bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity
Authors: Lee Dong-hee , Ahn Hyejin , Sim Hye-In , Choi Eunji , Choi Seunghyun , Jo Yunju , Yun Bohwan , Song Hyun Kyu , Oh Soo Jin , Denda-Nagai Kaori , Park Chan-Sik , Irimura Tatsuro , Park Yoon , Jin Hyung-seung 
Published: October 2023

Abstract
Background
Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies.

Methods
We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity.

Results
Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors.

Conclusions
These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.
Unnecessity of routine chest tube drainage after patent ductus arteriosus ligation in preterm neonates
Authors: Lee Youngok , Jung Hanna 
Published: October 2023

Abstract
Background
Conventionally, a chest tube drainage is placed following patent ductus arteriosus (PDA) ligation to monitor possible bleeding and drain air or effusion postoperatively. However, the necessity of chest tube drainage after thoracotomy in PDA ligation is controversial. We evaluated the feasibility and safety of omitting chest tube drainage in preterm neonates who underwent PDA ligation via thoracotomy.

Methods
We retrospectively reviewed the medical records of 56 preterm neonates who underwent surgical ligation of PDA via thoracotomy in the neonatal intensive care unit between January 2014 and March 2022.

Results
The median gestational age was 26.9 (interquartile range [IQR]: 25.9–28.8) weeks and the median body weight at birth was 895 (IQR: 795–1190) g. The median age on the day of surgery was 17.0 (IQR: 10.0–22.0) days and the median body weight on the day of surgery was 1100 (IQR: 958–1410) g. The median operative time was 44.5 (IQR: 35.5–54.0) minutes. There were no intraoperative events or procedure-related deaths. On postoperative chest radiographs, no patients had major complications, such as pneumothorax or hemothorax. Nineteen patients (34%) had minor complications of subcutaneous emphysema around the thoracotomy site. No patients required additional chest tube drainage for postoperative bleeding, pleural effusion, or progressive subcutaneous emphysema. No patients had surgical wound infections. There were seven in-hospital mortalities, which were unrelated to the surgery.

Conclusions
Omitting chest tube drainage is feasible and safe for the postoperative management of preterm neonates undergoing PDA ligation via thoracotomy.
Culex modestus: the overlooked mosquito vector
Authors: Soto Alina , Delang Leen 
Published: October 2023

AbstractCulex (Barraudius) modestus (Ficalbi 1889) are found in temperate regions across Europe, Asia, and Northern Africa. These mosquitoes thrive during the summer and prefer to breed in permanent vegetative habitats such as rice paddies and marshes. Culex modestus feed on a wide range of bird species but are highly attracted to humans, which makes them a potential ‘bridge’ vector for enzootic pathogens. There is compelling evidence that Culex modestus is an efficient vector for West Nile virus, potentially capable of causing epidemics in humans and other mammals. This species is also a likely vector for Usutu virus, avian malaria (Plasmodium spp.), and parasitic heartworms (Dirofilaria spp.). Culex modestus can be morphologically identified at the larval and adult stages, and a distinctive phenotype of this species is their ability to overwinter. Despite the widespread establishment of this mosquito species and their role as vectors for human pathogens, we lack sufficient knowledge on this species to implement and evaluate targeted vector control measures. Since Culex modestus can be considered a potential public health threat, there is a need for a better understanding of this mosquito species.
Graphical Abstract
Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization
Authors: Wang Tso-Fu , Liou Yu-Shan , Yang Shang-Hsien , Lin Guan-Ling , Chiang Ya-Wen , Lien Te-Sheng , Li Chi-Cheng , Wang Jen-Hung , Chang Hsin-Hou , Sun Der-Shan 
Published: October 2023

Abstract
Background
Granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of hematopoietic stem cells (HSCs) is a well-established method to prepare HSCs for transplantation nowadays. A sufficient number of HSCs is critical for successful HSC transplantation. However, approximately 2–6% of healthy stem cell donors are G-CSF-poor mobilizers for unknown reasons; thus increasing the uncertainties of HSC transplantation. The mechanism underlining G-CSF-mediated HSC mobilization remains elusive, so detailed mechanisms and an enhanced HSC mobilization strategy are urgently needed. Evidence suggests that P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are one of the cell–cell adhesion ligand–receptor pairs for HSCs to keep contacting bone marrow (BM) stromal cells before being mobilized into circulation. This study hypothesized that blockage of PSGL-1 and P-selectin may disrupt HSC-stromal cell interaction and facilitate HSC mobilization.

Methods
The plasma levels of soluble P-selectin (sP-sel) before and after G-CSF administration in humans and male C57BL/6J mice were analyzed using enzyme-linked immunosorbent assay. Male mice with P-selectin deficiency (Selp−/−) were further employed to investigate whether P-selectin is essential for G-CSF-induced HSC mobilization and determine which cell lineage is sP-sel derived from. Finally, wild-type mice were injected with either G-CSF or recombinant sP-sel to investigate whether sP-sel alone is sufficient for inducing HSC mobilization and whether it accomplishes this by binding to HSCs and disrupting their interaction with stromal cells in the BM.

Results
A significant increase in plasma sP-sel levels was observed in humans and mice following G-CSF administration. Treatments of G-CSF induced a decrease in the level of HSC mobilization in Selp−/− mice compared with the wild-type (Selp+/+) controls. Additionally, the transfer of platelets derived from wild-type mice can ameliorate the defected HSC mobilization in the Selp−/− recipients. G-CSF induces the release of sP-sel from platelets, which is sufficient to mobilize BM HSCs into the circulation of mice by disrupting the PSGL-1 and P-selectin interaction between HSCs and stromal cells. These results collectively suggested that P-selectin is a critical factor for G-CSF-induced HSC mobilization.

Conclusions
sP-sel was identified as a novel endogenous HSC-mobilizing agent. sP-sel injections achieved a relatively faster and more convenient regimen to mobilize HSCs in mice than G-CSF. These findings may serve as a reference for developing and optimizing human HSC mobilization in the future.
Quality management overview for the production of a tissue-engineered human skin substitute in Malaysia
Authors: Seet Wan Tai , Mat Afandi Mohd Asyraf , Ishak Mohamad Fikeri , Hassan Muhammad Najib Fathi , Ahmat Nazeha , Ng Min Hwei , Maarof Manira 
Published: October 2023

AbstractTreatments for skin injuries have recently advanced tremendously. Such treatments include allogeneic and xenogeneic transplants and skin substitutes such as tissue-engineered skin, cultured cells, and stem cells. The aim of this paper is to discuss the general overview of the quality assurance and quality control implemented in the manufacturing of cell and tissue product, with emphasis on our experience in the manufacturing of MyDerm®, an autologous bilayered human skin substitute. Manufacturing MyDerm®requires multiple high-risk open manipulation steps, such as tissue processing, cell culture expansion, and skin construct formation. To ensure the safety and efficacy of this product, the good manufacturing practice (GMP) facility should establish a well-designed quality assurance and quality control (QA/QC) programme. Standard operating procedures (SOP) should be implemented to ensure that the manufacturing process is consistent and performed in a controlled manner. All starting materials, including tissue samples, culture media, reagents, and consumables must be verified and tested to confirm their safety, potency, and sterility. The final products should also undergo a QC testing series to guarantee product safety, efficacy, and overall quality. The aseptic techniques of cleanroom operators and the environmental conditions of the facility are also important, as they directly influence the manufacturing of good-quality products. Hence, personnel training and environmental monitoring are necessary to maintain GMP compliance. Furthermore, risk management implementation is another important aspect of QA/QC, as it is used to identify and determine the risk level and to perform risk assessments when necessary. Moreover, procedures for non-conformance reporting should be established to identify, investigate, and correct deviations that occur during manufacturing. This paper provides insight and an overview of the QA/QC aspect during MyDerm®manufacturing in a GMP-compliant facility in the Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia.
Experimental transmission of ovine atypical scrapie to cattle
Authors: Konold Timm , Spiropoulos John , Hills Janet , Abdul Hasina , Cawthraw Saira , Phelan Laura , McKenna Amy , Read Lauren , Canoyra Sara , Marín-Moreno Alba , Torres Juan María 
Published: October 2023

AbstractClassical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.
The effect of spinal versus general anaesthesia on perioperative muscle weakness in patients having bilateral total hip arthroplasty: a single center randomized clinical trial
Authors: Van Boxstael Sam , Peene Laurens , Dylst Dimitri , Penders Joris , Hadzic Admir , Meex Ingrid , Corten Kristoff , Mesotten Dieter , Thiessen Steven 
Published: October 2023

Abstract
Background
Perioperative neuro-endocrine stress response may contribute to acquired muscle weakness. Regional anaesthesia has been reported to improve the outcome of patients having total hip arthroplasty. In this study, it was hypothesized that spinal anaesthesia (SA) decreases the perioperative neuro-endocrine stress response and perioperatively acquired muscle weakness (PAMW), as compared to general anaesthesia (GA).

Methods
Fifty subjects undergoing bilateral total hip arthroplasty (THA) were randomly allocated to receive a standardized SA (n = 25) or GA (n = 25). Handgrip strength was assessed preoperatively, on the first postoperative day (primary endpoint) and on day 7 and 28. Respiratory muscle strength was measured by maximal inspiratory pressure (MIP). Stress response was assessed by measuring levels of Adrenocorticotropic hormone (ACTH), cortisol and interleukin-6 (IL-6).

Results
Handgrip strength postoperatively (day 1) decreased by 5.4 ± 15.9% in the SA group, versus 15.2 ± 11.7% in the GA group (p = 0.02). The handgrip strength returned to baseline at day 7 and did not differ between groups at day 28. MIP increased postoperatively in patients randomized to SA by 11.7 ± 48.3%, whereas it decreased in GA by 12.2 ± 19.9% (p = 0.04). On day 7, MIP increased in both groups, but more in the SA (49.0 ± 47.8%) than in the GA group (14.2 ± 32.1%) (p = 0.006). Postoperatively, the levels of ACTH, cortisol and IL-6 increased in the GA, but not in the SA group (p < 0.004).

Conclusion
In patients having bilateral THA, SA preserved the postoperative respiratory and peripheral muscle strength and attenuated the neuro-endocrine and inflammatory responses.
Trial registration: clinicaltrials.gov NCT03600454.
Circulating Tumor DNA from Ascites as an alternative to tumor sampling for genomic profiling in ovarian cancer patients
Authors: Kfoury Maria , Hazzaz Reda El , Sanson Claire , Durand Felix Blanc , Michels Judith , Blameble Emeline Colomba , Tang Roseline , Le Formal Audrey , Lecerf Elodie , Gouy Sebastien , Maulard Amandine , Pautier Patricia , Rouleau Etienne , Leary Alexandra 
Published: October 2023

AbstractGenomic testing is crucial for the management of ovarian cancer. DNA from biopsies at diagnostic laparoscopies or interval debulking surgery after neoadjuvant chemotherapy, has a high failure rate. At relapse, biopsies may not be feasible. The aim of our study was to evaluate the feasibility and usefulness of measuring genomic instability score (GIS) on cell-free DNA (cfDNA) from ascites.Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples. CfDNA was extracted from 1 to 4 ml of double-centrifuged fresh ascites. Targeted Next-generation sequencing (NGS) including TP53 mutation (TP53m) was performed on cfDNA to confirm the presence of tumor cfDNA. Single Nucleotide Polymorphism Array estimating somatic copy number alterations (SCNA) was performed to calculate GIS for Homologous-Recombination deficiency (HRD).Twenty nine ascites were collected from 20 patients with suspected or confirmed OC. 93% (27/29) samples had detectable cfDNA (median 1120 ng [24-5732]) even when obtained during chemotherapy. A deleterious mutation was identified in 100%, with high allelic frequencies (median 60% [3.3–87%]), confirming that cfDNA was tumoral. SCNA analyses on 17 patients showed 11 high GIS, and 6 low GIS. 4 patients with confirmed BRCA mutation had a high GIS on ascites. When available from the same patient, SCNA profiles on ascites and tumor were superimposable.Ascites is frequent at diagnosis and relapse and yields large amounts of tumoral cfDNA. SCNA analysis on ascitic cfDNA is feasible and can detect the same HRD scar as tumor testing. Ascites could provide an alternative to tumor sampling for HRD and BRCA testing.
Exploring the potential of using ChatGPT in physics education
Authors: Liang Yicong , Zou Di , Xie Haoran , Wang Fu Lee 
Published: October 2023

AbstractThe pretrained large language models have been widely tested for their performance on some challenging tasks including arithmetic, commonsense, and symbolic reasoning. Recently how to combine LLMs with prompting techniques has attracted lots of researchers to propose their models to automatically solve math word problems. However, most research works focus on solving math problems at the elementary school level and few works aim to solve problems in science disciplines, e.g., Physics. In this exploratory study, we discussed the potential pedagogical benefits of using ChatGPT in physics and demonstrated how to prompt ChatGPT in solving physics problems. The results suggest that ChatGPT is able to solve some physics calculation problems, explain solutions, and generate new exercises at a human level.
Clockwise rotation of SW Japan and timing of Izanagi–Pacific ridge subduction revealed by arc migration
Authors: Yamaoka Ken , Wallis Simon R. 
Published: October 2023

AbstractIgneous rocks associated with the Cretaceous to Paleogene volcanic arc in SW Japan show ages that young from west to east in a direction parallel to the Median Tectonic Line suggesting corresponding translation of a heat source traditionally interpreted in terms of oblique subduction of a spreading ridge. However, recent oceanic plate reconstructions suggest ridge subduction may be younger than the main arc activity. Age compilations of 1227 points of felsic to intermediate Cretaceous and Cenozoic igneous rocks from the Japan arc show arc magmatism that can be separated into an early active period 130–60 Ma (stage 1), a subsequent period of quiescence 60–46 Ma (stage 2), which is followed by a resumption of igneous activity from 46 Ma onward (stage 3). In southwest Japan, the orientations of the magmatic arcs of stages 1 and 3 show and angular discordance of about 20°. The lack of active arc magmatism and the occurrence patterns of adakitic and high-Mg andesitic magmas indicate that ridge subduction occurred during stage 2. The arc age distribution pattern of stage 1 is explained by the slab shallowing related to a younging of the subducting slab as the ridge approaches. Furthermore, the obliquity of the arcs formed at stages 1 and 3 is explained by a 20° clockwise rotation of the inner zone of southwest Japan during the ridge-subduction phase. Oceanic plate reconstructions show counterclockwise rotation in the subduction direction after the ridge subduction phase, and coupling of the subducting oceanic plate with the upper plate would support microplate rotation in the inner zone. The new proposed tectonic reconstructions provide a framework to related Paleogene subduction of an active spreading ridge along the east Asia margin not only to the distribution of granitic bodies but also to rift-related basin formation on the eastern margin of the Eurasian continent and to rotation of crustal blocks indicated by paleomagnetic data of Cretaceous terranes.
Herpes zoster vaccine awareness and acceptance among adults in Saudi Arabia: a survey-based cross-sectional study
Authors: AlMuammar Sarah , Albogmi Afaf , Alzahrani Manar , Alsharef Fai , Aljohani Raghad , Aljilani Teif 
Published: October 2023

Abstract
Background
Herpes zoster (shingles) is caused by reactivation of the varicella-zoster virus. Despite the recommended herpes zoster vaccine for individuals aged ≥ 50 years, its uptake remains low in Saudi Arabia.

Methods
This cross-sectional study assessed knowledge and awareness of herpes zoster and its vaccine in individuals aged ≥ 50 years in Saudi Arabia. Data were collected through an online survey distributed via social media.

Results
Among 402 participants, 57.2% had heard of the shingles vaccine, but only 7.7% received it. However, 53.2% expressed willingness to be vaccinated. Multivariable analysis revealed that those aged 56–60 were 1.8 times more likely to accept the vaccine than those aged 50–55 years (p = 0.03). Men were 1.9 times more likely to accept the vaccine than women (p = 0.01). Additionally, participants with a primary education were 16.1 times more likely to accept the vaccine than those with a higher education (p = 0.01).

Conclusion
This study highlights the need for increased awareness and education among healthcare providers and the public in Saudi Arabia regarding shingles and its vaccine. The low vaccine uptake calls for effective strategies, such as awareness campaigns and provider reminders. Primary education and vaccine hesitancy influence willingness to be vaccinated.
Genetic characteristics of spouse selection based on short tandem repeats in DNA and lunula count on fingertip
Authors: Xia Qi , Anwar Ullah , Weijian Yu , Yingshuai Wang , Hui Liu 
Published: October 2023

AbstractObjectiveThe aim of this study was to assess the correlation of spouse selection withshort tandem repeats (STRs) in DNA and with the number of fingertip lunulae to investigate the role of heredity in spouse selection.MethodsWe randomly selected a total of 286 couples (husband and wife) as a couple group while 200 paired subjects (a man randomly matched with a woman as a pair of subjects) were selected as a non-spouse group for DNA typing, and to investigate lunulae in spouse selection, a total of 554 couples were selected as a couple group and 500 pairs of subjects were selected as a control group.ResultsA significant difference of STR matching number (a large value implies a higher genetic similarity) between spouse group and non-spouse group were observed (12.3 ± 2.7 vs. 11.8 ± 2.6; p < 0.05). A significant difference of the lunula matching number (difference of lunula counts between a paired subjects, a lower value implies a higher genetic similarity) between two groups were also observed for the lunula counts (1.55 ± 1.88 vs. 3.53 ± 2.40; p < 0.01).ConclusionSignificant and unprecedented relationships were found between the couples and polymorphic STRs, and between spouse selection and lunula counts. Polymorphic STRs and fingertip lunulae counts provide an initial insight into the potentially important contributions that genetic characteristics may play a key role in spouse selection.