bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fit for Work and Life—an eight-week program for improvement of functionality and quality of life
Authors: Pausch Kunigunde , Blanke Katrin , Niederberger Verena , Egli Sarah , Rufer Michael , Ajdacic-Gross Vladeta , Olbrich Sebastian , Müller Mario 
Published: April 2022

Summary
Background
The current two-stage study focused on work integration and quality of life of patients in an acute psychiatric day care unit. There is evidence that a longer absence from work due to illness negatively affects job retention, life satisfaction and clinical prognosis. Furthermore, there are individual supportive methods that proved to be effective in work integration. We therefore developed a specific group program Fit for Work and Life (FWL) for patients in an acute psychiatric day care unit focusing on work integration in the first labor market (in contrast to work in institutions for people with disabilities/second labor market).

Methods
Between 2018 and 2020, 62 patients (intervention group; IG) were enrolled in an 8‑week prospective job integration program and compared to 74 patients (control group; CG) who received treatment as usual (partly retrospective survey). Patients of both groups held a job when entering treatment. Main outcome was defined as their working status 4 weeks after the end of treatment as well as self-reported life satisfaction.

Results
At the end of treatment (i.e. the week prior to discharge), the IG participants reported higher overall life satisfaction as well as higher health-, self- and living condition-related satisfaction than controls. Functional and clinical improvement during treatment was linked to subsequently returning to work. Functional improvement was further linked to higher life satisfaction. Mediational analysis revealed an indirect path from functional improvement on life satisfaction via working status, i.e. the higher functional improvement during treatment, the higher the chance of successfully returning to work, which in turn increased life satisfaction.

Conclusion
Our findings suggest that programs such as FWL are useful interventions for employed patients to improve reintegration into work and life and to help to increase life satisfaction.
Anti-Parkinsonian Therapy: Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials
Authors: Cheng Guowang , Liu Yujing , Ma Rui , Cheng Guopan , Guan Yucheng , Chen Xiaojia , Wu Zhenfeng , Chen Tongkai 
Published: April 2022

AbstractParkinson’s disease (PD), a neurodegenerative disease that shows a high incidence in older individuals, is becoming increasingly prevalent. Unfortunately, there is no clinical cure for PD, and novel anti-PD drugs are therefore urgently required. However, the selective permeability of the blood–brain barrier (BBB) poses a huge challenge in the development of such drugs. Fortunately, through strategies based on the physiological characteristics of the BBB and other modifications, including enhancement of BBB permeability, nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB. Although nanomaterials are often used as carriers for PD treatment, their biological activity is ignored. Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects. In this review, we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment. Subsequently, we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects. Finally, we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field. Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.
Biochar-induced changes in the soil diazotroph community abundance and structure in a peanut field trial
Authors: Chen Kun , Li Na , Zhang Shiyu , Liu Ning , Yang Jinfeng , Zhan Xiumei , Han Xiaori 
Published: April 2022

AbstractBiological nitrogen fixation (BNF) can help replenish available nitrogen (N) in cropland and reduce the use of chemical N fertilizers, with diazotrophs playing an important role. However, the response of diazotroph community and BNF activity in biochar amendment soil, especially in the deep soil horizon, are poorly understood. In this study, soil samples were collected from topsoil (0–20 cm) and subsoil (20–40 cm) in the field experiment (established in 2013) comprising treatments with no chemical fertilizer (CK), chemical fertilizer (NPK), biochar (BC), and biochar plus chemical fertilizers (BNPK). Here, we investigated the diazotroph community using real-time PCR and high-throughput sequencing of the nifH gene, and assessed the soil N2 fixation rate (RNfix) using acetylene reduction assay (ARA). Results showed that in the topsoil, the treatments with biochar significantly increased nifH gene copies and RNfix, which was consistent with the increased soil organic matter (SOM), total carbon-to-nitrogen ratio (C/N), dissolved organic carbon (DOC) and pH. In the subsoil, applying chemical fertilizers (NPK) strongly decreased RNfix, but had no effect on diazotroph abundance; in contrast, biochar application (BC) had no effect on RNfix, but suppressed the growth of bacteria and diazotrophs while increasing the abundance of Rhizobiales order. Diazotroph and bacterial gene copies were significantly and positively correlated in both top- and sub-soil, and they were mainly influenced by SOM and total nitrogen (TN). In addition, soil nitrate nitrogen (NO3−–N) was the major factor in shaping the vertical stratification of diazotroph community structure. Although nifH gene abundance was significantly correlated with RNfix in the topsoil, the structure equation modeling (SEM) showed the highest correlation between diazotroph community structure and RNfix. Hence, we suggested that soil carbon and nitrogen sources were the key factors correlated with changes in the vertical pattern of diazotroph abundance. Biochar induced the dominant diazotroph community succession and increased soil carbon content and pH, which contributed to the BNF activity. Changes in the BNF activity were driven by the variation in diazotroph community structure.
Autonomy and the social dilemma of online manipulative behavior
Authors: Botes Marietjie 
Published: April 2022

AbstractPersuasive online technologies were initially designed and used to gain insights into the online behavior of individuals to personalize advertising campaigns in an effort to influence people and convince them to buy certain products. But recently, these technologies have blurred the lines and morphed into technologies that covertly and gradually manipulate people into attaining a goal that is predetermined by the algorithm and disregards the decision-making rights of the individual. This may lead to people exercising decisions that do not align with their personal values and beliefs, and rob them of their autonomy—an ethical principle, in the absence of which the application of these technologies may be unethical. However, not all technologies that are persuasive are necessarily manipulative which require the careful consideration of a couple of elements to determine whether or not technologies are manipulative and ultimately whether their application is ethical or not. In this article, we analyze the ethical principle of autonomy and unpack the underlying elements of this ethical principle which must be considered to determine whether the application of a technology is ethical or not in the context of it being persuasive or manipulative.
Maternal high salt-diet increases offspring's blood pressure with dysfunction of NO/PKGI signaling pathway in heart tissue
Authors: Huang Minshan , Li Xiuying , Ren Luwen , Huang Lin , Pan Jiahong , Yao Jinlin , Du Lili , Chen Dunjin , Chen Jingsi 
Published: April 2022

AbstractBackgroundHigh salt-diets have become significant threats to human health, resulting in hypertension and cardiovascular diseases. Hypertensive disorders during pregnancy are complicated, since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy. High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development. Therefore, we explored how high-salt diets during pregnancy could affect the offspring.MethodsRats were divided into three groups and fed with low, normal, and high salt diets. The offspring were separated into three groups after weaning based on dietary salt concentration. The blood pressure and urine protein content of both dams and offspring were measured. To evaluate cardiac function, we used Masson staining and immunodetection to confirm the fibrosis status. Finally, we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide (NO)/cGMP-dependent protein kinase I (PKGI) pathway and the angiotensin receptor.ResultsHigh-salt diets increased blood pressure, and offspring previously exposed to high-salt environments were predisposed to hypertension. High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition (EMT). Under these conditions, the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor (AT1R) was upregulated, though the type-2 angiotensin II receptor (AT2R) had the opposite effect.ConclusionHigh-salt diets induce high blood pressure and increase predisposition to hypertension in offspring. They are accompanied by cardiac fibrosis, which could be caused by the activation of NO/PKGI and upregulation of AT1R.
Beta-Thalassemia major with Gaucher disease
Authors: Ibrahimi Mohammad Akbar , Hakimi Turyalai , Halimi Sultan Ahmad 
Published: April 2022

ABSTRACT

Introduction and importance:
β-thalassemia major is an inherited disorder resulting from mutation or deletion of the beta-globin gene, causing a reduced beta-globin chain of hemoglobin. Gaucher's disease (GD) is a type of lysosomal storage disorder resulting from the deficiency of the glucocerebrosidase enzyme or storage of glucocerebrosides in the tissues. Coexistence of these two entities is very rare. The importance of reporting this case is that both medical conditions have overlapping clinical manifestations and the diagnosis of one will be mistaken for the other.

Case presentation:
A 12-year-old child was brought to our pediatric department with complaints of abdominal distension, anemia, hepatosplenomegaly, and iron overload due to frequent blood transfusions. Initially, anemia and iron overload were treated with blood transfusion and iron chelation therapy along with management of congestive heart failure (CHF) followed by splenectomy. The patient's follow-up result was favorable.

Clinical discussion:
β-thalassemia major is a genetic disorder that is prevalent in South Asian nations. GD, or lysosomal storage disease, is a rare medical condition requiring enzyme replacement therapy. Coexistence of both disorders is mostly missed where genetic screening is not available. β-thalassemia major is blood transfusion (BT) dependent, and the frequency of BT directly justifies the decision for splenectomy due to splenomegaly and iron overload.

Conclusion:
Our report highlights the similarities of Beta thalassemia major and GD due to overlapping clinical manifestations, therefore this is wise to do all relevant clinical investigations for the purpose of definite diagnosis and proper treatment of both medical conditions.

Highlights
Extreme Exospheric Dynamics at Charon: Implications for the Red Spot
Authors: Teolis Ben , Raut Ujjwal , Kammer Joshua A. , Gimar Caleb J. , Howett Carly J. A. , Gladstone G. Randall , Retherford Kurt D. 
Published: April 2022

AbstractCharon's exosphere may exhibit extreme seasonal dynamics, with centuries of quiescence punctuated by short lived (∼4 earth years) exospheric surges near the equinoxes, as spring sunrise bi‐annually drives frozen methane off the polar night zones. Charon's pole‐centric red spot has been proposed to be the product of Ly‐α photolysis of frozen methane into refractory hydrocarbon “tholins”, but the role of exospheric dynamics in the red material's formation has not been investigated. We show with exospheric modeling that methane “polar‐swap”, in which exospheric CH4 sublimated from the spring polar zone is rapidly re‐frozen onto the autumn hemisphere, deposits ∼30 μm polar frosts too thick for Ly‐α light to penetrate. Ethane, the primary methane photoproduct under these conditions, may unlike methane remain frozen decades after polar sunrise under solar wind exposure. Solar wind radiolysis of polar ethane frost synthesizes higher‐order refractories that may contribute to the coloration of Charon's polar zones.
Complex Patterns of Mantle Flow in Eastern SE Asian Subduction Zones Inferred From P‐Wave Anisotropic Tomography
Authors: Wei Wei , Zhao Dapeng , Yu Weiqian , Shi Yaolin 
Published: April 2022

AbstractWe determine 3‐D isotropic and anisotropic P‐wave velocity models beneath eastern SE Asia by inverting a large number of P‐wave arrival times selected from the ISC‐EHB database. Our results reveal detailed structures of the subducting South China Sea (SCS), Negros, Molucca Sea, Philippine Sea, and Banda slabs, the previously subducted Proto‐SCS slab and remnants of other paleo slabs, showing long‐lived subductions of these oceanic slabs in eastern SE Asia. There is an obvious change in the subduction angle of the SCS slab at 18°N along the Manila trench. We suggest that the relatively low dip angle of the SCS slab to the south of 18°N was caused by subduction of an extinct mid‐ocean ridge, and a slab tear is possibly formed at 18°N. This feature is supported by the resolved fast velocity directions (FVDs) of P‐wave azimuthal anisotropy in the mantle wedge, which show that 3‐D toroidal mantle flow may develop around the southern part of the SCS slab. Trench‐normal FVDs are revealed in the deeper mantle wedge of the Sangihe subduction zone, which are associated with the deep subduction and stagnancy of the Molucca Sea slab. A nearly trench‐parallel FVD is observed beneath the Molucca Sea slab, which may be caused by trench‐parallel extension due to the retreating slab or reflect subslab mantle flow associated with the double‐sided subduction. The subducting Banda slab exhibits a curved feature, which greatly affects the flow pattern in the mantle wedge.
Longitudinal body mass index trajectories at preschool age: children with rapid growth have differential composition of the gut microbiota in the first year of life
Authors: Reyna Myrtha E. , Petersen Charisse , Dai Darlene L. Y. , Dai Ruixue , Becker Allan B. , Azad Meghan B. , Miliku Kozeta , Lefebvre Diana L. , Moraes Theo J. , Mandhane Piushkumar J. , Boutin Rozlyn C. T. , Finlay B. Brett , Simons Elinor , Kozyrskyj Anita L. , Lou Wendy , Turvey Stuart E. , Subbarao Padmaja 
Published: April 2022

Abstract
Background/Objective
The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity. We aim to investigate whether longitudinal shifts within the bacterial community between 3 months and 1 year of life are associated with preschool BMI z-score trajectories.

Methods
BMI trajectories from birth to 5 years of age were identified using group-based trajectory modeling in 3059 children. Their association with familial and environmental factors were analyzed. Infant gut microbiota at 3 months and 1 year was defined by 16S RNA sequencing and changes in diversity and composition within each BMIz trajectory were analyzed.

Results
Four BMIz trajectories were identified: low stable, normative, high stable, and rapid growth. Infants in the rapid growth trajectory were less likely to have been breastfed, and gained less microbiota diversity in the first year of life. Relative abundance of Akkermansia increased with age in children with stable growth, but decreased in those with rapid growth, abundance of Ruminococcus and Clostridium at 1 year were elevated in children with rapid growth. Children who were breastfed at 6 months had increased levels of Sutterella, and decreased levels of Ruminococcus and Clostridium.

Conclusion
This study provides new insights into the relationship between the gut microbiota in infancy and patterns of growth in a cohort of preschool Canadian children. We highlight that rapid growth since birth is associated with bacteria shown in animal models to have a causative role in weight gain. Our findings support a novel avenue of research targeted on tangible interventions to reduce childhood obesity.
Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects
Authors: Canovas Nunes Sara , De Vita Serena , Anighoro Andrew , Autelitano François , Beaumont Edward , Klingbeil Pamela , McGuinness Meaghan , Duvert Beatrice , Harris Chad , Yang Lu , Pokharel Sheela Pangeni , Chen Chun-Wei , Ermann Monika , Williams David A. , Xu Haiming 
Published: April 2022

AbstractRAS mutations prevalent in high-risk leukemia have been linked to relapse and chemotherapy resistance. Efforts to directly target RAS proteins have been largely unsuccessful. However, since RAS-mediated transformation is dependent on signaling through the RAS-related C3 botulinum toxin substrate (RAC) small GTPase, we hypothesized that targeting RAC may be an effective therapeutic approach in RAS mutated tumors. Here we describe multiple small molecules capable of inhibiting RAC activation in acute lymphoblastic leukemia cell lines. One of these, DW0254, also demonstrates promising anti-leukemic activity in RAS-mutated cells. Using chemical proteomics and biophysical methods, we identified the hydrophobic pocket of phosphodiester 6 subunit delta (PDE6D), a known RAS chaperone, as a target for this compound. Inhibition of RAS localization to the plasma membrane upon DW0254 treatment is associated with RAC inhibition through a phosphatidylinositol-3-kinase/AKT-dependent mechanism. Our findings provide new insights into the importance of PDE6D-mediated transport for RAS-dependent RAC activation and leukemic cell survival.
Mesenchymal stem cell-derived exosomal microRNA-182-5p alleviates myocardial ischemia/reperfusion injury by targeting GSDMD in mice
Authors: Yue Rongchuan , Lu Shengzhong , Luo Yu , Zeng Jing , Liang Hao , Qin Dan , Wang Xiaobo , Wang Tao , Pu Jun , Hu Houxiang 
Published: April 2022

AbstractRecent evidence indicates that exosomes derived from mesenchymal stem cells (MSCs) confer protective effects against myocardial ischemia/reperfusion (I/R) injury. Exosomes are carriers of potentially protective endogenous molecules, including microRNAs (miRNAs/miRs). The current study set out to test the effects of transferring miR-182-5p from MSC-derived exosomes into myocardial cells on myocardial I/R injury. First, an I/R mouse model was developed by left anterior descending coronary artery occlusion, and myocardial cells were exposed to hypoxia/reoxygenation (H/R) for in vitro I/R model establishment. Loss- and gain-of-function experiments of miR-182-5p and GSDMD were conducted to explore the effects of miR-182-5p via MSC-derived exosomes on cell pyroptosis and viability. GSDMD was robustly expressed in I/R-injured myocardial tissues and H/R-exposed myocardial cells. GSDMD upregulation promoted H/R-induced myocardial cell pyroptosis and reduced viability, corresponding to increased lactate dehydrogenase release, reactive oxygen species production, and pyroptosis. A luciferase assay demonstrated GSDMD as a target of miR-182-5p. In addition, exosomal miR-182-5p was found to diminish GSDMD-dependent cell pyroptosis and inflammation induced by H/R. Furthermore, MSC-derived exosomes carrying miR-182-5p improved cardiac function and reduced myocardial infarction, accompanied with reduced inflammation and cell pyroptosis in vivo. Taken together, our findings suggest a cardioprotective effect of exosomal miR-182-5p against myocardial I/R injury, shedding light on an attractive therapeutic strategy.
SNORD1C maintains stemness and 5-FU resistance by activation of Wnt signaling pathway in colorectal cancer
Authors: Liu Yonghui , Zhao Chengwen , Wang Guihua , Chen Jing , Ju Shaoqing , Huang Jianfei , Wang Xudong 
Published: April 2022

AbstractSmall nucleolar RNAs (snoRNAs) are a class of non-coding RNAs that play indispensable roles in cancers, including colorectal cancer (CRC). However, the role of SNORD1C in CRC is unclear. In the current study, SNORD1C expression was measured in CRC tissues using quantitative real-time PCR. A series of in vivo and in vitro experiments were performed to examine the functional role of SNORD1C in CRC. Quantitative real-time PCR, western blotting, sphere formation assay, and chemotherapy resistance analysis were conducted to illustrate the SNORD1C molecular mechanism. SNORD1C was upregulated in CRC and that high SNORD1C expression was related to poor prognosis. After knocking down SNORD1C in CRC cell lines, cell proliferation, colony formation, cell migration, and invasion were alleviated, while apoptosis was increased. Transcriptional RNA-sequencing analysis revealed that following SNORD1C knockdown, β-catenin was downregulated, as was the transcription factor TCF7, which inhibited the Wnt/β-catenin pathway. Meanwhile, levels of the stem cell-related factors were reduced, diminishing cell stemness and tumorigenesis. Our findings suggest that SNORD1C functions via the Wnt/β-catenin pathway to enhance cancer cell stemness in CRC and could be a predictive biomarker for the prognosis ad aggressiveness of this malignancy. Additionally, targeting SNORD1C may be a novel therapeutic strategy for CRC.
Persistent ferroptosis promotes cervical squamous intraepithelial lesion development and oncogenesis by regulating KRAS expression in patients with high risk-HPV infection
Authors: Wang Tianming , Gong Min , Cao Yuting , Zhao Chengcheng , Lu Yingfei , Zhou Yu , Yao Shasha , Chen Jianquan , Zhao Chun , Ju Rong 
Published: April 2022

AbstractCervical squamous cell carcinoma (CSCC) is a type of female cancer that affects millions of families worldwide. Human papillomavirus (HPV) infection is the main reason for CSCC formation, and squamous intraepithelial lesions (SILs) induced by high-risk HPV (HR-HPV) infection are considered precancerous lesions. A previous study reported that HPV-infected cancer cells were able to counteract lipid peroxidation for survival. Recent research has reported that ferroptosis acts in an iron-dependent lipid peroxidation manner to kill cancer cells, and it is proposed as a new approach for female cancer therapy. Here, we investigated the role of ferroptosis throughout SIL development into CSCC. We found that ferroptosis occurred in SIL, but anti-ferroptosis emerged in CSCC. Our data further indicated that an antiferroptotic effect was formed in response to persistent ferroptosis and then promoted oncogenesis. Altogether, we provide novel insight into ferroptosis in cervical SIL development and suggest a potential therapeutic target for the treatment of CSCC.