bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between leisure-time physical activity and arterial stiffness in adults of the ELSA-Brasil study: a mediation analysis
Authors: Baldo Marcelo P. , Zaniqueli Divanei A. , Cunha Roberto S. , Griep Rosane H. , Barreto Sandhi M. , Bensenor Isabela , Lotufo Paulo A. , Mill José Geraldo 
Published: June 2024

Objectives:
We aimed at defining the direct and the mediated pathways for the association between leisure-time physical activity (LTPA) and carotid-to-femoral pulse wave velocity (cf-PWV), and also to identify whether these effects are influenced by sex and age.

Methods:
Cross-sectional data from 13 718 adults (35–74 years) were obtained at the baseline of the ELSA-Brasil study. The cf-PWV was obtained by measuring the pulse transit time and the distance traveled by the pulse between the carotid and the femoral, as well as clinical and anthropometric parameters were measured. The levels of LTPA were determined by applying the long form of the International Physical Activity Questionnaire (IPAQ).

Results:
Classical cardiovascular risk factors were independently associated with cf-PWV. Path analysis showed that increased levels of LTPA were directly associated with lower cf-PWV in both men and women (β: −0.123 ± 0.03 vs. 0.065 ± 0.029, P for sex = 0.165), except for diabetes. Also, the mediated effect of LTPA on SBP and DBPs, heart rate, BMI, and fasting glucose, was associated with lower cf-PWV in men and women (β: −0.113 ± 0.016 vs. −0.104 ± 0.016, P for sex = 0.692), except for diabetes. When age was tested as a moderator, the direct effect did not change significantly according to participants’ age, regardless of sex. However, the mediated effect increases in both men and women over 50 years.

Conclusion:
Our findings support that LTPA in adults reduces cf-PWV by acting in different ways according to age. Physical activity in older individuals improves cardiometabolic risk factors and thus mitigates the stiffening of large arteries.
Unraveling the neuroimmune interface in chronic pain—the association between cytokines in the cerebrospinal fluid and pain in patients with lumbar disk herniation or degenerative disk disease
Authors: Rosenström Alexander H.C. , Ahmed Aisha Siddiqah , Kultima Kim , Freyhult Eva , Berg Svante , Bersellini Farinotti Alex , Palada Vinko , Svensson Camilla I. , Kosek Eva 
Published: June 2024

Abstract
Recent evidence highlights the importance of the neuroimmune interface, including periphery-to-central nervous system (CNS) neuroimmune crosstalk, in chronic pain. Although neuroinflammatory processes have been implicated in central sensitization for a long time, their potential neuroprotective and analgesic effects remain relatively elusive. We have explored the relationships between cytokine expression and symptom severity, and candidates for periphery-to-CNS crosstalk. Patients with degenerative disk disease (DDD) (nociceptive pain) or patients with lumbar disk herniation (LDH) with radiculopathy (predominantly neuropathic pain) completed questionnaires regarding pain and functional disability, underwent quantitative sensory testing, and provided blood and cerebrospinal fluid (CSF) samples. Proximity extension assay (PEA) was used to measure the levels of 92 inflammatory proteins in the CSF and serum from a total of 160 patients and controls, and CSF/serum albumin quotients was calculated for patients with DDD and patients with LDH. We found signs of neuroimmune activation, in the absence of systemic inflammation. Regarding periphery-to-CNS neuroimmune crosstalk, there were significant associations between several cytokines and albumin quotient, despite the latter being primarily at subclinical levels. The cytokines CCL11, CD5, IL8, and MMP-10 were elevated in the CSF, had positive correlations between CSF and serum levels, and associated in a nonlinear manner with back, but not leg, pain intensity in the LDH, but not the DDD, group. In conclusion, we found evidence for neuroimmune activation in the CNS of both patient groups in the absence of systemic inflammation and signs of a communication between CSF and serum. Complex and disease-specific associations were found between cytokines in CSF and back pain intensity.
Vitamin C for all?
Authors: de Man Angelique , Long Micah T. , Stoppe Christian 
Published: June 2024

Purpose of review
Vitamin C can be a potential adjunctive treatment option for critically ill individuals due to its pleiotropic effects as electron donor in many enzymatic reactions throughout the body. Recently, several important randomized controlled trials (RCTs) investigating vitamin C in critically ill patients have been published.

Recent findings
Two recent large RCTs administering high-dose vitamin C to patients with sepsis and COVID-19 showed signs of harm. Though performed at high standard, these trials had several limitations. Recent studies in cardiac surgery and burns showed decreased cardiac enzymes and improved clinical outcomes after cardiac surgery, and decreased fluid requirements, reduced wound healing time and in-hospital mortality after burns. Vitamin C may hold benefit in the management of other ischemia/reperfusion injury populations, including postcardiac arrest patients and after solid organ transplantation. Currently, covering basal vitamin C requirements during critical illness is recommended, though the exact dose remains to be determined.

Summary
Future work should address optimal vitamin C timing, since early versus late drug administration are likely distinct, and duration of therapy, where withdrawal-induced injury is possible. Additionally accurate assessment of body stores with determination of individual vitamin requirements is crucial to ascertain patient and subgroups most likely to benefit from vitamin C.
Understanding the complexity of cardiogenic shock management: the added value of advanced computational modeling
Authors: Meuwese Christiaan L. , van Loon Lex M. , Donker Dirk W. 
Published: June 2024

Purpose of review
The purpose of this review is to explain the value of computational physiological modeling for in-depth understanding of the complex derangements of cardiopulmonary pathophysiology during cardiogenic shock, particularly when treated with temporary mechanical circulatory support (tMCS) devices.

Recent findings
Computational physiological models have evolved in recent years and can provide a high degree of clinical realism in the simulation of cardiogenic shock and related conservative and interventional therapies. These models feature a large spectrum of practically relevant hemodynamic and respiratory parameters tunable to patient-specific disease states as well as adjustable to medical therapies and support device settings. Current applications work in real-time and can operate on an ordinary computer, laptop or mobile device.

Summary
The use of computational physiological models is increasingly appreciated for educational purposes as they help to understand the complexity of cardiogenic shock, especially when sophisticated management of tMCS is involved in addition to multimodal critical care support. Practical implementation of computational models as clinical decision support tools at the bedside is at the horizon but awaits rigorous clinical validation.
Sex differences in the presentation and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock: a critical review of contemporary data and a look towards future directions
Authors: Smith Emily , Tamis-Holland Jacqueline E. 
Published: June 2024

Purpose of review
Cardiogenic shock (CS) is a devasting complicating of acute myocardial infarction (AMI), associated with significant mortality. Prior studies have reported sex differences in the presentation, management and outcomes of patients with AMI and CS. These differences are likely due to a variety of factors influencing therapeutic decision-making and impacting survival. This review highlights the more contemporary studies exploring differences in women and men with AMI-CS, providing a critical perspective towards understanding the factors that might lead to these differences and outlining potential opportunities to reduce disparities in treatment and improve survival for women with AMI-CS.

Recent findings
Recent reports demonstrate that women with AMI-CS are older than men and have more cardiovascular comorbidities. When examining an unselected population of patients with AMI-CS, women receive less aggressive treatment compared to men and have poorer outcomes. However, when examining a selected population of patients with AMI-CS treated with mechanical circulatory support (MCS) and/or admitted to centers that implement CS protocols to manage AMI-CS, these sex-based differences in outcomes are largely mitigated.

Summary
Standardizing protocols for the diagnosis and treatment of patients with AMI-CS, with an emphasis on early revascularization and appropriate invasive therapies, can improve outcomes in women and narrow the gender gap.
A practical approach to preparing your ICU for epidemics and pandemics
Authors: Maves Ryan C. , Cawcutt Kelly A. 
Published: June 2024

Purpose of review
Major outbreaks of infectious diseases, including epidemics and pandemics, are increasing in scope and frequency, threatening public health and straining the capacity of health systems worldwide. High-consequence infectious diseases (HCIDs), including highly pathogenic respiratory viruses and viral hemorrhagic fevers, are both contagious and virulent, and these pathogens thus are topics of special concern for pandemic planning.

Recent findings
The COVID-19 pandemic demonstrated how a major disease outbreak can negatively impact all aspects of hospital functioning. Identification of patients with HCIDs needs careful clinical evaluation and coordination with public health authorities. Staff safety and patient care require appropriate infection prevention precautions, including personal protective equipment. Surges of ill patients may lead to significant strain, with increased ICU patient mortality. Strategies to reduce the impact of surge appear to reduce mortality, such as tiered staffing models and load-leveling across health systems.

Summary
Pandemics and HCIDs are a significant threat to global health, and ICUs play a major role in the care of affected patients. Critical care professionals must work to ensure that our hospitals are prepared to identify and care for these patients in advance of the next emergency.
Clonal hematopoiesis: a shared risk factor for cardiovascular diseases and tumors
Authors: Zha Ling-Feng , Cheng Xiang 
Published: June 2024

Abstract
Clonal hematopoiesis (CH) is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation. Genes integral to critical cellular processes such as epigenetic regulation, DNA damage response, and inflammation frequently carry these mutations. Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions. Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis. Here, we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH, as well as look forward to future related studies, so as to provide valuable references for future research and clinical practice.
Endemic viral infections in immunocompromised hosts: Dengue, Chikungunya, Zika
Authors: Garnica Marcia , Ramos Jessica Fernandes , Machado Clarisse Martins 
Published: June 2024

Purpose of review
Arbovirus infections are a challenge for immunocompromised hosts who travel to or live in endemic regions or who receive organs or tissues from donors who travel or live in such areas. This review addresses Dengue (DENV), Chikungunya (CHIKV), and Zika (ZIKV) infections in hematological patients, hematopoietic cell or solid organ transplant recipients, and people with HIV (PWH).

Recent findings
Transmission is mainly due through Aedes mosquito bite. DENV and ZIKV may also be transmitted through blood, tissues or donor grafts. Clinical manifestations are quite similar and diagnosis requires laboratory confirmation to provide appropriate management. The best diagnostic method is PCR since serology may present false negative results in immunocompromised patients, or cross-reactivity as in the case of DENV and ZIKV. There is no specific treatment for any of these infections.

Summary
Educational and preventive measures are the best strategy: vector control, knowledge of the vector's habits, protection against mosquito bites, avoiding travel to endemic areas or with a current epidemic, and avoiding nonvector transmission according to local recommendations for donor deferral. Vaccination, currently only available for DENV, has not yet been studied in immunocompromised patients and is not currently recommended.
Comparison of microRNA expression levels in patients with schizophrenia before and after electroconvulsive therapy
Authors: Usta Saglam Nazife Gamze , Duz Mehmet Bugrahan , Salman Yilmaz Seda , Ozen Mustafa , Balcioglu Ibrahim 
Published: June 2024

Objective
Exploring the role of microRNAs in the antipsychotic efficacy of electroconvulsive therapy (ECT) will contribute to understanding the underlying mechanism through which ECT exerts its therapeutic effects. The primary objective of this study was to identify microRNA alterations before and after ECT in patients with schizophrenia.

Methods
We compared microarray-based microRNA profiles in peripheral blood from eight patients with schizophrenia before and after ECT and eight healthy controls. Then, we aimed to validate selected differentially expressed microRNAs in 30 patients with schizophrenia following a course of ECT, alongside 30 healthy controls by using quantitative reverse-transcription PCR.

Results
Microarray-based expression profiling revealed alterations in 681 microRNAs when comparing pre- and post-ECT samples. Subsequent quantitative reverse-transcription PCR analysis of the selected microRNAs (miR-20a-5p and miR-598) did not reveal any statistical differences between pre- and post-ECT samples nor between pre-ECT samples and those of healthy controls.

Conclusion
As neuroepigenetic studies on ECT are still in their infancy, the results reported in this study are best interpreted as exploratory outcomes. Additional studies are required to explore the potential epigenetic mechanisms underlying the therapeutic efficacy of ECT.
Interaction between gene expression and morphokinetic parameters in undisturbed human embryo culture
Authors: Xiao Hui , Stevens Adam , Smith Helen L. , Szczesna Karolina , Keramari Maria , Horne Gregory , Dinnyes Andras , Kimber Susan J. , Lio Pietro , Brison Daniel R. 
Published: June 2024

AbstractThe clinical in vitro fertilisation (IVF) need for optimal culture conditions and improved selection of human embryos for transfer led to the development of time-lapse systems built into incubators to allow a stable, well-defined and undisturbed culture environment with continual monitoring of embryo development. Clinical data suggest that both undisturbed culture of embryos and selection algorithms based on time-lapse morphometric parameters can potentially improve embryo development and live birth rates. However, there remains a need to validate and understand the mechanisms underlying the potential benefits of the time-lapse technology in IVF. In this study, we compared the gene expression of human embryos grown in an undisturbed time-lapse system with a conventional incubator and showed that there is no fundamental difference in the developmental program of the undisturbed embryos, which provides important reassurance concerning the time-lapse technology. We then performed a network-based integrative analysis based on the undisturbed blastocyst transcriptomes and identified time-lapse parameter correlated genes. These showed cross talk with identified embryo development gene functional modules, suggesting potential molecular mechanisms underlying the clinical predictive capabilities of embryo time-lapse morphokinetic parameters for subsequent live birth. This study suggests methodologies for assessing the impact of additional predictive correlates of value for optimal embryo development and understanding their mechanisms of action.
Accelerating CAR T cell manufacturing with an automated next-day process
Authors: Ahmadi Mina , Putnam Nicholas , Dotson Max , Hayoun Danny , Fatima Nujhat , Padilla Jasmine , Nonterah Gertrude , de Mollerat du Jeu Xavier , Ji Yongchang 
Published: June 2024

AbstractThe traditional method of CAR T cell production involves lengthyex vivoculture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient and contribute to disease progression. In this study, we describe an innovative and automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which have increased cytotoxic activity and cytokine release. The data supports the feasibility of implementing this streamlined manufacturing process in clinics. This approach also has the potential to enhance CAR T therapy efficacy and improve patient access to therapy.
Impact of Parental Time-Restricted Feeding on Offspring Metabolic Phenotypic Traits
Authors: Fan Yibo , Peng Xiangyuan , Tabassum Nishat I. , Cheng Xiangru , Selvaraji Sharmelee , Tran Vivian , Gibson Hughes Tayla A. , Wickramasinghe Buddhila , Jamal Abdulsatar , Dinh Quynh Nhu , Gelderblom Mathias , Drummond Grant R. , Sobey Christopher G. , Penman Jim , Johns Terrance G. , Vemuganti Raghu , Gunaratne Jayantha , Mattson Mark P. , Jo Dong-Gyu , Jelinic Maria , Arumugam Thiruma V. 
Published: June 2024

AbstractA substantial body of research elucidates the mechanisms and health advantages associated with intermittent fasting (IF). However, the impact of parental IF on offspring remains unclear. Through an investigation involving four IF andad libitumcombinations of parental mating groups, we demonstrate that parental IF (daily time-restricted feeding) influences offspring’s metabolic health indicators in male and female offspring in distinct ways. We found that when both parents are on IF their offspring exhibit protection against the adverse effects of a high-fat, high-sugar, and high-salt diet in a sex-specific manner. This study underscores the potential significance of parental lifestyle modifications involving dietary restriction for the metabolic status of their children and their risk for obesity and diabetes.
Up-regulated transcriptional regulators in mutant RAS gene signatures: a time-resolved multi-omics study in generic epithelial cell models
Authors: Kasack Katharina , Metzger Patrick , Koch Heiner , Klinger Bertram , Malek Anastasia , Tchernitsa Oleg , Gross Alexander , Wruck Wasco , Györffy Balazs , Küster Bernhard , Sers Christine , Börries Melanie , Schäfer Reinhold 
Published: June 2024

ABSTRACTThe expression of mutated RAS genes drives extensive transcriptome alterations. Perturbation experiments have shown that the transcriptional responses to downstream effector pathways are partially unique and non-overlapping, suggesting a modular organization of the RAS-driven expression program. However, the relationship between individual deregulated transcription factors and the entire cancer cell-specific genetic program is poorly understood. To identify potential regulators of the RAS/MAPK-dependent fraction of the genetic program, we monitored transcriptome and proteome changes following conditional, time-resolved expression of mutant HRASG12Vin human epithelial cells during neoplastic conversion. High mobility group AT hook2 (HMGA2), an architectural chromatin modulating protein and oncofetal tumour marker, was recovered as the earliest upregulated transcription factor. Knock-down of HMGA2 reverted anchorage-independent growth and epithelial-mesenchymal transition not only in HRAS-transformed cells but also in an independent, KRASG12V-driven rat epithelial model. Moreover, HMGA2 silencing reverted the deregulated expression of 60% of RAS-responsive target genes. These features qualify HMGA2 as a master regulator of mutant RAS-driven expression patterns. The delayed deregulation of FOSL1, ZEB1 and other transcription factors with known oncogenic activity suggests that HMGA2 acts in concert with a network of regulatory factors to trigger full neoplastic conversion. Although transcription factors are considered difficult to drug, the central role of HMGA2 in the transcription factor network as well as its relevance for cancer prognosis has motivated attempts to block its function using small molecular weight compounds. The further development of direct HMGA2 antagonists may prove useful in cancer cells that have developed resistance to signalling chain inhibition.
Delayed dichromatism in waterfowl as a convenient tool for assessing vital rates
Authors: Tableau Adrien , Henderson Iain , Reeber Sébastien , Guillemain Matthieu , Maillard Jean-François , Caizergues Alain 
Published: June 2024

AbstractMonitoring the number of individuals is by far the most popular strategy for studying the environmental factors that determine population dynamics and for measuring the effectiveness of management actions aimed at population recovery, control or eradication. Unfortunately, population size monitoring is inefficient in identifying the mechanisms underlying demographic processes and, in particular, in assessing the extent to which population growth rate is influenced by changes in adult survival rather than variations in reproductive parameters. In many waterfowl species, sexual dichromatism is observed in adults, while immatures of both sexes display a plumage pattern similar to that of adult females. In these species, the apparent proportion of males increases as the female-like immature males gradually take on the plumage of adult males. The difference between the apparent sex ratio before and after the young reach sexual maturity then provides information about the age ratio of a population. Using winter counts that distinguished between female-like and male-like individuals of two non-native populations of Ruddy duckOxyura jamaicensis, a species that exhibits such a plumage pattern, we present a non- invasive method based on the apparent sex ratio to split population growth rate into adult survival and recruitment rates (the latter also referred to as productivity). This method can correctly detect annual changes in vital rates, supporting the assumption that counts conducted in an appropriate time window reflect the age structure of a population. We exemplify how the respective contributions of survival and productivity to the population growth rate are essential for understanding the processes behind demo- graphic dynamics. Finally, we point out some best practices to correctly apply the “apparent sex ratio” method described here.