bluuebunny/crossref_metadata_2025 huggingface dataset:
“So at least now I know how to deal with things myself, what I can do if it gets really bad again”—experiences with a long-term cross-sectoral advocacy care and case management for severe multiple sclerosis: a qualitative study
Authors: Müller Anne , Hebben Fabian , Dillen Kim , Dunkl Veronika , Goereci Yasemin , Voltz Raymond , Löcherbach Peter , Warnke Clemens , Golla Heidrun ,   on behalf of the COCOS-MS trial group represented by Martin Hellmich, Müller Dirk , Hobus Dorthe , Bonmann Eckhard , Schwartzkopff Franziska , Nelles Gereon , Palmbach Gundula , Temmes Herbert , Franke Isabel , Haas Judith , Strupp Julia , Gerbershagen Kathrin , Becker-Peters Laura , Burghaus Lothar , Hellmich Martin , Paus Martin , Ungeheuer Solveig , Kochs Sophia , Stock Stephanie , Joist Thomas , Limmroth Volker
Published: April 2024

Background

Persons with severe Multiple Sclerosis (PwsMS) face complex needs and daily limitations that make it challenging to receive optimal care. The implementation and coordination of health care, social services, and support in financial affairs can be particularly time consuming and burdensome for both PwsMS and caregivers. Care and case management (CCM) helps ensure optimal individual care as well as care at a higher-level. The goal of the current qualitative study was to determine the experiences of PwsMS, caregivers and health care specialists (HCSs) with the CCM.

Methods

In the current qualitative sub study, as part of a larger trial, in-depth semi-structured interviews with PwsMS, caregivers and HCSs who had been in contact with the CCM were conducted between 02/2022 and 01/2023. Data was transcribed, pseudonymized, tested for saturation and analyzed using structuring content analysis according to Kuckartz. Sociodemographic and interview characteristics were analyzed descriptively.

Results

Thirteen PwsMS, 12 caregivers and 10 HCSs completed interviews. Main categories of CCM functions were derived deductively: (1) gatekeeper function, (2) broker function, (3) advocacy function, (4) outlook on CCM in standard care. Subcategories were then derived inductively from the interview material. 852 segments were coded. Participants appreciated the CCM as a continuous and objective contact person, a person of trust (92 codes), a competent source of information and advice (on MS) (68 codes) and comprehensive cross-insurance support (128 codes), relieving and supporting PwsMS, their caregivers and HCSs (67 codes).

Conclusions

Through the cross-sectoral continuous support in health-related, social, financial and everyday bureaucratic matters, the CCM provides comprehensive and overriding support and relief for PwsMS, caregivers and HCSs. This intervention bears the potential to be fine-tuned and applied to similar complex patient groups.

Trial registration

The study was approved by the Ethics Committee of the University of Cologne (#20–1436), registered at the German Register for Clinical Studies (DRKS00022771) and in accordance with the Declaration of Helsinki.
An investigation into the present status and influencing factors of nurse retention in grade-a tertiary general hospitals in Shanxi Province within the framework of the magnet hospital concept
Authors: Yue Li-Hong , Wang Lin-Ying , Guo Jin-Li , Li Wan-Ling , Zhang Jian-Wei
Published: April 2024

Background

The attrition of nursing staff significantly contributes to the shortage of healthcare professionals. This study entailed an examination of the propensity of nurses to sustain employment within Grade-A tertiary general hospitals and the various influencing factors.

Methods

A total of 2,457 nurses from three grade-A tertiary general hospitals were surveyed. The survey instruments included a general information questionnaire, a scale measuring their willingness to continue working, and a Chinese version of the Magnet Hospital Factor scale.

Results

The scores of the willingness to continue working scale and the Magnet Hospital Factor scale were 21.53 ± 4.52 and 145.46 ± 25.82, respectively. There were statistically significant differences in the scores of willingness of nurses to continue working across various factors, including the department, age, marital status, family location, length of service as nurses, professional title, position, and employment type, upon comparison (P < 0.001). The correlation analysis showed that there was a positive correlation between the willingness of nurses to continue working and the magnet hospital factors, with a correlation coefficient of 0.523 (P < 0.01). Regression analysis showed that department, length of service as nurses, professional title, position, average monthly income, number of night shifts, medical care relationship, educational support, and nursing manager support among the magnet hospital factors were important predictors of willingness to continue working (P < 0.001).

Conclusion

The willingness of nurses to continue working in grade-A tertiary general hospitals in Shanxi Province was determined to be at an upper-middle level. The magnet status of grade-A tertiary general hospitals needs to be improved, and there are many factors that influenced willingness of nurses to continue working. To cultivate a more favorable environment and bolster nurse recruitment and retention, all healthcare institutions should strive to establish a magnet nursing environment, thereby fostering the robust development of the nursing team.
Integrative analysis of transcriptomic and epigenomic data reveals distinct patterns for developmental and housekeeping gene regulation
Authors: Abnizova Irina , Stapel Carine , Boekhorst Rene te , Lee Jimmy Tsz Hang , Hemberg Martin
Published: April 2024

Background

Regulation of transcription is central to the emergence of new cell types during development, and it often involves activation of genes via proximal and distal regulatory regions. The activity of regulatory elements is determined by transcription factors (TFs) and epigenetic marks, but despite extensive mapping of such patterns, the extraction of regulatory principles remains challenging.

Results

Here we study differentially and similarly expressed genes along with their associated epigenomic profiles, chromatin accessibility and DNA methylation, during lineage specification at gastrulation in mice. Comparison of the three lineages allows us to identify genomic and epigenomic features that distinguish the two classes of genes.

We show that differentially expressed genes are primarily regulated by distal elements, while similarly expressed genes are controlled by proximal housekeeping regulatory programs. Differentially expressed genes are relatively isolated within topologically associated domains, while similarly expressed genes tend to be located in gene clusters. Transcription of differentially expressed genes is associated with differentially open chromatin at distal elements including enhancers, while that of similarly expressed genes is associated with ubiquitously accessible chromatin at promoters.

Conclusion

Based on these associations of (linearly) distal genes’ transcription start sites (TSSs) and putative enhancers for developmental genes, our findings allow us to link putative enhancers to their target promoters and to infer lineage-specific repertoires of putative driver transcription factors, within which we define subgroups of pioneers and co-operators.
Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study
Authors: Santulli Gaetano , Visco Valeria , Ciccarelli Michele , Ferrante Mario Nicola Vittorio , De Masi Piero , Pansini Antonella , Virtuoso Nicola , Pirone Armando , Guerra Germano , Verri Veronica , Macina Gaetano , Taurino Alessandro , Komici Klara , Mone Pasquale
Published: April 2024

Background

Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR).

Methods

We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min.

Results

237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable.

Conclusions

Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.
The development of a novel zeolite-based assay for efficient and deep plasma proteomic profiling
Authors: Li Nan , Huang Jingnan , He Shangwen , Zheng Qiaocong , Ye Feng , Qin Zhengxing , Wang Dong , Xiao Ting , Mao Mengyuan , Zhou Zhenhua , Tang Tingxi , Zhang Longshan , Wang Xiaoqing , Wang Yingqiao , Lyu Ying , Liu Laiyu , Dai Lingyun , Wang Jigang , Guan Jian
Published: April 2024

Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.

Graphical Abstract
Distinct actions of testicular endocrine and lumicrine signaling on the proximal epididymal transcriptome
Authors: Kiyozumi Daiji
Published: April 2024

The epididymal function and gene expression in mammals are under the control of the testis. Sex steroids are secreted from the testis and act on the epididymis in an endocrine manner. There is another, non-sex steroidal secreted signaling, named lumicrine signaling, in which testis-derived secreted proteins go through the male reproductive tract and act on the epididymis. The effects of such multiple regulations on the epididymis by the testis have been investigated for many genes. The recent development of high-throughput next-generation sequencing now enables us a further comparative survey of endocrine and lumicrine action-dependent gene expression. In the present study, testis-derived endocrine and lumicrine actions on epididymal gene expression were comparatively investigated by RNA-seq transcriptomic analyses. This investigation utilized experimental animal models in which testis-derived endocrine and/or lumicrine actions were interfered with, such as unilateral or bilateral orchidectomy. By bilateral orchidectomy, which interferes with both endocrine and lumicrine actions, 431 genes were downregulated. By unilateral orchidectomy, which also interferes with endocrine and lumicrine actions by the unilateral testis, but the endocrine action was compensated by the contralateral testis, 283 genes were downregulated. The content of such genes downregulated by unilateral orchidectomy was like those of lumicrine action-interfered efferent duct-ligation, W/Wv, and Nell2−/− mice. When genes affected by unilateral and bilateral orchidectomy were compared, 154 genes were commonly downregulated, whereas 217 genes were specifically downregulated only by bilateral orchidectomy, indicating the distinction between endocrine and lumicrine actions on the proximal epididymal transcriptome. Comparative transcriptome analyses also showed that the expressions of genes emerging since Amniota were notably impacted by bilateral orchidectomy, unilateral orchidectomy, and lumicrine action-interfering treatments; the degree of influence from these treatments varied based on the evolutionary stage beyond Amniota. These findings unveil an evolutional transition of regulated gene expression in the proximal epididymis by two different testis-derived signaling mechanisms.
Lack of shared neoantigens in prevalent mutations in cancer
Authors: Ragone Concetta , Cavalluzzo Beatrice , Mauriello Angela , Tagliamonte Maria , Buonaguro Luigi
Published: April 2024

Tumors are mostly characterized by genetic instability, as result of mutations in surveillance mechanisms, such as DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. Defect in one or more of these mechanisms causes additive accumulation of mutations. Some of these mutations are drivers of transformation and are positively selected during the evolution of the cancer, giving a growth advantage on the cancer cells. If such mutations would result in mutated neoantigens, these could be actionable targets for cancer vaccines and/or adoptive cell therapies. However, the results of the present analysis show, for the first time, that the most prevalent mutations identified in human cancers do not express mutated neoantigens. The hypothesis is that this is the result of the selection operated by the immune system in the very early stages of tumor development. At that stage, the tumor cells characterized by mutations giving rise to highly antigenic non-self-mutated neoantigens would be efficiently targeted and eliminated. Consequently, the outgrowing tumor cells cannot be controlled by the immune system, with an ultimate growth advantage to form large tumors embedded in an immunosuppressive tumor microenvironment (TME). The outcome of such a negative selection operated by the immune system is that the development of off-the-shelf vaccines, based on shared mutated neoantigens, does not seem to be at hand. This finding represents the first demonstration of the key role of the immune system on shaping the tumor antigen presentation and the implication in the development of antitumor immunological strategies.
Devices used for photobiomodulation of the brain—a comprehensive and systematic review
Authors: Fernandes Filipa , Oliveira Sofia , Monteiro Francisca , Gasik Michael , Silva Filipe S. , Sousa Nuno , Carvalho Óscar , Catarino Susana O.
Published: April 2024

A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer’s or Parkinson’s disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.
Immunopathological investigation and genetic evolution of Avian leukosis virus Subgroup-J associated with myelocytomatosis in broiler flocks in Egypt
Authors: Fotouh Ahmed , Shosha Eman Abd El-Menamm , Zanaty Ali Mahmood , Darwesh Marwa Mostafa
Published: April 2024

Background

Avian leukosis virus Subgroup-J (ALV-J) is a rapidly oncogenic evolving retrovirus infecting a variety of avian species; causing severe economic losses to the local poultry industry.

Methods

To investigate ALV-J, a total of 117 blood samples and 57 tissue specimens of different organs were collected for virological, and pathological identification, serological examinations, molecular characterization, and sequencing analysis. To the best of our knowledge, this is the first detailed report recorded in broiler flocks in Egypt. The present study targets the prevalence of a viral tumor disease circulating in broiler flocks in the El-Sharqia, El-Dakahliya, and Al-Qalyubiyya Egyptian governorates from 2021 to 2023 using different diagnostic techniques besides ALV-J gp85 genetic diversity determination.

Result

We first isolated ALV-J on chicken embryo rough cell culture; showing aggregation, rounding, and degeneration. Concerning egg inoculation, embryonic death, stunting, and curling were observed. Only 79 serum samples were positive for ALV-J (67.52%) based on the ELISA test. Histopathological investigation showed tumors consist of uniform masses, usually well-differentiated myelocytes, lymphoid cells, or both in the liver, spleen, and kidneys. Immunohistochemical examination showed that the myelocytomatosis-positive signals were in the spleen, liver, and kidney. The PCR assay of ALV-J gp85 confirmed 545 base pairs with only 43 positive samples (75.4%). Two positive samples were sequenced and submitted to the Genbank with accession numbers (OR509852–OR509853). Phylogenetic analysis based on the gp85 gene showed that the ALV-J Dakahlia-2 isolate is genetically related to ALV-EGY/YA 2021.3, ALV-EGY/YA 2021.4, ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9 with amino acid identity percentage 96%, 97%; 96%, 96%; respectively. Furthermore, ALV-J Sharqia-1 isolate is highly genetically correlated to ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9, ALV-J isolate QL1, ALV-J isolate QL4, ALV-J isolate QL3, ALV-EGY/YA 2021.4 with amino acid identity percentage 97%, 97%; 98%, 97%, 97%, 95%; respectively.

Conclusions

This study confirmed that ALV-J infection had still been prevalent in broilers in Egypt, and the genetic characteristics of the isolates are diverse.
The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis
Authors: Chen Min , Chen Siyuan , Wang Xinyu , Ye Zongjian , Liu Kehan , Qian Yijing , Tang Meng , Wu Tianshu
Published: April 2024

Background

Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development.

Results

In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson’s disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures.

Conclusion

These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.
Ethno-medicinal uses and cultural importance of stingless bees and their hive products in several ethnic communities of Bhutan
Authors: Gyeltshen Thubten , Bhatta Chet P. , Gurung Tulsi , Dorji Pelden , Tenzin Jigme
Published: April 2024

Background

Indigenous and non-indigenous people in subtropical and temperate areas of Bhutan share an intricate relationship with stingless bees for diverse purposes including ethno-medicinal uses. Stingless bees hold significant importance in the realms of social, economic, cultural, and spiritual aspects. Bhutan's cultural traditions demonstrate a strong bond with the environment, exemplified by the regular use of honey from stingless bees for remedies such as treating the common cold, cough, and sore throat.

Methods

Ethnographic research was conducted to document the ethno-medicinal uses and cultural importance of stingless bees in Bhutan. We deployed semi-structured interviews with stingless beekeepers and honey collectors including traditional healers who perform religious rituals for curing and preventing physical and mental illness.

Results

We documented 22 different uses of stingless bee honey in food, medicine, veterinary medicine, crafts, beliefs, and religious purposes. The relative cultural importance (RCI) of stingless bees among Bhutan's ethnic communities was assessed through our calculations. It was determined that these bees hold notably greater significance for the Lhotshampa communities compared to other ethnic groups in Bhutan. This finding demonstrates the dependence of Hindu ethnic communities on natural resources in their everyday life. All participant communities largely exploit these bees through destructive extraction practices. They often find the natural nests in nearby forests, transfer them as a log hive to their backyards, and practice traditional meliponiculture.

Conclusion

The ethnic communities of Bhutan use stingless bees for various purposes and the local knowledge are persistent. However, significant efforts should be made to address the ethno-medicinal, ecological, biological, and commercial perspectives of meliponiculture in Bhutan.
Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression
Authors: Qiao Yaya , Su Meng , Zhao Huifang , Liu Huanle , Wang Chenxi , Dai Xintong , Liu Lingling , Liu Guangju , Sun Huanran , Sun Mingming , Wang Jiyan , Li Zhen , Fan Jun , Zhang Quan , Li Chunshen , Situ Fangmin , Xue Jun , Jia Zhenghu , Zhang Chunze , Zhang Shuai , Shan Changliang
Published: April 2024

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.
Etiology of diarrheal hospitalizations following rotavirus vaccine implementation and association of enteric pathogens with malnutrition among under-five children in India
Authors: Varghese Tintu , Mills James A. Platts , Revathi R. , Antoni Sebastien , Soeters Heidi M. , Emmanuel Njambe Tondo Opute , Houpt Eric R. , Tate Jacqueline E. , Parashar Umesh D. , Kang Gagandeep
Published: April 2024

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition. In addition, we looked at the pathogen diversity of pediatric diarrhea, three years after the nationwide rotavirus vaccine introduction to understand the evolving landscape of pathogens, which is crucial for planning strategies to further reduce the diarrhea burden. Clinical details and diarrheal stool samples were collected from hospitalized children aged < 5 years from three sentinel sites in India for a period of one year. The samples were tested by qPCR for 16 established causes of diarrhea using TaqMan Array Cards. A total of 772 children were enrolled, from whom 482 (62.4%) stool specimens were tested. No specific pathogen was associated with diarrhea among children with acute or chronic malnutrition compared to those with better nutritional status. Overall, adenovirus was the leading pathogen (attributable fraction (AF) 16.9%; 95% CI 14.1 to 19.2) followed by rotavirus (AF 12.6%; 95% CI 11.8 to 13.1) and Shigella (AF 10.9%; 95% CI 8.4 to 16.4). The majority of diarrhea requiring hospitalization in children aged < 2 years could be attributed to viruses, while Shigella was the most common pathogen among children aged > 2 years. These data on the prevalence and epidemiology of enteropathogens identified potential pathogens for public health interventions.
Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals
Authors: Fujishima Motonobu , Kawasaki Yohei , Mitsuhashi Toshiharu , Matsuda Hiroshi ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2024

Background

Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods.

Methods

This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models.

Results

A total of 367 participants (48 A + T + , 86 A + T − , 63 A − T + , and 170 A − T − ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T − and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A − T − group (lateral ventricle: β = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T − , and β = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β =  − 0.19 /year [− 0.36 to − 0.02], P = .029 for A + T − , and β =  − 0.59 /year [− 0.80 to − 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β =  − 2.782 cm3/year [− 4.060 to − 1.504], P < .001), hippocampus (β =  − 0.057 cm3/year [− 0.085 to − 0.029], P < .001), and AD-signature regions (β =  − 0.02 mm/year [− 0.03 to − 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A − T − group (adjusted hazard ratio = 3.35 [1.76 to 6.39]).

Conclusions

In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression.
Surveillance of catheter-associated bloodstream infections: development and validation of a fully automated algorithm
Authors: Catho Gaud , Fortchantre Loïc , Teixeira Daniel , Galas-Haddad Murielle , Boroli Filippo , Chraïti Marie-Noëlle , Abbas Mohamed , Harbarth Stephan , Buetti Niccolò ,   Swissnoso group, Balmelli Carlo , Berthod Delphine , Jent Philipp , Marschall Jonas , Sax Hugo , Schlegel Matthias , Schweiger Alexander , Senn Laurence , Sommerstein Rami , Tschudin-Sutter Sarah , Troillet Nicolas , Vuichard-Gysin Danielle , Widmer Andreas F. , Wolfensberger Aline , Zingg Walter
Published: April 2024

Background

Most surveillance systems for catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI) are based on manual chart review. Our objective was to validate a fully automated algorithm for CRBSI and CLABSI surveillance in intensive care units (ICU).

Methods

We developed a fully automated algorithm to detect CRBSI, CLABSI and ICU-onset bloodstream infections (ICU-BSI) in patients admitted to the ICU of a tertiary care hospital in Switzerland. The parameters included in the algorithm were based on a recently performed systematic review. Structured data on demographics, administrative data, central vascular catheter and microbiological results (blood cultures and other clinical cultures) obtained from the hospital’s data warehouse were processed by the algorithm. Validation for CRBSI was performed by comparing results with prospective manual BSI surveillance data over a 6-year period. CLABSI were retrospectively assessed over a 2-year period.

Results

From January 2016 to December 2021, 854 positive blood cultures were identified in 346 ICU patients. The median age was 61.7 years [IQR 50–70]; 205 (24%) positive samples were collected from female patients. The algorithm detected 5 CRBSI, 109 CLABSI and 280 ICU-BSI. The overall CRBSI and CLABSI incidence rates determined by automated surveillance for the period 2016 to 2021 were 0.18/1000 catheter-days (95% CI 0.06–0.41) and 3.86/1000 catheter days (95% CI: 3.17–4.65). The sensitivity, specificity, positive predictive and negative predictive values of the algorithm for CRBSI, were 83% (95% CI 43.7–96.9), 100% (95% CI 99.5–100), 100% (95% CI 56.5–100), and 99.9% (95% CI 99.2–100), respectively. One CRBSI was misclassified as an ICU-BSI by the algorithm because the same bacterium was identified in the blood culture and in a lower respiratory tract specimen. Manual review of CLABSI from January 2020 to December 2021 (n = 51) did not identify any errors in the algorithm.

Conclusions

A fully automated algorithm for CRBSI and CLABSI detection in critically-ill patients using only structured data provided valid results. The next step will be to assess the feasibility and external validity of implementing it in several hospitals with different electronic health record systems.
Stress, interpersonal and inter-role conflicts, and psychological health conditions among nurses: vicious and virtuous circles within and beyond the wards
Authors: Vallone Federica , Zurlo Maria Clelia
Published: April 2024

Background

The increasing costs of nurses’ occupational-stress, conflicts, and violence within healthcare services have raised international interest. Yet, research/interventions should consider that perceived stress and conflicts– but also potential resources– within the wards can crossover the healthcare settings, impacting nurses’ private lives and viceversa, potentially creating vicious circles exacerbating stress, conflicts/violence or, conversely, virtuous circles of psychological/relational wellbeing. Based on the Demands-Resources-and-Individual-Effects (DRIVE) Nurses Model, and responding to the need to go in-depth into this complex dynamic, this study aims to explore potential vicious circles featured by the negative effects of the interplay (main/mediating effects) between perceived stressors in nursing linked to interpersonal conflicts (Conflicts-with-Physicians, Peers, Supervisors, Patients/their families), work-family inter-role conflicts (Work-Family/Family-Work-Conflicts), and work-related stress (Effort-Reward-Imbalance) on nurses’ psychological/relational health (Anxiety, Depression, Somatization, Interpersonal-Sensitivity, Hostility). The potential moderating role of work-resources (Job-Control, Social-Support, Job-Satisfaction) in breaking vicious circles/promoting virtuous circles was also explored.

Method

The STROBE Checklist was used to report this cross-sectional multi-centre study. Overall, 265 nurses completed self-report questionnaires. Main/mediating/moderating hypotheses were tested by using Correlational-Analyses and Hayes-PROCESS-tool.

Results

Data confirmed the hypothesized detrimental vicious circles (main/mediating effects), impairing nurses’ psychological health conditions at individual level (Anxiety, Depression, Somatization), but also at relational level (Hostility and Interpersonal-Sensitivity). The moderating role of all work resources was fully supported.

Conclusion

Findings could be used to implement interventions/practices to effectively prevent the maintenance/exacerbation of vicious circles and promote psychological/relational wellbeing in healthcare settings and beyond.
B-CAT: a model for detecting botnet attacks using deep attack behavior analysis on network traffic flows
Authors: Putra Muhammad Aidiel Rachman , Ahmad Tohari , Hostiadi Dandy Pramana
Published: April 2024

Threats on computer networks have been increasing rapidly, and irresponsible parties are always trying to exploit vulnerabilities in the network to do various dangerous things. One way to exploit vulnerabilities in a computer network is by employing malware. Botnets are a type of malware that infects and attacks targets in groups. Botnets develop quickly; the characteristics of initially sporadic attacks have grown into periodic and simultaneous. This rapid development has proved that the botnet is advanced and requires more attention and proper handling. Many studies have introduced detection models for botnet attack activity on computer networks. Apart from detecting the presence of botnet attacks, those studies have attempted to explore the characteristics of botnets, such as attack intensity, relationships between activities, and time segment analysis. However, there has been no research that explicitly detects those characteristics. On the other hand, each botnet characteristic requires different handling, while recognizing the characteristics of the botnet can help network administrators make appropriate decisions. Based on these reasons, this research builds a detection model that can recognize botnet characteristics using sequential traffic mining and similarity analysis. The proposed method consists of two main processes. The first is training to build a knowledge base, and the second is testing to detect botnet activity and attack characteristics. It involves dynamic thresholds to improve the model sensitivity in recognizing attack characteristics through similarity analysis. The novelty includes developing and combining analytical techniques of sequential traffic mining, similarity analysis, and dynamic threshold to detect and recognize the characteristics of botnet attacks explicitly on actual behavior in network traffic. Extensive experiments have been conducted for the evaluation using three different datasets whose results show better performance than others.
Improving medication prescribing-related outcomes for vulnerable elderly in transitions on high-risk medications (IMPROVE-IT HRM): a pilot randomized trial protocol
Authors: Holbrook Anne , Perri Dan , Levine Mitch , Mbuagbaw Lawrence , Jarmain Sarah , Thabane Lehana , Tarride Jean-Eric , Dolovich Lisa , Hyland Sylvia , Telford Victoria , Silva Jessyca , Nieuwstraten Carmine
Published: April 2024

Background

Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group.

Methods

The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility — recruitment, retention, costs, and clinical — number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge.

Discussion

If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely.

Trial registration number

ClinicalTrials.gov identifier: NCT04077281.
The diagnostic efficacy of diffusion tensor imaging in children with chronic kidney disease: correlation with histopathology and serum biomarkers
Authors: Mansour Manar , Elmokadem Ali H. , Elrazek Ahmed A. Abd , Hammad Ayman , Abd-Almoaty Marwa R. , Ali Khadiga M. , Ibrahim Dina Abdalla , Barakat Tarek Elsayed
Published: April 2024

Background

Children with chronic kidney disease (CKD) usually present with disease impact on growth besides cardiovascular problems that not only impact the patient's health during childhood but also affect their adult life. We aimed to identify the diagnostic role of diffusion tensor imaging (DTI) in CKD in pediatric using its metrics: apparent diffusion coefficient (ADC) and fraction anisotropy (FA).

Results

This prospective study was performed on thirty-five CKD patients (16 girls, 19 boys; mean age 12.3 ± 2.6 years) and 19 sex- and age-matched controls. Both groups underwent renal DTI and renal function tests. Based on renal biopsy, patients with CKD were further categorized into sclerotic CKD (n = 25) and non-sclerotic CKD (n = 10). Mean FA renal medulla/cortex in CKD (0.18 ± 0.18 and 0.20 ± 0.17) was lower significantly (p = 0.001) than volunteers' (0.31 ± 0.19, 0.27 ± 0.18). The cutoff FA of renal medulla/cortex used for CKD diagnosis was 0.22 and 0.23 with AUC of 0.828, 0.838 and accuracy of 80.8%, 82.8%. Mean of renal medulla/cortex ADC in CKD (2.13 ± 0.23 and 1.93 ± 0.22 × 10−3 mm2/s) was higher significantly (p = 0.001) than that of volunteers' (1.67 ± 0.15 and 1.64 ± 0.133 × 10−3 mm2/s. ADC cutoff value of renal medulla/cortex used for CKD diagnosis was 1.86 and 1.74 × 10−3 mm2/s with AUC of 0.827, 0.82, 0.827, and 0.911, and accuracy of 80.6%, 79.6%, 82.8%, and 84.2%. Renal medulla/cortex FA in sclerotic CKD was significantly different (p = 0.001) from non-sclerotic CKD (0.25 ± 0.07 and 0.26 ± 0.08). Cortical and medullary FA in CKD patients correlated with e-GFR (r = 0.363, r = 0.317) and serum creatinine (r = − 0.467, r = − 0.383).

Conclusions

Renal cortical/medullary FA can assist in diagnosing pediatric CKD, predict sclerotic CKD, and correlate with some serum biomarkers.
Brillouin microscopy monitors rapid responses in subcellular compartments
Authors: Coker Zachary N. , Troyanova-Wood Maria , Steelman Zachary A. , Ibey Bennett L. , Bixler Joel N. , Scully Marlan O. , Yakovlev Vladislav V.
Published: April 2024

Measurements and imaging of the mechanical response of biological cells are critical for understanding the mechanisms of many diseases, and for fundamental studies of energy, signal and force transduction. The recent emergence of Brillouin microscopy as a powerful non-contact, label-free way to non-invasively and non-destructively assess local viscoelastic properties provides an opportunity to expand the scope of biomechanical research to the sub-cellular level. Brillouin spectroscopy has recently been validated through static measurements of cell viscoelastic properties, however, fast (sub-second) measurements of sub-cellular cytomechanical changes have yet to be reported. In this report, we utilize a custom multimodal spectroscopy system to monitor for the very first time the rapid viscoelastic response of cells and subcellular structures to a short-duration electrical impulse. The cytomechanical response of three subcellular structures - cytoplasm, nucleoplasm, and nucleoli - were monitored, showing distinct mechanical changes despite an identical stimulus. Through this pioneering transformative study, we demonstrate the capability of Brillouin spectroscopy to measure rapid, real-time biomechanical changes within distinct subcellular compartments. Our results support the promising future of Brillouin spectroscopy within the broad scope of cellular biomechanics.
The exotic rust fungus
Puccinia abrupta
var.
partheniicola
on the invasive alien weed
Parthenium hysterophorus
in India: rediscovery and first report of an epiphytotic
Authors: Sreerama Kumar Prakya
Published: April 2024

Puccinia abrupta
var.
partheniicola
, the so-called winter rust of parthenium weed (
Parthenium hysterophorus
), an invasive alien weed in India, was rediscovered at an epiphytotic scale in February 2023 following a prolonged period of presumed absence in the field. Disease incidence was 80–90% in large tracts of
P. hysterophorus
stands along the roadsides in an area of 5 km
2
near Attibele–Sarjapura road (948A) in Anekal taluk of Bengaluru Urban district in Karnataka. Pycnial, aecial or telial stages of the rust were not found. The morphological parameters of uredinia and urediniospores completely matched those originally described, thus confirming the fungal identity. The significance of this rust epiphytotic to
P. hysterophorus
biocontrol in India is discussed together with the planned follow-up activities.
Numerical assessment of using FRP rebars as an alternative passive reinforcement in RC beams
Authors: Abdo Marwan , Abdelwahed Basem , El-Metwally Salah
Published: April 2024

Recent sustainable building strategies make the right decisions to be environmentally friendly and reduce carbon emissions. In some reinforced concrete (RC) elements, fiber-reinforced polymer (FRP) bars have been proposed as an alternative to conventional steel bars. The demand for using noncorrosive and/or nonmetallic reinforcing bars in various reinforced concrete projects has increased. Although these concrete elements are lightweight, have a long lifespan, and need little maintenance, their non-ductile nature and bond with the surrounding concrete create significant challenges. Several experimental investigations have been conducted to evaluate the behavior of RC elements, even with their high cost. This study aims to assess numerically the viability of using FRP bars instead of traditional steel ones in simply supported reinforced concrete beams (RCBs) as longitudinal reinforcement (passive reinforcement). Utilizing the three-dimensional (3D) nonlinear finite element analysis (FEA) software (ABAQUS), a total of eighteen models were carried out to validate the results available in reference case studies with FRP bars. The verification of the numerical results has been verified by comparing them with the reference experimental data. Next, in order to assess the rigidity of such RCBs with FRP bars, parametric research was carried out. The numerical results proved that RCBs with FRP bars have a positive impact on enhancing load-carrying capacities. But on the other hand, the strain energy of such RCBs with CFRP bars is reduced to about 75% of the strain energy of RCBs with steel bars, which leads to low beam ductility.