bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in efficacy of first-line abiraterone in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Marar Mallika , Long Qi , Mamtani Ronac , Narayan Vivek , Vapiwala Neha , Parikh Ravi Bharat 
Published: March 2021

20 Background: Prospective studies suggest that abiraterone (Abi) use in mCRPC is associated with improved progression-free survival in African-American (AA) patients (pts) compared to non-Hispanic White (NHW) pts. It is unclear whether racial disparities in Abi effectiveness exist for pts with mCRPC treated in real-world practice. Methods: In this retrospective cohort study, we used the nationwide Flatiron Health electronic health record-derived de-identified database to select pts who received first-line (1L) systemic therapy for mCRPC between January 1, 2012 and December 31, 2018. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression models of comparative effectiveness, using age, race, comorbidity index, prostate-specific antigen (PSA), baseline steroid or opioid use, insurance status, practice type, practice Abi prescribing rate, and practice region as covariates. The primary exposure was treatment with 1L Abi. Overall survival (OS) was the primary outcome, and time-to-next-treatment (TTNT), using Fine-Gray models with death as a competing risk, was the secondary outcome. Racial disparities between Abi vs. no Abi groups were explored with stratified analyses by race and race-treatment interaction terms. Results: Of 3808 pts, 1729 (45.4%) received 1L Abi, 1255 (33.0%) received 1L enzalutamide, and 549 (14.4%) received 1L docetaxel. The cohort included 2165 (68.7%) NHW and 404 (10.6%) AA pts. Pts receiving Abi were older (mean age 74 vs. 72) and more likely to be treated at academic centers (8% vs. 6%) than pts not receiving Abi. Among pts receiving Abi, AAs had improved OS compared to NHWs (Table). Compared to receipt of a non-Abi regimen, receipt of Abi was not associated with OS among AA pts but was associated with decreased OS among NHW pts. A significant race-by-treatment interaction for OS existed among patients receiving 1L Abi (interaction coeff = 0.27 95% CI = 0.02-0.53). There were no race-based disparities found in TTNT. Conclusions: In a large real-world analysis of pts who received 1L systemic therapy for mCRPC, AAs who received Abi had improved OS compared to NHWs – a finding consistent with ABI-RACE (NCT01940276). Among NHW pts, 1L Abi was associated with decreased OS. These real-world data suggest race-based differences in therapeutic response to Abi and future prospective evidence is needed to assess drivers of differential Abi efficacy in mCRPC. [Table: see text]
The positive impact of implementing an onsite guideline-based genetic testing procedure for prostate cancer in a multidisciplinary uro-oncology clinic.
Authors: Ramanathan Siddharth , Ramanathan Sadhna , Korman Andrew , Ballouz Samer , Ghilezan Michael , Levin Michael , Wojno Kirk , Martinez Alvaro , Korman Howard , Balaraman Savitha 
Published: March 2021

234 Background: Prior to the guidelines set forth by the 2017 Philadelphia consensus conference, genetic testing for prostate cancer was conducted based on personal and family history of malignancies pursuant to NCCN recommendations. The 2017 guidelines expanded testing criteria to included age at diagnosis, metastatic disease, and tumor sequencing. In spite of these advancements, limited literature is available regarding successful implementation of a streamlined system for genetic testing in prostate cancer. This paper explores the benefits of implementing an on-site guideline-based genetic testing process for prostate cancer patients treated at a multi-disciplinary uro-oncology practice. Methods: Data was retrospectively reviewed for 561 prostate cancer patients seen in a multi-disciplinary uro-oncology clinic since January 2017. Prior to January, 1, 2019 genetic testing was recommended to patients based on NCCN guidelines, and swabs for testing were procured off-site less than 1 mile from the clinic (n=107). After January, 1, 2019 genetic testing was recommended based on the guidelines set forth by the Philadelphia consensus conference, and swabs for testing were procured at the clinic itself (n=454). Results: A statistically significant increase in compliance with genetic testing was observed after the implementation of an on-site, guideline-based testing process. Patient compliance with genetic testing increased from 33.6% to 96.5%. The time to receive the genetic test results (calculated as the time between referral for genetic testing and obtaining the test results) was also significantly improved from 38 days to 21 days. Conclusions: The implementation of an on-site, guideline-based genetic testing model for prostate cancer patients significantly improved compliance with genetic testing to 96.5% and decreased the time to receive genetic test results by 17 days. Overall, adopting a guide-line based model with on-site genetic testing has the potential to significantly improve the detection rate for pathogenic and actionable mutations, increase the utilization of targeted therapies, and increase cascade testing to include at-risk family members.
Localized activation of the metastatic phenotype within the perineural region in prostate cancer.
Authors: Brown Mick D. , Hart Claire Alexandre , Sachdeva Ashwin , Faulkner Christian , Wedge David , Clarke Noel W. 
Published: March 2021

253 Background: Perineural Invasion (PNI) is defined as malignant epithelial cell invasion of the perineural space and nerves. Despite widespread acknowledgement of the clinical significance of PNI as a PCa pathological finding associated with recurrence, increased risk of bone metastasis and poor survival, the molecular mechanism underlying this pathology is relatively unknown. The malignant epithelial cells within the PNI potentially provides a spatially defined “snapshot” of disease progression, as the cells switch to a more migrational phenotype associated with metastatic progression. Here we present the initial spatial PNI phenotypic characterisation in PCa. Methods: Archival FFPE blocks, with associated full clinical history, from patients who underwent a radical prostatectomy for prostate cancer were retrieved under research ethics REC#07/H1003/161+5 10_NOCL_02. Biomarkers EphA2, pEphA2s897, pMLC2, E-Cadherin, Vimentin, TOMM20, MTC01, NDUFB8, PTEN were assessed on 4µm serial sections stained using a multiplex TSA protocol, with S100, pan-cytokeratin and DAPI acting as landmarks, on a Ventana Discovery platform prior to scanning on a Versa 3 platform with Halo image analysis. Prostate zones were defined at 500µm intervals either side of the prostate capsule. Univariate and multivariate (hierarchical clustering, UMap clustering) expression analysis and correlation with clinic-pathological features was conducted within R. Results: The PNI epithelial cells within each spatial zone of the prostate are significantly different to each other (Kruskal-Wallis test p < 2.2x10−16 except for MTC01 p = 5.3x10−10). In comparison with the local tumour lesion, PNI epithelial cells localised within 1000µm of the prostate edge and outside the tumour lesion, have undergone a migrational switch, gaining features associated with an activated metastatic phenotype, with increased expression of amoeboid signalling (EphA2, pEphA2s897, pMLC2) and mitochondrial defects (loss of Complex I and IV, gain of mitochondrial mass (TOMM20)). Patients clustering by multivariate expression trends across the prostate regions showed 4 distinct patient groups, with PNI epithelial cells in patient group 1 & 2 displaying a more epithelial to mesenchymal (EMT) phenotype, especially in the first 1000µm inside the prostate organ. Conclusions: Cells within PNI close to the edge of the prostate have features consistent with a switch to migrational/metastatic activation in contrast to the more indolent cell type found deeper within the tumour. Further characterisation of this localised migrational upregulation will help in understanding the transition from a localised to a metastatic phenotype.
Q-TWiST analysis of tivozanib (T) versus sorafenib (S) in patients with advanced renal cell carcinoma (RCC) in the TIVO-3 study.
Authors: Szarek Michael , Needle Michael N. , Rini Brian I. , Pal Sumanta K. , McDermott David F. , Atkins Michael B. , Hutson Thomas E. , Escudier Bernard 
Published: March 2021

298 Background: In the randomized phase III study TIVO-3, the VEGFR-TKI tivozanib (TIVO) increased progression-free survival with better tolerability but no difference in overall survival (OS) relative to sorafenib (SORA) as third- or fourth-line therapy in patients with metastatic RCC. These results provide motivation to apply quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of TIVO, in the presence of similar survival, when compared to SORA. Methods: In application of Q-TWiST, patient-level OS was subdivided into three mutually exclusive states: time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after progression/relapse (REL). Mean Q-TWiST was calculated by applying utility coefficients of 0.5, 1.0, and 0.5 to the restricted mean (max 36 months follow-up) health states of TOX, TWiST, and REL, respectively; 95% CIs for the means and mean differences were estimated by bootstrap distributions. Relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the SORA mean OS. Results: Mean TWiST was significantly longer for TIVO than for SORA (10.30 months v.5.35 months; Table). Mean REL time was significantly shorter for TIVO, with no difference in mean TOX time. Mean Q-TWiST was 15.04 and 12.78 months for TIVO and SORA, respectively, a statistically significant difference (p=0.0493). The relative gain for TIVO was 11.2%. Clinical trial information: NCT02627963 . Values in table are mean (95% CI) in months or p-value for difference in treatment group means. Conclusions: The difference in Q-TWiST in TIVO-3 was primarily driven by benefits of TIVO in TWiST, partially offset by superiority of SORA in REL time. As a third- or fourth-line treatment for RCC, TIVO significantly increased Q-TWiST relative to SORA, primarily through an increase in TWiST, which is generally considered to be the state with highest utility to patients. Consequently, Q-TWiST may be considered an alternative patient-centered measure of benefit of TIVO in these settings. [Table: see text]
Association between sites of metastases (mets) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).
Authors: Makrakis Dimitrios , Diamantopoulos Leonidas Nikolaos , Koshkin Vadim S , Alva Ajjai Shivaram , Bilen Mehmet Asim , Stewart Tyler Francis , Santos Victor Sacristan , Jain Jayanshu , Morales-Barrera Rafael , Devitt Michael E. , Carril-Ajuria Lucia , Nelson Ariel Ann , Sankin Alexander , Zakopoulou Roubini , Pinato David James , Fröbe Ana , Joshi Monika , Sonpavde Guru , Grivas Petros , Khaki Ali Raza 
Published: March 2021

445 Background: Different metastatic sites have variable prognostic implications in aUC. However, details on response and outcomes with ICI for particular mets is still unknown. We hypothesized that bone and liver mets would have poor response and outcomes with ICIs. Methods: We performed a retrospective cohort study in patients (pts) with aUC who received ICI. We compared overall response rate (ORR) and overall survival (OS) between pts with different mets at ICI initiation. We developed 4 different models: 1) lymph node (LN) only vs other; 2) visceral mets (bone, lung, liver) vs other; 3) bone + liver mets vs bone without liver vs liver without bone vs neither and 4) 6 factor model: a. LN +/- soft tissue/locoregional recurrence b. lung +/- (a) c. bone +/- (b) d. liver +/- (c) e. central nervous system (CNS) +/- (d) and f. other. ORR and OS were compared among groups using multivariable (adjusting for ECOG PS and hemoglobin<10g/dl) logistic regression and cox regression, respectively. Results: We identified 984 pts (24 institutions); 703 and 696 were included in OS and ORR analyses, respectively. Median age at ICI start was 71 (range 32-93), 77% white race, 74% men, 67% ever smokers, 72% pure UC, 18% upper tract UC, 55% extirpative surgery. Prevalence of LN, lung, bone and liver mets at ICI start was 74%, 32%, 27% and 21%, respectively. LN-only mets had significantly higher ORR (44% vs 22%, OR 2.6, p<0.05) and longer mOS (22 vs 8 months, HR 0.5, p<0.05) vs other mets. Visceral mets had significantly lower ORR (21% vs 35%, OR 0.5, p<0.05) and shorter mOS (7 vs 17 months, HR 1.8, p<0.05) vs non-visceral mets. Pts with bone and liver mets had significantly lower ORR and shorter OS vs those with bone or liver mets, which both had significantly lower ORR and shorter OS vs those with neither and with LN +/- local recurrence (Table). Conclusions: In the context of ICI treatment, bone, liver, lung or CNS mets were associated with lower ORR and/or shorter OS, and bone and liver mets were particularly associated with low ORR and short OS. LN-only mets were associated with higher ORR and longer OS. Further work is needed to interrogate site-specific tumor-host immune interactions and identify biomarkers. Research Sponsor: None[Table: see text]
An L-type lectin receptor-like kinase promotes starch accumulation during rice pollen maturation
Authors: He Zhiyuan , Zou Ting , Xiao Qiao , Yuan Guoqiang , Liu Miaomiao , Tao Yang , Zhou Dan , Zhang Xu , Deng Qiming , Wang Shiquan , Zheng Aiping , Zhu Jun , Liang Yueyang , Yu Xiumei , Wang Aijun , Liu Huainian , Wang Lingxia , Li Ping , Li Shuangcheng 
Published: March 2021

ABSTRACTStarch accumulation is key for the maturity of rice pollen grains; however, the regulatory mechanism underlying this process remains unknown. Here, we have isolated a male-sterile rice mutant, abnormal pollen 1 (ap1), which produces nonviable pollen grains with defective starch accumulation. Functional analysis revealed that AP1 encodes an active L-type lectin receptor-like kinase (L-LecRLK). AP1 is localized to the plasma membrane and its transcript is highly accumulated in pollen during the starch synthesis phase. RNA-seq and phosphoproteomic analysis revealed that the expression/phosphorylation levels of numerous genes/proteins involved in starch and sucrose metabolism pathway were significantly altered in the mutant pollen, including a known rice UDP-glucose pyrophosphorylase (OsUGP2). We further found that AP1 physically interacts with OsUGP2 to elevate its enzymatic activity, likely through targeted phosphorylation. These findings revealed a novel role of L-LecRLK in controlling pollen maturity via modulating sucrose and starch metabolism.
Social organization and the evolution of life-history traits in two queen morphs of the ant Temnothorax rugatulus
Authors: Negroni Matteo A. , Stoldt Marah , Oster Marie , Rupp Ann-Sophie , Feldmeyer Barbara , Foitzik Susanne 
Published: March 2021

ABSTRACT
During the evolution of social insects, not only did life-history traits diverge, with queens becoming highly fecund and long lived compared with their sterile workers, but also individual traits lost their importance compared with colony-level traits. In solitary animals, fecundity is largely influenced by female size, whereas in eusocial insects, colony size and queen number can affect the egg-laying rate. Here, we focused on the ant Temnothorax rugatulus, which exhibits two queen morphs varying in size and reproductive strategy, correlating with their colony's social organization. We experimentally tested the influence of social structure, colony and body size on queen fecundity and investigated links between body size, metabolic rate and survival under paraquat-induced oxidative stress. To gain insight into the molecular physiology underlying the alternative reproductive strategies, we analysed fat body transcriptomes. Per-queen egg production was lower in polygynous colonies when fecundity was limited by worker care. Colony size was a determinant of fecundity rather than body size or queen number, highlighting the super-organismal properties of these societies. The smaller microgynes were more frequently fed by workers and exhibited an increase in metabolic activity, yet they were similarly resistant to oxidative stress. Small queens differentially expressed metabolic genes in the fat body, indicating that shifts in molecular physiology and resource availability allow microgyne queens to compensate for their small size with a more active metabolism without paying increased mortality costs. We provide novel insights into how life-history traits and their associations were modified during social evolution and adapted to queen reproductive strategies.
Diversity in rest–activity patterns among Lake Malawi cichlid fishes suggests a novel axis of habitat partitioning
Authors: Lloyd Evan , Chhouk Brian , Conith Andrew J. , Keene Alex C. , Albertson R. Craig 
Published: March 2021

ABSTRACT
Animals display remarkable diversity in rest and activity patterns that are regulated by endogenous foraging strategies, social behaviors and predator avoidance. Alteration in the circadian timing of activity or the duration of rest–wake cycles provide a central mechanism for animals to exploit novel niches. The diversity of the &gt;3000 cichlid species throughout the world provides a unique opportunity to examine variation in locomotor activity and rest. Lake Malawi alone is home to over 500 species of cichlids that display divergent behaviors and inhabit well-defined niches throughout the lake. These species are presumed to be diurnal, though this has never been tested systematically. Here, we measured locomotor activity across the circadian cycle in 11 Lake Malawi cichlid species. We documented surprising variability in the circadian time of locomotor activity and the duration of rest. In particular, we identified a single species, Tropheops sp. ‘red cheek’, that is nocturnal. Nocturnal behavior was maintained when fish were provided shelter, but not under constant darkness, suggesting that it results from acute response to light rather than an endogenous circadian rhythm. Finally, we showed that nocturnality is associated with increased eye size after correcting for evolutionary history, suggesting a link between visual processing and nighttime activity. Together, these findings identify diversity of locomotor behavior in Lake Malawi cichlids and provide a system for investigating the molecular and neural basis underlying variation in nocturnal activity.
Evaluation of empathy and fatigue among physicians and surgeons in tertiary care hospitals of Rawalpindi
Authors: Rashid Zubaida , Sharif Imtenan , Khushk Imdad Ali , Raja Abdullah Anis 
Published: March 2021

Background and Objectives: Clinicians need to build an astute doctor-patient relationship. The term clinical empathy is the ability of doctor to cognitively appreciate a patient’s perspective, experiences, and deliver such an understanding back to patient. Studies associate high physician empathy with improved patient trust and clinical outcomes. In Pakistan, there is paucity of research data on this relationship. This study assessed the empathy and its relation to fatigue levels among physicians and surgeons.
Methods: This was a cross-sectional analytical study involving 262 Physicians and Surgeons (1:1) chosen by convenience sampling method. Physicians and Surgeons were included from three hospitals in Rawalpindi from September 2017 to February 2018 and RAO soft sample calculator was used. The Jefferson Scale for Physician empathy (JSPE) (score range 20-140) and Multidimensional Fatigue Inventory (MFI-20) (score range 20-100) were used as data collection tools. The data was analyzed using SPSS version 23. Statistical tests including T-test and Pearson Correlation were used.
Results: Overall, mean score of empathy was found to be 98.8±21.9 (range; 46-138). The empathy in Physicians (106.8±18.3) was found to be greater than Surgeons (89.4±22.1) and the difference was statistically significant (p value <0.01). Mean score of fatigue was 50.6±16.0. The fatigue level in Surgeons was greater than Physicians and the difference was found to be statistically significant (p value < 0.01). Strong negative correlation was observed between empathy and fatigue (r= -0.5, p=<0.01) using Pearson correlation.
Conclusion: Overall, physicians had better empathy than surgeons, while fatigue scores were higher among surgeons. Fatigue is associated with empathy decay. This research provides an understanding of empathy deterioration and other factors responsible for it.
doi: https://doi.org/10.12669/pjms.37.3.1973
How to cite this:Rashid Z, Sharif I, Khushk IA, Raja AA. Evaluation of empathy and fatigue among physicians and surgeons in tertiary care hospitals of Rawalpindi. Pak J Med Sci. 2021;37(3):663-667. doi: https://doi.org/10.12669/pjms.37.3.1973
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Retrospective analysis of the use of osteoporosis medication at the presentation of non-vertebral fragility fractures in a predominantly Hispanic population.
Authors: Torres-Reveron Annelyn , Serra-Torres Michael 
Published: March 2021

Background: Despite the high incidence of osteoporosis, many patients at risk of fragility fractures may not initiate treatment due to concerns about side effects, cost or under-diagnosis, such as the case of vertebral fractures. We aimed to identify whether the patient population with non-vertebral fragility fractures where already receiving prophylactic treatment for osteoporosis at presentation within a regional hospital in the southernmost region of the United States. This region is characterized by a high number of patients from Hispanic/Latino heritage (80%) and reduced access to healthcare services. Methods: We conducted a three-year, retrospective cohort study of patients presenting with low impact fractures of the humerus or the shoulder griddle, lower end of radius or ulna and forearm, hip fractures (femoral neck, intertrochanteric/ subtrochanteric), and ankle fractures. Male and female subjects of 50 years or older were included. Demographic data and information on medications reported at fracture presentation were extracted from electronic medical records. Results: We found that 42% of the patients were taking at least one medication to prevent osteoporosis. The predominant combination was vitamin D plus calcium and bisphosphonates. If patients taking only vitamin D plus calcium are excluded, 16.7% of the sample took osteoporosis medications at the fragility fracture presentation. The likelihood of taking osteoporosis medication was increased by age and type of health insurance (Medicare/private insurance), and concomitant diagnosis of impaired gait and mobility. The percentage of the patients taking prophylactic medications for osteoporosis at the time of a fragility fracture was comparable to reported national standards and associated with increased age and health insurance coverage. Conclusion: In a predominantly Hispanic/Latino patient population living in a medically underserved region, there is substantial recognition and prevention strategies for osteoporosis.