bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Topical 0.05% Cyclosporine A Eye Drops on Post–Femtosecond-Assisted Laser In Situ Keratomileusis Ocular Surface Recovery: A Randomized Clinical Trial
Authors: Zhao Lu , Duan Hongyu , Ma Baikai , Yang Tingting , Zhou Yifan , Liu Yilin , Chen Jiawei , Chen Yueguo , Qi Hong
Published: June 2024

Objectives:

To investigate the effect of topical 0.05% cyclosporine A (CsA) eye drops as an adjunct to conventional therapy in maintaining post–femtosecond-assisted laser in situ keratomileusis (FS-LASIK) ocular surface stability.

Methods:

Sixty-six patients (eyes) undergoing FS-LASIK were randomized into 2 groups: 33 patients (eyes) in group I (conventional treatment group) and 33 patients (eyes) in group II (CsA group). Conventional treatments include topical levofloxacin, fluorometholone, and artificial tears. Group II received topical 0.05% CsA eye drops twice daily for three months in addition to conventional treatment. Ocular Surface Disease Index (OSDI), numerical rating scale (NRS), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), conjunctival lissamine green (LG) staining, corneal sensitivity, and corneal nerve morphology were measured. In addition, tear inflammatory cytokine levels were measured using the Luminex assay. Follow-up was performed preoperatively and 1 and 3 months postoperatively.

Results:

In the CsA group, OSDI, TBUT, LG, corneal sensitivity, and corneal nerve fiber total branch density recovered better than in the conventional treatment group. As for tear inflammatory cytokines, interferon (INF) -γ, interleukin (IL)-10, and IL-6 levels were significantly higher in the conventional treatment group as compared with the CsA group. In addition, no significant differences in NRS, SIt, and CFS scores were observed between the two groups.

Conclusion:

In conclusion, 0.05% CsA eye drops is a useful adjunct to conventional treatment for restoring the ocular surface stability after corneal refractive surgery and is more potent in sustaining anti-inflammatory effects.
Losartan May Not Prevent Vestibular Schwannoma Growth or Related Hearing Loss During Observation
Authors: Lovin Benjamin D. , Nader Marc-Elie , Qing Yun , Hernandez Mike , Raza Shaan , DeMonte Franco , Gidley Paul W.
Published: June 2024

Objective

To evaluate the impact of losartan on vestibular schwannoma (VS) growth and related hearing loss during observation.

Study design

Retrospective cohort study

Setting

Tertiary referral center

Patients

Sporadic VS patients undergoing initial observation with at least two magnetic resonance imaging and audiologic examinations.

Intervention

Losartan

Main Outcome Measures

Endpoints included VS growth, quantitative audiologic changes, survival free of tumor growth, and survival free of nonserviceable hearing. Patient characteristics and endpoints were compared by losartan use.

Results

Seventy-nine patients were included, of which 33% were taking losartan. Tumor growth was observed in 50% of patients in the losartan group and 36% in the non-losartan group (p = 0.329). Survival analysis failed to show a significant difference in the hazard rate of VS growth between groups (hazard ratio, 1.38; 95% confidence interval, 0.70–2.70; p = 0.346). Throughout observation, mean decreases in normalized pure-tone average were 5.5 and 9.3 dB in the losartan and non-losartan groups, respectively (p = 0.908). Mean decreases in normalized word recognition score were 11.0 and 16.6% in the losartan and non-losartan groups, respectively (p = 0.757). Nonserviceable hearing developed in 19% of patients in the losartan group and 28% in the non-losartan group (p = 0.734). Survival analysis did not demonstrate a significant difference in the hazard rate of developing nonserviceable hearing between groups (hazard ratio, 1.71; 95% confidence interval, 0.56–5.21; p = 0.337).

Conclusions

Losartan use may not reduce the risk of VS growth or hearing loss during observation. A randomized trial would be ideal to further identify the true effect on growth and hearing.
Clinical efficacy of TEVAR utilizing fenestrated stent-grafts for zone 0 in an elderly frail patient with giant aortic arch aneurysm
Authors: Kurobe Hirotsugu , Hori Takaki , Fujita Hiroshi , Higaki Tomohide , Fukunishi Takuma , Sogabe Hitoshi , Izutani Hironori
Published: June 2024

Introduction and importance:

Elderly and frail patients with thoracic aortic aneurysms (TAAs) near to origins of cervical arteries present facing challenges with aortic arch replacement with cardiopulmonary bypass, and traditional tube-type stent-grafts are also inadequate for transcatheter endovascular aortic repair (TEVAR). Thus, necessitating precise treatment with fenestrated stent-grafts from zone 0. This approach is crucial for achieving favorable postoperative outcomes without compromising activities of daily living (ADL).

Case presentations:

An 85-year-old-man admitted to the hospital for treatment of a large TAA. While arch replacement is a definitive procedure, it is highly invasive, and the postoperative ADL are expected to be significantly lower than preoperative levels. Therefore, we performed a debranching TEVAR from Zone 0 with fenestrated stent-graft. The patient was discharged from the hospital on the 11th postoperative day.

Clinical discussion:

In frail and elderly patients for whom conventional surgery may not be viable, TEVAR emerges as a preferred alternative. However, TEVAR of TAA proximal to the aortic arch continues to pose challenges, necessitating meticulous attention to the cervical branches in the intervention strategy. While surgical intervention in these patients necessitates careful consideration of its suitability, including the potential for postoperative enhancement in ADL, the use of fenestrated stent-grafts from Zone 0 emerges as one of the treatment modalities.

Conclusion:

The authors present a very elderly case in which fenestrated stent-grafts were used to avoid aortic arch replacement for a large aortic arch aneurysm, resulting in a good postoperative course with no decline in ADL.
The Impact of Frailty on Chemotherapy Outcomes in Patients With Digestive System Tumors
Authors: Xu Weiyan , Yang Hailing , Li Weihua , Wang Yaqian , Zhang Xu , Chen Yuanyuan
Published: June 2024

Background

The prevalence of patients with digestive system tumors has been high. In recent years, frailty has been considered to be associated with poor prognosis of digestive system tumors, but there are conflicting research results. A better understanding of the relationship between frailty and outcomes after chemotherapy can help advance the development of oncology care.

Objective

The aim of this study was to evaluate the effects of prechemotherapy frailty on chemotherapy toxicity, overall mortality, unplanned hospitalization, and overall survival in patients with digestive system tumors.

Methods

Up to April 2023, observational studies assessing the impact of frailty on chemotherapy outcomes in patients with digestive system tumors were collected through searching 10 online research databases. Two evaluators independently extracted literature based on the inclusion and exclusion criteria and evaluated the quality of the studies using the Newcastle-Ottawa Scale.

Results

Eventually, 11 cohort studies encompassing 2380 patients were included. The meta-analysis revealed that the frail group exhibited an increased risk of overall mortality, with poorer overall survival than the nonfrail group.

Conclusion

Frailty increases the risk of chemotherapy-induced toxic effects, unplanned hospitalization, and death in patients. However, because of this study’s limited number of participants, large-sample, multicenter studies to verify these findings are required.

Implications for Practice

This study provides theoretical support for incorporating frailty assessment into the nursing evaluation of patients with digestive system tumors before chemotherapy. This integration aids in predicting patients at a high risk of chemotherapy toxicity, mortality, and unplanned hospitalization, therefore providing corresponding interventions in advance to reduce adverse outcomes.
Increasing Access to Cardiac Rehabilitation Services Among Disadvantaged Populations
Authors: Murphy Caitlin , Carter Ernest , Thomas Laurine , Stokes Twarnisha , Thomas Priscilla , Lichty-Hess Judy A. , Amuta Augustine , Zare Hossein , Gaskin Darrell
Published: June 2024

The Prince George’s County Health Department encountered several challenges to increasing access to cardiac rehabilitation (CR) services among disadvantaged populations. They include excessive patient out-of-pocket costs; requirements that CR orders must be signed by a physician; provider reluctance to refer patients to CR, with most primary care providers preferring to refer clients to cardiologists for the latter to determine whether the patient needs CR referral; limited availability of CR programs; and difficulty identifying patients eligible for CR services. Discussions with other local health departments and public health practitioners indicate that these challenges are not unique to Maryland but are indicative of policy and system barriers that prevent the optimal delivery of cardiovascular health services. This practice report documents the challenges and the Prince George’s County Health Department’s efforts to resolve them and provides recommendations for decision-makers seeking to make CR programs more accessible to disadvantaged populations.
The Critical Role of Health Educators: Findings from the 2021 Public Health Workforce Interests and Needs Survey (PH WINS)
Authors: Escoffery Cam , Auld M. Elaine , Arana Mayela , Ravenhall Sarah
Published: June 2024

Objective:

This analysis of governmental health educators from the 2021 Public Health Workforce Interest and Needs Survey (PH WINS) examines demographic and workplace characteristics, COVID-19 pandemic activities and beliefs, job satisfaction, training needs, mental health, and engagement in health equity.

Setting and Participants:

Participants were public health staff in public health agencies who completed the 2021 PH WINS.

Design and Main Outcome Measures:

Chi-square and means tests were used to compare job satisfaction, mental health status, training needs, and health equity concepts between health educators and other disciplines in the governmental public health workforce.

Results:

Like PH WINS 2017 findings, health educators were significantly younger, more likely to be female, more diverse, and more likely to work in regional/local health departments than the national governmental public health workforce. About 70% of health educators played a role in responding to the pandemic. Only 46.1% of health educators rated their mental health as excellent or very good as compared to 48.2% of other disciplines. About 31% considered leaving the organization due to stress, unsatisfactory opportunities, and lack of mentoring. Health educators expressed the need for training in financial and change management. Both health educators and other governmental workers expressed high levels of awareness of and confidence in addressing social determinants of health and health equity, but less confidence in addressing environmental justice. Certified health education specialists (CHES(R)) were significantly more likely to be aware of concepts of health equity, social determinants of health (SDOH), and structural racism than non-CHES(R).

Conclusion:

Overall, the training needs and job satisfaction of health educators changed little between the two surveys. However, COVID-19 had a significantly greater impact on their mental health status compared to other public health disciplines. They also are addressing racism in their communities and are more aware of health equity concepts than other public health disciplines. Implications for strengthening public health infrastructure, as well as recruitment/retention, professional preparation, and practice are provided.
Maintaining and Improving Virtual Call Centers for Public Health: The CUNY Recovery Corps Experience
Authors: Sharma Srividhya , El-Alfi Valerie , Greene Danielle
Published: June 2024

Context:

In the early stages of the COVID-19 pandemic in New York City, individuals who tested positive, exposed contacts, and their families faced significant challenges in accessing essential resources for successful quarantine and isolation. These resources included alternative housing, food access, grocery delivery, missed wage assistance, transportation for household members, medical care, and more.

Program:

The City University of New York (CUNY) Recovery Corps emerged as an innovative virtual resource navigation service to connect New Yorkers to essential resources and later to vaccinations, treatment, and services for Long COVID. The program prioritized reaching people living in underserved and under-resourced neighborhoods. Over 3 years, it made a substantial impact, reaching 374 728 New Yorkers and connecting 135 147 to crucial resources.

Implementation:

Implementing a successful virtual navigation center amidst a global pandemic posed unique challenges. It required well-established systems to provide services, manage staff, build community, and both assure and improve service quality.

Evaluation:

Continuous quality assurance and process improvement efforts resulted in a nearly 10-point increase in successful client-resource connections program-wide, with individual navigators showing improvements of up to 20%. Staff-led initiatives, such as population-specific resource guides and incentive awards, boosted morale and cohesion. Providing continuous professional development opportunities and requested training including trauma-informed care, self-care, and strategies for managing grief contributed to staff retention and improved client interactions.

Discussion:

The CUNY Recovery Corps provides a blueprint for setting up navigation services for emergency response and supporting health and social services. The current paper delves into the intensive quality improvement efforts, program management infrastructure, and staff support that made this program a success. By applying these lessons on establishing and maintaining a virtual call center prioritizing the client’s well-being and staff strengths, policymakers and social service leaders can effectively address various health and social service needs proactively rather than rebuilding after each disaster.
Is the Level of Consent to a National Research Registry Associated With Patient Outcomes After Traumatic Spinal Cord Injury? A Population-Based Study From the Rick Hansen Spinal Cord Injury Registry
Authors: Dionne Antoine , Mac-Thiong Jean-Marc , Hong Heather A. , Kurban Dilnur , Xu Jijie , Humphreys Suzanne , Bailey Chris , Barthélemy Dorothy , Christie Sean , Fourney Daryl , Linassi Gary , Loyola-Sanchez Adalberto , Paquet Jérôme , Sreenivasan Vidya , Townson Andrea , Tsai Eve , Noonan Vanessa , Richard-Denis Andréane ,   the RHSCIR Network
Published: June 2024

Objective

We examined the impact of consenting to the Rick Hansen Spinal Cord Injury Registry on outcomes: acute length of stay, in-hospital mortality, medical complications (pressure injuries and pneumonia), and the final discharge destination following a spinal cord injury using the national Rick Hansen Spinal Cord Injury Registry dataset.

Design

A retrospective cohort study was conducted using Rick Hansen Spinal Cord Injury Registry participant data from 2014 to 2019. Participants approached for enrollment were grouped into 1) PC: provided full consent including community follow-up interviews, 2) DWC: declined community follow-up interviews but accepted minimal data collection that may include initial/final interviews and/or those who later withdrew consent, and 3) DC: declined consent to any participation. As no data was collected for the DC group, descriptive, bivariate, and multivariable regression analysis was limited to the PC and DWC groups.

Results

Of 2811 participants, 2101 (74.7%) were PC, 553 (19.7%) were DWC, and 157 (5.6%) were DC. DWC participants had significantly longer acute length of stay, more acute pneumonias/pressure injuries, and were less likely to be discharged home than PC participants. All these associations—except pneumonia—remained significant in the multivariable analyses.

Conclusions

Not participating fully in Rick Hansen Spinal Cord Injury Registry was associated with more complications and longer hospital stays.
First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort
Authors: Fung Kelly , Hernandez-Diaz Sonia , Zash Rebecca , Chadwick Ellen G. , Van Dyke Russell B. , Broadwell Carly , Jao Jennifer , Powis Kathleen , Yee Lynn M. , Williams Paige L. ,   for the Pediatrics HIV/AIDS Cohort Study (PHACS)
Published: June 2024

Objective:

To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.

Design:

Longitudinal cohort of infants born 2012–2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.

Methods:

First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.

Results:

Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6–7.8%]. Cardiovascular (n = 43) and musculoskeletal (n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62–1.72) for darunavir, 0.91 (0.46–1.81) for raltegravir, 1.04 (0.58–1.85) for rilpivirine, 1.31 (0.71–2.41) for elvitegravir, 0.76 (0.37–1.57) for dolutegravir, and 0.34 (0.05–2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.

Conclusions:

The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.
Persistence and Sexual Dimorphism of Gut Dysbiosis and Pathobiome after Sepsis and Trauma
Authors: Munley Jennifer A. , Park Gwoncheol , Kelly Lauren S. , Kannan Kolenkode B. , Mankowski Robert T. , Casadesus Gemma , Chakrabarty Paramita , Wallet Shannon M. , Maile Robert , Bible Letitia E. , Wang Bo , Moldawer Lyle L. , Mohr Alicia M. , Nagpal Ravinder , Efron Philip A.
Published: June 2024

Objective:

To evaluate the persistence of intestinal microbiome dysbiosis and gut-plasma metabolomic perturbations following severe trauma or sepsis weeks after admission in patients experiencing chronic critical illness (CCI).

Trauma and sepsis can lead to gut dysbiosis and alterations in the plasma and fecal metabolome. However, the impact of these perturbations and correlations between gut dysbiosis and the plasma metabolome in chronic critical illness have not been studied.

Methods:

A prospective observational cohort study was performed with healthy subjects, severe trauma patients, and patients with sepsis residing in an intensive care unit for 2 to 3 weeks. A high-throughput multi-omics approach was utilized to evaluate the gut microbial and gut-plasma metabolite responses in critically ill trauma and sepsis patients 14 to 21 days after intensive care unit admission.

Results:

Patients in the sepsis and trauma cohorts demonstrated strikingly depleted gut microbiome diversity, with significant alterations and specific pathobiome patterns in the microbiota composition compared to healthy subjects. Further subgroup analyses based on sex revealed resistance to changes in microbiome diversity among female trauma patients compared to healthy counterparts. Sex--specific changes in fecal metabolites were also observed after trauma and sepsis, while plasma metabolite changes were similar in both males and females.

Conclusions:

Dysbiosis induced by trauma and sepsis persists up to 14 to 21 days after onset and is sex-specific, underscoring the implication of pathobiome and entero-septic microbial-metabolite perturbations in post-sepsis and posttrauma chronic critical illness. This indicates resilience to infection or injury in females’ microbiome and should inform and facilitate future precision/personalized medicine strategies in the intensive care unit.
Early-stage loss of ecological integrity drives the risk of zoonotic disease emergence
Authors: Marcolin Lara , Tonelli Andrea , Di Marco Moreno
Published: June 2024

Anthropogenic pressures have increasingly disrupted the integrity of ecosystems worldwide, jeopardizing their capacity to provide essential contributions to human well-being. Recently, the role of natural ecosystems in reducing disease emergence risk has gained prominence in decision-making processes, as scientific evidence indicates that human-driven pressure, such as habitat destruction and deforestation, can trigger the emergence of zoonotic infectious diseases. However, the intricate relationship between biodiversity and emerging infectious diseases (EIDs) remains only partially understood. Here, we updated the most comprehensive zoonotic EID event database with the latest reported events to analyse the relationship between EIDs of wildlife origin (zoonoses) and various facets of ecological integrity. We found EID risk was strongly predicted by structural integrity metrics such as human footprint and ecoregion intactness, in addition to environmental variables such as tropical rainforest density and mammal species richness. EID events were more likely to occur in areas with intermediate levels of compositional and structural integrity, underscoring the risk posed by human encroachment into pristine, undisturbed lands. Our study highlights the need to identify novel indicators and targets that can effectively address EID risk alongside other pressing global challenges in sustainable development, ultimately informing strategies for preserving both human and environmental health.
Dogs do not use their own experience with novel barriers to infer others’ visual access
Authors: Lonardo Lucrezia , Putnik Martina , Szewczak Veronika , Huber Ludwig , Völter Christoph J.
Published: June 2024

Despite extensive research into the Theory of Mind abilities in non-human animals, it remains controversial whether they can attribute mental states to other individuals or whether they merely predict future behaviour based on previous behavioural cues. In the present study, we tested pet dogs (in total,
N
= 92) on adaptations of the ‘goggles test’ previously used with human infants and great apes. In both a cooperative and a competitive task, dogs were given direct experience with the properties of novel screens (one opaque, the other transparent) inserted into identical, but differently coloured, tunnels. Dogs learned and remembered the properties of the screens even when, later on, these were no longer directly visible to them. Nevertheless, they were not more likely to follow the experimenter’s gaze to a target object when the experimenter could see it through the transparent screen. Further, they did not prefer to steal a forbidden treat first in a location obstructed from the experimenter’s view by the opaque screen. Therefore, dogs did not show perspective-taking abilities in this study in which the only available cue to infer others’ visual access consisted of the subjects’ own previous experience with novel visual barriers. We conclude that the behaviour of our dogs, unlike that of infants and apes in previous studies, does not show evidence of experience-projection abilities.
The roles of gene duplications in the dynamics of evolutionary conflicts
Authors: Castellanos María del Pilar , Wickramasinghe Chathuri Devmika , Betrán Esther
Published: June 2024

Evolutionary conflicts occur when there is antagonistic selection between different individuals of the same or different species, life stages or between levels of biological organization. Remarkably, conflicts can occur within species or within genomes. In the dynamics of evolutionary conflicts, gene duplications can play a major role because they can bring very specific changes to the genome: changes in protein dose, the generation of novel paralogues with different functions or expression patterns or the evolution of small antisense RNAs. As we describe here, by having those effects, gene duplication might spark evolutionary conflict or fuel arms race dynamics that takes place during conflicts. Interestingly, gene duplication can also contribute to the resolution of a within-locus evolutionary conflict by partitioning the functions of the gene that is under an evolutionary trade-off. In this review, we focus on intraspecific conflicts, including sexual conflict and illustrate the various roles of gene duplications with a compilation of examples. These examples reveal the level of complexity and the differences in the patterns of gene duplications within genomes under different conflicts. These examples also reveal the gene ontologies involved in conflict and the genomic location of the elements of the conflict. The examples provide a blueprint for the direct study of these conflicts or the exploration of the presence of similar conflicts in other lineages.
Selection on the joint actions of pairs leads to divergent adaptation and coadaptation of care-giving parents during pre-hatching care
Authors: Jarrett Benjamin J. M. , Mashoodh Rahia , Issar Swastika , Pascoal Sonia , Rebar Darren , Sun Syuan-Jyun , Schrader Matthew , Kilner Rebecca M.
Published: June 2024

The joint actions of animals in partnerships or social groups evolve under both natural selection from the wider environment and social selection imposed by other members of the pair or group. We used experimental evolution to investigate how jointly expressed actions evolve upon exposure to a new environmental challenge. Our work focused on the evolution of carrion nest preparation by pairs of burying beetlesNicrophorus vespilloides, a joint activity undertaken by the pair but typically led by the male. In previous work, we found that carrion nest preparation evolved to be faster in experimental populations without post-hatching care (No Care: NC lines) than with post-hatching care (Full Care: FC lines). Here, we investigate how this joint activity evolved. After 15 generations of experimental evolution, we created heterotypic pairs (NC females with FC males and NC males with FC females) and compared their carrion nest making with homotypic NC and FC pairs. We found that pairs with NC males prepared the nest more rapidly than pairs with FC males, regardless of the female’s line of origin. We discuss how social coadaptations within pairs or groups could act as a post-mating barrier to gene flow.
Flavobacterium poyangense sp. nov., an ammonifying bacterium isolated from a freshwater lake
Authors: Li Ya , Wang Xiyang , Deng Tao , Zheng Guohua , Tu Zuxin , Zhang Lili , Yuan Lin
Published: June 2024

A Gram-stain-negative, aerobic, non-spore-forming, nonmotile, rod-shaped, and yellow-pigmented bacterium, designated strain JXAS1T, was isolated from a freshwater sample collected from Poyang Lake in China. Phylogenetic analysis based on 16S rRNA gene sequence revealed that the isolate belonged to the genus Flavobacterium, being closest to Flavobacterium pectinovorum DSM 6368T (98.61 %). The genome size of strain JXAS1T was 4.66 Mb with DNA G+C content 35.7 mol%. The average nucleotide identity and in silico DNA–DNA hybridization values between strain JXAS1T and its closest relatives were below the threshold values of 95 and 70 %, respectively. The strain contained menaquinone 6 (MK-6) as the predominant menaquinone and the major polar lipids were phosphatidylethanolamine, one unidentified glycolipid, and one unidentified polar lipid. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C15 : 0, iso-C17 : 0 3OH, iso-C15 : 0 3OH, and summed feature 9 (iso-C17 : 1
 ω9c and/or 10-methyl C16 : 0). Based on phylogenetic, genotypic, and phenotypic evidence, the isolated strain represents a new species in the genus Flavobacterium, and the name Flavobacterium poyangense is proposed. The type strain is JXAS1T (=GDMCC 1.1378T=KCTC 62719T).
Cross-infection ofAscarisspp. in humans and pigs from a Guarani indigenous village in southern Brazil
Authors: Boeira Veridiana Lenartovicz , Bezagio Renata Coltro , Carvalho Marina Silva de , Gandra Rinaldo Ferreira , de Abreu Ana Paula , Massara Cristiano Lara , Colli Cristiane Maria , Toledo Max Jean de Ornelas
Published: June 2024

Background

Ascaris lumbricoidesandAscaris suumare nematode parasites that infect millions of people and pigs worldwide, respectively. Reports of cross-infection between the two host species has stimulated molecular epidemiological studies of theAscarisgenus. In this study, we evaluated the dynamics ofAscaristransmission between Guarani indigenous schoolchildren, pigs, and the environment of a village in the state of Paraná, southern Brazil.

Methodology/Principal findings

Parasitological and molecular analyses of fecal samples from humans and pigs, and soil samples from the village were carried out. Eggs ofAscarisspp. were observed in 8.4% (7/83) of human samples, 44.4% (8/18) of pig samples, and 8.9% (6/68) of soil samples. PCR amplification of theITS-1locus of the rDNA gene in samples that were positive in the parasitological examination revealed cross-infection by the two species,A. lumbricoidesandA. suum, in human and swine hosts. The soil, which was contaminated by both human and swine feces, also contained eggs of the twoAscarisspecies, thus constituting a source ofAscarisinfection for both hosts. DNA from both nematode species, individually and mixed, was detected in samples from both hosts and the soil.

Conclusions/Significance

The results of this study indicate that more effective control measures, aimed at the correct disposal of both human and animal feces, should be implemented.

Author Summary

Despite the control measures implemented in Brazilian Indigenous Lands, the prevalence of intestinal parasites continues to vary from moderate to high in its inhabitants. On the other hand, the number of indigenous people residing in Brazil has been increasing in last decades, including the South region of the country, where a much smaller proportion of indigenous people reside compared to the North region.Ascaris lumbricoidesandAscaris suumare the most prevalent helminth parasites in humans and pigs, respectively. The possibility of cross-infection byAscarisspp. between humans and pigs has been analyzed in order to propose more effective control measures. In this research, we use parasitological and molecular methods to verify the presence of these parasites in fecal samples from schoolchildren and pigs, in addition to soil samples, from a Guarani indigenous village in the state of Paraná, southern Brazil. Genetic material from both individual and associated nematode species was detected in host and soil samples, indicating cross-transmission in these populations. Control measures aimed at the correct disposal of human and animal feces must be implemented in order to minimize damage to health and prevent new infections.
Prevalence and Risk Factors of Hypertension Among Young Adults (26-35 Years Old) in Indonesia: Analysis of Secondary Data from Riskesdas 2018
Authors: Putri Laluna Rachma , Fibriana Arulita Ika , Azam Mahalul
Published: June 2024

Background

Worldwide, there are 54% adults diagnosed with hypertension. The prevalence of hypertension increased, based on the basic health survey (Riset Kesehatan Dasar; RISKESDAS) in 2013, the prevalence of hypertension was 25.8%, while the on the RISKESDAS 2018 data increased to 34.1%. This research aimed to find out the risk factors of hypertension among young adults in Indonesia using RISKESDAS 2018 data.

Method

The research design approach observational quantitative by cross-sectional design. This research used secondary data from RISKESDAS 2018 with a total of 140,073 subjects aged 26-35 years. All subjects who fulfil the inclusion criteria will be analyzed (n=78,000). Data analysed by chi-square test and binary logistic regression.

Results

The result of research exposed gender (p<0.001), marital status (p<0.001), education levels (p<0.001), working status (p<0.001), BMI (p<0.001), diabetes mellitus (p<0.001), emotional mental disorder (p<0.001), and instant food consumption (p<0.001) has a significant consequence of hypertension.

Conclusions

The results of research can be used as a consideration for creating programs and policies to control risk factors or hypertension among young adults in Indonesia. Promotive and preventive policies programs related to hypertension must reach the community to reduce hypertension morbidity and mortality rates.
Neutrophil extracellular traps formation and deposition of fibrin and von Willebrand factor during human coronary atherogenesis
Authors: Nakamura Eriko , Horiuchi Saki , Maekawa Kazunari , Gi Toshihiro , Oguri Nobuyuki , Aman Murasaki , Moriguchi-Goto Sayaka , Asada Yujiro , Yamashita Atsushi
Published: June 2024

Background and aims

Neutrophil extracellular traps (NETs), fibrin, and the von Willebrand factor (VWF) are present in acute coronary thrombotic plaques. However, the presence and extent of NETs, fibrin, and VWF in early-to-unstable coronary atherosclerotic lesions remain unclear. This study aims to determine the presence and extent of neutrophils, NETs, fibrin, and VWF formation during human coronary atherogenesis.

Methods

Coronary sections from autopsy patients with non-cardiac death (n=5, 37 sections) and ischemic heart diseases (n= 11, 65 sections) were classified by atherosclerosis classification: diffuse intimal thickening, pathological intimal thickening, fibrous cap atheroma, fibrocalcified plaque, thin-cap fibroatheroma, ruptured plaque, and intraplaque hemorrhage. We immunohistochemically assessed the expression of CD66b (neutrophils), citrullinated histone H3 (Cit-H3, a marker of NETs), fibrin, and VWF.

Results

Neutrophil and Cit-H3 expression were rarely observed, except in thin-cap fibroatheromas and ruptured plaques. Fibrin deposition was observed in pathological intimal thickening and necrotic cores of atheromas, and it was abundant in thin-cap fibroatheroma and ruptured plaques. VWF deposition was observed in the necrotic core of the atheromas and was abundant in ruptured plaques. In non-ruptured plaques, the immunopositive areas for Cit-H3 and fibrin were larger in hemorrhagic plaques than in non-hemorrhagic plaques.

Conclusions

These results suggest that NET formation is rare in stable coronary plaques, and fibrin formation begins in stable lesions and increases with plaque destabilization in the coronary artery. Intraplaque hemorrhage may promote NET formation and fibrin deposition in non-ruptured plaques. The abundance of neutrophilic infiltrates and VWF deposition may be a response to plaque rupture.
Impact of cardiometabolic factors and blood beta-amyloid on the volume of white matter hyperintensities in dementia-free subjects with cognitive complaints
Authors: Riquelme-Contreras Patricio , Hornberger Michael , Khondoker Mizanur , Henriquez Fernando , Gonzalez-Campo Cecilia , Altschuler Florencia , Fraile-Vazquez Matías , Lukasewicz-Ferreira Pamela , Bellaver Bruna , Karikari Thomas , Pascoal Tharick A. , Muniz-Terrera Graciela , Okuma Cecilia , Gonzalez-Billault Christian , Court Felipe , Cerda Mauricio , Lillo Patricia , Slachevsky Andrea
Published: June 2024

Introduction

White matter hyperintensities (WMH) in Alzheimer’s disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid β (Aβ) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs and cardiometabolic and Aβ blood biomarkers in a community-based cohort of Latin American CC participants.

Methods

We recruited 112 individuals with CC (69 – 92 YO, 90 females) with available plasma Aβ biomarkers and cardiometabolic markers (systolic – diastolic blood pressure and glycaemia). WMHs were quantified using a lesion segmentation tool based on SPM12 and segmented using the John Hopkins University (JHU) Atlas and ALVIN segmentation for periventricular and subcortical white matter. Linear multiple regression models were fitted to assess total WMH lesions and the segmented tract, using demographics, cardiometabolic, and Aβ blood biomarker measures as independent variables.

Results

After multiple comparison corrections, diastolic blood pressure was associated with WMHs, specifically in the right anterior thalamic radiation, left cingulum, minor forceps, and subcortical ALVIN segmentation. Glycaemia was associated with WMH volume in forceps major, forceps minor, and right fronto-occipital fasciculi. Conversely, Aβ blood biomarkers and systolic blood pressure showed no association with WMH overall or in specific tracts.

Conclusion

Our findings suggest that, in dementia-free CC individuals, WMH volume was more related to cardiometabolic factors, whereas Aβ blood biomarkers might be of less relevance. Dementia prevention strategies in individuals might be a useful focus for managing high peripheral vessel resistance and endothelial damage due to hypertension and hyperglycaemia.
Intra-organ cell specific mitochondrial quantitative interactomics
Authors: Bakhtina AA , Campbell MD , Sibley BD , Sanchez-Contreras M , Sweetwyne MT , Bruce JE
Published: June 2024

Almost every organ consists of many cell types, each with its unique functions. Proteomes of these cell types are thus unique too. But it is reasonable to assume that interactome (inter and intra molecular interactions of proteins) are also distinct since protein interactions are what ultimately carry out the function. Podocytes and tubules are two cell types within kidney with vastly different functions: podocytes envelop the blood vessels in the glomerulus and act as filters while tubules are located downstream of the glomerulus and are responsible for reabsorption of important nutrients. It has been long known that for tubules mitochondria plays an important role as they require a lot of energy to carry out their functions. In podocytes, however, it has been assumed that mitochondria might not matter as much in both normal physiology and pathology1. Here we have applied quantitative cross-linking mass spectrometry to compare mitochondrial interactomes of tubules and podocytes using a transgenic mitochondrial tagging strategy to immunoprecipitate cell-specific mitochondria directly from whole kidney. We have uncovered that mitochondrial proteomes of these cell types are quite similar, although still showing unique features that correspond to known functions, such as high energy production through TCA cycle in tubules and requirements for detoxification in podocytes which are on the frontline of filtration where they encounter toxic compounds and therefore, as a non-renewing cell type they must have ways to protect themselves from cellular toxicity. But we gained much deeper insight with the interactomics data. We were able to find pathways differentially regulated in podocytes and tubules based on changing cross-link levels and not just protein levels. Among these pathways are betaine metabolism, lysine degradation, and many others. We have also demonstrated how quantitative interactomics could be used to detect different activity levels of an enzyme even when protein abundances of it are the same between cell types. We have validated this finding with an orthogonal activity assay. Overall, this work presents a new view of mitochondrial biology for two important, but functionally distinct, cell types within the mouse kidney showing both similarities and unique features. This data can continue to be explored to find new aspects of mitochondrial biology, especially in podocytes, where mitochondria has been understudied. In the future this methodology can also be applied to other organs to uncover differences in the function of cell types.
Directed evolution of hyperactive integrases for site specific insertion of transgenes
Authors: Hew Brian E , Gupta Sabranth , Sato Ryuei , Waller David F , Stoytchev Ilko , Short James E , Sharek Lisa , Tran Christopher T , Badran Ahmed H , Owens Jesse B
Published: June 2024

The ability to deliver large transgenes to a single genomic sequence with high efficiency would accelerate biomedical interventions. Current methods suffer from low insertion efficiency and most rely on undesired double-strand DNA breaks. Serine integrases catalyze the insertion of large DNA cargos at attachment (att) sites. By targeting att sites to the genome using technologies such as prime editing, integrases can target safe loci while avoiding double-strand breaks. We developed a method of phage-assisted continuous evolution we call IntePACE, that we used to rapidly perform hundreds of rounds of mutagenesis to systematically improve activity of PhiC31 and Bxb1 serine integrases. Novel hyperactive mutants were generated by combining synergistic mutations resulting in integration of a multi-gene cargo at rates as high as 80% of target chromosomes. Hyperactive integrases inserted a 15.7 kb therapeutic DNA cargo containing Von Willebrand Factor. This technology could accelerate gene delivery therapeutics and our directed evolution strategy can easily be adapted to improve novel integrases from nature.
Predicting the Tumor Microenvironment Composition and Immunotherapy Response in Non-Small Cell Lung Cancer from Digital Histopathology Images
Authors: Patkar Sushant , Chen Alex , Basnet Alina , Bixby Amber , Rajendran Rahul , Chernet Rachel , Faso Susan , Kumar Prashant A. , Desai Devashish , El-Zammar Ola , Curtiss Christopher , Carello Saverio J. , Nasr Michel , Choyke Peter , Harmon Stephanie , Turkbey Baris , Jamaspishvili Tamara
Published: June 2024

Immune checkpoint inhibitors (ICI) have become integral to treatment of non-small cell lung cancer (NSCLC). However, reliable biomarkers predictive of immunotherapy efficacy are limited. Here, we introduce HistoTME, a novel weakly supervised deep learning approach to infer the tumor microenvironment (TME) composition directly from histopathology images of NSCLC patients. We show that HistoTME accurately predicts the expression of 30 distinct cell type-specific molecular signatures directly from whole slide images, achieving an average Pearson correlation of 0.5 with the ground truth on independent tumor cohorts. Furthermore, we find that HistoTME-predicted microenvironment signatures and their underlying interactions improve prognostication of lung cancer patients receiving immunotherapy, achieving an AUROC of 0.75[95% CI: 0.61-0.88] for predicting treatment responses following first-line ICI treatment, utilizing an external clinical cohort of 652 patients. Collectively, HistoTME presents an effective approach for interrogating the TME and predicting ICI response, complementing PD-L1 expression, and bringing us closer to personalized immuno-oncology.
Decoding the impact of fibroblast heterogeneity on prognosis and drug resistance in high-grade serous ovarian cancer through tumor evolution analysis
Authors: wang tingjie
Published: June 2024

Background: Tumor heterogeneity is associated with poor prognosis and drug resistance, leading to therapeutic failure. Here, we aim to utilize tumor evolution analysis to decode the intra- and inter-tumoral heterogeneity of high-grade serous ovarian cancer (HGSOC), unraveling the correlation between tumor heterogeneity and prognosis as well as chemotherapy response through single-cell and spatial transcriptomic analysis. Methods: We collected and curated 28 HGSOC patients single-cell transcriptomic data from five datasets. Then, we developed a novel text mining-based machine learning approach to deconstruct the evolutionary patterns of tumor cell functions. This allowed us to identify key tumor-related genes within different evolutionary branches, elucidate the microenvironmental cell compositions that various functional tumor cells depend on, and analyze the intra- and inter-heterogeneity of tumors and their microenvironments in relation to prognosis and chemotherapy response in HGSOC patients. We further validated our findings in two spatial and seven bulk transcriptomic datasets, totally 1,030 patients. Results: By employing transcriptomic clusters as proxies for functional clonality, we identified a significant increase in tumor cell state heterogeneity, which was strongly correlated with patient prognosis and treatment response. Furthermore, increased intra- and inter-tumoral functional clonality was associated with the characteristics of cancer-associated fibroblast (CAF). We also found that the spatial proximity between CXCL12-positive CAF and tumor cells, mediated through the CXCL12/CXCR4 interaction, is highly positively correlated with poor prognosis and chemotherapy resistance in HGSOC. Finally, we constructed a panel of 24 genes through statistical modeling, that are highly correlated with CXCL12-positive fibroblasts and can predict both prognosis and chemotherapy response in HGSOC. Conclusions: Our study offers insights into the collective behavior of tumor cell communities in HGSOC, as well as potential drivers of tumor evolution in response to therapy. Functional analyses and experiments revealed a strong association between CXCL12-positive fibroblasts and tumor progression as well as treatment outcomes. Our findings provide an important theoretical basis for clinical HGSOC treatment.
Species Distribution ofCannabis sativa: Past, Present and future
Authors: Halpin-McCormick Anna , Maaz Tai McClellan , Kantar Michael B. , Barton Kasey E. , Masalia Rishi R. , Batora Nick , Law Kerin , Kuntz Eleanor J.
Published: June 2024

Cannabis sativaL. is an annual flowering herb of Eurasian origin that has long been associated with humans. Domesticated independently at multiple locations at different times for different purposes (food, fiber, and medicine), these long-standing human associations have influenced its distribution. However, changing environmental conditions and climatic fluctuations have also contributed to the distribution of the species and define where it is optimally cultivated. Here we explore the shifts in distribution thatC. sativamay have experienced in the past and explore the likely shifts in the future. Modeling under paleoclimatic scenarios shows niche expansion and contraction in Eurasia through the timepoints examined. Temperature and precipitation variables and soil variable data were combined for species distribution modeling in the present day and showed high and improved predictive ability together as opposed to when examined in isolation. The five most important variables explaining ∼65% of the total variation were soil organic carbon content (ORCDRC), pH index measured in water solution (PHIHOX), annual mean temperature (BIO-1), mean temperature of the coldest quarter (BIO-11) and soil organic carbon density (OCDENS) (AUC = 0.934). Climate model projections where efforts are made to curb emissions (RCP45/SSP245) and the business as usual (RCP85/SSP585) models were evaluated. Under projected future climate scenarios, shifts worldwide are predicted with a loss of ∼43% in suitability areas with scores above 0.4 observed by 2050 and continued but reduced rates of loss by 2070. Changes in habitat range have large implications for the conservation of wild relatives as well as for the cultivation ofCannabisas the industry moves toward outdoor cultivation practices.