bluuebunny/crossref_metadata_2025_split huggingface dataset:
HROP68: A rare case of medullary pancreatic cancer—characterization and chemosensitivity of the first patient-derived cell line
Authors: von den Driesch Jens , Flöttmann Jana , Prall Friedrich , Mullins Christina S. , Linnebacher Michael , Bürtin Florian 
Published: January 2023

IntroductionMedullary pancreatic carcinoma (MPC) is a rare subtype of pancreatic ductal adenocarcinoma. MPCs represent less than 1% of all pancreatic cancers, and, with only 26 cases in the literature, knowledge regarding drug response and treatment outcome is very limited.Material and methodsWe present the case of a 64-year-old male patient with MPC who was treated by left pancreatic resection and adjuvant chemotherapy. Due to local recurrence, the patient underwent intended curative reoperation. From both surgical specimens, patient-derived xenografts (PDXs) and, from the recurrence, a patient-derived cell line (PDCL) were established. We subsequently performed an in-depth characterization of this cell line including phenotypic characterization, surface protein expression, growth, and migratory performance as well as mutational analysis using whole-exome sequencing (WES). Additionally, in vitro drug sensitivity toward the standard-of-care chemotherapeutic regimen and selected targeted therapies was evaluated.ResultsThe pathological and molecular properties of this rare MPC case observed in the patient’s tumors are preserved in the corresponding PDX and the PDCL of HROP68Tu2. Despite displaying an “immunogenic phenotype” with marked T-cell infiltration and a high-level expression of HLA II and Programmed death-ligand 1 (PD-L1), molecular analysis revealed microsatellite stability but a multitude of mutations affecting KRAS, TP53, KAT6B, FOXG1, RUNX1, and GRIK2 among others. Furthermore, HROP68Tu2 cells were susceptible toward 5-FU, irinotecan, oxaliplatin, gemcitabine, paclitaxel, and erlotinib as single agents, but only a moderate synergistic response was seen to the drugs of the FOLFIRINOX regimen. Even worse, the drugs of the two combinations gemcitabine plus paclitaxel and gemcitabine plus erlotinib showed antagonistic effects. Moreover, lapatinib, PRIMA-Met1, and olaparib selected as targeted therapeutics according to the mutational profiles and protein expression inhibited HROP68Tu2 cells’ growth.ConclusionThis study illustrates the establishment of the first preclinical MPC models as well as the first in-depth characterization of an MPC PDCL. Since the scientific and clinical knowledge of this rare pancreatic cancer type is very limited, the presented models contribute to a better understanding of MPC and might be a valuable tool for the development of future treatment options.
LAG-3+ tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients
Authors: Hu Guoming , Wang Shimin , Wang Songxiang , Ding Qiannan , Huang Liming 
Published: January 2023

PurposeImmune checkpoint molecule lymphocyte-activating gene-3 (LAG-3), which is expressed on active lymphocytes, has proven to be associated with immunosuppression and cancer progression in a variety of solid tumors. However, the role of LAG-3+ lymphocytes in human breast cancer (BC) is still not conclusive. We therefore performed a meta-analysis to clarify the role of these cells in prognosis prediction for BC.MethodsWe searched PubMed, Embase, and EBSCO to identify the studies evaluating the association of LAG-3+ lymphocyte infiltration and overall survival (OS) and/or disease-free survival (DFS) in BC patients, then combined extracted data with STATA 12.0.ResultsEight published studies involving 5,859 BC patients were incorporated into this meta-analysis. We noted that a high number of LAG-3+ tumor-infiltrating lymphocytes were not appreciably associated with OS and DFS in BC patients. Strikingly, in stratified analyses based on the molecular type of BC, LAG-3+ lymphocyte infiltration was remarkably associated with better OS rather than DFS in triple-negative breast cancer (TNBC), whereas it significantly influenced neither OS nor DFS in Her2-positive BC. However, an increased density of these lymphocytes indicated a trend for better OS in Her2-positive BC. In addition, we found that LAG-3+ lymphocyte infiltration was also remarkably associated with prolonged OS in Her2-positive BC patients when they were measured by immunohistochemistry (IHC). In addition, an elevated number of these lymphocytes did not correlate with pathological complete response rate or clinicopathological features including lymph node metastasis.ConclusionThe infiltration of LAG-3+ lymphocytes ameliorates OS in TNBC and Her2-positive BC, implicating that it is a valuable prognostic biomarker, and applications of anti-LAG-3 antagonists may possibly be not a promising therapeutic strategy for human BC especially for TNBC.
Predictors of residual disease after debulking surgery in advanced stage ovarian cancer
Authors: Abbas-Aghababazadeh Farnoosh , Sasamoto Naoko , Townsend Mary K. , Huang Tianyi , Terry Kathryn L. , Vitonis Allison F. , Elias Kevin M. , Poole Elizabeth M. , Hecht Jonathan L. , Tworoger Shelley S. , Fridley Brooke L. 
Published: January 2023

ObjectiveOptimal debulking with no macroscopic residual disease strongly predicts ovarian cancer survival. The ability to predict likelihood of optimal debulking, which may be partially dependent on tumor biology, could inform clinical decision-making regarding use of neoadjuvant chemotherapy. Thus, we developed a prediction model including epidemiological factors and tumor markers of residual disease after primary debulking surgery.MethodsUnivariate analyses examined associations of 11 pre-diagnosis epidemiologic factors (n=593) and 24 tumor markers (n=204) with debulking status among incident, high-stage, epithelial ovarian cancer cases from the Nurses’ Health Studies and New England Case Control study. We used Bayesian model averaging (BMA) to develop prediction models of optimal debulking with 5x5-fold cross-validation and calculated the area under the curve (AUC).ResultsCurrent aspirin use was associated with lower odds of optimal debulking compared to never use (OR=0.52, 95%CI=0.31-0.86) and two tissue markers, ADRB2 (OR=2.21, 95%CI=1.23-4.41) and FAP (OR=1.91, 95%CI=1.24-3.05) were associated with increased odds of optimal debulking. The BMA selected aspirin, parity, and menopausal status as the epidemiologic/clinical predictors with the posterior effect probability ≥20%. While the prediction model with epidemiologic/clinical predictors had low performance (average AUC=0.49), the model adding tissue biomarkers showed improved, but weak, performance (average AUC=0.62).ConclusionsAddition of ovarian tumor tissue markers to our multivariable prediction models based on epidemiologic/clinical data slightly improved the model performance, suggesting debulking status may be in part driven by tumor characteristics. Larger studies are warranted to identify those at high risk of poor surgical outcomes informing personalized treatment.
Lateral ventricle ectopic schwannoma: Case report and literature review
Authors: Li Yujian , Yang Xiang , Zhou Huiqing , Zheng Jun , Hui Xuhui , Li Hao , Liu Yanhui 
Published: January 2023

BackgroundCases of lateral ventricular ectopic schwannomas (LVES) are extremely rare, with only 23 cases reported thus far. This study aimed to obtain a better understanding of the disease.MethodsWe reported a rare case of LVES, in which the patient was admitted to our hospital, and reviewed the relevant literature on LVES to summarize and analyze the clinical manifestations, pathologies, imaging features and progress.ResultsOf the 23 patients, LVES was more common in men (74%, 17/23) than in women and was mostly located on the right side (78%, 18/23). The average age at clinical presentation was 28 years, with an age range between 8 and 68 years. Moreover, most cases were histologically benign, except in one case of malignancy. In all the benign cases, there were 2 cases of subtotal resection, but no recurrence was found during follow-up.ConclusionsThe origin of LVES could be the tumor transformation of autonomic nerve tissue in the perivascular choroid plexus. For lateral ventricle tumors,which are rare benign lesions with good prognosis after surgical resection, LVES should be considered in the differential diagnosis. Moreover, whether LVES could be considered for gamma knife treatment, similar to a small acoustic neuromas,requires further investigation.
When tissue is not the only issue: Poorly differentiated lung squamous-cell carcinoma with adrenal, costochondral, and cardiac metastases – case report
Authors: Clark Megan , Griborio-Guzman Andres G. , Burute Nishigandha P. , Lubbers Sonja , Anthes Margaret L. , Sadreddini Masoud , Aseyev Olexiy I. 
Published: January 2023

Nonmelanoma skin cancer is the most common cancer in the world, and lung cancer is the leading cause of death from cancer. Histologically, squamous cell carcinoma (SCC) is the second most prevalent type of both skin and lung cancers. We report the case of a 38-year-old female with metastatic, poorly differentiated lung SCC detected on chest X-ray after she presented to the hospital with cough and dyspnea. She had had a 7.5 cm moderately differentiated well-circumscribed posterior scalp SCC completely excised eight years earlier. CT scan showed a large right lung mass, nodular filling defect in the left atrium (LA), and metastases to the adrenal glands and the first rib. Her pulmonary tumor extends to the LA via the right superior pulmonary vein, which is rarely reported in the literature. Ultrasound-guided biopsy of the rib mass showed poorly differentiated SCC. The patient received urgent radiotherapy, given superior vena cava and mainstem bronchus compression. Head CT showed no brain metastasis. A biopsy of the left adrenal initially reported an undifferentiated pleomorphic sarcoma; however, a second pathologist reported it as a poorly differentiated carcinoma of lung origin. At least three pathologists verified the specimen, and it had a PD-L1 test with a 1-49% score. An initial echocardiogram confirmed the LA mass. The patient received a Paclitaxel-Carboplatin-Pembrolizumab regimen as the first-line treatment for metastatic SCC. A repeat echocardiogram after cycle 1 showed a decrease in the size of the tumor in the LA. Almost five months after her initial visit, this young woman’s symptoms and performance status have improved post-palliative radiotherapy and chemo-immunotherapy. Follow-up CT showed smaller lung, nodal, adrenal, and costochondral masses, and evidence of necrosis. This case is clinically relevant because it represents a common problem presenting uncommonly. Moreover, it highlights that ultrasound-guided interventions and medical imaging are essential in directing metastatic cancer diagnosis, treatment, and follow-up, especially when pathology cannot confirm but only presume a specific diagnosis.
Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats
Authors: Ou Chen Yin , Yu Ying Hao , Wu Chi-Wen , Kozłowska Anna , Shyu Bai-Chung , Huang Andrew Chih Wei 
Published: January 2023

To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20–40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30–40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30–40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.
Uracil restores susceptibility of methicillin-resistant Staphylococcus aureus to aminoglycosides through metabolic reprogramming
Authors: Fan Lvyuan , Pan Zhiyu , Liao Xu , Zhong Yilin , Guo Juan , Pang Rui , Chen Xinhai , Ye Guozhu , Su Yubin 
Published: January 2023

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has now become a major nosocomial pathogen bacteria and resistant to many antibiotics. Therefore, Development of novel approaches to combat the disease is especially important. The present study aimed to provide a novel approach involving the use of nucleotide-mediated metabolic reprogramming to tackle intractable methicillin-resistant S. aureus (MRSA) infections.Objective: This study aims to explore the bacterial effects and mechanism of uracil and gentamicin in S. aureus.Methods: Antibiotic bactericidal assays was used to determine the synergistic bactericidal effect of uracil and gentamicin. How did uracil regulate bacterial metabolism including the tricarboxylic acid (TCA) cycle by GC-MS-based metabolomics. Next, genes and activity of key enzymes in the TCA cycle, PMF, and intracellular aminoglycosides were measured. Finally, bacterial respiration, reactive oxygen species (ROS), and ATP levels were also assayed in this study.Results: In the present study, we found that uracil could synergize with aminoglycosides to kill MRSA (USA300) by 400-fold. Reprogramming metabolomics displayed uracil reprogrammed bacterial metabolism, especially enhanced the TCA cycle to elevate NADH production and proton motive force, thereby promoting the uptake of antibiotics. Furthermore, uracil increased cellular respiration and ATP production, resulting the generation of ROS. Thus, the combined activity of uracil and antibiotics induced bacterial death. Inhibition of the TCA cycle or ROS production could attenuate bactericidal efficiency. Moreover, uracil exhibited bactericidal activity in cooperation with aminoglycosides against other pathogenic bacteria. In a mouse mode of MRSA infection, the combination of gentamicin and uracil increased the survival rate of infected mice.Conclusion: Our results suggest that uracil enhances the activity of bactericidal antibiotics to kill Gram-positive bacteria by modulating bacterial metabolism.
Structural impairment and conflict load as vulnerability factors for burnout – A cross-sectional study from the German working population
Authors: Perlinger Julia , Gisch Hannes , Ehrenthal Johannes C. , Montag Christiane , Kretschmar Thomas 
Published: January 2023

IntroductionIndividual vulnerability and resilience factors are increasingly studied in burnout research. This is especially true for clinical variables that translate directly into intervention programs from a psychodynamic perspective. For example, few studies have examined the relationship between structural impairment and the individual spectrum of motivational conflicts according to the Operationalized Psychodynamic Diagnosis system (OPD) in relation to burnout. To substantiate previous findings, we hypothesized that structural impairment as well as motivational conflicts are related to burnout, but that structural impairment explained additional variance and mediated a possible relationship between conflicts and burnout.MethodThe present cross-sectional study was carried out on a sample of the German working population (N = 545). Questionnaires were used to measure structural impairment (OPD-SQS), the conflict-modes along with the category K0 (OPD-CQ), as well as burnout (BOSS-I/-II).ResultsStructural impairment, a number of conflict modes, and burnout were significantly associated. Moreover, structural impairment explained additional variance in burnout. The requirements for the conflict-specific mediation models were given for 9 of the 12 OPD conflict modes. In these models the impact of the conflict modes on burnout was mediated by structural impairment.DiscussionThe current study broadens the comprehension of the relations between structural impairment, the conflict modes and burnout. In addition it higlights the role of structural impairment in predicting burnout risk and possible prevention approaches.
Effects of positive social comparative feedback on motor sequence learning and performance expectancies
Authors: Lewis Allison F. , Bohnenkamp Rachel , Johnson Lynn , den Ouden Dirk B. , Wilcox Sara , Fritz Stacy L. , Stewart Jill Campbell 
Published: January 2023

IntroductionPositive social comparative feedback indicates to the learner that they are performing better than others. While this type feedback supports motor skill learning in some tasks, the effect of social comparative feedback on implicit motor sequence learning remains unknown. The aim of this study was to determine the effect of positive social comparative feedback on the learning of and expectancies for a motor sequence task.MethodsForty-eight individuals practiced a joystick-based sequence task and were divided into three feedback groups: CONTROL (no performance feedback), RT ONLY (response time only feedback), and RT+POS (response time plus positive social comparison). Participants attended sessions on two consecutive days: Day 1 for repetitive motor practice/skill acquisition and Day 2 for retention testing. Performance related expectancies, like perceived competence, were measured before and after motor practice on Day 1 and at retention on Day 2.ResultsWhile all groups improved with practice, the CONTROL group showed better overall performance/learning (faster response times) compared with the RT ONLY group. Despite similar response times, the RT+POS showed higher peak velocities than the RT ONLY group. Overall, the RT+POS and CONTROL demonstrated increases in perceived competence while the RT ONLY group did not.DiscussionThe results of this study suggest that feedback content is an important consideration during motor practice sessions since feedback without context (RT ONLY) may be detrimental to motor sequence learning. The results also suggest that, if providing performance related feedback during practice of a skill that relies on implicit sequence learning processes, comparative context may be necessary for enhancing expectancies and supporting.
Quality of life in multiple scenarios: The impact of work mode and social contact quantity
Authors: Leng Cheng-Han , Tsai Chi-Shiun , Chan Ta-Chien , Lee Hsuan-Wei 
Published: January 2023

IntroductionDuring the COVID-19 pandemic, many employees were encouraged to temporarily work from home as an attempt to decrease social contact with others. However, the employees' quality of life (QoL) may have been threatened by this mode of working. This study, therefore, aims to explore the employees' QoL given the new mode of working from home (WFH) as a result of the pandemic vs. working in the office (WIO), the amount of social contact that they were exposed to, and the ratio of face-to-face contact that they had.MethodsA total of 803 WFH employees and 588 WIO employees' QoL was assessed during the same time period using the WHOQOL-BREF, which contains four domains: physical health, psychological health, social relationship, and the environment. We then divided the participants into 16 groups in accordance with the levels of work mode, social contact quantity, and face-to-face contact ratio–forming a case-control study. A differential item functioning (DIF) analysis was used to analyze the responses on the WHOQOL-BREF under the 4-dimensional rating scale model fitting.ResultsThe results indicated that WFH employees' QoL was superior to that of WIO employees. The relationship between the WFH mode and the employees' QoL was specifically moderated by the amount of social contact and the ratio of face-to-face contact that was experienced. The results further demonstrated that the increased amount of non-face-to-face contact was better for WFH employees' QoL than that of WIO employees.DiscussionIn conclusion, the WFH mode was practical during the COVID-19 pandemic, as our findings indicated that WFH employees' QoL was better than WIO employees' QoL. However, maintaining social connections is equally important as this allows employees to perform better at their jobs and maintain such performance. The employees with a higher number of social support had a better QoL. Additionally, the facets detected as DIF items provided implications for the QoL with regard to the research methodology and insight into factors affecting the employees' QoL.
The prognostic value of the Barthel Index for mortality in patients with COVID-19: A cross-sectional study
Authors: Wang Erchuan , Liu Ao , Wang Zixuan , Shang Xiaoli , Zhang Lingling , Jin Yan , Ma Yanling , Zhang Lei , Bai Tao , Song Jun , Hou Xiaohua 
Published: January 2023

ObjectiveThis study aimed to analyze the association between the activity of daily living (ADL), coronavirus disease (COVID-19), and the value of the Barthel Index in predicting the prognosis of patients.MethodsThis study included 398 patients with COVID-19, whose ADL at admission to hospital were assessed with the Barthel Index. The relationship between the index and the mortality risk of the patients was analyzed. Several regression models and a decision tree were established to evaluate the prognostic value of the index in COVID-19 patients.ResultsThe Barthel Index scores of deceased patients were significantly lower than that of discharged patients (median: 65 vs. 90, P &lt; 0.001), and its decrease indicated an increased risk of mortality in patients (P &lt; 0.001). After adjusting models for age, gender, temperature, pulse, respiratory rate, mean arterial pressure, oxygen saturation, etc., the Barthel Index could still independently predict prognosis (OR = 0.809; 95% CI: 0.750–0.872). The decision tree showed that patients with a Barthel Index of below 70 had a higher mortality rate (33.3–40.0%), while those above 90 were usually discharged (mortality: 2.7–7.2%).ConclusionThe Barthel Index is of prognostic value for mortality in COVID-19 patients. According to their Barthel Index, COVID-19 patients can be divided into emergency, observation, and normal groups (0–70; 70–90; 90–100), with different treatment strategies.