bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery
Authors: Schupper Alexander J. , Rao Manasa , Mohammadi Nicki , Baron Rebecca , Lee John Y. K. , Acerbi Francesco , Hadjipanayis Constantinos G.
Published: July 2021

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.
Brainstem Correlates of Pathological Laughter and Crying Frequency in ALS
Authors: Tu Sicong , Huang Mengjie , Caga Jashelle , Mahoney Colin J. , Kiernan Matthew C.
Published: July 2021

Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS (p = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A (R2 = 0.14, p = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem (R2 = 0.46, p < 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: R2 = 0.44, p < 0.01; right: R2 = 0.44, p < 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS. The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter.
Bridging the Gap: Parent and Child Perspectives of Living With Cerebral Visual Impairments
Authors: Goodenough Trudy , Pease Anna , Williams Cathy
Published: July 2021

Cerebral Visual Impairment (CVI) is an umbrella term which includes abnormalities in visual acuity, or contrast sensitivity or colour; ocular motility; visual field and the conscious and unconscious filtering or processing of visual input. Children with CVI have specific needs and problems relating to their development from infancy to adulthood which can impact on their wellbeing. Recent research indicates the complexities of living with CVI but there remains limited information of the full impact of CVI on families’ everyday lives. The qualitative interviews reported here explored families’ experiences to discover the impact of CVI on all aspects of everyday life. Parents and children (aged 6–18) were invited to participate in semi-structured interviews, either face to face, by phone or video call between January 2018 and February 2019. Topics covered everyday practicalities of living with CVI, focusing on challenges and what worked well at school and home. Interviews were audio-recorded and subject to thematic analysis to look for patterns across the data. Twenty families took part in interviews, with eight children/young people within those families contributing interviews of their own. Four themes were developed from the interviews: (1) Assessment and understanding implications of CVI, (2) Education, (3) Family life, (4) Psychological wellbeing and quality of life. The interviews provide valuable insights into the impact of living with CVI and highlight the need for more awareness of the condition among professionals in both health and education settings.
Evaluating the Leucine Trigger Hypothesis to Explain the Post-prandial Regulation of Muscle Protein Synthesis in Young and Older Adults: A Systematic Review
Authors: Zaromskyte Gabriele , Prokopidis Konstantinos , Ioannidis Theofilos , Tipton Kevin D. , Witard Oliver C.
Published: July 2021

Background: The “leucine trigger” hypothesis was originally conceived to explain the post-prandial regulation of muscle protein synthesis (MPS). This hypothesis implicates the magnitude (amplitude and rate) of post-prandial increase in blood leucine concentrations for regulation of the magnitude of MPS response to an ingested protein source. Recent evidence from experimental studies has challenged this theory, with reports of a disconnect between blood leucine concentration profiles and post-prandial rates of MPS in response to protein ingestion.

Aim: The primary aim of this systematic review was to qualitatively evaluate the leucine trigger hypothesis to explain the post-prandial regulation of MPS in response to ingested protein at rest and post-exercise in young and older adults. We hypothesized that experimental support for the leucine trigger hypothesis will depend on age, exercise status (rest vs. post-exercise), and type of ingested protein (i.e., isolated proteins vs. protein-rich whole food sources).

Methods: This qualitative systematic review extracted data from studies that combined measurements of post-prandial blood leucine concentrations and rates of MPS following ingested protein at rest and following exercise in young and older adults. Data relating to blood leucine concentration profiles and post-prandial MPS rates were extracted from all studies, and reported as providing sufficient or insufficient evidence for the leucine trigger hypothesis.

Results: Overall, 16 of the 29 eligible studies provided sufficient evidence to support the leucine trigger hypothesis for explaining divergent post-prandial rates of MPS in response to different ingested protein sources. Of these 16 studies, 13 were conducted in older adults (eight of which conducted measurements post-exercise) and 14 studies included the administration of isolated proteins.

Conclusion: This systematic review underscores the merits of the leucine trigger hypothesis for the explanation of the regulation of MPS. However, our data indicate that the leucine trigger hypothesis confers most application in regulating the post-prandial response of MPS to ingested proteins in older adults. Consistent with our hypothesis, we provide data to support the idea that the leucine trigger hypothesis is more relevant within the context of ingesting isolated protein sources rather than protein-rich whole foods. Future mechanistic studies are warranted to understand the complex series of modulatory factors beyond blood leucine concentration profiles within a food matrix that regulate post-prandial rates of MPS.
Intraperitoneal Chemotherapy Using Fluorouracil Implants Combined With Radical Resection and Postoperative Adjuvant Chemotherapy for Stage III Gastric Cancer: A Multi-Center, Randomized, Open-Label, Controlled Clinical Study
Authors: Xu Yan , Zhang Rupeng , Li Chunfeng , Sun Zhe , Deng Jingyu , Wang Xiaona , Ding Xuewei , Wang Baogui , Xue Qiang , Ke Bin , Zhan Hongjie , Liu Ning , Liu Yong , Wang Xuejun , Liang Han , Xue Yingwei , Xu Huimian
Published: July 2021

Background

Reducing peritoneal recurrence after radical surgery is an important choice to improve the prognosis of patients with advanced gastric cancer. Intraoperative intraperitoneal chemotherapy has the potential to be a promising treatment strategy. In the present study, we conducted a multi-center, randomized, controlled clinical study to evaluate the efficacy and safety of intraoperative intraperitoneal chemotherapy using sustained-release fluorouracil implants plus radical gastrectomy and adjuvant chemotherapy for cTNM stage III gastric cancer.

Methods

The patients were randomized into intraperitoneal chemotherapy group (sustained-release fluorouracil implants administration after standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy) and control group (standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy). A total of 122 patients from three centers were enrolled from September 2015 to February 2017.

Results

One hundred and two eligible patients completed the treatment course. The median follow-up time was 41.7 months (36.1–52.9 months). The 3-year progression-free survival rate and overall survival of patients in the intraperitoneal chemotherapy group were 43.9% and 49.1%, respectively, which were significantly better than those of the control group, 31.0% and 38.4%. In the intraperitoneal chemotherapy group, the number of cases with peritoneal recurrence was significantly less than that of the control group, 9 cases (17.3%) vs. 19 cases (44.2%). There were neither significant differences between the groups in the incidence of hematogenous metastasis, lymph node metastasis, nor local metastasis.

Conclusion

For cTNM stage III gastric cancer, intraoperative sustained-release fluorouracil implants after radical resection combined with postoperative adjuvant chemotherapy, could significantly reduce the risk of peritoneal recurrence and prolong PFS.

Clinical Trial Registration

https://clinicaltrials.gov/, identifier (NCT02269904).
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma
Authors: Fisch David , Bozorgmehr Farastuk , Kazdal Daniel , Kuon Jonas , Klotz Laura V. , Shah Rajiv , Eichhorn Florian , Kriegsmann Mark , Schneider Marc A. , Muley Thomas , Stenzinger Albrecht , Bischoff Helge , Christopoulos Petros
Published: July 2021

Background

Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.

Methods

We retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.

Results

191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing.

Conclusions

Highly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival.
Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma
Authors: Romano Alessandra , Storti Paola , Marchica Valentina , Scandura Grazia , Notarfranchi Laura , Craviotto Luisa , Di Raimondo Francesco , Giuliani Nicola
Published: July 2021

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR)-T cells. In this review, we will highlight the mechanism of action of immuno-therapy currently available in clinical practice to target CD38, SLAMF7, and BCMA, focusing on the biological role of the targets and on mechanisms of actions of the different immunotherapeutic approaches underlying their advantages and disadvantages with critical review of the literature data.
The Ribosomal Protein L28 Gene Induces Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Shi Yi , Wang Xiaojiang , Zhu Qiong , Chen Gang
Published: July 2021

Background

Sorafenib is the first molecular-targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its treatment efficiency decreases after a short period of time because of the development of drug resistance. This study investigates the role of key genes in regulating sorafenib-resistance and elucidates the mechanism of drug resistance in hepatocellular carcinoma.

Methods

The HCC HepG2 cells were used to generate a sorafenib-resistant cell model by culturing the cells in gradually increasing concentration of sorafenib. RNA microarray was applied to profile gene expression and screen key genes associated with sorafenib resistance. Specific targets were knockdown in sorafenib-resistant HepG2 cells for functional studies. The HCC model was established in ACI rats using Morris hepatoma3924A cells to validate selected genes associated with sorafenib resistance in vivo.

Results

The HepG2 sorafenib-resistant cell model was successfully established. The IC50 of sorafenib was 9.988μM in HepG2 sorafenib-resistant cells. A total of 35 up-regulated genes were detected by expression profile chip. High-content screening technology was used and a potential drug-resistance related gene RPL28 was filtered out. After knocking down RPL28 in HepG2 sorafenib-resistant cells, the results of cell proliferation and apoptosis illustrated that RPL28 is the key gene involving in drug resistance. Furthermore, it was found that both RNA and protein expression of RPL28 increased in HepG2 sorafenib-resistant specimens of Morris Hepatoma rats. In addition, the expression of proliferative protein Ki-67 increased in sorafenib-resistant cells.

Conclusion

Our study suggested that RPL28 is a key gene inducing sorafenib resistance in HCC and could be a potential target for the treatment of drug-resistant HCC.
Improving Outcomes of Chemotherapy: Established and Novel Options for Myeloprotection in the COVID-19 Era
Authors: Lyman Gary H. , Kuderer Nicole M. , Aapro Matti
Published: July 2021

Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HPSCs) often results in myelosuppression that adversely affects patient health and quality of life. Currently, chemotherapy-induced myelosuppression is managed with chemotherapy dose delays/reductions and lineage-specific supportive care interventions, such as hematopoietic growth factors and blood transfusions. However, the COVID-19 pandemic has created additional challenges for the optimal management of myelosuppression. In this review, we discuss the impact of this side effect on patients treated with myelosuppressive chemotherapy, with a focus on the prevention of myelosuppression in the COVID-19 era. During the COVID-19 pandemic, short-term recommendations on the use of supportive care interventions have been issued with the aim of minimizing the risk of infection, reducing the need for hospitalization, and preserving limited blood supplies. Recently, trilaciclib, an intravenous cyclin-dependent kinase 4 and 6 inhibitor, was approved to decrease the incidence of myelosuppression in adult patients when administered prior to platinum/etoposide-containing or topotecan-containing chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). Approval was based on data from three phase 2 placebo-controlled clinical studies in patients with ES-SCLC, showing that administering trilaciclib prior to chemotherapy significantly reduced multilineage myelosuppression, with patients receiving trilaciclib having fewer chemotherapy dose delays/reductions and myelosuppression/sepsis-related hospitalizations, and less need for supportive care interventions, compared with patients receiving placebo. Several other novel agents are currently in clinical development for the prevention or treatment of multilineage or single-lineage myelosuppression in patients with various tumor types. The availability of treatments that could enable patients to maintain standard-of-care chemotherapy regimens without the need for additional interventions would be valuable to physicians, patients, and health systems.
Chronic Hepatitis Virus Infection Are Associated With High Risk of Gastric Cancer: A Systematic Review and Cumulative Analysis
Authors: Yang Yusha , Jiang Zufu , Wu Weizhou , Ruan Libin , Yu Chengyang , Xi Yuning , Wang Liling , Wang Kunpeng , Mo Jinggang , Zhao Shankun
Published: July 2021

Mounting studies demonstrated both chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection might be associated not only with an increased risk of hepatocellular carcinoma but also extrahepatic malignancies, i.e., gastric cancer (GC). However, a quantitative result addressing the association between HBV/HCV infection and GC development is scarce. A systematic search to identify the eligible studies was performed in four databases, including MEDLINE, EMBASE, Cochrane Library, and the PsychINFO. The relationship between HBV/HCV infection and the risk of GC was quantified by calculating the hazard ratio (HR) with a 95% confidence interval (CI). More methodologies of this study were available in the PROSPERO (ID: CRD42021243719). Thirteen included studies involving 7,027,546 individuals (mean age, 42.6-71.9 years) were enrolled in the pooled analyses. Two articles provided the clinical data of both HBV and HCV infections. The proportion of high methodological quality studies was 76.9% (10/13). Synthetic results from 10 eligible studies of HBV showed that HBV infection was associated with a significantly higher risk of GC when compared with the healthy controls without HBV infection (pooled HR, 1.26; 95% CI, 1.08–1.47; P = 0.003; heterogeneity, I2 = 89.3%; P< 0.001). In line with this finding, the combined effect derived from five included studies of HCV also supported a significant positive association between chronic HBV infection and GC development (pooled HR, 1.88; 95% CI, 1.28–2.76; P = 0.001; heterogeneity, I2 = 74.7%; P = 0.003). In conclusion, both chronic HBV and HCV infections were related to a high risk of GC. The plausible mechanisms underlying such association might be correlated to HBV/HCV infection-induced persistent inflammation, immune dysfunction, and cirrhosis.

Systematic Review Registration

PROSPERO (http://www.crd.york.ac.uk/PROSPERO), identifier (CRD42021243719).
Somatostatin Receptors and Chemokine Receptor CXCR4 in Lymphomas: A Histopathological Review of Six Lymphoma Subtypes
Authors: Juntikka Tiina , Vaittinen Samuli , Vahlberg Tero , Jyrkkiö Sirkku , Minn Heikki
Published: July 2021

Background

Somatostatin receptors (SSTR) and chemokine receptor CXCR4 are expressed in lymphomas, while the abundance is known to be heterogeneous in different subtypes of lymphomas. Targeting tumor cells expressing these receptors might add to therapeutic opportunities while radiolabeled ligands for both imaging and therapy have been developed. The aim of this study was to establish SSTR subtype 2, 3 and 5 and also CXCR4 status immunohistochemically in six different lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated marginal B-cell lymphoma (MALT), Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL).

Material and Methods

This study included a total of 103 lymphoma patients (24 DLBCL, 22 FL, 18 HL, 9 MALT, 20 MCL and 10 PTCL) diagnosed in the Southwest hospital district of Finland during 2010-2019. SSTR 2, 3 and 5 and CXCR4 expression was analyzed immunohistochemically (IHC) in lymphoma samples obtained from local archival Biobank tissue repository. Immunopositivity of each receptor was scored on a four-point scale accounting for staining intensity and proportion of positively stained tumor cells.

Results

Of different SSTR subtypes SSTR2 immunopositivity was most common and seen predominantly at the cell membrane of the malignant cells in 46-56% of DLBCL, HL and FL. CXCR4 co-expression was frequently present in these cases. SSTR3 and SSTR5 IHC were negative in DLBCL and FL but in HL SSTR expression was more heterogenous and SSTR3 and SSTR5 positivity was found in cytoplasm in 35% and 25% of cases. 2/4 blastoid MCL variants and one pleomorphic MCL variant had positive CXCR4 IHC whilst all other MCL cases (85%) were negative for all receptors. 30% (n=3) of the PTCL patients had positive SSTR5 IHC and CXCR4. MALT lymphomas were negative for all receptors.

Conclusion

SSTR2 and CXCR4 are found in DLBCL, FL and HL and co-expression of these receptors is common. Although in general expression of SSTRs and CXCR4 is heterogenous and very low in some subtypes such as MCL and MALT there are also patients with abundant expression. The latter are candidates for trials studying SSTR2 and/or CXCR4 based treatments in the future.
To Combine or Not to Combine Physical Therapy With tDCS for Stroke With Shoulder Pain? Analysis From a Combination Randomized Clinical Trial for Rehabilitation of Painful Shoulder in Stroke
Authors: Andressa de Souza Janaina , Ferrari Corrêa João Carlos , Marduy Anna , Dall'Agnol Letizzia , Gomes de Sousa Maria Helena , Nunes da Silva Victor , Alves André Barreto , Silva Soraia Micaela , Fregni Felipe , Corrêa Fernanda Ishida
Published: July 2021

Purpose: Transcranial Direct Current Stimulation (tDCS) is an intervention that seems to be an ideal tool to enhance the effects of rehabilitation therapies given it facilitates generation of plasticity in the stimulated brain area. In stroke this strategy has been highly utilized; however, the results have been mixed. In this trial we have evaluated the analgesic and functional effects of Transcranial Direct Current Stimulation (tDCS) combined with physiotherapy in stroke survivors with shoulder pain.

Methods: Twenty-six stroke surviving adults with shoulder pain received 10 sessions of passive mobilization and performed upper limb exercises using a cycle ergometer, combined with active or sham tDCS. The intensity of pain in the hemiplegic shoulder was measured using the Visual Analog Scale (VAS); secondary outcomes were the level of motor impairment, handgrip strength, range of motion, motor function of the upper limbs, and quality of life (QOL) assessed before and after 10 sessions and 1 month after the end of the treatment.

Results: A clinically important pain reduction (3 points) was found in both groups and was maintained at follow-up; there was no significant difference between groups (p = 0.3). Similarly, the shoulder range of motion improved, motor function and quality of life improved showed no significant differences between groups. One result that needs to be underscored is that both groups had a significant effect size toward improvement in all of these outcomes.

Conclusions: We discuss in this study that tDCS is not a useful combination strategy when the physical therapy has a large effect by itself and we also review other negative trials of combined therapy under this framework of ceiling effect of the main physical therapy.

Trial registry: Trial registration: Brazilian Registry of Clinical Trials, RBR-8F5MNY (http://www.ensaiosclinicos.gov.br/rg/RBR-8f5mny/). Registered on June 2, 2017.

Beginning of the recruitment of the volunteers: august, 2017.
The Clinical Characteristics of ARDS in Children With Hematological Neoplasms
Authors: Zhang Qiao , Hu Wen-ting , Yin Fan , Qian Han , Wang Ying , Li Bi-ru , Qian Juan , Tang Yan-jing , Ning Bo-tao
Published: July 2021

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.
Case Report: Hodgkin Lymphoma and Refractory Systemic Lupus Erythematosus Unveil Activated Phosphoinositide 3-Kinase-δ Syndrome 2 in an Adult Patient
Authors: Conti Francesca , Catelli Arianna , Cifaldi Cristina , Leonardi Lucia , Mulè Rita , Fusconi Marco , Stefoni Vittorio , Chiriaco Maria , Rivalta Beatrice , Di Cesare Silvia , Schifino Gioacchino , Sbrega Fabiana , Di Matteo Gigliola , Ferrari Simona , Cancrini Caterina , Pession Andrea
Published: July 2021

Introduction: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is a rare primary immune regulatory disorder caused by heterozygous gain of function mutation in the PIK3R1 gene encoding PI3Kδ regulatory p85α subunit and resulting in PI3Kδ hyperactivation. Clinical features range from recurrent infections to manifestations of immune dysregulation like autoimmunity, inflammation, systemic lymphoproliferation, and increased risk of cancer. We describe a new dominant PIK3R1 mutation causing APDS2 presenting with lymphoma and systemic refractory autoimmunity.

Case Presentation: A 30-year-old woman was referred to the Immunology Unit of our hospital for uncontrolled systemic lupus erythematosus, including chilblains lesions, systemic lymphoproliferation and IgA deficiency. At 19 years of age, she was diagnosed with Hodgkin's lymphoma. Subsequently, she presented systemic lupus erythematosus onset, with episodes of severe exacerbation, including autoimmune hemolytic anemia and pleuro-pericarditis. Initial clinical response to conventional treatments was reported. Immunological investigations performed during our first observation showed severe lymphopenia, IgA deficiency, elevated IgM with reduced IgG2 levels, and low vaccination antibody titers. Quantitative real-time polymerase chain reaction (PCR) assay for Cytomegalovirus and Epstein-Barr virus showed low viral loads for both viruses in serum. An increase of serum inflammatory markers highlighted persistent systemic hyperinflammation. The next-generation sequencing (NGS)-based gene panel tests for primary immunodeficiency showed a heterozygous A>G substitution in the splice acceptor site at c.1300-2 position of PIK3R1, leading to exon-skipping.

Conclusion: This case emphasizes the importance of suspecting primary immune regulatory disorders in young adults, predominantly showing a severe, aggressive, and refractory to treatment immune dysregulation phenotype, even in the absence of major infectious diseases at the onset. Different treatments can be promptly started, and a delayed diagnosis can highly impact the outcome. Targeted therapy against PI3Kδ pathway defect effectively improves drug-resistant autoimmunity, lymphoproliferation, and risk of progression to malignancy; eligible patients could benefit from its use even as a bridge therapy to transplantation, currently the only definitive curative treatment. Therefore, identifying genetic mutation and prompt targeted treatment are essential to control disease manifestations, prevent long-term sequelae, and enable curative HSCT in APDS2 patients.
Manipulation of Multielectron Dynamics of Molecules by Fourier-Synthesized Intense Laser Pulses: Effective Potential Analysis of CO
Authors: Ohmura Shu , Ohmura Hideki , Kato Tsuyoshi , Kono Hirohiko
Published: July 2021

We present a theoretical investigation as to how multielectron dynamics of CO are manipulated by Fourier-synthesized intense laser pulses. The pulses used are assumed to be comprised of harmonics up to the fourth order. The multiconfiguration time-dependent (TD) Hartree-Fock (MCTDHF) method, where the multielectron wavefunction Ψ(t) is expressed as a linear combination of various electron configurations, is employed to simulate the dynamics of CO interacting with Fourier-synthesized pulses. The multielectron nature such as electron correlation is quantified by using our effective potential approach. To begin with, the time-dependent natural orbitals {ϕj(r,t)} which diagonalize the first order reduced density matrix are obtained from Ψ(t), where r is the one-electron coordinate. The effective potentials υjeff(r,t) that determine the dynamics of ϕj(r,t) are then derived from the equations of motion for {ϕj(r,t)}. υjeff(r,t) consists of the one-body part υ1(t) including the interaction with the laser electric field ε(t) and the two-body part υ2,j(t) originating from electron-electron interaction. In this way, the role of electron correlation can be quantified by comparing υjeff(r,t) with those obtained by the TDHF method, where Ψ(t) is approximated by a single Slater determinant. We found a very similar profile in υ5σeff(r,t) of the 5σ highest occupied molecular orbital for both near-infrared one-color (ω) and directionally asymmetric ω+2ω two-color pulses; when ε(t) points from the nucleus C to O, a hump appears in υ5σeff(r,t) only 2 bohrs outward from C. The hump formation, which originates from the field-induced change in υ2,5σ(t) (especially, due to electron correlation), is responsible for preferential electron ejection from the C atom side (experimentally observed anisotropic ionization). A coherent superposition of ω and 2ω fields with an appropriate relative phase thus works as a one-color pulse of which either positive or negative peaks are filtered out. More sophisticated manipulation is possible by adding higher harmonics to a synthesized field. We show that the 5σ orbital can be squeezed toward the inside of the potential valley in υ5σeff(r,t), which encloses the molecule at a radius of ∼7 bohrs (semicircle in the region of z <0), by adjusting the phases of a ω+2ω+3ω+4ω field. The hump and valley formation in υ5σeff(r,t) are closely correlated with domains of increasing and decreasing electron density, respectively.
A Computational Study of the Electrophysiological Substrate in Patients Suffering From Atrial Fibrillation
Authors: Pagani S. , Dede' L. , Frontera A. , Salvador M. , Limite L. R. , Manzoni A. , Lipartiti F. , Tsitsinakis G. , Hadjis A. , Della Bella P. , Quarteroni A.
Published: July 2021

In the context of cardiac electrophysiology, we propose a novel computational approach to highlight and explain the long-debated mechanisms behind atrial fibrillation (AF) and to reliably numerically predict its induction and sustainment. A key role is played, in this respect, by a new way of setting a parametrization of electrophysiological mathematical models based on conduction velocities; these latter are estimated from high-density mapping data, which provide a detailed characterization of patients' electrophysiological substrate during sinus rhythm. We integrate numerically approximated conduction velocities into a mathematical model consisting of a coupled system of partial and ordinary differential equations, formed by the monodomain equation and the Courtemanche-Ramirez-Nattel model. Our new model parametrization is then adopted to predict the formation and self-sustainment of localized reentries characterizing atrial fibrillation, by numerically simulating the onset of ectopic beats from the pulmonary veins. We investigate the paroxysmal and the persistent form of AF starting from electro-anatomical maps of two patients. The model's response to stimulation shows how substrate characteristics play a key role in inducing and sustaining these arrhythmias. Localized reentries are less frequent and less stable in case of paroxysmal AF, while they tend to anchor themselves in areas affected by severe slow conduction in case of persistent AF.
Altered Jagged1-Notch1 Signaling in Enhanced Dysfunctional Neovascularization and Delayed Angiogenesis After Ischemic Stroke in HFD/STZ Induced Type 2 Diabetes Rats
Authors: Guo Zhihui , Jia Jia , Tu Yanling , Jin Chang , Guo Cen , Song Feifei , Wu Xuqing , Bao Haifeng , Fan Wei
Published: July 2021

Diabetes exacerbates brain damage in cerebral ischemic stroke. Our previous study has demonstrated that after cerebral ischemia, type 2 diabetes rats displayed worse neurological outcomes, larger cerebral infarction and severer blood-brain barrier disruption. However, our knowledge of the mechanisms of how diabetes impacts the cerebrovascular repair process is limited. This study was aimed to characterize structural alterations and potential mechanisms in brain microvessels before and after ischemic stroke in type 2 diabetic rats treated with high-fat diet and streptozotocin (HFD/STZ). Furtherly, we tested our hypothesis that dysregulated intercellular Jagged1-Notch1 signaling was involved in the dysfunctional cerebral neovascularization both before and after ischemic stroke in HFD/STZ rats. In our study, we found increased yet dysfunctional neovascularization with activated Jagged1-Notch1 signaling in the cerebrovasculature before cerebral ischemia in HFD/STZ rats compared with non-diabetic rats. Furthermore, we observed delayed angiogenesis as well as suppressed Jagged1-Notch1 signaling after ischemic stroke. Our results elucidate the potential mechanisms underlying diabetes-related cerebral microvasculature dysfunction after ischemic stroke.
Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice
Authors: Wu Chao , Yan Fang , Li Min , Tu Yimin , Guo Ziyu , Chen Yufei , Wu Yaxin , Li Qing , Yu Changan , Fu Yi , Wu Meihui , Kong Wei , Gao Yanxiang , Li Xiaowei , Zheng Jingang
Published: July 2021

Developing a three-dimensional (3D) visualization of the kidney at the whole-mount scale is challenging. In the present study, we optimized mouse whole-mount kidney clearing, which improved the transparency ratio to over 90% based on organ-specific perfusion (OSP)-clear, unobstructed brain imaging cocktails and computational analysis (CUBIC). The optimized OSP-CUBIC-compatible 3D immunostaining and imaging simultaneously visualized the high-resolution 3D structure of the whole-mount renal microvascular, glomerulus, and accompanying wrapped traveling sympathetic nerves in mice. A mouse model of pressure overload-induced heart failure (HF) was then established by minimally invasive transverse aortic constriction (MTAC). Further 3D quantification revealed renal sympathetic hyperinnervation (6.80 ± 1.04% vs. 3.73 ± 0.60%, P < 0.05) in mice with HF. In conclusion, this newly developed whole-organ tissue clearing and imaging system provides comprehensive information at the whole-mount scale and has great potential for kidney research. Our data suggest that renal sympathetic hyperinnervation is involved in HF associated with renal dysfunction.
Quantitative Analysis of UV-B Radiation Interception and Bioactive Compound Contents in Kale by Leaf Position According to Growth Progress
Authors: Yoon Hyo In , Kim Hyun Young , Kim Jaewoo , Son Jung Eek
Published: July 2021

UV-B (280–315 nm) radiation has been used as an effective tool to improve bioactive compound contents in controlled environments, such as plant factories. However, plant structure changes with growth progress induce different positional distributions of UV-B radiation interception, which cause difficulty in accurately evaluating the effects of UV-B on biosynthesis of bioactive compounds. The objective of this study was to quantitatively analyze the positional distributions of UV-B radiation interception and bioactive compound contents of kales (Brassica oleracea L. var. acephala) with growth progress and their relationships. Short-term moderate UV-B levels did not affect the plant growth and photosynthetic parameters. Spatial UV-B radiation interception was analyzed quantitatively by using 3D-scanned plant models and ray-tracing simulations. As growth progressed, the differences in absorbed UV-B energy between leaf positions were more pronounced. The concentrations of total phenolic compound (TPC) and total flavonoid compound (TFC) were higher with more cumulative absorbed UV-B energy. The cumulative UV energy yields for TFC were highest for the upper leaves of the older plants, while those for TPC were highest in the middle leaves of the younger plants. Despite the same UV-B levels, the UV-B radiation interception and UV-B susceptibility in the plants varied with leaf position and growth stage, which induced the different biosynthesis of TFC and TPC. This attempt to quantify the relationship between UV-B radiation interception and bioactive compound contents will contribute to the estimation and production of bioactive compounds in plant factories.
The Relationship Between K-Workers’ Leader–Member Exchange, Organizational Citizenship Behavior and Task Performance—Evidence From Chinese Hospitals
Authors: Che Xiaoli , Guo Zhecheng , Chen Qinyuan
Published: July 2021

Aiming to reduce the difficulty of managing and motivating knowledge workers (k-workers), and promote the psychological well-being of them in Chinese hospitals, this study examines how k-workers’ leader–member exchange (LMX) influences their task performance and the mediation effect of organizational citizenship behavior (OCB). Through a self-administered survey, valid questionnaires were collected from 384 k-workers in Chinese hospitals, and partial least squares structural equation modeling was employed for data analysis. The findings show that LMX is positively related to OCB and task performance, and that OCB mediates the relationship between LMX and task performance. This research has theoretical implications and also provides practical suggestions on how to manage, motivate, and inspire k-workers, and promote the psychological well-being of them, and finally enhance the organizational performance in Chinese hospitals.
“Music Has No Borders”: An Exploratory Study of Audience Engagement With YouTube Music Broadcasts During COVID-19 Lockdown, 2020
Authors: Fraser Trisnasari , Crooke Alexander Hew Dale , Davidson Jane W.
Published: July 2021

This exploratory study engages with eight case studies of music performances broadcast online to investigate the role of music in facilitating social cohesion, intercultural understanding and community resilience during a time of social distancing and concomitant heightened racial tensions. Using an online ethnographic approach and thematic analysis of video comments, the nature of audience engagement with music performances broadcast via YouTube during COVID-19 lockdown of 2020 is explored through the lens of ritual engagement with media events and models of social capital. The eight case studies featured virtual choirs, orchestras and music collaborations of various genres, including classical, pop and fusion styles drawing from European, Asia Minor, South African, West African, North African, Arabic, South Asian, and East Asian cultural origins. Five overarching themes resulted from thematic analysis of video comments, includingInteraction,Unity,Resilience,Identity, andEmotion. The paper contributes important theorisation that ritual engagement and social learning fosters intercultural understanding through engaging with music both cognitively and emotionally, which can in turn shape both individual and collective identity. Online platforms provide scope for both bonding and bridging opportunities. Community resilience is supported through the sharing of knowledge, sustaining music practice during social distancing, as well as emotional support shared among audience participants, with potential wellbeing outcomes.
Trait Emotional Intelligence and School Burnout Discriminate Between High and Low Alexithymic Profiles: A Study With Female Adolescents
Authors: Farina Eleonora , Pepe Alessandro , Ornaghi Veronica , Cavioni Valeria
Published: July 2021

Alexithymic traits, which entail finding it difficult to recognize and describe one’s own emotions, are linked with poor trait emotional intelligence (TEI) and difficulties in identifying and managing stressors. There is evidence that alexithymia may have detrimental consequences for wellbeing and health, beginning in adolescence. In this cross-sectional study, we investigated the prevalence and incidence of alexithymia in teenage girls, testing the statistical power of TEI and student burnout to discriminate between high- and low-alexithymic subjects. A sample of 884 female high school students (mean age 16.2 years, age range 14–19) attending three Italian academic-track high schools (social sciences and humanities curriculum) completed self-report measures of alexithymia, school burnout, and TEI. Main descriptive statistics and correlational analysis preceded the discriminant analysis. The mean alexithymia scores suggest a high prevalence of alexithymia in female adolescents; as expected, this trait was negatively correlated with TEI and positively associated with school burnout. Participants with high vs. low alexithymia profiles were discriminated by a combination of TEI and burnout scores. High scores for the emotionality and self-control dimensions of TEI were strongly associated with membership of the low alexithymia group; high scores for the emotional exhaustion dimension of school burnout were indicative of membership of the high alexithymia group. These findings suggest crucial focuses for educational intervention: efforts to reduce the risk of emotional exhaustion and school burnout should especially concentrate on enhancing emotional awareness and self-control skills, both strongly associated with low levels of alexithymia.
Collective Honesty? Experimental Evidence on the Effectiveness of Honesty Nudging for Teams
Authors: Dunaiev Yuri , Khadjavi Menusch
Published: July 2021

A growing literature in economics studies ethical behavior and honesty, as it is imperative for functioning societies in a world of incomplete information and contracts. A majority of studies found more pronounced dishonesty among teams compared to individuals. Scholars identified certain nudges as effective and cost-neutral measures to curb individuals' dishonesty, yet little is known about the effectiveness of such nudges for teams. We replicate a seminal nudge treatment effect, signing on the top of a reporting form vs. no signature, with individuals and confirm the original nudge treatment effect. We further ran the same experiment with teams of two that have to make a joint reporting decision. Our results show the effectiveness of the nudge for teams, which provides further confidence in the applicability of the nudge.