bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoleamine 2,3-dioxygenase 2 immunohistochemical expression in medullary thyroid carcinoma: implications in prognosis and immunomodulatory effects
Authors: Gu Pengfei , Ling Bin , Ma Weike , Zhang Jinming , Zhang Wei , Zeng Yu , Liu Yu , Chi Jiadong , Ruan Xianhui , Zheng Xiangqian , Wei Songfeng , Gao Ming 
Published: November 2022

Abstract
Background
The linkage between IDO2 expression and cancer progression is still unclear, particularly in medullary thyroid carcinoma (MTC). Our purpose is to unveil the potential correlations between IDO2 status, clinical-pathological parameters, patients’ prognosis, and the possible immunomodulatory functions in MTC.

Methods
Immunohistochemical expression levels of IDO2 were evaluated in the resected MTC surgical specimens and corresponding lymph nodes. CD4 + T cell infiltration was also evaluated by immunohistochemical analysis in the MTC tissues. The association of the IDO2 expression level with clinicopathologic characteristics, overall survival (OS)/recurrence-free survival (RFS), and CD4 + T cell infiltration were retrospectively investigated.

Results
High expression of IDO2 is closely associated with more aggressive clinicopathological features, such as multifocality, ETE, a higher pT stage and especially a higher pN stage. Moreover, a significant difference in RFS was observed between the IDO2-high and IDO2-low groups. IDO2 expression of lymph node tissues was significantly related to the metastasis status. Furthermore, we found that IDO2 expression is negatively correlated with CD4 + T cell infiltrations in MTC tissues.

Conclusion
The expression level of IDO2 is associated with aggressive characteristics and is predictive of poor prognosis in patients with MTC. Also, an interesting observation is that IDO2 involvement in MTC showed a moderate sexual dimorphism, of which female patients tend to be more affected by IDO2 status. Moreover, our results showed the potential immunomodulatory functions of IDO2. The close relationship between IDO2 and CD4 + T cell infiltration in the MTC microenvironment, together with its potential prognostic implications, makes it possible for IDO2 to serve as an alternative drug target in cancer immunotherapy and as a new prognostic tool.
High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration
Authors: Kim Sehui , Koh Jaemoon , Song Seung Geun , Yim Jeemin , Kim Miso , Keam Bhumsuk , Kim Young Tae , Kim Jihun , Chung Doo Hyun , Jeon Yoon Kyung 
Published: November 2022

Abstract
Background
Relationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated.

Methods
Forty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis. For validation, formalin-fixed tissues from 375 lung ADC, 118 lung squamous cell carcinoma (SqCC), 338 colon ADC, and 78 lung cancer patients treated with anti-PD-1/PD-L1 immunotherapy were immunostained for HK2, CD8, and FOXP3.

Results
Based on immunoprofiling of lung ADC, HK2 tumor expression was associated with the composition of lymphoid cells rather than myeloid cells. High HK2 tumor expression was associated with immunosuppressive/pro-tumorigenic features, especially decreased ratio of CD8 + T-cells to Tregs (rho = −0.415, P = 0.012). This correlation was also confirmed in four different cohorts including lung ADC and SqCC, colon ADC, and the immunotherapy cohort (rho = −0.175~-0.335, all P < 0.05). A low CD8 + T-cell to Treg ratio was associated with poor progression-free survival and overall survival in lung SqCC patients, and a shorter overall survival in the immunotherapy cohort (all, P < 0.05).

Conclusion
An increase in HK2 expression may contribute to shaping the immunosuppressive/pro-tumorigenic tumor microenvironment by modulating the CD8 + T-cell to Treg ratio. Targeting tumor HK2 expression might be a potential strategy for enhancing anti-tumor immunity.
Prevalence and factors associated with depression among older adults in the case of a low-income country, Ethiopia: a systematic review and meta-analysis
Authors: Kasa Ayele Semachew , Lee Shu-Chun , Chang Hui-Chen 
Published: November 2022

AbstractBackgroundDepression is among the common mental health problems in late-life and an important public health problem. Studies from both middle- and high-income countries have shown that depression is more common among older people than in adolescents. Many older people with depression are overlooked, and fewer efforts are made to mitigate their suffering. Despite depression being a major public health problem among older adults, its overall magnitude, and its main predictors were not determined for the development of appropriate measures. Hence, the objective of this study was, therefore, to estimate the overall prevalence of depression and identify its predictors among older adults in Ethiopia.MethodsAvailable articles were searched by means of different databases using the PRISMA guideline. The quality of the included studies was assessed using a JBI quality appraisal tool. STATA version 14.0 (STATA Corporation, College Station, Texas, USA) statistical software was used to analyze the eligible studies. Subgroup and sensitivity analyses were performed. Cochran’s Q and the I2test were used to assess heterogeneity. The presence of publication bias was evaluated by using Egger’s test and visual inspection of the symmetry in funnel plots.ResultIn this meta-analysis, we included 11 articles that assessed 6521 older adults. The overall prevalence of depression among older adults in Ethiopia was 41.85 (33.52, 50.18). The finding was higher in the Oromia region with a prevalence of 48.07% (95% CI: 35.62, 60.51). The finding also demonstrated that being female (AOR = 1.76, 95% CI: 1.17, 2.63), no formal education (AOR = 1.82, 95% CI: 1.03, 3.19), with chronic diseases (AOR = 2.46, 95% CI: 1.00-6.06), and no social support (AOR = 2.01, 95% CI: 1.06, 3.83) were found to be independent predictors of depression in older Ethiopian adults.ConclusionOur systematic review and meta-analysis showed that almost two out of five older adults had depression. Female sex, no formal education, having chronic diseases, and no social support were the independent predictors of depression among older adults in Ethiopia. The study emphasizes that depression among older adults in Ethiopia calls for appropriate screening and interventions to reduce the occurrence and its overwhelming consequences.
Prediction of violence in male schizophrenia using sMRI, based on machine learning algorithms
Authors: Yu Tao , Pei Wenzhi , Xu Chunyuan , Zhang Xulai , Deng Chenchen 
Published: November 2022

Abstract
Background
Violent behavior in patients with schizophrenia (SCZ) is a major social problem. The early identification of SCZ patients with violence can facilitate implementation of targeted intervention.

Methods
A total of 57 male SCZ patients were recruited into this study. The general linear model was utilized to compare differences in structural magnetic resonance imaging (sMRI) including gray matter volume, cortical surface area, and cortical thickness between 30 SCZ patients who had exhibited violence and 27 SCZ patients without a history of violence. Based on machine learning algorithms, the different sMRI features between groups were integrated into the models for prediction of violence in SCZ patients.

Results
After controlling for the whole brain volume and age, the general linear model showed significant reductions in right bankssts thickness, inferior parietal thickness as well as left frontal pole volume in the patients with SCZ and violence relative to those without violence. Among seven machine learning algorithms, Support Vector Machine (SVM) have better performance in differentiating patients with violence from those without violence, with its balanced accuracy and area under curve (AUC) reaching 0.8231 and 0.841, respectively.

Conclusions
Patients with SCZ who had a history of violence displayed reduced cortical thickness and volume in several brain regions. Based on machine learning algorithms, structural MRI features are useful to improve predictive ability of SCZ patients at particular risk of violence.
How users make judgements about the quality of online health information: a cross-sectional survey study
Authors: Pian Wenjing , Lin Laibao , Li Baiyang , Qin Chunxiu , Lin Huizhong 
Published: November 2022

Abstract
Background
People increasingly use the Internet to seek health information. However, the overall quality of online health information remains low. This situation is exacerbated by the unprecedented “infodemic”, which has had negative consequences for patients. Therefore, it is important to understand how users make judgements about health information by applying different judgement criteria.

Objective
The objective of this study is to determine how patients apply different criteria in their judgement of the quality of online health information during the pandemic. In particular, we investigate whether there is consistency between the likelihood of using a particular judgement criterion and its perceived importance among different groups of users.

Methods
A cross-sectional survey was conducted in one of the leading hospitals in a coastal province of China with a population of forty million. Combined-strategy sampling was used to balance the randomness and the practicality of the recruiting process. A total of 1063 patients were recruited for this study. Chi-square and Kruskal–Wallis analyses were used to analyse the survey data.

Results
In general, patients make quality judgement of health information more frequently based on whether it is familiar, aesthetic, and with expertise. In comparison, they put more weights on whether health information is secure, trustworthy, and with expertise when determining its quality. Criteria that were considered more important were not always those with a higher likelihood of being used. Patients may not use particular criteria, such as familiarity, identification, and readability, more frequently than others even if they consider them to be more important than other do and vice versa. Surprisingly, patients with a primary school degree put more weight on whether health information is comprehensive than those with higher degrees do in determining its quality. However, they are less likely to use this guideline in practice.

Conclusions
To the best of our knowledge, this is the first study to investigate the consistency between the likelihood of using certain quality judgement criteria and their perceived importance among patients grouped by different demographic variables and eHealth literacy levels. The findings highlight how to improve online health information services and provide fine-grained customization of information for users.
Work-family conflict and the professional quality of life and their sociodemographic characteristics among nurses: a cross-sectional study in Tehran, Iran
Authors: Dilmaghani Reza Biabani , Armoon Baharam , Moghaddam Ladan Fattah 
Published: November 2022

Abstract
Background
Nurses are exposed to work-family conflict (WFC) due to specific occupational conditions, such as exposure to patients and shift work, which can affect the professional quality of life (ProQoL). The aim of the present study was to determine the relationship between different levels of work-family conflicts and professional quality of life and their sociodemographic characteristics among the nurses in two hospitals in Tehran, Iran.

Methods
This cross-sectional study included 234 nurses from two hospitals. Data were collected using a three-part questionnaire, including items related to nurses’ demographic characteristics, the WFC questionnaire, and the ProQoL questionnaire.

Results
There was a significant positive correlation between conflict in terms of time and behavior with compassion satisfaction and between the three types of conflict with job burnout (p < 0.05). The results indicate that the WFC and ProQoL scores and the mean WFC were higher among women, people who had a disabled family member, and nurses who worked equal to or more than 175 hours a month. Regarding the dimensions of ProQoL, the mean compassion satisfaction was lower among people who lived with their parents, people who had a second job had a child younger than one-year-old, and a disabled family member had higher means of job burnout. Also, those who had younger children experienced less PTSD. Furthermore, the mean of WFC and burnout among single nurses was significantly lower than among married and divorced/widowed nurses. Additionally, the mean of WFC and burnout among nurses living in rental houses and nurses reporting the level of satisfying relationships with co-workers as ‘bad’ were significantly more than for other nurses.

Conclusion
Stable mental and emotional conditions are of great importance for nurses to provide safe and quality services to their patients. The results also revealed that nurses’ compassion satisfaction and job burnout were associated with different types of conflict. The WFC of nurses is related to their ProQoL and affects their job satisfaction and burnout. Reducing conflict may improve the nurses’ satisfaction and thus improve patient care and healthcare services.
Impaired trafficking and instability of mutant kidney anion exchanger 1 proteins associated with autosomal recessive distal renal tubular acidosis
Authors: Deejai Nipaporn , Sawasdee Nunghathai , Nettuwakul Choochai , Wanachiwanawin Wanchai , Sritippayawan Suchai , Yenchitsomanus Pa-thai , Rungroj Nanyawan 
Published: November 2022

Abstract
Background
Mutations in solute carrier family 4 member 1 (SLC4A1) encoding anion exchanger 1 (AE1) are the most common cause of autosomal recessive distal renal tubular acidosis (AR dRTA) in Southeast Asians. To explain the molecular mechanism of this disease with hematological abnormalities in an affected family, we conducted a genetic analysis of SLC4A1 and studied wild-type and mutant AE1 proteins expressed in human embryonic kidney 293T (HEK293T) cells.

Methods
SLC4A1 mutations in the patient and family members were analyzed by molecular genetic techniques. Protein structure modeling was initially conducted to evaluate the effects of mutations on the three-dimensional structure of the AE1 protein. The mutant kidney anion exchanger 1 (kAE1) plasmid construct was created to study protein expression, localization, and stability in HEK293T cells.

Results
We discovered that the patient who had AR dRTA coexisting with mild hemolytic anemia carried a novel compound heterozygous SLC4A1 mutations containing c.1199_1225del (p.Ala400_Ala408del), resulting in Southeast Asian ovalocytosis (SAO), and c.1331C > A (p.Thr444Asn). Homologous modeling and in silico mutagenesis indicated that these two mutations affected the protein structure in the transmembrane regions of kAE1. We found the wild-type and mutant kAE1 T444N to be localized at the cell surface, whereas the mutants kAE1 SAO and SAO/T444N were intracellularly retained. The half-life of the kAE1 SAO, T444N, and SAO/T444N mutants was shorter than that of the wild-type protein.

Conclusion
These results suggest impaired trafficking and instability of kAE1 SAO/T444N as the likely underlying molecular mechanism explaining the pathogenesis of the novel SLC4A1 compound heterozygous mutation identified in this patient.
Meat consumption and the risk of general and central obesity: the Shahedieh study
Authors: Khodayari Shaghayegh , Sadeghi Omid , Safabakhsh Maryam , Mozaffari-Khosravi Hassan 
Published: November 2022

Abstract
Objective
This study aimed to investigate the relations of total meat intake and its subtypes, including red and processed meat, white meat, poultry, fish, and organ meat to the risk of general/central obesity.

Methods
This cross-sectional study included a total of 7312 Iranian adults with the age range of 35–70 years from the Shahedieh cohort study, Yazd, Iran. Dietary intake of subjects was evaluated using a validated 120-item Food Frequency Questionnaire. General obesity was defined as body mass index ≥ 30 kg/m2 and central obesity as waist circumference ≥ 102 cm in men and ≥ 88 cm in women.

Results
After controlling for potential covariates including energy intake, age, marital status, gender, physical activity, supplement use, house possession, education, family size, current smoking, night shift working, history of thyroid disease and depression, and intakes of vegetables, legumes, nuts, fruits, whole grains, and dairy, a significant direct association was found between the higher consumption of white meat (OR = 1.31; 95% CI: 1.06–1.61) and poultry (OR = 1.23; 95% CI: 1.04–1.45) with odds of general obesity. Processed meat was a significant predictor for central obesity in the fully adjusted model, so that individuals in the fourth quartile of processed meat intake, compared with those in the first quartile, had a 22% (OR = 1.22; 95% CI: 1.04–1.43) increased risk to be centrally obese.

Conclusion
This study reveals that higher intakes of white meat and poultry are associated with increased risk of general obesity, while, processed meat consumption was associated with central obesity.
Differentially hypomethylated cell-free DNA and coronary collateral circulation
Authors: Ahn Jongseong , Heo Sunghoon , Ahn Soo-jin , Bang Duhee , Lee Sang-Hak 
Published: November 2022

Abstract
Background
The factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronary collateral circulation (CCC).

Result
In this case–control study, clinical and angiographic data were obtained from 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted from the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions from which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Through random forest preparation process, 256 differentially methylated region (DMR) candidates showing strong association with CCC were selected. A random forest classifier was then constructed, and the area under the curve of the receiver operating characteristic curve indicated an appropriate predictive function for CCC. Finally, 20 DMRs were identified to have significantly different AMF values between the good and poor CCC groups. Particularly, the good CCC group exhibited hypomethylated DMRs. Pathway analysis revealed five pathways, including TGF-beta signaling, to be associated with good CCC.

Conclusion
These data have demonstrated that differential hypomethylation was identified in dozens of cfDNA regions in patients with good CCC. Our results support the clinical utility of noninvasively obtained epigenetic signatures for predicting collateral circulation in patients with vascular diseases.
Type II Pfieffer misdiagnosed as Crouzon syndrome with additional features of supernumerary teeth and localized symmetrical gigantism: a case report
Authors: Manji Karim P. , Massomo Mariam Mngoya , Akyoo Edna Samson , Luvinga McLean Abisai 
Published: November 2022

Abstract
Background
Pfieffer syndrome is among the syndromes seen in the recognized variant of the FGFR2 gene. There are several conditions related to this variant and a very closely related condition is Crouzon syndrome. This case is important to report because the neonate was a delayed referral from another region, without clear counseling and information on the gravity of situation. We describe additional features , not previously described in Pfieffer or Crouzon syndrome, supernumerary teeth and localized symmetrical gigantism of thumbs and great toes on both sides. That a genetic testing is essential to further manage and counsel to avoid lost opportunities for future births. Several cases are seen in this unit annually, and there is need for a more consolidated and comprehensive counseling and genetic testing. Once early diagnosis is done and the case is recognized to be untreatable, it was avert the need to refer.

Case presentation
A 2-week-old male African neonate referred from outside the region, presented with massive proptosis soon after delivery, with signs of pan-ophthalmitis and neonatal sepsis. The infant had additional multiple malformations and features initially diagnosed as Crouzon syndrome , but later confirmed after genetic testing to be Type II Pfieffer syndrome. A through clinical evaluation and genetic testing would prevent undue referral to a tertiary center, or if needed, the baby should have been referred much earlier. The uniqueness of this case is the presence of supernumerary teeth.

Conclusion
A complicated, difficult to remedy case, referred to tertiary center, investigated, and sent back home with no significant intervention. Genetic test confirmed the typical findings of Pfieffer Type II. Presented for describing additional unique features of supernumerary teeth and localized gigantism and ethical challenges in management.
Homemade plasmid Miniprep solutions for affordable research in low-fund laboratories
Authors: Elnagar Mohamed A. , Ibrahim Mohamed F. , Albert Magdy , M.Talal Maya , Abdelfattah Mahmoud M. , El-Dabaa Ehab , Helwa Reham 
Published: November 2022

AbstractAs a consequence of Covid-19 pandemic, the basic lab consumables are in shortage, especially in the low-income countries. Thus, the main objective of the present study is to develop and evaluate homemade solution to isolate plasmid. To pursue this objective, RNase A was overexpressed in Bl21 DE3 cells (E. coli strain) and prepared as crude refolding reaction with proper activity. Also, lysis buffers, neutralization buffer, and washing buffers were prepared. The homemade miniprep kit showed successful isolation of the px48SpCas9 plasmid. The prepared plasmid purity was enough to be used successfully in PCR amplification. In addition, to get extra benefits from this study, seven primers were designed to match the plasmid backbone to produce DNA ladder (100–1500 bp). In conclusion, we were able to have attainable working solutions for plasmid miniprep and DNA ladder.