Miracle-dz/UniFAR-FTUs huggingface dataset:
Methotrexate treatment suppresses osteoblastic differentiation by inducing Notch2 signaling and blockade of Notch2 rescues osteogenesis by preserving Wnt/β‐catenin signaling

Methotrexate (MTX) is a commonly used antimetabolite in cancer treatment. Its intensive use is linked with skeletal adverse effects such as reduced bone formation and bone loss, and yet little information is available on molecular mechanisms underlying MTX‐induced impaired bone formation. This study investigated the effects of MTX treatment at a clinical chemotherapy relevant dose on osteogenic differentiation in MC3T3E1 osteoblastic cells. To investigate the potential mechanisms, the expression of 87 genes regulating osteoblast differentiation and bone homeostasis was screened in MTX‐treated versus untreated cells by polymerase chain reaction (PCR) arrays and results illustrated significant upregulation of Notch2 and Notch target genes at both early and late stages of MC3T3E1 differentiation following MTX treatment. To confirm the roles of Notch2 pathway and its potential action mechanisms, MC3T3E1 cells were treated with MTX with an anti‐Notch2 neutralizing antibody or control IgG and effects were examined on osteogenesis and activation of the Wnt/β‐catenin pathway. Our results demonstrated that induction of Notch2 activity is associated with MTX adverse effects on osteogenic differentiation and blocking Notch2 rescues osteoblast differentiation by preserving activation of the Wnt/β‐catenin pathway.
“Isn’t There Any Other Way than Calling the Cops?”: How Differences in Initiation of Police Intervention Influence Survivor Safety

As formal crisis responders, police are trained in de-escalation tactics that are expected to mitigate intimate partner violence and promote survivor safety. However, the alignment between expected and actual practice of police intervention varies, especially when the survivor does not initiate the call, police treat the survivor poorly, or provide an undesirable arrest outcome. At best, unsuccessful interventions do not change survivors’ risk level, and at worse, elevate their risk of experiencing harm. The purpose of this qualitative study was to explore survivors’ perspectives on the process of police intervention, specifically how variations in initiation, quality of engagement, and arrest influence survivors’ safety. Twenty-four women whose partners were in a relationship violence intervention program were recruited to participate in the study. Results showed that many survivors described a range of ongoing, strategic violence perpetrated by their partners that required intervention; yet the complex nature of the violence often extended beyond police capacity. Either survivors called the police, or they were initiated externally by neighbors or strangers; some survivors had dual initiations. Whether survivors reported that police used safety practices during the intervention was related to who initiated the police. Arrests of abusive partners were inconsistent, and they varied based on number of previous calls to the police and visible signs of injury. Survivors of color, specifically Black women, self-initiated at higher rates, experienced fewer safety strategies used by police, and had fewer arrests. No matter the outcomes of police intervention, survivors actively engaged in strategies outside of formal systems to protect themselves and their families. Study results imply that police intervention may be ill-suited to support survivors’ safety goals and highlight a need for alternative interventions focused on de-escalation and prevention.
A calculation method of field current of synchronous machines at sudden short‐circuit

The mutual leakage reactance between D‐axis damper and field windings is ignored in conventional D‐axis equivalent circuits. It has been pointed out, however, that the calculated value of the field current differs considerably from the measured value if this reactance is not taken into account. This is due to the difficulty of determining the physically correct damper winding impedance value. A method of determining the equivalent circuit constants using the mutual leakage reactance has been reported previously, where the D‐axis damper winding time constant is measured from the upper and lower envelopes of field current at sudden three‐phase short‐circuit. Yet there are machines for which the upper and lower envelopes of field current are not readily established, and in this case the method is unsatisfactory. The authors describe a method to accurately identify the equivalent circuit constants taking into account the mutual leakage reactance, using a standstill test with a small‐capacity DC power supply (DC decay testing method). The field current at sudden short‐circuit can be simulated accurately using these equivalent circuit constants. The validity of the proposed method is demonstrated by implementation results on two salient‐pole synchronous machines at the same specifications (one with damper winding, the other without). Furthermore, the dependent relation between the armature leakage reactance and mutual leakage reactance, as well as its influence on the calculation of field transient currents, are made clear. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 151(3): 61–70, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20113
Assembly of Bioactive Nanoparticles via Metal–Phenolic Complexation

The integration of bioactive materials (e.g., proteins and genes) into nanoparticles holds promise in fields ranging from catalysis to biomedicine. However, it is challenging to develop a simple and broadly applicable nanoparticle platform that can readily incorporate distinct biomacromolecules without affecting their intrinsic activity. Herein, a metal–phenolic assembly approach is presented whereby diverse functional nanoparticles can be readily assembled in water by combining various synthetic and natural building blocks, including poly(ethylene glycol), phenolic ligands, metal ions, and bioactive macromolecules. The assembly process is primarily mediated by metal–phenolic complexes through coordination and hydrophobic interactions, which yields uniform and spherical nanoparticles (mostly <200 nm), while preserving the function of the incorporated biomacromolecules (siRNA and five different proteins used). The functionality of the assembled nanoparticles is demonstrated through cancer cell apoptosis, RNA degradation, catalysis, and gene downregulation studies. Furthermore, the resulting nanoparticles can be used as building blocks for the secondary engineering of superstructures via templating and cross‐linking with metal ions. The bioactivity and versatility of the platform can potentially be used for the streamlined and rational design of future bioactive materials.
Late‐life exercise mitigates skeletal muscle epigenetic aging

There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late‐life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial‐specific examination of methylation, targeted high‐resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late‐life PoWeR from 22–24 months of age modestly but significantly attenuates an age‐associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR‐trained for eight weeks was approximately eight weeks younger than 24‐month‐old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging.
Antibody-drug conjugates in HER2-positive breast cancer

Abstract Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
The Economic Peace Between Democracies: Economic Sanctions and Domestic Institutions

This article argues that the influence of democratic institutions in international relations extends beyond the military realm and into the economic. The authors extend Bueno de Mesquita et al.’s institutional theoryof political regimes to explain the use and variety of economic sanctions in world politics. It is argued that democracies impose sanctions more oftenthan other regime types because they encompass a greater variety of interest groups. Yet, institutional incentives for successful foreign policies lead democracies to prefer sanctioning non-democracies instead of democracies.The pacifying influence of jointly democratic regimes, then, extends into the economic realm. Further, these same institutional incentives account forvariation across regime types in the choice of sanctions used and the goalspursued. Owing to incentives to minimize harm to their public and achieve successful foreign policies, democratic regimes are more likely than non-democracies to impose financial sanctions and pursue minor foreign policy goals. The authors use the Hufbauer, Schott & Elliott sanctions dataset to empirically evaluate each hypothesis. The empirical analysis supports the argument that domestic political institutions affect the incentives of leaders and, therefore, the foreign policies of states.
Video Head Impulse Test in Darkness, Without Visual Fixation: A Study on Healthy Subjects

Objective: The head impulse test (HIT) is triggered by the vestibulo-ocular reflex (VOR), complemented by the optokinetic and pursuit systems. This study aimed to evaluate the possibility of individualizing the VOR contribution to the HIT. Design: Thirty-six healthy individuals (19 males, 17 females; age 21–64 years, mean 39 years) underwent horizontal video HIT (vHIT). This was first conducted in darkness, without visual fixation, and then visually tracked. Results: Seventy percent of the impulses delivered ocular responses opposite to the direction of the head, matching its velocity to a point where quick anticompensatory eye movements (SQEM) stopped the response (SQEM mean latency 58.21 ms, interquartile range 50–67 ms). Of these, 75% recaptured the head velocity after culmination. Thirty percent of the responses completed a bell-shaped curve. The completed bell-shaped curve gains and instantaneous gains (at 40, 60, and 80 ms) before SQEM were equivalent for both paradigms. Females completed more bell-shaped traces (42%) than males (15%); p = 0.01. The SQEM latency was longer (62.81 versus 55.71 ms, p < 0.01), and the time to recapture the bell-shaped curve was shorter (77.51 versus 92.52 ms, p < 0.01) in females than in males. The gains were comparable between sexes in both paradigms. Conclusions: The VOR effect can be localized in the first 70 ms of the vHIT response. In addition, other influences may take place in estimating the vHIT responses. The study of these influences might provide useful information that can be applied to patient management.
Rapid Comprehension of Verbal and Symbolic Traffic Sign Messages

A “same”-“different” reaction time procedure was used in two experiments to measure the times required to comprehend the meanings of projected slides of traffic signs. The results indicated that signs with symbolic messages could be understood more quickly than those with verbal messages. Visually degrading the signs resulted in a greater decrement in performance for verbal than for symbolic signs. Correlational analyses demonstrated reaction time to correlate significantly with a previously obtained measure of sign legibility taken from a moving motor vehicle on a roadway. The utility of reaction time as an index of traffic sign adequacy is discussed along with some possible practical implications of the research.
Military Airframe Costs. The Effects of Advanced Materials and Manufacturing Processes

Abstract : Good cost estimates can make important contributions to effective acquisition policy. RAND has a long history of producing cost-estimating methodologies. Two of its more recent studies are Hess and Romanoff (1987) and Resetar, Rogers, and Hess (1991). This report both updates and extends these earlier studies, focusing on the effects of material mix, manufacturing technique, and part geometric complexity on cost. We collected two types of information on these effects. First, we surveyed the military airframe industry for estimates of how aircraft production costs vary with airframe structure material mix. Second, we analyzed a large set of actual part data from recent aircraft manufacturing efforts that we collected from industry. We also estimated a set of airframe relationships (CERs) for labor hours based on MACDAR, a historical airframe database. We then integrated the effects of material mix into these estimates.
Estrogen and Progesterone Therapy and Meningiomas.

Meningiomas are common intracranial tumors with female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA- associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple; may harbor P1K3CA mutations in up to 1/3 of cases and are favored by a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs. non treated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive (OC) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment.
What stands behind the gender gap in entrepreneurship? Untangling the intergenerational parental role

This research examines the entrepreneurship gender gap by offering an additional novel explanation for the higher share of men in entrepreneurial activity focusing on intergenerational parental role. Participants (N = 1288) aged 18–81, including 259 actual entrepreneurs, completed questionnaires about entrepreneurship tendency, personality traits and socioeconomic background. The gender gap in actual entrepreneurship continues a significant difference in entrepreneurial tendency, which is developed in the first and the second stages of the entrepreneurial trajectory. When women reach the third stage of entrepreneurial development, the execution stage, they have already acquired a self-perception of an incapable and incommensurate entrepreneurial personality. The results indicate that role modeling behavioral channel significantly accounts for the gender gap in entrepreneurial personality. The results suggest that both parents contribute to women’s’ inferior perception of entrepreneurial personality and that their contribution affects all four aspects of the entrepreneurial tendency. It appears that the impact of fathers’ role modeling is larger than that of mothers, and furthermore fathers transfer other entrepreneurial role models from their side in the family.
Use of antifibrotic drugs in familial interstitial pneumonia: analysis of one family

Familial interstitial pneumonia (FIP) is defined as the occurrence of interstitial lung disease (ILD) in two or more individuals within the same family. (1,2) The majority of FIP kindreds present autosomal dominant inheritance with a pattern of incomplete penetrance. (2) The prevalence of idiopathic pulmonary fibrosis (IPF) among patients with FIP is 0.5% 20.0%; nonetheless, FIP has also been reported in fibrotic hypersensitivity pneumonitis (fHP) and connective tissue disease-associated ILD. (2,3)
Augmentation index and pulse wave velocity in normotensive versus preeclamptic pregnancies: a prospective case–control study using a new oscillometric method

Abstract Objectives The objective of this study was to investigate whether oscillometric AS measurements are different in pregnant women with and without preeclampsia (PE). Study design This was a prospective case–control study in singleton pregnancies that had been diagnosed with PE (n = 46) versus normotensive controls (n = 46) between 2014 and 2019. In the case group, pregnancies complicated by PE were classified as either early-onset (<34 weeks of gestation) or late-onset (≥34 weeks of gestation) PE and subgroup analysis was performed. Main outcome measures Pulse wave velocity (PWV), augmentation index (Alx), and Alx at a heart rate of 75 beats per minute (Alx-75) were measured using a brachial cuff-based automatic oscillometric device (Mobil-O-Graph 24 h PWA). Results In pregnancies complicated by PE, in comparison with normotensive pregnancies, there were significant differences in PWV (p ˂ .001), and Alx-75 (p ˂ .001). In pregnancies complicated by early-onset PE, in comparison with pregnancies complicated by late-onset PE, there were significant differences in PWV (p = .006), and Alx-75 (p = .009). There was no significant difference in Alx in either of the analyses. Conclusions PWV and Alx-75 are higher in pregnancies complicated by PE, in comparison with normotensive pregnancies, as well as in early-onset PE, in comparison with late-onset PE. Key messages Pulse wave velocity is higher in pregnancies complicated by preeclampsia. Augmentation index at a heart rate of 75 beats per minute is higher in pregnancies complicated by preeclampsia. Arterial stiffness assessment is a promising risk-stratification tool for future cardiovascular complications but further studies are required.
Single Cord Blood Transplantation Versus HLA-Haploidentical-related Donor Transplantation Using Posttransplant Cyclophosphamide in Patients With Hematological Malignancies

Background. Unrelated cord blood (UCB) and haploidentical related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a HLA-matched donor. Methods. We conducted a retrospective study using registry data from the Kyoto Stem Cell Transplantation Group for patients with hematological malignancies who received their first allogeneic hematopoietic cell transplantation using a single UCB unit (n = 460) or PTCy-haplo (N = 57) between 2013 and 2019. Results. We found that overall survival in the UCB group was comparable to that in the PTCy-haplo group (hazard ratio, 1.00; 95% confidence interval, 0.66-1.52), although neutrophil and platelet engraftment were significantly delayed. Nonrelapse mortality risk and the incidence of graft-versus-host disease in the UCB group were also comparable to those in the PTCy-haplo group. Although the relapse risk was similar between the UCB group and the PTCy-haplo group regardless of the disease risk, acute myeloid leukemia patients benefit from UCB transplant with a significantly lower relapse rate (hazard ratio, 0.38; 95% confidence interval, 0.18-0.76). Conclusions. UCB transplant gives outcomes comparable to PTCy-haplo transplant, and both UCB and PTCy-haplo units are suitable as alternative donor sources for patients without an HLA-matched sibling or unrelated donor.
Analysis of muscle tissue in vivo using fiber-optic autofluorescence and diffuse reflectance spectroscopy

Abstract. Significance: Current methods for analyzing pathological muscle tissue are time consuming and rarely quantitative, and they involve invasive biopsies. Faster and less invasive diagnosis of muscle disease may be achievable using marker-free in vivo optical sensing methods. Aim: It was speculated that changes in the biochemical composition and structure of muscle associated with pathology could be measured quantitatively using visible wavelength optical spectroscopy techniques enabling automated classification. Approach: A fiber-optic autofluorescence (AF) and diffuse reflectance (DR) spectroscopy device was manufactured. The device and data processing techniques based on principal component analysis were validated using in situ measurements on healthy skeletal and cardiac muscle. These methods were then applied to two mouse models of genetic muscle disease: a type 1 neurofibromatosis (NF1) limb-mesenchyme knockout (Nf1Prx1 − / − ) and a muscular dystrophy mouse (mdx). Results: Healthy skeletal and cardiac muscle specimens were separable using AF and DR with receiver operator curve areas (ROC-AUC) of >0.79. AF and DR analyses showed optically separable changes in Nf1Prx1 − / − quadriceps muscle (ROC-AUC >0.97) with no differences detected in the heart (ROC-AUC <0.67), which does not undergo gene deletion in this model. Changes in AF spectra in mdx muscle were seen between the 3 week and 10 week time points (ROC-AUC = 0.96) and were not seen in the wild-type controls (ROC-AUC = 0.58). Conclusion: These findings support the utility of in vivo fiber-optic AF and DR spectroscopy for the assessment of muscle tissue. This report highlights that there is considerable scope to develop this marker-free optical technology for preclinical muscle research and for diagnostic assessment of clinical myopathies and dystrophies.