Miracle-dz/UniFAR-FTUs huggingface dataset:
Pomalidomide, cyclophosphamide, and dexamethasone for elderly patients with relapsed and refractory multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP‐164 study)

Patients with transplant‐ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28‐day treatment cycle: pomalidomide (4 mg/day on days 1‐21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64‐86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7‐9.0) and 18.48 months (95% CI, 9.4‐27.6), respectively. The incidence rate of grade ≥ 3 non‐hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment‐associated infection is the main cause of morbidity and mortality.
The Well-Being of Carers of Older Aboriginal People Living in the Kimberley Region of Remote Western Australia: Empowerment, Depression, and Carer Burden

Objective: To describe demographic features and well-being of carers of Aboriginal Australians aged ≥45 years in remote Western Australia. Method: Carer burden, empowerment, and depression were assessed in 124 Aboriginal carers in four remote Aboriginal communities. Results: Carers were aged 38.8 ± 15.0 years, 73.4% were female, and 75.8% were children or grandchildren of the person cared for. The mean Zarit-6 score was 3.7 ± 3.6. Attending high school (odds ratio [OR] = 0.3; 95% confidence interval [CI] = [0.1, 0.7]) and feeling empowered (OR = 0.2; 95% CI = [0.1, 0.8]) were inversely associated with carer burden; female carers were less likely to feel empowered (OR = 0.4; 95% CI = [0.2, 0.9]); and empowerment was inversely associated with depression (OR = 0.3; 95% CI = [0.1, 0.7]). Discussion: Aboriginal carers in remote communities are relatively young and most are children or grandchildren. Carer burden was lower than anticipated. However, existing tools may not adequately measure Aboriginal perspectives. Education and empowerment are key factors which support programs must consider.
How Doctors Do Things with Empathy in Online Medical Consultations in China: A Discourse-analytic Approach

ABSTRACT It is widely acknowledged that doctors’ expressions of empathy are fundamental to a successful medical consultation. While extensive work has been done on empathic communication in face-to-face medical encounters, few studies explored expressions of empathy in online medical consultations. Such research is particularly scarce in Chinese contexts, even though China has recently seen substantial growth in e-healthcare activities. To gain a better understanding of clinical empathic communication in online environment, this study, using discourse-analytic tools, explores the pragmatic functions of doctors’ empathic responses in text-based online medical consultations in China. The study finds that most empathic responses by doctors can be said to perform the function of facilitating the institutional task of problem-solving, and a few serve the function of self-promotion that is likely to be triggered by the e-commerce model for online medical services.
Synergistic relationship between TSLP and IL‐33/ST2 signaling pathways in allergic rhinitis and the effects of hypoxia

The World Health Organization (WHO) has noted that allergic diseases are a major health problem of the 21st century. Allergic rhinitis (AR) is a type I allergic disease characterized by nasal mucosa and immune system abnormalities. AR is mediated by various inflammatory cells and is mainly characterized by altered secretion of cytokines. Thymic stromal lymphopoietin (TSLP) and the interleukin‐33/stimulation‐expressed gene 2 (IL‐33/ST2) signaling pathway are cytokines that play pivotal roles in many inflammatory responses and allergic reactions. There have been reports of interactions between the 2 pathways in many diseases. Hypoxia is a common pathologic manifestation of AR. The aim of this study was to explore the relationship and expressions and biologic functions of TSLP and IL‐33/ST2 in AR, and also to determine the effects of hypoxia on these cytokines.
Validation and multidimensional analysis of the japanese penn acoustic neuroma quality‐of‐life scale

In the management of vestibular schwannoma (VS), patient‐perceived outcomes should be given as much attention as physician‐reported objective outcomes. Concomitant symptoms can be annoying for sufferers, lowering quality of life (QoL). However, it is difficult to determine the degree to which these symptoms lower QoL using only objective measures. The Penn Acoustic Neuroma Quality of Life Scale (PANQOL) is a validated disease‐specific questionnaire commonly used to assess QoL in VS patients. It was developed and published in English. In this study, we translated the PANQOL questionnaire into Japanese and validated its reliability and utility. We also evaluated patient factors that could influence PANQOL scores.
Cerebral oxygen metabolism in adults with sickle cell disease

In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2) directly reflects oxygen supply and consumption and may therefore be more insightful than flow‐based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2. CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2‐prepared tissue relaxation with inversion recovery (T2‐TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P < .001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 μmol O2/100g/min, P = .69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P < .001), resulting in lower CMRO2 in patients versus controls (102 ± 24 versus 127 ± 20 μmol O2/100g/min, P = .002). After acetazolamide, CMRO2 declined further in patients (P < .01) and did not decline significantly in controls (P = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen‐deprived, hence increasing the risk of localized ischemia.
Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya

Objective HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies. Methods A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay. Results Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive. Conclusion HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.
Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma

Abstract Objectives: The current survival of patients with distal cholangiocarcinoma (dCCA) is poor. There is a need to develop new prognostic and predictive biomarkers to improve the survival of patients. Fibroblast activation protein (FAP) expression has been associated with survival in several solid malignancies. The goal of this study was to evaluate the expression pattern and prognostic significance of FAP in dCCA. Materials and methods: FAP expression was examined in 57 resected dCCA specimens and 28 paired lymph node metastasis specimens, as well as 10 benign bile ducts using immunohistochemistry. FAP expression was scored in the epithelial and stromal component of the dCCA specimens. The association between FAP expression and prognosis was evaluated using univariable and multivariable statistical modeling. Results: FAP expression was absent in the benign controls. FAP expression was evident in the epithelial 43 (75%) and stromal compartment 34 (60%) of dCCA. There was no association between epithelial or stromal FAP expression and clinicopathological factors. Epithelial FAP expression (HR 0.4 95% CI 0.20–0.78; p=.007) but not stromal FAP expression was significantly associated with better survival in univariable and multivariable analysis. Conclusions: FAP overexpression is evident in dCCA. There was a positive association between epithelial FAP expression and better survival which merits further evaluation.
Pyrroloquinoline quinone attenuates isoproterenol hydrochloride-induced cardiac hypertrophy in AC16 cells by inhibiting the NF-κB signaling pathway

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox co-factor that functions as an essential nutrient and antioxidant, and has been reported to exert potent anti-inflammatory effects. However, the therapeutic potential of PQQ for isoproterenol hydrochloride (Iso)-induced cardiac hypertrophy has not yet been explored, at least to the best of our knowledge. In the present study, the anti-inflammatory effects of PQQ were investigated in Iso-treated AC16 cells, a myocardial injury cellular model characterized by an increase in the apparent surface area of the cells and the activation of intracellular cardiac hypertrophy-associated proteins. The results revealed that pre-treatment with PQQ significantly inhibited the expression of cardiac hypertrophy marker proteins, such as atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain. PQQ also inhibited the activation of the nuclear factor (NF)-κB signaling pathway in Iso-treated AC16 cells, thus inhibiting the nuclear translocation of NF-κB and reducing the phosphorylation levels of p65. On the whole, the findings of this study suggest that PQQ may be a promising therapeutic agent for effectively reversing the progression of cardiac hypertrophy.
Individual and county-level variation in outcomes following non-fatal opioid-involved overdose

Background A lack of large-scale, individually linked data often has impeded efforts to disentangle individual-level variability in outcomes from area-level variability in studies of many diseases and conditions. This study investigated individual and county-level variability in outcomes following non-fatal overdose in a state-wide cohort of opioid overdose patients. Methods Participants were 24 031 patients treated by emergency medical services or an emergency department for opioid-involved overdose in Indiana between 2014 and 2017. Outcomes included repeat non-fatal overdose, fatal overdose and death. County-level predictors included sociodemographic, socioeconomic and treatment availability indicators. Individual-level predictors included age, race, sex and repeat non-fatal opioid-involved overdose. Multilevel models examined outcomes following non-fatal overdose as a function of patient and county characteristics. Results 10.9% (n=2612) of patients had a repeat non-fatal overdose, 2.4% (n=580) died of drug overdose and 9.2% (n=2217) died overall. Patients with a repeat overdose were over three times more likely to die of drug-related causes (OR=3.68, 99.9% CI 2.62 to 5.17, p<0.001). County-level effects were limited primarily to treatment availability indicators. Higher rates of buprenorphine treatment providers were associated with lower rates of mortality (OR=0.82, 95% CI 0.68 to 0.97, p=0.024), but the opposite trend was found for naltrexone treatment providers (OR=1.20, 95% CI 1.03 to 1.39, p=0.021). Cross-level interactions showed higher rates of Black deaths relative to White deaths in counties with high rates of naltrexone providers (OR=1.73, 95% CI 1.09 to 2.73, p=0.019). Conclusion Although patient-level differences account for most variability in opioid-related outcomes, treatment availability may contribute to county-level differences, necessitating multifaceted approaches for the treatment and prevention of opioid abuse.
Biomarker recommendation for PD‐1/PD‐L1 immunotherapy development in pediatric cancer based on digital image analysis of PD‐L1 and immune cells

Anti‐PD‐1/PD‐L1 immunotherapy could offer an alternative to traditional chemo‐ and/or radiotherapy to treat pediatric cancer patients. To unveil the potential benefit of this new therapeutic approach, the prevalence of PD‐L1 and other relevant immune markers using quantitative digital image analysis (DIA) could help to clarify this point. A bridging study was first conducted using commercially available normal formalin‐fixed paraffin‐embedded (FFPE) tonsils to compare immunostaining patterns and intensities from PD‐L1, tumor infiltrating lymphocyte (TIL) markers CD3, CD8, FoxP3, CD45RO, and macrophage marker CD68 in adult (n = 5) and pediatric (n = 10) samples. Then, commercially available pediatric FFPE tumor samples from five prevalent pediatric solid tumor indications: ganglioneuroblastoma (n = 7); neuroblastoma (n = 23); nephroblastoma (n = 30); osteosarcoma (n = 24); and rhabdomyosarcoma (n = 25) were immunostained and their images (n = 654) digitally analyzed using predefined algorithms. The qualitative analysis of staining patterns and intensities in all 15 tonsils for all 6 biomarkers was similar regardless of age category. Quantitative DIA showed that PD‐L1 values varied across cancer‐types, nephroblastoma having the lowest counts. PD‐L1 counts in ganglioneuroblastoma, our pediatric indication with the highest average value, was approximately 12‐times lower than in a similar nonsmall cell lung cancer study, an indication approved for anti‐PD‐1/PD‐L1 immunotherapies. Variable values were measured for the TIL markers CD3, CD8, and CD45RO. FoxP3 was scant across all indications. The macrophage marker CD68 showed highest values in ganglioneuroblastoma, with lowest levels in nephroblastoma. In conclusion, the low PD‐L1 levels uncorrelated with TIL values from the present biomarker morphological study suggest that a PD‐L1 immunohistochemistry patient selection strategy used for anti‐PD‐1/PD‐L1 monotherapy in adult tumors may not succeed in these pediatric indications.
Dystrophic microglia in late‐onset Alzheimer's disease

Here, we summarize current understanding of functional involvement of microglial cells in the most common neurodegenerative disease to affect humans, which is sporadic or late‐onset Alzheimer's disease (LOAD). Our review narrowly focuses on insights obtained from post‐mortem neuropathological examinations of human brains paying particular attention to microglia as these cells have long been implicated as pivotal players in the cellular processes that lead to AD‐type neurodegeneration. Although complete understanding of the roles played by microglia in AD neurodegeneration remains elusive, our studies thus far have illuminated microglial involvement in LOAD, showing that microglial dystrophy, the morphological manifestation of senescence, can be integrated with other hallmark pathological features of AD, such as intraneuronal neurofibrillary degeneration (NFD) and extracellular deposits of amyloid‐beta (Aβ) protein. We have demonstrated an in situ correlation between microglial dystrophy and presence of NFD suggesting that neurodegeneration is secondary to aging‐related microglial deterioration, a concept founded on the notion that proper neuronal function is dependent on presence of healthy microglia. Diseased or weakened glia are detrimental for neuronal well‐being because their ability to provide neuronal support may be impaired. Our most recent work also links microglial dystrophy with Aβ deposits by showing that there is a chronic, yet futile microglial reaction to insoluble amyloid deposits. This inability of microglia to remove aggregated amyloid (a foreign body) causes microglial exhaustion and thereby exacerbates already ongoing aging‐dependent microglial deterioration. An eventual total loss of functional microglia in advanced LOAD promotes widespread NFD, dementia, and brain failure.
Highly Efficient and Tunable Filtering of Electrons' Spin by Supramolecular Chirality of Nanofiber‐Based Materials

Organic semiconductors and organic–inorganic hybrids are promising materials for spintronic‐based memory devices. Recently, an alternative route to organic spintronic based on chiral‐induced spin selectivity (CISS) is suggested. In the CISS effect, the chirality of the molecular system itself acts as a spin filter, thus avoiding the use of magnets for spin injection. Here, spin filtering in excess of 85% in helical π‐conjugated materials based on supramolecular nanofibers at room temperature is reported. The high spin‐filtering efficiency can even be observed in nanofibers assembled from mixtures of chiral and achiral molecules through chiral amplification effect. Furthermore and most excitingly, it is shown that both “up” and “down” orientations of filtered spins can be obtained in a single enantiopure system via the temperature‐dependent helicity (P and M) inversion of supramolecular nanofibers. The findings showcase that materials based on helical noncovalently assembled systems are modular platforms with an emerging structure–property relationship for spintronic applications.
Rethinking Repetition: Selective Scanpath Recapitulation Supports Mnemonic Performance on a Change Detection Task

Stimulus repetition improves processing efficiency and performance on a variety of mnemonic tasks. When images are successfully retrieved from memory, the accompanying pattern of fixations or “scanpath” is highly similar to that elicited during encoding. However, it remains unclear how scanpath repetition promotes efficiency gains on goal-directed tasks. The present study used eye-movement monitoring to test the predictions of scanpath theory against a repeated change detection task. Fixations at repeated-viewing were highly similar to first and final novelviewing fixations, suggesting that speeded search results from a strategic collapsing of the encoding scanpath based on goal-productivity of novel-viewing fixations. Moreover, older adults repeated more initial encoding fixations than younger adults, designating a specialized role for memory in repetition of the recognition sequence. Results support and extend theories of eyemovement-based repetition effects to account for efficiency gains on change detection as a function of goal-relevance and memory.
MULTIPLE ROLES AND SENSE OF IDENTITY AMONG WOMEN IN EARLY AND LATER ADULTHOOD

The article presents the results of a study conduct e on a sample of 80 women aged 19-25 and 72 women aged 40-74. The relationships of the two comp onents of self-complexity (the quantity of self-aspects and the amount of overlap between thei r contents) with the multidimensionally defined sense of identity were examined. Additionally, phas e of life differences in the magnitude of these relationships were also investigated. I used the Se lf-Complexity Questionnaire (SCQ; Barczak, Besta, & Bazi ńska, 2007) and the Multidimensional Questionnaire o f Identity (MQI; Pilarska, 2012). The obtained results showed that the predict ive importance of the number of roles for the sense of identity was marginal, whereas the similar ity in the content of roles seemed to favor maintaining the sense of identity. In addition, althoug h significant differences were observed in the self -concept structure and the strength of the sense of identity between the two groups of women, the relationships between these areas of personality we re not affected by the phase of the life cycle.
Plastic Dynamic Response of Simply Supported Thick Square 1 Plates Subject to Localised Blast Loading 2

Plastic Dynamic Response of Simply Supported Thick Square 1 Plates Subject to Localised Blast Loading 2 N. Mehreganiana, A. S. Fallahb,c*, L.A. Loucaa 3 a Department of Civil & Environmental Engineering, Skempton Building, South Kensington Campus, Imperial 4 College London, London SW7 2AZ, UK 5 b Department of Aeronautics, Roderic Hill Building, South Kensington Campus, Imperial College London, 6 London SW7 2AZ, UK 7