bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between central nervous system tumor diagnosis stage and survival and Medicaid enrollment among children, adolescents, and young adults
Authors: Johnson Kimberly J , Brown Derek S , Thompson Tess , Barnes Justin M , King Allison A
Published: October 2024

Background

Medicaid enrollment has been associated with disparities in younger cancer patient survival. To further understand this association for central nervous system (CNS) tumor patients, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid-linked data to examine associations between Medicaid enrollment and enrollment timing and (1) diagnosis stage, and (2) CNS tumor death.

Methods

Individuals diagnosed with a first malignant primary CNS tumor between 0 and 39 years from 2006 to 2013 were included. Medicaid enrollment was first classified as enrolled versus not enrolled with those enrolled further classified as having continuous, discontinuous (at diagnosis or other discontinuous), or other enrollment. We used logistic and Cox Proportional Hazards regression stratified by age to calculate adjusted odds ratios (ORs) and hazard ratios (HRs) for those 0–14 and 15–39 years.

Results

Among 10 107 CNS tumor patients, we found significantly higher odds of regional/distant versus in situ/localized stage diagnoses for those with other discontinuous (OR0–14 = 1.50, 95% CI: 1.15–1.95) and at diagnosis (OR15–39 = 1.41, 95% CI: 1.11–1.78) Medicaid enrollment versus those not enrolled. Those enrolled versus not enrolled in Medicaid had a higher hazard of CNS tumor death for both age groups (HR0–14 = 1.60 95% CI: 1.37–1.86; HR15–39 = 1.50, 95% CI: 1.39–1.62) with the highest hazards for those enrolled at diagnosis (HR0–14 = 1.83, 95% CI: 1.51–2.22; HR15–39 = 1.93, 95% CI: 1.77–2.10).

Conclusions

Medicaid enrollment is associated with a higher risk of CNS tumor death with an almost 2-fold higher risk for young CNS tumor patients enrolled at diagnosis. These results support the critical need for consistent health insurance coverage for young CNS tumor patients.
Ancestral origins and post-admixture adaptive evolution of highland Tajiks
Authors: Wen Jia , Liu Jiaojiao , Feng Qidi , Lu Yan , Yuan Kai , Zhang Xiaoxi , Zhang Chao , Gao Yang , Wang Xiaoji , Mamatyusupu Dolikun , Xu Shuhua
Published: October 2024

It remains debatable how many genes and how various the mechanisms are behind human adaptation to extreme environments, such as high altitudes. Despite extensive studies on Tibetans, Andeans and Ethiopians, new insights are expected to be provided with careful analysis of underrepresented highlanders living in a different geographical region, such as the Tajiks, who reside on the Pamir Plateau at an average altitude exceeding 4000 meters. Moreover, genetic admixture, as we observed in the current whole-genome deep-sequencing study of Xinjiang Tajiks (XJT), offers a unique opportunity to explore how admixture may facilitate adaptation to high-altitude environments. Compared with other extensively studied highlanders, XJT showed pronounced admixture patterns: most of their ancestry are derived from West Eurasians (34.5%–48.3%) and South Asians (21.4%–40.0%), and some minor ancestry from East Asians and Siberians (3.62%–17.5%). The greater genetic diversity in XJT than in their ancestral source populations provides a genetic basis for their adaptation to high-altitude environments. The admixture gain of functional adaptive components from ancestral populations could facilitate adaptation to high-altitude environments. Specifically, admixture-facilitated adaptation was strongly associated with skin-related candidate genes that respond to UV radiation (e.g. HERC2 and BNC2) and cardiovascular-system-related genes (e.g. MPI and BEST1). Notably, no adaptive variants of genes showing outstanding natural selection signatures in the Tibetan or Andean highlanders were identified in XJT, including EPAS1 and EGLN1, indicating that a different set of genes contributed to XJT's survival on the Pamir Plateau, although some genes underlying natural selection in XJT have been previously reported in other highlanders. Our results highlight the unique genetic adaptations in XJT and propose that admixture may play a vital role in facilitating high-altitude adaptation. By introducing and elevating diversity, admixture likely induces novel genetic factors that contribute to the survival of populations in extreme environments like the highlands.
Widening the Price Gap: The Effect of The Netherlands’ 2020 Tax Increase on Tobacco Prices
Authors: Geboers Cloé , Candel Math J J M , van Walbeek Corné , Nagelhout Gera E , de Vries Hein , van den Putte Bas , Fong Geoffrey T , Willemsen Marc C
Published: October 2024

Introduction

The public health impact of a tobacco tax increase depends on the extent to which the industry passes the increase onto consumers, also known as tax-pass through. In 2020, the Netherlands announced tax increases aimed at increasing the retail price by €1 per 20 factory-made (FM) cigarettes and €2.50 per 50 g of roll-your-own (RYO) tobacco. This study examines the pass-through rate after the tax increase, and whether this differed by type of tobacco and brand segment.

Aims and Methods

Self-reported prices of 117 tobacco brand varieties (cigarettes = 72, RYO = 45) pre- and post-tax increases were extracted from the 2020 International Tobacco Control Netherlands Surveys (n = 2959 respondents). We calculated the tax pass-through rate per variant, examining differences between the type of tobacco and brand segments.

Results

On average, cigarette prices increased by €1.12 (SD = 0.49; 112% of €1) and RYO prices by €2.53 (SD = 0.60; 101% of €2.50). Evidence of differential shifting across segments was found, with evidence of overshifting in non-discount varieties. The average price of discount varieties increased by €0.20 less than non-discount varieties. Similarly, the net-of-tax price decreased in discount varieties (cigarettes = −€0.02; RYO = −€0.05), but increased in non-discount varieties (cigarettes = +€0.14; RYO = +€0.20).

Conclusions

Despite the large tax increase, the industry increased prices in line with or above the required level. Through differential shifting, the price gap between discount and non-discount varieties has widened, which may reduce the public health impact of the tax increase. Measures aimed at reducing price variability should be strengthened in taxation policy, such as the European Tobacco Tax Directive (TTD).

Implications

We found that the industry used differential shifting after a significant tobacco tax increase in the Netherlands. Prices increased more than required in higher-priced products, but not in lower-priced products. This pattern was found both for FM cigarettes and RYO tobacco. Through differential shifting, the industry undermines the potential public health impact of tobacco tax increases, by offering a relatively cheaper alternative, which discourages people to quit or reduce consumption. The revision of the European TTD provides an opportunity to address the widening price gap—both between and within product segments—across the European Union.
Cognitive impairment and exploitation: connecting fragments of a bigger picture through data
Authors: Abubakar Aisha M , Seymour Rowland G , Gardner Alison , Lambert Imogen , Fyson Rachel , Wright Nicola
Published: October 2024

Background

Exploitation poses a significant public health concern. This paper highlights ‘jigsaw pieces’ of statistical evidence, indicating cognitive impairment as a pre- or co-existing factor in exploitation.

Methods

We reviewed English Safeguarding Adults Collection (SAC) data and Safeguarding Adults Reviews (SARs) from 2017 to 22. Data relevant to exploitation and cognitive impairment were analysed using summary statistics and ‘analysis of variance’.

Results

Despite estimates suggesting cognitive impairments may be prevalent among people experiencing exploitation in England, national datasets miss opportunities to illuminate this issue. Although SAC data include statistics on support needs and various forms of abuse and exploitation, they lack intersectional data. Significant regional variations in recorded safeguarding investigations and potential conflation between abuse and exploitation also suggest data inconsistencies. Increased safeguarding investigations for people who were not previously in contact with services indicate that adults may be ‘slipping through the net’. SARs, although representing serious cases, provide stronger evidence linking cognitive impairment with risks of exploitation.

Conclusions

This study identifies opportunities to collect detailed information on cognitive impairment and exploitation. The extremely limited quantitative evidence-base could be enhanced using existing data channels to build a more robust picture, as well as improve prevention, identification and response efforts for ‘at-risk’ adults.
Seven insights from Albert Camus’s Plague about epidemics, public health and morality
Authors: Kraaijeveld Steven R
Published: October 2024

For Albert Camus, plague was both a fact of life and a powerful metaphor for the human condition. Camus engaged most explicitly and extensively with the subject of plague in his 1947 novel, The Plague (La peste), which chronicles an outbreak of what is presumably cholera in the French-Algerian city of Oran. I often thought of this novel—and what it might teach us—during the recent COVID-19 pandemic. In this article, I discuss seven important insights from The Plague about epidemics, public health and morality.
How Refugees Conceptualise Success: Grounding Definitions and Examining Heterogeneity
Authors: Bennouna Cyril , Moinester Margot , Stark Lindsay , Lateef Ali , Qushua Najat , Seff Ilana
Published: October 2024

The global refugee system prioritises self-sufficiency as a prime objective, but refugees may have different views of their success. To assess how refugees across varying contexts of exit and reception conceptualise success, this study draws on in-depth interviews with 36 adult refugees from Iraq and Democratic Republic of Congo resettled in Denver, Colorado, and St Louis, Missouri. This article makes four main contributions to the refugee resettlement literature. First, we find that refugees have multidimensional and contextually situated understandings of success that extend beyond self-sufficiency or economic performance. Secondly, when refugees did define success in terms of economic performance, their conceptualisations were more holistic than conventional views of financial independence or social mobility. Thirdly, most refugees defined success in terms of their ability to give back to their extended families and communities—a facet of social connectedness that receives little attention in existing scholarship. Lastly, using these definitions of success, most (89 per cent) participants considered the period of resettlement to be the most successful in their lives. Findings underscore the achievements of refugees but also the limits of resettlement policies and practices that prioritise expedient economic self-sufficiency over the development of strong social ties and sustainable community support systems.
Joint Liability: A Brief History of the Criminalization of Cannabis, Ganja, Marihuana and Marijuana in the Cayman Islands and Pathways towards Legalization or Decriminalization
Authors: Bromby Michael , Awai Ryan Vince
Published: October 2024

This paper chronicles legislative developments in the Cayman Islands regarding the movement towards decriminalizing marijuana use and possession through various legislative measures. The exposition commences with an explanation on the nuanced contrast between decriminalization and full legalization. Subsequently, it delves into the historical evolution of legislation governing marijuana-related offences and offenders. Judicial interpretations arising from these statutory changes are also examined. Additionally, the article critically evaluates the legislative reforms pertaining to the expungement of offences associated with marijuana. Finally, it offers recommendations to address identified statutory anomalies and discrepancies, with a view to establishing a viable legislative framework conducive to achieving the objectives of decriminalization.
Responses in weanling pigs fed low protein diets supplemented with dietary nucleotides
Authors: Lawal Abiola S , Ogunribido Tobi Z , Fu Yuechi , Adeola Olayiwola , Ajuwon Kolapo M
Published: October 2024

Evidence suggests that nucleotide supplementation in diets improves intestinal development, immune function, and cell growth. Stressful events such as weaning in pigs may increase nucleotide demand, making exogenous supplementation potentially beneficial. This study evaluated the effects of low-protein (LP) diets supplemented with dietary nucleotides on growth performance, postweaning diarrhea (PWD), nutrient digestibility, and blood metabolites. A total of 210 piglets were weaned at 21 d of age, allowing a 3-d adaptation to a common nursery diet. At 24 d, pigs were reweighed (6.02 ± 0.05 kg) and allocated to 5 dietary treatments in a randomized complete block design to give 7 replicates per treatment (n = 6 piglets per replicate). The 5 dietary treatments included (i) a high protein positive control diet (PC) with 24% crude protein (CP); (ii) a low protein negative control (NC) with 16% CP; (iii) an NC diet with nucleotide supplementation at 1 g/kg (NC01), 3 g/kg (NC03), or 9 g/kg (NC09). Diets were provided ad libitum for 35 d, and weekly feed intake (FI) and body weight (BW) were recorded. Blood samples were collected on day 32 and fecal samples were collected on days 33, 34, and 35 to determine serum metabolites and nutrient digestibility, respectively. Relative to PC, the NC diet had lower overall average daily gain (ADG) (343.5 vs. 305.5 g/d), incidence of PWD (2.5 vs. 1.2 diarrhea score), and blood urea nitrogen (BUN) (11.3 vs. 3.4 mg/dL); (P < 0.05, < 0.05, and < 0.0001, respectively). The nucleotide-supplemented diets, NC01, NC03, and NC09, had comparable (P > 0.05) overall ADG to the PC and decreased (P < 0.0001) BUN. Additionally, NC09 had decreased (P < 0.05) incidence of PWD compared to PC. The apparent total tract digestibility (ATTD) of nitrogen increased linearly (P < 0.05) with nucleotide supplementation, although reducing CP decreased (P < 0.05) serum glutathione and insulin-like growth factor-1 (IGF-1) concentrations. However, IGF-1 concentration was linearly increased (P < 0.05) with nucleotide supplementation. Results suggest that feeding LP diets supplemented with dietary nucleotides after weaning can increase ATTD of nitrogen and protein utilization, reduce the incidence of PWD, and increase serum IGF-1 concentration while partially ameliorating the negative effects of LP diets on growth performance.
Impacts of gentamycin toxicity: nephroprotective role of guarana through different signaling pathways
Authors: Alkhedaide Adel Qlayel
Published: October 2024

Gentamicin is a widely used aminoglycosidic antibiotic since its discovery. Like any other medication gentamicin causes unwanted side effects such as hepatotoxicity and nephrotoxicity. This study aims to examine the antioxidant effect of the guarana seed extract in protecting renal tissue. Forty male mice were divided into four groups (group one was control with free access to food and water, group two was treated orally with 300 mg/kg of guarana seed extract daily, group three was injected intraperitoneally with 100 mg/kg of gentamicin daily and the fourth group was co-treated with both 300 mg/kg of guarana seed extract orally and injected intraperitoneally with 100 mg/kg of gentamicin daily) for two weeks. Serum levels of urea, creatinine, AST, ALT, IL-1β and IL-6 have significantly elevated in the gentamicin treated group and those changes were not found in the guarana co-treated group. In gentamicin treated mice, a significant reduction was observed in two antioxidants SOD and GPX accompanied by downregulation of Ho-1 and Nrf2 while, that did not happen in the guarana seed extract co-treated group. Histopathology and immunohistochemistry slides show that the guarana seed extract prevents degenerative and necrotic events in tubular epithelial tissues caused by gentamicin toxicity. In conclusion, current data suggest that gentamicin can damage renal tissues when given at 100 mg/kg/day, however, the guarana seed extract may be capable of preventing that event when cotreated with the gentamicin as a supplement.
Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons
Authors: Bendall Emily E , Zhu Yuwei , Fitzsimmons William J , Rolfes Melissa , Mellis Alexandra , Halasa Natasha , Martin Emily T , Grijalva Carlos G , Talbot H Keipp , Lauring Adam S
Published: October 2024

While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at <2% frequency. Children (0–5 years) had marginally higher within-host evolutionary rates than adolescents (6–18 years) and adults (>18 years, 4.4 × 10−6 vs. 9.42 × 10−7 and 3.45 × 10−6, P < .001). Forty-five iSNVs had evidence of parallel evolution but were not over-represented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNVs across segments. A Wright–Fisher approximate Bayesian computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to genetic drift and purifying selection, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected.
Screening Characteristics of Hemoglobin and Mean Corpuscular Volume for Detection of Iron Deficiency in Pregnancy
Authors: Chao Hui Xiao , Zack Travis , Leavitt Andrew D.
Published: October 2024

Iron deficiency in pregnancy remains underdiagnosed despite professional society recommendations for first-trimester complete blood count (CBC) screening. To determine the effectiveness of the CBC hemoglobin and mean corpuscular volume (MCV) to identify iron deficiency in pregnancy, we conducted a retrospective analysis of 20,550 pregnancies from 2009 to 2022 at the University of California, San Francisco, obstetrics clinics. A total of 16,547 (80.5%) pregnant individuals had first-trimester screening CBC; 345 (2.1%) had a coincident ferritin test. Hemoglobin level less than 11 g/dL and MCV level less than 80 fL each had sensitivity of only 30% (95% CI, 20–41%) to detect first-trimester iron deficiency (ferritin level less than 30), corresponding to a negative likelihood ratio of 0.90 (95% CI, 0.77–1.05) and 0.85 (95% CI, 0.73–0.99), respectively. More than 50% of the 1,749 women with documented iron deficiency anytime during pregnancy were neither anemic nor microcytic at the time of diagnosis.
Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma
Authors: Paolino Giovanni , Podo Brunetti Antonio , De Rosa Carolina , Cantisani Carmen , Rongioletti Franco , Carugno Andrea , Zerbinati Nicola , Valenti Mario , Mascagni Domenico , Tosti Giulio , Mercuri Santo Raffaele , Pampena Riccardo
Published: October 2024

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM’s diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.
Mortality Patterns of Esophageal Cancer in the United States
Authors: Kamal Usama Hussain , Jamil Adeena , Fatima Eeshal , Khurram Abiha , Khan Zoha , Kamdi Zainab Anwar , Ahmed Sana , Farooq Muhammad Zain , Jaglal Michael
Published: October 2024

Objectives:

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths in the United States, with a mere 20% survival rate in the first 5 years, making it a significant public health concern. Considering the lack of comprehensive evaluations of mortality trends, this study aims to provide an update on the mortality rates of esophageal cancer and its trends in the United States.

Methods:

The mortality trends among adults with EC were analyzed using data from the CDC WONDER database. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs with 95% CI were obtained using joinpoint regression analysis across different demographic (sex, race/ethnicity, and age) and geographic (state, urban-rural, and regional) subgroups.

Results:

Between 1999 and 2020, 309,725 documented deaths were attributed to esophageal cancer. The overall AAMR decreased from 1999 to 2020 (6.69 to 5.68). Males had higher consistently higher AAMRs than females (10.96 vs. 2.24). NH White had the highest overall AAMR (6.88), followed by NH Black (6.46), NH American Indian (4.95), Hispanic or Latino (3.31), and NH Asian or Pacific Islander (2.57). AAMR also varied by region (overall AAMR: Midwest: 7.18; Northeast: 6.75; South: 6.07; West: 5.76), and nonmetropolitan areas had higher AAMR (non-core areas: 7.09; micropolitan areas: 7.19) than metropolitan areas (large central metropolitan areas: 5.75; large fringe areas: 6.33). The states in the upper 90th percentile of esophageal cancer-related AAMR were Vermont, District of Columbia, West Virginia, Ohio, New Hampshire, and Maine, and exhibited an approximately two-fold increase in AAMRs, compared with states falling in the lower 10th percentile.

Conclusions:

Over the last 2 decades, there has been an overall decline in mortality related to EC in the United States. However, demographic and geographic discrepancies in EC-related mortality persist, necessitating additional exploration and development of specifically directed treatments.
Aftercare following second trimester abortion procedures
Authors: Spach Natalie C. , Henkel Andrea
Published: October 2024

Purpose of review

The purpose of this review is to examine patient experiences following second-trimester abortion care to identify clinical interventions to improve aftercare.

Recent findings

Early validation of a five-question Reproductive Grief Screen suggests that this instrument may be useful for clinicians to identify patients with maladaptive grief responses following a second-trimester abortion. Patients want to talk with their healthcare providers about grief following abortion and desire frequent mental health check-ins. Most people will have breast symptoms following a second-trimester abortion; a one-time dose of cabergoline at time of abortion appears to be an effective intervention to prevent bothersome breast symptoms. As patient desires vary regarding disposition of fetal remains, clinicians should be prepared to discuss donation for research or cremation/ burial as alternatives to routine disposal. With significant variation in availability and cost of ceremonial disposition, clinicians and healthcare systems should identify local resources to facilitate this aspect of aftercare.

Clinical practices and healthcare systems should prioritize the aftercare experience including the management of breast symptoms, bereavement, disposition of fetal remains, and follow-up care.
Rh sensitization in abortion care: where we’ve been and where we’re going
Authors: Amaya Stephanie I. , Cahill Erica , Blumenthal Paul D.
Published: October 2024

Purpose of review

The purpose of this review is to summarize the historical context and recent literature that contribute to the debate about preventive strategies for Rhesus (Rh)-alloimmunization in abortion are.

Recent findings

Recent studies repeatedly demonstrate that the risk of Rh-alloimmunization in first trimester abortion care is very low.

Recent high-quality studies have demonstrated the physiologic presence of fetal red blood cells in maternal circulation even prior to abortion. Thus, establishing the low utility of Rh immunoglobulin prior to abortion before 12 weeks of gestation. There is yet to exist a consensus guideline that balances the desire to prevent a rare devastating outcome and the need to create practical guidelines based on evidence-based risk assessments.
Biologic grafts for pelvic organ prolapse repairs: what have we learned in the last 20 years?
Authors: Lorente Karla , Chang Olivia
Published: October 2024

Purpose of review

The ideal graft material for the augmentation of pelvic organ prolapse (POP) has yet to be discovered. While synthetic mesh offers durable repairs this can be at the expense of mesh complications. Biologic grafts have been considered an alternative. This chapter reviews biologic graft materials as applied to POP surgery.

Recent findings

The heterogeneity of available graft materials and definitions of success in POP literature make comparisons difficult. There may be utility in the augmentation of apical prolapse with autologous grafts. There is also modest evidence to support anterior wall augmentation with biologic grafts. However, a 2024 Cochrane review concluded there is not enough evidence to support routine use of grafts for transvaginal repairs.

Biologic grafts can be considered in certain cases. There continues to be a need for finding the ideal “graft-patient” combination. The field particularly needs more robust research in the recurrent POP patient population.
A review of ethnic disparities in preeclampsia
Authors: Raphael Katie , Wiles Kate , Iliodromiti Stamatina , Greco Elena
Published: October 2024

Purpose of review

Recent reports have reiterated the inequities in maternal morbidity and mortality for minority ethnic groups, with preeclampsia being a significant concern. Females of Black and South Asian ethnicity have an increased risk of preeclampsia with disproportionately higher adverse outcomes compared to white females.

Recent findings

This review will explore ethnic disparities in preeclampsia outcomes, prediction, diagnosis, prevention and management. Recent evidence has demonstrated that biochemical and biophysical markers that are used for preeclampsia prediction and diagnosis vary for females of different ethnic groups. This needs careful consideration given the current need for accurate prediction models. Furthermore, recent reports have highlighted the disparity in maternal morbidity for those of minority ethnic groups. The reasons for this are multifactorial but underlying biases and racism have been attributed as major contributors to poor care and adverse outcomes.

Exploring disparities in preeclampsia care is essential to address ethnic inequities that lead to increased adverse outcomes. We must alter current clinical practice to break down the barriers that result in substandard care for females from minority ethnic backgrounds.
Chimeric antigen receptor-T-cell therapies going viral: latent and incidental viral infections
Authors: Kampouri Eleftheria , Reynolds Gemma , Teh Benjamin W. , Hill Joshua A.
Published: October 2024

Purpose of review

Infections are the leading cause of non-relapse mortality following chimeric antigen receptor (CAR)-T-cell therapy, with viral infections being frequent both in the early and late phases post-infusion. We review the epidemiology of viral infections and discuss critical approaches to prevention and management strategies in this setting.

Recent findings

Herpesviruses dominate the early period. herpes simplex virus and varicella zoster virus infections are rare due to widespread antiviral prophylaxis, but cytomegalovirus (CMV) reactivation is increasingly observed, particularly in high-risk groups including B cell maturation antigen (BCMA)-CAR-T-cell therapy recipients and patients receiving corticosteroids. While CMV end-organ disease is rare, CMV is associated with increased mortality, emphasizing the need to evaluate the broader impact of CMV on long-term hematological, infection, and survival outcomes. Human herpesvirus-6 (HHV-6) has also emerged as a concern, with its diagnosis complicated by overlapping symptoms with neurotoxicity, underscoring the importance of considering viral encephalitis in differential diagnoses. Respiratory viruses are the most common late infections with a higher incidence after BCMA CAR-T-cell therapy. Vaccination remains a critical preventive measure against respiratory viruses but may be less immunogenic following CAR-T-cell therapy. The optimal timing, type of vaccine, and dosing schedule require further investigation.

A better understanding of viral epidemiology and preventive trials are needed to improve infection prevention practices and outcomes following CAR-T-cell therapies.
Density Spectral Array EEG for Sleep Staging in Pediatric Patients
Authors: Rudock Robert J. , Turner Ashley D. , Binkley Michael , Landre Rebekah , Morrissey Michael J. , Tomko Stuart R. , Guerriero Réjean M.
Published: October 2024

Purpose:

Sleep is an essential physiologic process, which is frequently disrupted in children with illness and/or injury. Accurate identification and quantification of sleep may provide insights to improve long-term clinical outcomes. Traditionally, however, the identification of sleep stages has relied on the resource-intensive and time-consuming gold standard polysomnogram. We sought to use limited EEG data, converted into density spectrum array EEG, to accurately identify sleep stages in a clinical pediatric population.

Methods:

We reviewed 87 clinically indicated pediatric polysomnographic studies with concurrent full montage EEG, between March 2017 and June 2020, of which 11 had normal polysomnogram and EEG interpretations. We then converted the EEG data of those normal studies into density spectral array EEG trends and had five blinded raters classify sleep stage (wakefulness, nonrapid eye movement [NREM] 1, NREM 2, NREM 3, and rapid eye movement) in 5-minute epochs. We compared the classified sleep stages from density spectral array EEG to the gold standard polysomnogram.

Results:

Inter-rater reliability was highest (κ = 0.745, P < 0.0001) when classifying state into wakefulness, NREM sleep, and rapid eye movement sleep. Agreement between group classification and polysomnogram was highest (κ = 0.873, [0.819, 0.926], P < 0.0001) when state was classified into wakefulness and sleep and was lowest (κ = 0.674 [0.645, 0.703], P < 0.0001) when classified into wakefulness, NREM 1, NREM 2, NREM 3, and rapid eye movement. The most common error that raters made was overscoring of NREM 1.

Conclusions:

Density spectral array EEG can be used to identify sleep stages in clinical pediatric patients without relying on traditional polysomnography.
Abf1 negatively regulates the expression of EPA1 and affects adhesion in Candida glabrata
Authors: Hernández-Hernández Grecia , Vera-Salazar Laura A. , Gutiérrez-Escobedo Guadalupe , Gómez-Hernández Nicolás , Leiva-Peláez Osney , De Las Peñas Alejandro , Castaño Irene
Published: October 2024

Introduction. Adherence is a major virulence trait in Candida glabrata that, in many strains, depends on the EPA (epithelial adhesin) genes, which confer the ability to adhere to epithelial and endothelial cells of the host. The EPA genes are generally found at subtelomeric regions, which makes them subject to subtelomeric silencing. In C. glabrata, subtelomeric silencing depends on different protein complexes, such as silent information regulator and yKu complexes, and other proteins, such as Repressor/activator protein 1 (Rap1) and Abf1. At the EPA1 locus, which encodes the main adhesin Epa1, we previously found at least two cis-acting elements, the protosilencer Sil2126 and the negative element, that contribute to the propagation of silencing from the telomere to the subtelomeric region.

Hypothesis. Abf1 binds to the regulatory regions of EPA1 and other regions at the telomere E-R, thereby negatively regulating EPA1 transcription.

Aim. To determine whether Abf1 and Rap1 silencing proteins bind to previously identified cis-acting elements on the right telomere of chromosome E (E-R subtelomeric region), resulting in negative regulation of EPA1 transcription and infer Abf1 and Rap1 recognition sites in C. glabrata.

Methodology. We used chromatin immunoprecipitation (ChIP) followed by quantitative PCR to determine the binding sites for Abf1 and Rap1 in the intergenic regions between EPA1 and EPA2 and HYR1 and EPA1, and mutants were used to determine the silencing level of the EPA1 promoter region.

Results. We found that Abf1 predominantly binds to the EPA1 promoter region, leading to negative regulation of EPA1 expression. Furthermore, the mutant abf1-43, which lacks the last 43 amino acids at its C-terminal end and is defective for subtelomeric silencing, exhibits hyperadherence to epithelial cells in vitro compared to the parental strain, suggesting that EPA1 is derepressed. We also determined the motif-binding sequences for Abf1 and Rap1 in C. glabrata using data from the ChIP assays.

Conclusion. Together these data indicate that Abf1 negatively regulates EPA1 expression, leading to decreased adhesion of C. glabrata to epithelial cells.
Targeting Neuropilin-1 to Enhance Immunotherapy in Melanoma: Reducing Peripheral Treg-Mediated Immunosuppression and Tumour Progression
Authors: Khamaru Somlata , Tung Kshyama Subhadarsini , Chattopadhyay Subhasis
Published: October 2024

Melanoma, the most aggressive type of skin cancer with a high mutation rate, is the fifth most common cancer among Caucasians. Despite advancements in treatments like immune checkpoint inhibitors and targeted therapies, over 40% of patients experience immune-related side effects, presenting significant challenges. Neuropilin-1 (NRP1) has become an essential target in cancer therapy due to its overexpression in various cancers, where it enhances regulatory T cell (Treg) function and supports tumor growth, often leading to poor outcomes.

This study investigated the effects of NRP1 inhibition in B16-F10 melanoma and its impact on immune responses regulated by Tregs. NRP1 was overexpressed in several cancers, including B16-F10 cells, compared to non-cancerous NIH-3T3 cells. Inhibiting NRP1 selectively caused apoptosis in B16-F10 cells without affecting NIH-3T3 cells. It also reversed the immunosuppression of splenic T cells induced by B16-F10-conditioned media, reducing Treg markers (NRP1, NKG2A, FOXP3), Treg activity, and the production of immunosuppressive cytokines (IL-10, IL-17A). Furthermore, NRP1 inhibition increased T cell proliferation and boosted the release of effector cytokines (TNF, IFN-γ, IL-6, IL-2). NRP1 inhibition also suppressed the STAT, ERK MAPK, and Smad2/3 pathways while activating the PI3K/AKT pathway. In splenic T cells from B16-F10 tumor-bearing mice treated with an NRP1 inhibitor, there was a decrease in Treg markers and activity, along with enhanced T cell proliferation. Additionally, NRP1 inhibitor treatment reduced lung metastasis, decreased tumor size, and improved survival in these mice.

This study shows that inhibiting NRP1 may slow B16-F10 melanoma progression and reduce Treg-mediated immunosuppression. This suggests its potential as a promising approach in future cancer immunotherapies, especially in combination with other treatments.
Unwrapping the ciliary coat: high-resolution structure and function of the ciliary glycocalyx
Authors: Hoepfner Lara M. , Nievergelt Adrian P. , Matrino Fabrizio , Scholz Martin , Foster Helen E. , Rodenfels Jonathan , von Appen Alexander , Hippler Michael , Pigino Gaia
Published: October 2024

The glycocalyx, a highly heterogeneous glycoprotein layer of cilia regulates adhesion and force transduction, and is involved in signalling. The high-resolution molecular architecture of this layer is currently not understood. We describe the structure of the ciliary coat in the green algaChlamydomonas reinhardtiiby cryo-electron tomography and proteomic approaches and present the high-resolution cryoEM structure of the main component, FMG1B. We describe FMG1B as a mucin orthologue which lacks the majorO-glycosylation of mammalian mucins, but isN-glycosylated. FMG1A, a previously undescribed isoform of FMG1B is expressed inC. reinhardtii. By microflow-based adhesion assays we observe increased surface adhesion in the glycocalyx deficient double-mutantfmg1a-fmg1b. We find this mutant to be capable of surface-gliding, with neither isoform required for extracellular force transduction by intraflagellar transport. Our results find FMG1 to form a protective layer with adhesion-regulative instead of adhesion-conferring properties and an example of an undescribed class of mucins.
Association between SARS-CoV-2 and Stroke: Perspectives from a metaumbrella-review
Authors: Baldo de Souza Andreza Maria Luzia , de Araújo Enoque Fernandes , Carvas Nelson , Raimundo Augusto César , Pereira Antonio Carlos , de Castro Meneghim Marcelo
Published: October 2024

In the face of the global COVID-19 pandemic, the need arose to investigate potential complications associated with SARS-CoV-2, including the risk of Stroke.

Objective

This study aimed to verify the association between SARS-CoV-2 and the risk of Stroke, based on systematic reviews and meta-analyses, in order to assess the inclusion of the virus as a new risk factor for cerebrovascular diseases.

Methods

A metaumbrella was conducted, which included 34 systematic reviews, of which 4 were selected for the final analysis based on methodological quality and consistency. The analysis aggregated the results of 70 primary studies, considering different stroke subtypes and outcomes associated with COVID-19. Study heterogeneity was assessed using the I² index, and significance bias was verified using Egger’s test.

Results

The analysis showed that the severity of COVID-19 is significantly associated with an increased risk of stroke (eOR = 2.48; 95%CI: 1.55 – 3.95), particularly for ischemic stroke (eOR = 1.76; 95%CI: 1.11 – 2.80) and hemorrhagic stroke (eOR = 3.86; 95%CI: 1.79 – 8.33). Additionally, patients with cerebrovascular comorbidities had higher mortality (eOR = 2.48; 95%CI: 2.48 – 19.63), as did those who had previously suffered a stroke (eOR = 6.08; 95%CI: 3.73 – 9.91).

Conclusion

The association between SARS-CoV-2 and stroke was consistent and significant, suggesting that COVID-19 should be considered a new risk factor for cerebrovascular diseases. However, the high heterogeneity among the studies analyzed reinforces the need for further research to consolidate this relationship.
Causal links between mitophagy and Alzheimer’s disease: a Mendelian randomization study
Authors: Zhang Weijian , Chen Wenjia , Guo Zhendong , Li Hui
Published: October 2024

Background

Emerging evidence highlights the dysregulation of mitophagy, the process of clearing damaged mitochondria, as a potential contributor to Alzheimer’s disease (AD) pathology. However, the precise mechanisms linking mitophagy to AD remain poorly understood. This study utilized summary-data-based Mendelian Randomization (SMR) combined with multi-omics data to explore the causal relationships between them, and to uncover potential epigenetic mechanisms of gene regulation.

Methods

Mitophagy-related genes were identified through the integration of three databases, and transcriptomic data of AD patients were obtained from the Gene Expression Omnibus (GEO) database. A meta-analysis was conducted to recognize differentially expressed genes (DEGs) associated with mitophagy in AD. Through SMR tools, genome-wide association study (GWAS) summary data of AD from the GWAS Catalog (n=487,511) were separately integrated with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from blood and brain tissues to identify potentially causal genes and methylation sites. The findings from primary analysis were validated with data from the UK Biobank (n=301,478).

Results

In total, 111 mitophagy-related genes were found to be differentially expressed in AD. The three-step SMR analysis identified two genes, PARL and BCL2L1, from blood tissues and three genes, ATG13, TOMM22, and SPATA33, from brain tissues as causal candidate genes associated with AD. The analysis pinpointed the possible epigenetic mechanisms, where specific methylation sites regulate the expression of these genes, potentially contributing to their association with AD. All findings were successfully replicated in UK Biobank cohorts.

Conclusions

The study emphasized the putatively causal relationships of mitophagy-related gene with AD. These underlying pathogenic mechanisms could pave the way for new approaches in early detection and therapeutic intervention for AD.
Soft X-ray tomography reveals variations inB.subtilisbiofilm structure upontasAdeletion
Authors: Chatzimpinou Anthoula , Diehl Anne , Harhoff A. Tobias , Driller Kristina , Vanslembrouck Bieke , Chen Jian-Hua , Kairiss Kristaps , Loconte Valentina , Le Gros Mark A , Larabell Carolyn , Turgay Kürşad , Oschkinat Hartmut , Weinhardt Venera
Published: October 2024

Bacterial biofilms are complex communities of cells within a self-produced extracellular matrix. They play crucial roles in healthcare, nutrition, agriculture and environmental research, yet an analysis of their elaborate 3D architecture remains challenging. Understanding mechanisms of biofilm formation, particularly the effects of chemical, physical, and genetic influences or modifications, is crucial but requires structural information at subcellular resolution to enable a community-level analysis of biofilms. In this work, we developed a “biofilm-in-capillary” growth method compatible with full-rotation soft X-ray tomography, providing high-resolution 3D imaging of bacterial cells and their surrounding extracellular matrix during biofilm formation, without drying or fixation steps. This approach offers 50 nm isotropic spatial resolution, rapid imaging time, and quantitative native analysis of biofilm structure. We demonstrate the potential of our method usingBacillus subtilisbiofilms, detecting coherent alignment and chaining of wild-type cells while they are travelling towards the oxygen-rich capillary tip region. In stark contrast, the genetic knock-out ΔtasAshows a loss of cellular orientation, including changes in the extracellular matrix in volume and chemical density. Notably, we show that the addition of TasA protein to a culture of a ΔtasAstrain restores the extracellular matrix density and leads to a compaction of cell assemblies, yet no chaining is observed as for the wildtype. Our approach to imaging biofilms is scalable and transferable, opening new avenues for examining biofilm structure and function across various species, including mixed biofilms, and observing 3D reorganization in response to genetic and environmental factors.
Partially Shared Multi-Modal Embedding Learns Holistic Representation of Cell State
Authors: Zhang Xinyi , Shivashankar GV , Uhler Caroline
Published: October 2024

Experimental technologies for jointly measuring different data modalities at the single-cell level offer different windows into cell state. To obtain a holistic understanding of cell state, computational methods are needed that carefully integrate the different views to capture shared information as well as tease apart modality-specific information. We present a computational framework that automatically learns partial information sharing between multiple modalities by using anAutoencoder with aPartiallyOverlappingLatent space learned throughLatentOptimization (APOLLO). On paired scRNA-seq and scATAC-seq data (SHARE-seq) and paired scRNA-seq and surface protein data (CITE-seq), we demonstrate that APOLLO comprehensively and automatically identifies and distinguishes between information captured by both modalities, in the shared latent space, and modality-specific information. Beyond sequencing modalities, large-scale multiplexed single-cell imaging datasets, such as the Human Protein Atlas, are becoming available that allow studying how protein localization relates to function. While chromatin, microtubules or ER are standardly stained as a reference, little is known about the information shared between these stains. We found that APOLLO enables the prediction of missing modalities, such as unmeasured protein stains, and allows disentangling which modality or cellular compartment is linked with a specific phenotype, such as the variability in protein localization observed across single cells. Collectively, APOLLO enables explicit learning of shared and modality-specific information leading to a more holistic understanding of cell state and the underlying regulatory mechanisms. APOLLO is a general framework that can be applied to any multi-modal data well beyond the single-cell domain including, for example, large-scale medical biobanks.
ADrosophilascreen of schizophrenia-related genes highlights the requirement of neural and glial matrix metalloproteinases for neuronal remodeling
Authors: Keret Shir , Meltzer Hagar , Marmor-Kollet Neta , Schuldiner Oren
Published: October 2024

Schizophrenia (SCZ) is a multifactorial neuropsychiatric disorder of complex and mostly unknown etiology, affected by genetic, developmental and environmental factors. Neuroanatomical abnormalities, such as loss of grey matter, are apparent prior to the onset of symptoms, suggesting neurodevelopmental origin. Indeed, it has been hypothesized, and recently experimentally supported, that SCZ is associated with dysregulation of developmental synaptic pruning. Here, we explore the molecular link between SCZ-associated genes and developmental neuronal remodeling, focusing on theDrosophilamushroom body (MB), which undergoes stereotypic remodeling during metamorphosis. We conducted a loss-of-function screen in which we knocked downDrosophilahomologs of human genes that genomic studies have associated with SCZ. Out of our ‘positive hits’, we focused on matrix metalloproteinases (MMPs), mostly known for their role in remodeling of the extracellular matrix. We found that both Mmp1 and Mmp2, which are closely-related to mammalian MMPs, are required in neurons and in glia for the pruning of MB axons. Our combinatorial loss-of-function experiments suggest that Mmp2 secretion from glia is the most important promoter of axon pruning. Our results shed new light on potential molecular players underlying neurodevelopmental defects in SCZ and highlight the advantage of genetically tractable model organisms in the study of human neurodevelopmental disorders.