bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the emotional functioning in clinical practice to detect psychological distress in patients with advanced thoracic and colorectal cancer
Authors: Rodriguez-Gonzalez Adán , Hernández Raquel , Cruz-Castellanos Patricia , Fernández-Montes Ana , Castillo-Trujillo Oscar , Muñoz María M. , Cano-Cano Juana M. , Corral María J. , Esteban Emilio , Jiménez-Fonseca Paula , Calderon Caterina 
Published: February 2023

Abstract
Purpose
Patients with advanced cancer suffer significant decline of their psychological state. A rapid and reliable evaluation of this state is essential to detect and treat it and improve quality of life. The aim was to probe the usefulness of the emotional function (EF) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EF-EORTC-QLQ-C30) to assess psychological distress in cancer patients.

Methods
This is a multicenter, prospective, observational study involving 15 Spanish hospitals. Patients diagnosed with unresectable advanced thoracic or colorectal cancer were included. Participants completed the Brief Symptom Inventory 18 (BSI-18), the current the gold standard, and the EF-EORTC-QLQ-C30 to assess their psychological distress prior to initiating systemic antineoplastic treatment. Accuracy, sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were calculated.

Results
The sample comprised 639 patients: 283 with advanced thoracic cancer and 356 with advanced colorectal cancer. According to the BSI scale, 74% and 66% displayed psychological distress with an EF-EORTC-QLQ-C30 accuracy of 79% and 76% in detecting psychological distress in individuals with advanced thoracic and colorectal cancer, respectively. Sensitivity was 79 and 75% and specificity was 79 and 77% with a PPV of 92 and 86% and a NPV of 56 and 61% (scale cut-off point, 75) for patients with advanced thoracic and colorectal cancer, respectively. The mean AUC for thoracic cancer was 0.84 and, for colorectal cancer, it was 0.85.

Conclusion
This study reveals that the EF-EORTC-QLQ-C30 subscale is a simple and effective tool for detecting psychological distress in people with advanced cancer.
Circular RNA METTL9 contributes to neuroinflammation following traumatic brain injury by complexing with astrocytic SND1
Authors: Huang Chunling , Sun Lulu , Xiao Chenyang , You Wenjun , Sun Li , Wang Siye , Zhang Zhijun , Liu Su 
Published: February 2023

Abstract
Background
Circular RNAs (circRNAs) are highly enriched in the central nervous system and have been implicated in neurodegenerative diseases. However, whether and how circRNAs contribute to the pathological processes induced by traumatic brain injury (TBI) has not been fully elucidated.

Methods
We conducted a high-throughput RNA sequencing screen for well-conserved, differentially expressed circRNAs in the cortex of rats subjected to experimental TBI. Circular RNA METTL9 (circMETTL9) was ultimately identified as upregulated post-TBI and further characterized by RT-PCR and agarose gel electrophoresis, Sanger sequencing, and RNase R treatment. To examine potential involvement of circMETTL9 in neurodegeneration and loss of function following TBI, circMETTL9 expression in cortex was knocked-down by microinjection of a shcircMETTL9 adeno-associated virus. Neurological functions were evaluated in control, TBI, and TBI-KD rats using a modified neurological severity score, cognitive function using the Morris water maze test, and nerve cell apoptosis rate by TUNEL staining. Pull-down assays and mass spectrometry were conducted to identify circMETTL9-binding proteins. Co-localization of circMETTL9 and SND1 in astrocytes was examined by fluorescence in situ hybridization and immunofluorescence double staining. Changes in the expression levels of chemokines and SND1 were estimated by quantitative PCR and western blotting.

Results
CircMETTL9 was significantly upregulated and peaked at 7 d in the cerebral cortex of TBI model rats, and it was abundantly expressed in astrocytes. We found that circMETTL9 knockdown significantly attenuated neurological dysfunction, cognitive impairment, and nerve cell apoptosis induced by TBI. CircMETTL9 directly bound to and increased the expression of SND1 in astrocytes, leading to the upregulation of CCL2, CXCL1, CCL3, CXCL3, and CXCL10, and ultimately to enhanced neuroinflammation.

Conclusion
Altogether, we are the first to propose that circMETTL9 is a master regulator of neuroinflammation following TBI, and thus a major contributor to neurodegeneration and neurological dysfunction.

Graphical Abstract
Relationship between efficacy and common metabolic parameters in first-treatment drug-naïve patients with early non-response schizophrenia: a retrospective study
Authors: Zhu Junhong , Wu Jiajia , Liu Xuebing , Ma Jun 
Published: February 2023

Abstract
Background
Comorbid metabolic disorders in patients with schizophrenia are very common. Patients with schizophrenia who respond to therapy early are often strongly predictive of better treatment outcomes. However, the differences in short-term metabolic markers between early responders and early non-responders in schizophrenia are unclear.

Methods
143 first-treatment drug-naïve schizophrenia patients were included in this study and were given a single antipsychotic medication for 6 weeks after admission. After 2 weeks, the sample was divided into an early response group and an early non-response group based on psychopathological changes. For the study endpoints, we depicted the change curves of psychopathology in both subgroups and compared the differences between the two groups in terms of remission rates and multiple metabolic parameters.

Results
The early non-response had 73 cases (51.05%) in the 2nd week. In the 6th week, the remission rate was significantly higher in the early response group than in the early non-response group (30,42.86% vs. 8,10.96%); the body weight, body mass index, blood creatinine, blood uric acid, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, and prolactin of the enrolled samples were significantly increased, and high-density lipoprotein was significantly decreased. ANOVAs revealed a significant effect of treatment time on abdominal circumference, blood uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, fasting blood glucose and prolactin, and a significant negative effect of early non-response to treatment on abdominal circumference, blood creatinine, triglyceride, fasting blood glucose.

Conclusions
Schizophrenia patients with early non-response had lower rates of short-term remission and more extensive and severe abnormal metabolic indicators. In clinical practice, patients with early non-response should be given a targeted management strategy, antipsychotic drugs should be switched on time, and active and effective interventions for their metabolic disorders should be given.
Intravenous ketamine for severe alcohol use disorder at Moi Teaching & Referral Hospital, Kenya: a case report
Authors: Jaguga Florence , Kirwa Philip , Gakinya Benson , Manji Imran , Andale Thomas , Kinyanjui Daniel , Kwobah Edith Kamaru , Mwangi Felicita , Werunga Kituyi , Kerema Josephat , Kwobah Charles , Temet Eunice , Songok Julia , Aruasa Wilson K. 
Published: February 2023

Abstract
Background
Alcohol use disorder is prevalent globally and in Kenya, and is associated with significant health and socio-economic consequences. Despite this, available pharmacological treatment options are limited. Recent evidence indicates that intravenous (IV) ketamine can be beneficial for the treatment of alcohol use disorder, but is yet to be approved for this indication. Further, little has been done to describe the use of IV ketamine for alcohol use disorder in Africa. The goal of this paper, is to: 1) describe the steps we took to obtain approval and prepare for off-label use of IV ketamine for patients with alcohol use disorder at the second largest hospital in Kenya, and 2) describe the presentation and outcomes of the first patient who received IV ketamine for severe alcohol use disorder at the hospital.

Case presentation
In preparing for the off-label use of ketamine for alcohol use disorder, we brought together a multi-disciplinary team of clinicians including psychiatrists, pharmacists, ethicists, anesthetists, and members of the drug and therapeutics committee, to spearhead the process. The team developed a protocol for administering IV ketamine for alcohol use disorder that took into account ethical and safety issues. The national drug regulatory authority, the Pharmacy and Poison’s Board, reviewed and approved the protocol.
Our first patient was a 39-year-old African male with severe alcohol use disorder and comorbid tobacco use disorder and bipolar disorder. The patient had attended in-patient treatment for alcohol use disorder six times and each time had relapsed between one to four months after discharge. On two occasions, the patient had relapsed while on optimal doses of oral and implant naltrexone. The patient received IV ketamine infusion at a dose of 0.71 mg/kg. The patient relapsed within one week of receiving IV ketamine while on naltrexone, mood stabilizers, and nicotine replacement therapy.

Discussion & conclusions
This case report describes for the first time the use of IV ketamine for alcohol use disorder in Africa. Findings will be useful in informing future research and in guiding other clinicians interested in administering IV ketamine for patients with alcohol use disorder.
Cross-analyzing addiction specialist and patient opinions and experiences about addictive disorder screening in primary care to identify interaction-related obstacles: a qualitative study
Authors: Pautrat Maxime , Renard Caroline , Riffault Vincent , Ciolfi David , Edeline Agathe , Breton Hervé , Brunault Paul , Lebeau Jean Pierre 
Published: February 2023

Abstract
Background
Promptly identifying individuals with addictive disorders reduces mortality and morbidity and improves quality of life. Although screening in primary care with the Screening, Brief Intervention and Referral Treatment strategy has been recommended since 2008, it remains underutilized. This may be due to barriers including lack of time, patient reluctance or perhaps the timing and approach for discussing addiction with their patients.

Objective
This study aims to explore and cross-analyze patient and addiction specialist experiences and opinions about early addictive disorder screening in primary care to identify interaction-related screening obstacles.

Design and participants
Qualitative study with purposive maximum variation sampling among nine addiction specialists and eight individuals with addiction disorders conducted between April 2017 and November 2019 in Val-de-Loire, France.

Main Measures
Using a grounded theory approach, verbatim data was collected from face-to-face interviews with addiction specialists and individuals with addiction disorders. These interviews explored their opinions and experiences with addiction screening in primary care. Initially, two independent investigators analyzed the coded verbatim according to the data triangulation principle. Secondly, convergences and divergences between addiction specialist and addict verbatim categories were identified, analyzed, and conceptualized.

Key Results
Four main interaction-related obstacles to early addictive disorder screening in primary care were identified and conceptualized: the new concepts of shared self-censorship and the patient's personal red line, issues not addressed during consultations, and opposition between how physicians and patients would like to approach addictive disorder screening.

Conclusions
To continue analysis of addictive disorder screening dynamics, further studies to examine the perspectives of all those involved in primary care are required. The information revealed from these studies will provide ideas to help patients and caregivers start discussing addiction and to help implement a collaborative team-based care approach.

Trial registration
This study is registered with the Commission Nationale de l’Informatique et des Libertés (CNIL) under No. 2017–093.
A Trem2R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques
Authors: Tran Kristine M. , Kawauchi Shimako , Kramár Enikö A. , Rezaie Narges , Liang Heidi Yahan , Sakr Jasmine S. , Gomez-Arboledas Angela , Arreola Miguel A. , Cunha Celia da , Phan Jimmy , Wang Shuling , Collins Sherilyn , Walker Amber , Shi Kai-Xuan , Neumann Jonathan , Filimban Ghassan , Shi Zechuan , Milinkeviciute Giedre , Javonillo Dominic I. , Tran Katelynn , Gantuz Magdalena , Forner Stefania , Swarup Vivek , Tenner Andrea J. , LaFerla Frank M. , Wood Marcelo A. , Mortazavi Ali , MacGregor Grant R. , Green Kim N. 
Published: February 2023

AbstractBackgroundThe TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many currentTrem2R47Hmouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed theTrem2R47H NSS(NormalSpliceSite) mouse model in which theTrem2allele is expressed at a similar level to the wild-typeTrem2allele without evidence of cryptic splicing products.MethodsTrem2R47H NSSmice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain’s response to plaques.ResultsTrem2R47H NSSmice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes inTrem2R47H NSSmice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygousTrem2R47H NSS(5xFAD/Trem2R47H NSS) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity forTrem2R47H NSSsuppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/Trem2R47H NSSmice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month oldTrem2R47H NSSmice also display LTP deficits and postsynaptic loss.ConclusionsTheTrem2R47H NSSmouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.
The Matthews correlation coefficient (MCC) should replace the ROC AUC as the standard metric for assessing binary classification
Authors: Chicco Davide , Jurman Giuseppe 
Published: February 2023

AbstractBinary classification is a common task for which machine learning and computational statistics are used, and the area under the receiver operating characteristic curve (ROC AUC) has become the common standard metric to evaluate binary classifications in most scientific fields. The ROC curve has true positive rate (also called sensitivity or recall) on the y axis and false positive rate on the x axis, and the ROC AUC can range from 0 (worst result) to 1 (perfect result). The ROC AUC, however, has several flaws and drawbacks. This score is generated including predictions that obtained insufficient sensitivity and specificity, and moreover it does not say anything about positive predictive value (also known as precision) nor negative predictive value (NPV) obtained by the classifier, therefore potentially generating inflated overoptimistic results. Since it is common to include ROC AUC alone without precision and negative predictive value, a researcher might erroneously conclude that their classification was successful. Furthermore, a given point in the ROC space does not identify a single confusion matrix nor a group of matrices sharing the same MCC value. Indeed, a given (sensitivity, specificity) pair can cover a broad MCC range, which casts doubts on the reliability of ROC AUC as a performance measure. In contrast, the Matthews correlation coefficient (MCC) generates a high score in its $$[-1; +1]$$

[
-
1
;
+
1
]

interval only if the classifier scored a high value for all the four basic rates of the confusion matrix: sensitivity, specificity, precision, and negative predictive value. A high MCC (for example, MCC $$=$$
=
0.9), moreover, always corresponds to a high ROC AUC, and not vice versa. In this short study, we explain why the Matthews correlation coefficient should replace the ROC AUC as standard statistic in all the scientific studies involving a binary classification, in all scientific fields.
Novel DNA methylation biomarkers in stool and blood for early detection of colorectal cancer and precancerous lesions
Authors: Shen Yuguang , Wang Dongyang , Yuan Tianli , Fang Hongsheng , Zhu Chen , Qin Juan , Xu Xiaojing , Zhang Cheng , Liu Jiahua , Zhang Yuanruohan , Wen Zhoujin , Tang Jian , Wang Zheng 
Published: February 2023

Abstract
Background
Early detection and prevention of precancerous lesions can significantly reduce the morbidity and mortality of colorectal cancer (CRC). Here, we developed new candidate CpG site biomarkers for CRC and evaluated the diagnostic value of their expression in blood and stool samples of CRC and precancerous lesions.

Methods
We analyzed 76 pairs of CRC and adjacent normal tissue samples, 348 stool samples, and 136 blood samples. Candidate biomarkers for CRC were screened using a bioinformatics database and identified using a quantitative methylation-specific PCR method. The methylation levels of the candidate biomarkers were validated using blood and stool samples. The divided stool samples were used to construct and validate a combined diagnostic model and to analyze the independent or combined diagnostic value of candidate biomarkers in stool samples of CRC and precancerous lesions.

Results
Two candidate CpG site biomarkers for CRC, cg13096260 and cg12993163, were identified. Although both biomarkers demonstrated diagnostic performance to a certain extent when using blood samples, they showed better diagnostic value for different stages of CRC and AA with stool samples.

Conclusions
cg13096260 and cg12993163 detection in stool samples could be a promising approach for screening and early diagnosis of CRC and precancerous lesions.
Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis
Authors: Allen Peter C. , Smith Sarah , Wilson Robert C. , Wirth Jena R. , Wilson Nathan H. , Baker Frost DeAnna , Flume Jonathan , Gilkeson Gary S. , Cunningham Melissa A. , Langefeld Carl D. , Absher Devin M. , Ramos Paula S. 
Published: February 2023

Abstract
Background
Systemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans. In this study, we sought to investigate DNA methylation and gene expression patterns in classical monocytes in a health disparity population.

Methods
Classical monocytes (CD14+ + CD16−) were FACS-isolated from 34 self-reported African American women. Samples from 12 SSc patients and 12 healthy controls were hybridized on MethylationEPIC BeadChip array, while RNA-seq was performed on 16 SSc patients and 18 healthy controls. Analyses were computed to identify differentially methylated CpGs (DMCs), differentially expressed genes (DEGs), and CpGs associated with changes in gene expression (eQTM analysis).

Results
We observed modest DNA methylation and gene expression differences between cases and controls. The genes harboring the top DMCs, the top DEGs, as well as the top eQTM loci were enriched for metabolic processes. Genes involved in immune processes and pathways showed a weak upregulation in the transcriptomic analysis. While many genes were newly identified, several other have been previously reported as differentially methylated or expressed in different blood cells from patients with SSc, supporting for their potential dysregulation in SSc.

Conclusions
While contrasting with results found in other blood cell types in largely European-descent groups, the results of this study support that variation in DNA methylation and gene expression exists among different cell types and individuals of different genetic, clinical, social, and environmental backgrounds. This finding supports the importance of including diverse, well-characterized patients to understand the different roles of DNA methylation and gene expression variability in the dysregulation of classical monocytes in diverse populations, which might help explaining the health disparities.
Single-cell transcriptome analysis reveals stem cell-like subsets in the progression of Waldenström’s macroglobulinemia
Authors: Qiu Yu , Wang Xiao-shuang , Yao Yuan , Si Yan-min , Wang Xue-zhu , Jia Ming-nan , Zhou Dao-bin , Yu Jia , Cao Xin-xin , Li Jian 
Published: February 2023

AbstractWaldenström’s macroglobulinemia (WM) is an uncommon lymphoproliferative disorder, and the precise cellular landscape and the mechanisms of progression from IgM monoclonal gammopathy of undetermined significance (MGUS) to WM remain unclear. We performed single-cell RNA sequencing of CD19 + and CD19-CD38 + cells from healthy donors, IgM MGUS and WM patients. We found that samples from IgM MGUS and WM patients were composed of fewer early B-cell subsets and more T cells and NK cells than those from healthy controls. Compared with those of IgM MGUS patients, mature B cells of WM patients showed upregulation of HES1, GADD45B, NEAT1, DUSP22, RGS1, RGS16, and PIM1. We also identified a subpopulation of CD3 + CD19 + cells in IgM MGUS and WM patients, and trajectory analysis suggested that this subpopulation might be a stem cell-like subset. Further targeted gene sequencing of CD3 + CD19 + and CD3-CD19 + cells proved that MYD88 might be the early events in tumorigenesis according to variant allele fraction analysis. Additional subclonal hits such as CXCR4 and MAP2K1 mutations could be acquired during tumor progression. CXCL signaling, CCL signaling, IL2 signaling and TGFβ signaling pathways were involved in communication between CD3 + CD19 + cells and other immune cells. Our findings reveal the composition of CD38 + immune microenvironment together with B cells and plasma cells in IgM MGUS and WM patients, and provide comprehensive insights into mechanisms of progression from IgM MGUS to WM. The rare CD3 + CD19 + cells might be cells with “stemness” feature.