bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy in melanoma
Authors: Yang Yuqi , Wang Sijia , Wang Xiang-xu , Guo Sen , Wang Huina , Shi Qiong , Tian Yangzi , Wang Hao , Zhao Tao , Zhang Hengxiang , Zhang Baolu , Gao Tianwen , Li Chunying , Yi Xiuli , Guo Weinan 
Published: January 2024

Abstract
Background
Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive.

Methods
Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism.

Results
We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo.

Conclusions
Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.
K-Ras(V12) differentially affects the three Akt isoforms in lung and pancreatic carcinoma cells and upregulates E-cadherin and NCAM via Akt3
Authors: Geißert Rebekka , Lammert Angela , Wirth Stefanie , Hönig Rabea , Lohfink Dirk , Unger Monika , Pek Denis , Schlüter Konstantin , Scheftschik Theresa , Smit Daniel J. , Jücker Manfred , Menke Andre , Giehl Klaudia 
Published: January 2024

AbstractK-Ras is the most frequently mutated Ras variant in pancreatic, colon and non-small cell lung adenocarcinoma. Activating mutations in K-Ras result in increased amounts of active Ras-GTP and subsequently a hyperactivation of effector proteins and downstream signaling pathways. Here, we demonstrate that oncogenic K-Ras(V12) regulates tumor cell migration by activating the phosphatidylinositol 3-kinases (PI3-K)/Akt pathway and induces the expression of E-cadherin and neural cell adhesion molecule (NCAM) by upregulation of Akt3. In vitro interaction and co-precipitation assays identified PI3-Kα as a bona fide effector of active K-Ras4B but not of H-Ras or N-Ras, resulting in enhanced Akt phosphorylation. Moreover, K-Ras(V12)-induced PI3-K/Akt activation enhanced migration in all analyzed cell lines. Interestingly, Western blot analyses with Akt isoform-specific antibodies as well as qPCR studies revealed, that the amount and the activity of Akt3 was markedly increased whereas the amount of Akt1 and Akt2 was downregulated in EGFP-K-Ras(V12)-expressing cell clones. To investigate the functional role of each Akt isoform and a possible crosstalk of the isoforms in more detail, each isoform was stably depleted in PANC-1 pancreatic and H23 lung carcinoma cells. Akt3, the least expressed Akt isoform in most cell lines, is especially upregulated and active in Akt2-depleted cells. Since expression of EGFP-K-Ras(V12) reduced E-cadherin-mediated cell-cell adhesion by induction of polysialylated NCAM, Akt3 was analyzed as regulator of E-cadherin and NCAM. Western blot analyses revealed pronounced reduction of E-cadherin and NCAM in the Akt3-kd cells, whereas Akt1 and Akt2 depletion upregulated E-cadherin, especially in H23 lung carcinoma cells. In summary, we identified oncogenic K-Ras4B as a key regulator of PI3-Kα-Akt signaling and Akt3 as a crucial regulator of K-Ras4B-induced modulation of E-cadherin and NCAM expression and localization.
MyD88 in myofibroblasts enhances nonalcoholic fatty liver disease-related hepatocarcinogenesis via promoting macrophage M2 polarization
Authors: Liu Yu , Chen Haiqiang , Yan Xuanxuan , Zhang Jie , Deng Zhenzhong , Huang Maosheng , Gu Jianchun , Zhang Jinhua 
Published: January 2024

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown.

Results
Myofibroblast MyD88-deficient (SMAMyD88−/−) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on the CCR1 receptor and STAT6/ PPARβ pathway. Furthermore, liver tumor growth was attenuated in mice treated with a CCR1 inhibitor. CCLl5 (homologous protein CCL9 in humans) expression was increased in myofibroblasts of HCC and was associated with shorter survival of patients with HCC. Thus, our results indicate that MyD88 in myofibroblasts promotes NAFLD-related HCC progression and may be a promising therapeutic target for HCC treatment.

Conclusion
This study demonstrates that MyD88 in myofibroblasts can promote nonalcoholic fatty liver disease-related hepatocarcinogenesis by enhancing macrophage M2 polarization, which might provide a potential molecular therapeutic target for HCC.

Graphical Abstract
Weight development from childhood to motherhood—embodied experiences in women with pre-pregnancy obesity: a qualitative study
Authors: Sandsæter Heidi L. , Eik-Nes Trine Tetlie , Getz Linn Okkenhaug , Haugdahl Hege S. , Magnussen Elisabeth Balstad , Rich-Edwards Janet W. , Horn Julie 
Published: January 2024

Abstract
Background
Pre-pregnancy obesity increases the risk of perinatal complications. Post-pregnancy is a time of preparation for the next pregnancy and lifestyle advice in antenatal care and postpartum follow-up is therefore recommended. However, behavioral changes are difficult to achieve, and a better understanding of pregnant women’s perspectives and experiences of pre-pregnancy weight development is crucial.

Methods
We used a qualitative design and conducted semi-structured interviews with 14 women in Norway with pre-pregnancy obesity 3–12 months postpartum. Data were analyzed using thematic analysis.

Results
Four themes addressing women’s experiences and understanding of their weight development were generated: (1) Unmet essential needs, (2) Genetic predisposition for obesity, challenging life course transitions and turning points, (3) Under a critical eye: an ever-present negative bodily awareness, and (4) Wrestling with food. Parents’ inability to meet children’s essential needs caused weight gain through an unbalanced diet, increased stress, and emotional eating patterns. Body criticism and a feeling of not belonging led to negative body awareness that influenced behavioral patterns and relationships. Participants reporting having had a good childhood more often described their weight development as a result of genetic predisposition, challenging life course transitions and turning points, such as illness and injuries. Nevertheless, these participants also described how eating patterns were influenced by stress and negative emotions.

Conclusions
Healthcare providers should pay attention to the insider perspectives of pre-pregnancy weight development. An open and shared understanding of the root causes of these women’s weight development can form a basis for more successful lifestyle guidance.
Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine)
Authors: Gjorgjievski Marko , Madden Kim , Bullen Conner , Koziarz Frank , Koziarz Alex , Cenic Aleksa , Li Silvia , Bhandari Mohit , Johal Herman 
Published: January 2024

Abstract
Background
Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis.

Methods
This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use.

Results
259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2–6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3–58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6–52.8%) of their current analgesics. Age (β = − 0.3, CI − 0.6–0.0), higher pain severity (β = 0.4, CI 0.1–0.6) and previous cannabis use (β = 14.7, CI 5.1–24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier.

Conclusions
Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.
Comparison of analgesic effects of percutaneous and transthoracic intercostal nerve block in video-assisted thoracic surgery: a propensity score-matched study
Authors: Hui Hongliang , Miao Haoran , Qiu Fan , Li Huaming , Lin Yangui , Jiang Bo , Zhang Yiqian 
Published: January 2024

Abstract
Background
This study aimed to compare the analgesic efficacy of transthoracic intercostal nerve block (TINB) and percutaneous intercostal nerve block (PINB) for video-assisted thoracic surgery (VATS) using a retrospective analysis.

Methods
A total of 336 patients who underwent VATS between January 2021 and June 2022 were reviewed retrospectively. Of the participants, 194 received TINB and were assigned to the T group, while 142 patients received PINB and were assigned to the P group. Both groups received 25 ml of ropivacaine via TINB or PINB at the end of the surgery. The study measured opioid consumption, pain scores, analgesic satisfaction, and safety. Propensity score matching (PSM) analysis was performed to minimize selection bias due to nonrandom assignment.

Results
After propensity score matching, 86 patients from each group were selected for analysis. The P group had significantly lower cumulative opioid consumption than the T group (p < 0.01). The Visual Analogue Scale (VAS) scores were lower for the P group than the T group at 6 and 12 h post-surgery (p < 0.01); however, there was no significant difference in the scores between the two groups at 3, 24, and 48 h (p > 0.05). The analgesic satisfaction in the P group was higher than in the T group (p < 0.05). The incidence of back pain, nausea or vomiting, pruritus, dizziness, and skin numbness between the two groups was statistically insignificant (p > 0.05).

Conclusion
The study suggests that PINB provides superior analgesia for patients undergoing thoracic surgery compared to TINB without any extra adverse effects.
Evaluation of a multi-component early warning system for pastoralist populations in Doolo zone, Ethiopia: mixed-methods study
Authors: Baertlein Luke , Dubad Bashir Ali , Sahelie Birhanu , Damulak Istifanus Chindong , Osman Mohammed , Stringer Beverley , Bestman Agatha , Kuehne Anna , van Boetzelaer Elburg , Keating Patrick 
Published: January 2024

Abstract
Background
This study evaluated an early warning, alert and response system for a crisis-affected population in Doolo zone, Somali Region, Ethiopia, in 2019–2021, with a history of epidemics of outbreak-prone diseases. To adequately cover an area populated by a semi-nomadic pastoralist, or livestock herding, population with sparse access to healthcare facilities, the surveillance system included four components: health facility indicator-based surveillance, community indicator- and event-based surveillance, and alerts from other actors in the area. This evaluation described the usefulness, acceptability, completeness, timeliness, positive predictive value, and representativeness of these components.

Methods
We carried out a mixed-methods study retrospectively analysing data from the surveillance system February 2019–January 2021 along with key informant interviews with system implementers, and focus group discussions with local communities. Transcripts were analyzed using a mixed deductive and inductive approach. Surveillance quality indicators assessed included completeness, timeliness, and positive predictive value, among others.

Results
1010 signals were analysed; these resulted in 168 verified events, 58 alerts, and 29 responses. Most of the alerts (46/58) and responses (22/29) were initiated through the community event-based branch of the surveillance system. In comparison, one alert and one response was initiated via the community indicator-based branch. Positive predictive value of signals received was about 6%. About 80% of signals were verified within 24 h of reports, and 40% were risk assessed within 48 h. System responses included new mobile clinic sites, measles vaccination catch-ups, and water and sanitation-related interventions. Focus group discussions emphasized that responses generated were an expected return by participant communities for their role in data collection and reporting. Participant communities found the system acceptable when it led to the responses they expected. Some event types, such as those around animal health, led to the community’s response expectations not being met.

Conclusions
Event-based surveillance can produce useful data for localized public health action for pastoralist populations. Improvements could include greater community involvement in the system design and potentially incorporating One Health approaches.
Chromosomal microarray analysis for prenatal diagnosis of uniparental disomy: a retrospective study
Authors: Xu Chenxia , Li Miaoyuan , Gu Tiancai , Xie Fenghua , Zhang Yanfang , Wang Degang , Peng Jianming 
Published: January 2024

Abstract
Background
Chromosomal microarray analysis (CMA) is a valuable tool in prenatal diagnosis for the detection of chromosome uniparental disomy (UPD). This retrospective study examines fetuses undergoing invasive prenatal diagnosis through Affymetrix CytoScan 750 K array analysis. We evaluated both chromosome G-banding karyotyping data and CMA results from 2007 cases subjected to amniocentesis.

Results
The detection rate of regions of homozygosity (ROH) ≥ 10 Mb was 1.8% (33/2007), with chromosome 11 being the most frequently implicated (17.1%, 6/33). There were three cases where UPD predicted an abnormal phenotype based on imprinted gene expression.

Conclusion
The integration of UPD detection by CMA offers a more precise approach to prenatal genetic diagnosis. CMA proves effective in identifying ROH and preventing the birth of children affected by imprinting diseases.
The protective effect of apolipoprotein H in paediatric sepsis
Authors: Yu Zhicai , Xiao Changxue , Liu Rong , Pi Dandan , Jin Bian , Zou Zhen , Xu Feng 
Published: January 2024

Abstract
Background
Sepsis is a severe condition characterized by acute organ dysfunction resulting from an imbalanced host immune response to infections. Apolipoprotein H (APOH) is a critical plasma protein that plays a crucial role in regulating various biological processes. However, the precise role of APOH in the immunopathology of paediatric sepsis remains unclear.

Methods
In this study, we evaluated the concentration of APOH in paediatric patients with sepsis and healthy individuals. In an experimental sepsis model of caecal ligation and puncture (CLP), the impact of APOH on survival, organ injury, and inflammation was measured. Furthermore, the anti-inflammatory effects of APOH were investigated across diverse immune cell types, encompassing peripheral blood mononuclear cells (PBMCs), peritoneal macrophages (PMs), bone marrow-derived macrophages (BMDMs), and RAW 264.7 macrophages.

Results
In the pilot cohort, the relative abundance of APOH was found to be decreased in patients with sepsis (2.94 ± 0.61) compared to healthy controls (1.13 ± 0.84) (p < 0.001), non-survivors had lower levels of APOH (0.50 ± 0.37) compared to survivors (1.45 ± 0.83) (p < 0.05). In the validation cohort, the serum concentration of APOH was significantly decreased in patients with sepsis (202.0 ± 22.5 ng/ml) compared to healthy controls (409.5 ± 182.9 ng/ml) (p < 0.0001). The application of recombinant APOH protein as a therapeutic intervention significantly lowered the mortality rate, mitigated organ injury, and suppressed inflammation in mice with severe sepsis. In contrast, neutralizing APOH with an anti-APOH monoclonal antibody increased the mortality rate, exacerbated organ injury, and intensified inflammation in mice with non-severe sepsis. Intriguingly, APOH exhibited minimal effects on the bacterial burden, neutrophil, and macrophage counts in the sepsis mouse model, along with negligible effects on bacterial phagocytosis and killing during Pseudomonas aeruginosa infection in PMs, RAW 264.7 cells, and PBMCs. Mechanistic investigations in PMs and RAW 264.7 cells revealed that APOH inhibited M1 polarization in macrophages by suppressing toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalling pathway.

Conclusion
This proof-of-concept study demonstrated that APOH has a protective role in the host defense response to sepsis, highlighting the potential therapeutic value of APOH in sepsis treatment.

Graphical abstract
Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial
Authors: Lai Ming-Hui , Yu Xiao-Ming , Lu Yan , Wang Hong-Lin , Fu Wang , Zhou Huan-Xia , Li Yuan-Li , Hu Jun , Xia Jiayi , Hu Zekai , Shan Chun-Lei , Wang Feng , Wang Cong 
Published: January 2024

Abstract
Background
Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI).

Methods
This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase.

Discussion
The study’s findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment.

Trial registration
Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.
Geography, phylogeny and host switch drive the coevolution of parasitic Gyrodactylus flatworms and their hosts
Authors: Lei Hong-Peng , Jakovlić Ivan , Zhou Shun , Liu Xiang , Yan Chuan , Jin Xiao , Wang Bo , Li Wen-Xiang , Wang Gui-Tang , Zhang Dong 
Published: January 2024

Abstract
Background
Gyrodactylus is a lineage of monogenean flatworm ectoparasites exhibiting many features that make them a suitable model to study the host-parasite coevolutionary dynamics. Previous coevolutionary studies of this lineage mainly relied on low-power datasets (a small number of samples and a single molecular marker) and (now) outdated algorithms.

Methods
To investigate the coevolutionary relationship of gyrodactylids and their fish hosts in high resolution, we used complete mitogenomes (including two newly sequenced Gyrodactylus species), a large number of species in the single-gene dataset, and four different coevolutionary algorithms.

Results
The overall coevolutionary fit between the parasites and hosts was consistently significant. Multiple indicators confirmed that gyrodactylids are generally highly host-specific parasites, but several species could parasitize either multiple (more than 5) or phylogenetically distant fish hosts. The molecular dating results indicated that gyrodactylids tend to evolve towards high host specificity. Speciation by host switch was identified as a more important speciation mode than co-speciation. Assuming that the ancestral host belonged to Cypriniformes, we inferred four major host switch events to non-Cypriniformes hosts (mostly Salmoniformes), all of which occurred deep in the evolutionary history. Despite their relative rarity, these events had strong macroevolutionary consequences for gyrodactylid diversity. For example, in our dataset, 57.28% of all studied gyrodactylids parasitized only non-Cypriniformes hosts, which implies that the evolutionary history of more than half of all included lineages could be traced back to these major host switch events. The geographical co-occurrence of fishes and gyrodactylids determined the host use by these gyrodactylids, and geography accounted for most of the phylogenetic signal in host use.

Conclusions
Our findings suggest that the coevolution of Gyrodactylus flatworms and their hosts is largely driven by geography, phylogeny, and host switches.

Graphical Abstract