bluuebunny/crossref_metadata_2025 huggingface dataset:
The History of Digital Ethics
Authors: Müller Vincent C.
Published: January 2023

Digital ethics, also known as computer ethics or information ethics, is now a lively field that draws a lot of attention. But what were the developments that led to its existence and present state? What are the traditions, concerns, and technological and social developments that guided digital ethics? How did ethical issues change with the digitalization of human life? How did the traditional discipline of philosophy respond and how was ‘applied ethics’ influenced by these developments? This chapter proposes to view the history of digital ethics in three phases: pre-digital modernity (before the invention of digital technology), digital modernity (with digital technology but analogue lives), and digital post-modernity (with digital technology and digital lives). For each phase, the developments in digital ethics are explained with the background of the technological and social conditions. Finally, a brief outlook is provided.
Shade represses photosynthetic genes by disrupting the DNA binding of GOLDEN2-LIKE1
Authors: Kim Namuk , Jeong Jinkil , Kim Jeongheon , Oh Jeonghwa , Choi Giltsu
Published: January 2023

PHYTOCHROME-INTERACTING FACTORs (PIFs) repress photosynthetic genes partly by upregulating REPRESSOR OF PHOTOSYNTHETIC GENES 1 (RPGE1) and RPGE2. However, it is unknown how RPGEs inhibit gene expression at the molecular level. Here, we show that Arabidopsis (Arabidopsis thaliana) RPGE overexpression lines display extensive similarities to the golden2-like 1 (glk1)/glk2 double mutant at the phenotypic and transcriptomic levels, prompting us to hypothesize that there is a close molecular relationship between RPGEs and chloroplast development-regulating GLK transcription factors. Indeed, we found that RPGE1 disrupts the homodimerization of GLK1 by interacting with its dimerization domain and debilitates the DNA-binding activity of GLK1. The interaction was not restricted to the Arabidopsis RPGE1-GLK1 pair, but rather extended to RPGE-GLK homolog pairs across species, providing a molecular basis for the pale green leaves of Arabidopsis transgenic lines expressing a rice (Oryza sativa) RPGE homolog. Our discovery of RPGE-GLK regulatory pairs suggests that any condition leading to an increase in RPGE levels would decrease the expression levels of GLK target genes. Consistently, we found that shade, which upregulates the RPGE mRNA by stabilizing PIFs, represses the expression of photosynthetic genes partly by inhibiting the DNA-binding activity of GLK1. Taken together, these results indicate that RPGE-GLK regulatory pairs regulate photosynthetic gene expression downstream of PIFs.
Activity-dependent nocturnal decrease in leaf respiration
Authors: Bruhn Dan
Published: January 2023

Nocturnal decrease in leaf respiratory CO2-release measured at constant temperature within a plant species is correlated with the level of respiratory activity at onset of the dark period.
Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition
Authors: Shankar Kartik , Ali Sumera A , Ruebel Meghan L , Jessani Saleem , Borengasser Sarah J , Gilley Stephanie P , Jambal Puujee , Yazza Deaunabah N , Weaver Nicholas , Kemp Jennifer F , Westcott Jamie L , Hendricks Audrey E , Saleem Sarah , Goldenberg Robert L , Hambidge K Michael , Krebs Nancy F
Published: January 2023

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta, Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and Z-scores of birth length and head circumference. Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins, and mTORC1 signaling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively, the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.
Populism as Dog-Whistle Politics: Anti-Elite Discourse and Sentiments Toward Minority Groups
Authors: Bonikowski Bart , Zhang Yueran
Published: January 2023

Past research has devoted more attention to the consequences of populism for party politics and democratic governance than to its effects on public attitudes—and particularly, how populist claims interact with nationalism to exacerbate exclusionary beliefs among the public. Using online survey experiments, we examine whether exposure to populism increases out-group antipathy among Democrats and Republicans. In Study 1, we randomly assign respondents to three conditions featuring vignettes based on political speeches: a morally neutral argument, a populist critique of political elites and a morally framed anti-immigration appeal. The results demonstrate that the populist treatment generates lower feeling-thermometer ratings of minority groups than the control condition, but only among Republicans and Trump supporters. Study 2 uses a similar design to evaluate the link between left-wing economic populism and economic nationalism: the populist condition features a critique of economic elites, the nationalist condition blames China for the offshoring of US jobs and the outcome variable measures respondents’ sentiments toward China. Economic nationalism generates increased anti-China sentiment among moderate and conservative Democrats but economic populism does not. Together, these findings suggest that the effects of populism on nationalist antipathies observed in Study 1 are driven by the discursive bundling of anti-elite talk with ethno-nationalism on the political right, which stands in contrast to the decoupling of economic populism from economic nationalism on the left. The former has effectively turned populism into a form of dog-whistle politics among Republicans, and Trump supporters in particular.
Biological Disease Control by Beneficial (Micro)Organisms: Selected Breakthroughs in the Past 50 Years
Authors: Sarrocco Sabrina
Published: January 2023

Biological control of plant disease by beneficial (micro)organisms is one of the main tools available to preserve plant health within the wider context of One Health and in line with the goals of the Agenda 2030 for Sustainable Development. The commercial development of biocontrol agents, together with a new perspective on the resident microbial community, all supported by innovative “omics” technologies, continues to gain in prominence in plant pathology, addressing the need to feed the increasing world population and to assure safe and secure access to food. The present review considers selected advances within the last 50 years, highlighting those that can be considered as breakthroughs for the biological control research field. Selected examples of successful biocontrol agents and strategies are reported, including the history of the progress in researching Trichoderma isolates as commercial biocontrol agents, the exploitation of mycoviruses to confer hypovirulence to plant pathogenic fungi, the role of microbial communities in the suppressiveness of soils, and evolving approaches including the establishment of synthetic microbial communities.
Clinical Faculty Perceptions of Online Learning in Health Professions Education
Authors: Roberts Amy Lynn , Rizzolo Denise
Published: January 2023

Introduction

The purpose of this study was to investigate clinical faculty perceptions of online learning in health professions education.

Methods

Clinical faculty members from various health professions programs in New York were surveyed to determine whether there was a relationship between clinical faculty members' attitudes toward online learning competencies and their ability to teach online. Additionally, this study explored what type of impact years of teaching experience and online training had on clinical faculty perceptions of online learning.

Results

The study received 60 responses from clinical faculty, most of whom were teaching on Long Island, New York. Although the findings were not significant for most variables, a t-test demonstrated a significant statistical difference between online training and faculty perceptions of online learning. When clinical faculty completed online training, they had a more positive attitude toward online learning. The study also found that clinical faculty members' attitudes toward technology in online learning positively influenced their ability to troubleshoot technical issues in online environments. Years of online teaching experience did not affect how clinical faculty perceived online learning; however, clinical faculty with 1-5 years and 6-10 years of teaching experience rated their attitudes and abilities the lowest out of all the groups.

Discussion

While there appears to be a correlation between faculty perceptions of online learning and online training, more research is needed to objectively determine which specific trainings would be most advantageous.
Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts
Authors: Embleton Nicholas David , Jennifer Moltu Sissel , Lapillonne Alexandre , van den Akker Chris H.P. , Carnielli Virgilio , Fusch Christoph , Gerasimidis Konstantinos , van Goudoever Johannes B. , Haiden Nadja , Iacobelli Silvia , Johnson Mark J. , Meyer Sascha , Mihatsch Walter , de Pipaon Miguel Saenz , Rigo Jacques , Zachariassen Gitte , Bronsky Jiri , Indrio Flavia , Köglmeier Jutta , de Koning Barbara , Norsa Lorenzo , Verduci Elvira , Domellöf Magnus
Published: January 2023

Objectives:

To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g.

Methods:

The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached.

Results:

In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier.

Conclusions:

We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants
Postvaccination Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine and Its Predictors in Pediatric Inflammatory Bowel Disease
Authors: Bronsky Jiri , Copova Ivana , Durilova Marianna , Kazeka Denis , Kubat Michal , Lerchova Tereza , Vlckova Eva , Mitrova Katarina , Rataj Michal , Klocperk Adam , Sediva Anna , Hradsky Ondrej
Published: January 2023

Objectives:

We prospectively compared the postvaccination immunity to messenger ribonucleic acid BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine of our pediatric patients over 12 years old with inflammatory bowel disease (IBD) to that of healthy controls and looked for predictors of its robustness.

Methods:

Anti-receptor binding domain, anti-spike S2, and anti-nucleocapsid immunoglobin-G (IgG) and immunoglobin-A levels were measured in 139 pediatric patients with IBD [65 fully vaccinated (2 doses), median age 16.3, interquartile range (IQR) 15.2–17.8 years, median time from vaccination (IQR) 61.0 (42.0–80.0) days] and 1744 controls (46, 37–57 years) using microblot array.

Results:

All IBD and control patients developed positive anti-receptor binding domain IgG antibodies at comparable titers. The proportion of observations with positive anti-spike S2 IgG was higher in patients with IBD than in controls [63% vs 21%, odds ratio 2.99 (1.51–5.90)], as was its titer [median (IQR) 485 (92–922) vs 79 [33–180] IU/mL]. Anti-receptor binding domain and anti-spike S2 IgG levels were associated with IBD status. We found an association between anti-spike S2 IgG levels and time since vaccination (β −4.85, 95% CI −7.14 to 2.71, P = 0.0001), history of SARS-CoV-2 polymerase chain reaction positivity (206.76, 95% CI 39.93–374.05, P = 0.0213), and anti-tumor necrosis factor treatment (−239.68, 95% CI −396.44–83.55, P = 0.0047). Forty-three percent of patients reported vaccination side effects (mostly mild). Forty-six percent of observations with positive anti-nucleocapsid IgG had a history of SARS-CoV-2 infection.

Conclusions:

Patients with IBD produced higher levels of postvaccination anti-spike S2 antibodies than controls. Previous SARS-CoV-2 infection is associated with higher production of postvaccination antibodies and anti-tumor necrosis factor treatment with lower production.
Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis
Authors: Nasr Alexander , Hornung Lindsey , Thompson Tyler , Lin Tom K. , Vitale David S. , Nathan Jaimie D. , Varni James W. , Abu-El-Haija Maisam
Published: January 2023

Objectives:

This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents.

Methods:

Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls.

Results:

Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains.

Conclusions:

Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.
Characterizing the Pain Experience of Children With Acute Gastroenteritis Based on Identified Pathogens
Authors: Ma Keon , Ali Samina , Xie Jianling , Maki Claudia , Lee Bonita , Chui Linda , Pang Xiao-Li , Zhuo Ran , Parsons Brendon , Vanderkooi Otto , Poonai Naveen , MacDonald Shannon E. , Tarr Phillip , Freedman Stephen B. ,   on behalf of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) and Pediatric Emergency Research Canada (PERC)
Published: January 2023

Objectives:

Pain is common with acute gastroenteritis (AGE) yet little is known about the severity associated with specific enteropathogens. We sought to explore the correlation of pain severity with specific enteropathogens in children with AGE.

Methods:

Participants were prospectively recruited by the Alberta Provincial Pediatric EnTeric Infection TEam at 2 pediatric emergency departments (EDs) (December 2014–August 2018). Pain was measured (by child and/or caregiver) using the 11-point Verbal Numerical Rating Scale.

Results:

We recruited 2686 participants; 46.8% (n = 1256) females, with median age 20.1 months (interquartile range 10.3, 45.3). The mean highest pain scores were 5.5 [standard deviation (SD) 3.0] and 4.2 (SD 2.9) in the 24 hours preceding the ED visit, and in the ED, respectively. Prior to ED visit, the mean highest pain scores with bacterial detection were 6.6 (SD 2.5), compared to 5.5 (SD 2.9) for single virus and 5.5 (SD 3.1) for negative stool tests. In the ED, the mean highest pain scores with bacterial detection were 5.5 (SD 2.7), compared to 4.1 (SD 2.9) for single virus and 4.2 (SD 3.0) for negative stool tests. Using multivariable modeling, factors associated with greater pain severity prior to ED visit included older age, fever, illness duration, number of diarrheal or vomiting episodes in the preceding 24 hours, and respiratory symptoms, but not enteropathogen type.

Conclusion:

Children with AGE experience significant pain, particularly when the episode is associated with the presence of a bacterial enteric pathogen. However, older age and fever appear to influence children’s pain experiences more than etiologic pathogens.
What You Need to Know About Sacroiliac Dysfunction
Authors: Riczo Deborah B.
Published: January 2023

Low back pain is the leading cause of disability worldwide, and sacroiliac dysfunction is estimated to occur in 15%–30% of those with nonspecific low back pain. Nurses are in the unique position to support and provide education to patients who may be experiencing sacroiliac dysfunction or possibly apply this knowledge to themselves, as low back pain is a significant problem experienced by nurses. A patient's clinical presentation, including pain patterns and characteristics, functional limitations, common etiologies and musculoskeletal system involvement, current diagnostic tools, and realm of treatments, are discussed along with their respective efficacy. Distinction is made between specific diagnosis and treatment of joint involvement and that of sacroiliac regional pain, as well as other factors that play a role in diagnosis and treatment for the reader's consideration.
Orthopaedic Nurse Navigator Involvement in Preoperative Optimization for Total Joint Arthroplasty
Authors: Dlott Chloe C. , Miguez Sofia , Wilkins Sarah G. , Khunte Akshay , Johnson Charla B. , Kurek Donna , Wiznia Daniel H.
Published: January 2023

Patients seeking total joint arthroplasty frequently undergo preoperative optimization with the assistance of nurse navigators to facilitate interactions between patients, consulting services, and the orthopaedic surgical team. Given the enormous impact nurse navigator programs have on reducing postoperative complications, our aim is to characterize the involvement of nurse navigators in preoperative optimization programs across the country. We conducted a survey of nurse navigators identified through the National Association of Orthopaedic Nurses to assess the involvement of nurse navigators in the preoperative optimization process. Sixty-seven percent of responding nurse navigators were involved in preoperative optimization, including components such as heart disease (53%) and poorly controlled diabetes (52%). Orthopaedic nurse navigators are commonly involved in preoperative optimization programs for total joint arthroplasty but most of these involve gated yes/no checklists with limited established referral care pathways. Only some of the programs include standardized referrals for specific medical comorbidities.
2020 Charles F. Prentice Lecture: I Can See Clearly Now
Authors: Zadnik Karla
Published: January 2023

The Charles F. Prentice Medal, which was first given the year I was born, is the highest research honor bestowed by the American Academy of Optometry. I received the Prentice Medal in 2020 and gave my presentation at the 2020 American Academy of Optometry meeting, which was entirely virtual. As the first female optometrist to receive the Prentice Medal, I am honored to be given the opportunity to provide this summary of my presentation.

Myopia treatment choices to slow the progression of juvenile-onset myopia, especially in the first year of treatment, range from spectacles to contact lenses to pharmaceuticals. The value of the work described here that aims to predict the onset of myopia in children based on measurements that could be made by the optometrist is about to become more relevant than ever. What if the age-specific cutpoints could be used to use a low-risk treatment that would actually prevent the development of myopia altogether?
Relationship between Diurnal Variation in Intraocular Pressure and Central Corneal Power
Authors: Biswas Sayantan , Biswas Partha
Published: January 2023

SIGNIFICANCE

Relationship between intraocular pressure (IOP) change and central corneal curvature is complicated by measurement techniques and corneal biomechanical parameters. Findings from this study indicate that it is worthwhile to observe the association between diurnal change in IOP and corneal power.

PURPOSE

This study aimed to investigate the relationship between the diurnal change in IOP and central corneal power among eyes with and without myopia.

METHODS

Sixty healthy eyes of 24 emmetropes and 36 myopes were recruited for this cross-sectional study. Both anterior and posterior central corneal powers of the steep (Ks), flat (Kf), mean meridian (Km), best-fit spheres, and central corneal thickness were recorded followed by the IOP (Goldmann-correlated IOP [IOPg] and corneal-compensated IOP) and corneal biomechanics (corneal hysteresis and corneal resistance factor). Measurements were obtained every 3 hours from 9.30 am to 6.30 pm. Linear-mixed model was used to determine the relationship between the change in IOP and the associated change in corneal measurements (adjusted for age, sex, refractive error, central corneal thickness, and biomechanics) among the myopic and nonmyopic eyes.

RESULTS

Group mean, amplitude of change, and the diurnal change in IOPg were (mean ± standard deviation) 15.14 ± 2.50, 3.33 ± 1.44, and 1.81 ± 1.25 mmHg, respectively. Overall, an IOP increase was associated with a decrease in the adjusted anterior corneal powers. Myopic eyes were associated with a decrease of 0.04 D (95% confidence interval [CI], 0.07 to 0.01 D; P = .02) in Ks and 0.03 D (95% CI, 0.06 to 0.001 D; P = .047) in Kf per mmHg increase in IOP, whereas for emmetropes, per mmHg increase in IOP only flattened the Kf by 0.03 D (95% CI, 0.06 to 0.004 D; P = .02).

CONCLUSIONS

Change in anterior corneal power was inversely related to the change in IOPg, with myopic and nonmyopic eyes reporting a significant but differential impact of IOP. Clinicians must keep in mind the impact of large IOP fluctuation on the anterior corneal power.
Analysis of Ear Nose Throat Consultations Requested From the Pediatric Emergency Service in a Tertiary Hospital
Authors: Uğur Cüneyt , Yüksel Fatih
Published: January 2023

Objective

The aim of this study is to examine the reasons and the methods of approach to the patients for the ear nose and throat (ENT) consultations requested from the patients who applied to the pediatric emergency department.

Methods

The files of 351 patients who applied to the pediatric emergency outpatient clinic and were asked for consultation from the ENT clinic were reviewed retrospectively. Demographic data, complaints on admission, diagnostic examinations, diagnoses, treatment methods, and hospitalizations were recorded.

Results

Of the patients included in the study, 190 (54.1%) were female and 161 (45.9%) were male. The median age of the patients was 4.0 years (3.0–8.0 years). The most common diagnoses after ENT examination are; 120 patients (34.2%) had foreign body (FB) in the nose, 58 patients (16.5%) had FB in the ear, 16 patients (4.6%) had FB in the throat, 16 patients (4.6%) had epistaxis, and 15 patients (4.3%) had Bell's palsy. According to age group, it was determined that FB in the nose and ear was more common in the 0- to 5- and 6- to 11-year age group, and Bell's palsy, FB in the ear and epistaxis were more common in the 12- to 17-year age group. A normal examination was also an important finding in 83 of the patients (23.6%).

Conclusions

Foreign bodies are the most common reason for admission to the emergency services in children, and it is frequently seen between 0 and 5 years of age. Informing and raising awareness of parents on this topic will reduce both unwanted complications and ENT consultations along with admission to pediatric emergency services.
A CIRCULATION-FIRST APPROACH FOR RESUSCITATION OF TRAUMA PATIENTS WITH HEMORRHAGIC SHOCK
Authors: Chio Jonathon Chon Teng , Piehl Mark , De Maio Valerie J. , Simpson John T. , Matzko Chelsea , Belding Cameron , Broome Jacob M. , Duchesne Juan
Published: January 2023

The original guidelines of cardiopulmonary resuscitation focused on the establishment of an airway and rescue breathing before restoration of circulation through cardiopulmonary resuscitation. As a result, the airway-breathing-circulation approach became the central guiding principle of resuscitation. Despite new guidelines by the American Heart Association for a circulation-first approach, Advanced Trauma Life Support guidelines continue to advocate for the airway-breathing-circulation sequence. Although definitive airway management is often necessary for severely injured patients, endotracheal intubation (ETI) before resuscitation in patients with hemorrhagic shock may worsen hypotension and precipitate cardiac arrest. In severely injured patients, a paradigm shift should be considered, which prioritizes restoration of circulation before ETI and positive pressure ventilation while maintaining a focus on basic airway assessment and noninvasive airway interventions. For this patient population, the most reasonable current strategy may be to target a simultaneous resuscitation approach, with immediate efforts to control hemorrhage and provide basic airway interventions while prioritizing volume resuscitation with blood products and deferring ETI until adequate systemic perfusion has been attained. We believe that a circulation-first sequence will improve both survival and neurologic outcomes for a traumatically injured patient and will continue to advocate this approach, as additional clinical evidence is generated to inform how to best tailor circulation-first resuscitation for varied injury patterns and patient populations.
Recurring Pancreatic Neuroendocrine Tumor: Timing and Pattern of Recurrence and Current Treatment
Authors: Pulvirenti Alessandra , Javed Ammar A. , Michelakos Theodoros , Sekigami Yurie , Zheng Jian , Kalvin Hannah L. , McIntyre Caitlin A. , Nebbia Martina , Chou Joanne F. , Gonen Mithat , Raj Nitya , Reidy-Lagunes Diane L. , Zureikat Amer H. , Ferrone Cristina R. , He Jin , Wei Alice C. ,   PAncreatic Neuroendocrine Disease Alliance (PANDA)
Published: January 2023

Objective:

The objective of this study was to describe the pattern of recurrence, treatments received, as well the oncological outcomes, of pancreatic neuroendocrine tumors (PanNETs) following curative surgery.

Background:

PanNETs recur in 10% to 15% of cases following surgery. Information on the natural history and management of recurring disease is lacking.

Materials and Methods:

Patients with PanNET that underwent curative surgery at 4 institutions between 2000 and 2019 were identified. Patients with poorly differentiated tumors, unknown tumor grade and differentiation, hereditary syndromes, unknown margin or R2 status, metastatic, and those that had neoadjuvant treatment or perioperative mortality were excluded. Clinical variables were assessed including first site of recurrence, treatment received, and survival outcomes.

Results:

A total of 1402 patients were included: 957 (74%) had grade 1, 322 (25%) had grade 2, and 13 (1%) had grade 3 tumors. Median follow-up was 4.8 years (interquartile range: 2–8.2 years). Cumulative incidence of recurrence at 5 years was 13% (95% CI: 11%–15.2%) for distant disease, 1.4% (95% CI: 0.8%–2.3%) for locoregional recurrence, and 0.8% (95% CI: 0.4%–1.5%) for abdominal nodal recurrence. Patients who recurred had 2.89 increased risk of death (95% CI: 2–4.1) as compared with patients who did not recur. Therapy postrecurrence included: somatostatin analogs in 111 (61.0%), targeted therapies in 48 (26.4%), liver-directed therapies in 61 (33.5%), peptide receptor radionuclide therapy in 30 (16.5%), and surgery in 46 (25.3%) patients. Multiple treatments were used in 103 (57%) cases. After the first recurrence, 5-year overall survival was 74.6% (95% CI: 67.4%–82.5%).

Conclusions:

Recurrence following surgery is infrequent but reduces survival. Most recurrences are distant and managed with multiple therapies. Prospective studies are needed to establish strategies for surveillance and the sequence of treatment to control the disease and prolong survival.
Modern Outcomes After Liver Retransplantation: A Single-center Experience
Authors: Connor Ashton A. , Saharia Ashish , Mobley Constance M. , Hobeika Mark J. , Victor David W. , Kodali Sudha , Brombosz Elizabeth W. , Graviss Edward A. , Nguyen Duc T. , Moore Linda W. , Gaber A. Osama , Ghobrial R. Mark
Published: January 2023

Background.

The need for liver retransplantation (reLT) has increased proportionally with greater numbers of liver transplants (LTs) performed, use of marginal donors, degree of recipient preoperative liver dysfunction, and longer survival after LT. However, outcomes following reLT have been historically regarded as poor.

Methods.

To evaluate reLT in modern recipients, we retrospectively examined our single-center experience. Analysis included 1268 patients undergoing single LT and 68 patients undergoing reLT from January 2008 to December 2021.

Results.

Pre-LT mechanical ventilation, body mass index at LT, donor–recipient ABO incompatibility, early acute rejection, and length of hospitalization were associated with increased risk of needing reLT following index transplant. Overall and graft survival outcomes in the reLT cohort were equivalent to those after single LT. Mortality after reLT was associated with Kidney Donor Profile Index, national organ sharing at reLT, and LT donor death by anoxia and blood urea nitrogen levels. Survival after reLT was independent of the interval between initial LT and reLT, intraoperative packed red blood cell use, cold ischemia time, and preoperative mechanical ventilation, all previously linked to worse outcomes.

Conclusions.

These data suggest that reLT is currently a safer option for patients with liver graft failure, with comparable outcomes to primary LT.
Temporary Mechanical Circulatory Support Use and Clinical Outcomes of Simultaneous Heart/Kidney Transplant Recipients in the Pre– and Post–heart Allocation Policy Change Eras
Authors: Agdamag Arianne C. , Riad Samy , Maharaj Valmiki , Jackson Scott , Fraser Meg , Charpentier Victoria , Nzemenoh Bellony , Martin Cindy M. , Alexy Tamas
Published: January 2023

Background.

The use of temporary mechanical circulatory support (tMCS) devices (intra-aortic balloon pump; Impella 2.5, CP, 5.0; venoarterial extracorporeal membrane oxygenation) increased significantly across the United States for heart transplant candidates after the allocation policy change. Whether this practice change also affected simultaneous heart-kidney (SHK) candidates and recipient survival is understudied.

Methods.

We used the Scientific Registry of Transplant Recipients database to identify adult SHK recipients between January 2010 and March 2022. The population was stratified into pre– and post–heart allocation change cohorts. Kaplan–Meier curves were generated to compare 1-y survival rates. A Cox proportional hazards model was used to investigate the effect of allocation period on patient survival. Recipient outcomes bridged with eligible tMCS devices were compared in the post–heart allocation era. In a separate analysis, SHK waitlist mortality was evaluated between the allocation eras.

Results.

A total of 1548 SHK recipients were identified, and 1102 were included in the final cohort (534 pre-allocation and 568 post-allocation change). tMCS utilization increased from 17.9% to 51.6% after the allocation change, with venoarterial extracorporeal membrane oxygenation use rising most significantly. However, 1-y post-SHK survival remained unchanged in the full cohort (log-rank P = 0.154) and those supported with any of the eligible tMCS devices. In a separate analysis (using a larger cohort of all SHK listings), SHK waitlist mortality at 1 y was significantly lower in the current allocation era (P  = 0.002).

Conclusions.

Despite the remarkable increase in tMCS use in SHK candidates after the heart allocation change, 1 y posttransplant survival remained unchanged. Further studies with larger cohorts and longer follow-ups are needed to confirm these findings.
Exosomes for the diagnosis and treatment of dementia
Authors: Joo Hyeon Su , Jeon Ha Yeong , Hong Eun Be , Kim Ha Young , Lee Jung Min
Published: January 2023

Purpose of review

Dementia is a syndrome with several possible pathologies. To date, definitive methods for diagnosis and treatment of sub-types of dementia have not been established. Emerging evidence suggests that exosomes can provide important information for the diagnosis and treatment of several subtypes of dementia. This article reviews recent studies on the application of exosomes in dementia.

Recent findings

Exosomes are involved in the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD) through transporting toxic proteins such as amyloid beta (Aβ), tau, and α-synuclein. Exosomal microRNAs (miR) and proteins reflect the disease state, and therefore, exosomes can be used as diagnostic markers for diseases such as AD, PD, Huntington's disease (HD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Mesenchymal stem cell (MSC)-derived exosomes have been shown to ameliorate disease pathology, and improve cognitive function in AD, PD, and VAD.

Recent studies have shown that exosomes could be novel diagnostic agents for dementia because they contain molecules that could be potential biomarker candidates indicative of the type and stage of dementia. Therapeutic application of exosomes in dementia has revealed that exosomes only, or exosomes loaded with an active pharmaceutical ingredient (API), ameliorate disease phenotype of dementia. Further work is needed to exploit this potential.
Further development needed: models of post-diagnostic support for people with dementia
Authors: Low Lee-Fay , Gresham Meredith , Phillipson Lyn
Published: January 2023

Purpose of review

There is increasing recognition of a service gap immediately after diagnosis for people with dementia and carers. This narrative review of models of post-diagnostic support focuses on recent developments and offers suggestions for future development. We present the current evidence for these models and consider the service components they provide against the recommendations of clinical guidelines and principles underpinning ideal post-diagnostic support.

Recent findings

Models of post-diagnostic support include a short-term support worker, ongoing support worker, centre-based support, primary care management, and specialist dementia clinics. Of these, specialist dementia clinics that include ongoing support workers provide most components of an ideal and timely post-diagnostic support framework, but may be more costly to implement universally. The greatest research evidence is for the benefits of long-term support models, specifically case management, though this does not necessarily include medical care or nonpharmacological interventions. There is sparce evidence for the benefits of short-term support worker models such as dementia advisers for people with dementia and carers.

Further development is needed to create whole-system models of dementia support which meet the needs of people with dementia and their carers, are timely, accessible and equitable, and can be implemented universally.
Multidrug-resistant toxigenic Corynebacterium diphtheriae sublineage 453 with two novel resistance genomic islands
Authors: Arcari Gabriele , Hennart Mélanie , Badell Edgar , Brisse Sylvain
Published: January 2023

Antimicrobial therapy is important for case management of diphtheria, but knowledge on the emergence of multidrug-resistance in

Corynebacterium diphtheriae

is scarce. We report on the genomic features of two multidrug-resistant toxigenic isolates sampled from wounds in France 3 years apart. Both isolates were resistant to spiramycin, clindamycin, tetracycline, kanamycin and trimethoprim-sulfamethoxazole. Genes ermX, cmx, aph(3’)-Ib, aph(6)-Id, aph(3’)-Ic, aadA1, dfrA15, sul1, cmlA, cmlR and tet(33) were clustered in two genomic islands, one consisting of two transposons and one integron, the other being flanked by two IS6100 insertion sequences. One isolate additionally presented mutations in gyrA and rpoB and was resistant to ciprofloxacin and rifampicin. Both isolates belonged to sublineage 453 (SL453), together with 25 isolates from 11 other countries (https://bigsdb.pasteur.fr/diphtheria/). SL453 is a cosmopolitan toxigenic sublineage of C. diphtheriae, a subset of which acquired multidrug resistance. Even though penicillin, amoxicillin and erythromycin, recommended as the first line in the treatment of diphtheria, remain active, surveillance of diphtheria should consider the risk of dissemination of multidrug-resistant strains and their genetic elements.
Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlightsAPOL1as a high risk locus in patients with diabetic macular edema
Authors: Stockwell Amy D. , Chang Michael C. , Mahajan Anubha , Forrest William , Anegondi Neha , Pendergrass RK , Selvaraj Suresh , Reeder Jens , Wei Eric , Iglesias VA , Creps Natalie M. , Macri Laura , Neeranjan Andrea N. , van der Brug Marcel P. , Scales Suzie J. , McCarthy Mark I. , Yaspan Brian L.
Published: January 2023

Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5×10−8). The strongest association was rs2239785, (K150E) inAPOL1. The second finding was rs10402468, which co-localized toPLVAPandANKLE1in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the geneAPOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries.
Breastfeeding support for mothers of low birth weight infants using mother-to-mother peers in rural western Kenya - a feasibility study
Authors: Dickinson Fiona M , Achieng Florence , K’Oloo Alloys , Otiti Iwaret , Tindi Linda , Boga Mwanamvua , Kimani Mary , Kiige Laura , Mellor Kathy , Dellicour Stephanie , Barsosio Hellen C. , Kariuki Simon , Nabwera Helen M
Published: January 2023

The majority of the 2.4 million neonates (infants<28 days) who died in 2020 were born weighing <2500g i.e. low birth weight (LBW). In Africa, approximately 1 in 10 neonates are LBW. The majority of those who survive beyond the neonatal period are undernourished, have neuro-developmental impairment, or die before their second birthday. Unaddressed feeding difficulties contribute significantly to these adverse outcomes. This study assessed the feasibility and acceptability of using trained mother-to-mother peers (peer-mothers) to deliver breastfeeding support to mothers of LBW infants in healthcare facilities in rural Kenya.

A mixed methods approach was employed, using structured observations, and pre- and post-intervention semi-structured interviews, with mothers, healthcare providers and peer-mothers. Six trained peer-mothers delivered the interventions to the mother-LBW infant pairs across eight healthcare facilities in Homa Bay County. Descriptive statistics were used to analyse the quantitative data and thematic analysis for the qualitative data.

From September-November 2021, 23 mothers and 26 LBW infants were recruited and received the intervention. All infants were born in a hospital, the median age of the infants was 1 day (Interquartile range, IQR 1,3), birth weight 2100g (IQR 1900, 2260) and recorded gestation 34 weeks (IQR 34,36). Although all mothers looked well, 4 (17%) showed no signs of bonding with their infant. One infant was too weak to suckle and was referred to healthcare providers. Key themes were challenges with infant feeding decision-making among mothers of LBW infants, community misconceptions of recommended infant feeding practices for LBW infants, and the integral role of peer-mothers in maternity units.

Facility-based, breastfeeding peer support for LBW infants was feasible and acceptable in the context of resource constraints. It could improve uptake of appropriate infant feeding practices among these vulnerable infants and enhance their post-discharge survival and growth outcomes. This strategy warrants further evaluation in a larger study.
Effectiveness of Ferritin-guided Donation Intervals in Blood Donors: Results of the Stepped-wedge Cluster Randomised FIND’EM Trial
Authors: Meulenbeld Amber , Ramondt Steven , Sweegers Maike G. , Quee Franke A. , Prinsze Femmeke J. , Hoogendijk Emiel O. , Swinkels Dorine W. , van den Hurk Katja
Published: January 2023

Background

Whole blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin (Hb) monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We determine the effects of ferritin-guided donation intervals for blood donors and the blood supply.

Methods

A ferritin-guided donation interval policy was implemented and evaluated through a stepped-wedge cluster-randomised controlled trial in all blood collection centres in the Netherlands. Ferritin was measured in new donors and at every 5th donation. Subsequent donation intervals were extended to six months if ferritin was 15 - 30 ng/mL and to twelve months if ferritin was <15 ng/mL. Primary outcomes are ferritin and Hb levels, iron deficiency, Hb deferral, and donor return. Secondary outcomes are self-reported iron deficiency-related symptoms. Operational statistics assessed the impact on the blood supply.

Findings

Among 412,888 whole blood donors, 36,099 were measured. Ferritin-guided intervals increased ferritin levels by 0.24 log10 ng/mL (95% CI 0.22 – 0.27, p <0.001) and Hb by 0.37 g/dL (95% CI 0.31 –0.43, p <0.001). Donors were less likely to be iron deficient (OR 0.15, 95% CI 0.10 – 0.21, p <0.001) or deferred based on Hb (OR 0.23, 95% CI 0.11 – 0.41, p <0.001). However, donors returned less frequently (OR 0.60, 95% CI 0.51 – 0.67, p <0.001), necessitating more invitations and reducing the average donation frequency. No improvement in self-reported symptoms was observed.

Interpretation

Ferritin-guided donation intervals significantly improved Hb and ferritin levels, reducing iron deficiency and Hb deferrals. While beneficial for iron and Hb maintenance, efforts are needed to recruit and retain donors and remedy self-reported symptoms.

Funding and registration

This project received support from the ’Product and Process Development Cellular Products Grant’ (PPOC18-15) granted to K. van den Hurk by the Research Programming Committee of Sanquin. The trial was registered in the Dutch trial registry (NTR6738) on September 29th, 2017 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6738).
Atypical cognitive training-induced learning and brain plasticity and their relation to insistence on sameness in children with autism
Authors: Liu Jin , Chang Hyesang , Abrams Daniel A. , Kang Julia Boram , Chen Lang , Rosenberg-Lee Miriam , Menon Vinod
Published: January 2023

Children with autism spectrum disorders (ASD) often display atypical learning styles, however little is known regarding learning-related brain plasticity and its relation to clinical phenotypic features. Here, we investigate cognitive learning and neural plasticity using functional brain imaging and a novel numerical problem-solving training protocol. Children with ASD showed comparable learning relative to typically developing children but were less likely to shift from rule-based to memory-based strategy. Critically, while learning gains in typically developing children were associated with greater plasticity of neural representations in the medial temporal lobe and intraparietal sulcus, learning in children with ASD was associated with more stable neural representations. Crucially, the relation between learning and plasticity of neural representations was moderated by insistence on sameness, a core phenotypic feature of ASD. Our study uncovers atypical cognitive and neural mechanisms underlying learning in children with ASD, and informs pedagogical strategies for nurturing cognitive abilities in childhood autism.