ASEAN
Authors: Glas Aarie , Laurence Marion
Published: March 2022

Noninterference is a foundational governance norm for international and regional organizations. In the United Nations and the Association of Southeast Asian Nations, the norm has long undergirded the practice of interstate governance in fundamental ways. However, the noninterference norm has been understood and enacted in disparate ways between these organizations and over time within them. While theories of norm diffusion and contestation have long examined the variable understanding of norms within different contexts, we argue that they are inadequate to analyze cases—like those we examine in this article—where divergent practices do not spring from a conscious desire to contest a norm's relevance, meaning, or requirements. To understand dynamics of norm change, we argue that the growing literature on international practices should be placed in dialogue with both traditional accounts of norm diffusion and existing scholarship on norm contestation. We build on these literatures to offer a novel and productive framework to explore shifting beliefs about the competent enactment of norms within disparate communities over time. Empirically, we center attention on the recent United Nations (UN) peace operation in Côte d'Ivoire and the Association of Southeast Asian Nations (ASEAN) response to the ongoing Rohingya crisis. In each case, we show that divergent interpretations of the noninterference norm are embedded in seemingly mundane practices that have the potential to transform that norm over the long term. We draw on detailed empirical evidence to illustrate the changing practice of the noninterference norm in each case, relying on seventy-six interviews with officials from both organizations.
A Lot of Cyber Fizzle But Not A Lot of Bang: Evidence about the Use of Cyber Operations from Wargames
Authors: Schneider Jacquelyn , Schechter Benjamin , Shaffer Rachael
Published: March 2022

Despite a burgeoning focus on cyber and international security, there is still great debate about how cyber operations fit among other military and foreign policy means. Are they a substitution option—a way to create similar effects with different, potentially less risky, means? Or are they a support to other means, meant to enable and increase the efficacy of military operations and foreign policy options? Finally, are they a new complement to existing means—a unique way to influence, coerce, and derive military outcomes? The answer to these questions is significant because how cyber operations are used has implications for crisis stability as well as the ways wars are fought. In order to test these theories of cyber and state power, we use a crisis wargame that examines the use of cyberspace operations across a game series played over two years with 500+ players. We find that, despite a general increase in focus within the game on cyber operations, these operations still have little influence on the overall violence of the crises. Instead, cyber operations are primarily used to shape narratives as a complement to diplomacy prior to war and then as a support to military operations after war has escalated. Cyber operations, therefore, show an increasing and important amount of fizzle but not a lot of bang.
A ruptured pancreatic pseudocyst causes acute peritonitis with clinical characteristics of a gastrointestinal tract perforation
Authors: Son Tran Que , Hoc Tran Hieu , Huong Tran Thu , Dinh Ngo Quang , Van Tuyen Pham
Published: March 2022

Intraperitoneal air in pancreatic pseudocysts is a rare complication that can jeopardize hemodynamic stability and requires emergency surgery. A 61-year-old man was admitted to our hospital after abdominal pain, vomiting and diarrhea. Computed tomography showed a hollow visceral perforation with intraperitoneal air and two pseudocysts close to the pancreas. The patient was transferred to the emergency operating room with symptoms of septic shock. We histopathologically diagnosed a ruptured pancreatic pseudocyst combined with an intracystic haemorrhage. We resected a portion of the pseudocyst wall using surface electrocautery inside the lumen, cholecystectomy and peritoneal toilet and maintained adequate external drainage. The patient was discharged on postoperative Day 12. The patient achieved relapse-free survival for 12 months postoperatively. Ruptured pancreatic pseudocysts with extraluminal gas are dangerous if effective medical interventions are not performed. Emergency surgery should be completed as soon as possible to drain the pancreatic cyst and cleanse the abdomen.
A country classification system to inform rabies prevention guidelines and regulations
Authors: Henry Ronnie E , Blanton Jesse D , Angelo Kristina M , Pieracci Emily G , Stauffer Kendra , Jentes Emily S , Allen Jessica , Glynn Marielle , Brown Clive M , Friedman Cindy R , Wallace Ryan
Published: March 2022

Background

Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies.

Methods

CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high.

Results

A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk.

Conclusions

We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.
The PEPSI exoplanet transit survey (PETS) I: investigating the presence of a silicate atmosphere on the super-earth 55 Cnc e
Authors: Keles Engin , Mallonn Matthias , Kitzmann Daniel , Poppenhaeger Katja , Hoeijmakers H Jens , Ilyin Ilya , Alexoudi Xanthippi , Carroll Thorsten A , Alvarado-Gomez Julian , Ketzer Laura , Bonomo Aldo S , Borsa Francesco , Gaudi B Scott , Henning Thomas , Malavolta Luca , Molaverdikhani Karan , Nascimbeni Valerio , Patience Jennifer , Pino Lorenzo , Scandariato Gaetano , Schlawin Everett , Shkolnik Evgenya , Sicilia Daniela , Sozzetti Alessandro , Foster Mary G , Veillet Christian , Wang Ji , Yan Fei , Strassmeier Klaus G
Published: March 2022

The study of exoplanets and especially their atmospheres can reveal key insights on their evolution by identifying specific atmospheric species. For such atmospheric investigations, high-resolution transmission spectroscopy has shown great success, especially for Jupiter-type planets. Towards the atmospheric characterization of smaller planets, the super-Earth exoplanet 55 Cnc e is one of the most promising terrestrial exoplanets studied to date. Here, we present a high-resolution spectroscopic transit observation of this planet, acquired with the PEPSI instrument at the Large Binocular Telescope. Assuming the presence of Earth-like crust species on the surface of 55 Cnc e, from which a possible silicate-vapor atmosphere could have originated, we search in its transmission spectrum for absorption of various atomic and ionized species such as Fe , Fe +, Ca , Ca +, Mg, and K , among others. Not finding absorption for any of the investigated species, we are able to set absorption limits with a median value of 1.9 × RP. In conclusion, we do not find evidence of a widely extended silicate envelope on this super-Earth reaching several planetary radii.
Suppression of axonal attractant netrin-1 injured dopaminergic neuronal and motor function of mice during manganese overexposure
Authors: Wen Yi , Qi Zhipeng , Li Jiashuo , Zhang Lei , Wang Shuang , Cui Rong , Xu Bin , Liu Wei , Xu Zhaofa , Deng Yu
Published: March 2022

Manganese (Mn) can accumulate in the striatum through the blood–brain barrier and cause neurotoxicity. It is mainly due to the decrease of dopamine (DA) levels in the striatum, which leads to extrapyramidal dysfunction. Netrin-1, as an axon guidance factor, can regulate the normal transmission of DA. However, few people have explored the role of netrin-1 in Mn-induced neurotoxicity. The purpose of the present study is to verify whether overexposure of Mn inhibits the axon attractant netrin-1, thereby damaging dopaminergic neuronal and motor function of mice. Here, we found that excessive Mn exposure reduces the expression of striatum netrin-1, tyrosine hydroxylase, DA receptor D3, and dopamine transporter 1, and the levels of serum netrin-1, and promotes dopaminergic neuronal and striatum injury, leading to DA transmission and motor dysfunction. Notably, recombinant mouse netrin-1 protein significantly antagonized Mn-induced neurotoxicity. These findings suggest that netrin-1 participates in Mn-induced motor dysfunction. Our findings may provide an experimental basis for fully elucidating the effects of Mn-induced neurotoxicity.
Epigenetic alterations at distal enhancers are linked to proliferation in human breast cancer
Authors: Ankill Jørgen , Aure Miriam Ragle , Bjørklund Sunniva , Langberg Severin ,   Oslo Breast Cancer Consortium (OSBREAC), Bathen Tone F , Borgen Elin , Engebråten Olav , Fritzman Britt , Garred Norway Øystein , Geisler Jürgen , Geitvik Gry Aarum , Hofvind Solveig , Kåresen Rolf , Langerød Anita , Lingjærde Ole Christian , Mælandsmo Gunhild Mari , Naume Bjørn , Russnes Hege G , Sauer Torill , Skjerven Helle Kristine , Sørlie Therese , Kristensen Vessela N , Vitelli Valeria , Tekpli Xavier , Fleischer Thomas
Published: March 2022

Aberrant DNA methylation is an early event in breast carcinogenesis and plays a critical role in regulating gene expression. Here, we perform genome-wide expression-methylation Quantitative Trait Loci (emQTL) analysis through the integration of DNA methylation and gene expression to identify disease-driving pathways under epigenetic control. By grouping the emQTLs using biclustering we identify associations representing important biological processes associated with breast cancer pathogenesis including regulation of proliferation and tumor-infiltrating fibroblasts. We report genome-wide loss of enhancer methylation at binding sites of proliferation-driving transcription factors including CEBP-β, FOSL1, and FOSL2 with concomitant high expression of proliferation-related genes in aggressive breast tumors as we confirm with scRNA-seq. The identified emQTL-CpGs and genes were found connected through chromatin loops, indicating that proliferation in breast tumors is under epigenetic regulation by DNA methylation. Interestingly, the associations between enhancer methylation and proliferation-related gene expression were also observed within known subtypes of breast cancer, suggesting a common role of epigenetic regulation of proliferation. Taken together, we show that proliferation in breast cancer is linked to loss of methylation at specific enhancers and transcription factor binding and gene activation through chromatin looping.
TargetGeneReg 2.0: a comprehensive web-atlas for p53, p63, and cell cycle-dependent gene regulation
Authors: Fischer Martin , Schwarz Robert , Riege Konstantin , DeCaprio James A , Hoffmann Steve
Published: March 2022

In recent years, our web-atlas at www.TargetGeneReg.org has enabled many researchers to uncover new biological insights and to identify novel regulatory mechanisms that affect p53 and the cell cycle – signaling pathways that are frequently dysregulated in diseases like cancer. Here, we provide a substantial upgrade of the database that comprises an extension to include non-coding genes and the transcription factors ΔNp63 and RFX7. TargetGeneReg 2.0 combines gene expression profiling and transcription factor DNA binding data to determine, for each gene, the response to p53, ΔNp63, and cell cycle signaling. It can be used to dissect common, cell type and treatment-specific effects, identify the most promising candidates, and validate findings. We demonstrate the increased power and more intuitive layout of the resource using realistic examples.
A m6Avalue predictive of prostate cancer stemness, tumor immune landscape and immunotherapy response
Authors: Zou Cheng , He Qinju , Feng Yuqing , Chen Mengjie , Zhang Dingxiao
Published: March 2022

The molecular mechanisms underpinning prostate cancer (PCa) progression are incompletely understood, and precise stratification of aggressive primary PCa (pri-PCa) from indolent ones poses a major clinical challenge. Here, we comprehensively dissect, genomically and transcriptomically, the m6A (N6-methyladenosine) pathway as a whole in PCa. Expression, but not the genomic alteration, repertoire of the full set of 24 m6A regulators at the population level successfully stratifies pri-PCa into three m6A clusters with distinct molecular and clinical features. These three m6A modification patterns closely correlate with androgen receptor signaling, stemness, proliferation and tumor immunogenicity of cancer cells, and stroma activity and immune landscape of tumor microenvironment (TME). We observe a discrepancy between a potentially higher neoantigen production and a deficiency in antigen presentation processes in aggressive PCa, offering insights into the failure of immunotherapy. Identification of PCa-specific m6A phenotype-associated genes provides a basis for construction of m6Avalue to measure m6A methylation patterns in individual patients. Tumors with lower m6Avalue are relatively indolent with abundant immune cell infiltration and stroma activity. Interestingly, m6Avalue separates PCa TME into fibrotic and nonfibrotic phenotypes (instead of previously reported immune-proficient or -desert phenotypes in other cancer types). Significantly, m6Avalue can be used to predict drug response and clinical immunotherapy efficacy in both castration-resistant PCa and other cancer types. Therefore, our study establishes m6A methylation modification pattern as a determinant in PCa progression via impacting cancer cell aggressiveness and TME remodeling.
Multiplicity does not significantly affect outcomes in brain metastasis patients treated with surgery
Authors: Yang Kaiyun , Gutiérrez-Valencia Enrique , Landry Alexander P , Kalyvas Aristotelis , Millesi Matthias , Leite Matheuss , Jablonska Paola Anna , Weiss Jessica , Millar Barbara-Ann , Conrad Tatiana , Laperriere Normand , Bernstein Mark , Zadeh Gelareh , Shultz David , Kongkham Paul N
Published: March 2022

Background

Brain metastasis quantity may be a negative prognostic factor for patients requiring resection of at least one lesion.

Methods

We retrospectively reviewed patients who underwent surgical resection of brain metastases from July 2018 to June 2019 at our institution, and examined outcomes including overall survival (OS), progression free survival (PFS), and rates of local failure (LF). Patients were grouped according to the number of metastases at the time of surgery (single vs multiple).

Results

We identified 130 patients who underwent surgical resection as the initial treatment modality. At the time of surgery, 87 patients had only one lesion (control) and 43 had multiple (>1). Two-year OS for the entire cohort was 46%, with equal rates in both the multiple metastases group and the control group (P = .335). 2-year PFS was 27%; 21% in the multiple metastases group and 31% in the control group (P = .766). The rate of LF at 2 years was 32%, with equal rates in both the multiple lesion group and control group (P = .889). On univariate analysis, multiplicity was not significantly correlated to OS (HR = 0.80, 95% CI: 0.51–1.26, P = .336), PFS (HR = 1.06, 95% CI: 0.71–1.59, P = .766) or LF (HR = 1.06, 95% CI: 0.57–1.97, P = .840). Multivariate analysis revealed preoperative tumor volume of the resected lesion to be the single correlate for OS (P = .0032) and PFS (P = .0081).

Conclusions

Having more than one metastasis does not negatively impact outcomes in patients treated with surgery. In carefully selected patients, especially those with large tumors, surgery should be considered regardless of the total number of lesions.
The Effect of Systemic Antibiotics for Suppurative Skin and Soft Tissue Infections on the Skin Microbiome
Authors: Chan Alfred A , Flores Evelyn A , Navarrete Marian , Phan Tran Donna , Lee Delphine J , Miller Loren G
Published: March 2022

Background

Skin and soft tissue infections (SSTIs) are very common bacterial infections. There are few data on the microbiome of persons with and without SSTIs and the effects of systemic antibiotic therapy.

Methods

We sampled the skin microbiome from 10 outpatients with acute suppurative SSTI before and after systemic antibiotic therapy and enrolled 10 matched controls. Samples were collected at 6 skin body sites (occipital scalp, axilla, interdigital hand web spaces, gluteal crease, inguinal creases, and popliteal fossa), 2 mucosal sites (throat, anterior nares), and the site of skin infection (for case subjects) at baseline and a week later after abscess incision, drainage, and oral antibiotics.

Result

Among 10 SSTI cases, mean age was 41.5 years and 3 had diabetes mellitus. The gluteal crease at baseline had higher α-diversity in controls vs cases (P = .039); β-diversity analysis showed significant differences in overall bacterial community composition (P = .046). However, at other body sites there were no significant differences by either α- or β-diversity. Systemic antibiotic use did not affect body site diversity indices except at the SSTI site (α-diversity increased, P = .001).

Conclusions

We surprisingly found no significant differences in microbiome comparing noninfected skin sites before and after systemic SSTI antibiotic therapy nor significant differences at noninfected skin sites between SSTI cases and uninfected controls. We also found minimal significant differences between microbiome diversity and bacterial signatures at noninfected skin sites between patients with acute skin infection and uninfected controls. Our findings challenge the dogma that systemic antibiotics impact the skin microbiome.
LONGL-Net: temporal correlation structure guided deep learning model to predict longitudinal age-related macular degeneration severity
Authors: Ganjdanesh Alireza , Zhang Jipeng , Chew Emily Y , Ding Ying , Huang Heng , Chen Wei
Published: March 2022

Age-related macular degeneration (AMD) is the principal cause of blindness in developed countries, and its prevalence will increase to 288 million people in 2040. Therefore, automated grading and prediction methods can be highly beneficial for recognizing susceptible subjects to late-AMD and enabling clinicians to start preventive actions for them. Clinically, AMD severity is quantified by Color Fundus Photographs (CFP) of the retina, and many machine-learning-based methods are proposed for grading AMD severity. However, few models were developed to predict the longitudinal progression status, i.e. predicting future late-AMD risk based on the current CFP, which is more clinically interesting. In this paper, we propose a new deep-learning-based classification model (LONGL-Net) that can simultaneously grade the current CFP and predict the longitudinal outcome, i.e. whether the subject will be in late-AMD in the future time-point. We design a new temporal-correlation-structure-guided Generative Adversarial Network model that learns the interrelations of temporal changes in CFPs in consecutive time-points and provides interpretability for the classifier's decisions by forecasting AMD symptoms in the future CFPs. We used about 30,000 CFP images from 4,628 participants in the Age-Related Eye Disease Study. Our classifier showed average 0.905 (95% CI: 0.886–0.922) AUC and 0.762 (95% CI: 0.733–0.792) accuracy on the 3-class classification problem of simultaneously grading current time-point's AMD condition and predicting late AMD progression of subjects in the future time-point. We further validated our model on the UK Biobank dataset, where our model showed average 0.905 accuracy and 0.797 sensitivity in grading 300 CFP images.
Promoting organic food production through flagship regions
Authors: Mennig Philipp , Sauer Johannes
Published: March 2022

Mitigating the environmental impact of agriculture is a major issue in negotiations on the future of the European Union's Common Agricultural Policy. Organic farming is commonly put forward in these discussions as a promising way to reduce the negative environmental impact of agriculture. Consequently, different promotional strategies aiming at the adoption of organic farming practices have been developed. In 2013, the German federal state of Bavaria initiated an innovative programme that resulted in ‘organic flagship regions’ being appointed in the years that followed. These regions are allocated support with the main goal of motivating farmers to switch to organic production. By applying a difference-in-differences estimator, we evaluate whether the programme has achieved its aims, i.e. whether more farmers have adopted organic farming practices within the flagship regions as compared to farmers outside such regions. The Theory of Planned Behaviour provides the conceptual framework to identify the main factors influencing a farmer's decision to go organic. Our results suggest that the programme fails to motivate farmers to switch to organic production and that there is a need to more effectively target decision-influencing factors.
Microorganisms and Antibiotic Resistance of Bacterial Keratitis at a Rural County Hospital in Seville
Authors: Lorente Pascua José , García Bernal Ana , Garcia Sanchez Estefania , Almeida González Carmen V.
Published: March 2022

Purpose:

To review the incidence, resistance patterns, and management of bacterial keratitis during the past 4 years.

Methods:

We retrospectively reviewed the clinical records of microbiological isolates from patients with a clinical diagnosis of bacterial keratitis.

Results:

A total of 159 patients were analyzed, and 102 microorganisms were isolated from 129 cultures. In these cultures, 23.7% of the microorganisms were gram positive, 60.8% were gram negative, and 15.5% were fungi. Pseudomonas aeruginosa was the most common bacteria (9.2%), followed by Serratia marcescens (4.4%) and Staphylococcus aureus (4%). Resistance to fluoroquinolones and aminoglycosides was found to be 23.1% and 53.1% in gram-positive and 2.8% and 13.9% in gram-negative bacteria, respectively. Resistance to ceftazidime against gram-negative bacteria was 13.9%. No resistance to vancomycin was observed.

Conclusions:

A high resistance rate to aminoglycosides and fluoroquinolones was observed in gram-positive bacteria. We concluded that fluoroquinolones or aminoglycosides may not be suitable for initial monotherapy in patients with severe bacterial keratitis.
The Role of Orthokeratology in Myopia Management
Authors: Lipson Michael J.
Published: March 2022

Intervention to slow axial elongation and progressing degree of myopia has become an important public health issue. Although orthokeratology (OrthoK) has been prescribed to temporarily reduce or eliminate refractive error, myopic children undergoing OrthoK have shown significant slowing of axial elongation and myopic progression. This review presents data on the efficacy, benefits, and risks of the use of OrthoK to slow axial elongation in myopic children. It also discusses how OrthoK fits into an overall strategy of myopia management in practice compared with alternative prescribed interventions to slow myopic progression. Other factors discussed are patient candidacy, impact on vision-related quality of life, and use of OrthoK in combination with pharmaceutical agents. With precise fitting, careful follow-up, and patient compliance with recommended lens cleaning and disinfection, OrthoK is a safe and effective method to slow axial elongation in children.
Predictors of Dual E-Cigarette and Cigarette Use
Authors: Nagel Casey , Hugueley Brandon , Cui Yan , Nunez Denise M. , Kuo Tony , Kuo Alice A.
Published: March 2022

Objective:

To compare prevalence of e-cigarette and cigarette use and to determine predictors of dual use.

Design, Setting, and Participants:

Using a countywide random digit dial telephone health survey conducted during January 2018 to March 2019, we analyzed data from a random sample of 6966 adults. Bivariate analyses described vaping, cigarette use, and sociodemographics. A multivariable logistic regression model examined dual use.

Results:

Young adults 18 to 24 years of age had the highest prevalence of e-cigarette-only use (11.5%), the second-highest prevalence of dual use (3.9%), and the lowest prevalence of cigarette-only use (5.8%). Males were more likely than females to use e-cigarettes (5.1% vs 2.7%), traditional cigarettes (11.1% vs 6.9%), or be dual users (3.6% vs 1.1%). Of those who used e-cigarettes or both, approximately half had also used marijuana in the past 30 days.

Conclusions:

E-cigarette use among young adults is concerning because it could lead to eventual dual use of e-cigarettes and traditional cigarettes.
Utility of Poison Control Center Data for Automated Opioid Overdose Surveillance
Authors: Radloff Christina L. , Bennett Heather , Staes Catherine J.
Published: March 2022

Context:

Overdosing on opioids is a national epidemic and the number one cause of death from unintentional injury in the United States. Poison control centers (PCCs) may be a source of timely data that can track opioid exposure cases, identify clusters of opioid exposure cases by geographic region, and capture opioid exposure cases that may not seek medical attention from health care facilities.

Objective:

The objectives were to (a) identify data requirements for opioid overdose case ascertainment and classification and visualization in a dashboard, and (b) assess the availability and quality of the relevant PCC data for state-based opioid overdose surveillance.

Design:

We identified types of opioid exposure, demographic characteristics, and other features that may be relevant for public health officials to monitor and respond to opioid overdose events in the community. We operationalized case definitions for an opioid overdose event based on the Centers for Disease Control and Prevention case classification definitions. We assessed the PCC database for concepts and metrics needed to operationalize case definitions for opioid overdose events to determine the feasibility of using the PCC for automated surveillance.

Main Outcome Measure:

Quality and availability of required concepts to operationalize metrics and case definitions using PCC data.

Results:

A subset of the probable case definition may be used for automated surveillance with available structured PCC data. In contrast, logic for confirmed, suspected, and part of the probable case definitions requires additional structured data or analysis of narrative text, which may not contain needed concepts. For example, the confirmed case definition currently requires evidence from narrative text of laboratory confirmation of an opioid in a clinical specimen or diagnosis of opioid overdose in a health care record.

Conclusion:

PCC data are a timely and potentially useful source for automated surveillance of a subset of opioid overdose events, but additional structured and/or coded data are required.
Evaluating the use of a thermoplastic socket in Kenya: A pilot study
Authors: Barbareschi Giulia , Teerlink Wesley , Njuguna Josepg Gakunga , Musungu Purity , Kirino Mary Dama , Holloway Catherine
Published: March 2022

Background:

Many people with amputations who live in low-resourced settings struggle to access the workshops where qualified prosthetists provide appropriate care. Novel technologies such as the thermoplastic Confidence Socket are emerging, which could help facilitate easier access to prosthetic services.

Objectives:

The objective of this study was to evaluate the satisfaction and the performance of transtibial prosthesis featuring the Confidence Socket.

Study design:

This is a longitudinal repeated-measures design study.

Methods:

A convenience sample of 26 participants who underwent transtibial amputation were fitted with the Confidence Socket. The performance of the socket was evaluated after a follow-up period between 1 month and 6 months using the L test of functional mobility and the amputee mobility predictor. Satisfaction with the prosthesis was measured using the Trinity Amputation and Prosthetic Experience Scales and purposefully designed 7-point Likert scales.

Results:

Ten of the 26 participants returned for follow-up. Perceived activity restriction and L test times improved significantly at follow-up, but the self-reported satisfaction with the Confidence Socket was lower at follow-up compared with that after fitting.

Conclusions:

The Amparo Confidence Socket represents a potentially viable alternative to improve access to appropriate prosthesis in Kenya, but some aspects of users’ self-reported satisfaction should be further investigated.
Firing patterns of ventral hippocampal neurons predict the exploration of anxiogenic locations
Authors: Malagon-Vina Hugo , Ciocchi Stéphane , Klausberger Thomas
Published: March 2022

The ventral hippocampus (vH) plays a crucial role in anxiety-related behaviour and vH neurons increase their firing when animals explore anxiogenic environments. However, if and how such neuronal activity induces or restricts the exploration of an anxiogenic location remains unexplained. Here, we developed a novel behavioural paradigm to motivate rats to explore an anxiogenic area. Rats ran along an elevated linear maze with protective sidewalls, which were subsequently removed in parts of the track to introduce an anxiogenic location. We recorded neuronal action potentials during task performance and found that vH neurons exhibited remapping of activity, overrepresenting anxiogenic locations. Direction-dependent firing was homogenised by the anxiogenic experience. We further showed that the activity of vH neurons predicted the extent of exploration of the anxiogenic location. Our data suggest that anxiety-related firing does not solely depend on the exploration of anxiogenic environments, but also on intentions to explore them.
Why is the average collateral effect of synonymous mutations so similar across alternative reading frames?
Authors: Wichmann Stefan , Ardern Zachary
Published: March 2022

The standard genetic code has been shown to have multiple interesting properties which impact on molecular biology and the evolutionary process. One facet of molecular biology where code structure is particularly important is the origin and evolution of overlapping genes. We have previously reported that the structure of the standard genetic code ensures that synonymous mutations in a protein coding gene will lead to a remarkably similar average “collateral” mutation effect size in at least four out of the five alternative reading frames. Here we show that only 0.26% of alternative codes with the block structure of the standard genetic code perform at least as well as the standard code in this property. Considering this finding within a code optimality framework suggests that this consistent effect size across the different frames may be adaptive. Here we give context for this finding and present a simple model where a trade-off between evolvability and robustness leads to an average mutation effect size which maximises population fitness. This supports the intuition that similar mutation effects across the different alternative reading frames may be an adaptive property of the standard genetic code which facilitates evolvability through the use of alternative reading frames.
Fusarium solanispecies complex genomes reveal bases of compartmentalisation and animal pathogenesis
Authors: Hoh Daphne Z. , Lee Hsin-Han , Wada Naohisa , Liu Wei-An , Lu Min R. , Lai Cheng-Kuo , Ke Huei-Mien , Sun Pei-Feng , Tang Sen-Lin , Chung Wen-Hsin , Chen Ying-Lien , Chung Chia-Lin , Tsai Isheng Jason
Published: March 2022

TheFusarium solanispecies complex (FSSC) comprises fungal pathogens responsible for mortality in a diverse range of animals and plants, but their genome diversity and transcriptome responses in animal pathogenicity remain to be elucidated. We sequenced and compared six chromosome-level FSSC clade 3 genomes of aquatic animal and plant host origins and revealed a spectrum of conservation patterns in chromosomes categorised into three compartments: core, fast-core (FC), and lineage-specific (LS). Each chromosome type varied in structural architectures, with FC and LS chromosomes containing significantly higher proportions of repetitive elements and methylation levels than core chromosomes, with genes exhibiting higherdN/dS and enriched in functions related to pathogenicity and niche expansion. Mesosynteny were detected between FC chromosomes ofFusariumgenomes, indicating that these chromosomes were present in a common ancestor that predated FSSC species. These findings provide evidence that genome compartmentalisation was the outcome of multi-speed evolution amongst FSSC chromosomes. We further demonstrated thatF. falciformeandF. keratoplasticumare opportunistic pathogens by inoculatingPelodiscus sinensiseggs and identified differentially expressed genes also associated with plant pathogenicity. These included the most upregulated genes encoding the CFEM (Common in Fungal Extracellular Membrane) domain. The study establishes genomic resources and an animal model for fungal pathogens of trans-kingdom hosts.
Development of a Model for Differentiating PDAC from Benign Pancreatic Conditions: A Prospective Case-control Study
Authors: Zardab Mohamed , Balarajah Vickna , Banerjee Abhirup , Stasinos Konstantinos , Saad Amina , Imrali Ahmet , Hughes Christine , Roberts Rhiannon , Vajrala Ajith , Chelala Claude , Kocher Hemant M , Dayem Ullah Abu Z M
Published: March 2022

Background & aims

Pancreatic ductal adenocarcinoma (PDAC) continues to be a devastating disease with late diagnosis and poor overall survival, complicated by clinical presentations similar to benign pancreatic diseases. We aimed to analyse clinical parameters with the goal of developing a prediction model for differentiating suspected PDAC from benign pancreatic conditions.

Methods and results

We used a prospectively recruited cohort of patients with pancreatic disease (n=762) enrolled at the Barts Pancreas Tissue Bank between January 1, 2008 and September 21, 2021 to perform a case-control study examining the association of PDAC (n=340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Using a machine learning approach, candidate PDAC risk-prediction algorithms were trained on 75% of the cohort, using a subset of the predictor variables identified from a preliminary observational association study. Models were assessed on the remaining 25%. Multiple imputed datasets were used for both training and validation to accommodate for unknown data.

Age (over 55), weight loss in hypertensive patients, recent symptom of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low lymphocyte count and low serum sodium were the most important features when separating putative PDAC cases from less severe pancreatic conditions. A simple logistic regression model had the best performance with an area under the curve (AUC) of 0.88. Setting a probability threshold of 0.17 guided by the maximum F2 score, a sensitivity of 95.6% was reached in the full cohort which could lead to early detection of around 84% of the PDAC patients.

Conclusion

The resultant prediction model significantly outperformed the current UK guidelines for suspected pancreatic cancer referral and could improve detection rates of PDAC in the community. After further work this approach could lead to an easy to understand, utilisable risk score to be applied in the primary and secondary care setting for referring patients to specialist hepato-pancreatico-biliary services.
Risk factors for SARS-CoV-2 transmission in student residences: a case-ascertained study in Leuven, Belgium from October 2020 until May 2021
Authors: Vanbesien Marte , Molenberghs Geert , Geenen Caspar , Thibaut Jonathan , Gorissen Sarah , André Emmanuel , Raymenants Joren
Published: March 2022

Background

Student residences are at high risk for rapid COVID-transmission due to crowding and frequent close contact.

Aim

We aimed to investigate the overall secondary attack rates (SAR) in student residences and to discern risk factors for higher transmission in order to improve the evidence base for screening efforts and preventive measures.

Methods

In this retrospective case-ascertained study, we analysed data from student residences screened in Leuven, Belgium between October 2020 and May 2021, following detection of a COVID-19 case in the residence. We investigated the impact on the SAR in the living units screened of delay-time until follow-up, shared use of kitchen or sanitary facilities, presence of an external infection source and occurrence of social gatherings attended by the index case.

Results

We included 200 residence units, representing 2326 screened residents, of which 68 units showed secondary transmission. The overall SAR was estimated at 0.0813 (95%CI 0.0705-0.0936). Both sharing sanitary facilities (p=0.04) and social gatherings attended by the index case (p=0.033) significantly impacted SAR, which increased from 3% to 13% when both risk factors were present compared to absent.

Conclusions

We identify risk factors which should be considered when selecting students for screening during an outbreak of COVID-19 in student residences to improve comprehensiveness and proportionality of testing. The identified risk factors improve the evidence base for preventive measures aimed at limiting social gatherings and improving ventilation of shared spaces in outbreak-prone settings. Lastly, they should be considered when designing student accommodation and other shared households.