bluuebunny/crossref_metadata_2025 huggingface dataset:
A New One-Pot Way to Prepare Enzyme-Containing Coordination Polymers by Sonochemistry
Authors: Scano Alessandra , Cabras Valentina , Ennas Guido
Published: March 2021

Enzyme-containing Coordination Polymers (CPs) were prepared by a one-pot sonochemical method, mixing Glucose Oxidase (GOx) enzyme, 4,4′-bipyridine as spacer ligand, and chloride zinc salt. The reaction took place in a very short time (a few minutes) with a minimum use of solvents compared to conventional methods. The obtained composite material, named GOx-[Zn(4,4′-bipy)Cl2]∞, resulted from embedding the GOx molecules into uniformly sized [Zn(4,4′-bipy)Cl2] nanocrystals. The structural and thermal characterization, confirmed that the adopted strategy allows the preparation of hybrid bio-nanomaterials in a very fast, facile and eco-friendly method, by simply synthesising the [Zn(4,4′-bipy)Cl2] nanocrystals in the presence of the enzyme.
Fine-Tuning Synthesis of Fluorescent Silver Thiolate Nanoclusters
Authors: Suber Lorenza , Pilloni Luciano , Khanna Kshitij , Righi Giuliana , Primitivo Ludovica , De Angelis Martina , Caschera Daniela
Published: March 2021

Noble metal thiolate nanoclusters are a new class of nanomaterials with molecular-like properties such as high dispersibility and fluorescence in the visible and infrared spectral region, properties highly requested in biomedicine for imaging, sensing and drug delivery applications.
We report on three new silver phenylethane thiolate nanoclusters, differing for slight modifications of the preparation, i.e., the reaction solvent and the thiolate quantity, producing changes in the nanocluster composition as well as in the fluorescence behavior. All samples, excited in the
range 250–500 nm, emit around 400 and 700 nm differing in the emission maxima and behavior. The silver thiolate nanoclusters have been characterized by way of C, H, S elemental analyses and Thermal Gravimetric Analysis (TGA) to determine the nanocluster composition, Scanning Transmission
Electron Microscopy (STEM) to investigate the nanocluster morphology and UV-Vis and fluorescence spectroscopy to study their optical properties.
Warpage Simulation During Fan-Out Wafer-Level Packaging Process with Uncertainty of Material Properties
Authors: Kim Geumtaek , Kwon Daeil
Published: March 2021

Along with the reduction in semiconductor chip size and enhanced performance of electronic devices, high input/output density is a desired factor in the electronics industry. To satisfy the high input/output density, fan-out wafer-level packaging has attracted significant attention.
While fan-out wafer-level packaging has several advantages, such as lower thickness and better thermal resistance, warpage is one of the major challenges of the fan-out wafer-level packaging process to be minimized. There have been many studies investigating the effects of material properties
and package design on warpage using finite element analysis. Current warpage simulations using finite element analysis have been routinely conducted with deterministic input parameters, although the parameter values are uncertain from the manufacturing point of view. This assumption may lead
to a gap between the simulation and the field results. This paper presents an uncertainty analysis of wafer warpage in fan-out wafer-level packaging by using finite element analysis. Coefficient of thermal expansion of silicon is considered as a parameter with uncertainty. The warpage and
the von Mises stress are calculated and compared with and without uncertainty.
Effects of Wave–Current Interaction on the Eastern China Coastal Waters during Super Typhoon Lekima (2019)
Authors: Wu Renhao , Wu Shimei , Chen Tianhua , Yang Qinghua , Han Bo , Zhang Han
Published: March 2021

Lekima was a devastating super typhoon hitting China in 2019. Here, we use a high-resolution wave–current coupling model to investigate the impacts of wave–current interaction during Lekima on wave height, storm surge, ocean currents, and momentum balance. The model results were in good agreement with observations. It was found that, in the open waters, the strong currents generated by the typhoon winds reduced the typhoon-induced maximum significant wave heights (MSWHs) by 6%–15%. The baroclinicity of seawater also slightly reduced the MSWHs by approximately 3%. In the coastal waters, the MSWHs were increased by 6%–15% when feedbacks from water levels were considered. The typhoon-induced highest storm surge occurred in the coastal waters right of the typhoon’s landing position. The nonconservative wave forces contributed by approximately 0.1–0.4 m to the most severe storm surge (3 m), with this effect being most prominent in coastal waters. The baroclinicity of seawater generally increased the storm surge but had little influence on very shallow waters. Tides tend to exacerbate storm surge in most nearshore waters, except in a small bay. Waves generally increased the velocity of offshore ocean currents via the wave-breaking-induced acceleration. A cross-shore momentum balance analysis shows that when the typhoon was near the shore, the dominant terms in the momentum equation were the horizontal pressure gradient force and the surface wind stress, and the contribution of wave breaking had similar pattern to that of the wind stress but a lower magnitude. Our findings have significant implications for the numerical modeling of typhoons and the prediction of their impacts in the coastal environment.
The effect of short-term storage temperature on the key headspace volatile compounds observed in Canadian faba bean flour
Authors: Akkad Rami , Kharraz Ereddad , Han Jay , House James D , Curtis Jonathan M
Published: March 2021

The odour emitted from the high-tannin fab bean flour ( Vicia faba var. minor), was characterized by headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC–MS). The relative odour activity value (ROAV) was used to monitor the changes in key volatile compounds in the flour during short-term storage at different temperature conditions. The key flavour compounds of freshly milled flour included hexanal, octanal, nonanal, decanal, 3-methylbutanal, phenyl acetaldehyde, (E)-2-nonenal, 1-hexanol, phenyl ethyl alcohol, 1-octen-3-ol, β-linalool, acetic acid, octanoic acid, and 3-methylbutyric acid; these are oxidative degradation products of unsaturated fatty acids and amino acids. Despite the low lipid content of faba beans, the abundances of aldehydes arising during room temperature storage greatly contributed to the flavour of the flour due to their very low odour thresholds. Two of the key volatiles responsible for beany flavour in flour (hexanal, nonanal) increased greatly after 2 weeks of storage at room temperature or under refrigerated conditions. These volatile oxidation products may arise as a result of enzymatic activity on unsaturated fatty acids, and was seen to be arrested by freezing the flour.
Effect of COVID-19 pandemic on workflows and infection prevention strategies of endoscopy units in Hungary: a cross-sectional survey
Authors:   Hungarian GI Endoscopy COVID-19 Study Group, Bor Renáta , Szántó Kata Judit , Fábián Anna , Farkas Klaudia , Szűcs Mónika , Rutka Mariann , Tóth Tibor , Bálint Anita , Milassin Ágnes , Dubravcsik Zsolt , Szepes Zoltán , Molnár Tamás
Published: March 2021

Background

Health care professionals in endoscopic labs have an elevated risk for COVID-19 infection, therefore, we aimed to determine the effect of current pandemic on the workflow and infection prevention and control strategies of endoscopy units in real-life setting.

Methods

All members of Hungarian Society of Gastroenterology were invited between 7 and 17 April 2020 to participate in this cross-section survey study and to complete an online, anonymous questionnaire.

Results

Total of 120 endoscopists from 83 institutes were enrolled of which 35.83% worked in regions with high cumulative incidence of COVID-19. Only 33.33% of them had undergone training about infection prevention in their workplace. 95.83% of endoscopists regularly used risk stratification of patients for infection prior endoscopy. While indications of examinations in low risk patients varied widely, in high-risk or positive patients endoscopy was limited to gastrointestinal bleeding (95.00%), removal of foreign body from esophagus (87.50%), management of obstructive jaundice (72.50%) and biliary pancreatitis (67.50%). Appropriate amount of personal protective equipment was available in 60.85% of endoscopy units. In high-risk or positive patients, surgical mask, filtering facepiece mask, protective eyewear and two pairs of gloves were applied in 30.83%, 76.67%, 90.00% and 87.50% of cases, respectively. Personal protective equipment fully complied with European guideline only in 67.50% of cases.

Conclusions

Survey found large variability in indications of endoscopy and relative weak compliance to national and international practical recommendations in terms of protective equipment. This could be improved by adequate training about infection prevention.
Improvement of renal function after transcatheter aortic valve replacement and its impact on survival
Authors: Kylies Dominik , Freitag-Wolf Sandra , Fulisch Florian , Seoudy Hatim , Kuhn Christian , Kihm Lars Philipp , Pühler Thomas , Lutter Georg , Dempfle Astrid , Frey Norbert , Feldkamp Thorsten , Frank Derk
Published: March 2021

Background

Chronic kidney disease as well as acute kidney injury are associated with adverse outcomes after transcatheter aortic valve replacement (TAVR). However, little is known about the prognostic implications of an improvement in renal function after TAVR.

Methods

Renal improvement (RI) was defined as a decrease in postprocedural creatinine in μmol/l of ≥1% compared to its preprocedural baseline value. A propensity score representing the likelihood of RI was calculated to define patient groups which were comparable regarding potential confounders (age, sex, BMI, NYHA classification, STS score, log. EuroSCORE, history of atrial fibrillation/atrial flutter, pulmonary disease, previous stroke, CRP, creatinine, hsTNT and NT-proBNP). The cohort was stratified into 5 quintiles according to this propensity score and the survival time after TAVR was compared within each subgroup.

Results

Patients in quintile 5 (n = 93) had the highest likelihood for RI. They were characterized by higher creatinine, lower eGFR, higher NYHA class, higher NT-proBNP, being mostly female and having shorter overall survival time. Within quintile 5, patients without RI had significantly shorter survival compared to patients with RI (p = 0.002, HR = 0.32, 95% CI = [0.15–0.69]). There was no survival time difference between patients with and without RI in the whole cohort (p = 0.12) and in quintiles 1 to 4 (all p > 0.16). Analyses of specific subgroups showed that among patients with NYHA class IV, those with RI also had a significant survival time benefit (p < 0.001, HR = 0.15; 95%-CI = [0.05–0.44]) compared to patients without RI.

Conclusions

We here describe a propensity score-derived specific subgroup of patients in which RI after TAVR correlated with a significant survival benefit.
Correction to: A nanobody-horseradish peroxidase fusion protein-based competitive ELISA for rapid detection of antibodies against porcine circovirus type 2
Authors: Mu Yang , Jia Cunyu , Zheng Xu , Zhu Haipeng , Zhang Xin , Xu Haoran , Liu Baoyuan , Zhao Qin , Zhou En-Min
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
The role of antimicrobial resistance on long-term mortality and quality of life in critically ill patients: a prospective longitudinal 2-year study
Authors: Koukoubani Triantafyllia , Makris Demosthenes , Daniil Zoe , Paraforou Theoniki , Tsolaki Vasiliki , Zakynthinos Epaminondas , Papanikolaou John
Published: March 2021

Background

In the recent era, antimicrobial resistance has been identified as one of the most important threats to human health worldwide. The rapid emergence of antibiotic-resistant pathogens (ABRP) in the modern intensive care unit (ICU) also represents a “nightmare scenario” with unknown clinical consequences. In the Greek ICU, in particular, gram negative ABRPs are now considered endemic. However, the possible longitudinal impact of ABRPs on long-term outcomes of ICU patients has not yet been determined.

Methods

In this two-year (January 2014-December 2015) single-centre observational longitudinal study, 351 non-neurocritical ICU patients ≥ 18 year-old were enrolled. Patients’ demographic, clinical and outcome data were prospectively collected. Quality-adjusted life years (QALY) were calculated at 6, 12, 18 and 24 months after ICU admission.

Results

Fifty-eight patients developed infections due to ABRP (ABRP group), 57 due to non-ABRP (non-ABRP group), and 236 demonstrated no infection (no-infection group) while in ICU. Multiple regression analysis revealed that multiple organ dysfunction syndrome score (OR: 0.676, 95%CI 0.584–0.782; P < 0.001) and continuous renal replacement therapy (OR: 4.453, 95%CI 1.805–10.982; P = 0.001) were the only independent determinants for ABRP infections in ICU. Intra-ICU, 90-day and 2-year mortality was 27.9%, 52.4% and 61.5%, respectively. Compared to the non-ABRP and no-infection group, the ABRP group demonstrated increased intra-ICU, 90-day and 2-year mortality (P ≤ 0.022), worse 2-year survival rates in ICU patients overall and ICU survivor subset (Log-rank test, P ≤ 0.046), and poorer progress over time in 2-year QALY kinetics in ICU population overall, ICU survivor and 2-year survivor subgroups (P ≤ 0.013). ABRP group was further divided into multi-drug and extensively-drug resistant subgroups [MDR (n = 34) / XDR (n = 24), respectively]. Compared to MDR subgroup, the XDR subgroup demonstrated increased ICU, 90-day and 2-year mortality (P ≤ 0.031), but similar 90-day and 2-year QALYs (P ≥ 0.549). ABRP infections overall (HR = 1.778, 95% CI 1.166–2.711; P = 0.008), as well as XDR [HR = 1.889, 95% CI 1.075–3.320; P = 0.027) but not MDR pathogens, were independently associated with 2-year mortality, after adjusting for several covariates of critical illness.

Conclusions

The present study may suggest a significant association between ABRP (especially XDR) infections in ICU and increased mortality and inability rates for a prolonged period post-discharge that requires further attention in larger-scale studies.
Characterization of polycystic ovary syndrome among Flo app users around the world
Authors: Jain Tarun , Negris Olivia , Brown Dannielle , Galic Isabel , Salimgaraev Rodion , Zhaunova Liudmila
Published: March 2021

Background

Polycystic ovary syndrome (PCOS) is a complex and multi-faceted endocrine disorder that affects 5–20% of women. Literature is limited regarding potentially differing PCOS phenotypes among women around the world.

Objective

To use Flo app technology to understand the multifaceted characteristics of PCOS across several countries and identify contributing risk factors to the development of this condition.

Study design

Flo is a widely used female health and wellbeing app with period tracking functionality that provides a globally representative and medically unbiased perspective on PCOS symptomatology. A chatbot dialog on PCOS was subsequently administered on the Flo application (app) to users from 142 countries (with at least 100 respondents) who have the app running in English during September–October 2019.

Results

For analyses, we selected the five countries with the greatest number of respondents: US (n = 243,238), UK (n = 68,325), India (n = 40,092), Philippines (n = 35,131), and Australia (n = 29,926). Bloating was the most frequently reported symptom among PCOS-positive women and appeared to be the main predictor of PCOS in our model (odds ratio 3·76 [95% CI 3·60–3·94];p < 0·0001). Additional top predictors of PCOS are high blood cholesterol and glucose levels. As BMI increased, the percentage of women who reported a physician-confirmed PCOS diagnosis also increased. However, women in India did not follow this trend.

Conclusion

Our findings are based on the largest known PCOS dataset and indicate that symptoms are more complex than previously understood. The most frequently reported symptoms (bloating, facial hirsutism, irregular cycles, hyperpigmentation, and baldness) are broader than those included in the Rotterdam criteria. Future work should reevaluate and refine the criteria utilized in PCOS diagnosis.
Aging in psoriasis vulgaris: female patients are epigenetically older than healthy controls
Authors: Borsky Pavel , Chmelarova Marcela , Fiala Zdenek , Hamakova Kvetoslava , Palicka Vladimir , Krejsek Jan , Andrys Ctirad , Kremlacek Jan , Rehacek Vit , Beranek Martin , Malkova Andrea , Svadlakova Tereza , Holmannova Drahomira , Borska Lenka
Published: March 2021

Background

Psoriasis vulgaris is a skin autoimmune disease. Psoriatic patients have significantly lowered life expectancy and suffer from various comorbidities. The main goal of the study was to determine whether psoriatic patients experience accelerated aging. As accelerated aging might be the reason for the higher prevalence of comorbidities at lower chronological ages, we also wanted to investigate the relationship between aging and selected parameters of frequent psoriatic comorbidities - endocan, vascular endothelial growth factor and interleukin-17. Samples were obtained from 28 patients and 42 healthy controls. Epigenetic age measurement was based on the Horvath clock. The levels of endocan, vascular endothelial growth factor and interleukin-17 were analyzed using standardized ELISA methods.

Results

The difference between the epigenetic age and the chronological age of each individual subject did not increase with the increasing chronological age of patients. We cannot conclude that psoriasis causes accelerated aging. However, the epigenetic and chronological age difference was significantly higher in female patients than in female controls, and the difference was correlated with endocan (r = 0.867, p = 0.0012) and vascular endothelial growth factor (r = 0.633, p = 0.0365) only in female patients.

Conclusions

The findings suggest a possible presence of pathophysiological processes that occur only in female psoriatic patients. These processes make psoriatic females biologically older and might lead to an increased risk of comorbidity occurrence. This study also supports the idea that autoimmune diseases cause accelerated aging, which should be further explored in the future.
Pharmacist medication instructions are associated with continued medication self-management in older adults: a retrospective observational study
Authors: Kose Eiji , Endo Hidetatsu , Hori Hiroko , Hosono Shingo , Kawamura Chiaki , Kodama Yuta , Yamazaki Takashi , Yasuno Nobuhiro
Published: March 2021

Background

Various factors are related to self-management of medication. However, few reports comprehensively examine the factors related to patients, medication levels, and other factors related to the recuperative environment, such as family support. The aim of this study was to investigate factors affecting the continuation of medication self-management among hospitalized older adults receiving convalescent rehabilitation.

Methods

We conducted a retrospective observational study with 274 consecutive patients newly admitted to the convalescent rehabilitation wards at a single hospital in Japan between January 2017 and May 2018. Participants who were assessed for their ability to take their medication using the Japanese Regimen Adherence Capacity Tests, were deemed to be self-manageable, and were able to successfully continue to self-manage their medication from admission to discharge were categorized as the “continuation group,” and those who were not able to continue were categorized as the “non-continuation group.” We analyzed the groups’ demographic data, laboratory data, and Functional Independence Measure. The primary outcome was the continuation of medication self-management from admission to discharge.

Results

After enrollment, 134 patients (median age 82 years; 62.7% women) were included in the final analysis. Some 60.4% of eligible patients were able to maintain medication self-management during their hospitalization. The multiple logistic regression analysis for the continuation of medication self-management during hospitalization after adjusting for confounding factors revealed that pharmacist medication instructions were independently and positively correlated with successful continuation of medication self-management (odds ratio: 1.378; 95% confidence interval 1.085–1.831;p = 0.0076).

Conclusion

Successful continuation of medication self-management is associated with pharmacist medication instructions among hospitalized older adults undergoing rehabilitation.

Trail registration

The Ethics Committee’s registration number is “TGE01216–066”.
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

Starch 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

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

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 >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.
Ana Margarida Arruda, Daniela Ferreira y Elisa de Sousa, A cerámica grega do Castelo de Castro Marim. Estudos & Momórias 13. Centro de Arqueología da Universidade de Lisboa, Lisboa 2020.
Authors: Ferrer Albelda Eduardo
Published: March 2021

Recensión crítica a la obra de A.M. Arruda, D. Ferreira y E. de Sousa, A ceramica grega de Castro Marim, Lisboa, 2020
Human rights and maternity care
Authors: Booker Maria
Published: March 2021

Birthrights is an organisation that believes human rights law is an effective and powerful route to respectful maternity care
What is the significance of hearing a heart murmur during the newborn physical examination?
Authors: Seignior Helen Louise
Published: March 2021

Background

Newborn screening for congenital heart disease (CHD) forms part of the newborn physical examination (NPE) in the UK. However, research has shown that up to 50% of cases of CHD can be missed by this examination. The purpose of this literature review is to investigate the significance of hearing an asymptomatic heart murmur at the NPE in relation to the presence of CHD.

Methodology

A critical literature review was conducted to answer the research question. The findings were discussed using a narrative synthesis approach.

Findings

There was considerable heterogeneity of results. The prevalence of murmur in newborns ranged between 0.6%–10.7%. Between 13%–67% of those newborns had some form of CHD, although many had clinically insignificant lesions. Between 2%–9% of newborns with murmurs had a form of critical CHD (CCHD). The ability to discern whether a heart murmur relates to pathology or not improves with experience. No single optimal timing for the NPE was identified. Pulse oximetry was shown to increase sensitivity of screening for CCHD.

Conclusion

There is a significant increase in the prevalence of CHD when a newborn has a heart murmur, hence referral for diagnostic echocardiography is required when a heart murmur is identified. Pulse oximetry is an important adjunct to newborn screening for CCHD. Some newborns affected by CCHD will not present with murmur at the NPE. Therefore, those caring for newborns during the early days must know the signs and symptoms of CHD so that appropriate medical assistance can be sought.
Buddying up: implementing a personal protective equipment buddy system in a care home environment
Authors: Hayes Karen , Beckett Gail
Published: March 2021

With the third wave of COVID-19 once again gripping the country, care home staff are under increasing pressure. Karen Hayes and Gail Beckett outline the introduction of a personal protective equipment buddy system that was well received by those working in a care home environment in their locality.
Engineering light absorption at critical coupling via bound states in the continuum
Authors: Xiao Shuyuan , Wang Xing , Duan Junyi , Liu Tingting , Yu Tianbao
Published: March 2021

Recent progress in nanophotonics is driven by the desire to engineer light–matter interaction in two-dimensional (2D) materials using high-quality resonances in plasmonic and dielectric structures. Here, we demonstrate a link between radiation control at critical coupling and metasurface-based bound states in the continuum (BIC) physics, and develop a generalized theory to engineer light absorption of 2D materials in coupling resonance metasurfaces. In a typical example of hybrid graphene–dielectric metasurfaces, we present manipulation of the absorption bandwidth by more than one order of magnitude by simultaneously adjusting the asymmetry parameter of silicon resonators governed by BIC and graphene surface conductivity while the absorption efficiency remains maximum. This work reveals the generalized role of BIC in radiation control at critical coupling, and provides promising strategies in engineering light absorption of 2D materials for high-efficiency optoelectronics device applications, e.g.,  light emission, detection, and modulation.