Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating the efficacy of combination and single-agent immunotherapies in real-world patterns of disease progression and survival of metastatic melanoma patients

The objective of this study is to describe survival outcomes in patients with metastatic melanoma in a real-world setting receiving combination and single-agent immunotherapy outside the clinical trial context. We conducted a retrospective single-institution study of patients with metastatic melanoma in a real-world setting. Survival was calculated using log-rank test. Contingency tables were analyzed using Fisher’s Exact test. CD8 + T-cell densities were measured using quantitative immunofluorescence and analyzed using Mann-Whitney U test. The median overall survival (OS) for 132 patients was 45.3 months. Brain metastasis did not confer a higher risk of death relative to liver and/or bone disease (39.53 versus 30.00 months, respectively; P = 0.687). Anti-PD-1 monotherapy was the most common first-line treatment, received by 49.2% of patients. There was no significant difference in OS between patients receiving single-agent anti-PD-1 and combination anti-PD-1 plus CTLA-4 (39.4 months versus undefined; P = 0.643). Patients treated with combination therapy were more likely to be alive without progression at the last follow-up than those who received monotherapy (70.4% versus 49.2%; P = 0.0408). Median OS was 21.8 months after initiation of second-line therapy after anti-PD-1 monotherapy. CD8+ T-cell densities were higher in patients who achieved disease control on first-line immunotherapy (P = 0.013). In a real-world setting, patients with metastatic melanoma have excellent survival rates, and treatment benefit can be achieved even after progression on first-line therapy. Combination immunotherapy may produce more favorable long-term outcomes in a real-world setting. High pretreatment CD8+ T-cell infiltration correlates with immunotherapy efficacy.
Andesitic crustal growth via mélange partial melting: Evidence from Early Cretaceous arc dioritic/andesitic rocks in southern Qiangtang, central Tibet

Deciphering the petrogenesis of andesitic/dioritic rocks is fundamental to understanding the formation of the continental crust. Here we present detailed petrology, geochronology, major and trace element, Sr–Nd–Hf–O isotope data for the Early Cretaceous (∼122 Ma) dioritic rocks in the Bizha area in southern Qiangtang, Tibet. The dioritic rocks are characterized by large ion lithophile elements, Pb, and light rare earth elements but depletion of high field strength elements with slightly enriched and variable εNd(t) values of −0.01 to −3.31 and initial 87Sr/86Sr isotopic ratios of 0.7053–0.7062. They also have variable magmatic zircon Hf‐O isotope compositions (εHf(t) = −5.3 to +3.6 and δ18O = +7.3 to +9.5 ‰). Combined with contemporary andesitic lavas in southern Qiangtang, we suggest that the intermediate magmatic rocks in this area were most probably derived by partial melting of a subduction mélange, which is a mixture of mid‐oceanic ridge basalts (MORBs), sediments, and mantle wedge peridotites, formed along the interface between the subducted slab and the overlying mantle wedge in a subduction channel before ∼124 Ma. The mélange diapir melting was triggered by the asthenospheric upwelling and hot corner flow caused by roll‐back of the northward subducted Bangong‐Nujiang oceanic slab during the Early Cretaceous. The Early Cretaceous intermediate magmatic rocks in southern Qiangtang have an overall continental crust‐like andesitic composition. Therefore, partial melting of mélange provides an important support for the generation of andesitic magmas in continental arcs and the “andesite model” for crustal growth.
Career outlook and satisfaction in the presence of workload intensification-a survey of early career pharmacists.

BACKGROUND The demographics of the pharmacy workforce is changing with an increased proportion of pharmacists less than 30 years old (early career pharmacists-ECPs). In parallel, the profession has experienced workload intensification and workforce attrition. It is important to understand ECPs career satisfaction to retain this section of the pharmacy profession. OBJECTIVES This study aimed to collect data on the current career satisfaction of ECPs, and identify workplace factors that were most important to this group. Further, to use these findings to inform sector recommendations. METHODS A steering group of ECPs in Aotearoa New Zealand developed a survey based on one used previously. An invitation email was sent to all pharmacists who had been registered for less than 10 years and were members of the Pharmaceutical Society of New Zealand. RESULTS A total of 1418 ECPs were identified and invited to participate, and responses were received by 416 of these. While 90% believe that they are making a useful contribution to the health of their patients, over half are unhappy and discontented, with over a third dissatisfied with their careers. A large proportion (44%) were considering leaving the profession in the next 5 years. The top three factors for career satisfaction were ability to progress and learn new skills, the people they work with, and the remuneration. CONCLUSIONS This study provides a starting point for understanding the current environment and level of dissatisfaction of young pharmacists. There are several areas of concern that need to be addressed if a strong vibrant viable pharmacy profession is to be achieved.
Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases

Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children. Methods: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls. Results: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01). Conclusions: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.
Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

Senescence, particularly in the nucleus pulposus (NP) cells, has been implicated in the pathogenesis of disc degeneration, however, the mechanism(s) of annulus fibrosus (AF) cell senescence is still not well understood. Both TNFα and H2O2, have been implicated as contributors to the senescence pathways, and their levels are increased in degenerated discs when compared to healthy discs. Thus, the objective of this study is to identify factor(s) that induces inner AF (iAF) cell senescence. Under TNFα exposure, at a concentration previously shown to induce senescence in NP cells, bovine iAF cells did not undergo senescence, indicated by their ability to continue to proliferate as demonstrated by Ki67 staining and growth curves and lack of expression of the senescent markers, p16 and p21. The lack of senescent response occurred even though iAF express higher levels of TNFR1 than NP cells. Interestingly, iAF cells showed no increase in intracellular ROS or secreted H2O2 in response to TNFα which contrasted to NP cells that did. Following TNFα treatment, only iAF cells had increased expression of the superoxide scavengers SOD1 and SOD2 whereas NP cells had increased NOX4 gene expression, an enzyme that can generate H2O2. Treating iAF cells with low dose H2O2 (50 μM) induced senescence, however unlike TNFα, H2O2 did not induce degenerative-like changes as there was no difference in COL2, ACAN, MMP13, or IL6 gene expression or number of COL2 and ACAN immunopositive cells compared to untreated controls. The latter result suggests that iAF cells may have distinct degenerative and senescent phenotypes. To evaluate paracrine signalling by senescent NP cells, iAF and TNFα-treated NP cells were co-cultured. In contact co-culture the NP cells induced iAF senescence. Thus, senescent NP cells may secrete soluble factors that induce degenerative and senescent changes within the iAF. This may contribute to a positive feedback loop of disc degeneration. It is possible these factors may include H2O2 and cytokines (such as TNFα). Further studies will investigate if human disc cells respond similarly.
Overview of Maritime Accidents Involving Chemicals Worldwide and in the Baltic Sea

Transport and handling of hazardous chemicals and chemical products around the world’s waters and ports have considerably increased over the last 20 years. Thus, the risk of major pollution accidents has also increased. Past incidents/accidents are, when reported in detail, first hand sources of information on what may happen again. This paper provides an overview of the past tanker accidents in the Baltic Sea and chemical related accidents in seas worldwide. The aim is to find out what can be learned from past accidents, especially from the environmental point of view. The study is carried out as a literature review and as a statistical review.
Exploring suspended sediment delivery dynamics of two Mediterranean nested catchments

This paper investigates suspended sediment transport and dynamics of two nested agricultural lowland Mediterranean catchments with a difference of two orders of magnitude in the surface area (i.e., 1 and 264 km2). The effects of the drainage catchment area over the specific suspended sediment yield are assessed by using the nested approach over various timeframes. A detailed analysis of the rainfall–runoff–sediment transport relationships during the 2‐year study period shows that the hydrological and sedimentological responses were extremely variable for both catchments. Very low or no correlations were observed between the rainfall intensity and the selected hydrological variables and sediment loads. However, remarkable or high correlations were obtained between the rainfall intensity and the maximum and average suspended sediment concentrations, indicating that rainfall per unit time has little control on the hydrological response, but that, simultaneously, its high‐erosive power triggers sediment production, increasing the sedimentary response of the catchments. This study also illustrates how sediment is mainly transported during floods, producing predominantly clockwise hysteretic loops. Moreover, the small headwater catchment exerts a reduced (or even negligible) effect over the hydro‐sedimentary response of the larger downstream catchment, caused by the reduced sediment availability in a landscape with an inherent disconnection of the sediment pathways.
Comparing physician associates and foundation year 1 doctors-in-training undertaking emergency medicine consultations in England: a quantitative study of outcomes

Objectives To compare the contribution of physician associates (PAs) to the outcomes of emergency medicine consultations with that of foundation year 1 doctors-in-training (FY1s). Design A quantitative study using retrospective chart review of adult patients seen by PAs or FY1s from August 2018 to January 2020 using 16 months of anonymised clinical record data. Setting One emergency department (ED) in England. Participants The outcomes of 7405 patients seen by 11 PAs and 7 FY1s were recorded, with n=4580 PAs and n=2825 FY1s having complete records. Outcome measures The study aimed to evaluate wait times to consultation as the primary outcome. Secondary outcomes included length of stay (LOS), patients leaving without being seen (LWBS) and unplanned returns to the ED within 72 hours with the same complaint. Results PAs working in an ED in England treated patients mainly in Majors and Resus and saw more patients out of hours compared with FY1s. Following adjustments for confounding factors, there was no significant difference in wait times to consultation between those PAs or FY1s patients (116 min vs 109 min, respectively, p=0.84). Patients seen by PAs versus FY1s had a significantly longer LOS (52 min); 237 min vs 185 min, p<0.001 (95% CI 45.03 to 59.67). LWBS rates (n=89; 1.94% for PAs vs n=34; 1.2% for FY1s) showed no significant difference (p=0.073). Unplanned reattendance rates patients within 72 hours with the same presenting complaint showed no difference between PAs and FY1s (n=261 (5.70%) vs n=128 (4.58%), respectively, p=0.167). Conclusion PAs working in an ED in England managed patients with a range of conditions with a similar level of impact on three emergency medicine outcome measures as FY1s (wait times to consultation, numbers of patients LWBS or returning within 72 hours with the same presenting complaint). However, patients seen by PAs had a longer LOS.
Trust the Facts: The Impact of Reviews’ Written Style and Subject-Focus on Peer-to-Peer Accommodation Consumption

Applying dual-process theory, the current research examines the impact of written style (i.e., fact-based vs. emotion-based) and subject focus of online reviews (i.e., property-focused vs. host-focused) on customer trust and booking intention in the peer-to-peer (P2P) accommodation context. Following a theory-led conceptualization of customer trust in the P2P accommodation context, a series of three scenario-based experimental studies are conducted to examine the proposed hypotheses. Study results show that fact-based (vs. emotion-based) reviews of the property/host enhance customers’ booking intention, which is mediated by trust in the property/host, respectively. Moreover, among fact-based reviews, host-focused (vs. property-focused) reviews lead to a higher level of booking intention among female customers, but male customers show no significant difference in booking intention when reading either host-focused or property-focused reviews. The present research findings bear important theoretical and managerial implications for researchers and P2P accommodation practitioners alike, which are discussed at the end.
Bridging Software-Hardware for CXL Memory Disaggregation in Billion-Scale Nearest Neighbor Search

We propose CXL-ANNS, a software-hardware collaborative approach to enable scalable approximate nearest neighbor search (ANNS) services. To this end, we first disaggregate DRAM from the host via compute express link (CXL) and place all essential datasets into its memory pool. While this CXL memory pool allows ANNS to handle billion-point graphs without an accuracy loss, we observe that the search performance significantly degrades because of CXL’s far-memory-like characteristics. To address this, CXL-ANNS considers the node-level relationship and caches the neighbors in local memory, which are expected to visit most frequently. For the uncached nodes, CXL-ANNS prefetches a set of nodes most likely to visit soon by understanding the graph traversing behaviors of ANNS. CXL-ANNS is also aware of the architectural structures of the CXL interconnect network and lets different hardware components collaborate with each other for the search. Further, it relaxes the execution dependency of neighbor search tasks and allows ANNS to utilize all hardware in the CXL network in parallel. Our evaluation shows that CXL-ANNS exhibits 93.3% lower query latency than state-of-the-art ANNS platforms that we tested. CXL-ANNS also outperforms an oracle ANNS system that has unlimited local DRAM capacity by 68.0%, in terms of latency.
Characteristics of Retinal Image Associated with Premature Ovarian Insu�ciency

Purpose To establish a prediction model for premature ovarian insu�ciency (POI) identi�cation. Methods A total of 78 women with spontaneous POI and 48 healthy women were recruited from the A�liated Shenzhen Maternity & Child Healthcare Hospital in the study. Retinal characteristics were analyzed using an automated retinal image analysis system. Binary logistic regression was used to identify POI cases and develop predictive models. Results Compared to the normal group, the POI group had larger central retinal artery equivalent (CRAE) (P=0.006), central retinal vein equivalent (CRVE) (P=0.001), index of venules asymmetry (Vasym) (P=0.000); larger bifurcation angles of arterioles (Aangle) (P=0.001), bifurcation coe�cient of venule (BCV) (P=0.001) and more obvious arteriovenous nipping (Nipping) (P=0.005), but lower arteriole-to-venule ratio (AVR) (P=0.012). In the POI group, the odds ratio (OR) of Vasym was 6.72e-32 (95% C.I. 4.62e-49–9.79e-15, P=0.000), the OR of BCV was 5.66e-20 (95% C.I. 1.93e-34–.0000, P=5.66e-20) and the OR of Nipping was 6.65e-06 (95% C.I. 6.33e-10–.0698, P=0.012). Moreover, the area under the ROC curve for the binary logistic regression with retinal characteristics was 0.8582, and the �tting degree of regression models was 60.48% (Prob> chi-square = 0.6048). Conclusion This study demonstrated that retinal image analysis can provide useful information for POI identi�cation and certain characteristics may help with early clinical diagnosis of POI.
Oscillations of meteorological elements and their climate variations in the municipality of Barbalha – CE

The impact of climatical variability, even within the normal range, can have significant representation in agricultural activities. Thus, the aim of this study was to analyze climate variability in Barbalha, State of Ceara (CE), focusing on the variations as a means to understand future climate change, in order to analyze the climatic variables that influence agriculture. For this research we used data of maximum air temperature, relative air humidity and total rainfall monthly and yearly in the period 1973-2013, the Conventional Meteorological Station belonging to INMET, city Barbalha - CE. The data showed variations in the temperature of maximum annual air showed great variation among the studied period, also it appears that the relative humidity is being incremented along the series studied, which may be related to increasing temperature. The years with the lowest relative humidity were the years of 1981 and 1983 and the larger 2009 and 2011 were years related to the effects El Nino and La Nina. Fluctuations of meteorological elements and its climatic changes Barbalha - CE contributes significantly to the knowledge of the climatic situation of the municipality aiding decision making in agricultural crops and other economic sectors in the municipality partners.
Comparing GP, nurse and pharmacist prescribers 1 Medication Decision Making and Patient Outcomes in GP, Nurse and Pharmacist Prescriber Consultations Comparing GP, nurse and pharmacist prescribers

(2015) Medication decision making and patient outcomes in GP, nurse and pharmacist prescriber consultations. We recommend you cite the published version. (no note) Disclaimer UWE has obtained warranties from all depositors as to their title in the material deposited and as to their right to deposit such material. UWE makes no representation or warranties of commercial utility, title, or fitness for a particular purpose or any other warranty, express or implied in respect of any material deposited. UWE makes no representation that the use of the materials will not infringe any patent, copyright, trademark or other property or proprietary rights. UWE accepts no liability for any infringement of intellectual property rights in any material deposited but will remove such material from public view pending investigation in the event of an allegation of any such infringement. Abstract (300 words) Aim: The aims of this study were twofold: (a) to explore whether specific components of shared decision making were present in consultations involving nurse prescribers (NPs), pharmacist prescribers (PPs) and general practitioners (GPs) and (b) to relate these to self-reported patient outcomes including satisfaction, adherence and patient perceptions of practitioner empathy. Background: There are a range of ways for defining and measuring the
Response of a Preexisting Cyclonic Ocean Eddy to a Typhoon

AbstractThe three-dimensional responses of a cyclonic ocean eddy (COE) for 1–2 months following a typhoon were investigated using altimeter data and numerical experiments. Two significant features were found: 1) the cyclonic eddy was enhanced, and the three-dimensional structure was changed, and 2) the cyclonic eddy underwent two processes: elliptical deformation and reaxisymmetrization in the horizontal plane. These two features are generally associated with typhoon-induced upwelling and the dynamic processes of eddy adjustment. These results imply that the local ocean processes can be affected by a typhoon through low-frequency response.
Tomography of the source zone of the 2016 South Taiwan earthquake

On February 6, 2016, a Mw 6.4 earthquake occurred in Kaohsiung City, southern Taiwan, at a depth of 17 km (hereinafter we call it the 2016 South Taiwan earthquake). It caused 116 fatalities and widespread damage to infrastructures, especially in the Tainan city. To clarify the generating mechanism of this damaging earthquake, we conducted seismic tomography for high-resolution 3-D V p, Vs and Poisson’s ratio (σ) structures in the epicentral area. We used 91,703 P- and 51,718 S -wave arrival times from 7,038 local earthquakes (0.6≤M≤5.8) recorded at 41 seismic stations operated by the Central Weather Bureau in South Taiwan during 2000-2011. Our tomographic images reveal significant variations of up to 6% for Vp and Vs, and 10% for Poisson’s ratio in the crust and uppermost mantle beneath South Taiwan. In the upper crust (depth≤ 10 km), the most remarkable feature is low-Vp, low-Vs and high-σ anomalies in areas with known active faults in the southwest and easternmost parts of Taiwan. In contrast, high-Vp, high-Vs and low-σ anomalies become dominant in the lower crust. The hypocenter of the 2016 South Taiwan earthquake is located in a boundary zone where seismic velocity and Poisson’s ratio change drastically in both the horizontal and vertical directions. Furthermore, the hypocenter is underlain by a vertically elongated high-σ anomaly at depths of 23-40 km, which may reflect ascending fluids from the upper (or uppermost) mantle. The low-V and high-σ anomalies in the upper crust with of heat flow negative Bouguer gravity and low magnetotelluric which may reflect crustal fluids