bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrepancies Between Explicit Feelings of Power and Implicit Power Motives Are Related to Anxiety in Women With Anorexia Nervosa
Authors: Weineck Felicitas , Schultchen Dana , Dunker Freya , Hauke Gernot , Lachenmeir Karin , Schnebel Andreas , Karačić Matislava , Meule Adrian , Voderholzer Ulrich , Pollatos Olga
Published: February 2021

Background

Several studies identified low subjective feelings of power in women with anorexia nervosa (AN). However, little is known about implicit power motives and the discrepancy between explicit feelings of power and implicit power motives in AN.

Aim

The study investigated the discrepancy between explicit feelings of power and implicit power motives and its relationship to anxiety in patients with AN.

Method

Fifty-three outpatients and inpatients with AN and 48 participants without AN were compared regarding subjective feelings of power and anxiety. Explicit power [investigated with the Personal Sense of Power Scale (trait focus) and a visual analog scale (state focus)], implicit power motives [investigated with the Multi-Motive Grid (MMG)] and trait anxiety [measured with the State-Trait Anxiety Inventory (STAI)], were assessed.

Results

Explicit feelings of power (state and trait level) were lower in patients with AN compared to non-AN participants. No differences in implicit power motives were found when comparing the groups against each other. However, looking at the groups separately, women with AN had similar levels of implicit fear of losing power and hope for power, whereas woman without AN had significantly lower fear of losing power than hope for power. Focusing on discrepancies between powerful feelings and power motives, results were mixed, depending on the subscale of the MMG. Lastly, discrepancies between implicit power motives and explicit feelings of power were positively correlated with trait anxiety in AN patients.

Conclusion

These findings underline that individuals with AN display significantly lower explicit feelings of power, however, they show similar implicit power motives compared to individuals without AN. The discrepancy between explicit feelings of power and implicit power motives is related to anxiety in AN and may represent a vulnerability factor to illness maintenance.
Prioritizing Indecent Image Offenders: A Systematic Review and Economic Approach to Understand the Benefits of Evidence-Based Policing Strategies
Authors: Giles Susan , Alison Laurence
Published: February 2021

In 2013, there were an estimated 50,000 individuals involved in downloading and sharing indecent images of children (IIOC) in the United Kingdom (UK). This poses challenges for limited police resources. We argue that police officers can make most effective use of limited resources by prioritizing those offenders who pose the greatest risk of contact offending, by nature of demonstrable pedophilia, hebephilia or dual offending status and thus, those at highest risk must be dealt with first. What is currently lacking is a clear idea of the potential scale of the problem in socio-economic terms and why, therefore, it is so important that evidence-based approaches to offender detection and investigation continue to be a top priority for funders and policy makers. A systematic literature review was undertaken to address two related questions. First, what is the scale of the problem in the UK, in terms of the number of pedophilic and hebephilic individuals who pose a risk of contact offending against a child? Second, what is the potential socio-economic burden generated by the national IIOC suspect pool if left unattended to by targeted police action? Applying population estimates of pedophilia and hebephilia to the male population (16–89 years), we estimate there are between 2,365–5,991 males with paedophila and 12,218–30,952 males with hebephilia who are likely contact offenders. Applying average prevalence and incidence based costing methods to a conservative estimate of one victim per offender, the combined socio-economic burden from these persons could amount to £236-£597 million (incident costs) increasing to £2.9-£7.3 billion (lifetime costs; £3.3-£8.3 billion including QALY measures). Applying the same costs to CEOP (2013) estimate of 50,000 IIOC offenders we estimate that between 6,000 and 27,500 dual offenders could have already committed past contact offenses, contributing an economic burden of between £97–£445 million (incident costs) increasing to £1.2–£5.4 billion (lifetime costs; £1.4–£6.2 billion including QALY measures). Future contact offenses could contribute a further burden of £16–£18.6 million (incident costs) increasing to £198–£227 million (lifetime costs; £226–£260 million including QALY measures). Drawing upon these findings, we argue for the benefits of a research-informed prioritization approach to target IIOC offenders.
Differential Physical and Mental Benefits of Physiotherapy Program Among Patients With Schizophrenia and Healthy Controls Suggesting Different Physical Characteristics and Needs
Authors: Szortyka Michele Fonseca , Batista Cristiano Viviane , Belmonte-de-Abreu Paulo
Published: February 2021

In contrast to several other severe illnesses marked by inflammation and autoimmunity that now have potent and efficient treatments and even cures, schizophrenia (SCZ) is a disease still associated with poor outcome, incapacity, and social burden. Even after decades of research on the brain and behavior, this illness is still associated with profound effects on both mental health and physical health, with recent studies showing that treatment is more efficient when associating drugs with psychological and physical treatments. Most of the studies measured the effects of physical intervention compared with usual care and demonstrated a positive effect as an add-on treatment. What remains unclear is the different effects of the same intervention in normal subjects in a sample of patients with the illness. The study aimed to evaluate the effects of physical intervention over motor functional capacity and mental health in patients with SCZ compared with healthy controls (HC). The outcomes were (a) functional capacity [by 6-min walk test (6MWT)], (b) body flexibility index (Wells' bench), (c) disease severity [by Brief Psychiatric Rating Scale (BPRS)], (d) quality of life [by 36-Item Short Form (SF-36) questionnaire], and (e) physical activity [Simple Physical Activity Questionnaire (SIMPAQ)]. The intervention was associated with significant decrease of body mass index (BMI), blood pressure, disease severity, and improvement in daily life activities. Unexpectedly, it was observed that schizophrenics, compared with matched HC, were at a lower level of performance in the beginning, remained below HC over the studied time despite similar physical intervention, and had different changes. The intervention had lower effects over physical capacity and better effects over quality of life and disease severity. The results confirm previous studies comparing patients receiving physical intervention but suggest that they may receive different types of intervention, suited for their different baseline fitness, motivation, and capacity to engage in physical effort over sustained time. Additionally, they point to extended time of intervention of multidisciplinary treatment (physical and psychological–cognitive techniques) to improve outcomes in SCZ.
Interpreting Bibliometric Data
Authors: Szomszor Martin , Adams Jonathan , Fry Ryan , Gebert Chris , Pendlebury David A. , Potter Ross W. K. , Rogers Gordon
Published: February 2021

Many academic analyses of good practice in the use of bibliometric data address only technical aspects and fail to account for and appreciate user requirements, expectations, and actual practice. Bibliometric indicators are rarely the only evidence put before any user group. In the present state of knowledge, it is more important to consider how quantitative evaluation can be made simple, transparent, and readily understood than it is to focus unduly on precision, accuracy, or scholarly notions of purity. We discuss how the interpretation of ‘performance’ from a presentation using accurate but summary bibliometrics can change when iterative deconstruction and visualization of the same dataset is applied. From the perspective of a research manager with limited resources, investment decisions can easily go awry at governmental, funding program, and institutional levels. By exploring select real-life data samples we also show how the specific composition of each dataset can influence interpretive outcomes.
Early Initiation of a Standardized Open Abdomen Treatment With Vacuum Assisted Mesh-Mediated Fascial Traction Achieves Best Results
Authors: Berrevoet Frederik , Lampaert Silvio , Singh Kashika , Jakipbayeva Kamilya , van Cleven Stijn , Vanlander Aude
Published: February 2021

Background: The open abdomen (OA) is an important approach for managing intra-abdominal catastrophes and continues to be the standard of care. Complete fascial closure is an essential treatment objective and can be achieved by the use of different dynamic closure techniques. Both surgical technique and—decision making are essential for optimal patient outcome in terms of fascial closure. The aim of this study was to analyse patients' outcome after the use of mesh-mediated fascial traction (MMFT) associated with negative pressure wound therapy (NPWT) and identify important factors that negatively influenced final fascial closure.

Methods: A single center ambispective analysis was performed including all patients treated for an open abdomen in a tertiary referral center from 3/2011 till 2/2020. All patients with a minimum survival >24 h after initiation of treatment were analyzed. The data concerning patient management was collected and entered into the Open Abdomen Route of the European Hernia Society (EHS). Patient basic characteristics considering OA indication, primary fascial closure, as well as important features in surgical technique including time after index procedure to start mesh mediated fascial traction, surgical closure techniques and patients' long-term outcomes were analyzed.

Results: Data were obtained from 152 patients who underwent open abdomen therapy (OAT) in a single center study. Indications for OAT as per-protocol analysis were sepsis (33.3%), abdominal compartment syndrome (31.6%), followed by peritonitis (24.2%), abdominal trauma (8.3%) and burst abdomen (2.4%). Overall fascial closure rate was 80% as in the per-protocol analysis. When patients that started OA management with MMFT and NPWT from the initial surgery a significantly better fascial closure rate was achieved compared to patients that started 3 or more days later (p < 0.001). An incisional hernia developed in 35.8% of patients alive with a median follow-up of 49 months (range 6–96 months).

Conclusion: Our main findings emphasize the importance of a standardized treatment plan, initiated early on during management of the OA. The use of vacuum assisted closure in combination with MMFT showed high rates of fascial closure. Absence of initial intraperitoneal NPWT as well as delayed start of MMFT were risk factors for non-fascial closure. Initiation of OA with VACM should not be unnecessary delayed.
Effect of a Synbiotic Supplement on Fear Response and Memory Assessment of Broiler Chickens Subjected to Heat Stress
Authors: Mohammed Ahmed , Mahmoud Manal , Murugesan Raj , Cheng Heng-wei
Published: February 2021

The aim of this study was to evaluate the effect of a synbiotic containing a probiotic (Enterococcus faecium, Pediococcus acidilactici, Bifidobacterium animalis, and Lactobacillus reuteri) and a prebiotic (fructooligosaccharides) on fear response, memory assessment, and selected stress indicators in broilers subjected to heat stress. A total of 360 1-day-old Ross 708 chicks were evenly divided among three treatments: a basal diet mixed with a synbiotic at 0 (G-C), 0.5 (G-0.5X), and 1.0 (G-1.0X) g/kg. After 15 d, the broilers were exposed to 32 °C for 9 h daily until 42 d. The object memory test was conducted at 15 day; touch, novel object, and isolation tests were conducted at 35 day; tonic immobility (TI) took place at 41 day. At 42 day, plasma corticosterone and tryptophan concentrations and heterophile/lymphocyte (H/L) ratios were measured. Compared to controls, synbiotic-fed broilers, regardless of concentration, had a shorter latency to make the first vocalization, with higher vocalization rates during the isolation test (p = 0.001). the G-1.0 group had the lowest H/L ratio (p = 0.001), but higher plasma tryptophan concentrations and a greater number of birds could reach the observer during the touch test (p = 0.001 and 0.043, respectively). The current results indicate that the synbiotic can be used as a growth promoter to reduce the fear response and stress state of heat-stressed broilers.
Efficiency of GnRH–Loaded Chitosan Nanoparticles for Inducing LH Secretion and Fertile Ovulations in Protocols for Artificial Insemination in Rabbit Does
Authors: Hassanein Eman M. , Hashem Nesrein M. , El-Azrak Kheir El-Din M. , Gonzalez-Bulnes Antonio , Hassan Gamal A. , Salem Mohamed H.
Published: February 2021

Gonadotropin-releasing hormone (GnRH)–loaded chitosan nanoparticles (GnRH–ChNPs) were used at different doses and routes of administration to induce ovulation in rabbits as an attempt to improve artificial insemination (AI) procedures and outcomes. In this study, the characteristics (size, polydispersity, loading efficiency, and zeta-potential) of GnRH–ChNPs and the GnRH release pattern were determined in an in vitro study. A first in vivo study assessed the pituitary and ovarian response to different GnRH–ChNPs doses and routes of administration (two i.m. doses, Group HM = 0.4 µg and Group QM = 0.2 µg, and two intravaginal doses, Group HV = 4 µg and Group QV = 2 µg) against a control group (C) receiving bare GnRH (0.8 µg). The HM, QM, and HV treatments induced an earlier LH-surge (90 min) than that observed in group C (120 min), whilst the QV treatment failed to induce such LH surge. The number of ovulation points was similar among treatments, except for the QV treatment (no ovulation points). A second in vivo study was consequently developed to determine the hormonal (progesterone, P4, and estradiol, E2) profile and pregnancy outcomes of both HM and HV treatments against group C. The treatment HM, but not the treatment HV, showed adequate P4 and E2 concentrations, conception and parturition rates, litter size, litter weight, and viability rate at birth. Overall, the use of GnRH–ChNPs allows for a reduction in the conventional intramuscular GnRH dose to half without compromising fertility. However, the addition of GnRH–ChNPs to semen extenders, although successfully inducing ovulation, has negative impacts on fertility. Thus, more studies are needed to explore this point and allow further adjustments.
Study on Time Reversal Maximum Ratio Combining in Underwater Acoustic Communications
Authors: Zhao Anbang , Zeng Caigao , Hui Juan , Wang Keren , Tang Kaiyu
Published: February 2021

Time reversal (TR) can achieve temporal and spatial focusing by exploiting spatial diversity in complex underwater environments with significant multipath. This property makes TR useful for underwater acoustic (UWA) communications. Conventional TR is realized by performing equal gain combining (EGC) on the single element TR output signals of each element of the vertical receive array (VRA). However, in the actual environment, the signal-to-noise ratio (SNR) and the received noise power of each element are different, which leads to the reduction of the focusing gain. This paper proposes a time reversal maximum ratio combining (TR-MRC) method to process the received signals of the VRA, so that a higher output SNR can be obtained. The theoretical derivation of the TR-MRC weight coefficients indicates that the weight coefficients are only related to the input noise power of each element, and are not affected by the multipath structure. The correctness of the derivation is demonstrated with the experimental data of the long-range UWA communications conducted in the South China Sea. In addition, the experimental results illustrate that compared to the conventional TR, TR-MRC can provide better performance in terms of output SNR and bit error rate (BER) in UWA communications.
Review on System Identification and Mathematical Modeling of Flapping Wing Micro-Aerial Vehicles
Authors: Khan Qudrat , Akmeliawati Rini
Published: February 2021

This paper presents a thorough review on the system identification techniques applied to flapping wing micro air vehicles (FWMAVs). The main advantage of this work is to provide a solid background and domain knowledge of system identification for further investigations in the field of FWMAVs. In the system identification context, the flapping wing systems are first categorized into tailed and tailless MAVs. The most recent developments related to such systems are reported. The system identification techniques used for FWMAVs can be classified into time-response based identification, frequency-response based identification, and the computational fluid-dynamics based computation. In the system identification scenario, least mean square estimation is used for a beetle mimicking system recognition. In the end, this review work is concluded and some recommendations for the researchers working in this area are presented.
Response of Methane and Nitrous Oxide Emissions from Peatlands to Permafrost Thawing in Xiaoxing’an Mountains, Northeast China
Authors: Sun Xiaoxin , Wang Hongjun , Song Changchun , Jin Xin , Richardson Curtis J. , Cai Tijiu
Published: February 2021

Permafrost thawing may lead to the release of carbon and nitrogen in high-latitude regions of the Northern Hemisphere, mainly in the form of greenhouse gases. Our research aims to reveal the effects of permafrost thawing on CH4 and N2O emissions from peatlands in Xiaoxing’an Mountains, Northeast China. During four growing seasons (2011–2014), in situ CH4 and N2O emissions were monitored from peatland under permafrost no-thawing, mild-thawing, and severe-thawing conditions in the middle of the Xiaoxing’an Mountains by a static-chamber method. Average CH4 emissions in the severe-thawing site were 55-fold higher than those in the no-thawing site. The seasonal variation of CH4 emission became more aggravated with the intensification of permafrost thawing, in which the emission peaks became larger and the absorption decreased to zero. The increased CH4 emissions were caused by the expansion of the thawing layer and the subsequent increases in soil temperature, water table, and shifts of plant communities. However, N2O emissions did not change with thawing. Permafrost thawing increased CH4 emissions but did not impact N2O emissions in peatlands in the Xiaoxing’an Mountains. Increased CH4 emissions from peatlands in this region may amplify global warming.
Dynamics of the Creation of a Rotating Bose–Einstein Condensation by Two Photon Raman Transition Using a Laguerre–Gaussian Laser Pulse
Authors: Mukherjee Koushik , Bandyopadhyay Soumik , Angom Dilip , Martin Andrew M. , Majumder Sonjoy
Published: February 2021

We present numerical simulations to unravel the dynamics associated with the creation of a vortex in a Bose–Einstein condensate (BEC), from another nonrotating BEC using two-photon Raman transition with Gaussian (G) and Laguerre–Gaussian (LG) laser pulses. In particular, we consider BEC of Rb atoms at their hyperfine ground states confined in a quasi two dimensional harmonic trap. Optical dipole potentials created by G and LG laser pulses modify the harmonic trap in such a way that density patterns of the condensates during the Raman transition process depend on the sign of the generated vortex. We investigate the role played by the Raman coupling parameter manifested through dimensionless peak Rabi frequency and intercomponent interaction on the dynamics during the population transfer process and on the final population of the rotating condensate. During the Raman transition process, the two BECs tend to have larger overlap with each other for stronger intercomponent interaction strength.
Alignment Effects in Spatial Perspective Taking from an External Vantage Point
Authors: Hatzipanayioti Adamantini , Avraamides Marios N.
Published: February 2021

In three experiments, we examined, using a perceptual task, the difficulties of spatial perspective taking. Participants imagined adopting perspectives around a table and pointed from them towards the positions of a target. Depending on the condition, the scene was presented on a virtual screen in Virtual Reality or projected on an actual screen in the real world (Experiment 1), or viewed as immediate in Virtual Reality (Experiment 2). Furthermore, participants pointed with their arm (Experiments 1 and 2) vs. a joystick (Experiment 3). Results showed a greater alignment effect (i.e., a larger difference in performance between trials with imagined perspectives that were aligned vs. misaligned with the orientation of the participant) when executing the task in a virtual rather than in the real environment, suggesting that visual access to body information and room geometry, which is typically lacking in Virtual Reality, influences perspective taking performance. The alignment effect was equal across the Virtual Reality conditions of Experiment 1 and Experiment 2, suggesting that being an internal (compared to an external) observer to the scene induces no additional difficulties for perspective taking. Equal alignment effects were also found when pointing with the arm vs. a joystick, indicating that a body-dependent response mode such as pointing with the arm creates no further difficulties for reasoning from imagined perspectives.
Cancer-Associated Fibroblast Subgroups Showing Differential Promoting Effect on HNSCC Progression
Authors: Kang Soo Hyun , Oh Su Young , Lee Heon-Jin , Kwon Tae-Geon , Kim Jin-Wook , Lee Sung-Tak , Choi So-Young , Hong Su-Hyung
Published: February 2021

Background: The critical effect of the tumor microenvironment on cancer progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may be attributed to fibroblasts. However, the effect of cancer-associated fibroblast (CAF) on the progression of head and neck squamous cell carcinoma (HNSCC) is not well known. Methods: From the immunohistochemical analysis of head and neck squamous cell carcinoma (HNSCC) tissues, we divided CAF into two groups depending on the presence or absence of a well-demarcated boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM). Primary culture of CAF was performed, followed by co-transplantation with HNSCC cells into mice oral mucosa, and the tumorigenesis was compared. The mRNA expression patterns between these two CAF groups were compared using DNA microarray analysis. Results: CAFs from cancer tissues that showed no demarcation between ECM and epithelial cancer cells (CAF-Promote) tended to stimulate Matrigel invasion of HNSCC cells. Conversely, CAFs from cancer tissues that showed a boundary with epithelial cancer cells (CAF-Delay) caused no remarkable increase in Matrigel invasion. Compared with CAF-P, CAF-D is less effective in promoting FaDu tumorigenicity in the mouse model. In DNA microarray analysis, COL3A1 and COL6A6 showed particularly high expression in the CAF-D group. Conclusions: These cancer stroma-derived collagen proteins might delay the HNSCC progression. These findings are expected to provide vital information for predicting HNSCC prognosis and developing drug targets in the future.
Diagnostic and Prognostic Characteristics of Circulating Free DNA Methylation Detected by the Electrochemical Method in Malignant Tumors
Authors: Sun Li-Yue , Du Zi-Ming , Liu Yu-Ying , Li Yan-Hong , Liu Xiao-Min , Wang Ting , Shao Jian-Yong
Published: February 2021

Prior research has established an electrochemical method based on the differential adsorption capacity of gold surfaces with different methylated DNA degrees and found that this method might be valuable for cancer diagnosis by detecting circulating free DNA methylation. However, further investigation on the underlying mechanism and validation of its diagnostic and prognostic values in a large cohort of malignant tumors was limited. We found that DNA with different methylation levels formed particles of diverse sizes on the gold surface. Hydrophobic bonds played a significant role in the binding process of methylated DNA to the gold surface. The detection condition of an adsorption time of 10 min and temperature of 20 °C was optimal. In a large cohort of plasma samples from the patients with different malignant tumors, as well as normal individuals, we found that the electrochemical detection method based on the differential adsorption capacity of methylated DNA degree on a gold surface could be used as a noninvasive tool for malignant tumor diagnosis and prognostic evaluation. The diagnostic efficiency of this method in malignant tumors was even slightly better than that of the current tumor biomarkers widely used in routine clinical practice (circulating free DNA (cfDNA) vs. carcinoembryonic antigen (CEA), 0.8131 vs. 0.7191 and cfDNA vs. CA19-9, 0.7687 vs. 0.6693).
Feasibility and Safety of Repeated Carbon Ion Radiotherapy for Locally Advanced Unresectable Pancreatic Cancer
Authors: Okamoto Masahiko , Shiba Shintaro , Okazaki Shohei , Miyasaka Yuhei , Shibuya Kei , Kiyohara Hiroki , Ohno Tatsuya
Published: February 2021

Purpose: The feasibility and safety of re-irradiation with carbon ion beams for locally recurrent unresectable pancreatic cancer (URPC) after carbon ion radiotherapy (CIRT) was evaluated. Methods: Medical records from patients with re-irradiated URPC who were treated with CIRT between November 2017 and February 2019 were reviewed. Inclusion criteria were (1) isolated local recurrence after CIRT, (2) URPC, and (3) tumor located at least 3 mm from the gastrointestinal tract. The first and second CIRT irradiation doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Results: Ten patients met the inclusion criteria. The median follow-up period was 25.5 months (range, 16.0–69.1) after the first CIRT and 8.9 months (range, 6.4–18.9) after the second CIRT. The median interval between the initial CIRT and the local recurrence was 15.8 months (range, 8.0–50.1). One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were attributed to CIRT. The estimated 1-year overall survival, local control, and progression-free survival rates after the second CIRT were 48%, 67%, and 34%, respectively. Conclusion: Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT.
Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment
Authors: Altamura Concetta , Greco Maria Raffaella , Carratù Maria Rosaria , Cardone Rosa Angela , Desaphy Jean-François
Published: February 2021

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.
Quantification and Optimization of Standard-of-Care Therapy to Delay the Emergence of Resistant Bone Metastatic Prostate Cancer
Authors: Araujo Arturo , Cook Leah M. , Frieling Jeremy S. , Tan Winston , Copland John A. , Kohli Manish , Gupta Shilpa , Dhillon Jasreman , Pow-Sang Julio , Lynch Conor C. , Basanta David
Published: February 2021

Background: Bone metastatic prostate cancer (BMPCa), despite the initial responsiveness to androgen deprivation therapy (ADT), inevitably becomes resistant. Recent clinical trials with upfront treatment of ADT combined with chemotherapy or novel hormonal therapies (NHTs) have extended overall patient survival. These results indicate that there is significant potential for the optimization of standard-of-care therapies to delay the emergence of progressive metastatic disease. Methods: Here, we used data extracted from human bone metastatic biopsies pre- and post-abiraterone acetate/prednisone to generate a mathematical model of bone metastatic prostate cancer that can unravel the treatment impact on disease progression. Intra-tumor heterogeneity in regard to ADT and chemotherapy resistance was derived from biopsy data at a cellular level, permitting the model to track the dynamics of resistant phenotypes in response to treatment from biological first-principles without relying on data fitting. These cellular data were mathematically correlated with a clinical proxy for tumor burden, utilizing prostate-specific antigen (PSA) production as an example. Results: Using this correlation, our model recapitulated the individual patient response to applied treatments in a separate and independent cohort of patients (n = 24), and was able to estimate the initial resistance to the ADT of each patient. Combined with an intervention-decision algorithm informed by patient-specific prediction of initial resistance, we propose to optimize the sequence of treatments for each patient with the goal of delaying the evolution of resistant disease and limit cancer cell growth, offering evidence for an improvement against retrospective data. Conclusions: Our results show how minimal but widely available patient information can be used to model and track the progression of BMPCa in real time, offering a clinically relevant insight into the patient-specific evolutionary dynamics of the disease and suggesting new therapeutic options for intervention. Trial registration: NCT # 01953640. Funding: Funded by an NCI U01 (NCI) U01CA202958-01 and a Moffitt Team Science Award. CCL and DB were partly funded by an NCI PSON U01 (U01CA244101). AA was partly funded by a Department of Defense Prostate Cancer Research Program (W81XWH-15-1-0184) fellowship. LC was partly funded by a postdoctoral fellowship (PF-13-175-01-CSM) from the American Cancer Society.
Safety and Efficacy of Robotic Radiosurgery for Visceral and Lymph Node Metastases of Renal Cell Carcinoma: A Retrospective, Single Center Analysis
Authors: Rodler Severin , Schott Melanie , Tamalunas Alexander , Marcon Julian , Graser Annabel , Mumm Jan-Niclas , Casuscelli Jozefina , Stief Christian G. , Fürweger Christoph , Muacevic Alexander , Staehler Michael
Published: February 2021

Despite rapid advances of systemic therapy options in renal cell carcinoma (RCC), local tumor or metastases treatment remains important in selected patients. Here, we assess the safety and efficacy of robotic radiosurgery (RRS) as an ablative therapy for visceral and lymph node metastases of RCC. Patients with histologically confirmed RCC and radiologically confirmed progression of visceral or lymph node metastases underwent RRS and were retrospectively analyzed. Overall survival and progression free survival were calculated by the Kaplan–Meier method and log-rank test. Sixty patients underwent RRS and were included in the analysis. Patients presented for RRS treatment with a median age at RRS treatment of 64 years (range 42–83), clear cell histology (88.3%) and favorable international metastatic renal cell carcinoma database (IMDC) risk score (58.3%). Treatment parameters differed for the number of fractions (median visceral metastases: 1, range 1–5; median lymph node metastases: 1, range 0–5; p = 0.003) and prescription dose (median visceral metastases 24 Gy, range 8–26; median lymph node metastases 18 Gy, range 7–26, p < 0.001). The median overall survival was 65.7 months (range: 2.9–108.6), the median progression free survival was 17.4 months (range: 2.7–70.0) and local tumor control was achieved in 96.7% of patients. Adverse events were limited to 8.3% of patients, with one grade 4 toxicity within 6 weeks after RRS therapy. RRS is a safe and effective treatment option in selected patients with metastatic RCC in a multimodal approach. Further research is warranted to confirm our findings prospectively.
Subcellular Localization of uc.8+ as a Prognostic Biomarker in Bladder Cancer Tissue
Authors: Terreri Sara , Mancinelli Sara , Ferro Matteo , Vitale Maria Concetta , Perdonà Sisto , Castaldo Luigi , Gigantino Vincenzo , Mercadante Vincenzo , De Cecio Rossella , Aquino Gabriella , Montella Marco , Angelini Claudia , Del Prete Eugenio , Aprile Marianna , Ciaramella Angelo , Liguori Giovanna L. , Costa Valerio , Calin George A. , La Civita Evelina , Terracciano Daniela , Febbraio Ferdinando , Cimmino Amelia
Published: February 2021

Non-coding RNA transcripts originating from Ultraconserved Regions (UCRs) have tissue-specific expression and play relevant roles in the pathophysiology of multiple cancer types. Among them, we recently identified and characterized the ultra-conserved-transcript-8+ (uc.8+), whose levels correlate with grading and staging of bladder cancer. Here, to validate uc.8+ as a potential biomarker in bladder cancer, we assessed its expression and subcellular localization by using tissue microarray on 73 human bladder cancer specimens. We quantified uc.8+ by in-situ hybridization and correlated its expression levels with clinical characteristics and patient survival. The analysis of subcellular localization indicated the simultaneous presence of uc.8+ in the cytoplasm and nucleus of cells from the Low-Grade group, whereas a prevalent cytoplasmic localization was observed in samples from the High-Grade group, supporting the hypothesis of uc.8+ nuclear-to-cytoplasmic translocation in most malignant tumor forms. Moreover, analysis of uc.8+ expression and subcellular localization in tumor-surrounding stroma revealed a marked down-regulation of uc.8+ levels compared to the paired (adjacent) tumor region. Finally, deep machine-learning approaches identified nucleotide sequences associated with uc.8+ localization in nucleus and/or cytoplasm, allowing to predict possible RNA binding proteins associated with uc.8+, recognizing also sequences involved in mRNA cytoplasm-translocation. Our model suggests uc.8+ subcellular localization as a potential prognostic biomarker for bladder cancer.
Genomic Landscape of Hodgkin Lymphoma
Authors: Brune Magdalena M. , Juskevicius Darius , Haslbauer Jasmin , Dirnhofer Stefan , Tzankov Alexandar
Published: February 2021

Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but recently developed methods (especially laser capture microdissection, flow cytometry/fluorescence-activated cell sorting) facilitated molecular investigation, elucidating the pathophysiological principles of “Hodgkin lymphomagenesis”. Methods: We reviewed the relevant literature of the last three decades focusing on the genomic landscape of classic and nodular lymphocyte predominant HL (NLPHL) and summarized molecular cornerstones. Results: Firstly, the malignant cells of HL evade the immune system by altered expression of PDL1/2, B2M and MHC class I and II due to various genetic alterations. Secondly, tumor growth is promoted by permanently activated JAK/STAT signaling due to pervasive mutations of multiple genes involved in the pathway. Thirdly, apoptosis of neoplastic cells is prevented by alterations of NF-κB compounds and the PI3K/AKT/mTOR axis. Additionally, Epstein-Barr virus infection can simultaneously activate JAK/STAT and NF-κB, similarly leading to enhanced survival and evasion of apoptosis. Finally, epigenetic phenomena such as promoter hypermethylation lead to the downregulation of B-lineage-specific, tumor-suppressor and immune regulation genes. Conclusion: The blueprint of HL genomics has been laid, paving the way for future investigations into its complex pathophysiology.
Understanding How Genetic Mutations Collaborate with Genomic Instability in Cancer
Authors: Jilderda Laura J. , Zhou Lin , Foijer Floris
Published: February 2021

Chromosomal instability is the process of mis-segregation for ongoing chromosomes, which leads to cells with an abnormal number of chromosomes, also known as an aneuploid state. Induced aneuploidy is detrimental during development and in primary cells but aneuploidy is also a hallmark of cancer cells. It is therefore believed that premalignant cells need to overcome aneuploidy-imposed stresses to become tumorigenic. Over the past decade, some aneuploidy-tolerating pathways have been identified through small-scale screens, which suggest that aneuploidy tolerance pathways can potentially be therapeutically exploited. However, to better understand the processes that lead to aneuploidy tolerance in cancer cells, large-scale and unbiased genetic screens are needed, both in euploid and aneuploid cancer models. In this review, we describe some of the currently known aneuploidy-tolerating hits, how large-scale genome-wide screens can broaden our knowledge on aneuploidy specific cancer driver genes, and how we can exploit the outcomes of these screens to improve future cancer therapy.
Limitation of Cytokinin Export to the Shoots by Nucleoside Transporter ENT3 and Its Linkage with Root Elongation in Arabidopsis
Authors: Korobova Alla , Kuluev Bulat , Möhlmann Torsten , Veselov Dmitriy , Kudoyarova Guzel
Published: February 2021

The trans-membrane carrier AtENT3 is known to transport externally supplied cytokinin ribosides and thus promote uptake by cells. However, its role in distributing either exogenous or endogenous cytokinins within the intact plant has not hitherto been reported. To test this, we used ent3-1 mutant Arabidopsis seedlings in which the gene is not expressed due to a T-DNA insertion, and examined the effect on the concentration and distribution of either endogenous cytokinins or exogenous trans-zeatin riboside applied to the roots. In the mutant, accumulation of endogenous cytokinins in the roots was reduced and capacity to deliver externally supplied trans-zeatin riboside to the shoots was increased suggesting involvement of equilibrative nucleoside (ENT) transporter in the control of cytokinin distribution in the plants. Roots of ent3-1 were longer in the mutant in association with their lower cytokinin concentration. We concluded that the ENT3 transporter participates in partitioning endogenous cytokinins between the apoplast and the symplast by facilitating their uptake by root cells thereby limiting cytokinin export to the shoots through the xylem. Dilution of the mineral nutrient solution lowered endogenous cytokinin concentration in the roots of both wild type (WT) and ent3-1 plants accompanied by promotion of root elongation. Nevertheless, cytokinin content was lower, while roots were longer in the ent3-1 mutant than in the WT under either normal or deficient mineral nutrition suggesting a significant role of ENT3 transporter in the control of cytokinin level in the roots and the rate of their elongation.
Nanocrystalline Oxides NixCo3−xO4: Sub-ppm H2S Sensing and Humidity Effect
Authors: Prikhodko Kseniya , Nasriddinov Abulkosim , Vladimirova Svetlana , Rumyantseva Marina , Gaskov Alexander
Published: February 2021

In this work, p-type oxide semiconductors, Co3O4 and complex oxides NixCo3−xO4 (x = 0.04, 0.07, 0.1), were studied as materials for sub-ppm H2S sensing in the temperature range of 90–300 °C in dry and humid air. Nanocrystalline Co3O4 and NixCo3−xO4 (x = 0.04, 0.07, 0.1) were prepared by coprecipitation of cobalt and nickel oxalates from nitrate solutions and further annealing at 300 °C. The surface reactivity of the obtained materials toward H2S both in dry and humid atmosphere (relative humidity at 25 °C R.H. = 60%) was investigated using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Sensor measurements showed a decrease in sensor signal toward 1 ppm H2S with an increase in Ni content because of a decrease in chemisorbed surface oxygen species. On the other hand, sensor signal increases for all samples with increasing the relative humidity that depends on reactivity of the surface hydroxyl groups, which stimulate the decomposition of surface sulfites and provide better surface regeneration at higher temperature. This assumption was additionally confirmed by the faster saturation of the conductivity curve and a decrease in the sensor response time in humid air.
Dysregulation of Ki-67 Expression in T Cells of Children with Autism Spectrum Disorder
Authors: Alhosaini Khaled , Ansari Mushtaq A. , Nadeem Ahmed , Attia Sabry M. , Bakheet Saleh A. , Al-Ayadhi Laila Y. , Mahmood Hafiz M. , Al-Mazroua Haneen A. , Ahmad Sheikh F.
Published: February 2021

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT–PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.
Does the Duration of Each Waldenström Stage Affect the Final Outcome of Legg–Calvé–Perthes Disease Onset before 6 Years of Age?
Authors: Oh Ho-Seok , Sung Myung-Jin , Lee Young-Min , Kim Sungmin , Jung Sung-Taek
Published: February 2021

The purpose of this study was to evaluate the outcomes of patients with Legg–Calvé–Perthes disease (LCPD) with disease onset before 6 years of age who were treated with conservative methods and to identify prognostic factors. Moreover, we evaluated the duration of the Waldenström stage and its correlation with the disease outcome. Disease severity was assessed using the lateral pillar classification, and the final outcome was evaluated using the Stulberg classification. We divided patients with LCPD into two groups according to the age at onset: group 1 (<4 years) and group 2 (4–6 years). The final outcomes of the two groups were compared. We also assessed the duration of each Waldenström stage. LCPD was noted in 49 hips of 49 patients. The lateral pillar class was A in one patient, B in 29 patients, and B/C or C in 19 patients. The Stulberg class was I or II (good) in 30 patients, III (fair) in 13 patients, and IV or V (poor) in six patients. The lateral pillar class significantly correlated with the final outcome. Groups 1 and 2 comprised 25 and 24 patients, respectively. The prevalence of good outcomes did not significantly differ between the groups (p = 0.162). The duration of the initial stage was 4.1 months in the good outcome group and 6.2 months in the fair or poor outcome group. The duration of the fragmentation stage of the femoral head was 5.9 months in the good outcome group and 11.9 months in the fair or poor outcome group. The durations of initial and fragmentation stages significantly differed between good outcome group and fair or poor outcome group (p = 0.009 and p < 0.001, respectively). The prognosis of patients with disease onset before the age of 6 years was favorable. The disease severity and duration of each Waldenström stage can be predictors of the outcome. Patients with prolonged initial and fragmentation stages showed worse outcomes and often required more active treatment to shorten the durations of the initial and fragmentation stages.
Development of an Actuator for Translatory Movement by Means of a Detented Switching Shaft Based on a Shape Memory Alloy Wire for Repeatable Mechanical Positioning
Authors: Schmelter Tobias , Theren Benedict , Fuchs Sebastian , Kuhlenkötter Bernd
Published: February 2021

Actuators based on the shape memory effect have recently become more and more economically important due to the many advantages of shape memory alloys (SMAs), such as their high energy density. SMAs are usually used to control the end/maximum positions, thus the actuators always move between two positions. The repeatable control of intermediate positions has so far proven difficult, because in most cases, external sensors are necessary to determine the length of the SMA element. Additionally control strategies for SMA actuators are rather complex due to the non-linear behavior of this material. The SMA actuator presented here is able to control intermediate positions with repeatable accuracy without the need of a separate control technology. The integrated control unit is based on a mechanical principle using a shaft with a circumference groove. This groove has a height profile that turns the shafts rotation, generated by the SMA, into a translational movement. Therefore, the SMA wire generates a partial stroke at each complete activation, turning the shaft partially. With several activation cycles in a row, the stroke adds up until reaching the maximum. A further activation cycle of the wire resets the actuators stroke to its initial position. Each part of the stroke can, thereby, be controlled precisely and repeatedly within the scope of each complete cycle of the actuator. Based on an integrated ratchet, each stroke of the actuator can hold energy free.