bluuebunny/crossref_metadata_2025_split huggingface dataset:
B7-H4 is a potential diagnostic and prognostic biomarker in colorectal cancer and correlates with the epithelial-mesenchymal transition
Authors: Yan Xiaotian , Hong Bo , Feng Jie , Jin Yuanqing , Chen Mengting , Li Fugang , Qian Yun 
Published: October 2022

Abstract
Background
As a negative co-stimulatory molecule of the B7 family, B7-H4 has recently attracted increased attention. However, the clinical value of B7-H4 in colorectal cancer (CRC) remains controversial and requires further investigation. This study aimed to investigate the role of B7-H4 in the clinical diagnosis and survival prognosis of CRC.

Methods
The relationships between B7-H4 expression, immune cell infiltration, epithelial-mesenchymal transition (EMT), clinicopathological features, and survival prognosis were determined through the TCGA database and verified in a large CRC cohort (n = 1118).

Results
The results showed the level of B7-H4 mRNA expression was significantly increased in the CRC tumor tissues compared with normal tissues (P <  0.001). Immunohistochemistry showed that B7-H4 protein expression was also up-regulated in CRC. The positive rate of B7-H4 in CRC tumor tissues was 76.38%, which was significantly higher than that in non-tumor tissues (P <  0.001). Overexpression of B7-H4 was positively correlated with lymph node metastasis, advanced TNM stage, and poor tumor differentiation (P = 0.012; 0.009; 0.014). Prognostic analysis showed high B7-H4 expression was associated with significantly shorter OS. Multivariate analysis demonstrated the risk of death in CRC patients with high B7-H4 expression is 1.487 times that of low B7-H4 expression. In addition, B7-H4 expression was negatively correlated with the epithelial marker E-cadherin (P <  0.001) and positively correlated with the mesenchymal marker vimentin (P <  0.001) in CRC tissues. However, B7-H4 expression was not associated with the immunosuppressive microenvironment in CRC.

Conclusion
B7-H4 may represent a potential biomarker for the diagnosis and prognosis of CRC and enhance CRC invasion by promoting EMT.
Comparison of different correction formulas and measurement methods for the accurate determination of intraocular pressure after SMILE and FS-LASIK surgery
Authors: Yang Zhiqing , Miao Na , Wang Lixiang , Ma Ke 
Published: October 2022

Abstract
Background
To compare the accuracy of non-contact tonometry, Pentacam, and corneal visualization Scheimpflug technology (Corvis ST) for the measurement of intraocular pressure (IOP) after small incision lenticule extraction (SMILE) or femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery.

Methods
A total of 49 patients (98 eyes) undergoing FS-LASIK or SMILE surgery at West China Hospital, Sichuan University from January to March 2021 were enrolled in this prospective, comparative, self-controlled study. IOP values were measured with non-contact tonometer, Pentacam, and Corvis ST before surgery and 1 month after surgery. Pentacam-derived postoperative IOP values were corrected using five correction formulas (Ehlers, Shah, Dresden, Orssengo-Pye, and Kohlhaas), while Corvis ST-derived values were corrected using a single formula.

Results
In the SMILE group, no significant differences were observed between the IOP values corrected with the Shah formula before and after surgery (t = 0.17, P = 0.869), whereas postoperative IOP values corrected with the other formulas were significantly different from the corresponding preoperative measurements (P < 0.05). In the FS-LASIK group, postoperative IOP values corrected with the Ehlers, Shah, or Corvis ST formulas were significantly different from the corresponding preoperative IOP measurements (P < 0.05), but no significant differences were observed between pre- and postoperative IOP values corrected with the Dresden (t =  − 0.08, P = 0.941), Orssengo-Pye (t =  − 0.52, P = 0.604), or Kohlhaas (t = 1.22, P = 0.231) formulas.

Conclusions
Pentacam’s Shah correction formula seemed to be the most appropriate method for accurately measuring postoperative IOP in patients undergoing SMILE surgery, while the Dresden, Orssengo-Pye, and Kohlhaas correction formulas of Pentacam were identified as the most reliable methods for estimating IOP in patients after FS-LASIK surgery.
Preoperative anemia and deep vein thrombosis in patients with perioperative bone trauma: a cohort study
Authors: Zhang Hui , Wu Linqin , Cheng Bo 
Published: October 2022

AbstractBackgroundIn current active prevention (including physical and drug prevention), the incidence of perioperative deep vein thrombosis (DVT) of the lower extremities remains high in patients with bone trauma. Risk factors need to be further optimized, and high-risk patients must be identified early. Preoperative comorbidities, especially preoperative anemia, and DVT in patients with perioperative bone trauma are not clear. The purpose of this study was to explore the causal relationship between preoperative anemia and DVT in patients with perioperative bone trauma, and further reduce the incidence of DVT in patients with bone trauma.ObjectivesTo analyze the relationship between preoperative anemia and perioperative DVT in patients with femoral and pelvic fractures and provide a reference for the optimization of risk factors for DVT.MethodsThe clinical data of 1049 patients with femoral and pelvic fractures who received surgical treatment from May 2018 to June 2021 were retrospectively analyzed. Propensity score matching (PSM) was performed for the covariates of DVT. Modified Poisson regression was used to analyze the relationship between preoperative anemia and DVT.ResultsAfter matching 1:1 propensity scores in 1049 patients included in this study, there were 258 patients in the anemic and non-anemic groups. Preoperative anemia was statistically significant for the formation of DVT in patients with perioperative bone trauma (P = 0.000, RR = 1.567 [95% CI 1.217–2.017]). This conclusion remained true after PSM (P = 0.009, RR = 1.500 [95% CI 1.105–2.036]). Preoperative anemia has some predictive value for perioperative DVT, with DVT-associated preoperative anemia thresholds of 125 g/L and area under the receiver operating characteristic curve of 0.5877 (95% CI 0.5345 to 0.6408). On this basis, sensitivity and specificity were 89.2 and 30.3%, respectively, with a Youden index of 0.195. In addition, we conducted an E-value determination of the propensity score; the E-value analysis showed robustness to unmeasured confounding.ConclusionsPreoperative anemia is highly correlated with perioperative DVT in patients with bone trauma, which is the cause of perioperative DVT in these patients.
Diversification of phenolic glucosides by two UDP-glucosyltransferases featuring complementary regioselectivity
Authors: Guo Fei , Zhang Xingwang , You Cai , Zhang Chengjie , Li Fengwei , Li Nan , Xia Yuwei , Liu Mingyu , Qiu Zetian , Zheng Xianliang , Ma Li , Zhang Gang , Luo Lianzhong , Cao Fei , Feng Yingang , Zhao Guang-Rong , Zhang Wei , Li Shengying , Du Lei 
Published: October 2022

AbstractBackgroundGlucoside natural products have been showing great medicinal values and potentials. However, the production of glucosides by plant extraction, chemical synthesis, and traditional biotransformation is insufficient to meet the fast-growing pharmaceutical demands. Microbial synthetic biology offers promising strategies for synthesis and diversification of plant glycosides.ResultsIn this study, the two efficient UDP-glucosyltransferases (UGTs) (UGT85A1 and RrUGT3) of plant origin, that are capable of recognizing phenolic aglycons, are characterized in vitro. The two UGTs show complementary regioselectivity towards the alcoholic and phenolic hydroxyl groups on phenolic substrates. By combining a developed alkylphenol bio-oxidation system and these UGTs, twenty-four phenolic glucosides are enzymatically synthesized from readily accessible alkylphenol substrates. Based on the bio-oxidation and glycosylation systems, a number of microbial cell factories are constructed and applied to biotransformation, giving rise to a variety of plant and plant-likeO-glucosides. Remarkably, several unnaturalO-glucosides prepared by the two UGTs demonstrate better prolyl endopeptidase inhibitory and/or anti-inflammatory activities than those of the clinically used glucosidic drugs including gastrodin, salidroside and helicid. Furthermore, the two UGTs are also able to catalyze the formation ofN- andS-glucosidic bonds to produceN- andS-glucosides.ConclusionsTwo highly efficient UGTs, UGT85A1 and RrUGT3, with distinct regioselectivity were characterized in this study. A group of plant and plant-like glucosides were efficiently synthesized by cell-based biotransformation using a developed alkylphenol bio-oxidation system and these two UGTs. Many of theO-glucosides exhibited better PEP inhibitory or anti-inflammatory activities than plant-origin glucoside drugs, showing significant potentials for new glucosidic drug development.
Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
Authors: Xue Chen , Gu Xinyu , Zhao Yalei , Jia Junjun , Zheng Qiuxian , Su Yuanshuai , Bao Zhengyi , Lu Juan , Li Lanjuan 
Published: October 2022

Abstract
Background
L-tryptophan (Trp) metabolism involved in mediating tumour development and immune suppression. However, comprehensive analysis of the role of the Trp metabolism pathway is still a challenge.

Methods
We downloaded Trp metabolism-related genes’ expression data from different public databases, including TCGA, Gene Expression Omnibus (GEO) and Hepatocellular Carcinoma Database (HCCDB). And we identified two metabolic phenotypes using the ConsensusClusterPlus package. Univariate regression analysis and lasso Cox regression analysis were used to establish a risk model. CIBERSORT and Tracking of Indels by DEcomposition (TIDE) analyses were adopted to assess the infiltration abundance of immune cells and tumour immune escape.

Results
We identified two metabolic phenotypes, and patients in Cluster 2 (C2) had a better prognosis than those in Cluster 1 (C1). The distribution of clinical features between the metabolic phenotypes showed that patients in C1 tended to have higher T stage, stage, grade, and death probability than those of patients in C2. Additionally, we screened 739 differentially expressed genes (DEGs) between the C1 and C2. We generated a ten-gene risk model based on the DEGs, and the area under the curve (AUC) values of the risk model for predicting overall survival. Patients in the low-risk subgroup tended to have a significantly longer overall survival than that of those in the high-risk group. Moreover, univariate analysis indicated that the risk model was significantly correlated with overall survival. Multivariate analysis showed that the risk model remained an independent risk factor in hepatocellular carcinoma (p < 0.0001).

Conclusions
We identified two metabolic phenotypes based on genes of the Trp metabolism pathway, and we established a risk model that could be used for predicting prognosis and guiding immunotherapy in patients with hepatocellular carcinoma.
Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
Authors: Choi Sungim , Choi Heun , Park Seong Yeon , Kwak Yee Gyung , Song Je Eun , Shin So Youn , Baek Ji Hyeon , Shin Hyun-IL , Cho Shin-Hyung , Lee Sang-Eun , Kwon Jeong-Ran , Park Sookkyung , Kim Miyoung , Oh Hong Sang , Kim Yong Chan , Kim Min Jae , Yeom Joon-Sup 
Published: October 2022

Abstract
Background
Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients.

Methods
A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined.

Results
Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14–4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029).

Conclusion
This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.
CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression
Authors: Beider Katia , Voevoda-Dimenshtein Valeria , Zoabi Ali , Rosenberg Evgenia , Magen Hila , Ostrovsky Olga , Shimoni Avichai , Weiss Lola , Abraham Michal , Peled Amnon , Nagler Arnon 
Published: October 2022

AbstractBackgroundWe assessed the mechanism by which multiple myeloma (MM) shapes the bone marrow (BM) microenvironment and affects MΦ polarization.MethodsIn vivo xenograft model of BM-disseminated human myeloma, as well as analysis of MM cell lines, stromal components, and primary samples from patients with MM, was utilized.ResultsAnalysis of the BM from MM-bearing mice inoculated with human CXCR4-expressing RPMI8226 cells revealed a significant increase in M2 MΦ cell numbers (p < 0.01). CXCL13 was one of the most profoundly increased factors upon MM growth with increased levels in the blood of MM-bearing animals. Myeloid cells were the main source of the increased murine CXCL13 detected in MM-infiltrated BM. MM cell lines induced CXCL13 and concurrent expression of M2 markers (MERTK, CD206, CD163) in co-cultured human MΦ in vitro. Interaction with MΦ reciprocally induced CXCL13 expression in MM cell lines. Mechanistically, TGFβ signaling was involved in CXCL13 induction in MM cells, while BTK signaling was implicated in MM-stimulated increase of CXCL13 in MΦ. Recombinant CXCL13 increased RANKL expression and induced TRAP+ osteoclast (OC) formation in vitro, while CXCL13 neutralization blocked these activities. Moreover, mice inoculated with CXCL13-silenced MM cells developed significantly lower BM disease. Reduced tumor load correlated with decreased numbers of M2 MΦ in BM, decreased bone disease, and lower expression of OC-associated genes. Finally, higher levels of CXCL13 were detected in the blood and BM samples of MM patients in comparison with healthy individuals.ConclusionsAltogether, our findings suggest that bidirectional interactions of MΦ with MM tumor cells result in M2 MΦ polarization, CXCL13 induction, and subsequent OC activation, enhancing their ability to support bone resorption and MM progression. CXCL13 may thus serve as a potential novel target in MM.
A novel promising diagnostic candidate selected by screening the transcriptome of Babesia gibsoni (Wuhan isolate) asexual stages in infected beagles
Authors: Guo Jiaying , Yang Furong , Wang Lingna , Xuan Xuenan , Zhao Junlong , He Lan 
Published: October 2022

Abstract
Background
Babesia gibsoni is one of the causative agents of canine babesiosis worldwide. Some dogs infected with B. gibsoni show severe clinical signs with progressive anemia, hemoglobinuria and splenomegaly. However, most infected dogs present a state of chronic infection and thereby may be a persistent pathogen carrier, increasing the risk of pathogen spreading. To date, little is known about this pathogen, with genomic and transcriptomic data in particular generally unavailable. This lack of knowledge extensively limits the development of effective diagnostic strategies and vaccines.

Methods
High-throughput RNA sequencing of total RNA of B. gibsoni asexual stages collected from infected beagles was performed. The unigenes were annotated in seven databases. The genes were sorted according to their fragments per kilobase per million (FPKM) value, which was used as an indicator for expression level. The gene with the highest FPKM value was cloned from the genome of B. gibsoni and further tested for immunogenicity, cellular localization and efficacy as a potential diagnostic candidate for detecting B. gibsoni in sera collected from beagles.

Results
A total of 62,580,653 clean reads were screened from the 64,336,475 raw reads, and the corresponding 70,134 transcripts and 36,587 unigenes were obtained. The gene with the highest FPKM value was screened from the unigenes; its full length was 1276 bp, and it was named BgP30. The BgP30 gene comprised three exons and two introns, with a 786-bp open reading frame, and encoded 261 amino acids with a predicted molecular weight of 30 kDa. The cellular localization assay confirmed the existence of P30 protein in B. gibsoni parasites. Moreover, P30 was detected in the serum of experimentally B. gibsoni-infected beagles, from 15 days up to 422 days post-infection, suggesting its usefulness as a diagnostic candidate for both acute and chronic infections.

Conclusions
We sequenced the transcriptome of B. gibsoni asexual stages for the first time. The BgP30 gene was highly expressed in the transcriptome screening experiments, with further studies demonstrating that it could induce immune response in B. gibsoni-infected dogs. These results lead us to suggest that bgP30 may be a good diagnostic candidate marker to detect both acute and chronic B. gibsoni infections.

Graphical Abstract
Delay in diagnosing a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome who presented with status epilepticus and lactic acidosis: a case report
Authors: Alenezi Ahmad F. , Almelahi Mariam A. , Fekih-Romdhana Feten , Jahrami Haitham A. 
Published: October 2022

AbstractBackgroundMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome is a rare mitochondrial genetic disorder that can present with a variety of clinical manifestations, including stroke, hearing loss, seizures, and lactic acidosis. The most common genetic mutation associated with this syndrome is M.3243A>G. The main underlying mechanism of the disease relates to protein synthesis, energy depletion, and nitric oxide deficiency. Controlling disease complications and improving patient quality of life are the primary aims of treatment options.Case presentationA 28-year-old Arabic female visited Al-Amiri Hospital in Kuwait. The patient was newly diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome following her admission as a case of status epilepticus requiring further investigation. The patient’s seizures were controlled, and she was evaluated to rule out the most serious complications by carrying out appropriate clinical, laboratory, and radiological imaging. The patient was discharged from the hospital after 2 weeks with a follow-up plan.ConclusionThis case report emphasizes the importance of considering mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome as a potential cause of status epilepticus with lactic acidosis in a young female patient with a past history of stroke-like episodes. It also stresses the most important workup to rule out every possible life-threatening complication to improve patients’ lives.
“Balancing within a closed family system”: a grounded theory study of how family life is affected by having a family member with an eating disorder
Authors: Karlstad Jannike , Moe Cathrine F. , Adelsten Stokland Ragni , Brinchmann Berit S. 
Published: October 2022

Abstract
Background
This qualitative study explores how having an adult daughter or sister with anorexia nervosa or bulimia nervosa affects the family’s daily life. Previous research has focused on the family’s role in the development of an eating disorder, while more recently the focus has been on the illness’s impact on the family. Caring for an individual with an eating disorder can involve distress, guilt, extra burdens, and unmet needs. By interviewing the family members of adults with eating disorders this study aims to gain insights into how the family members experience the impact of the eating disorder over time.

Methods
A constructivist grounded theory approach was comprised to gather and analyse data to develop a theory on how families experience life with an adult daughter or sister with an eating disorder. Semi-structured individual interviews were conducted with 21 parents and siblings from across Norway.

Results
The participants reported a lack of professional help and the families had to handle the challenges related to the illness themselves, hence being left to themselves as a family was identified as the participants’ main concern. To manage this concern the families had to balance a pattern of care within the closed family system, and this comprises the core category of the study. Families balanced a pattern of care by shifting roles, adapting meal routines, and maintaining openness within the family.

Conclusions
The findings implicate that families need clarification of roles and responsibilities in relation to the health services in caring for the individual with an eating disorder. More research on taking a family perspective concerning adults with eating disorders is needed.
Stability of levothyroxine tablets in blister packaging versus bottles and vials under simulated in-use conditions
Authors: Chun Jonathan 
Published: October 2022

Abstract

Introduction
Levothyroxine, the standard-of-care treatment for hypothyroidism, is susceptible to degradation when exposed to light and moisture and is an FDA-designated narrow therapeutic index drug. In this report, we examined how different packaging (e.g., cold form blister packs, manufacturer’s bottles, or pharmacy amber vials) affects the physicochemical integrity and potency of levothyroxine in conditions simulating real-world patient use.

Methods
In part 1 of this study, we evaluated changes in the physicochemical properties (e.g., moisture gain, hardness, and disintegration time) of levothyroxine tablets stored in high-density polyethylene (HDPE) bottles, amber vials, and blister packs when exposed intermittently to different relative humidities (RH), 25 °C/75% RH and 25 °C/90% RH for 90 days, or 54 °C/75% RH continuously for 2 days. In part 2 of the study, we compared the potency of levothyroxine tablets in bottles and aluminum/aluminum cold form blister packs exposed to 28 °C/65% RH intermittently over 105 days and continuously over 30 days.

Results
Moisture content, hardness, and disintegration time were relatively unchanged for blister-packaged levothyroxine tablets under all conditions studied. Conversely, the physicochemical properties of tablets stored in amber vials and bottles were altered over time. Levothyroxine potency remained relatively consistent for blister-packaged tablets (100.8% at baseline, 99.6% at day 105) and decreased for bottled levothyroxine (101.4% at baseline to 93.9% at day 105).

Conclusion
Levothyroxine packaging can influence tablet integrity. Blister packages preserved physicochemical properties and potency better than bulk bottles. Additional studies are needed to determine the impact of packaging and changes in tablet integrity on patient outcomes.