bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenocorticotropic hormone-producing pituitary adenoma with pituitary apoplexy treated by surgical decompression: a case report
Authors: Tanaka Sachiyo , Suzuki Shuji , Oishi Mana , Soeta Satoshi , Namiki Ryosuke , Hara Yasushi 
Published: November 2022

AbstractBackgroundPituitary-dependent hypercortisolism (PDH) is one of the most common endocrine disorders in veterinary medicine. However, there are few reports on pituitary tumor apoplexy (PTA) in dogs and no reports on its surgical intervention in veterinary medicine. Accordingly, the appropriate treatment is unknown. Herein, a case of PDH and PTA in a dog treated surgically is described.Case presentationA mongrel female dog (spayed; age, 8 years and 8 months; weight, 6.1 kg) with persistently elevated alkaline phosphatase underwent adrenocorticotropic hormone (ACTH) stimulation testing (post-stimulation cortisol: 20.5 μg/dL), abdominal ultrasonography (adrenal gland thickness: left, 5.7 mm; right, 8.1 mm), and brain magnetic resonance imaging (MRI) (pituitary-to-brain ratio [PBR], 0.61) at the referral hospital, resulting in a diagnosis of PDH (day 0). On day 9, the dog visited XXXX for the preparation of pituitary surgery to treat PDH. However, on days 10–15, the dog developed a loss of energy and appetite, bloody diarrhea, vomiting, and a decreased level of consciousness. However, on day 16, the dog’s condition recovered. A preoperative MRI scan performed on day 52 (the day of surgery) showed apoplexy in the dorsal pituitary region (PBR, 0.68). Based on the PTA findings, the risks of surgery were described to the owner, and approval was obtained. At the time of trans-sphenoidal surgery, a partial pituitary resection was performed with preservation of the PTA area due to adhesions between the PTA area of the right side of the pituitary and surrounding tissues. The resected pituitary tissue was diagnosed as an ACTH-producing adenoma, with necrotic and hemorrhagic findings. As of day 290, endogenous ACTH and cortisol levels did not exceed the reference range.ConclusionsThe acute signs that occurred on days 10–15 were most likely caused by PTA. Therefore, when signs similar to those detected in acute hypoadrenocorticism are observed in dogs with PDH, it is necessary to include PTA as a differential diagnosis. Trans-sphenoidal surgery may be effective in PDH-affected dogs that develop PTA, but careful attention should be paid to tissue adhesions secondary to hemorrhage that may occur after PTA.
Expression profile and prognostic values of LSM family in skin cutaneous melanoma
Authors: Sun Xiaofang , Zhang Jianping , Xiao Can , Ge Zili 
Published: November 2022

Abstract
Background
The like-Smith (LSM) family is a group of RNA-binding proteins involved in RNA metabolism. However, their involvement in tumors, particularly skin cutaneous melanoma (SKCM), is not fully understood. In this study, we focused on the expression profiles and prognostic values of the LSM family in SKCM.

Methods
Raw data were downloaded from The Cancer Genome Atlas. The expression profile and prognostic value of LSM genes in SKCM were explored using the GEPIA, cBioPortal, and HPA databases. Protein–protein and gene–gene interaction analyses were performed using STRING and GeneMANIA. Enrichment and Cox regression analysis were conducted using R software. The TISIDB database was used to explore the relationship between LSMs and immunomodulators. Receiver operating characteristic curves and nomogram models were constructed to validate prognostic values.

Results
mRNA and protein expression levels of LSM2, LSM4, and LSM12 were significantly elevated in SKCM. The upregulated mRNA expression of LSM2 (p = 0.0013) and LSM4 (p = 0.0043) was significantly correlated with poor overall survival in patients with SKCM, whereas only LSM2 (p = 0.049) overexpression was markedly associated with worse disease-free survival. LSM2 overexpression was an independent risk factor (p = 0.013) and was confirmed to have a high prognostic value in SKCM using the receiver operating characteristic curve (AUC = 0.942) and nomogram models. All LSM genes were identified as genomic mutations, whereas alteration of LSM2 (p = 0.0153) significantly affected the overall survival in patients with SKCM. Significant correlations were observed between LSM family expression, immune cell infiltration, and immunomodulator. Furthermore, function and pathway enrichment analysis showed that the LSM family was mainly RNA binding proteins and involved in RNA splicing and degradation.

Conclusion
Expression profiles and prognostic values of LSM in SKCM were inconsistent. Among the LSM family, only LSM2 may serve as a potential poor prognosticator and immunotherapeutic target of SKCM.
SWI/SNF complex gene variations are associated with a higher tumor mutational burden and a better response to immune checkpoint inhibitor treatment: a pan-cancer analysis of next-generation sequencing data corresponding to 4591 cases
Authors: Li Yue , Yang Xinhua , Zhu Weijie , Xu Yuxia , Ma Jiangjun , He Caiyun , Wang Fang 
Published: November 2022

Abstract
Background
Genes related to the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex are frequently mutated across cancers. SWI/SNF-mutant tumors are vulnerable to synthetic lethal inhibitors. However, the landscape of SWI/SNF mutations and their associations with tumor mutational burden (TMB), microsatellite instability (MSI) status, and response to immune checkpoint inhibitors (ICIs) have not been elucidated in large real-world Chinese patient cohorts.

Methods
The mutational rates and variation types of six SWI/SNF complex genes (ARID1A, ARID1B, ARID2, SMARCA4, SMARCB1, and PBRM1) were analyzed retrospectively by integrating next-generation sequencing data of 4591 cases covering 18 cancer types. Thereafter, characteristics of SWI/SNF mutations were depicted and the TMB and MSI status and therapeutic effects of ICIs in the SWI/SNF-mutant and SWI/SNF-non-mutant groups were compared.

Results
SWI/SNF mutations were observed in 21.8% of tumors. Endometrial (54.1%), gallbladder and biliary tract (43.4%), and gastric (33.9%) cancers exhibited remarkably higher SWI/SNF mutational rates than other malignancies. Further, ARID1A was the most frequently mutated SWI/SNF gene, and ARID1A D1850fs was identified as relatively crucial. The TMB value, TMB-high (TMB-H), and MSI-high (MSI-H) proportions corresponding to SWI/SNF-mutant cancers were significantly higher than those corresponding to SWI/SNF-non-mutant cancers (25.8 vs. 5.6 mutations/Mb, 44.3% vs. 10.3%, and 16.0% vs. 0.9%, respectively; all p  < 0.0001). Furthermore, these indices were even higher for tumors with co-mutations of SWI/SNF genes and MLL2/3. Regarding immunotherapeutic effects, patients with SWI/SNF variations showed significantly longer progression-free survival (PFS) rates than their SWI/SNF-non-mutant counterparts (hazard ratio [HR], 0.56 [95% confidence interval {CI} 0.44–0.72]; p < 0.0001), and PBRM1 mutations were associated with relatively better ICI treatment outcomes than the other SWI/SNF gene mutations (HR, 0.21 [95% CI 0.12–0.37]; p = 0.0007). Additionally, patients in the SWI/SNF-mutant + TMB-H (HR, 0.48 [95% CI 0.37–0.54]; p  < 0.0001) cohorts had longer PFS rates than those in the SWI/SNF-non-mutant + TMB-low cohort.

Conclusions
SWI/SNF complex genes are frequently mutated and are closely associated with TMB-H status, MSI-H status, and superior ICI treatment response in several cancers, such as colorectal cancer, gastric cancer, and non-small cell lung cancer. These findings emphasize the necessity and importance of molecular-level detection and interpretation of SWI/SNF complex mutations.
The association between preventive health and outpatient spending and life expectancy by income quartile
Authors: Barnard Mason S. , Hagos Rama M. 
Published: November 2022

Abstract
Background
To describe the relationship between longevity and local access to preventive healthcare at the county level.

Methods
We used Medicare outpatient reimbursement data from the 2010 Dartmouth Health Atlas and longevity data from Chetty et al. (2016) to identify the cross-sectional associations between county longevity, access to outpatient care, and the quality of primary care.

Results
We find that the cost of outpatient care is inversely correlated with area life expectancy for individuals in the bottom income quartile. Much of this correlation is driven by men in the bottom income quartile. We also find that disaggregating a preventive care index produces significant relationships between components of the index and longevity where none were previously found.

Conclusions
These results counter prior assertions that local health costs are not associated with life expectancy. Additionally, the results also suggest that the local cost of outpatient care and the quality of that care may influence the longevity of low-income populations, especially for low-income men.
Phthalates and bone mineral density: a systematic review
Authors: Heilmann Nina Z. , Reeves Katherine W. , Hankinson Susan E. 
Published: November 2022

AbstractBackgroundExposure to endocrine disruptors, such as phthalates, may impact bone mineral density (BMD) through a variety of mechanisms. Studies of phthalate exposure and BMD in humans are scarce.ObjectivesTo synthesize published data on the association between phthalate metabolites and BMD in humans and to provide methodological suggestions for future research.MethodsA single investigator searched PubMed for relevant studies, including observational studies of phthalate exposure and BMD in children and postmenopausal women. Twelve studies were screened with 5 meeting the eligibility criteria and included for review. A quality assessment form was used as a quality measure and key information was extracted from the included studies.ResultsIn one prospective study among postmenopausal women, higher levels of monocarboxyoctyl phthalate (MCOP) and monocarboxynonyl phthalate (MCNP) were significantly associated with lower BMD among nonusers of hormone therapy (HT). In cross-sectional studies of postmenopausal women, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono (3-carboxypropyl) phthalate (MCPP), and mono-benzyl phthalate (MBzP) were negatively associated with BMD, and MCNP was positively associated with BMD, but these results were not replicated across studies. In studies of fetal exposure to phthalates and childhood BMD, significant positive associations between MCPP and BMD in children at age 12 years were found in 1 study, while associations were null in the other study.ConclusionsStudies among postmenopausal women provide suggestive evidence of an association between urinary phthalate metabolite concentration and decreased BMD. Results from studies of childhood BMD are inconclusive given the limited data and their limitations. More research is needed to address limitations and further investigate the association between phthalate exposure and human BMD.
Spatial accessibility to health facilities in Sub-Saharan Africa: comparing existing models with survey-based perceived accessibility
Authors: Bihin Jérémie , De Longueville Florence , Linard Catherine 
Published: November 2022

Abstract
Background
Mapping geographical accessibility to health services is essential to improve access to public health in sub-Saharan Africa. Different methods exist to estimate geographical accessibility, but little is known about the ability of these methods to represent the experienced accessibility of the population, and about the added-value of sophisticated and data-demanding methods over simpler ones. Here we compare the most commonly used methods to survey-based perceived accessibility in different geographical settings.

Methods
Modelled accessibility maps are computed for 12 selected sub-Saharan African countries using four methods: Euclidean distance, cost-distance considering walking and motorized speed, and Kernel density. All methods are based on open and large-scale datasets to allow replication. Correlation coefficients are computed between the four modelled accessibility indexes and the perceived accessibility index extracted from Demographic and Health Surveys (DHS), and compared across different socio-geographical contexts (rural and urban, population with or without access to motorized transports, per country).

Results
Our analysis suggests that, at medium spatial resolution and using globally-consistent input datasets, the use of sophisticated and data-demanding methods is difficult to justify as their added value over a simple Euclidian distance method is not clear. We also highlight that all modelled accessibilities are better correlated with perceived accessibility in rural than urban contexts and for population who do not have access to motorized transportation.

Conclusions
This paper should guide researchers in the public health domain for knowing strengths and limits of different methods to evaluate disparities in health services accessibility. We suggest that using cost-distance accessibility maps over Euclidean distance is not always relevant, especially when based on low resolution and/or non-exhaustive geographical datasets, which is often the case in low- and middle-income countries.
Automatic segmentation of the gross target volume in radiotherapy for lung cancer using transresSEUnet 2.5D Network
Authors: Xie Hui , Chen Zijie , Deng Jincheng , Zhang Jianfang , Duan Hanping , Li Qing 
Published: November 2022

Abstract
Objective
This paper intends to propose a method of using TransResSEUnet2.5D network for accurate automatic segmentation of the Gross Target Volume (GTV) in Radiotherapy for lung cancer.

Methods
A total of 11,370 computed tomograms (CT), deriving from 137 cases, of lung cancer patients under radiotherapy developed by radiotherapists were used as the training set; 1642 CT images in 20 cases were used as the validation set, and 1685 CT images in 20 cases were used as the test set. The proposed network was tuned and trained to obtain the best segmentation model and its performance was measured by the Dice Similarity Coefficient (DSC) and with 95% Hausdorff distance (HD95). Lastly, as to demonstrate the accuracy of the automatic segmentation of the network proposed in this study, all possible mirrors of the input images were put into Unet2D, Unet2.5D, Unet3D, ResSEUnet3D, ResSEUnet2.5D, and TransResUnet2.5D, and their respective segmentation performances were compared and assessed.

Results
The segmentation results of the test set showed that TransResSEUnet2.5D performed the best in the DSC (84.08 ± 0.04) %, HD95 (8.11 ± 3.43) mm and time (6.50 ± 1.31) s metrics compared to the other three networks.

Conclusions
The TransResSEUnet 2.5D proposed in this study can automatically segment the GTV of radiotherapy for lung cancer patients with more accuracy.
Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium
Authors: Shen Zheng , Patel Mickey V. , Rodriguez-Garcia Marta , Wira Charles R. 
Published: November 2022

AbstractBackgroundRegulation of endometrial (EM) CD8+ T cells, which provide protection through cell-mediated cytotoxicity, is essential for successful reproduction, and protection against sexually transmitted infections and potential tumors. We have previously demonstrated that EM CD8+ T cell cytotoxicity is suppressed directly and indirectly by sex hormones and enhanced after menopause. What remains unclear is whether CD8+ T cell protection and the contribution of tissue-resident (CD103+) and non-resident (CD103-) T cell populations in the EM change as women age following menopause.ResultsUsing hysterectomy EM tissues, we found that EM CD8+ T cell numbers declined significantly in the years following menopause. Despite an overall decline in CD8+ T cells, cytotoxic activity per cell for both CD103- and CD103 + CD8+ T cells increased with age. Investigation of the underlying mechanisms responsible for cytotoxicity indicated that the percentage of total granzyme A and granzyme B positive CD8+ T cells, but not perforin, increased significantly after menopause and remained high and constant as women aged. Additionally, baseline TNFα production by EM CD8+ T cells increased significantly in the years following menopause, and estradiol suppressed TNFα secretion. Moreover, in response to PMA activation, TNFα and IFNγ were significantly up-regulated, and CD103-CD8+ T cells up-regulation of TNFα, IFNγ and IL-6 increased as women aged.ConclusionsUnderstanding the underlying factors involved in regulating cell-mediated protection of the EM by CD8+ T cells will contribute to the foundation of information essential for developing therapeutic tools to protect women against gynecological cancers and infections as they age.
Tissue dissociation for single-cell and single-nuclei RNA sequencing for low amounts of input material
Authors: Wiegleb Gordon , Reinhardt Susanne , Dahl Andreas , Posnien Nico 
Published: November 2022

Abstract
Background
Recent technological advances opened the opportunity to simultaneously study gene expression for thousands of individual cells on a genome-wide scale. The experimental accessibility of such single-cell RNA sequencing (scRNAseq) approaches allowed gaining insights into the cell type composition of heterogeneous tissue samples of animal model systems and emerging models alike. A major prerequisite for a successful application of the method is the dissociation of complex tissues into individual cells, which often requires large amounts of input material and harsh mechanical, chemical and temperature conditions. However, the availability of tissue material may be limited for small animals, specific organs, certain developmental stages or if samples need to be acquired from collected specimens. Therefore, we evaluated different dissociation protocols to obtain single cells from small tissue samples of Drosophila melanogaster eye-antennal imaginal discs.

Results
We show that a combination of mechanical and chemical dissociation resulted in sufficient high-quality cells. As an alternative, we tested protocols for the isolation of single nuclei, which turned out to be highly efficient for fresh and frozen tissue samples. Eventually, we performed scRNAseq and single-nuclei RNA sequencing (snRNAseq) to show that the best protocols for both methods successfully identified relevant cell types. At the same time, snRNAseq resulted in less artificial gene expression that is caused by rather harsh dissociation conditions needed to obtain single cells for scRNAseq. A direct comparison of scRNAseq and snRNAseq data revealed that both datasets share biologically relevant genes among the most variable genes, and we showed differences in the relative contribution of the two approaches to identified cell types.

Conclusion
We present two dissociation protocols that allow isolating single cells and single nuclei, respectively, from low input material. Both protocols resulted in extraction of high-quality RNA for subsequent scRNAseq or snRNAseq applications. If tissue availability is limited, we recommend the snRNAseq procedure of fresh or frozen tissue samples as it is perfectly suited to obtain thorough insights into cellular diversity of complex tissue.
Emergence of equine influenza virus H3Nx Florida clade 2 in Arabian racehorses in Egypt
Authors: Ahmed Basem Mohamed , Bayoumi Mahmoud Mohamed , Farrag Mohamed Ali , Elgamal Mahmoud Aly , Daly Janet Mary , Amer Haitham Mohamed 
Published: November 2022

Abstract
Background
Equine influenza is an important cause of respiratory disease in equids. The causative virus; EIV, is highly variable and can evolve by accumulation of mutations, particularly in the haemagglutinin (HA) gene. Currently, H3N8 is the sole subtype circulating worldwide with Florida clade 1 (FC1) is most prevalent in the Americas and FC2 in Asia and Europe. In Egypt, EIV was detected in two occasions: subtype H7N7 in 1989 and subtype H3N8 (FC1) in 2008. No data is available on the circulation pattern of EIV during the last decade despite frequent observation of suspected cases.

Methods
Twenty-two nasal swabs were collected from vaccinated and non-vaccinated horses showing respiratory signs suggestive of EIV infection in 2017–18. Three additional swabs were retrieved during a national race event in January 2018 from Arabian mares with high fever, gait stiffness and dry cough. Samples were screened by RT-qPCR and HA1 domain of the hemagglutinin gene was amplified and sequenced for sequence and phylogenetic analysis.

Results
RT-qPCR screening revealed that only the 3 samples from the race were positive with cycle thresholds ranging from 16 to 21 indicating high viral load. Isolation attempts in hen’s eggs were unsuccessful. Sequence analysis of the HA1 domain gene has revealed two identical nucleotide sequences, while the third contained 3 synonymous mutations. Phylogenetic analysis clustered study sequences with recent FC2 sequences from Europe. Amino acid alignments revealed 14 and 13 amino acid differences in the study sequences compared to A/equine/Egypt/6066NANRU-VSVRI/08 (H3N8) and A/equine/Kentucky/1997 (H3N8), respectively, available as EIV vaccines in Egypt. Nine amino acids were different from A/equine/Richmond/1/2007 (H3N8), the recommended FC2 vaccine strain by the world organization of animal health expert surveillance panel (OIE-ESP), two of which were unique to the Egyptian sequences while the remaining 7 changes were shared with the FC2-144V subgroup detected in the United Kingdom from late 2015 to 2016.

Conclusions
The study represents the first reported detection of FC2-144V related EIV from Arabian mares in Egypt, and probably from the entire middle east region. The presented information about EIV epidemiology and spread may require reconsideration of the vaccine strains used in the national vaccination programs.
An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs
Authors: Li Jianglong , Liu Qi , Liu Jun , Wu Xiaohong , Lei Yixin , Li Shuang , Zhao Danhua , Li Zhi , Luo Liping , Peng Sophia , Ou Yingrao , Yang Hong , Jin Jing , Li Yuhua , Peng Yucai 
Published: November 2022

AbstractRabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capacity in mice and dogs. LVRNA001 induced neutralizing antibody production and a strong Th1 cellular immune response in mice. In both mice and dogs, LVRNA001 provided protection against challenge with 50-fold lethal dose 50 (LD50) of RABV. With regards to protective efficiency, an extended dosing interval (14 days) induced greater antibody production than 3- or 7-day intervals in mice. Finally, post-exposure immunization against RABV was performed to evaluate the survival rates of dogs receiving two 25 μg doses of LVRNA001 vs. five doses of inactivated vaccine over the course of three months. Survival rate in the LVRNA001 group was 100%, whereas survival rate in the inactivated vaccine control group was only 33.33%. In conclusion, these results demonstrated that LVRNA001 induced strong protective immune responses in mice and dogs, which provides a new and promising prophylactic strategy for rabies.