bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases
Authors: Saeedi-Boroujeni Ali , Purrahman Daryush , Shojaeian Ali , Poniatowski Łukasz A. , Rafiee Fatemeh , Mahmoudian-Sani Mohammad-Reza 
Published: January 2023

AbstractImmune dysregulation has been identified as a critical cause of the most common types of cardiovascular diseases (CVDs). Notably, the innate and adaptive immune responses under physiological conditions are typically regulated with high sensitivity to avoid the exacerbation of inflammation, but any dysregulation can probably be associated with CVDs. In this respect, progranulin (PGRN) serves as one of the main components of the regulation of inflammatory processes, which significantly contributes to the immunopathogenesis of such disorders. PGRN has been introduced among the secreted growth factors as one related to wound healing, inflammation, and human embryonic development, as well as a wide variety of autoimmune diseases. The relationship between the serum PGRN and TNF-α ratio with the spontaneous bacterial peritonitis constitute one of the independent predictors of these conditions. The full-length PGRN can thus effectively reduce the calcification of valve interstitial cells, and the granulin precursor (GRN), among the degradation products of PGRN, can be beneficial. Moreover, it was observed that, PGRN protects the heart against ischemia-reperfusion injury. Above all, PGRN also provides protection in the initial phase following myocardial ischemia-reperfusion injury. The protective impact of PGRN on this may be associated with the early activation of the PI3K/Akt signaling pathway. PGRN also acts as a protective factor in hyperhomocysteinemia, probably by down-regulating the wingless-related integration site Wnt/β-catenin signaling pathway. Many studies have further demonstrated that SARS-CoV-2 (COVID-19) has dramatically increased the risks of CVDs due to inflammation, so PGRN has drawn much more attention among scholars. Lysosomes play a pivotal role in the inflammation process, and PGRN is one of the key regulators in their functioning, which contributes to the immunomodulatory mechanism in the pathogenesis of CVDs. Therefore, investigation of PGRN actions can help find new prospects in the treatment of CVDs. This review aims to summarize the role of PGRN in the immunopathogenesis of CVD, with an emphasis on its treatment.
Factors affecting the quality of life after ischemic stroke in young adults: a scoping review
Authors: Gurková Elena , Štureková Lenka , Mandysová Petra , Šaňák Daniel 
Published: January 2023

Abstract
Purpose
To synthesize the body of knowledge on the factors influencing the quality of life (QoL) after ischemic stroke (IS) in young adults.

Methods
Guidelines regarding the scoping review methodology developed by the Joanna Briggs Institute, and the PRISMA-ScR checklist for a scoping review was used in this paper. A total of 1197 studies were identified through a bibliographic search in Web of Science, MEDLINE, PsycInfo, ScienceDirect, Scopus, and ProQuest Science Database. Articles published between the years 2000–2021 were included.

Results
A total of nine papers were finally selected to respond to the research question. Three studies were prospective longitudinal studies compared QoL between young stroke and age-matched controls from the general population. Across all the analysed studies, 14 variables potentially associated with QoL were identified. QoL in young patients is mainly affected by clinical outcomes after IS (scored by the modified Rankin scale and the Barthel index—favourable initial functional status and higher independence in ADL leads to higher QoL) and psychological factors (post-stroke fatigue and depression—higher levels of fatigue and depression lead to lower QoL). The reviewed studies emphasized the importance of functional outcomes, post-stroke depression, fatigue and anxiety and early return to work.

Conclusion
Further longitudinal studies are needed to identify the trajectory of post-stroke psychosocial symptoms over time and other potential predictors of unfavourable long-term QoL, thus specific young stroke rehabilitation and stroke self-management support programmes should be developed (address physical, psychological factors which influence the psychosocial adaptation post-stroke and the perception of the QoL).
Sequestration of Gβγ by deubiquitinated arrestins into the nucleus as a novel desensitization mechanism of G protein–coupled receptors
Authors: Min Xiao , Sun Ningning , Wang Shujie , Zhang Xiaohan , Kim Kyeong-Man 
Published: January 2023

Abstract
Background
Desensitization of G protein–coupled receptors (GPCRs) refers to a rapid attenuation of responsiveness that occurs with repeated or continuous exposure to agonists. GRK-mediated phosphorylation and subsequent binding with arrestins in the activated receptor cytoplasmic cavity in competition with G proteins has been suggested as the conventional mechanism of desensitization. Along with widely accepted conventional mechanism of desensitization, studies of various GPCRs including dopamine D2-like receptors (D2R, D3R, D4R) have suggested the existence of another desensitization mechanism. In this study, loss-of-function approaches and D2-like receptor mutants that display different desensitization properties were used to elucidate the molecular mechanisms responsible for desensitization.

Results
Desensitization development entailed the signaling cascade composed of Src, PDK1, and Akt, the latter of which in turn interacted with USP33, an arrestin deubiquitinase, to promote arrestin deubiquitination. The deubiquitinated arrestin subsequently formed a complex with Gβγ and translocated to the nucleus via an importin complex, wherein it sequestered Gβγ from the receptor and Gα, thereby attenuating receptor signaling. As in D2-like receptors, both USP33 and importin β1 were involved in the desensitization of the β2 adrenoceptor.

Conclusions
In addition to the conventional mechanism of desensitization, which occurs on the plasma membrane and in the cytosol, this study provides a new insight that another desensitization pathway in which nuclear trafficking plays a critical role is operating. It is plausible that multiple, complementary desensitization measures are in place to properly induce desensitization depending on receptor characteristics or the surrounding environment.
Role of Calcr expressing neurons in the medial amygdala in social contact among females
Authors: Fukumitsu Kansai , Huang Arthur J. , McHugh Thomas J. , Kuroda Kumi O. 
Published: January 2023

AbstractSocial animals become stressed upon social isolation, proactively engaging in affiliative contacts among conspecifics after resocialization. We have previously reported that calcitonin receptor (Calcr) expressing neurons in the central part of the medial preoptic area (cMPOA) mediate contact-seeking behaviors in female mice. Calcr neurons in the posterodorsal part of the medial amygdala (MeApd) are also activated by resocialization, however their role in social affiliation is still unclear. Here we first investigated the functional characteristics of MeApd Calcr + cells; these neurons are GABAergic and show female-biased Calcr expression. Next, using an adeno-associated virus vector expressing a short hairpin RNA targeting Calcr we aimed to identify its molecular role in the MeApd. Inhibiting Calcr expression in the MeApd increased social contacts during resocialization without affecting locomotor activity, suggesting that the endogenous Calcr signaling in the MeApd suppresses social contacts. These results demonstrate the distinct roles of Calcr in the cMPOA and MeApd for regulating social affiliation.
Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains
Authors: Spadar Anton , Perdigão João , Campino Susana , Clark Taane G. 
Published: January 2023

Abstract
Background
Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions.

Methods
Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp.

Results
We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones.

Conclusions
Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.
Does inflammation markers or treatment type moderate exercise intensity effects on changes in muscle strength in cancer survivors participating in a 6-month combined resistance- and endurance exercise program? Results from the Phys-Can trial
Authors: Henriksson Anna , Strandberg Emelie , Stenling Andreas , Mazzoni Anne-Sophie , Sjövall Katarina , Börjeson Sussanne , Raastad Truls , Demmelmaier Ingrid , Berntsen Sveinung , Nordin Karin 
Published: January 2023

AbstractBackgroundResistance exercise has a beneficial impact on physical function for patients receiving oncological treatment. However, there is an inter-individual variation in the response to exercise and the tolerability to high-intensity exercise. Identifying potential moderating factors, such as inflammation and treatment type, for changes in muscle strength is important to improve the effectiveness of exercise programs. Therefore, we aimed to investigate if inflammation and type of oncological treatment moderate the effects of exercise intensity (high vs. low-moderate) on muscular strength changes in patients with breast (BRCA) or prostate cancer (PRCA).MethodsParticipants with BRCA (n = 286) and PRCA (n = 65) from the Physical training and Cancer study (Phys-Can) were included in the present study. Participants performed a combined resistance- and endurance exercise program during six months, at either high or low-moderate intensity. Separate regression models were estimated for each cancer type, with and without interaction terms. Moderators included in the models were treatment type (i.e., neo/adjuvant chemotherapy—yes/no for BRCA, adjuvant androgen deprivation therapy (ADT)—yes/no for PRCA)), and inflammation (interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα)) at follow-up.ResultsFor BRCA, neither IL6 (b = 2.469, 95% CI [− 7.614, 12.552]) nor TNFα (b = 0.036, 95% CI [− 6.345, 6.418]) levels moderated the effect of exercise intensity on muscle strength change. The same was observed for chemotherapy treatment (b = 4.893, 95% CI [− 2.938, 12.724]). Similarly, for PRCA, the effect of exercise intensity on muscle strength change was not moderated by IL6 (b = − 1.423, 95% CI [− 17.894, 15.048]) and TNFα (b = − 1.905, 95% CI [− 8.542, 4.732]) levels, nor by ADT (b = − 0.180, 95% CI [− 11.201, 10.841]).ConclusionsThe effect of exercise intensity on muscle strength is not moderated by TNFα, IL6, neo/adjuvant chemotherapy, or ADT, and therefore cannot explain any intra-variation of training response regarding exercise intensity (e.g., strength gain) for BRCA or PRCA in this setting.Trial registration: ClinicalTrials.gov NCT02473003.
Acceptability and use of waist-worn physical activity monitors in Jamaican adolescents: lessons from the field
Authors: Smith Joanne A. , Christie Sara-Lou , Rockette-Wagner Bonny , Wilson Lorraine , Govia Ishtar O. , Facey Keri-Ann , Tulloch-Reid Marshall K. 
Published: January 2023

Abstract
Objective
We report our experience with a validated waist-worn activity monitor in Jamaican adolescents attending urban high schools. Seventy-nine adolescents from the Global Diet and Activity Research (GDAR) study, recruited from 5 urban Jamaican high schools (two coeducational (n = 37), two all-female schools (n = 32) and one all-boys school (n = 10)) were asked to wear Actigraph wGT3X-BT accelerometers for 7 days (24-h), removing the device only when bathing or swimming. They also logged wake up and bed times in an activity diary. Accelerometry was considered valid if at least 4 days with ≥ 10-h monitor wear were recorded. Validity was compared by adolescent demographic and school characteristics. We also reviewed the students’ written feedback on objective physical activity measurement.

Results
Participants, 80.5% female, had a mean age of 15.5 ± 0.8 years with 60% attending schools in low-income communities. Accelerometer return rates were > 98% with 84% providing valid data. Validity did not vary by age group, sex and school setting. While participants were excited about participating in the accelerometer sub-study, commonly reported challenges included monitor discomfort during sleep and maintaining the study diary. Objective measurement of physical activity using 24-h waist-worn accelerometers is feasible and acceptable in Jamaican adolescents.
Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells
Authors: Kim Jee Yeon , Jelinek Jaroslav , Lee Young Ho , Kim Dae Hyun , Kang Keunsoo , Ryu Su Hyun , Moon Hye Rin , Cho Kwangjo , Rha Seo Hee , Cha Jae Kwan , Issa Jean-Pierre J. , Kim Jei 
Published: January 2023

Abstract
Background
Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be used as an epigenetic tool to evaluate the impact of aging and the environment on atherosclerosis development. However, gene-specific methylation changes are currently inadequate epigenetic markers for predicting atherosclerosis and cardiovascular disease pathogenesis.

Results
We profiled and validated changes in gene-specific promoter methylation associated with atherosclerosis using stenosis radiophenotypes of cranial vessels and blood inflammatory cells rather than direct sampling of atherosclerotic plaques. First, we profiled gene-specific promoter methylation changes using digital restriction enzyme analysis of methylation (DREAM) sequencing in peripheral blood mononuclear cells from eight samples each of cranial vessels with and without severe-stenosis radiophenotypes. Using DREAM sequencing profiling, 11 tags were detected in the promoter regions of the ACVR1C, ADCK5, EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PACSIN3, PAX8-AS1, TLDC1, and ZNF7 genes. Using methylation evaluation, we found that EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PAX8-AS1, and TLDC1 showed > 5% promoter methylation in non-plaque intima, atherosclerotic vascular tissues, and buffy coats. Using logistic regression analysis, we identified hypomethylation of MTNR1B as an independent variable for the stenosis radiophenotype prediction model by combining it with traditional atherosclerosis risk factors including age, hypertension history, and increases in creatinine, lipoprotein (a), and homocysteine. We performed fivefold cross-validation of the prediction model using 384 patients with ischemic stroke (50 [13%] no-stenosis and 334 [87%] > 1 stenosis radiophenotype). For the cross-validation, the training dataset included 70% of the dataset. The prediction model showed an accuracy of 0.887, specificity to predict stenosis radiophenotype of 0.940, sensitivity to predict no-stenosis radiophenotype of 0.533, and area under receiver operating characteristic curve of 0.877 to predict stenosis radiophenotype from the test dataset including 30% of the dataset.

Conclusions
We identified and validated MTNR1B hypomethylation as an epigenetic marker to predict cranial vessel atherosclerosis using stenosis radiophenotypes and blood inflammatory cells rather than direct atherosclerotic plaque sampling.
Isolation and screening of low-density polyethylene (LDPE) bags degrading bacteria from Addis Ababa municipal solid waste disposal site “Koshe”
Authors: Nademo Zuriash Mamo , Shibeshi Nurelegne Tefera , Gemeda Mesfin Tafesse 
Published: January 2023

Abstract
Purpose
This study aims to screen bacterial isolates from the Addis Ababa municipal solid waste dumping site (Koshe) for the biodegradation of low-density polyethylene bags and analyzes their efficiency in degrading plastic bags.

Methods
In this study, low-density polyethylene bag-degrading bacteria were isolated from the Koshe municipal solid waste disposal area in Addis Ababa, Ethiopia. Screening of isolates for low-density polyethylene bag biodegradation was carried out using a clear zone method. Additionally, the efficiency of the isolates for low-density polyethylene biodegradation was evaluated using the weight loss method, scanning electron microscopy analysis, and Fourier transform infrared analysis. Finally, molecular identification of potential low-density polyethylene degrader bacterial isolates was done by 16S rDNA sequencing.

Results
Isolates KS35, KS14, and KS119 resulted in significant weight loss of low-density polyethylene film (42.87 ± 1.91%, 37.2 ± 3.06%, and 23.87 ± 0.11% weight loss, respectively). These isolates were selected for further biodegradation study using scanning electron microscopy and Fourier transform infrared analysis. Scanning electron microscopy analysis shows the formation of pores, pits, and distortion of the plastic surface. Fourier transform infrared analysis indicates the appearance of new peaks at the surface of low-density polyethylene films. Phylogenetic analysis of the three potential bacterial isolates was also carried out, and the result indicates that the sequence of isolate KS35 had 99% similarity with sequences of Methylobacterium radiotolerans MN525302. Isolate KS119 had 100% similarity with Methylobacterium fujisawaense KT720189, and the sequence of isolate KS14 had 99% similarity with species of Lysinibacillus fusiformis.

Conclusions
Weight loss, scanning electron microscopy analysis, and Fourier transform infrared analysis results show that isolates KS35, KS14, and KS119 have high potential in degrading low-density polyethylene bags.
Dimensionally reduced machine learning model for predicting single component octanol–water partition coefficients
Authors: Kenney David H. , Paffenroth Randy C. , Timko Michael T. , Teixeira Andrew R. 
Published: January 2023

AbstractMF-LOGP, a new method for determining a single component octanol–water partition coefficients ($$LogP$$

LogP

) is presented which uses molecular formula as the only input. Octanol–water partition coefficients are useful in many applications, ranging from environmental fate and drug delivery. Currently, partition coefficients are either experimentally measured or predicted as a function of structural fragments, topological descriptors, or thermodynamic properties known or calculated from precise molecular structures. The MF-LOGP method presented here differs from classical methods as it does not require any structural information and uses molecular formula as the sole model input. MF-LOGP is therefore useful for situations in which the structure is unknown or where the use of a low dimensional, easily automatable, and computationally inexpensive calculations is required. MF-LOGP is a random forest algorithm that is trained and tested on 15,377 data points, using 10 features derived from the molecular formula to make $$LogP$$

LogP

predictions. Using an independent validation set of 2713 data points, MF-LOGP was found to have an average $$RMSE$$

RMSE

= 0.77 ± 0.007, $$MAE$$

MAE

= 0.52 ± 0.003, and $${R}^{2}$$

R

2

= 0.83 ± 0.003. This performance fell within the spectrum of performances reported in the published literature for conventional higher dimensional models ($$RMSE$$

RMSE

= 0.42–1.54, $$MAE$$

MAE

= 0.09–1.07, and $${R}^{2}$$

R

2

= 0.32–0.95). Compared with existing models, MF-LOGP requires a maximum of ten features and no structural information, thereby providing a practical and yet predictive tool. The development of MF-LOGP provides the groundwork for development of more physical prediction models leveraging big data analytical methods or complex multicomponent mixtures.
Graphical Abstract
COMA: efficient structure-constrained molecular generation using contractive and margin losses
Authors: Choi Jonghwan , Seo Sangmin , Park Sanghyun 
Published: January 2023

Abstract
Background
Structure-constrained molecular generation is a promising approach to drug discovery. The goal of structure-constrained molecular generation is to produce a novel molecule that is similar to a given source molecule (e.g. hit molecules) but has enhanced chemical properties (for lead optimization). Many structure-constrained molecular generation models with superior performance in improving chemical properties have been proposed; however, they still have difficulty producing many novel molecules that satisfy both the high structural similarities to each source molecule and improved molecular properties.

Methods
We propose a structure-constrained molecular generation model that utilizes contractive and margin loss terms to simultaneously achieve property improvement and high structural similarity. The proposed model has two training phases; a generator first learns molecular representation vectors using metric learning with contractive and margin losses and then explores optimized molecular structure for target property improvement via reinforcement learning.

Results
We demonstrate the superiority of our proposed method by comparing it with various state-of-the-art baselines and through ablation studies. Furthermore, we demonstrate the use of our method in drug discovery using an example of sorafenib-like molecular generation in patients with drug resistance.