bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm
Authors: Shao Sihui , Yao Minghua , Li Chunxiao , Li Xin , Wang Jianfeng , Chen Jing , Zheng Yi , Wu Rong 
Published: March 2023

BackgroundSome women die despite the favorable prognosis of small breast cancers. Breast ultrasound features may reflect pathological and biological characteristics of a breast tumor. This study aimed to explore whether ultrasound features could identify small breast cancers with poor outcomes.MethodsThis retrospective study examined confirmed breast cancers with a size of &lt;20 mm diagnosed in our hospital between 02/2008 and 08/2019. Clinicopathological and ultrasound features were compared between alive and deceased breast cancer patients. Survival was analyzed using the Kaplan-Meier curves. Multivariable Cox proportional hazards models were used to examine the factors associated with breast cancer-specific survival (BCSS) and disease-free survival (DFS).ResultsAmong the 790 patients, the median follow-up was 3.5 years. The deceased group showed higher frequencies of spiculated (36.7% vs. 11.2%, P&lt;0.001), anti-parallel orientation (43.3% vs. 15.4%, P&lt;0.001), and spiculated morphology combined with anti-parallel orientation (30.0% vs. 2.4%, P&lt;0.001). Among 27 patients with spiculated morphology and anti-parallel orientation, nine cancer-specific deaths and 11 recurrences occurred, for a 5-year BCSS of 77.8% and DFS of 66.7%, while 21 breast-cancer deaths and 41 recurrences occurred among the remaining patients with higher 5-year BCSS (97.8%, P&lt;0.001) and DFS (95.4%, P&lt;0.001). Spiculated and anti-parallel orientation (HR=7.45, 95%CI: 3.26-17.00; HR=6.42, 95%CI: 3.19-12.93), age ≥55 years (HR=5.94, 95%CI: 2.24-15.72; HR=1.98, 95%CI: 1.11-3.54), and lymph nodes metastasis (HR=3.99, 95%CI: 1.89-8.43; HR=2.99, 95%CI: 1.71-5.23) were independently associated with poor BCSS and DFS.ConclusionsSpiculated and anti-parallel orientation at ultrasound are associated with poor BCSS and DFS in patients with primary breast cancer &lt;20 mm.
Association of serum metabolome profile with the risk of breast cancer in participants of the HUNT2 study
Authors: Mrowiec Katarzyna , Kurczyk Agata , Jelonek Karol , Debik Julia , Giskeødegård Guro F. , Bathen Tone F. , Widłak Piotr 
Published: March 2023

BackgroundThe serum metabolome is a potential source of molecular biomarkers associated with the risk of breast cancer. Here we aimed to analyze metabolites present in pre-diagnostic serum samples collected from healthy women participating in the Norwegian Trøndelag Health Study (HUNT2 study) for whom long-term information about developing breast cancer was available.MethodsWomen participating in the HUNT2 study who developed breast cancer within a 15-year follow-up period (BC cases) and age-matched women who stayed breast cancer-free were selected (n=453 case-control pairs). Using a high-resolution mass spectrometry approach 284 compounds were quantitatively analyzed, including 30 amino acids and biogenic amines, hexoses, and 253 lipids (acylcarnitines, glycerides, phosphatidylcholines, sphingolipids, and cholesteryl esters).ResultsAge was a major confounding factor responsible for a large heterogeneity in the dataset, hence age-defined subgroups were analyzed separately. The largest number of metabolites whose serum levels differentiated BC cases and controls (82 compounds) were observed in the subgroup of younger women (&lt;45 years old). Noteworthy, increased levels of glycerides, phosphatidylcholines, and sphingolipids were associated with reduced risk of cancer in younger and middle-aged women (≤64 years old). On the other hand, increased levels of serum lipids were associated with an enhanced risk of breast cancer in older women (&gt;64 years old). Moreover, several metabolites could be detected whose serum levels were different between BC cases diagnosed earlier (&lt;5 years) and later (&gt;10 years) after sample collecting, yet these compounds were also correlated with the age of participants. Current results were coherent with the results of the NMR-based metabolomics study performed in the cohort of HUNT2 participants, where increased serum levels of VLDL subfractions were associated with reduced risk of breast cancer in premenopausal women.ConclusionsChanges in metabolite levels detected in pre-diagnostic serum samples, which reflected an impaired lipid and amino acid metabolism, were associated with long-term risk of breast cancer in an age-dependent manner.
Somatic mutation detection and KRAS amplification in testicular germ cell tumors
Authors: Cabral Eduardo R. M. , Pacanhella Marilia F. , Lengert Andre V. H. , Reis Mariana B. dos , Leal Leticia F. , Lima Marcos A. de , Silva Aline L. V. da , Pinto Icaro A. , Reis Rui M. , Pinto Mariana T. , Cárcano Flavio M. 
Published: March 2023

BackgroundTesticular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center.Materials and methodsA cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan–Meier method and log-rank test.ResultsKRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.ConclusionAlthough larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.
Pathologic complete response to chemoimmunotherapy of an advanced gastric cancer patient with high PD-L1 expression, dMMR, and unique gut microbiota composition: A case report
Authors: Jiang Hongpeng , Wang Junyun , Deng Wei 
Published: March 2023

BackgroundAdvanced gastric cancer (AGC) is a malignant disease with limited therapeutic options and a poor prognosis. Recently, immune checkpoint inhibitors (ICIs), represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential gastric cancer (GC) therapy.Case presentationThis case study aimed to reveal the tumor response to neoadjuvant chemotherapy combined with camrelizumab in a patient with AGC based on the characteristics of the clinical pathology, genomics variation, and gut microbiome. Samples from a 59-year-old male patient diagnosed with locally advanced unresectable GC (cT4bN2M0, high grade) presenting PD-L1-positive, deficient mismatch repair (dMMR), and highly specific gut microbiota enrichment were subjected to target region sequencing, metagenomic sequencing, and immunohistochemistry staining. The patient received neoadjuvant therapy, including camrelizumab, apatinib, S-1, and abraxane, which eventually promoted dramatic tumor shrinkage without serious adverse effects and allowed subsequent radical gastrectomy and lymphadenectomy. Finally, the patient achieved pathologic complete response (pCR), and the recurrence-free survival time was 19 months at the last follow-up in April 2021.ConclusionsThe patient with PD-L1-positive, dMMR, and a highly specific gut microbiota enrichment exhibited a pCR to neoadjuvant chemoimmunotherapy.
Sex-related differences in the efficacy of Baclofen enantiomers on self-administered alcohol in a binge drinking pattern and dopamine release in the core of the nucleus accumbens
Authors: Jeanblanc Jérôme , Sauton Pierre , Houdant Charles , Fernandez Rodriguez Sandra , de Sousa Sofia Vilelas , Jeanblanc Virginie , Bodeau Sandra , Labat Laurence , Soichot Marion , Vorspan Florence , Naassila Mickael 
Published: March 2023

Introduction: Clinical studies on the effectiveness of Baclofen in alcohol use disorder (AUD) yielded mixed results possibly because of differential effects of the enantiomers and sex-related differences. Here we examined the effect of the different Baclofen enantiomers on alcohol intake and on evoked dopamine release in the core of the nucleus accumbens (NAcc) in male and female Long Evans rats.Methods: Rats were trained to chronically self-administer 20% alcohol solution in daily binge drinking sessions and were treated with the different forms of Baclofen [RS(±), R(+) and S(−)]. The effects on the evoked dopamine release within the core of the nucleus accumbens were measured in brain slices from the same animals and the alcohol naïve animals using the fast scan cyclic voltammetry technique.Results: RS(±)-Baclofen reduced alcohol intake regardless of sex but more females were non-responders to the treatment. R(+)-Baclofen also reduced alcohol intake regardless of sex but females were less sensitive than males. S(−)-Baclofen did not have any effect on average but in some individuals, especially in the females, it did increase alcohol intake by at least 100%. There were no sex differences in Baclofen pharmacokinetic but a strong negative correlation was found in females with a paradoxical effect of increased alcohol intake with higher blood Baclofen concentration. Chronic alcohol intake reduced the sensitivity to the effect of Baclofen on evoked dopamine release and S(−)-Baclofen increased dopamine release specifically in females.Discussion: Our results demonstrate a sex-dependent effect of the different forms of Baclofen with no or negative effects (meaning an increase in alcohol self-administration) in subgroup of females that could be linked to a differential effect on dopamine release and should warrant future clinical studies on alcohol use disorder pharmacotherapy that will deeply analyze sex difference.
Characterization of ligand-induced thermal stability of the human organic cation transporter 2 (OCT2)
Authors: Maane Max , Xiu Fangrui , Bellstedt Peter , Kullak-Ublick Gerd A. , Visentin Michele 
Published: March 2023

Introduction: The human organic cation transporter 2 (OCT2) is involved in the transport of endogenous quaternary amines and positively charged drugs across the basolateral membrane of proximal tubular cells. In the absence of a structure, the progress in unraveling the molecular basis of OCT2 substrate specificity is hampered by the unique complexity of OCT2 binding pocket, which seemingly contains multiple allosteric binding sites for different substrates. Here, we used the thermal shift assay (TSA) to better understand the thermodynamics governing OCT2 binding to different ligands.Methods: Molecular modelling and in silico docking of different ligands revealed two distinct binding sites at OCT2 outer part of the cleft. The predicted interactions were assessed by cis-inhibition assay using [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) as a model substrate, or by measuring the uptake of radiolabeled ligands in intact cells. Crude membranes from HEK293 cells harboring human OCT2 (OCT2-HEK293) were solubilized in n-Dodecyl-β-D-Maltopyranoside (DDM), incubated with the ligand, heated over a temperature gradient, and then pelleted to remove heat-induced aggregates. The OCT2 in the supernatant was detected by western blot.Results: Among the compounds tested, cis-inhibition and TSA assays showed partly overlapping results. Gentamicin and methotrexate (MTX) did not inhibit [3H]MPP+ uptake but significantly increased the thermal stabilization of OCT2. Conversely, amiloride completely inhibited [3H]MPP+ uptake but did not affect OCT2 thermal stabilization. [3H]MTX intracellular level was significantly higher in OCT2-HEK293 cells than in wild type cells. The magnitude of the thermal shift (ΔTm) did not provide information on the binding. Ligands with similar affinity showed markedly different ΔTm, indicating different enthalpic and entropic contributions for similar binding affinities. The ΔTm positively correlated with ligand molecular weight/chemical complexity, which typically has high entropic costs, suggesting that large ΔTm reflect a larger displacement of bound water molecules.Discussion: In conclusion, TSA might represent a viable approach to expand our knowledge on OCT2 binding descriptors.
Relationship of insight to neurocognitive function and risk of recurrence in depression: A naturalistic follow-up study
Authors: Wang Min , Liu Qiong , Yang Xiao , Dou Yikai , Wang Yu , Zhang Zijian , Luo Ruiqing , Ma Yangrui , Wang Qiang , Li Tao , Ma Xiaohong 
Published: March 2023

IntroductionMajor depressive disorder (MDD) is a highly recurrent mental illness accompanied by impairment of neurocognitive function. Lack of insight may affect patients’ motivation to seek treatment, resulting in poor clinical outcomes. This study explores the relationship of insight to neurocognitive function and the risk of recurrence of depressive episodes in patients with MDD.MethodsDemographic, clinical variables, and neurocognitive function measured with Intra-Extra Dimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were collected from 277 patients with MDD. Among them, 141 participants completed a follow-up visit within 1–5 years. Insight was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). To explore the factors associated with recurrence, binary logistic regression models were used.ResultsPatients with MDD, without insight, had significantly higher total and factor scores (anxiety/somatization, weight, retardation, and sleep) on the HAM-D and worse performance in the neurocognition task, compared to those with insight. Furthermore, binary logistic regression revealed that insight and retardation can predict recurrence.ConclusionLack of insight is associated with recurrence and impaired cognitive flexibility in patients with MDD.
Downregulation of cyclic adenosine monophosphate levels in leukocytes of hibernating captive black bears is similar to reported cyclic adenosine monophosphate findings in major depressive disorder
Authors: Tsiouris John A. , Flory Michael 
Published: March 2023

IntroductionCyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation.MethodsTo compare cAMP levels between human MDD and mammalian hibernation and to investigate whether cAMP downregulation is another state-dependent neurobiological finding, we measured cAMP concentrations in lysed leukocytes, plasma, and serum in serial blood specimens from nine female captive black bears (Ursus americanus; CBBs), and cortisol levels in serum from 10 CBBs.ResultsCortisol levels were significantly higher during hibernation in CBBs, confirming previous findings in hibernating black bears and similar to findings in humans with MDD. cAMP levels were significantly lower during hibernation versus active states (pre-hibernation and exit from hibernation) and were similar to the cAMP downregulation reported in MDD patients versus euthymic patients or controls. cAMP level changes during the different states (hibernation, pre-hibernation, active) confirm their state-dependent status.DiscussionThese findings are similar to the neurobiological findings associated with the hypometabolism (metabolic depression) observed during mammalian hibernation and reported during MDD. A sudden increase in cAMP levels was observed before entrance into pre-hibernation and during exit from hibernation. Further investigation is suggested into the possible role of elevated cAMP levels in initiation of the chain reaction of changes in gene expression, proteins, and enzymes leading to the suppression of mitochondrial metabolism and to low ATP turnover. This process leads to hypometabolism, the old adaptive mechanism that is used by organisms for energy preservation and is associated with both mammalian hibernation and human MDD.
Hyperfocus symptom and internet addiction in individuals with attention-deficit/hyperactivity disorder trait
Authors: Ishii Sayuri , Takagi Shunsuke , Kobayashi Nanase , Jitoku Daisuke , Sugihara Genichi , Takahashi Hidehiko 
Published: March 2023

BackgroundHyperfocus symptom is the intense concentration on a certain object. It is a common but often overlooked symptom in those with attention-deficit/hyperactivity disorder (ADHD). Hyperfocus disrupts attention control and results in a focus on inappropriate behaviors. It allows individuals to focus on internet use and make them use internet excessively. This excessive internet use can lead to an addiction. This study investigated the status of IA and hyperfocus, the mediation effect of hyperfocus in relation to IA, and the relationship between ADHD subtypes and hyperfocus in those with ADHD symptoms.MethodsThis web-based cross-sectional study included 3,500 Japanese adults who completed internet-based questionnaires, which included the Adult ADHD Self-Report Scale (ASRS), Internet Addiction Test (IAT), and Hyperfocus Scale (HFS) to assess ADHD symptoms, internet dependence, and hyperfocus symptoms, respectively. The mediating role of HFS in the relationship between ASRS and IAT was assessed by mediation analysis. To analyze the relationship between hyperfocus symptoms and ADHD subtypes, we compared the correlation of HFS with the Inattention and Hyperactive Scores of ASRS.ResultsADHD traits were associated with higher IAT scores (p &lt; 0.001) and higher HFS scores (p &lt; 0.001). Mediation analysis and bootstrap testing showed that HFS significantly mediated the association between ASRS and IAT. Analyses of ADHD subtypes demonstrated that HFS was significantly correlated with the Inattention (R = 0.597, p &lt; 0.001) and Hyperactive (R = 0.523, p &lt; 0.001) Scores. The correlation between HFS and the Inattention Score was significantly higher than that between HFS and the Hyperactive Score (p &lt; 0.001).ConclusionOur findings suggest that hyperfocus may play an important role in addictive behavior in ADHD as a manifestation of attentional control malfunction.
First-line Immuno-chemotherapy for extensive-stage small-cell lung cancer: A network meta-analysis and cost-effectiveness analysis
Authors: Zhu Youwen , Liu Kun , Yang Qiuping , Zeng Manting , Peng Libo 
Published: March 2023

IntroductionMany randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients.MethodsMultiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost–benefit ratio (ICER) were estimated by CEA.ResultsWe identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively.ConclusionThe NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.
Accelerated aging in people experiencing homelessness: A rapid review of frailty prevalence and determinants
Authors: Mantell Rhys , Hwang Ye In Jane , Radford Kylie , Perkovic Silvija , Cullen Patricia , Withall Adrienne 
Published: March 2023

IntroductionOlder people experiencing homelessness (PEH) are a rapidly growing population at risk of accelerated aging and the early onset of geriatric conditions. One construct that shows promise in predicting age-related decline is frailty. Better understanding the rates and causes of frailty in PEH may improve understanding of its antecedents, thereby facilitating more targeted health and aged care service interventions. The aim of this study was to conduct a rapid review on the prevalence and determinants of frailty in adult PEH.MethodsWe conducted a rapid review of primary research papers studying PEH and frailty or frailty-related concepts.ResultsFourteen studies were included, which indicate that frailty presents earlier and at higher rates in PEH than community-dwelling cohorts. A notable difficulty for many aging PEH was early-onset cognitive impairment which was associated with a range of negative functional outcomes. Another recurrent theme was the negative impact that drug and alcohol use and dependence can have on the health of PEH. Further, psychosocial and structural determinants such as loneliness, living in an impoverished neighborhood and being female had statistically significant associations with frailty and functional decline in PEH.Discussion and implicationsPEH in their 40s and 50s can be frail and experience geriatric conditions, including cognitive impairment. Factors that have important relationships to frailty and functional decline in PEH include cognitive deficits, drug and alcohol dependence and loneliness, as well as upstream determinants such as gender and ethnicity. More targeted data and research on these factors, including cohort studies to better investigate their potentially causal effects, is important for researchers and practitioners assessing and treating frailty in PEH, particularly those interested in early intervention and prevention.Prospero registration IDCRD42022292549.