bluuebunny/crossref_metadata_2025 huggingface dataset:
The Threshold of Legibility
Authors: Smith Murray
Published: June 2022

Recognition is the first of the three levels of engagement in the model of character engagement, and describes the most basic and fundamental relationship we can form with a character—which is to say, the very act of perceiving a character as a character. Recognition is in turn constituted by two component activities: individuation (distinguishing a character from adjacent ones) and reidentification (grasping that a given character at one point in a narrative is ‘the same as’—continuous with—a character at other points in the narrative). The roles of the body and of language in securing recognition, introduced in Chapter 1, are elaborated further. The Man Who Knew Too Much serves as an exemplar of the classical handling of recognition, while alternative approaches to character recognition are explored through Buñuel’s That Obscure Object of Desire, Ruiz’ The Suspended Vocation, and Dovzhenko’s Arsenal.
Unintentional cannabis exposures in children pre- and post-legalization: A retrospective review from a Canadian paediatric hospital
Authors: Coret Alon , Rowan-Legg Anne
Published: June 2022

Objectives

Canada legalized recreational cannabis in October 2018. Cannabis is increasingly available in numerous forms—especially edibles—that make children vulnerable to unintentional intoxication. We sought to: determine the frequency of visits due to cannabis intoxication pre- and post-legalization; characterize the clinical features and circumstances of cannabis intoxication in the paediatric population; and create greater awareness among healthcare providers about this issue.

Methods

We performed a retrospective chart review of Emergency Department visits at the Children’s Hospital of Eastern Ontario (Ottawa, ON) between March 2013 and September 2020. Inclusion criteria were: age <18 years; unintentional cannabis ingestion, identified by ICD-10 codes T40.7 and X42. We assessed basic demographics, clinical signs and symptoms, exposure details, investigations, and patient disposition.

Results

A total of 37 patients (22 male) met inclusion criteria, mean age 5.9±3.8 years. Most visits (32; 86%) occurred in the 2-year period after legalization. Altered levels of consciousness, lethargy/somnolence, tachycardia, and vomiting were the most common presenting signs and symptoms. The majority of exposures were to edibles (28; 76%) in the home setting (30; 81%). Poison control and child protective services were involved in 19 (51%) and 22 (59%) of cases, respectively. Twelve patients (32%) required admission to the hospital, the majority of whom stayed <24 h.

Conclusions

Our data confirm increased paediatric hospital visits related to unintentional cannabis exposures post-legalization. Consideration of this clinical presentation is critical for acute care providers. Advocacy for safe storage strategies and appropriate enforcement of marketing/packaging legislation are imperative for public health policymakers.
Patterns and Distribution of Botryosphaeriaceae Fungi Related to Dieback in Big Berry Manzanita
Authors: Drake-Schultheis Laura , D'Antonio Carla M. , Oono Ryoko
Published: June 2022

Dieback and mortality in wildland plant species due to climate change have been on the rise in recent decades, and latent fungal pathogens might play a significant role in these events. During a severe multiyear drought, canopy dieback associated with latent pathogens in the Botryosphaeriaceae ( Bot) family was observed in stands of a dominant shrub species, big berry manzanita ( Arctostaphylos glauca), across chaparral landscapes in California. These fungi are significant pathogens of woody agricultural species, especially in hosts experiencing stress, and have become a threat to economically important crops worldwide. However, little is known regarding their occurrence, distribution, and impact in wildland systems. We conducted a field survey of 300 A. glauca shrubs across an elevational gradient to identify Bot species infection as it relates to (i) A. glauca dieback severity and (ii) landscape variables associated with plant drought stress. Our results show that Bots are widely infecting A. glauca across the landscape, and there is a significant correlation between elevation and dieback severity. Dieback severity was significantly higher at lower elevations, suggesting that infected shrubs at lower elevations are at greater risk than those at higher elevations. Furthermore, two Bot species, Neofusicoccum australe and Botryosphaeria dothidea, were most frequently isolated, with N. australe being the most common and, based on haplotype analysis, likely the most recently introduced of the two. Our results confirm the wide distribution of latent Bot fungi in a wild shrubland system and provide valuable insight into areas of greatest risk for future shrub dieback and mortalit y. These findings could be particularly useful for informing future wildlands management strategies with regard to introduced latent pathogens.
Rethinking the Physician–Scientist Pathway
Authors: Eshel Neir , Chivukula Raghu R.
Published: June 2022

Physician–scientists have the potential to generate fundamental as well as translational breakthroughs. But many trainees who intend to pursue a hybrid career in research and patient care ultimately leave one or the other behind. In this Invited Commentary, the authors draw from their experience as early-career physician–scientists to frame physician–scientist training as having 2 phases: first, learning to think like a physician–scientist; second, learning to act like a physician–scientist. These phases roughly correspond to (1) clinical training (from medical school through residency or fellowship) that incorporates research exposure, and (2) a structured period of graduated research independence once the physician–scientist has become clinically autonomous. There are many effective ways to pursue each phase; what matters most is flexibility in the first phase and sustained support in the second. Accordingly, the authors suggest many potential reforms, including at the levels of the National Institutes of Health, private funders, as well as universities and research hospitals. The authors argue that rethinking physician–scientist training to support individualized paths to an independent hybrid career can help recruit and retain physician–scientists for years to come.
Mind the target: human epidermal growth factor receptor 2 in colorectal cancer
Authors: Saúde-Conde Rita , Rasschaert Gertjan , Bregni Giacomo , Hendlisz Alain , Sclafani Francesco
Published: June 2022

Purpose of review

In this article, we briefly summarise the current knowledge about human epidermal growth factor receptor 2 (HER2) alterations in colorectal cancer (CRC) and provide an overview of the latest published evidence especially regarding standardisation of detection methods/diagnostic criteria, prognostication, prediction and targeted treatments.

Recent findings

Over the last 18 months, the results of many studies have been presented confirming the therapeutic potential of established anti-HER2 agents either as a monotherapy or in combination, as well as new anti-HER2 agents like antibody-drug-conjugates and tyrosine kinase inhibitors. Also, we have seen confirmation of the utility of liquid biopsy and ctDNA analyses as tool for HER2 detection and patient selection.

Despite concerning only 5% of metastatic CRC, HER2 represents a valuable target for emerging anti-HER2 therapies that might significantly improve the outcome of these patients. Standardising HER2 detection methods/diagnostic criteria, and producing high-quality, randomised evidence are the next challenges to meet the standards of regulatory authorities and ultimately have anti-HER2 agents available for use in routine practice.
Psycho-oncology interventions focusing on fatigue and sleep disturbances
Authors: Grégoire Charlotte , Faymonville Marie-Elisabeth , Jerusalem Guy , Gosseries Olivia , Vanhaudenhuyse Audrey
Published: June 2022

Purpose of the review

Cancer-related fatigue (CRF) and sleep disturbances are common symptoms among patients with cancer. They are often conceptualized as a part of a larger symptom cluster, also comprising pain and emotional distress. Despite their prevalence and long-lasting effects, CRF and sleep disturbances are still poorly addressed in clinical settings. Specific interventions are needed to manage these symptoms.

Recent findings

In addition to conventional pharmacological therapies, other kinds of interventions are increasingly being developed in oncology. This review will discuss three categories of interventions for patients with cancer and their interest in alleviating CRF and sleep disturbances: physical exercises (e.g., aerobic, resistance training, running, free weights), psychological interventions (e.g., cognitive-behavioural therapy, psychoeducational interventions), and mind-body interventions (e.g., yoga, mindfulness, hypnosis). The multicomponent aspect of these interventions seems particularly important to address these symptoms.

The findings detailed in this review will allow the scientific community, as well as health professionals working in oncology settings, to be informed about new nonpharmacological therapeutic options to help patients to manage their symptoms. It could eventually help to improve existing interventions for these patients.
A Low-cost, Sterile System for Fat Collection Using a Syringe Tube as a Reservoir
Authors: Alshawaf Solaiman M. , Burhamah Waleed , AlYouha Sarah , Alwazzan Sabika , Gerges Yousef
Published: June 2022

Fat grafting is a widely performed procedure in the field of plastic surgery. It involves fat extraction, processing, and injection into a recipient site. It is imperative that the fat is collected and processed in a sterile system. A wide variety of equipment is required to perform the procedure (eg, a liposuction device, a vacuum pump, and syringes). Limitations often arise in the operating room, especially in low-resource areas, where task-specific equipment might be unavailable. This can present an opportunity for the surgeon to improvise and create a temporary solution. In this report, we describe our solution in dealing with the unavailability of a sterile vacuum pump canister during a large volume fat grafting procedure. We constructed a sterile reservoir using two syringes, through which negative pressure was delivered without breaking sterility. The items used were a 60-cm3 syringe barrel, a 10-cm3 syringe barrel, a 60-cm3 syringe plunger seal, a tube connected to the nonsterile vacuum pump, and the liposuction cannula. This technique allowed us to extract the fat in a sterile environment under the assistance of a suction device. Our novel technique was used for harvesting fat in a sterile reservoir, while still utilizing the assisted suction from the nonsterile vacuum pump, without breaking sterility.
Blood pressure and kidney outcomes in patients with severely decreased glomerular filtration rate: a nationwide observational cohort study
Authors: Al-Sodany Ehab , Chesnaye Nicholas C. , Heimbürger Olof , Jager Kitty J. , Bárány Peter , Evans Marie
Published: June 2022

Objectives:

To investigate the association between blood pressure (BP) and kidney outcomes in patients with estimated glomerular filtration rate less than 30 ml/min per 1.73 m2 and different degrees of albuminuria.

Methods:

National observational cohort study of 18 071 chronic kidney disease (CKD) stage 4–5 patients in routine nephrology care 2010–2017. The association between both baseline and repeated clinic office BP and eGFR slope and kidney replacement therapy (KRT) was explored using multivariable adjusted joint models. The analyses were stratified on albuminuria at baseline.

Results:

The adjusted yearly eGFR slope became increasingly steeper from −0,91 (95% CI −0.83 to −1.05) ml/min per 1.73 m2 per year in those with SBP less than 120 mmHg at baseline to −2.09 (−1.83 to −2.37) ml/min per 1.73 m2 in those with BP greater than 160 mmHg. Similarly, eGFR slope was steeper with higher DBP. Lower SBP and DBP was associated with slower eGFR decline in patients with albuminuria grade A3 (>30 mg/mmol) but not consistently in albuminuria A1–A2. Those with diabetes progressed faster and the association between BP and eGFR slope was stronger. In repeated BP measurement analyses, every 10 mmHg higher SBP over time was associated with 39% additional risk of KRT.

Conclusion:

In people with eGFR less than 30 ml/min per 1.73 m2, lower clinic office BP is associated with more favorable kidney outcomes. Our results support lower BP targets also in people with CKD stage 4–5.
Impact of a Digital Diabetes Prevention Program on Estimated 8-Year Risk of Diabetes in a Workforce Population
Authors: Birse Charles E. , McPhaul Michael J. , Arellano Andre R. , Fragala Maren S. , Lagier Robert J.
Published: June 2022

Objective

We asked whether the estimated 8-year risk of diabetes could be reduced within the first 2 years of a digital Diabetes Prevention Program (dDPP) in a workforce population.

Methods

Employees and spouses were eligible if they had prediabetes-range fasting glucose or hemoglobin A1c and body mass index ≥25 kg/m2. Diabetes risk was assessed using the Framingham diabetes risk score in the year before and the 2 years after dDPP initiation.

Results

Among participants completing at least nine dDPP lessons (n = 286), diabetes risk decreased 5.3% the year after dDPP initiation, after a 5.4% increase the year before initiation (difference in differences, −10.6%; 95% confidence interval, −13.4% to −7.9%; P < 0.001), with risk maintained at reduced levels after the second year of the program.

Conclusion

This dDPP reduced the estimated 8-year risk of diabetes over the first 2 years of the program.
Examination of the Contributing Factors to Fatalities in Electrical Trades Due to Contact With Electricity
Authors: Rodriguez-Franco Oscar , Zreiqat Majed , Wachter Jan K. , Janicak Christopher
Published: June 2022

Objective

The aim of this study was to examine contributing factors to fatalities in electrical occupations due to contact with electricity.

Methods

Proportionate mortality ratios were calculated along with the Mantel-Haenszel chi-square test of significance using Occupational Safety and Health Administration data. Cross-tabulation analyses were examined by the Pearson chi-square test of independence.

Results

Electricians and electrical power installers/repairers experienced significantly higher proportions of fatalities due to contact with electric current of machine, tool, or light fixture and contact with overhead power lines, respectively. Factors such as accident date, location, union status, project type, cost, electrical event, human factor, part of body, source of injury, and fatality cause, exhibited significant associations with electrical trade fatalities.

Conclusions

Fatalities in electrical occupations are attributable to increased exposures to electrical hazards during regular work activities. Strict adherence to safe work practices and procedures is critical to electrical fatality prevention.
The Variable Response to Teduglutide in Pediatric Short Bowel Syndrome: A Single Country Real-Life Experience
Authors: Guz-Mark Anat , Hino Bayan , Berkowitz Drora , Hartman Corina , Millman Peri N. , Orlanski-Meyer Esther , Shaoul Ron , Spector-Cohen Inna , Weiss Batia , Zangen Tsili , Shamir Raanan
Published: June 2022

Objectives:

The glucagon-like peptide-2 analog Teduglutide has been shown to enhance intestinal absorption and decrease parenteral nutrition (PN) requirements in short bowel syndrome (SBS). As data in children is limited, we evaluated nationwide real-life experience and treatment outcome in children with SBS.

Methods:

Longitudinal data of children treated with Teduglutide for ≥3 months was collected. Data included demographic and medical background, anthropometrics, laboratory assessments and PN requirements. Treatment response was defined as >20% reduction in PN requirement.

Results:

The study included 13 patients [54% males, median (interquartile range {IQR}) age of 6 (4.7–7) years]. The most common SBS etiology was necrotizing enterocolitis (38%), and median (IQR) small bowel length was 20 (15–40) cm. Teduglutide treatment ranged between 3 and 51 months [median (IQR) of 18 (12–30) months], with 10 patients (77%) treated >1 year. Response to treatment was observed in 8 patients (62%), with a mean [±standard deviation (SD)] treatment duration of 5.9 (±3.2) months. Among responders, 2 patients were weaned off PN and additional 4 decreased PN needs by >40%. There was a median (IQR) reduction in PN volume/kg of 36% (15%–55%) and in PN energy/kg of 27% (6%–58%). Response was not associated with patients’ background, and no correlation was found with bowel length or PN dependency at baseline.

Conclusions:

Real-life response to Teduglutide is highly variable among children with SBS. While most patients did reach 20% reduction in PN, less achieved further significant reduction or enteral autonomy. No predictive factors of response to treatment were identified, and large multicenter studies are needed to elucidate predictive factors and long-term outcome.
Diffuse Anaplastic Wilms Tumor in a Child With LAMA2-related Muscular Dystrophy
Authors: Shah Rachana , Mohamed Deena , Ramos-Platt Leigh M. , Grikscheit Tracy C. , Zhou Shengmei , Wong Kenneth K. , Mascarenhas Leo
Published: June 2022

Laminin alpha-2-related muscular dystrophy (LAMA2-MD), caused by mutations in the LAMA2 gene, is inherited in an autosomal recessive manner. There is no known association of LAMA2-MD with cancer predisposition. We present a 4-year-old female with LAMA2-MD and Children’s Oncology Group stage III diffuse anaplastic Wilms tumor (DAWT). Given our patient’s comorbidities, it was essential to tailor her adjuvant chemotherapy by omitting vincristine and doxorubicin to avoid the potential worsening of her neuromuscular dysfunction and cardiomyopathy. This report illustrates the sporadic occurrence of 2 rare events in our patient and highlights the successful risk-adapted management of DAWT based on the pathophysiology of LAMA2-MD.
Associations between HIV viremia during antiretroviral therapy and cardiovascular disease
Authors: Elvstam Olof , Marrone Gaetano , Engström Gunnar , Nilsson Peter M. , Carlander Christina , Treutiger Carl Johan , Gisslén Magnus , Björkman Per
Published: June 2022

Objective:

To investigate the association between HIV viremia exposure during antiretroviral therapy (ART) and cardiovascular disease (CVD) risk.

Design:

Nationwide observational cohort.

Methods:

Participants (age >15 years) from the Swedish nationwide InfCareHIV register initiating ART 1996–2017 were categorized in a time-updated manner into four viremia categories, starting from 12 months after ART initiation: suppression (<50 copies/ml), low-level viremia (50–199 copies/ml and 200–999 copies/ml, respectively), and high-level viremia (≥1000 copies/ml). In addition, cumulative viremia was estimated as the area under the log viral load (VL) curve. Proportional subhazard models adjusted for sex, age, pre-ART CD4 and VL, injection drug use, and country of birth were used to analyze the association between viremia exposure and CVD risk (ischemic heart disease, stroke, and heart failure; data obtained by linkage to national registers), accounting for the competing risk of non-CVD death.

Results:

In all, 337 cases of CVD were observed during 44 937 person-years of follow-up (n = 6562). Higher viremia exposure was associated with CVD, both when parameterized as cumulative viremia (adjusted subhazard ratio [aSHR] per 1 log10 copy × year/ml, 1.03; 95% confidence interval [CI], 1.01–1.05) and as viremia category (aSHR for high-level viremia versus suppression, 1.45; 95% CI, 1.03–2.05). We observed no association between CVD and low-level viremia compared with those with suppression.

Conclusions:

Higher exposure to HIV viremia was linked to CVD in ART recipients, whereas no increased risk was detected for people with low-level viremia compared with viral suppression. Causal inference is limited by the observational nature of this study.
Industrial mining and HIV risk: evidence from 39 mine openings across 16 countries in sub-Saharan Africa
Authors: Dietler Dominik , Farnham Andrea , Lyatuu Isaac , Fink Günther , Winkler Mirko S.
Published: June 2022

Objectives:

The aim of this study was to assess the impact of natural resource extraction projects on HIV transmission risks in local communities in sub-Saharan Africa.

Design:

Difference-in-differences design using repeated cross-sectional data from around newly opened mines.

Methods:

We combined data on mine openings with HIV data from the Demographic and Health Surveys (DHS). Using logistic regression models, we compared HIV-related indicators between mining (i.e. up to 10 km distance from the mine) and comparison (i.e. 10–50 km) areas before and after mine opening to identify their impact on HIV prevalence, sexual behavior and HIV knowledge.

Results:

A total of 33 086 individuals across 39 mine openings were analyzed. Adjusting for baseline differences and temporal trends in the study regions, mine opening increased the odds of HIV infection almost two-fold [odds ratio (OR): 1.93, 95% confidence interval (CI): 1.19–3.14]. Strongest effects were seen in high-prevalence countries and in the 20–29 years age group. In mining communities around operational mines, there was a tendency towards lower HIV knowledge (OR: 0.81, 95% CI: 0.63–1.04). New mine openings increased the odds of risky sexual behaviors, such as having multiple sex partners (OR: 1.61, 95% CI: 1.02–2.55), high-risk sexual partners (OR: 1.45, 95% CI: 1.03–2.05) and unprotected sex with high-risk partners (OR: 1.77, 95% CI: 1.18–2.67).

Conclusion:

The findings suggest that in our sample of households surrounding industrial mines, HIV infection risks substantially increase upon mine opening. Existing strategies for addressing mining-related risks for HIV transmission seem to be insufficient. Further efforts for mitigating and monitoring impacts of mines are needed.
Analysis of Patients With Blowout Fracture Caused by Baseball Trauma
Authors: Hong Suji , Choi Kwang-Eon , Kim Joohyun , Lee Hyunkyu , Lee Hwa , Baek Sehyun
Published: June 2022

The purpose of this study was to investigate the characteristics of blowout fractures caused by baseball trauma. The authors reviewed 337 cases of blowout fracture surgeries and included 330 eyes of 330 patients who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea university Hospital.

Medical records including patient demography, trauma etiology, accompanied ocular disease, and preoperative computed tomography images were evaluated. Patients were categorized into 2 groups: a group with blowout fracture caused by baseball trauma and another group with trauma due to other causes. Two-wall blowout fracture (orbital floor fracture and medial wall fracture) was most common (63.16%) in the baseball group, followed by medial wall fracture (21.05%). In contrast, orbital floor fracture accounted for the largest proportion (42.11%) among other causes, and 2-wall blowout fracture accounted for the second largest proportion (31.83%). The most common accompanied ocular disease was traumatic hyphema and traumatic iridocyclitis (36.84%) in the baseball blowout fracture group. in contrast, subconjunctival hemorrhage was the most common ocular disease in the other-causes group (16.08%). The frequency of traumatic hyphema and irido-cyclitis was significantly different among the 2 groups (P 
< 0.05). Distribution of blowout fracture sites and frequent ocular disease differed between baseball blowout fracture patients and other-cause blowout fracture patients.
Potential for identification of wild night-flying moths by remote infrared microscopy
Authors: Li Meng , Seinsche Clara , Jansson Samuel , Hernandez Julio , Rota Jadranka , Warrant Eric , Brydegaard Mikkel
Published: June 2022

There are hundreds of thousands of moth species with crucial ecological roles that are often obscured by their nocturnal lifestyles. The pigmentation and appearance of moths are dominated by cryptic diffuse shades of brown. In this study, 82 specimens representing 26 moth species were analysed using infrared polarimetric hyperspectral imaging in the range of 0.95–2.5 µm. Contrary to previous studies, we demonstrate that since infrared light does not resolve the surface roughness, wings appear glossy and specular at longer wavelengths. Such properties provide unique reflectance spectra between species. The reflectance of the majority of our species could be explained by comprehensive models, and a complete parametrization of the spectral, polarimetric and angular optical properties was reduced to just 11 parameters with physical units. These parameters are complementary and, compared with the within-species variation, were significantly distinct between species. Counterintuitively to the aperture-limited resolution criterion, we could deduce microscopic features along the surface from their infrared properties. These features were confirmed by electron microscopy. Finally, we show how our findings could greatly enhance opportunities for remote identification of free-flying moth species, and we hypothesize that such flat specular wing targets could be expected to be sensed over considerable distances.
Demographic and Clinical Characteristics of Pediatric COVID-19 in Arkansas: March-December 2020
Authors: Sanders Sara C. , Taylor Maxwell D. , Filipek Jacob , Williford Dustin , Nguyen Cindy , Fisher Charalene R. , Scheffler Stephanie M. , Smith Emily S. , Martin Phoebe , Latch Rebecca L. , Snowden Jessica , Wu Chang L. , Cantu Rebecca M.
Published: June 2022

The COVID-19 pandemic reached the United States in early 2020 and spread rapidly across the country. This retrospective study describes the demographic and clinical characteristics of 308 children presenting to an Arkansas Children’s emergency department or admitted to an Arkansas Children’s hospital with COVID-19 in the first ten months of the COVID-19 pandemic, prior to the emergence of clinically significant variants and available vaccinations. Adolescents aged 13 and older represented the largest proportion of this population. The most common presenting symptoms were fever, gastrointestinal symptoms, and upper respiratory symptoms. Patients with multisystem inflammatory syndrome in children (MIS-C) had a longer length of stay than patients with acute COVID-19. Children from urban zip codes had lower odds of admission but were more likely to be readmitted after discharge. Nearly twenty percent of the study population incidentally tested positive for COVID-19. Despite lower mortality in children with COVID than in adults, morbidity and resource utilization are significant. With many Arkansas children living in rural areas and therefore far from pediatric hospitals, community hospitals should be prepared to evaluate children presenting with COVID-19 and to determine which children warrant transport to pediatric-specific facilities.
Yin-Yang 1, a player regulated systematic inflammatory involved in cognitive impairment of depression
Authors: Lu Jing , Jin Kangyu , Jiao Jianping , Liu Ripeng , Mou Tingting , Chen Bing , Zhang Zhihan , Jiang Chaonan , Zhao Haoyang , Wang Zheng , Zhou Rui , Huang Manli
Published: June 2022

A growing number of clinical and preclinical studies suggest that alterations in peripheral and brain immunal system and followed inflammation are associated with the pathophysiology of depression, also leading to the changes in local glucose metabolism in the brain. Here, we identified Yin-yang 1 (YY1), a transcription factor that has been reported to be closely associated with central and peripheral inflammation. The levels of YY1 and IL-1β were significantly increased in blood samples from depressed individuals, and significantly decreased after treatment with Vortioxetine. Meanwhile, it was found that the level of YY1 in plasma was negatively correlated with visual learning reasoning and problem solving in MDD patients, and positively correlated with the level of IL-1β in plasma. CUMS animals showed depressive-like behavior. Compared with the control group, MicroPET analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum and mPFC was reversed after treatment. After treatment, these changes were reversed. In conclusion, Our study suggested that YY1-NF-κB - IL-1β inflammatory pathway may play an essential part on both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in the emotion regulation and cognition related brain regions. These findings provide new evidence for the inflammatory mechanisms of depression.
Impact of healthcare capacity disparities on the COVID-19 vaccination coverage in the United States: A cross-sectional study
Authors: Cuadros Diego F , Gutierrez Juan D , Moreno Claudia M , Escovar Santiago , Miller F. DeWolfe , Musuka Godfrey , Omori Ryosuke , Coule Phillip , MacKinnon Neil J
Published: June 2022

Background
The impact of the COVID-19 vaccination campaign in the US has been hampered by a substantial geographical heterogeneity of the vaccination coverage. Several studies have proposed vaccination hesitancy as a key driver of the vaccination uptake disparities. However, the impact of other important structural determinants such as local disparities in healthcare capacity is virtually unknown.

Methods
In this cross-sectional study, we conducted causal inference and geospatial analyses to estimate the impact of healthcare capacity on the vaccination coverage disparity in the US. We evaluated the causal relationship between the healthcare system capacity of 2,417 US counties and their COVID-19 vaccination rate. We also conducted geospatial analyses using spatial scan statistics to identify areas with low vaccination rates.

Findings
We found a positive association between the healthcare capacity of a county and vaccination uptake. We estimated that a 1% increase in the Resource-Constrained Health System Index of a county increases by 0.37% the occurrence of that county in the set of counties classified as low-vaccinated (≤50% vaccination rate). We also found that COVID-19 vaccinations in the US exhibit a distinct spatial structure with defined vaccination coldspots.

Interpretation
We found that the healthcare capacity of a county is an important determinant of low vaccine uptake. Our study highlights that even in high-income nations, internal disparities in healthcare capacity play an important role in the health outcomes of the nation. Therefore, strengthening the funding and infrastructure of the healthcare system, particularly in rural underserved areas, should be intensified to help vulnerable communities.
Genomic epidemiology of circulating SARS-CoV-2 variants during first two years of the pandemic in Colombia
Authors: Jimenez-Silva Cinthy , Rivero Ricardo , Douglas Jordan , Bouckaert Remco , Villabona-Arenas Julian , Atkins Katherine , Gastelbondo Bertha , Calderon Alfonso , Guzman Camilo , Echeverri-De la Hoz Daniel , Muñoz Marina , Ballesteros Nathalia , Castañeda Sergio , Patiño Luz H. , Ramirez Angie , Luna Nicolas , Paniz-Mondolfi Alberto , Serrano-Coll Hector , Ramirez Juan David , Mattar Salim , Drummond Alexei
Published: June 2022

The emergence of highly transmissible SARS-CoV-2 variants has led to surges in cases and the need for global genomic surveillance. While some variants rapidly spread worldwide, other variants only persist nationally. There is a need for more fine-scale analysis to understand transmission dynamics at a country scale. For instance, the Mu variant of interest, also known as lineage B.1.621, was first detected in Colombia and was responsible for a large local wave but only a few sporadic cases elsewhere. To provide a better understanding of the epidemiology of SARS-Cov-2 variants in Colombia, we used 14,049 complete SARS-CoV-2 genomes from the 32 states of Colombia, and performed Bayesian phylodynamic analyses to estimate the time of variants introduction, their respective effective reproductive number, and effective population size, and the impact of disease control measures. We detected a total of 188 SARS-CoV-2 Pango lineages circulating in Colombia since the start of the pandemic. We showed that the effective reproduction number oscillated drastically throughout the first two years of the pandemic, with Mu showing the highest transmissibility (Re and growth rate estimation). Our results reinforce that genomic surveillance programs are essential for countries to make evidence-driven interventions towards the emergence and circulation of novel SARS-CoV-2 variants.
The economic burden of RSV-associated illness in children aged <5 years, South Africa 2011-2016
Authors: Moyes Jocelyn , Tempia Stefano , Walaza Sibongile , McMorrow Meredith L. , Treurnicht Florette , Wolter Nicole , von Gottberg Anne , Kahn Kathleen , Cohen Adam L , Dawood Halima , Variava Ebrahim , Cohen Cheryl
Published: June 2022

Introduction

Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated these costs in fine age bands to allow more accurate cost-effectiveness models to account for limited duration of protection conferred by short or long acting interventions.

Methods

We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalisations or clinic visits; the PDE was multiplied by the number of days of care to provide a case-cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged <1 years and as a single group for children aged 1-4 years. We then applied our data to a modified version of the World Health Organization tool for estimating mean annual national cost burden, including medically and non-medically attended RSV-associated illness.

Results

The estimated mean annual cost of RSV-associated Illness in children aged <5 years was United States dollars ($)137 204 393, of which 81% ($111 742 713) were healthcare system incurred, 6% ($8 881 612) were out of pocket expenses and 13% ($28 225 801) were indirect costs. Thirty-three percent ($45 652 677/$137 204 393) of the total cost in children aged <5 years was in the <3-month age group, of which 52% ($71 654 002) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3 307 218 in the <3-month age group to $8 603 377 in the 9-11-month age group.

Conclusion

Among children <5 years of age with RSV in South Africa, the highest cost burden was in young infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness.
A mechanistic model explains oscillatory slowing and neuronal hyperactivity in Alzheimer’s disease
Authors: Alexandersen Christoffer G. , de Haan Willem , Bick Christian , Goriely Alain
Published: June 2022

Alzheimer’s disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-β and tau proteins throughout the brain. Recent studies have highlighted stark differences in how amyloid-β and tau affect neurons at the cellular scale. On a larger scale, Alzheimer’s patients are observed to undergo a period of early-stage neuronal hyperactivation followed by neurodegeneration and frequency-slowing of neuronal oscillations. Herein, we model the spreading of both amyloid-β and tau across a human connectome and investigate how the neuronal dynamics are affected by disease progression. By including the effects of both amyloid-β and tau pathology, we find that our model explains AD-related frequency slowing, early-stage hyperactivation, and late-stage hypoactivation. By testing different hypotheses, we show that hyperactivation and frequency-slowing are not due to the topological interactions between different regions but are mostly the result of local neurotoxicity induced by amyloid-β and tau protein.
Applications of a Novel Reciprocating Positive Displacement Pump in the Simulation of Pulsatile Arterial Blood Flow
Authors: Menkara Adam , Faryami Ahmad , Viar Daniel , Harris Carolyn A
Published: June 2022

Pulsatile arterial blood flow plays an important role in vascular system mechanobiology, especially in the study of mechanisms of pathology. Limitations in cost, setup time, sample size, and control across current in-vitro and in-vivo methods prevent future exploration of novel treatments. Presented is the verification of a novel reciprocating positive displacement pump aimed at resolving these issues through the simulation of human ocular, human fingertip and skin surface, human cerebral, and rodent spleen organ systems. A range of pulsatile amplitudes, frequencies, and flow rates were simulated using pumps made of 3D printed parts incorporating a tubing system, check valve and proprietary software. Volumetric analysis of 430 total readings across a flow range of 0.025ml/min to 16ml/min determined that the pump had a mean absolute error and mean relative error of 0.041 ml/min and 1.385%, respectively. Linear regression of flow rate ranges yielded R2 between 0.9987 and 0.9998. Waveform analysis indicated that the pump could recreate accurate beat frequency for flow ranges above 0.06ml/min at 70BPM. The verification of accurate pump output opens avenues for the development of novel long-term in-vitro benchtop models capable of looking at fluid flow scenarios previously unfeasible, including low volume-high shear rate pulsatile flow.
Autophagy degrades myelin proteins and is essential for maintaining CNS myelin homeostasis
Authors: Ktena Niki , Kaplanis Stefanos Ioannis , Kolotuev Irina , Georgilis Alexandros , Stavroulaki Vasiliki , Kallergi Emmanouela , Nikoletopoulou Vassiliki , Karagogeos Domna , Savvaki Maria
Published: June 2022

(Macro)autophagy comprises a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an essential mechanism for oligodendrocyte maturation in vitro. Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated atg5, a core gene of the autophagic machinery, specifically in myelinating glial cells in vivo by tamoxifen administration (plp-CreERT2; atg5F/F) and showed that myelin maintenance is perturbed, leading to PLP accumulation. Significant morphological defects in myelin membrane such as decompaction accompanied with increased axonal degeneration are observed. As a result, the mice exhibit behavioral deficits. In summary, our data highlight that the maintenance of adult myelin homeostasis in the CNS requires the involvement of a fully functional autophagic machinery.
Theropod dinosaurs had primate-like numbers of telencephalic neurons
Authors: Herculano-Houzel Suzana
Published: June 2022

Understanding the neuronal composition of the brains of dinosaurs and other fossil amniotes would offer fundamental insight into their behavioral and cognitive capabilities, but brain tissue is only rarely fossilized. However, when the bony brain case is preserved, the volume and therefore mass of the brain can be estimated with computer tomography; and if the scaling relationship between brain mass and numbers of neurons for the clade is known, that relationship can be applied to estimate the neuronal composition of the brain. Using a recently published database of numbers of neurons in the telencephalon of extant sauropsids (birds, squamates and testudines), here I show that the neuronal scaling rules that apply to these animals can be used to infer the numbers of neurons that composed the telencephalon of dinosaur, pterosaur and other fossil sauropsid species. The key to inferring numbers of telencephalic neurons in these species is first using the relationship between their estimated brain and body mass to determine whether bird-like (endothermic) or squamate-like (ectothermic) rules apply to each fossil sauropsid species. This procedure shows that the notion of “mesothermy” in dinosaurs is an artifact due to the mixing of animals with bird-like and squamate-like scaling, and indicates that theropods such asTyrannosaurusandAllosauruswere endotherms with baboon- and monkey-like numbers of telencephalic neurons, respectively, which would make these animals not only giant but also long-lived and endowed with flexible cognition, and thus even more magnificent predators than previously thought.
Psychophysics with R: The R Package MixedPsy
Authors: Balestrucci Priscilla , Ernst Marc O. , Moscatelli Alessandro
Published: June 2022

Psychophysical methods are widely used in neuroscience to investigate the quantitative relation between a physical property of the world and its perceptual representation provided by the senses. Recent studies introduced the Generalized Linear Mixed Model (GLMM) to fit the responses of multiple participants in psychophysical experiments. Another approach (two-level approach) requires fitting psychometric functions to each individual participant data using a Generalized Linear Model (GLM), and then testing the hypotheses on the multiple participants by means of a second level analysis. For either options, the implementation of the statistical analysis in R is possible and beneficial. Here, we introduce the package MixedPsy to model and fit psychometric data in R, either with two-level and GLMM approaches. The package, freely available in the CRAN repository, uses different methods for the estimation of Point of Subjective Equivalence (PSE) and Just Noticeable Difference (JND), and provides utilities for immediate visualization and plotting of the fitted results. This manuscript aims to provide researchers with a practical tutorial for implementing a complete analysis pipeline for psychophysical data using MixedPsy and other packages and basic functionalities of the R programming environment.
Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience
Authors: Carvalho Joana , Fernandes Francisca F. , Shemesh Noam
Published: June 2022

Understanding the dynamics of stability/plasticity balances during adulthood is pivotal for learning, disease, and recovery from injury. However, the brain-wide topography of sensory remapping remains unknown. Here, using a first-of-its-kind setup for delivering patterned visual stimuli in a rodent Magnetic Resonance Imaging (MRI) scanner, coupled with biologically-inspired computational models, we noninvasively mapped brain-wide properties - receptive fields (RFs) and spatial frequency (SF) tuning curves - that were insofar only available from invasive electrophysiology or optical imaging. We then tracked the RF dynamics in the chronic Visual Deprivation Model (VDM) of plasticity, and found that light exposure progressively promoted a large-scale topographic remapping in adult rats. Upon light exposure, the initially unspecialized visual pathway progressively evidenced sharpened RFs (smaller and more spatially selective) and enhanced spatial frequency tuning curves. Our findings reveal that visual experience following VDM reshapes both structure and function of the visual system and shifts the stability/plasticity balance in adults.
Synthetic Coolant WS-23 increases E-Cigarette Generated Aerosolized Acellular Reactive Oxygen Species (ROS) Levels
Authors: Yogeswaran Shaiesh , Manevski Marko , Chand Hitendra S. , Rahman Irfan
Published: June 2022

There has been a substantial rise in e-cigarette (e-cig) use or vaping in the past decade, prompting growing concerns about their adverse health effects. Recently, e-cig manufacturers have been using synthetic cooling agents, like WS-23 and WS-3, to provide a cooling sensation without the “menthol taste”. Studies have shown that aerosols/vapes generated by e-cigs can contain significant levels of reactive oxygen species (ROS). However, studies investigating the role of synthetic coolants in modulating ROS levels generated by e-cigs are lacking. This study seeks to understand the potential of synthetic coolants, e-cigarette additives that have become increasingly prevalent in e-liquids sold in the United States (US), on acellular ROS production. Aerosols were generated from e-liquids with and without synthetic coolants through a single-puff aerosol generator; subsequently, acellular ROS was semi-quantified in H2O2 equivalents via fluorescence spectroscopy. Our data suggest that adding WS-3 to e-liquid base (PG:VG), regardless of nicotine content, has a minimal impact on modifying e-cigarette-generated acellular ROS levels. Additionally, our data also suggest that the addition of WS-23 to nicotine-containing e-liquid base significantly modifies e-cigarette-generated acellular ROS levels. Together, our data provide insight into whether adding synthetic coolants to e-liquids significantly impacts vaping-induced oxidative stress in the lungs.
The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses
Authors: Tope Parker , Farah Eliya , Ali Rami , El-Zein Mariam , Miller Wilson H. , Franco Eduardo L.
Published: June 2022

Background

The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or ‘lag time’, on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes.

Methods

We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality-(i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval.

Results

We identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported contradictory findings regarding survival outcomes among pediatric patients with Ewing’s sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design.

Conclusions

Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic’s long-term effect on patients with cancer.