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  • Online Resource  (11)
  • MDPI AG  (11)
  • 1
    Online Resource
    Online Resource
    The Addition of Transarterial Chemoembolization to Palliative Chemotherapy Extends Survival in Intrahepatic Cholangiocarcinoma
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 12 ( 2021-06-21), p. 2732-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 12 ( 2021-06-21), p. 2732-
    Abstract: Incidence and mortality of intrahepatic cholangiocarcinoma (iCCA) have been increasing continuously. Recent studies suggest that the combination of palliative chemotherapy (pCTX) and transarterial chemoembolization (TACE) improves overall survival (OS). This study aimed to evaluate the outcome of patients treated with TACE and pCTX in unresectable iCCA at our tertiary care center. A group of 14 patients was treated with both pCTX and TACE. The non-randomized control group of 59 patients received pCTX alone. Patients received a median of two pCTX lines in both groups. Those treated with TACE underwent a median number of 3.5 sessions. Median OS from the time of unresectability was 26.2 months in the pCTX + TACE group versus 13.1 months in the pCTX group (p = 0.008). Controlling for albumin, bilirubin, ECOG (Eastern Cooperative Oncology Group) performance status, and UICC (Union for International Cancer Control) stage, the addition of TACE still conferred an OS benefit of 12.95 months (p = 0.014). A propensity score matching analysis yielded an OS benefit of 14 months from the time of unresectability for the pCTX + TACE group (p = 0.020). The addition of TACE to pCTX may provide an OS benefit for patients with unresectable iCCA. Thus, patients with liver-dominant iCCA undergoing standard-of-care pCTX should be considered for additional treatment with TACE.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10122732
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    Functional Loss of Terminal Complement Complex Protects Rabbits from Injury-Induced Osteoarthritis on Structural and Cellular Level
    MDPI AG ; 2023
    In:  Biomolecules Vol. 13, No. 2 ( 2023-01-22), p. 216-
    Details
    In: Biomolecules, MDPI AG, Vol. 13, No. 2 ( 2023-01-22), p. 216-
    Abstract: The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6−/−) and C6-sufficient (C6+/−) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6−/− animals revealed no hemolytic activity. After ACLT surgery, joints of C6−/− rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6−/− rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom13020216
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2701262-1
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  • 3
    Online Resource
    Online Resource
    Musical Performance in Adolescents with ADHD, ADD and Dyslexia—Behavioral and Neurophysiological Aspects
    MDPI AG ; 2022
    In:  Brain Sciences Vol. 12, No. 2 ( 2022-01-18), p. 127-
    Details
    In: Brain Sciences, MDPI AG, Vol. 12, No. 2 ( 2022-01-18), p. 127-
    Abstract: Research has shown that dyslexia and attention deficit (hyperactivity) disorder (AD(H)D) are characterized by specific neuroanatomical and neurofunctional differences in the auditory cortex. These neurofunctional characteristics in children with ADHD, ADD and dyslexia are linked to distinct differences in music perception. Group-specific differences in the musical performance of patients with ADHD, ADD and dyslexia have not been investigated in detail so far. We investigated the musical performance and neurophysiological correlates of 21 adolescents with dyslexia, 19 with ADHD, 28 with ADD and 28 age-matched, unaffected controls using a music performance assessment scale and magnetoencephalography (MEG). Musical experts independently assessed pitch and rhythmic accuracy, intonation, improvisation skills and musical expression. Compared to dyslexic adolescents, controls as well as adolescents with ADHD and ADD performed better in rhythmic reproduction, rhythmic improvisation and musical expression. Controls were significantly better in rhythmic reproduction than adolescents with ADD and scored higher in rhythmic and pitch improvisation than adolescents with ADHD. Adolescents with ADD and controls scored better in pitch reproduction than dyslexic adolescents. In pitch improvisation, the ADD group performed better than the ADHD group, and controls scored better than dyslexic adolescents. Discriminant analysis revealed that rhythmic improvisation and musical expression discriminate the dyslexic group from controls and adolescents with ADHD and ADD. A second discriminant analysis based on MEG variables showed that absolute P1 latency asynchrony |R-L| distinguishes the control group from the disorder groups best, while P1 and N1 latencies averaged across hemispheres separate the control, ADD and ADHD groups from the dyslexic group. Furthermore, rhythmic improvisation was negatively correlated with auditory-evoked P1 and N1 latencies, pointing in the following direction: the earlier the P1 and N1 latencies (mean), the better the rhythmic improvisation. These findings provide novel insight into the differences between music processing and performance in adolescents with and without neurodevelopmental disorders. A better understanding of these differences may help to develop tailored preventions or therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci12020127
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2651993-8
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  • 4
    Online Resource
    Online Resource
    Problematic Internet Use among Adolescents 18 Months after the Onset of the COVID-19 Pandemic
    MDPI AG ; 2022
    In:  Children Vol. 9, No. 11 ( 2022-11-10), p. 1724-
    Details
    In: Children, MDPI AG, Vol. 9, No. 11 ( 2022-11-10), p. 1724-
    Abstract: Studies in recent years and especially since the beginning of the COVID-19 pandemic have shown a significant increase in the problematic use of computer games and social media. Adolescents having difficulties in regulating their unpleasant emotions are especially prone to Problematic Internet Use (PIU), which is why emotion dysregulation has been considered a risk factor for PIU. The aim of the present study was to assess problematic internet use (PIU) in adolescents after the third wave (nearly 1.5 years after the onset in Europe) of the COVID-19 pandemic. In the German region of Siegen-Wittgenstein, all students 12 years and older from secondary-level schools, vocational schools and universities were offered a prioritized vaccination in August 2021 with an approved vaccine against COVID-19. In this context, the participants filled out the Short Compulsive Internet Use Scale (SCIUS) and two additional items to capture a possible change in digital media usage time and regulation of negative affect due to the COVID-19 pandemic. A multiple regression analysis was performed to identify predictors of PIU. The original sample consisted of 1477 participants, and after excluding invalid cases the final sample size amounted to 1268 adolescents aged 12–17 (x = 14.37 years, SD = 1.64). The average prevalence of PIU was 43.69%. Gender, age, digital media usage time and the intensity of negative emotions during the COVID-19 pandemic were all found to be significant predictors of PIU: female gender, increasing age, longer digital media usage time and higher intensity of negative emotions during the COVID-19 pandemic were associated with higher SCIUS total scores. This study found a very high prevalence of PIU among 12- to 17-year-olds for the period after the third wave of the COVID-19 pandemic, which has increased significantly compared to pre-pandemic prevalence rates. PIU is emerging as a serious problem among young people in the pandemic. Besides gender and age, pandemic-associated time of digital media use and emotion regulation have an impact on PIU, which provides starting points for preventive interventions.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children9111724
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2732685-8
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  • 5
    Online Resource
    Online Resource
    Immunotherapy in Gastric Cancer
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 3 ( 2022-03-02), p. 1559-1574
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 3 ( 2022-03-02), p. 1559-1574
    Abstract: Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29030131
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 6
    Online Resource
    Online Resource
    Integrative Analysis of Intrahepatic Cholangiocarcinoma Subtypes for Improved Patient Stratification: Clinical, Pathological, and Radiological Considerations
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 13 ( 2022-06-28), p. 3156-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 13 ( 2022-06-28), p. 3156-
    Abstract: Intrahepatic cholangiocarcinomas (iCCAs) may be subdivided into large and small duct types that differ in etiology, molecular alterations, therapy, and prognosis. Therefore, the optimal iCCA subtyping is crucial for the best possible patient outcome. In our study, we analyzed 148 small and 84 large duct iCCAs regarding their clinical, radiological, histological, and immunohistochemical features. Only 8% of small duct iCCAs, but 27% of large duct iCCAs, presented with initial jaundice. Ductal tumor growth pattern and biliary obstruction were significant radiological findings in 33% and 48% of large duct iCCAs, respectively. Biliary epithelial neoplasia and intraductal papillary neoplasms of the bile duct were detected exclusively in large duct type iCCAs. Other distinctive histological features were mucin formation and periductal-infiltrating growth pattern. Immunohistochemical staining against CK20, CA19-9, EMA, CD56, N-cadherin, and CRP could help distinguish between the subtypes. To summarize, correct subtyping of iCCA requires an interplay of several factors. While the diagnosis of a precursor lesion, evidence of mucin, or a periductal-infiltrating growth pattern indicates the diagnosis of a large duct type, in their absence, several other criteria of diagnosis need to be combined.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14133156
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Online Resource
    Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 8 ( 2021-07-21), p. 1420-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 8 ( 2021-07-21), p. 1420-
    Abstract: Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13081420
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 8
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    Online Resource
    The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 10 ( 2021-05-11), p. 2296-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 10 ( 2021-05-11), p. 2296-
    Abstract: Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13102296
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Online Resource
    Morbidity and Mortality of Neutropenic Patients in Visceral Surgery: A Narrative Review
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 20 ( 2022-10-21), p. 3314-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 20 ( 2022-10-21), p. 3314-
    Abstract: Leukocytes are essential for the function of the immune system and cell–cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell–cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11203314
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 10
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    Online Resource
    Misjudgement of One’s Own Performance? Exploring Attention Deficit (Hyperactivity) Disorder (ADHD) and Individual Difference in Complex Music and Foreign Language Perception
    MDPI AG ; 2023
    In:  International Journal of Environmental Research and Public Health Vol. 20, No. 19 ( 2023-09-27), p. 6841-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 19 ( 2023-09-27), p. 6841-
    Abstract: In previous research, we detected that children and adolescents who were diagnosed with ADHD showed deficits in both complex auditory processing of musical stimuli and in musical performance when compared to controls. In this study, we were interested in whether we could detect similar or distinct findings when we use foreign speech perception tasks. Therefore, we recruited musically naïve participants (n = 25), music-educated participants (n = 25) and participants diagnosed with ADHD (n = 25) who were assessed for their short-term memory (STM) capacity and the ability to discriminate music and speech stimuli and we collected self-ratings of the participants’ music and language performances. As expected, we found that young adults with ADHD show deficits in the perception of complex music and difficult speech perception stimuli. We also found that STM capacity was not impaired in young adults with ADHD and may not persist into young adulthood. In addition, subjective self-estimation about the participants’ language and music performances revealed that the ADHD group overestimated their performance competence relatively compared to both control groups. As a result, the findings of our study suggest that individuals diagnosed with ADHD require a special training program that not only focuses on improving performance in perceptual skills of music and language but also requires metacognitive training to develop realistic self-assessment skills.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph20196841
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2175195-X
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