bluuebunny/crossref_metadata_2025 huggingface dataset:
The Moral and Gender Implications of Measures Used to Modulate the Mobility of People With Dementia Living in Residential Care Environments: A Scoping Review
Authors: Sturge Jodi , Janus Sarah , Zuidema Sytse , Frederiks Brenda , Schweda Mark , Landeweer Elleke
Published: June 2023

Background and Objectives

Policies and measures often restrict the mobility of people with dementia living in residential care environments to protect them from harm. However, such measures can violate human rights and affect the quality of life. This review aims to summarize the literature on what is known about measures used to modulate the life-space mobility of residents with dementia living in a residential care environment. Furthermore, moral and sex and gender considerations were explored.

Research Design and Methods

A scoping review framework was referenced to summarize the literature. A total of 5 databases were searched: PubMed, Embase, CINAHL, SCOPUS, and Web of Science. The studies for eligibility using the Rayyan screening tool.

Results

A total of 30 articles met the inclusion criteria. A narrative description of the findings of the articles is presented across 3 themes: (1) measures and strategies used to modulate the life-space mobility; (2) moral aspects; and (3) sex and gender considerations.

Discussion and Implications

Various measures are used to modulate the life-space mobility of people with dementia living in residential care facilities. Research exploring the sex and gender differences of people with dementia is lacking. With a focus on human rights and quality of life, measures used to restrict or support mobility must support the diverse needs, capacity, and dignity of people with dementia. Noting the capacity and diversity of people with dementia will require society and public space to adopt strategies that promote safety and mobility to support the quality of life of people with dementia.
Older Adults’ Perspectives of Independence Through Time: Results of a Longitudinal Interview Study
Authors: Taylor Emily , Goodwin Victoria A , Ball Susan , Clegg Andrew , Brown Lesley , Frost Julia
Published: June 2023

Background and Objectives

Understanding how older people experience independence has implications for person-centered care. Existing understanding of older people’s experience of independence, generated through methods that provide a “snapshot” view of a person’s independence at a given time point, provides little insight into the process of maintaining independence through time. The aim of this study was to explore older participants’ perceptions to understand the processes and resources that were most important for maintaining independence.

Research Design and Methods

Two semistructured interviews were conducted longitudinally to explore the perspectives of 12 community-dwelling, older people, aged 76–85 years. A social constructivist approach, using dramaturgical and descriptive codes, facilitated the interpretation of the data. Sixteen analytical questions guided the exploration of participants’ perceptions of independence through time.

Results

Older people suggested that objective representations underestimated, and omitted, important aspects of their independence through time. Some participants perceived “snapshot” judgments of their independence as insensitive to their individual values and context. Change over time required some participants to adapt their methods for maintaining independence. The stability of participants’ sense of independence was value dependent and informed by the purpose a participant ascribed to maintaining independence.

Discussion and Implications

This study augments the understanding of independence as a complex and multifaceted construct. The findings challenge the congruence of common interpretations of independence with older people’s views, showing areas of commonality, and discrepancy. Exploration of independence in terms of form and function provides an important understanding of how function takes precedence to form in determining the maintenance of independence through time.
No apology necessary? How narratives impact redress for colonialism in Namibia and India
Authors: Miller Manjari Chatterjee
Published: June 2023

Why do victim states not ask for redress from perpetrator states? Focusing on former extractive colonies, the vast majority of which, despite having suffered brutal colonial rule, have not asked for redress—apologies, reparations or restitution—from their former colonizers, this article argues that the content of historical narratives in the victim state matters for interstate redress. When meta and sub-narratives in victim states do not conform with each other, framing and consensus mobilization on interstate redress is stymied. To show this, I code interstate redress in the Correlates of War data set of colony/colonizer states, and then use primary sources—interviews and school textbooks—to examine two victim states: Namibia, a ‘less likely’ case which has sought interstate redress, and India, a ‘more likely’ case which has not. Academic and policy conversations on interstate redress have thus far largely focused on perpetrator states. This not only denies victim states, most of which are developing countries, agency but skews our understanding of the phenomenon of seeking justice across international borders.
Blue paradigms: understanding the intellectual revolution in global ocean politics
Authors: Bueger Christian , Mallin Felix
Published: June 2023

The oceans have received extraordinary international attention in global policy and research. New insecurities and uncertainties, ranging from intensifying interstate disputes to persistent piracy and overfishing as well as to pollution, deoxygenation and climate change imply that the oceans are increasingly seen as being in crisis. This revolution in thinking about and addressing the oceans is driven by new ideas of why the oceans need political attention and care. In this article we demonstrate how four key new ‘blue paradigms’—maritime security, blue economy, ocean health and blue justice—have evolved and turned the oceans into a new area of priority. Each of these paradigms drives global ocean politics in different directions, which implies risks of fragmentation and conflicts. We work out the key differences between paradigms, investigating their underlying problematization, priorities and communities of practices involved. This provides a new map for navigating the complexity of global ocean politics useful for policy-makers and scholars. Thinking through paradigms also establishes a new analytical framework that allows for identifying conflicting priorities, tensions between ocean communities of practice, and ideas of how these can be managed. We conclude with a call for creative thinking of how synergies between the blue paradigms can be achieved in strategy, planning and research.
Systemic immunometabolism and responses to vaccines: insights from T and B cell perspectives
Authors: Nettelfield Sam , Yu Di , Cañete Pablo F
Published: June 2023

Vaccination stands as the cornerstone in the battle against infectious diseases, and its efficacy hinges on several host-related factors like genetics, age, and metabolic status. Vulnerable populations, such as malnourished individuals, the obese, and the elderly, commonly exhibit diminished vaccine responses and efficacy. While the specific factors contributing to this impairment may vary, these individuals typically display a degree of metabolic dysregulation, thereby underscoring its potential significance as a fundamental determinant of suboptimal vaccine responses. The emerging field of immunometabolism aims to unravel the intricate interplay between immune regulation and metabolic pathways, and recent research has revealed diverse metabolic signatures linked to various vaccine responses and outcomes. In this review, we summarize the major metabolic pathways utilized by B and T cells during vaccine responses, their complex and varied metabolic requirements, and the impact of micronutrients and metabolic hormones on vaccine outcomes. Furthermore, we examine how systemic metabolism influences vaccine responses and the evidence suggesting that metabolic dysregulation in vulnerable populations can lead to impaired vaccine responses. Lastly, we reflect on the challenge of proving causality with respect to the contribution of metabolic dysregulation to poor vaccine outcomes, and highlight the need for a systems biology approach that combines multimodal profiling and mathematical modelling to reveal the underlying mechanisms of such complex interactions.
Unethical Issues in Twenty-First Century International Development and Global Health Policy
Authors: Hanson-DeFusco Jessi , Malik Sakil , Assamoi Rosine , Chiromba Antony , Davis Decontee , Hounnouvi Fidèle Marc , Irfan Furqan B , Faley Patrick , Matangwa Djo Dieudonne , Muzenda Tambu , Nakiryowa Hanifa , Obondoh Andiwo , Parveen S , Pinales Ana Julia , Zimunya Rugare
Published: June 2023

Billions in development aid is provided annually by international donors in the Majority World, much of which funds health equity. Yet, common neocolonial practices persist in development that compromise what is done in the name of well-intentioned policymaking and programming. Based on a qualitative analysis of fifteen case studies presented at a 2022 conference, this research examines trends involving unethical partnerships, policies, and practices in contemporary global health. The analysis identifies major modern-day issues of harmful policy and programming in international aid. Core issues include inequitable partnerships between and representation of international stakeholders and national actors, abuse of staff and unequal treatment, and new forms of microaggressive practices by Minority World entities on low-/middle-income nations (LMICs), made vulnerable by severe poverty and instability. When present, these issues often exacerbate institutionalized discrimination, hostile work environments, ethnocentrism, and poor sustainability in development. These unbalanced systems perpetuate a negative development culture and can place those willing to speak out at risk. At a time when the world faces increased threats including global warming and new health crises, development and global health policy and practice must evolve through inclusive dialogue and collaborative effort.
Integrating human-centered design in public health data dashboards: lessons from the development of a data dashboard of sexually transmitted infections in New York State
Authors: Ansari Bahareh , Martin Erika G
Published: June 2023

Objective

The increased availability of public data and accessible visualization technologies enhanced the popularity of public health data dashboards and broadened their audience from professionals to the general public. However, many dashboards have not achieved their full potential due to design complexities that are not optimized to users’ needs.

Material and Methods

We used a 4-step human-centered design approach to develop a data dashboard of sexually transmitted infections for the New York State Department of Health: (1) stakeholder requirements gathering, (2) an expert review of existing data dashboards, (3) a user evaluation of existing data dashboards, and (4) an usability evaluation of the prototype dashboard with an embedded experiment about visualizing missing race and ethnicity data.

Results

Step 1 uncovered data limitations and software requirements that informed the platform choice and measures included. Step 2 yielded a checklist of general principles for dashboard design. Step 3 revealed user preferences that influenced the chart types and interactive features. Step 4 uncovered usability problems resulting in features such as prompts, data notes, and displaying imputed values for missing race and ethnicity data.

Discussion

Our final design was accepted by program stakeholders. Our modifications to traditional human-centered design methodologies to minimize stakeholders’ time burden and collect data virtually enabled project success despite barriers to meeting participants in-person and limited public health agency staff capacity during the COVID-19 pandemic.

Conclusion

Our human-centered design approach and the final data dashboard architecture could serve as a template for designing public health data dashboards elsewhere.
Purification methods to reduce interference by dextran sodium sulfate with quantification of gene expression in intestinal tissue samples from a piglet model of colitis
Authors: Sommer Kaitlyn M , Lee Youngsoo , Donovan Sharon M , Dilger Ryan N
Published: June 2023

Dextran sodium sulfate (DSS) is commonly used to induce intestinal (i.e., colonic) inflammation in a variety of animal models. However, DSS is known to cause interference when using quantitative-real time polymerase chain reaction (qRT-PCR) methods, thereby invalidating accurate and precise measurement of tissue gene expression. Therefore, the goal of this study was to determine whether different mRNA purification methods would reduce DSS-interference. Colonic tissue samples were collected at postnatal days (PND) 27 or 28 from pigs that had not been administered DSS (Control), and two independent groups of pigs that received 1.25 g of DSS/kg of BW/d (DSS-1 and DSS-2) from PND 14 to 18. Tissue samples collected were subsequently stratified into three purification methods (i.e., 9 total treatment × method combinations), including: 1) no purification, 2) purification with lithium chloride (LiCl), or 3) purification using spin column filtration. All data were analyzed using a one-way ANOVA in the Mixed procedure of SAS. The average RNA concentrations across all treatments were between 1,300 and 1,800 μg/μL for all three in vivo groups. Although there were statistical differences among purification methods, the 260/280 and 260/230 ratios fell between acceptable limits of 2.0 to 2.1 and 2.0 to 2.2, respectively, for all treatment groups. This confirms the RNA quality was adequate and not influenced by purification method in addition to suggesting the absence of phenol, salts, and carbohydrate contamination. For pigs in the Control group that did not receive DSS, qRT-PCR Ct values of four cytokines were achieved, though these values were not altered by purification method. For pigs that had undergone DSS dosing, those tissues subjected to either no purification or purification using LiCl did not generate applicable Ct values. However, when tissues derive from DSS-treated pigs underwent spin column purification, half of the samples from DSS-1 and DSS-2 groups generated appropriate Ct estimates. Therefore, spin column purification appeared to be more effective than LiCl purification, but no method was 100% effective, so caution should be exercised when interpreting gene expression results from studies where animals are exposed to DSS-induced colitis.
Jujuboside A ameliorates cognitive deficiency in delirium through promoting hippocampal E4BP4 in mice
Authors: Du Jianhao , Zhang Fugui , Chen Min , Xiao Yifei , Zhang Li , Dong Linlin , Dong Dong , Wu Baojian
Published: June 2023

Objective

Delirium (acute brain syndrome) is a common and serious neuropsychiatric disorder characterized by an acute decline in cognitive function. However, there is no effective treatment clinically. Here we investigated the potential effect of jujuboside A (JuA, a natural triterpenoid saponin) on cognitive impairment in delirium.

Methods

Delirium models of mice were established by injecting lipopolysaccharide (LPS) plus midazolam and implementing a jet lag protocol. Novel object recognition test and Y maze test were used to evaluate the effects of JuA on delirium-associated cognitive impairment. The mRNA and protein levels of relevant clock factors and inflammatory factors were measured by qPCR and Western blotting. Hippocampal Iba1+ intensity was determined by immunofluorescence staining.

Key findings

JuA ameliorated delirium (particularly delirium-associated cognitive impairment) in mice, which was proved by the behavioural tests, including a preference for new objects, an increase of spontaneous alternation and improvement of locomotor activity. Furthermore, JuA inhibited the expression of ERK1/2, p-p65, TNFα and IL-1β in hippocampus, and repressed microglial activation in delirious mice. This was attributed to the increased expression of E4BP4 (a negative regulator of ERK1/2 cascade and microglial activation). Moreover, loss of E4bp4 in mice abrogated the effects of JuA on delirium as well as on ERK1/2 cascade and microglial activation in the hippocampus of delirious mice. Additionally, JuA treatment increased the expression of E4BP4 and decreased the expression of p-p65, TNFα and IL-1β in LPS-stimulated BV2 cells, supporting a protective effect of JuA on delirium.

Conclusions

JuA protects against delirium-associated cognitive impairment through promoting hippocampal E4BP4 in mice. Our findings are of great significance to the drug development of JuA against delirium and related disorders.
The promising application of hydrogel microneedles in medical application
Authors: Wu Yanping , Tang Ziyan , Ma Shan , Du Lina
Published: June 2023

Objectives

Hydrogel microneedles are emerging, and promising microneedles mainly composed of swelling polymers. This review is intended to summarize the preparation materials, formation mechanisms, applications and existing problems of hydrogel microneedles.

Methods

We collected the literature on the materials, preparation and application of hydrogel microneedles in recent years, and summarized their mechanism and application in drugs delivery.

Key findings

Hydrogel microneedles have higher safety and capabilities of controlled drug release, and have been mainly used in tumour and diabetes treatment, as well as clinical monitoring. In recent years, hydrogel microneedles have shown great potential in drug delivery, and have played the role of whitening, anti-inflammatory and promoting healing.

Conclusions

As an emerging drug delivery idea, hydrogel microneedles for drug delivery has gradually become a research hotspot. This review will provide a systematic vision for the favourable development of hydrogel microneedles and their promising application in medicine, especially drug delivery.
Is a giant incisional hernia a contraindication for laparoscopic cholecystectomy?
Authors: Boyer Nicolas , Koliakos Nikolaos , Pau Luca , Poras Mathilde , Maréchal Marie-Therese , Farinella Eleonora
Published: June 2023

Laparoscopic cholecystectomy (LC) is one of the most commonly performed surgical procedures worldwide. A previous abdominal operation is not considered a significant risk factor for conversion to open cholecystectomy. We describe the case of an 80-year-old woman with a surgical history of a giant uncomplicated incisional midline hernia presenting at our department with choledocholithiasis and acute cholangitis. After an ERCP with extraction of common bile duct stones, a LC was planned. The first trocar was inserted in the right midclavicular line, using an open technique and a careful inspection of the abdominal cavity and the hernia sac content. An uncomplicated cholecystectomy was performed and the postoperative course was uneventful.
‘Chest gossypiboma after spinal surgery, not so easy to forget’
Authors: Endara Santiago A , Dávalos Gerardo A , Zamora E Elizabeth , Redrobán Ligia M , Molina Gabriel A
Published: June 2023

During any surgical procedure, complications may arise, some of which are fortuitous, whereas others, unfortunately, occur because of errors of the surgical team. Fortunately, most are minor and do not affect the patient’s recovery, but others can cause severe morbidity and even mortality. A retained cotton or gauze surgical sponge inadvertently left in the body during an operation is known as a gossypiboma. This dreadful oversight is a marked complication that can cause serious postoperative complications, a severe economic burden on the healthcare system, and many medicolegal implications. We report the case of a 30-year-old male, who suffered a spinal fracture which was repaired through an anterior fixation approach 12 years ago in a local state hospital without complications. Suddenly, he presented with chest pain and cough, and sought medical attention. An 8 × 5 × 8 cm low-density heterogeneous mass was discovered on his chest; after successful surgery, a gossypiboma formed by several gauzes without radiopaque markers was discovered.
Idiopathic pneumoperitoneum in a single case: an unusual entity
Authors: Sodade Oluwafolaranmi E , Austin Cindy L , Draper Brian B
Published: June 2023

Idiopathic pneumoperitoneum (IP) cases are rare and presents with varying symptoms, which makes propositions of standard treatments, clinically impracticable. There are limited IP therapies in the literature, necessitating a need, to continually highlight unique cases for the purpose of clinical education and training. This case describes an IP and management of a 34-year-old male who recently underwent a laparoscopic cholecystectomy. Patient presented to the emergency room with recurrent gastrointestinal (GI) symptoms. Despite two negative exploratory laparotomies without confirmatory evidence of GI perforations, the GI symptoms persisted, making it an unusual case. The surgeons elected to a multispecialty approach, detailing patient-specific symptoms, and corresponding treatments of the case. Based on the successful outcome of this patient, detailed knowledge of medical history, repeated physical assessments and patient-specific and comprehensive approach was shown to reduce unnecessary exploratory laparotomy, improved clinical outcomes and decrease in complications.
New diagnosis of conversion disorder following anterior lumbar interbody fusion: a case report
Authors: Mitchell Brendan P , Bianco Jake M , Kim Faith M G , Whitaker M Camden
Published: June 2023

Neurologic deficit after lumbar spine surgery is a rare and serious complication that must be promptly diagnosed and treated to avoid long-term neurologic disability. Anterior lumbar interbody fusion (ALIF) is an effective technique for the treatment of recurrent disc herniation and lumbar disc degeneration. This case report describes a 20-year-old female with L5-S1 recurrent disc herniation and lumbar degeneration. She underwent an L5-S1 ALIF complicated by post-operative lower left extremity paralysis. Revision surgery with downsizing of the ALIF cage was performed with normal neuromonitoring throughout the procedure. The patient displayed persistent post-operative neurologic deficits despite no evidence of central or foraminal compression. Patient was later diagnosed with conversion disorder by neurology during her hospitalization. This case report presents the initial diagnosis of conversion disorder after a routine ALIF procedure, which led to surgical re-exploration and prolonged inpatient hospital stay. Psychiatric diagnoses must be considered when neurologic deficits are present with no apparent organic cause.
A rare case of benign pneumatosis intestinalis in Sjogren’s syndrome
Authors: Tsang Chi F , Davis Brandon , Chan Daniel L , Yeo David
Published: June 2023

Pneumatosis intestinalis (PI)—the presence of intramural bowel gas—is an uncommon radiological finding, the severity of which depends on the underlying pathological process, ranging from benign disease to life-threatening ischaemia and intra-abdominal sepsis. PI has been described in systemic sclerosis and mixed connective tissue disease; however, few cases have been reported in Sjogren’s syndrome (SjS). The exact pathogenesis of PI in systemic connective tissue disorders is not fully understood and likely multifactorial. We have described a unique case of PI without evidence of peritonitis in a stable patient with long-standing SjS managed non-operatively. An awareness of such benign PI, particularly amongst patients with systemic connective tissue disease, is crucial for diagnostic accuracy and safe patient care, particularly in preventing unnecessary surgical intervention.
Evaluation of the antifungal and antibiofilm activity of postbiotics derived fromLactobacillus spp. onPenicillium expansoum in vitroand in food model
Authors: Khani Nader , Soleimani Roya Abedi , Milani Payam Gonbari , Rad Aziz Homayouni
Published: June 2023

Food degradation made by mycotoxigenic molds represents a significant challenge too food security. Postbiotics are associated with soluble compounds liberated by living bacterial cells or their construction release after lysis, and these metabolites offer the host biological action and specific physiological benefits. In this work, the postbiotics from tree strains of Lactobacillus spp. (Limosilactobacillus reuteri ATCC 367, Lacticaseibacillus casei431and Levilactobacillus brevisATCC) were lyophilized, filtered, and tested to evaluate the antimicrobial and anti-biofilm activity in vitro and milk against P. expansoum. Also, to assess the antioxidant efficacy and the free radical scavenging possibility of the postbiotic, DPPH, and ABTS + methods were used. Antimicrobial activity and biofilm removal activity of postbiotics depended on the Lactobacillus strains used. The minimum inhibitory concentration (MIC) of the prepared postbiotic was determined to be 70ug/ml. The lowest minimum effective concentration (MEC) of postbiotics were significantly differed, in the food matrix, and a low MEC index (100 mg/ml) was detected for postbiotic of L. brevis. Postbiotics derived from L. brevis showed the highest antimicrobial activity compared to L. casei and L. reuteri. The postbiotic extracted from Lactobacillus strain may have functional properties (potential antimicrobial and anti-biofilm) in vitro and food models.
The impact of smartphone app–based interventions on adolescents’ dietary intake: a systematic review and evaluation of equity factor reporting in intervention studies
Authors: Schaafsma Holly N , Jantzi Heather A , Seabrook Jamie A , McEachern Louise W , Burke Shauna M , Irwin Jennifer D , Gilliland Jason A
Published: June 2023

Context

Adolescence is a critical stage for improving nutrition. The popularity of smartphones makes them an ideal platform for administering interventions to adolescents. A systematic review has yet to assess the impact of smartphone app–based interventions exclusively on adolescents’ dietary intake. Furthermore, despite the impact of equity factors on dietary intake and the claim for mobile health of increased accessibility, there is minimal research on the reporting of equity factors in the evaluation of smartphone app–based nutrition-intervention research.

Objectives

This systematic review examines the effectiveness of smartphone app–based interventions on adolescents’ dietary intake and the frequency with which equity factors and statistical analyses specific to equity factors are reported in these intervention studies.

Data Sources

Databases (ie, Scopus, CINAHL, EMBASE, MEDLINE, PsycINFO, ERIC, and Cochrane Central Register for Randomized Control Trials) were searched for studies published from January 2008 to October 2022. Smartphone app–based intervention studies that were nutrition focused, evaluated at least 1 dietary intake variable, and included participants with a mean age between 10 and 19 years were included. All geographic locations were included.

Data Extraction and Analysis

Study characteristics, intervention results, and reported equity factors were extracted. Because of the heterogeneity of dietary outcomes, findings were reported as a narrative synthesis.

Conclusion

In total, 3087 studies were retrieved, 14 of which met the inclusion criteria. Eleven studies reported a statistically significant improvement in at least 1 dietary outcome because of the intervention. Reporting of at least 1 equity factor across articles’ Introduction, Methods, Results, and Discussion sections was minimal (n = 5), and statistical analyses specific to equity factors were rare, occurring in only 4 of the 14 included studies. Future interventions should include a measurement of intervention adherence and report the impact of equity factors on the effectiveness and applicability of interventions for equity-deserving groups.
Does Color Matter: Review Article of Skin Color, Power, and Politics in America
Authors: Masuoka Natalie
Published: June 2023

This is a review article of Skin Color, Power, and Politics in America by Mara Cecilia Ostfeld and Nicole Yadon, published by Russell Sage Foundation in 2022. The core premise of the book argues that skin color is another important dimension of the construction of race in America and that it can also provide insight into how individuals experience the world. This article provides an overview of the book and offers reflections on its interventions into the fields of race, ethnicity and politics, public opinion, and political psychology.
Enabling Population Biology Studies of Stemphylium vesicarium from Onion with Microsatellites
Authors: Heck Daniel W. , Hay Frank , Pethybridge Sarah J.
Published: June 2023

Stemphylium leaf blight (SLB), caused by the fungus Stemphylium vesicarium, is dominant within the foliar disease complex affecting onion production in New York (NY). The disease causes premature defoliation and significant reductions in bulb weight and quality. Foliar diseases of onion are usually managed by an intensive fungicide program, but SLB management is complicated by resistance to multiple single-site modes of action. The design of integrated disease management strategies is limited by incomplete knowledge surrounding the dominant sources of S. vesicarium inoculum. To facilitate genomic-based studies of S. vesicarium populations, nine microsatellite markers were developed. The markers were multiplexed into two PCR assays containing four and five fluorescently labeled microsatellite markers. Initial testing of the S. vesicarium isolates found the markers were highly polymorphic and reproducible with an average of 8.2 alleles per locus. The markers were used to characterize 54 S. vesicarium isolates from major NY onion production regions in 2016 (n = 27) and 2018 (n = 27). Fifty-two multilocus genotypes (MLGs) were identified between these populations. Genotypic and allelic diversities were high in both the 2016 and 2018 populations. A greater degree of genetic variation was observed within populations than between years. No distinct pattern of MLGs according to population was identified and some MLGs were closely related between 2016 and 2018. The lack of evidence for linkage among loci also was strongly suggestive of clonal populations with only minor differences between the two populations. These microsatellite markers will be a foundational resource for the testing of hypotheses surrounding the population biology of S. vesicarium and therefore informing disease management.
Evaluation of Grafting for Management of Southern Blight in Processing Tomatoes in California
Authors: Solares Natalie , Nuñez Joe J. , Putman Alexander I.
Published: June 2023

Options for managing southern blight of processing tomato (caused by Athelia rolfsii) in California are limited. The objectives of this study were to: (i) evaluate grafting with the resistant rootstock Maxifort for southern blight management in processing tomato and (ii) evaluate increasing the height of the graft union to further reduce incidence of southern blight in grafted plants. We evaluated two cultivars (Heinz 5608 or Heinz 8504) and a grafting factor with three levels (grafted to Maxifort rootstock with standard scion height, grafted to Maxifort rootstock at a tall height, and nongrafted) in a field study with natural inoculum or in inoculated greenhouse experiments. Southern blight severity was low in both greenhouse experiments in 2018 and 2019, and no consistent trends were observed. In field experiments in 2018 and 2019, mean incidence in nongrafted plots was 6.2 to 17.0 times higher when compared with either the standard or tall grafted treatments. Southern blight was numerically lower in tall grafted plots compared with standard, but the magnitude was small and not statistically significant. Based on our studies, grafting can reduce losses of processing tomato in California to southern blight, but increasing the height of the graft union does not offer a tangible benefit.
PLAAT1 deficiency alleviates high‐fat diet‐induced hepatic lipid accumulation in mice
Authors: Rahman S. M. Khaledur , Sasaki Sumire , Uyama Toru , Hussain Zahir , Sikder Mohammad Mamun , Saiga Hiroyuki , Ohmura‐Hoshino Mari , Ohta Ken‐ichi , Miki Yoshimi , Hoshino Katsuaki , Ueno Masaki , Murakami Makoto , Ueda Natsuo
Published: June 2023

The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid‐metabolizing enzymes exhibiting phospholipase A1/A2 and acyltransferase activities. Plaat3‐deficient (Plaat3−/−) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high‐fat diet (HFD) feeding, while Plaat1−/− mice have not been analyzed. In the present study, we generated Plaat1−/− mice and investigated the effects of PLAAT1 deficiency on HFD‐induced obesity, hepatic lipid accumulation, and insulin resistance. After HFD treatment, PLAAT1 deficiency caused a lower body weight gain compared to wild‐type mice. Plaat1−/− mice also showed reduced liver weight with negligible hepatic lipid accumulation. In accordance with these findings, PLAAT1 deficiency improved HFD‐induced hepatic dysfunction and lipid metabolism disorders. Lipidomics analysis in the liver revealed that in Plaat1−/− mice, the levels of various glycerophospholipids tended to increase, while all classes of lysophospholipids examined tended to decrease, suggesting that PLAAT1 functions as phospholipase A1/A2 in the liver. Interestingly, the HFD treatment of wild‐type mice significantly increased the mRNA level of PLAAT1 in the liver. Furthermore, the deficiency did not appear to elevate the risk of insulin resistance in contrast to PLAAT3 deficiency. These results suggested that the suppression of PLAAT1 improves HFD‐induced overweight and concomitant hepatic lipid accumulation.
Proximity‐dependent biotin identification links cholesterol catabolism with branched‐chain amino acid degradation in Mycobacterium smegmatis
Authors: Veyron‐Churlet Romain , Lecher Sophie , Lacoste Anne‐Sophie , Saliou Jean‐Michel , Locht Camille
Published: June 2023

Cholesterol is a crucial component in Mycobacterium tuberculosis virulence as it is required for phagocytosis of mycobacteria by macrophages. In addition, the tubercle bacilli can grow using cholesterol as the sole carbon source. Thus, cholesterol catabolism represents a valuable target for the development of new antitubercular drugs. However, the molecular partners of cholesterol catabolism remain elusive in mycobacteria. Here, we focused on HsaC and HsaD, enzymes involved in two consecutive steps of cholesterol ring degradation and identified putative partners, using a BirA‐based proximity‐dependent biotin identification (BioID) approach in Mycobacterium smegmatis. In rich medium, the fusion protein BirA‐HsaD was able to fish the endogenous cognate HsaC, thus validating this approach to study protein–protein interactions and to infer metabolic channeling of cholesterol ring degradation. In chemically defined medium, both HsaC and HsaD interacted with four proteins, BkdA, BkdB, BkdC, and MSMEG_1634. BkdA, BkdB, and BkdC are enzymes that participate in the degradation of branched‐chain amino acids. As cholesterol and branched‐chain amino acid catabolism both generate propionyl‐CoA, which is a toxic metabolite for mycobacteria, this interconnection suggests a compartmentalization to avoid dissemination of propionyl‐CoA into the mycobacterial cytosol. Moreover, the BioID approach allowed us to decipher the interactome of MSMEG_1634 and MSMEG_6518, two proteins of unknown function, which are proximal to the enzymes involved in cholesterol and branched‐chain amino acid catabolism. In conclusion, BioID is a powerful tool to characterize protein–protein interactions and to decipher the interconnections between different metabolic pathways, thereby facilitating the identification of new mycobacterial targets.
Transmorphic phage‐guided systemic delivery of TNFα gene for the treatment of human pediatric medulloblastoma
Authors: Al‐Bahrani Mariam , Asavarut Paladd , Waramit Sajee , Suwan Keittisak , Hajitou Amin
Published: June 2023

Medulloblastoma is the most common childhood brain tumor with an unfavorable prognosis and limited options of harmful treatments that are associated with devastating long‐term side effects. Therefore, the development of safe, noninvasive, and effective therapeutic approaches is required to save the quality of life of young medulloblastoma survivors. We postulated that therapeutic targeting is a solution. Thus, we used a recently designed tumor‐targeted bacteriophage (phage)‐derived particle, named transmorphic phage/AAV, TPA, to deliver a transgene expressing the tumor necrosis factor‐alpha (TNFα) for targeted systemic therapy of medulloblastoma. This vector was engineered to display the double‐cyclic RGD4C ligand to selectively target tumors after intravenous administration. Furthermore, the lack of native phage tropism in mammalian cells warrants safe and selective systemic delivery to the tumor microenvironment. In vitro RGD4C.TPA.TNFα treatment of human medulloblastoma cells generated efficient and selective TNFα expression, subsequently triggering cell death. Combination with the chemotherapeutic drug cisplatin used clinically against medulloblastoma resulted in augmented effect through the enhancement of TNFα gene expression. Systemic administration of RGD4C.TPA.TNFα to mice‐bearing subcutaneous medulloblastoma xenografts resulted in selective tumor homing of these particles and consequently, targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature. Thus, our RGD4C.TPA.TNFα particle provides selective and efficient systemic delivery of TNFα to medulloblastoma, yielding a potential TNFα anti‐medulloblastoma therapy while sparing healthy tissues from the systemic toxicity of this cytokine.
Cryo-EM studies of the fourE. coliparalogs establish ABCF proteins as master plumbers of the peptidyl-transferase center of the ribosome
Authors: Singh Shikha , Gentry Riley C. , Fu Ziao , Bailey Nevette A. , Altomare Clara G. , Wong Kam-Ho , Neky Matthew J. , Wang Chi , Ray Korak Kumar , Chi Ying-Chih , Zhang Zhening , Grassucci Robert A. , Frank Joachim , Boël Grégory , Gonzalez Ruben L. , Hunt John F.
Published: June 2023

The genomes of most mesophilic organisms encode multipleATP-BindingCassetteF(ABCF) proteins. EttA, one of fourE. coliparalogs, regulates synthesis of the first peptide bond on the ribosome dependent on ATP/ADP ratio, whileAntibioticResistance factors (AREs), paralogs in other organisms, both regulate and directly mediate resistance to ribosome-targeted antibiotics. However, the physiological functions remain unclear for most paralogs, and the mechanism-of-action has yet to be rigorously established for any paralog. We herein present single particle cryogenic electron microscopy structures of ribosome complexes of all fourE. coliABCF paralogs (EttA, Uup, YbiT, and YheS), which, together with previously determined ARE structures, show that ABCFs control the binding geometry of the tRNA in the peptidyl-tRNA-binding (P) site on the ribosome. They modulate the position of its acceptor stem relative to the peptidyl transferase center (PTC) in a manner that can either promote (EttA and Uup) or disrupt (YbiT, YheS, and the AREs) proper catalytic geometry. The YbiT/70S reconstructions include a conformation with no density for ribosomal protein bL33, and structural analyses support the exchange of this sub-stoichiometric ribosomal protein being functionally related to conformational changes in YbiT controlled by sequence variations in the strongly non-canonical Signature Sequence in its first ABC domain. Our studies establish general structural/enzymological principles by which the ATPase activity of ABCF proteins controls translation elongation coupled to modulation of conformation and stereochemistry in the catalytic core of the ribosome.
Disruption of maternal ACKR3 has profound effects on embryos and offspring
Authors: Fukuoka Ayumi , Wilson Gillian J. , Pitmon Elise , Foley Lily Koumbas , Johnsson Hanna , Pingen Marieke , Graham Gerard J.
Published: June 2023

ACKR3, scavenges and degrades the stem cell recruiting chemokine CXCL12 which is essential for proper embryonic, and in particular hematopoietic, development. Here we demonstrate strong expression of ACKR3 on trophoblasts. Using a pharmacological blocker we demonstrate that ACKR3 is essential for preventing movement of CXCL12 from the mother to the embryo with elevated plasma CXCL12 levels being detected in embryos from ACKR3-blocker treated mothers. Mice born to mothers treated with the blocker are lighter and shorter than those born to vehicle-treated mothers and, in addition, display profound anaemia associated with a markedly reduced bone marrow hematopoietic stem cell population. Importantly, whilst the hematopoietic abnormalities are corrected as mice age, our studies reveal a postnatal window during which offspring of ACKR3 blocker treated mice are unable to mount effective inflammatory responses to inflammatory/infectious stimuli. Overall, these data demonstrate that ACKR3 is essential for preventing CXCL12 transfer from mother to embryo and for ensuring properly regulated CXCL12 control over the development of the hematopoietic system.
OverlookedCandida glabratapetites are echinocandin tolerant, induce host inflammatory responses, and display poorin vivofitness
Authors: Arastehfar Amir , Daneshnia Farnaz , Hovhannisyan Hrant , Fuentes Diego , Cabrera Nathaly , Quintin Christopher , Ilkit Macit , Ünal Nevzat , Hilmioğlu-Polat Suleyha , Jabeen Kauser , Zaka Sadaf , Desai Jigar V. , Lass-Flörl Cornelia , Shor Erika , Gabaldon Toni , Perlin David S.
Published: June 2023

Small colony variants (SCVs) are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly,Candida glabrata– a major intracellular fungal pathogen – produces small and slow-growing respiratory-deficient colonies, termed “petite.” Despite reports of clinical petiteC.glabratastrains, our understanding of petite behavior in the host remains obscure. Moreover, controversies exist regarding in-host petite fitness and its clinical relevance. Herein, we employed whole-genome sequencing (WGS), dual-RNAseq, and extensiveex vivoandin vivostudies to fill this knowledge gap. WGS identified multiple petite-specific mutations in nuclear and mitochondrially-encoded genes. Consistent with dual-RNAseq data, petiteC.glabratacells did not replicate inside host macrophages and were outcompeted by their non-petite parents in macrophages and in gut colonization and systemic infection mouse models. The intracellular petites showed hallmarks of drug tolerance and were relatively insensitive to the fungicidal activity of echinocandin drugs. Petite-infected macrophages exhibited a pro-inflammatory and type I IFN-skewed transcriptional program. Interrogation of internationalC.glabratablood isolates (n=1000) showed that petite prevalence varies by country, albeit at an overall low prevalence (0–3.5%). Collectively, our study sheds new light on the genetic basis, drug susceptibility, clinical prevalence, and host-pathogen responses of a clinically overlooked phenotype in a major fungal pathogen.

Importance

Candida glabratais a major fungal pathogen, which is able to lose mitochondria and form small and slow-growing colonies, called “petite”. This attenuated growth rate has created controversies and questioned the clinical importance of petiteness. Herein, we have employed multiple omicstechnologies and in vivo mouse models to critically assess the clinical importance of petite phenotype. Our WGS identifies multiple genes potentially underpinning petite phenotype. Interestingly, petiteC. glabratacells engulfed by macrophages are dormant and therefore are not killed by the frontline antifungal drugs. Interestingly, macrophages infected with petite cells mount distinct transcriptomic responses. Consistent with our ex-vivo observations, mitochondrial-proficient parental strains outcompete petites during systemic and gut colonization. Retrospective examination ofC. glabrataisolates identified petite prevalence a rare entity, can significantly vary from country to country. Collectively, our study overcomes the existing controversies and provides novel insights regarding the clinical relevance of petiteC. glabrataisolates.
CapTrap-Seq: A platform-agnostic and quantitative approach for high-fidelity full-length RNA transcript sequencing
Authors: Carbonell-Sala Silvia , Lagarde Julien , Nishiyori Hiromi , Palumbo Emilio , Arnan Carme , Takahashi Hazuki , Carninci Piero , Uszczynska-Ratajczak Barbara , Guigó Roderic
Published: June 2023

Long-read RNA sequencing is essential to produce accurate and exhaustive annotation of eukaryotic genomes. Despite advancements in throughput and accuracy, achieving reliable end-to-end identification of RNA transcripts remains a challenge for long-read sequencing methods. To address this limitation, we developed CapTrap-seq, a cDNA library preparation method, which combines the Cap-trapping strategy with oligo(dT) priming to detect 5’capped, full-length transcripts, together with the data processing pipeline LyRic. We benchmarked CapTrap-seq and other popular RNA-seq library preparation protocols in a number of human tissues using both ONT and PacBio sequencing. To assess the accuracy of the transcript models produced, we introduced a capping strategy for synthetic RNA spike-in sequences that mimics the natural 5’cap formation in RNA spike-in molecules. We found that the vast majority (up to 90%) of transcript models that LyRic derives from CapTrap-seq reads are full-length. This makes it possible to produce highly accurate annotations with minimal human intervention.
GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS
Authors: Voigt Andrew P. , Mullin Nathaniel K. , Navratil Emma M. , Flamme-Wiese Miles J. , Lin Li-Chun , Scheetz Todd E. , Han Ian C. , Stone Edwin M. , Tucker Budd A. , Mullins Robert F.
Published: June 2023

Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process. In this study, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We identified genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes. Within the area of neovascularization, endothelial cells were predicted to increase expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we also investigated spatial gene expression patterns within the macular neural retina and between the macular and peripheral choroid. We recapitulated previously described regional-specific gene expression patterns across both tissues. Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.