bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble PD-L1: a potential dynamic predictive biomarker for immunotherapy in patients with proficient mismatch repair colorectal cancer
Authors: He Yinjun , Zhang Xiang , Zhu Ming , He Wenguang , Hua Hanju , Ye Feng , Zhou Xile , Chen Nan , Li Yandong , Zhong Weixiang , Wu Guosheng , Cai Hui , Jiang Weiqin 
Published: January 2023

Abstract
Background
Circulating soluble programmed death ligand 1 (sPD-L1) can negatively regulate T-cell function and serve as a prognostic or predictive marker in a variety of cancers. However, rare studies have evaluated the potential roles of sPD-L1, and no study has estimated its predictive value for the efficacy of immune treatment in colorectal cancer (CRC).

Methods
Plasma samples from 192 CRC patients were used to estimate correlations between clinicopathological features and sPD-L1, secreted PD-L1 (secPD-L1) and exosomal PD-L1 (exoPD-L1). Baseline and posttreatment sPD-L1 levels were also investigated in 55 patients with metastatic CRC (mCRC) treated with chemotherapy ± targeted therapy and 40 patients with proficient mismatch repair (pMMR) mCRC treated with combination immunotherapy. Both sPD-L1 and secPD-L1 were quantified by enzyme-linked immunosorbent assay, while exoPD-L1 was analyzed using flow cytometry.

Results
secPD-L1 was the major component and positively correlated with sPD-L1 in CRC, while exoPD-L1 was almost undetectable. Higher levels of sPD-L1 were detected in patients with distant metastasis, especially those with distant lymph node metastasis and tissue combined positive score (CPS) instead of tumor proportion score (TPS). Chemotherapy or targeted therapy did not significantly impact sPD-L1 concentration. Progressive disease on combination immunotherapy was associated with an increase in sPD-L1 level, whereas no significant change was observed in patients with durable clinical benefit.

Conclusion
sPD-L1 mainly consisted of secPD-L1, and its level was higher in patients with distant metastasis, especially distant lymph node metastasis and positive CPS. sPD-L1 is a potential dynamic marker to identify rapid progression on combination immunotherapy and avoid ineffective treatment for pMMR CRC.
Prevalence and morbidity of neck pain: a cross-sectional study of 3000 elderly men
Authors: Damm Henrik , Jönsson Anette , Rosengren Björn E. , Jehpsson Lars , Ohlsson Claes , Ribom Eva , Mellström Dan , Karlsson Magnus K. 
Published: January 2023

Abstract
Background
The purpose of this study is to determine the prevalence and morbidity of neck pain with or without cervical rhizopathy, upper extremity motor deficit and/or thoracolumbar pain in elderly men.

Methods
We conducted a cross-sectional questionnaire study of 3,000 community-dwelling older men with a mean age of 75.4 ± 3.2 years (range 69–81) to determine if they had experienced neck pain with or without cervical rhizopathy/upper extremity motor deficit/thoracolumbar pain (yes/no) during the preceding 12 months, and if so, morbidity with the condition (no/minor/moderate/severe).

Results
Among the participants, 865 (29%) reported they had experienced neck and 1,619 (54%) thoracolumbar pain. Among the men with neck pain, 59% had experienced only neck pain, 17% neck pain and cervical rhizopathy and 24% neck pain, rhizopathy and motor deficit. For men with only neck pain, the morbidity was severe in 13%, for men with neck pain and rhizopathy it was 24%, and for men with pain, rhizopathy and motor deficit it was 46% (p < 0.001). Among the men with neck pain, 23% had experienced only neck pain and no thoracolumbar pain; the remaining 77% had both neck and thoracolumbar pain. The morbidity was severe in 10% of the men with neck pain but no thoracolumbar pain and 30% in men with neck and thoracolumbar pain (p < 0.001).

Conclusion
Neck pain in elderly men is common but symptoms and morbidity vary. For men who only have neck pain, 1/8 rated their morbidity as severe, while almost half who also had cervical rhizopathy and motor deficit and almost 1/3 of those who also had thoracolumbar pain reported severe morbidity.
Advances in sequencing technologies for amyotrophic lateral sclerosis research
Authors: Udine Evan , Jain Angita , van Blitterswijk Marka 
Published: January 2023

AbstractAmyotrophic lateral sclerosis (ALS) is caused by upper and lower motor neuron loss and has a fairly rapid disease progression, leading to fatality in an average of 2-5 years after symptom onset. Numerous genes have been implicated in this disease; however, many cases remain unexplained. Several technologies are being used to identify regions of interest and investigate candidate genes. Initial approaches to detect ALS genes include, among others, linkage analysis, Sanger sequencing, and genome-wide association studies. More recently, next-generation sequencing methods, such as whole-exome and whole-genome sequencing, have been introduced. While those methods have been particularly useful in discovering new ALS-linked genes, methodological advances are becoming increasingly important, especially given the complex genetics of ALS. Novel sequencing technologies, like long-read sequencing, are beginning to be used to uncover the contribution of repeat expansions and other types of structural variation, which may help explain missing heritability in ALS. In this review, we discuss how popular and/or upcoming methods are being used to discover ALS genes, highlighting emerging long-read sequencing platforms and their role in aiding our understanding of this challenging disease.
STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent
Authors: Zhang Xilin , Chen Qiuqiang , He Ying , Shi Qian , Yin Chengyi , Xie Yanping , Yu Huanming , Bao Ying , Wang Xiang , Tang Chengwu , Dong Zhaohui 
Published: January 2023

Abstract
Background
Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown.

Methods
The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo.

Results
Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes.

Conclusions
Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.
The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?
Authors: Moreno Rui , Rhodes Andrew , Piquilloud Lise , Hernandez Glenn , Takala Jukka , Gershengorn Hayley B. , Tavares Miguel , Coopersmith Craig M. , Myatra Sheila N. , Singer Mervyn , Rezende Ederlon , Prescott Hallie C. , Soares Márcio , Timsit Jean-François , de Lange Dylan W. , Jung Christian , De Waele Jan J. , Martin Greg S. , Summers Charlotte , Azoulay Elie , Fujii Tomoko , McLean Anthony S. , Vincent Jean-Louis 
Published: January 2023

AbstractThe Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.
Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest
Authors: Kang Changshin , Min Jin Hong , Park Jung Soo , You Yeonho , Jeong Wonjoon , Ahn Hong Joon , In Yong Nam , Lee In Ho , Jeong Hye Seon , Lee Byung Kook , Jeong Jinwoo 
Published: January 2023

AbstractBackgroundThis study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest.MethodsWe conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1–2) or poor (CPC 3–5).ResultsOf the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38–69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0–4.0 h), and the PHSIon DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSIgroup had a good neurological outcome compared with 48 (75%) patients in the AHSIgroup. In the AHSIgroup, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4–30.7] ng/mL vs. 84.3 [32.4–167.0] ng/mL,P < 0.001). The area under the curve for PHSIon DW-MRI was 0.87 (95% confidence interval [CI] 0.80–0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%–100%) and 74.2% (95% CI 62.0–83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1–95.1%]; 100% specificity).ConclusionsIn this cohort study, PHSIfindings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.
Systematic optimization of Cas12a base editors in wheat and maize using the ITER platform
Authors: Gaillochet Christophe , Peña Fernández Alexandra , Goossens Vera , D’Halluin Katelijn , Drozdzecki Andrzej , Shafie Myriam , Van Duyse Julie , Van Isterdael Gert , Gonzalez Camila , Vermeersch Mattias , De Saeger Jonas , Develtere Ward , Audenaert Dominique , De Vleesschauwer David , Meulewaeter Frank , Jacobs Thomas B. 
Published: January 2023

Abstract
Background
Testing an ever-increasing number of CRISPR components is challenging when developing new genome engineering tools. Plant biotechnology has few high-throughput options to perform iterative design-build-test-learn cycles of gene-editing reagents. To bridge this gap, we develop ITER (Iterative Testing of Editing Reagents) based on 96-well arrayed protoplast transfections and high-content imaging.

Results
We validate ITER in wheat and maize protoplasts using Cas9 cytosine and adenine base editors (ABEs), allowing one optimization cycle — from design to results — within 3 weeks. Given that previous LbCas12a-ABEs have low or no activity in plants, we use ITER to develop an optimized LbCas12a-ABE. We show that sequential improvement of five components — NLS, crRNA, LbCas12a, adenine deaminase, and linker — leads to a remarkable increase in activity from almost undetectable levels to 40% on an extrachromosomal GFP reporter. We confirm the activity of LbCas12a-ABE at endogenous targets in protoplasts and obtain base-edited plants in up to 55% of stable wheat transformants and the edits are transmitted to T1 progeny. We leverage these improvements to develop a highly mutagenic LbCas12a nuclease and a LbCas12a-CBE demonstrating that the optimizations can be broadly applied to the Cas12a toolbox.

Conclusion
Our data show that ITER is a sensitive, versatile, and high-throughput platform that can be harnessed to accelerate the development of genome editing technologies in plants. We use ITER to create an efficient Cas12a-ABE by iteratively testing a large panel of vector components. ITER will likely be useful to create and optimize genome editing reagents in a wide range of plant species.
Efficient biosynthesis of (R)-mandelic acid from styrene oxide by an adaptive evolutionary Gluconobacter oxydans STA
Authors: Liu Fei , Zhou Junping , Hu Mengkai , Chen Yan , Han Jin , Pan Xuewei , You Jiajia , Xu Meijuan , Yang Taowei , Shao Minglong , Zhang Xian , Rao Zhiming 
Published: January 2023

Abstract
Background
(R)-mandelic acid (R-MA) is a highly valuable hydroxyl acid in the pharmaceutical industry. However, biosynthesis of optically pure R-MA remains significant challenges, including the lack of suitable catalysts and high toxicity to host strains. Adaptive laboratory evolution (ALE) was a promising and powerful strategy to obtain specially evolved strains.

Results
Herein, we report a new cell factory of the Gluconobacter oxydans to biocatalytic styrene oxide into R-MA by utilizing the G. oxydans endogenous efficiently incomplete oxidization and the epoxide hydrolase (SpEH) heterologous expressed in G. oxydans. With a new screened strong endogenous promoter P12780, the production of R-MA was improved to 10.26 g/L compared to 7.36 g/L of using Plac. As R-MA showed great inhibition for the reaction and toxicity to cell growth, adaptive laboratory evolution (ALE) strategy was introduced to improve the cellular R-MA tolerance. The adapted strain that can tolerate 6 g/L R-MA was isolated (named G. oxydans STA), while the wild-type strain cannot grow under this stress. The conversion rate was increased from 0.366 g/L/h of wild type to 0.703 g/L/h by the recombinant STA, and the final R-MA titer reached 14.06 g/L. Whole-genome sequencing revealed multiple gene-mutations in STA, in combination with transcriptome analysis under R-MA stress condition, we identified five critical genes that were associated with R-MA tolerance, among which AcrA overexpression could further improve R-MA titer to 15.70 g/L, the highest titer reported from bulk styrene oxide substrate.

Conclusions
The microbial engineering with systematic combination of static regulation, ALE, and transcriptome analysis strategy provides valuable solutions for high-efficient chemical biosynthesis, and our evolved G. oxydans would be better to serve as a chassis cell for hydroxyl acid production.
Effects of storage conditions and digestion time on DNA amplification of biting midge (Culicoides) blood meals
Authors: Bellekom Ben , Bailey Abigail , England Marion , Langlands Zoe , Lewis Owen T. , Hackett Talya D. 
Published: January 2023

Abstract
Background
Molecular analysis of blood meals is increasingly used to identify the hosts of biting insects such as midges and mosquitoes. Successful host identification depends on the availability of sufficient host DNA template for PCR amplification, making it important to understand how amplification success changes under different storage conditions and with different durations of blood meal digestion within the insect gut before being placed into the storage medium.

Method
We characterised and compared the digestion profile of two species of Culicoides over a 96-h period using a novel set of general vertebrate primers targeting the 16S rRNA gene. A set number of individuals from each species were killed over 13 time points post-blood feeding and preserved in 95% ethanol. Samples were stored either at ambient room temperature or in a − 20 °C freezer to examine the effect of storage condition on the PCR amplification success of host DNA.

Results
We found that amplification success across the 96-h sampling period post-feeding was reduced from 96 to 6% and 96% to 14% for Culicoides nubeculosus and Culicoides sonorensis, respectively. We found no effect of storage condition on PCR amplification success, and storage in 95% ethanol was sufficient to maintain high rates of amplifiable host DNA for at least 9 months, even at room temperature.

Conclusions
These findings highlight the limited time frame during which an individual may contain amplifiable host DNA and demonstrate the importance of timely sample capture and processing post-blood feeding. Moreover, storage in 95% ethanol alone is sufficient to limit host DNA degradation. These results are relevant to the design of studies investigating the biting behaviour and disease transmission potential of Culicoides and other biting Diptera.

Graphical Abstract
The first successful desensitization protocol in exenatide allergy: a case report
Authors: Yeğit Osman Ozan , Sarıbeyliler Göktuğ , Karadağ Pelin , Demir Semra , Gül Nurdan , Ünal Derya , Gelincik Akkor Aslı 
Published: January 2023

Abstract
Background
Glucagon-like peptide-1 (GLP-1) receptor agonists are important treatment options in obese patients with type 2 diabetes. To date, few immediate allergic reactions due to GLP-1 receptor agonists were reported. One report revealed that a patient with a level 1 anaphylaxis according to Brighton Criteria due to an exendin based GLP-1 receptor agonist was able to tolerate liraglutide (Human GLP-1 analogue), the alternative GLP-1 receptor agonist. Since exenatide is the only available GLP-1 receptor agonist covered by insurance in Turkey, a drug desensitization protocol, the only therapeutic method in hypersensitivity reactions used in case of absence of an alternative drug, was considered. Here, we report a successful desensitization protocol for the first time in two obese diabetic patients with an immediate hypersensitivity to exenatide.

Case presentation
The first patient was a 47 year-old female. She was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes after the last dose, following a week of an exenatide BID 5 mcg/20 mcl treatment. Although the reaction was sudden onset, it did not meet the Brighton Criteria of anaphylaxis. The second patient was a 46 year-old female. She had a large local immediate injection site reaction that appeared 15 min following an exenatide BID 5 mcg/20 mcl injection. The injection site reaction was not accompanied by a systemic allergic reaction. We performed desensitization with exenatide to two patients who need GLP-1 receptor agonist treatment. Protocol was completed in 7 steps in approximately 3 h, with the aim of reaching the daily dosage of exenatide. Throughout this process, we observed that both cases tolerated the protocol without any complaints or complications. Following the protocol, the patients safely tolerated the treatment for 3 months.

Conclusions
We present the first successful desensitization protocol to exenatide in both local and/or systemic immediate hypersensitivity reactions and indicate the importance of desensitization in patients who do not have alternative therapies.
Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling
Authors: Sui Liyan , Zhao Yinghua , Wang Wenfang , Chi Hongmiao , Tian Tian , Wu Ping , Zhang Jinlong , Zhao Yicheng , Wei Zheng-Kai , Hou Zhijun , Zhou Guoqiang , Wang Guoqing , Wang Zedong , Liu Quan 
Published: January 2023

Abstract
Background
Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive.

Results
We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus.

Conclusion
Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.