Miracle-dz/UniFAR-FTUs huggingface dataset:
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial

Abstract Purpose: Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844). Patients and Methods: Twenty patients with luminal breast carcinomas with PRA/PRB > 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment. Results: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling. Conclusions: Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients. See related commentary by Ronchi and Brisken, p. 833
Cytokeratin 13 (CK13) expression in cancer: a tissue microarray study on 10,439 tumors

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1–92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1–77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed – a usually weak – CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p < 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p = 0.0295) and shortened recurrence‐free (p = 0.0094) and overall survival (p = 0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p = 0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors.
Self-Deception Unmasked

Preface ix Chapter 1. Introduction: Approaches, Puzzles, Biases,and Agency 3 Chapter 2. Graden-Variety Straight Self-Deception: Some Psychological Process 25 Chapter 3. Self-Deception without Puzzles 50 Chapter 4. Attempted Empirical Demostrations of Strict Self-Deception 76 Chapter 5. Twisted Self-Deception 94 Chapter 6. Conclusion 119 Notes 125 References 137 Index 145
Anion Storage Chemistry of Organic Cathodes for High‐Energy and High‐Power Density Divalent Metal Batteries

Abstract Multivalent batteries show promising prospects for next‐generation sustainable energy storage applications. Herein, we report a polytriphenylamine (PTPAn) composite cathode capable of highly reversible storage of tetrakis(hexafluoroisopropyloxy) borate [B(hfip)4] anions in both Magnesium (Mg) and calcium (Ca) battery systems. Spectroscopic and computational studies reveal the redox reaction mechanism of the PTPAn cathode material. The Mg and Ca cells exhibit a cell voltage >3 V, a high‐power density of ∼∼3000 W kg−1 and a high‐energy density of ∼∼300 Wh kg−1, respectively. Moreover, the combination of the PTPAn cathode with a calcium‐tin (Ca−Sn) alloy anode could enable a long battery‐life of 3000 cycles with a capacity retention of 60 %. The anion storage chemistry associated with dual‐ion electrochemical concept demonstrates a new feasible pathway towards high‐performance divalent ion batteries.
Introduction to the Special Issue on Productive Aging in Honor of Frank Caro

This special issue covers topics related to productive aging around the globe, with data informing the studies coming from countries as diverse as Belgium, Italy, Korea, Spain, and the United States. The authors provide insights into productive aging research and explore potential strategies to handle key challenges posed by our 21 century aging societies. This special issue honors the legacy of Frank Caro, a pioneer in the area of productive aging. In his personal and professional life, Frank Caro studied and mobilized the productive potential of older people in society, organizing projects that responded to how society could draw more effectively on older adults to address community service needs, and creating new opportunities for productive participation of older adults (e.g., civic participation such as volunteering or providing long-term care).
Scaling the propulsive performance of heaving and pitching foils

Scaling laws for the propulsive performance of rigid foils undergoing oscillatory heaving and pitching motions are presented. Water tunnel experiments on a nominally two-dimensional flow validate the scaling laws, with the scaled data for thrust, power and efficiency all showing excellent collapse. The analysis indicates that the behaviour of the foils depends on both Strouhal number and reduced frequency, but for motions where the viscous drag is small the thrust closely follows a linear dependence on reduced frequency. The scaling laws are also shown to be consistent with biological data on swimming aquatic animals.
Continued P2X7 activation leads to mitochondrial fission and compromising microglial phagocytosis after subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) has a high rate of disability and mortality. Extremely damaging molecules, including adenosine triphosphate (ATP), are released from extravasated red blood cells and nerve cells, which activate microglia and induce sterile tissue injury and organ dysfunction. P2X purinoceptor 7 (P2X7) is one of the most important purine receptors on the microglial surface and is involved in the proinflammatory activation of microglia. While P2X7 can also affect microglial phagocytosis, the mechanism is not clear. Here, we demonstrated that microglial phagocytosis is progressively impaired under continued BzATP exposure and P2X7 activation. Furthermore, we found that P2X7 activation leads to increased intracellular Ca2+ levels and activates Calcineurin, which dephosphorylates dynamin‐related protein 1 (DRP1) S637. The dephosphorylation of DRP1 at S637 leads to increased mitochondrial fission and decreased mitochondrial function, which may be responsible for the decreased microglial phagocytosis. Finally, we pharmacologically inhibited P2X7 activation in mice, which resulted in rescue of mitochondrial function and decreased microglial proliferation, but improved phagocytosis after SAH. Our study confirmed that P2X7 activation after SAH leads to the impairment of microglial phagocytosis through mitochondrial fission and verified that P2X7 inhibition restores microglial phagocytosis both in vitro and in vivo.
Three‐ and five‐year follow‐up results of a randomized controlled trial on the effects of cognitive behavioral therapy before bariatric surgery

Abstract Objective Up to 37% of bariatric surgery patients suffer from insufficient weight loss or weight regain and mental health symptoms in the longer term. Cognitive behavioral therapy (CBT) may be an effective adjunct intervention to optimize patients' psychological functioning and weight loss results. To examine the value of adding preoperative CBT to bariatric surgery, three‐ and five‐year follow‐up data are presented. Method In this multi‐center randomized controlled trial (RCT; N = 130), a CBT group was compared to a treatment‐as‐usual (TAU) control group. Measurements were conducted at five time points: pretreatment (T0) and posttreatment/presurgery (T1) and at one‐ (T2; N = 120), three‐ (T3; N = 117), and five‐year postsurgery (T4; N = 115). The intervention group received a 10‐weeks, individual, preoperative CBT focused on self‐monitoring, identifying triggers for disordered eating and goal setting for eating behavior and physical exercise, as well as postoperative lifestyle. Outcome measures included weight change, eating behavior, eating disorders, depression, quality of life (QoL), and overall psychological health. Results Preoperative CBT was not associated with better three‐ and five‐year results than TAU regarding weight, dysfunctional eating behaviors, eating disorders, depression, overall psychological health, and QoL. Discussion Contrary to our hypothesis, three‐ and five‐year postsurgery differences between groups regarding weight change and mental health were not significant. Further exploration suggested that in both groups weight problems and depressive symptoms worsened at three and five‐year follow‐up. Future research should focus on long‐term postoperative monitoring of weight and mood and on associated postoperative interventions and their specific timing. Public Significance After bariatric surgery, in the longer term weight problems re‐occur in 30% of patients, which is probably partly related to psychopathology. We investigated whether cognitive behavior therapy (CBT) prior to bariatric surgery improved weight maintenance and mental health after surgery. Our study provided definite proof that preoperative CBT is not effective. Long‐term postoperative monitoring and prompt psychological intervention after first signs of deterioration, are important to prevent further problems.
Native defects in Al2O3 and their impact on III-V/Al2O3 metal-oxide-semiconductor-based devices

Al2O3 is a promising material for use as a dielectric in metal-oxide-semiconductor devices based on III-V compound semiconductors. However, the presence of deep levels and fixed charge in the Al2O3 layer is still a concern, with native defects being a possible cause of traps, leakage, and fixed charge. We report hybrid density functional calculations for vacancies, self-interstitials, and antisites in Al2O3. The energetic positions of defect levels are discussed in terms of the calculated band alignment at the interface between the oxide and relevant III-V materials. We find that oxygen vacancies are the defects most likely to introduce gap levels that may induce border traps or leakage current in a gate stack. In addition, both self-interstitials and aluminum vacancies introduce fixed charge that leads to increased carrier scattering in the channel and shifts the threshold voltage of the device.
L/sub /spl infin// identification in the frequency domain based on the set-membership approach

This paper is concerned with system identification for robust control in the frequency domain. The authors propose a new method for identification of both the nominal plant model and the uncertainty bounding function. The method produces the models that approximately minimize the given L/sub /spl infin// norm costs via the set-membership approach. In addition, the method is applicable to both continuous and discrete time systems. Numerical examples are given to demonstrate the validity of the proposed identification method.
Activities Performed by ASCO-Sponsored Oncology Student Interest Groups in Latin America: Assessing Members' Preferences and Leaders' Challenges

PURPOSE In response to the worldwide shortage of oncologists, ASCO established Oncology Student Interest Groups (OSIGs) to increase oncology exposure at medical schools. However, there is limited guidance on the activities they should undergo. The main purposes of this study were (1) to assess the preferences and perceptions of OSIG members about their group events and (2) to describe the difficulties faced by leaders to carry out OSIGs' tasks. METHODS In this multicenter, cross-sectional study, group members and leaders from five active Latin American OSIGs were invited to answer anonymous web-based surveys exploring members' attitudes toward group activities and leaders' challenges when carrying them out. Data collection was conducted from March to June 2021. RESULTS Responses from 142 medical students and four OSIGs leaders were analyzed. In total, 83% of student members considered that lectures with an oncology-related expert was very useful for increasing their overall interest in oncology. For increasing interest in cancer research, 87% deemed that participating in oncology research projects was very useful. Shadowing oncology professionals was very useful for at least 70% of members to increase their oncology knowledge and their interest in following an oncology-related career. Moreover, leaders' main challenges were having a high academic load, little response from members, lack of interesting ideas and protected time for OSIGs' events, and limited support from their school. CONCLUSION OSIGs' leaders, medical schools, and international oncology organizations should work together to design activities that increase medical students' exposure to oncology-related professionals and encourage their participation in international oncological events. These schools and organizations should actively support OSIG leaders when facing difficulties to prevent members' disengagement and groups' discontinuation.
In vitro versus cryo-induced capacitation of bovine spermatozoa, part 1: Structural, functional, and oxidative similarities and differences

Low temperatures during cryopreservation activate a cascade of changes, which may lead into irreversible damage and reduction of the fertilization potential, including the process of premature capacitation. The aim of our study was to evaluate the range of cell damage following the cryopreservation process and possible activation of cryocapacitation in bovine spermatozoa. For the experiments semen samples were obtained from 30 sexually mature Holstein bulls. Within the analysed parameters, we focused on the functional activity, structural integrity, capacitation status and oxidative profile. The samples were divided into three experimental groups, control (CTRL), in vitro capacitated (CAP) and cryopreserved (CRYO). Based on the collected data, there was a significant decrease in the sperm motility, mitochondrial membrane potential and concentration of cyclic adenosine monophosphate in the CRYO group when compared to CAP and CTRL (P<0.0001). A significant decrease (P<0.01; P<0.0001) in the membrane and acrosome integrity as well as DNA fragmentation index and a significant increase (P<0.0001) of necrotic cells were observed in the CRYO group. Following capacitation, a significant increase (P<0.01; P<0.0001) was recorded in the number of cells which underwent the acrosome reaction in the CRYO group against CAP and CTRL. Changes in the oxidative profile of the CRYO group indicates an increase (P<0.0001) in the reactive oxygen species generation, except for the superoxide radical, which was significantly higher (P<0.0001; P<0.001) in the CAP group in comparison with CRYO and CTRL. In summary, premature capacitation may be considered a consequence of cryopreservation and the assessed parameters could serve as physical markers of cryogenic damage to bovine spermatozoa in the future.
Exploring the limits to turning performance with size and shape variation in dogs.

Manoeuvrability, the ability to make rapid changes in direction, is central to animal locomotion. Turning performance may depend on the ability to successfully complete key challenges including; Withstanding additional lateral forces, Maintaining sufficient friction, Lateral leaning during a turn, and Rotating the body to align with the new heading. We filmed high-speed turning in domestic dogs (Canis lupus familiaris) to quantify turning performance and explore how performance varies with body size and shape. Maximal speed decreased with higher angular velocity, greater centripetal acceleration, and smaller turning radii supporting a force limit for wider turns and a friction limit for sharp turns. Variation in turning ability with size was complex, medium sized dogs produced greater centripetal forces, had relatively higher friction coefficients, and generally aligned the body better with the heading compared to smaller and larger bodied dogs. Body shape further had complex pattern, with longer forelimbs but shorter hindlimbs being associated with better turning ability. Further, while more crouched forelimbs were associated with an increased ability to realign the body in the direction of movement, more upright hindlimbs were related to greater centripetal and tangential accelerations. Thus, we demonstrate that these biomechanical challenges to turning can vary not only with changes in speed or turning radius, but also changes in morphology. These results will have significant implications for understanding the link between form and function in locomotory studies, but also in predicting the outcome of predator prey encounters.
Molecular and functional analysis of chitin synthase genes in Chilo suppressalis (Lepidoptera: Crambidae)

The rice stem borer, Chilo suppressalis, has developed a high level of resistance to many of the compounds currently used for control. There is therefore an urgent need to develop novel control methods for C. suppressalis. Insect chitin synthases (CHS) have attracted interest as a potential target for insect pest management. However, to date, CHS have not been characterized in C. suppressalis. Two CHS genes (CsCHS1 and CsCHS2) were identified and cloned from C. suppressalis. Two transcript variants were identified for CsCHS1, CsCHS1a and CsCHS1b. Spatiotemporal expression profiling showed that both transcripts of CsCHS1 are most highly expressed on the last day of each larval instar stage and show the highest expression levels in the integument. In contrast, CsCHS2 is predominantly expressed during the larval feeding stages and shows the highest expression levels in the midgut. Knockdown of CsCHS1 by RNA interference significantly inhibited the molting and pupation of C. suppressalis, and knockdown of CsCHS2 significantly affected growth during the larval stage, but had no significant effect on the pupation. Moreover, knockout of CsCHS1 by CRISPR/Cas9 genome editing severely lowered the hatching rate, larval survivorship, pupation rate, and eclosion rate, but only larval survivorship at the G0 generation was lowered after the knockout of CsCHS2. These results demonstrate that CsCHS1 and CsCHS2 play vital roles in the growth and development of C. suppressalis, and so have potential as insecticidal targets for the control of this highly damaging pest.
An Updated Review on the Treatment Strategy for Spinal Metastasis from the Spine Surgeon’s Perspective

Spinal metastasis is a common issue causing significant pain and disability in cancer patients. A multidisciplinary approach consisting of chemotherapy, radiotherapy, and surgical treatment is used for treating patients with metastatic spinal tumors. Due to recent advancements in medical and radiation oncology, like tumor genetics and stereotactic radiotherapy, this treatment strategy would change inevitably. Therefore, the decision-making systems developed for assisting physicians and surgeons to choose the most appropriate treatment for each patient with spinal metastasis need to evolve. In this review, the recent developments, validations, and modifications of these systems, as well as suggestions for future systems have been discussed. Recently, separation surgery combined with stereotactic radiotherapy (hybrid therapy) has gained popularity. Additionally, the evidence for hybrid therapy presented in the literature has been reviewed.
Transwell-Hypoxia Method Facilitates the Outgrowth of 3D-Printed Collagen Scaffolds Loaded with Cryopreserved Patient-Derived Melanoma Explants

A previous study from our laboratory demonstrated the effects of in vitro three-dimensional (3D)-printed collagen scaffolds on the maintenance of cryopreserved patient-derived melanoma explants (PDMEs). However, it remains unknown whether 3D-printed collagen scaffolds (3D-PCSs) can be harmonized with any external culture conditions to increase the growth of cryopreserved PDMEs. In this study, 3D-PCSs were manufactured with a 3DX bioprinter. The 3D-printed collagen scaffold-on-frame construction was loaded with fragments of cryopreserved PDMEs (approximately 1–2 mm). 3D-PCSs loaded with patient-derived melanoma explants (3D-PCS-PDMEs) were incubated using two types of methods: (1) in transwells in the presence of a low concentration of oxygen (transwell-hypoxia method) and (2) using a traditional adherent attached to the bottom flat surface of a standard culture dish (traditional flat condition). In addition, we used six different types of media (DMEM high glucose, MEM α, DMEM/F12, RPMI1640, fibroblast basal medium (FBM), and SBM (stem cell basal medium)) for 7 days. The results reveal that the culture conditions of MEM α, DMEM/F12, and FBM using the transwell-hypoxia method show greater synergic effects on the outgrowth of the 3D-PCS-PDME compared to the traditional flat condition. In addition, the transwell-hypoxia method shows a higher expression of the MMP14 gene and the multidrug-resistant gene product 1 (MDR1) than in the typical culture method. Taken together, our findings suggest that the transwell-hypoxia method could serve as an improved, 3D alternative to animal-free testing that better mimics the skin’s microenvironment using in vitro PDMEs.