bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Sensitivity to Venetoclax and Microenvironment Protection in Hairy Cell Leukemia
Authors: Vereertbrugghen Alexia , Colado Ana , Gargiulo Ernesto , Bezares Raimundo Fernando , Fernández Grecco Horacio , Cordini Gregorio , Custidiano Maria del Rosario , François Jean-Hugues , Berchem Guy , Borge Mercedes , Paggetti Jerome , Moussay Etienne , Gamberale Romina , Giordano Mirta , Morande Pablo Elías
Published: July 2021

Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often repeatedly. Venetoclax (ABT-199) is a Bcl-2 inhibitor currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) in adult patients ineligible for intensive chemotherapy. Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax as a potential therapy for HCL. We found that clinically relevant concentrations of venetoclax (0.1 and 1 µM) induced primary HCL cell apoptosis in vitro as measured by flow cytometry using Annexin V staining. As microenvironment induces resistance to venetoclax in CLL, we also evaluated its effect in HCL by testing the following stimuli: activated T lymphocytes, stromal cells, TLR-9 agonist CpG, and TLR-2 agonist PAM3. We found decreased levels of venetoclax-induced cytotoxicity in HCL cells exposed for 48 h to any of these stimuli, suggesting that leukemic B cells from HCL patients are sensitive to venetoclax, but this sensitivity can be overcome by signals from the microenvironment. We propose that the combination of venetoclax with drugs that target the microenvironment might improve its efficacy in HCL.
Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications
Authors: Wang Hui , Zhang Hongyi , Zhu Yihao , Wu Zhonghang , Cui Chunhong , Cai Fengfeng
Published: July 2021

Breast cancer (BC) is the most frequent cancer among women worldwide and is the leading cause of cancer-related deaths in women. Cancer cells with stem cell-like features and tumor-initiating potential contribute to drug resistance, tumor recurrence, and metastasis. To achieve better clinical outcomes, it is crucial to eradicate both bulk BC cells and breast cancer stem cells (BCSCs). Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis. There is increasing evidence that salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis. Therefore, salinomycin is a promising therapeutic drug for BC. In this review, we summarize established mechanisms by which salinomycin protects against BC and discuss its future clinical applications.
Correlation Between Early Endpoints and Overall Survival in Non-Small-Cell Lung Cancer: A Trial-Level Meta-Analysis
Authors: Shameer Khader , Zhang Youyi , Jackson Dan , Rhodes Kirsty , Neelufer Imran Khan A. , Nampally Sreenath , Prokop Andrzej , Hutchison Emmette , Ye Jiabu , Malkov Vladislav A. , Liu Feng , Sabin Antony , Weatherall Jim , Duran Cristina , Iacona Renee Bailey , Khan Faisal M. , Mukhopadhyay Pralay
Published: July 2021

Early endpoints, such as progression-free survival (PFS), are increasingly used as surrogates for overall survival (OS) to accelerate approval of novel oncology agents. Compiling trial-level data from randomized controlled trials (RCTs) could help to develop a predictive framework to ascertain correlation trends between treatment effects for early and late endpoints. Through trial-level correlation and random-effects meta-regression analysis, we assessed the relationship between hazard ratio (HR) OS and (1) HR PFS and (2) odds ratio (OR) PFS at 4 and 6 months, stratified according to the mechanism of action of the investigational product. Using multiple source databases, we compiled a data set including 81 phase II–IV RCTs (35 drugs and 156 observations) of patients with non-small-cell lung cancer. Low-to-moderate correlations were generally observed between treatment effects for early endpoints (based on PFS) and HR OS across trials of agents with different mechanisms of action. Moderate correlations were seen between treatment effects for HR PFS and HR OS across all trials, and in the programmed cell death-1/programmed cell death ligand-1 and epidermal growth factor receptor trial subsets. Although these results constitute an important step, caution is advised, as there are some limitations to our evaluation, and an additional patient-level analysis would be needed to establish true surrogacy.
Prognostic Significance of Gene Signature of Tertiary Lymphoid Structures in Patients With Lung Adenocarcinoma
Authors: Feng Hong , Yang Fujun , Qiao Lihong , Zhou Kai , Wang Junfei , Zhang Jiao , Tian Tian , Du Ying , Shangguan Hong
Published: July 2021

Background

Lung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes.

Methods

Clinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort.

Results

TLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups.

Conclusion

This study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.
Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis
Authors: Meng Jun , Wu XiaoQin , Sun Zhen , Xun RenDe , Liu MengSi , Hu Rui , Huang JianChao
Published: July 2021

Background

Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.

Methods

Two reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.

Results

Thirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27–0.35 and 55%; 95% CI: 0.45–0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.

Conclusion

Both axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.
PHF6 Mutations in Hematologic Malignancies
Authors: Kurzer Jason H. , Weinberg Olga K.
Published: July 2021

Next generation sequencing has uncovered several genes with associated mutations in hematologic malignancies that can serve as potential biomarkers of disease. Keeping abreast of these genes is therefore of paramount importance in the field of hematology. This review focuses on PHF6, a highly conserved epigenetic transcriptional regulator that is important for neurodevelopment and hematopoiesis. PHF6 serves as a tumor suppressor protein, with PHF6 mutations and deletions often implicated in the development of T-lymphoblastic leukemia and less frequently in acute myeloid leukemia and other myeloid neoplasms. PHF6 inactivation appears to be an early event in T-lymphoblastic leukemogenesis, requiring cooperating events, including NOTCH1 mutations or overexpression of TLX1 and TLX3 for full disease development. In contrast, PHF6 mutations tend to occur later in myeloid malignancies, are frequently accompanied by RUNX1 mutations, and are often associated with disease progression. Moreover, PHF6 appears to play a role in lineage plasticity within hematopoietic malignancies, with PHF6 mutations commonly present in mixed phenotype acute leukemias with a predilection for T-lineage marker expression. Due to conflicting data, the prognostic significance of PHF6 mutations remains unclear, with a subset of studies showing no significant difference in outcomes compared to malignancies with wild-type PHF6, and other studies showing inferior outcomes in certain patients with mutated PHF6. Future studies are necessary to elucidate the role PHF6 plays in development of T-lymphoblastic leukemia, progression of myeloid malignancies, and its overall prognostic significance in hematopoietic neoplasms.
Single-Center Experience of Focal Thermo-Ablative Therapy After Pelvic Radiotherapy for In-Field Prostate Cancer Oligo-Recurrence
Authors: Giraud Nicolas , Buy Xavier , Vuong Nam-Son , Gaston Richard , Cazeau Anne-Laure , Catena Vittorio , Palussiere Jean , Roubaud Guilhem , Sargos Paul
Published: July 2021

Purpose

In-field prostate cancer (PCa) oligo-recurrence after pelvic radiotherapy is a challenging situation for which metastasis-directed treatments may be beneficial, but options for focal therapies are scarce.

Methods

We retrospectively reviewed data for patients with three or less in-field oligo-recurrent nodal, bone and/or locally recurrent (prostate, seminal vesicles, or prostatic bed) PCa lesions after radiation therapy, identified with molecular imaging (PET and/or MRI) and treated by focal ablative therapy (cryotherapy or radiofrequency) at the Institut Bergonié between 2012 and 2020. Chosen endpoints were the post-procedure PSA response (partially defined as a >50% reduction, complete as a PSA <0.05 ng/ml), progression-free survival (PFS) defined as either a biochemical relapse (defined as a rise >25% of the Nadir and above 2 ng/ml), radiological relapse (on any imaging technique), decision of treatment modification (hormonotherapy initiation or line change) or death, and tolerance.

Results

Forty-three patients were included. Diagnostic imaging was mostly 18F-Choline positron emission tomography/computerized tomography (PET/CT) (75.0%), prostate specific membrane antigen (PSMA) PET/CT (9.1%) or a combination of pelvic magnetic resonance imaging (MRI), CT, and 99 mTc-bone scintigraphy (11.4%). PSA response was observed in 41.9% patients (partial in 30.3%, complete in 11.6%). In the hormone-sensitive exclusive focal ablation group (n = 31), partial and complete PSA responses were 32.3 and 12.9% respectively. Early local control (absence of visible residual active target) on the post-procedure imaging was achieved with 87.5% success. After a median follow-up of 30 months (IQR 13.3–56.8), the median PFS was 9 months overall (95% CI, 6–17), and 17 months (95% CI, 11–NA) for PSA responders. Complications occurred in 11.4% patients, with only one grade IIIb Dindo–Clavien event (uretral stenosis requiring endoscopic uretrotomy).

Conclusion

In PCa patients showing in-field oligo-recurrence after pelvic radiotherapy, focal ablative treatment is a feasible option, possibly delaying a systemic treatment initiation or modification. These invasive strategies should preferably be performed in expert centers and discussed along other available focal strategies in multi-disciplinary meetings.
Outcome of Elderly Patients With Surgically Treated Brain Metastases
Authors: Heimann Muriel , Schäfer Niklas , Bode Christian , Borger Valeri , Eichhorn Lars , Giordano Frank A. , Güresir Erdem , Jacobs Andreas H. , Ko Yon-Dschun , Landsberg Jennifer , Lehmann Felix , Radbruch Alexander , Schaub Christina , Schwab Katjana S. , Weller Johannes , Herrlinger Ulrich , Vatter Hartmut , Schuss Patrick , Schneider Matthias
Published: July 2021

Object

In the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.

Methods

Between 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI).

Results

A total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected “multiple intracranial metastases” (p=0.001), “infratentorial localization” (p=0.011), “preoperative CRP >5 mg/l” (p=0.01) and “frailest patients (mFI ≥ 0.27)” (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM.

Conclusions

In this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.
LIT01-196, a Metabolically Stable Apelin-17 Analog, Normalizes Blood Pressure in Hypertensive DOCA-Salt Rats via a NO Synthase-dependent Mechanism
Authors: Flahault Adrien , Keck Mathilde , Girault-Sotias Pierre-Emmanuel , Esteoulle Lucie , De Mota Nadia , Bonnet Dominique , Llorens-Cortes Catherine
Published: July 2021

Apelin is a neuro-vasoactive peptide that plays a major role in the control of cardiovascular functions and water balance, but has an in-vivo half-life in the minute range, limiting its therapeutic use. We previously developed LIT01-196, a systemically active metabolically stable apelin-17 analog, produced by chemical addition of a fluorocarbon chain to the N-terminal part of apelin-17. LIT01-196 behaves as a potent full agonist for the apelin receptor and has an in vivo half-life in the bloodstream of 28 min after intravenous (i.v.) and 156 min after subcutaneous (s.c.) administrations in conscious normotensive rats. We aimed to investigate the effects of LIT01-196 following systemic administrations on arterial blood pressure, heart rate, fluid balance and electrolytes in conscious normotensive and hypertensive deoxycorticosterone acetate (DOCA)-salt rats. Acute i.v. LIT01-196 administration, in increasing doses, dose-dependently decreases arterial blood pressure with ED50 values of 9.8 and 3.1 nmol/kg in normotensive and hypertensive rats, respectively. This effect occurs for both via a nitric oxide-dependent mechanism. Moreover, acute s.c. LIT01-196 administration (90 nmol/kg) normalizes arterial blood pressure in conscious hypertensive DOCA-salt rats for more than 7 h. The LIT01-196-induced blood pressure decrease remains unchanged after 4 consecutive daily s.c. administrations of 90 nmol/kg, and does not induce any alteration of plasma sodium and potassium levels and kidney function as shown by the lack of change in plasma creatinine and urea nitrogen levels. Activating the apelin receptor with LIT01-196 may constitute a novel approach for the treatment of hypertension.
A Fluid–Structure Interaction Study of Different Bicuspid Aortic Valve Phenotypes Throughout the Cardiac Cycle
Authors: Yan Wentao , Li Jianming , Wang Wenshuo , Wei Lai , Wang Shengzhang
Published: July 2021

The bicuspid aortic valve (BAV) is a congenital malformation of the aortic valve with a variety of structural features. The current research on BAV mainly focuses on the systolic phase, while ignoring the diastolic hemodynamic characteristics and valve mechanics. The purpose of this study is to compare the differences in hemodynamics and mechanical properties of BAV with different phenotypes throughout the cardiac cycle by means of numerical simulation. Based on physiological anatomy, we established an idealized tricuspid aortic valve (TAV) model and six phenotypes of BAV models (including Type 0 a–p, Type 0 lat, Type 1 L–R, Type 1 N-L, Type 1 R-N, and Type 2), and simulated the dynamic changes of the aortic valve during the cardiac cycle using the fluid–structure interaction method. The morphology of the leaflets, hemodynamic parameters, flow patterns, and strain were analyzed. Compared with TAV, the cardiac output and effective orifice area of different BAV phenotypes decreased certain degree, along with the peak velocity and mean pressure difference increased both. Among all BAV models, Type 2 exhibited the worst hemodynamic performance. During the systole, obvious asymmetric flow field was observed in BAV aorta, which was related to the orientation of BAV. Higher strain was generated in diastole for BAV models. The findings of this study suggests specific differences in the hemodynamic characteristics and valve mechanics of different BAV phenotypes, including different severity of stenosis, flow patterns, and leaflet strain, which may be critical for prediction of other subsequent aortic diseases and differential treatment strategy for certain BAV phenotype.
Patient-Specific Virtual Stent-Graft Deployment for Type B Aortic Dissection: A Pilot Study of the Impact of Stent-Graft Length
Authors: Kan Xiaoxin , Ma Tao , Dong Zhihui , Xu Xiao Yun
Published: July 2021

Thoracic endovascular aortic repair (TEVAR) has been accepted as a standard treatment option for complicated type B aortic dissection. Distal stent-graft-induced new entry (SINE) is recognised as one of the main post-TEVAR complications, which can lead to fatal prognosis. Previous retrospective cohort studies suggested that short stent-graft (SG) length (<165 mm) might correlate with increased risk of distal SINE. However, the influence of SG length on changes in local biomechanical conditions before and after TEVAR is unknown. In this paper, we aim to address this issue using a virtual SG deployment simulation model developed for application in type B aortic dissection. Our model incorporates detailed SG design and hyperelastic behaviour of the aortic wall. By making use of patient-specific geometry reconstructed from pre-TEVAR computed tomography angiography (CTA) scan, our model can predict post-TEVAR SG configuration and wall stress. Virtual SG deployment simulations were performed on a patient who underwent TEVAR with a short SG (158 mm in length), mimicking the actual clinical procedure. Further simulations were carried out on the same patient geometry but with different SG lengths (183 mm and 208 mm) in order to evaluate the effect of SG length on changes in local stress in the treated aorta. Comparisons of simulation results for different SG lengths showed the location of maximum stress varied with the SG length. With the short SG (deployed in the patient), the maximum von Mises stress of 238.9 kPa was found on the intimal flap at the distal landing zone where SINE was identified at 3-month follow-up. Increasing the SG length caused the maximum von Mises stress to move away from the distal landing zone where stress values were reduced by approximately 17% with the medium-length SG and by 60% with the long SG. This pilot study demonstrates the potential of using the virtual SG deployment model as a pre-surgical planning tool to help select the most appropriate SG length for individual patients.
Coupling Between the Responses of Plants, Soil, and Microorganisms Following Grazing Exclusion in an Overgrazed Grassland
Authors: Wang Zhen , Li Xiliang , Ji Baoming , Struik Paul C. , Jin Ke , Tang Shiming
Published: July 2021

Grazing exclusion is an effective management practice to restore grassland ecosystem functioning. However, little is known about the role of soil microbial communities in regulating grassland ecosystem functioning during long-term ecosystem restorations. We evaluated the recovery of a degraded semiarid grassland ecosystem in northern China by investigating plant and soil characteristics and the role of soil microbial communities in ecosystem functioning after 22 years of grazing exclusion. Grazing exclusion significantly increased the alpha diversity and changed the community structure of bacteria, but did not significantly affect the alpha diversity or community structure of fungi. The higher abundance of copiotrophicProteobacteriaandBacteroideteswith grazing exclusion was due to the higher carbon and nutrient concentrations in the soil, whereas the high abundance ofAcidobacteriain overgrazed soils was likely an adaptation to the poor environmental conditions. Bacteria of theSphingomonadaceaefamily were associated with C cycling under grazing exclusion. Bacteria of theNitrospiraceaefamily, and especially of theNitrospiragenus, played an important role in changes to the N cycle under long-term exclusion of grazing. Quantitative PCR further revealed that grazing exclusion significantly increased the abundance of nitrogen fixing bacteria (nifH), ammonia oxidizers (AOA and AOB), and denitrifying bacteria (nirKandnosZ1). Denitrifying enzyme activity (DEA) was positively correlated with abundance of denitrifying bacteria. The increase in DEA under grazing exclusion suggests that the dependence of DEA on the availability of NO3–produced is due to the combined activity of ammonia oxidizers and denitrifiers. Our findings indicate that decades-long grazing exclusion can trigger changes in the soil bacterial diversity and composition, thus modulating the restoration of grassland ecosystem functions, carbon sequestration and soil fertility.
VaSDC1 Is Involved in Modulation of Flavonoid Metabolic Pathways in Black and Red Seed Coats in Adzuki Bean (Vigna angularis L.)
Authors: Chu Liwei , Zhao Pu , Wang Kaili , Zhao Bo , Li Yisong , Yang Kai , Wan Ping
Published: July 2021

Seed coat colour is an important nutritional quality trait. Variations in anthocyanins and flavonoids induce the diversity of seed coat colour in adzuki bean (Vigna angularis L.). Red seed coat and black seed coat are important adzuki bean cultivars. Insights into the differences of flavonoid metabolic pathways between black and red adzuki bean are significant. In this study, we explored that the difference in seed coat colour between the red (Jingnong6) and the black (AG118) is caused by the accumulation of anthocyanins. The RNA-sequencing (RNA-Seq) and real-time reverse transcription (qRT)-PCR results showed that the Vigna angularis L. seed coat color (VaSDC1) gene, an R2R3-MYB transcription factor, should be the key gene to regulate the black and red seed coat colours. In three different colouring staes of seed development, VaSDC1 was specifically expressed in the black seed coat (AG118) landrace, which activates the structural genes of flavonoid metabolic pathways. As a result, this caused a substantial accumulation of anthocyanins and created a dark blue-black colour. In the red (Jingnong6) seed coat variety, low expression levels of VaSDC1 resulted in a lower accumulation of anthocyanins than in AG118. In addition, VaSDC1 was genetically mapped in the interval between simple-sequence repeat (SSR) markers Sca326-12, Sca326-4, and BAgs007 on chromosome 3 using an F4 segregating population derived from the cross between Jingnong6 and AG118. These results will facilitate the improvement of nutritional quality breeding in adzuki beans.
Transforming Connections: A Trauma-Informed and Attachment-Based Program to Promote Sensitive Parenting of Trans and Gender Non-conforming Youth
Authors: Dangaltcheva Antonia , Booth Chris , Moretti Marlene M.
Published: July 2021

Gender non-conforming and trans youth experience high rates of bullying and victimization, placing them at risk for serious mental health challenges. Parent support is one of the most significant protective factors in this population, and yet few programs are specifically developed to promote parenting sensitivity, understanding, and acceptance. Connect, a trauma-informed and attachment-based group program for caregivers of at-risk adolescents, has been shown to reduce parent stress and depressed mood, increase parents' sense of efficacy and satisfaction, and reduce parent-teen conflict. Teens benefit from increased attachment security and improved mental health and well-being. Treatment effects have been documented to continue for up to 2 years post-treatment. This paper describes the adaptation of the Connect program to create a new program, Transforming Connections, for caregivers of transgender and gender non-conforming youth. Participants in the first three groups were 20 parents of 16 gender non-conforming youth (ages 12–18). Common themes in group discussions related to gender included: coming out, connecting with peers, affirming pronouns/names, medical transition, parental reactions (e.g., confusion, isolation, grief, acceptance), and concerns about safety and mental health. All parents completed the full program, attending on average 9 of 10 sessions. Caregivers reported feeling respected, safe, and welcomed in the program and indicated that learning about attachment enhanced their understanding of their teen and their gender journey as well as themselves as a parent. Additionally, all parents reported applying the ideas discussed in the group frequently (60%) or somewhat frequently (40%). The majority indicated that their relationship with their teen had improved somewhat (65%) or a great deal (20%). Findings provide positive preliminary evidence of the fit and value of Transforming Connections for these families.
Immigrant Patients Adapt to the Culture of Admission and Experience Less Safety in Forensic Psychiatric Care
Authors: Titze Larissa , Gros Julia , Büsselmann Michael , Lutz Maximilian , Streb Judith , Dudeck Manuela
Published: July 2021

Patients with an immigrant background are overrepresented in forensic psychiatric hospitals. As a result, daily work is impeded by language barriers and cultural differences. Furthermore, general therapy processes have not yet been adapted to this special patient population, and little reliable knowledge is available. All immigrants go through an acculturation process, which is related to their mental well-being. Four acculturation strategies exist: integration, separation, assimilation, and marginalization. The strategy chosen depends on the extent of someone’s orientation toward their country of origin and the country of admission. The current study aimed to expand knowledge of forensic patients with a migration background in Germany by evaluating their self-reported acculturation processes and associated individual and social factors, e.g., the ward climate. Therefore, we studied forensic patients with a migration background from 11 forensic hospitals in Bavaria, Germany. Besides completing the Frankfurter Acculturation Scale (FRACC) and Essen Climate Evaluation Schema (EssenCES), the participants provided information on their clinical and biographical history. We recruited 235 patients with a migration background and found that the participants oriented themselves more toward the culture of admission and less toward the country of origin than the reference sample did. Moreover, the patients experienced significantly less safety on the ward than the forensic reference sample did. A possible explanation for the patients’ orientation is the lack of possibilities to adhere to their cultural traditions. Patients may feel less safe because of their limited knowledge of German and cultural misunderstandings.
Borderline Personality Disorder in a “Life History Theory” Perspective: Evidence for a Fast “Pace-of-Life-Syndrome”
Authors: Otto Benjamin , Kokkelink Lisa , Brüne Martin
Published: July 2021

“Borderline Personality Disorder” (BPD) is associated with heightened risk for cardiovascular disease and other stress-associated somatic consequences, which is poorly understood in terms of causal mechanisms, such as childhood trauma. Here, we tested the hypothesis suggesting that BPD reflects a fast “Pace-of-Life-Syndrome” (PoLS). Ninety-five women (44 diagnosed with BPD) were recruited to examine psychological correlates of PoLS, including life history features, personality dimensions, aggressiveness, chronic stress, borderline symptom severity, childhood trauma, and allostatic load (AL). In line with expectations, BPD patients had significantly higher scores suggestive of a fast PoLS than controls, they were more aggressive, more burdened with chronic stress and were exposed to more severe childhood adversity. Childhood trauma predicted PoLS, which in turn predicted AL. The present study thus provides direct evidence of psychological and somatic traits associated with the fast end of the PoLS spectrum in females with BPD. Findings are discussed with regard to clinical implications.
Predictors of Post-stroke Cognition Among Geriatric Patients: The Role of Demographics, Pre-stroke Cognition, and Trajectories of Depression
Authors: Kang Christiana
Published: July 2021

Stroke is a prevalent disease among geriatric population, which tends to deteriorate cognitive ability and mental health. In such context, cognitive impairment and geriatric depression generate mutually deteriorating impacts on each other. Using the Health and Retirement Study, this study examined depression and cognition before, immediately after, and 2 years after the onset of stroke. Through latent growth mixture modeling, four different trajectories of depression were identified: resilience, recovery, emergent depression, and chronicity. We used demographics including gender, age, race, and ethnicity, activity of daily life, baseline cognition, and trajectories of depression to predict cognitive ability 2 years after the stroke. Both aforementioned demographic factors and pre-stroke cognition were predictive of post-stroke cognition, but the inclusion of depression trajectories further improved the predictive ability. Emergent depression and chronicity were two significant predictors of worse post-stroke cognition. This study showed the importance of considering a more specific trajectotrial interrelationship between depression and cognition in geriatric stroke patients.
Involvement of Kynurenine Metabolism in Bipolar Disorder: An Updated Review
Authors: Zhang Peifen , Huang Huimin , Gao Xingle , Jiang Jiajun , Xi Caixi , Wu Lingling , Fu Yaoyang , Lai Jianbo , Hu Shaohua
Published: July 2021

Bipolar disorder (BD) is a severe affective disorder, mainly characterized by alternative depressive and manic or hypomanic episodes, yet the pathogenesis of BD has not been fully elucidated. Recent researches have implicated the altered kynurenine (KYN) metabolism involved in the neurobiology of BD. Excessive activation of the immune system also occurs in patients with BD, which further accelerates the KYN pathway for tryptophan metabolism. Changes of the KYN metabolites have effects on neuronal receptors and are involved in neuroendocrine transmissions. Interactions between KYN metabolism and the immune system may contribute to the neuropathogenesis of BD. Various studies have shown that alterations of the KYN metabolites were associated with mood, psychotic symptoms, and cognitive functions in patients with BD. In this review, we briefly introduce the KYN pathway and describe the immune dysregulation in BD as well as their interactions. We then focus on the research advances on the KYN metabolism in BD, which hold promise for identifying novel treatment targets in patients stricken with this disorder.
Shared Decision-Making and Role Preference Among Patients With Schizophrenia in Malaysia: A Cross-Sectional Study
Authors: Ismail Mohamad Ayob , Midin Marhani
Published: July 2021

Introduction: Shared decision-making (SDM) is recognized as a promising strategy for improving collaboration between clinicians and their patients in achieving recovery. In Malaysia, SDM among people with schizophrenia is still lacking both in practice and in research. This study aimed to determine the level of SDM and role preference and their associated factors among patients with schizophrenia in Malaysia.

Methods: A cross-sectional study was conducted on 86 outpatient attendees with schizophrenia at a teaching hospital in Kuala Lumpur, Malaysia. The nine-item Shared Decision Making Questionnaire and Control Preference Scale were used to assess perceived SDM experience and role preference, respectively. Linear and logistic regression models were used to analyze the factors associated with SDM and role preference, respectively. Factors with a p <0.25 from the simple regression analyses were controlled as the covariates in the multiple regression analyses.

Results: The study respondents were predominantly female, single, and unemployed, with a mean age of 44 years. Only 35% of the participants reported having high SDM experiences, even though the majority (56%) preferred autonomous role preference. Among the participants who preferred autonomous roles, only 40% experienced high SDM. High SDM was found to be significantly associated with being younger (B = −0.33, 95% CI = −0.67 to −0.003) and being non-clozapine users (B = 19.90, 95% CI = 9.39–30.41), while autonomous role preference was significantly associated with a lower level of insight [adjusted odds ratio (AOR) = 0.84, 95% CI = 0.72–0.99] and being on oral antipsychotic drugs only (AOR = 2.94, 95% CI = 1.10–7.82).

Conclusion: The practice of SDM is still lacking in the treatment of patients with schizophrenia in Malaysia, even though many of them preferred to be involved in the decision-making pertaining to their treatment. This study indicates the need for clinicians to improve their patients' involvement in the treatment process. More research is needed on how SDM can be implemented in patients with schizophrenia, especially in Asian population settings.
Prevalence of Child Maltreatment in Adults With Congenital Heart Disease and Its Relationship With Psychological Well-Being, Health Behavior, and Current Cardiac Function
Authors: Proskynitopoulos Phileas J. , Heitland Ivo , Glahn Alexander , Bauersachs Johann , Westhoff-Bleck Mechthild , Kahl Kai G.
Published: July 2021

Background: The prevalence of child maltreatment in adults with congenital heart disease (ACHD) has not been assessed so far. Child maltreatment is a major risk factor for unfavorable behavioral, mental, and physical health outcomes and has been associated with decreased quality of life. Given the increased survival time of ACHD, it is essential to assess factors that may worsen the quality of life and interact with classical cardiovascular risk factors and mental well-being.

Methods: In a cross-sectional study, 196 ACHD (mean age 35.21 ± 11.24 y, 44,4% female, 55.6% male) completed a thorough psychiatric and cardiac evaluation. Child maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ) and rates were compared to already existing data from the German general population. Further psychological measurements included the WHO Quality of Life Questionnaire, Hospital Anxiety and Depression Scale (HADS) and assessment of lifestyle factors (exercise, smoking, alcohol consumption, body mass index). To identify a relationship between current cardiac function and child maltreatment, we used logistic regression.

Results: ACHD reported significantly higher rates of emotional neglect and emotional abuse and sexual abuse and lower rates of physical neglect when compared to the general German population. In addition, total CTQ-scores, emotional abuse, emotional neglect, physical abuse, and sexual abuse correlated with symptoms of depression, anxiety, and negatively correlated with QoL. Furthermore, CTQ scores contributed significantly in predicting higher New York Heart Association (NYHA) scores (p = 0.009).

Conclusion: Child maltreatment is more common in ACHD and associated with decreased quality of life and depression and anxiety. Furthermore, we found evidence that self-reported child maltreatment is associated with decreased cardiac function. Given the longer survival time of patients with ACHD, identifying factors that may negatively influence the disease course is essential. The negative consequences of child maltreatment may be the subject of psychosocial interventions that have demonstrated efficacy in treating posttraumatic stress disorders.
The Neighborhood Food Environment and the Onset of Child-Hood Obesity: A Retrospective Time-Trend Study in a Mid-sized City in China
Authors: Zhou Peiling , Li Ruifang , Liu Kun
Published: July 2021

Nowadays, obesity and its associated chronic diseases have become a steadily growing public health problem, spreading from the older to younger age groups. Studies have contended that the built environment, particularly the food environment and walkability, may contribute to the prevalence of childhood obesity. In Asian countries which are characterized by rapid urbanization, high population density and oriental diets, little is known about how such urban built environment affects the onset of childhood obesity. This study juxtaposes the effect of food environment, walkability, and outdoor activity spaces at the neighborhood level upon childhood body weight in a mid-sized city in China. This observational study utilizes a retrospective time-trend study design to examine the associations between neighborhood built environment and children's body weight in Zhanjiang City, a mid-sized city in Guangdong Province, China. Robust multiple linear and logistic regression models were used to estimate associations between the built environments and child BMI and weight status (i.e., overweight/obesity and obesity only). This study finds that: (1) Western-style fast food and Chinese-style fast food have divergent impacts on childhood body weight. At neighborhood level, while increased exposure to Western-style fast food may increase child BMI and the risk of overweight and obesity, increased exposure to Chinese-style fast food, on the contrary, may reduce child BMI and the risk of overweight and obesity, indicating a positive health impact of Chinese-style fast food. (2) However, the positive health impacts brought about by Chinese-style fast food, walkable environments and accessible traditional fruit/vegetable markets have gradually disappeared in recent years. This study is among the first to simultaneously consider the divergent and changing impact of food environment upon childhood body weight in urban China. The findings provide important implications for healthy city design and the management of food retail industry in addressing the obesity epidemic in younger generations living in Asian cities. As prominent differences exist in food culture between Asian and Western cities, more attention should be paid to healthy food environment in future studies and related urban planning strategies formulation.
The Impact of Medical Insurance on Household Stock Market Participation: Evidence From China Household Finance Survey
Authors: Shi Gui Fen , Li Mei , Shen Tao-Tao , Ma Yue
Published: July 2021

This paper explores the impact of medical insurance on the possibility of household participation in the stock market and the portfolio share of equity, applying Probit, and Tobit models with the data from China Household Finance Survey (CHFS). The empirical results highlight that participating in medical insurance can significantly increase the possibility of households participating in the stock market and the portfolio share of equity, and have passed the robustness tests, including propensity score matching (PSM), altering estimation methods, replacing explained variables, and eliminating samples. Besides, heterogeneity analysis shows that the impact of medical insurance on household stock market participation is more significant in eastern region, urban areas, and households with higher income level. Further mechanism analysis implies that household participation in medical insurance mainly affects their stock market participation through preventive savings effect. It is necessary to improve the medical insurance system and encourage household participation in stock market so as to further promote financial development in China.
IEEE P7001: A Proposed Standard on Transparency
Authors: Winfield Alan F. T. , Booth Serena , Dennis Louise A. , Egawa Takashi , Hastie Helen , Jacobs Naomi , Muttram Roderick I. , Olszewska Joanna I. , Rajabiyazdi Fahimeh , Theodorou Andreas , Underwood Mark A. , Wortham Robert H. , Watson Eleanor
Published: July 2021

This paper describes IEEE P7001, a new draft standard on transparency of autonomous systems1. In the paper, we outline the development and structure of the draft standard. We present the rationale for transparency as a measurable, testable property. We outline five stakeholder groups: users, the general public and bystanders, safety certification agencies, incident/accident investigators and lawyers/expert witnesses, and explain the thinking behind the normative definitions of “levels” of transparency for each stakeholder group in P7001. The paper illustrates the application of P7001 through worked examples of both specification and assessment of fictional autonomous systems.
Re-conceptualizing the Soil and Water Assessment Tool to Predict Subsurface Water Flow Through Macroporous Soils
Authors: Poon David , Whalen Joann K. , Michaud Aubert R.
Published: July 2021

More water and nutrients from artificially-drained agricultural land reach surface waters by leaching through macropores than by percolating through the soil matrix. However, the Soil and Water Assessment Tool (SWAT) describes water flows poorly in land with subsurface drainage because it does not partition water between macropore and matrix transport processes. We produced a new percolation algorithm to distinguish the macropore flow pathway, which was integrated in the SWAT-MAC model and used to predict water flows in a 30 km2 agricultural subwatershed in southern Quebec, Canada. Partitioning of subsurface flow between macropore and matrix components was reasonable, compared to a chemical-based hydrograph separation of streamflow in this subwatershed. The macropore flow algorithm also improved water allocation between the annual surface runoff and subsurface flow in the SWAT-MAC model. We predict more macropore flow into tile drains under fine-textured soils than coarse-textured soils, which is consistent with experimental observations. However, macropore flow was underestimated in the non-growing season and over-predicted during the growing season, which can be adjusted in the macropore flow algorithm by accounting for dynamic macropore connectivity or effective macroporosity. There are too few observations of regional-specific effects of soil moisture and management practices on macropore flow to correct the algorithm at this time. We conclude that the percolation algorithm of SWAT-MAC represents the macropore flow pathway and improves the description of water movement through agricultural soils with subsurface drainage systems, which are important for transferring water and nutrients to downstream aquatic systems in cold, humid temperate regions.
Multilayer Mirror Based High-Resolution Solar Soft X-Ray Spectrometer
Authors: Panini S. S. , Narendranath S. , Sreekumar P. , Sankarasubramanian K.
Published: July 2021

Soft X-ray spectroscopy of the Sun is an important tool to understand the coronal dynamics and composition. The solar coronal X-ray spectrum below 1 keV is the least explored with high-resolution spectroscopy. Recent observations with Hinode XRT using coarse spectroscopy along with high-resolution imaging have shown that abundances in the coronae have variability associated with structures on the Sun. Disk averaged abundances with better spectral resolution spectrometers show time variability associated with flares. Both spatial and temporal variabilities seem to be related to changes in the magnetic field topology. Understanding such short term variabilities is necessary to model the underlying dynamics and mixing of material between different layers of the Sun. A Sensitive high-resolution spectrometer that covers the range in plasma temperatures and emission line complexes would uniquely reveal the entire evolution of flares. We are investigating a design of a multi-layer mirror-based X-ray spectrograph in the spectral range from 0.5 to 7 keV. The instrument operates in four asynchronous spectral channels operating one at a time. The multi-layer mirror placed at the focus of a Wolter type I telescope reflects a narrow band X-rays to the CCD which is placed at Nasmyth defocus. Converging X-rays from the front end optics helps to increase the spectral range of each channel while preserving the spectral resolution. This design is estimated to achieve a spectral resolution of 20 eV in the spectral range of 0.5–7 keV. With such high spectral resolution, we can resolve individual spectral features e.g., 6.7 keV Fe complex which can be used to diagnose high-temperature transient plasma during flares. The instrument design estimated performance and the science capabilities of this instrument will be discussed in detail in the paper.
Quantum Fluctuations in the Effective Relational GFT Cosmology
Authors: Marchetti L. , Oriti D.
Published: July 2021

We analyze the size and evolution of quantum fluctuations of cosmologically relevant geometric observables, in the context of the effective relational cosmological dynamics of GFT models of quantum gravity. We consider the fluctuations of the matter clock observables, to test the validity of the relational evolution picture itself. Next, we compute quantum fluctuations of the universe volume and of other operators characterizing its evolution (number operator for the fundamental GFT quanta, effective Hamiltonian and scalar field momentum). In particular, we focus on the late (clock) time regime, where the dynamics is compatible with a flat FRW universe, and on the very early phase near the quantum bounce produced by the fundamental quantum gravity dynamics.