bluuebunny/crossref_metadata_2025 huggingface dataset:
HNRNPC regulates RhoA to induce DNA damage repair and cancer‐associated fibroblast activation causing radiation resistance in pancreatic cancer
Authors: Xia Ning , Yang Nannan , Shan Qungang , Wang Ziyin , Liu Xiaoyu , Chen Yingjie , Lu Jian , Huang Wei , Wang Zhongmin
Published: March 2022

Pancreatic cancer (PC) is one of the most lethal types of cancer due to its asymptomatic nature in the early stages and consequent late diagnosis. Its mortality rate remains high despite advances in treatment strategies, which include a combination of surgical resection and adjuvant therapy. Although these approaches may have a positive effect on prognosis, the development of chemo‐ and radioresistance still poses a significant challenge for successful PC treatment. Heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) and RhoA have been implicated in the regulation of tumour cell proliferation and chemo‐ and radioresistance. Our study aims to investigate the mechanism for HNRNPC regulation of PC radiation resistance via the RhoA pathway. We found that HNRNPC and RhoA mRNA and protein expression levels were significantly higher in PC tissues compared to adjacent non‐tumour tissue. Furthermore, high HNRNPC expression was associated with poor patient prognosis. Using HNRNPC overexpression and siRNA interference, we demonstrated that HNRNPC overexpression promoted radiation resistance in PC cells, while HNRNPC knockdown increased radiosensitivity. However, silencing of RhoA expression was shown to attenuate radiation resistance caused by HNRNPC overexpression. Next, we identified RhoA as a downstream target of HNRNPC and showed that inhibition of the RhoA/ROCK2‐YAP/TAZ pathway led to a reduction in DNA damage repair and radiation resistance. Finally, using both in vitro assays and an in vivo subcutaneous tumour xenograft model, we demonstrated that RhoA inhibition can hinder the activity of cancer‐related fibroblasts and weaken PC radiation resistance. Our study describes a role for HNRNPC and the RhoA/ROCK2‐YAP/TAZ signalling pathways in mediating radiation resistance and provides a potential therapeutic target for improving the treatment of PC.
Rosacea, an infectious disease: why rosacea with papulopustules should be considered a demodicosis. A narrative review
Authors: Forton F.M.N.
Published: March 2022

Rosacea and demodicosis are common facial conditions in dermatology practice. While demodicosis is clearly the result of Demodex mite infestation, the pathogenicity of rosacea is still not sufficiently explained, so that it is defined by its symptoms, and not by its cause. It is usually considered as a disease of the immune system associated with neurogenic inflammation triggered by various factors (ultraviolet light, heat, spicy food, alcohol, stress and microorganisms). Its links with demodicosis remain controversial, although there is increasing evidence that Demodex mites may play a key role in the inflammatory process. Indeed, high Demodex densities are observed in nearly all cases of rosacea with papulopustules (PPR) and the papulopustules of rosacea can be effectively treated with topical acaricidal agents. Recent studies suggest that Demodex induces two opposite actions on host immunity: a defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favouring its own proliferation. Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T‐cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor, which may also explain the favourable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation. In this review, the evidence for and against a causal role of Demodex in rosacea is discussed, applying three systems traditionally used to attribute causality to a disease (modified Koch criteria, Hill criteria for causality and Rothman model). The findings suggest that PPR can reasonably be attributed to Demodex proliferation, which appears to be a necessary factor in the centre of a causal network in which multiple co‐factors interact and influence the occurrence and severity of inflammatory symptoms, from limited (pityriasis folliculorum) to more marked (PPR). PPR could, therefore, be considered as a chronic infection by Demodex mites with associated T‐cell exhaustion.
Out‐of‐pocket costs attributable to dementia: A longitudinal analysis
Authors: Oney Melissa , White Lindsay , Coe Norma B.
Published: March 2022

Background

Alzheimer's disease and related dementias (ADRD) affect 5.7 million Americans, and are expensive despite the lack of a cure or even treatments effective in managing the disease. The literature thus far has tended to focus on the costs to Medicare, even though one of the main characteristics of ADRD (the loss of independence and ability to care for oneself) incurs costs not covered by Medicare.

Methods

In this paper, we use survey data for 2002–2016 from the Health and Retirement Study to estimate the out‐of‐pocket costs of ADRD for the patient and their family through the first 8 years after the onset of symptoms, as defined by a standardized 27‐point scale of cognitive ability. A two‐part model developed by Basu and Manning (2010) allows us to separate the costs attributable to ADRD into two components, one driven by differences in longevity and one driven by differences in utilization.

Results

We identified a cohort of 3619 incident dementia cases, 38.9% were male, and 66.9% were non‐Hispanic White. Dementia onset was 77.7 years of age, on average. OOP costs attributable to dementia are $8751 over the first 8 years after the onset. These incremental costs are driven by nursing home expenditures, which are largely uninsured in the US. OOP spending is highest for whites and women.

Conclusion

The financial burden of ADRD is significant, and largely attributable to the lack of wide‐spread long‐term care insurance.
Molecular detection of Toxoplasma gondii and Neospora caninum in neotropical primates
Authors: Cândido Stéfhano Luís , Fonseca Maria Julia de Oliveira Rosa , Pacheco Richard de Campos , Campos Camila Gonçalves de , Morgado Thais Oliveira , Colodel Edson Moleta , Nakazato Luciano , Dutra Valéria
Published: March 2022

Background

Toxoplasma gondii and Neospora caninum infections in primates are potentially fatal and directly impact the conservation of these animals and public health.

Materials and methods

A total of 38 blood/clot samples collected from free‐living and captive neotropical primates undergoing clinical care or found dead by environmental authorities in the Mato Grosso State, Brazil, were analyzed by PCR for DNA detection of T. gondii and N. caninum. Furthermore, eight animals were submitted to immunohistochemistry for the detection of T. gondii.

Results

DNA of T. gondii and N. caninum was amplified in 11 (28.95%) 10 (26.32%) of samples analyzed, respectively. Coinfection was observed in three individuals. One animal returned a positive result in the immunohistochemistry for the detection of T. gondii.

Conclusion

These findings reflect a concern for the conservation of these animals, as the pathogen–host interaction is unpredictable and infections by these protozoa can lead to animal mortality, which has a substantial impact on endangered species.
Maternal thrombocytopenia precedes fetal death associated with COVID‐19
Authors: Sagara Akihito , Yamaguchi Munekage , Mikami Yoshiki , Motohara Takeshi , Ohba Takashi , Kondoh Eiji
Published: March 2022

Acute coagulopathy, specific placental pathology, and an increased risk of fetal death have been reported in pregnant women with COVID‐19; however, the association between coagulopathy and fetal death remains unknown. We report two pregnant women with COVID‐19 who showed acute coagulopathy prior to fetal death. Both pregnant women presented with thrombocytopenia after testing positive for SARS‐CoV‐2 (days 5 and 7). They had mild symptoms, but coagulopathy progressed, and their fetuses died on day 9 at 27 and 22 weeks of pregnancy. Their coagulability improved after delivery. Placental histology in both cases showed intervillous infiltration of histiocytes, necrosis of trophoblasts, and intervillous fibrin deposition, which were consistent with previously reported pathological findings related to SARS‐CoV‐2. In the management of pregnant women with COVID‐19, thrombocytopenia may be a predictive marker of fetal death following coagulopathy and placental inflammatory changes due to SARS‐CoV‐2 infection.
Determining the lower limit of detection required for HCV viral load assay for test of cure following direct‐acting antiviral‐based treatment regimens: Evidence from a global data set
Authors: Morgan Jake R. , Marsh Elizabeth , Savinkina Alexandra , Shilton Sonjelle , Shadaker Shaun , Tsertsvadze Tengiz , Kamkamidze George , Alkhazashvili Maia , Morgan Timothy , Belperio Pam , Backus Lisa , Doss Waheed , Esmat Gamal , Hassany Mohamed , Elsharkawy Aisha , Elakel Wafaa , Mehrez Mai , Foster Graham R. , Wose Kinge Constance , Chew Kara W. , Chasela Charles S. , Sanne Ian M. , Thanung Yin M. , Loarec Anne , Aslam Khawar , Balkan Suna , Easterbrook Philippa J. , Linas Benjamin P.
Published: March 2022

Achieving global elimination of hepatitis C virus requires a substantial scale‐up of testing. Point‐of‐care HCV viral load assays are available as an alternative to laboratory‐based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post‐treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical‐sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low‐level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170–276). Females and those with minimal fibrosis were more likely to experience low‐level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30–1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15–1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low‐level treatment failure.
Urinary cortisol metabolites are reduced in MDR1 mutant dogs in a pilot targeted GC‐MS urinary steroid hormone metabolome analysis
Authors: Gramer Irina , Karakus Emre , Hartmann Michaela F. , Wudy Stefan A. , Bauer Natali , Moritz Andreas , Aktürk Zekeriya , Geyer Joachim
Published: March 2022

P‐glycoprotein (P‐gp) is the gene product of the multidrug resistance gene (MDR1, syn. ABCB1) that normally restricts the transfer of cortisol across the blood–brain barrier. In the absence of P‐gp, cortisol access to the hypothalamus is increased and, by feedback inhibition, this finally leads to lower endogenous plasma cortisol levels in dogs with homozygous nt230(del4) MDR1 mutation (MDR1−/− mutant dogs). While a previous study only focused on plasma cortisol levels, the present study used urinary steroid hormone metabolites to analyze cortisol metabolism in MDR1−/− mutant dogs. Morning void urine was collected from 23 MDR1−/− mutant and 16 MDR1+/+ normal dogs and was subjected to targeted GC‐MS steroid hormone metabolome analysis. Seven cortisol metabolites, cortisol itself, and 13 other steroid metabolites were detected. In general, all cortisol metabolites were lower in the urine of the MDR1−/− mutant dogs, with allo‐tetrahydro‐cortisol and β‐cortol reaching the level of significance. In addition, 11‐keto‐pregnanetriol levels were significantly lower in the urine of the MDR1−/− mutant dogs, indicating that also the 17alpha‐OH‐progesterone‐derived metabolism was altered. In conclusion, the present study provides the first steroid hormone metabolome analysis in the urine of MDR1−/− mutant dogs. Significant differences in the steroid metabolome of MDR1−/− mutant dogs point to a significant role of P‐gp for cortisol metabolism and excretion and so indirectly also for hypothalamic–pituitary–adrenal axis regulation in dogs.
Linking perspectives: A role for poetry in philosophical inquiry
Authors: Simecek Karen
Published: March 2022

There is a long‐standing debate about whether poetry can make a substantive contribution to philosophy with compelling arguments to show that poetry and philosophy involve distinct modes of thought and aims, albeit with similar concerns. This paper argues that reading lyric poetry can play a substantive role in philosophy by helping the philosopher understand how to forge connections with the perspectives of others. The paper takes the view that poetry is not directly philosophical but can play an important role in developing the philosopher's awareness of how perspective shapes beliefs and thought processes. Following Robert Nozick, David Lewis, and Helen Beebee, it argues for the need to broaden our conception of the aims of philosophy beyond aiming for conclusive proof, at the least where philosophical inquiry is focused on questions of value. It then shows how poetry cultivates an intellectual virtue essential to philosophy aimed at uncovering equilibria and collective understanding.
Convection volume, β2‐microglobulin and α1‐microglobulin reduction ratios, and body composition in pre‐dilution online haemodiafiltration
Authors: Mizuiri Sonoo , Nishizawa Yoshiko , Doi Toshiki , Okubo Aiko , Shigemoto Kenichiro , Usui Koji , Arita Michiko , Naito Takayuki , Doi Shigehiro , Masaki Takao
Published: March 2022

Aim

The effect of convection volume (CV) in patients on pre‐dilution online haemodiafiltration (Pre‐OL‐HDF) was evaluated.

Methods

We conducted a retrospective, cross‐sectional study in 126 patients on Pre‐OL‐HDF. Dialysis conditions, laboratory data, and same day post‐dialysis body composition measurements using bioimpedance spectroscopy were assessed. Patients were divided into two groups according to their CV: ≥ median value and < median value. Linear regression analyses for reduction ratios (RRs) of β2‐microglobulin and α1‐microglobulin, and body composition, were conducted.

Results

Age, dialysis vintage, and CVs of the study patients were 64 ± 12 years, 81 (48–154) months, and 43.2 (38.5–55.9) L/session, respectively. The higher CV (≥ 43 L/session) group (n = 66) had significantly higher RRs of β2‐microglobulin and α1‐microglobulin, lean tissue index, body cell mass index, total body water (TBW), extracellular water (ECW), and intracellular water (ICW) compared with the lower CV (< 43 L/session) group (n = 60, p <  .01). Serum albumin and fat tissue index were not significantly different between the groups. CV/ECW, CV/TBW, and CV/ICW but not un‐adjusted CV, were significant determinants for β2‐microglobulin and α1‐microglobulin RRs (p <  .05). Lean tissue and body cell mass indexes, but not the fat tissue index, showed significant associations with CV, and RRs of β2‐microglobulin and α1‐microglobulin (p < kb.05).

Conclusions

Among patients on Pre‐OL‐HDF, higher values in the lean tissue index and body cell mass index were observed in those with higher CV versus lower CV, and CV adjusted to body water may be useful to prescribe individualized conditions for Pre‐OL‐HDF.
Laser microirradiation as a versatile system for probing protein recruitment and protein–protein interactions at DNA lesions in plants
Authors: Nešpor Dadejová Martina , Franek Michal , Dvořáčková Martina
Published: March 2022

Plant protoplasts are generated by treatment with digestion enzymes, producing plant cells devoid of the cell wall and competent for efficient polyethylene glycol mediated transformation. This way fluorescently tagged proteins can be introduced to the protoplasts creating an excellent system to probe the localization and function of uncharacterized plant proteins in vivo.

We implement the method of laser microirradiation to generate DNA lesions in Arabidopsis thaliana, which enables monitoring the recruitment and dynamics of the DNA repair factors as well as bimolecular fluorescence complementation assay to test transient, conditional interactions of proteins directly at sites of DNA damage.

We demonstrate that laser microirradiation in protoplasts yields a physiological cellular response to DNA lesions, based on proliferating cell nuclear antigen (PCNA) redistribution in the nucleus and show that factors involved in DNA repair, such as MRE11 or PCNA are recruited to induced DNA lesions.

This technique is relatively easy to adopt by other laboratories and extends the current toolkit of methods aimed to understand the details of DNA damage response in plants. The presented method is fast, flexible and facilitates work with different mutant backgrounds or even different species, extending the utility of the system.
Global and National Declines in Life Expectancy: An End‐of‐2021 Assessment
Authors: Heuveline Patrick
Published: March 2022

Timely, high‐quality mortality data have allowed for assessments of the impact of the novel coronavirus disease 2019 (COVID‐19) on life expectancies in upper‐middle‐ and high‐income countries. Extant data, though imperfect, suggest that the bulk of the pandemic‐induced mortality might have occurred elsewhere. This article reports on changes in life expectancies around the world as far as they can be estimated from the evidence available at the end of 2021. The global life expectancy appears to have declined by 0.92 years between 2019 and 2020 and by another 0.72 years between 2020 and 2021, but the decline seems to have ended during the last quarter of 2021. Uncertainty about its exact size aside, this represents the first decline in global life expectancy since 1950, the first year for which a global estimate is available from the United Nations. Annual declines in life expectancy (from a 12‐month period to the next) appear to have exceeded two years at some point before the end of 2021 in at least 50 countries. Since 1950, annual declines of that magnitude had only been observed on rare occasions, such as Cambodia in the 1970s, Rwanda in the 1990s, and possibly some sub‐Saharan African nations at the peak of the acquired immunodeficiency syndrome (AIDS) pandemic.
Persistence of parental‐reported asthma at early ages: A longitudinal twin study
Authors: Slob Elise Margaretha Adriana , Longo Cristina , Vijverberg Susanne J. H. , Beijsterveldt Toos C. E. M. van , Bartels Meike , Hottenga Jouke Jan , Pijnenburg Mariëlle W. , Koppelman Gerard H. , Maitland‐van der Zee Anke‐Hilse , Dolan Conor V. , Boomsma Dorret I.
Published: March 2022

Background

Currently, we cannot predict whether a pre‐school child with asthma‐like symptoms will have asthma at school age. Whether genetic information can help in this prediction depends on the role of genetic factors in persistence of pre‐school to school‐age asthma. We examined to what extent genetic and environmental factors contribute to persistence of asthma‐like symptoms at ages 3 to asthma at age 7 using a bivariate genetic model for longitudinal twin data.

Methods

We performed a cohort study in monozygotic and dizygotic twins from the Netherlands Twin Register (NTR, n = 21,541 twin pairs). Bivariate genetic models were fitted to longitudinal data on asthma‐like symptoms reported by parents at age 3 and 7 years to estimate the contribution of genetic and environmental factors.

Results

Bivariate genetic modeling showed a correlation on the liability scale between asthma‐like symptoms at age 3 and asthma at age 7 of 0.746 and the contribution of genetics was estimated to be 0.917. The genetic analyses indicated a substantial influence of genetic factors on asthma‐like symptoms at ages 3 and 7 (heritability 80% and 90%, respectively); hence, contribution of environmental factors was low. Persistence was explained by a high (rg = 0.807) genetic correlation.

Conclusion

Parental‐reported asthma‐like symptoms at age 3 and asthma at age 7 are highly heritably. The phenotype of asthma‐like symptoms at age 3 and 7 was highly correlated and mainly due to heritable factors, indicating high persistence of asthma development over ages 3 and 7.
A Partnership for the Ages
Authors: Dees Richard H.
Published: March 2022

Burke suggests that we should view society as a partnership between the past, the present, and the future. I defend this idea by outlining how we can understand the interests of the past and future people and the obligations that they have towards each other. I argue that we have forward‐looking obligations to leave the world a decent place and backward‐looking obligations to respect the legacy of the past. The latter obligation requires an understanding of the role that traditions and meta‐traditions should (and should not) play in tying together societies—especially national societies—over time.
Inventory control in production–inventory systems with random yield and rework: The unit‐tracking approach
Authors: Berling Peter , Sonntag Danja R.
Published: March 2022

This paper considers a single‐stage make‐to‐stock production–inventory system under random demand and random yield, where defective units are reworked. We examine how to set cost‐minimizing production/order quantities in such imperfect systems, which is challenging because a random yield implies an uncertain arrival time of outstanding units and the possibility of them crossing each other in the pipeline. To determine the order/production quantity in each period, we extend the unit‐tracking/decomposition approach, taking into account the possibility of order‐crossing, which is new to the literature and relevant to other planning problems. The extended unit‐tracking/decomposition approach allows us to determine the optimal base‐stock level and to formulate the exact and an approximate expression of the per‐period cost of a base‐stock policy. The same approach is also used to develop a state‐dependent ordering policy. The numerical study reveals that our state‐dependent policy can reduce inventory‐related costs compared to the base‐stock policy by up to 6% and compared to an existing approach from the literature by up to 4.5%. From a managerial perspective, the most interesting finding is that a high mean production yield does not necessarily lead to lower expected inventory‐related costs. This counterintuitive finding, which can be observed for the most commonly used yield model, is driven by an increased probability that all the units in a batch are either of good or unacceptable quality.
Biological control of plant diseases – What has been achieved and what is the direction?
Authors: Collinge David B. , Jensen Dan Funck , Rabiey Mojgan , Sarrocco Sabrina , Shaw Michael W. , Shaw Richard H.
Published: March 2022

The global sustainability agenda is increasing the demand for reduction in inputs into agricultural production while maintaining profitable yield of quality products. Plant diseases are a major constraint for both yield and product quality, but often tools for their control are ineffective or lacking. Biological control using antagonistic microorganisms has long been a subject of research resulting in a wide range of products that are now available and marketed in specific territories around the world. These preparations are often niche products with narrow uses. The research effort is intense both to develop new biological control agents (BCAs) and to obtain knowledge of the mechanisms underlying biological disease control. The prospects for biological control are promising. As a minimum, BCAs supplement other sustainable disease management practices such as disease resistance, and present opportunities for controlling diseases for which other approaches are ineffective or unavailable. We can realistically expect increasing use of BCAs to control crop diseases in ways that will benefit the environment. This review paper arose from a webinar held by the British Society for Plant Pathology as part of the International Year of Plant Heath (IYPH2020), at which many of the 300 participants posed or discussed interesting questions. This review is based on that input and the panel members at the webinar are all included as co‐authors in this review.
The Racialized Dimensions of Contemporary Immigration and Border Enforcement Policies and Practices
Authors: Martínez Daniel E.
Published: March 2022

Immigration policies in the United States have not been explicitly race‐based since the mid‐20th Century. Nevertheless, the effects of contemporary US immigration enforcement practices are highly racialized. The further development of a “race conscious” approach in public policy and administration will help expand our understanding of the racialized dimensions of these policies and practices. Specifically, I call attention to how current approaches to immigration control disproportionately negatively affect non‐White immigrants from the so‐called “Global South,” contribute to racialization processes, and perpetuate racial inequality in the United States. Examples include the ways that undocumented immigration status is leading to the emergence of a new “underclass” in the United States, the separation and dissolution of Latino families through mass deportation, and the systematic criminalization of non‐White undocumented immigrants from Mexico, Guatemala, Honduras, and El Salvador.
Fear changes traits and increases survival: a meta‐analysis evaluating the efficacy of antipredator training in captive‐rearing programs
Authors: Zhu Jennifer , Gosnell J. Stephen , Akallal Laila , Goltsman Micah
Published: March 2022

Captive rearing is commonly used to support efforts to restore extirpated or diminished wild populations. Many rearing programs include antipredator training in an effort to reduce post‐release mortality due to predation, but the value such training adds to restoration efforts is not fully understood. Analyses of antipredator training impacts often focus on changes in prey following training and not the actual effects when prey are exposed to predators. Studies also commonly assess prey traits instead of fitness. However, changes in prey following training may not translate to desired increase in fitness upon release for a self‐sustaining population. To consider these relationships, we identified studies that analyzed changes in organisms following both training and lethal exposure to predators. Notably, we identified only 12 studies that analyzed outcomes in both training and lethal exposure settings and found the majority of measurements focused on traits. Although meta‐analysis indicated that antipredator training changed prey traits and increased prey survival, relationships between changes in traits and fitness could not be assessed given the rarity of studies that included both outcomes. While these results support the general use of antipredator training, they also suggest that trait changes cannot be reliably used as proxies for fitness impacts. Future work should seek to more clearly measure impacts on fitness and determine when changes in traits can truly be used as a surrogate for training efficacy. These issues reflect recent concerns regarding research on non‐consumptive effects and highlight potential avenues for future collaborative research on fear.
Mapping and assessing the knowledge base of ecological restoration
Authors: Heger Tina , Jeschke Jonathan M. , Febria Catherine , Kollmann Johannes , Murphy Stephen , Rochefort Line , Shackelford Nancy , Temperton Vicky M. , Higgs Eric
Published: March 2022

Information on restoration science and practice is dispersed across large numbers of scientific papers, reports, books, and other resources, and there is a lack of synthetic approaches and of linkages between ecological theory and practice. With recent calls for scaling up ecological restoration, there is an urgent need for improving the effectiveness of restoration ecology by presenting existing knowledge in an organized and accessible form. Practitioners benefit from knowing which theories explain patterns and processes in a specific ecosystem, and scientists need an overview of empirical evidence supporting current theories. Strengthening links between restoration practice and science benefits both areas. Based on a new approach used for organizing and assessing hypotheses in invasion biology, we suggest the development of an interactive online platform that promotes the integration of restoration science and practice by (1) presenting an overview of restoration ecology; (2) mapping theoretical work relevant for ecological restoration; (3) displaying direct links to relevant publications; and (4) providing summaries of empirical evidence for ecological theories in specific settings. This online knowledge base should be developed in an open process, bringing together the restoration community with experts in semantic web and natural language processing, library scientists, web designers, and other specialists. The platform should become an evolving, searchable, openly accessible, and intuitively organized tool for future ecological restoration.
Hydrology shapes microbial communities and microbiome‐mediated growth of an Everglades tree island species
Authors: Almeida Brianna K. , Cline Eric , Sklar Fred , Afkhami Michelle E.
Published: March 2022

Plant‐associated microbiomes can improve plant fitness by ameliorating environmental stress, providing a promising avenue for improving outplantings during restoration. However, the effects of water management on these microbial communities and their cascading effects on primary producers are unresolved for many imperiled ecosystems. One such habitat, Everglades tree islands, has declined by 54% in some areas, releasing excess nutrients into surrounding wetlands and exacerbating nutrient pollution. We conducted a factorial experiment, manipulating the soil microbiome and hydrological regime experienced by a tree island native, Ficus aurea, to determine how microbiomes impact growth under two hydrological management plans. All plants were watered to simulate natural precipitation, but plants in the “unconstrained” management treatment were allowed to accumulate water above the soil surface, while the “constrained” treatment had a reduced stage to avoid soil submersion. We found significant effects of the microbiomes on overall plant performance and aboveground versus belowground investment; however, these effects depended on hydrological treatment. For instance, microbiomes increased investment in roots relative to aboveground tissues, but these effects were 142% stronger in the constrained compared to unconstrained water regime. Changes in hydrology also resulted in changes in the prokaryotic community composition, including a >20 log2fold increase in the relative abundance of Rhizobiaceae, and hydrology‐shifted microbial composition was linked to changes in plant performance. Our results suggest that differences in hydrological management can have important effects on microbial communities, including taxa often involved in nitrogen cycling, which can in turn impact plant performance.
Validation and Assessment of a Tool to Measure Psychosocial Readiness to Use Modern Contraceptives among Women in Tigray, Ethiopia
Authors: Anderson Elizabeth J. , Hinson Laura , Berhe Hailemariam , Berhane Kesete , Warholak Terri , Equar Awala , Hailu Desta , Abraha Atsbaha
Published: March 2022

Social norms, beliefs, and attitudes around modern contraception (MC) use can influence the decision to take up a method, but susceptibility to these factors varies between individuals. The effect of psychosocial readiness to use MC at the individual level is not established for women in Ethiopia. Data from 349 women were used for validity and reliability testing of a 12‐item MC psychosocial readiness scale. A rating‐scale Rasch model tested for unidimensionality, rating scale functioning, and construct and content validity. Multiple linear regression assessed the effect of respondent characteristics on MC psychosocial readiness scores. The psychometric properties of the univariate MC psychosocial readiness scale were satisfactory after the stepwise removal of two items. Prior MC use, socioeconomic status, geographic zone, and education were significantly associated with increased endorsement of MC psychosocial readiness. The 10‐item scale measures the extent of endorsement of MC psychosocial readiness for childbearing women in Tigray, Ethiopia. Further research should qualitatively explore the identified influence of education on MC psychosocial readiness.
Optimal subsampling for multiplicative regression with massive data
Authors: Wang Tianzhen , Zhang Haixiang
Published: March 2022

Faced with massive data, subsampling is a popular way to downsize the data volume for reducing computational burden. The key idea of subsampling is to perform statistical analysis on a representative subsample drawn from the full data. It provides a practical solution to extracting useful information from big data. In this article, we develop an efficient subsampling method for large‐scale multiplicative regression model, which can largely reduce the computational burden due to massive data. Under some regularity conditions, we establish consistency and asymptotic normality of the subsample‐based estimator, and derive the optimal subsampling probabilities according to the L‐optimality criterion. A two‐step algorithm is developed to approximate the optimal subsampling procedure. Meanwhile, the convergence rate and asymptotic normality of the two‐step subsample estimator are established. Numerical studies and two real data applications are carried out to evaluate the performance of our subsampling method.
HLA‐B*58:41, a variant of HLA‐B*58, detected in a Taiwanese individual
Authors: Yang Kuo‐Liang , Li Chi‐Cheng , Lin Py‐Yu
Published: March 2022

One nucleotide substitution in codon 9 of HLA‐B*58:01:01:01 results in a novel allele, HLA‐B*58:41.
Identification of the novel HLA‐DPB1*03:01:14 allele by next‐generation sequencing in a Chinese cord blood donor
Authors: Dong Lina , Zhao Shuoxian , Chen Nanying , Xu Jian , Zhu Faming
Published: March 2022

HLA‐DPB1*03:01:14 differs from HLA‐DPB1*03:01:01:01 by a single nucleotide substitution at position 390 C > A.
Evolution of pathological findings in surveillance biopsies of lung transplant recipients infected with SARS‐CoV‐2
Authors: Wein Alexander N. , Liu Jing , Lin Chieh‐Yu
Published: March 2022

Background

Previous reports of coronavirus disease 2019 (COVID‐19) following lung transplantation generally described a grim prognosis, but these were anecdotal case series of symptomatic patients. A systematic study of the outcomes and pathology of SARS‐CoV‐2 infection in a large cohort of lung transplant patients is lacking.

Methods

To determine the histopathologic evolution of COVID‐19 in lung transplant recipients, we identified all patients who underwent surveillance transbronchial biopsies at our institution, tested positive for SARS‐CoV‐2, and had multiple pathology specimens available for evaluation. Histology was reviewed and immunofluorescence for SARS‐CoV‐2 nucleocapsid protein was performed.

Results

Ten patients met inclusion criteria. Half (5/10) had incidental diagnosis on routine respiratory pathogen testing at the time of transbronchial biopsy. Six patients were hospitalized, with three requiring intensive care unit (ICU) admission. One patient died. Two specimens showed new onset International Society for Heart and Lung Transplantation (ISHLT) Grade A2 rejection at or following diagnosis. One patient developed bronchiolitis obliterans 111 days following diagnosis and 1 year post transplant. Two patients had organizing pneumonia at diagnosis and three patients showed evolving lung injury following diagnosis. The SARS‐CoV‐2 nucleocapsid protein was detected in a subset of samples at diagnosis and up to 111 days following diagnosis.

Conclusions

Overall, the pathology of SARS‐CoV‐2 infection in lung transplant patients is varied, ranging from no pathologic alterations to organizing pneumonia and lung injury. The pathology findings did not necessarily correlate with clinical acuity, as one patient admitted to the ICU had normal pathology. These findings may be generalizable to non‐transplant patients and require more follow‐up regarding long‐term outcomes.

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Paraneoplastic syndrome associated with gynaecological malignancy: a review of the evidence
Authors: Brown Adam , McKenna Sarah , Forbes Deborah , Harley Ian
Published: March 2022

Key content

Paraneoplastic syndrome (PNS) is a clinical manifestation of both benign and malignant tumours. Symptoms are not attributable to direct organ involvement of the cancer nor as a therapeutic adverse effect; instead, they are a result of hormones, cytokines or growth factors released by the tumour, or an immunological response.

Paraneoplastic syndromes can affect any body system, so can cause myriad potential symptoms. These clinical manifestations often pre‐date those of the underlying disease process.

The incidence of PNS attributable to gynaecological tumours is increasing, resulting in considerable morbidity in those affected.

There is an overall lack of awareness of PNS among clinicians; this, combined with wide‐ranging signs and symptoms, creates an opportunity for diagnostic difficulty and therapeutic delay.

Learning objectives

To raise awareness among clinicians to aid earlier diagnosis and treatment of paraneoplastic syndromes.
The management of haemoglobinopathies in pregnancy and childbirth
Authors: Jackson Lucy A , Hill Quentin A , Ciantar Etienne
Published: March 2022

Key Content

The haemoglobinopathies encompass a complex collection of red blood cell disorders that are responsible for considerable morbidity and mortality in women and their unborn children.

Sickle cell disease and the thalassaemias are the commonest haemoglobinopathies encountered in UK clinical practice.

A consistent standard of care will enable women with haemoglobinopathies to have a pregnancy that is as safe as possible, with good outcomes and minimal long‐term effects on their health and the health of their babies.

The most effective way to deliver a consistent standard of care for these women is via the multidisciplinary team (MDT). The MDT should include a haematologist, cardiologist, maternal medicine obstetrician, specialist midwife, reproductive medicine specialist and a nurse specialist.

The care of these women, within the MDT, should start with pre‐conception advice and continue through their antenatal care, intrapartum support and finally, provide postnatal considerations including contraception advice.

Learning Objectives

To understand the inheritance, incidence, detection and pathophysiology of the commonest haemoglobinopathies.

To appreciate the role of pre‐conception advice and prenatal diagnosis in the management of women with a haemoglobinopathy.

To appreciate the multidisciplinary team approach in managing women with these conditions.

Ethical Issues

Prenatal diagnostic techniques can be used to diagnose an affected pregnancy; however, diagnosis after conception means families must address the option of terminating the pregnancy. This requires expert counselling to minimise long‐term sequelae.

The definitive prenatal tests – chorionic villus sampling and amniocentesis – are both associated with a small risk of miscarriage.

Non‐invasive free fetal DNA (ffDNA) tests that will minimise the risk of testing to the developing fetus are being developed, but use of these tests will still require expert counselling both before and after a test is taken.
Diverse roles of MYB transcription factors in regulating secondary metabolite biosynthesis, shoot development, and stress responses in tea plants (Camellia sinensis)
Authors: Li Penghui , Xia Enhua , Fu Jiamin , Xu Yujie , Zhao Xuecheng , Tong Wei , Tang Qian , Tadege Million , Fernie Alisdair R. , Zhao Jian
Published: March 2022

Tea (Camellia sinensis) is concocted from tea plant shoot tips that produce catechins, caffeine, theanine, and terpenoids, which collectively determine the rich flavors and health benefits of the infusion. However, little is known about the integrated regulation of shoot tip development and characteristic secondary metabolite biosynthesis in tea plants. Here, we demonstrate that MYB transcription factors (TFs) play key and yet diverse roles in regulating leaf and stem development, secondary metabolite biosynthesis, and environmental stress responses in tea plants. By integrating transcriptomic and metabolic profiling data in different tissues at a series of developmental stages or under various stress conditions, alongside biochemical and genetic analyses, we predicted the MYB TFs involved in regulating shoot development (CsMYB2, 98, 107, and 221), epidermal cell initiation (CsMYB184, 41, 139, and 219), stomatal initiation (CsMYB113 and 153), and the biosynthesis of flavonoids (including catechins, anthocyanins, and flavonols; CsMYB8 and 99), caffeine (CsMYB85 and 86), theanine (CsMYB9 and 49), carotenoids (CsMYB110), mono‐/sesquiterpenoid volatiles (CsMYB68, 147, 148, and 193), lignin (CsMYB164 and 192), and indolic compounds (CsMYB139, 162, and 198), as well as the MYB TFs that are likely involved in hormone signaling‐mediated environmental stress and defense responses. We characterized the functions of some key MYBs in regulating flavonoid and carotenoid biosynthesis for tea quality and flavor. This study provides a cross‐family analysis of MYBs in tea alongside new insights into the coordinated regulation of tea plant shoot development and secondary metabolism, paving the way towards understanding of tea quality trait formation and genetic improvement of quality tea plants.
Novel insights into the dissemination route of Japanese apricot (Prunus mume Sieb. et Zucc.) based on genomics
Authors: Huang Xiao , Ni Zhaojun , Shi Ting , Tao Ryutaro , Yang Qin , Luo Changguo , Li Yongping , Li Hantao , Gao Haidong , Zhou Xiangyang , Xu Lei , Gao Zhihong
Published: March 2022

Japanese apricot (Prunus mume) is an attractive fruit tree originating from China, and its cultivation history dates back 7000 years. In this study, we investigated the genetic diversity, population structure, and genetic relationship of Japanese apricots in different regions of China and Japan. The analyses of the genetic variation between wild and cultivated populations improved our understanding of the general mechanisms of domestication and improvement. A total of 146 accessions of Japanese apricot from different geographic locations were sequenced. The genetic diversity of wild and domesticated accessions (3.60 × 10−3 and 3.51 × 10−3, respectively) from China was high, and the effect of artificial selection pressure on domesticated accessions was small; however, the genetic diversity of artificially bred accessions decreased significantly (2.68 × 10−3) compared to domesticated accessions, which had an obvious improvement bottleneck effect. The chloroplast genome results showed that 41 haplotypes were detected, and Japanese apricots from the Yunnan region had the most haplotypes and the highest genetic diversity. The results revealed the dissemination route of Japanese apricot, not only along the Yangtze River basin system (from southwest China to Hunan, Jiangxi, and Anhui, and finally to the Jiangsu, Zhejiang, and Shanghai areas). Additionally, we discovered a second route for Japanese apricot dispersion, which was mostly in the Pearl River basin system, from southwest China to Libo of Guizhou and then to the Guangdong, Fujian, and Taiwan areas. This also showed that Japanese‐bred accessions originated from Zhejiang, China. In addition, selective sweep analysis showed that most of the high‐impact single nucleotide polymorphisms were identified in genes related to glucose metabolism, aromatic compound metabolism, flowering time, dormancy, and resistance to abiotic stress during the domestication and improvement of Japanese apricot.
Ageing and exercise‐induced motor unit remodelling
Authors: Jones Eleanor J. , Chiou Shin‐Yi , Atherton Philip J. , Phillips Bethan E. , Piasecki Mathew
Published: March 2022

A motor unit (MU) comprises the neuron cell body, its corresponding axon and each of the muscle fibres it innervates. Many studies highlight age‐related reductions in the number of MUs, yet the ability of a MU to undergo remodelling and to expand to rescue denervated muscle fibres is also a defining feature of MU plasticity. Remodelling of MUs involves two coordinated processes: (i) axonal sprouting and new branching growth from adjacent surviving neurons, and (ii) the formation of key structures around the neuromuscular junction to resume muscle–nerve communication. These processes rely on neurotrophins and coordinated signalling in muscle–nerve interactions. To date, several neurotrophins have attracted focus in animal models, including brain‐derived neurotrophic factor and insulin‐like growth factors I and II. Exercise in older age has demonstrated benefits in multiple physiological systems including skeletal muscle, yet evidence suggests this may also extend to peripheral MU remodelling. There is, however, a lack of research in humans due to methodological limitations which are easily surmountable in animal models. To improve mechanistic insight of the effects of exercise on MU remodelling with advancing age, future research should focus on combining methodological approaches to explore thein vivophysiological function of the MU alongside alterations of the localised molecular environment.

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Physics Modeling for Conceptual Designs of Proposed Experiments in the Zero Energy Deuterium-2 Critical Facility for Testing Small Modular Reactor-Type Fuels
Authors: Watts D. G. , Adams F. P. , Masala E. , Blomeley L. , Bromley B. P.
Published: March 2022

To enable the deployment of small modular reactors (SMRs) in Canada, Canadian Nuclear Laboratories (CNL) is interested in the applicability of zero energy deuterium-2 (ZED-2) experiments for validation of Monte Carlo reactor physics codes and models for SMR reactor fuels. This applicability is investigated here by considering potential ZED-2 experiments for testing fuel assemblies (FAs) for two different SMR technologies: the pressurized-water reactor (PWR), and the fluoride-salt-cooled high-temperature reactor (FHR). Each proposed set of mixed-lattice substitution experiments uses driver fuel channels containing CANDU flexible low enriched uranium/recovered uranium (CANFLEX-LEU/RU) fuel bundles. Simulation results indicate that a number of critical core configurations are possible, and should provide suitable reactor physics measurement data that can be used for physics design verification, and also for benchmarking and validation of computational reactor physics codes used in the design, operations, and safety analysis of SMRs based on PWR or FHR technologies.