bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENZA‐p trial protocol: a randomized phase II trial using prostate‐specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration‐resistant prostate cancer treated with enzalutamide (ANZUP 1901)
Authors: Emmett Louise , Subramaniam Shalini , Joshua Anthony M. , Crumbaker Megan , Martin Andrew , Zhang Alison Y. , Rana Nisha , Langford Ailsa , Mitchell Jenna , Yip Sonia , Francis Roslyn , Hofman Michael S. , Sandhu Shahneen , Azad Arun , Gedye Craig , McJannett Margaret , Stockler Martin R. , Davis Ian D. ,   the Australian, New Zealand Urogenital, Prostate Cancer Trials Group (ANZUP), the ENZA‐p investigators
Published: May 2021

ObjectivesTo determine the activity and safety of lutetium‐177 (177Lu)‐prostate‐specific membrane antigen (PSMA)‐617 in men with metastatic castration‐resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue.Participants and MethodsENZA‐p (ANZUP 1901) is an open‐label, randomized, two‐arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177Lu‐PSMA‐617 7.5 GBq on Days 15 and 57. Two additional 177Lu‐PSMA‐617 doses are allowed, informed by Day‐92 Gallium‐68 (68Ga)‐PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate‐specific antigen (PSA) progression‐free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health‐related quality of life, adverse events and cost‐effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68Ga‐PSMA PET‐avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high‐risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68Ga‐PSMA PET at baseline, Days 15 and 92, and at progression, and 18F‐fluorine deoxyglucose (18F‐FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68Ga‐PSMA and 18F‐FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two‐sided type‐1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA‐PFS of 5 months with enzalutamide alone.Results and ConclusionThe combination of 177Lu‐PSMA‐617 and enzalutamide may be synergistic. ENZA‐p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
Mesenchymal stem cells and extracellular vesicles for the treatment of pain: Current status and perspectives
Authors: Bryk Marta , Karnas Elżbieta , Mlost Jakub , Zuba‐Surma Ewa , Starowicz Katarzyna 
Published: May 2021

Mesenchymal stem/stromal cells (MSCs) are multipotent progenitor cells of mesodermal origin. Due to their capacity for self‐renewal and differentiation into several cell types, MSCs have been extensively studied in experimental biology and regenerative medicine in recent years. Moreover, MSCs release extracellular vesicles (EVs), which might be partly responsible for their regenerative properties. MSCs regulate several processes in target cells via paracrine signalling, such as immunomodulation, anti‐apoptotic signalling, tissue remodelling, angiogenesis and anti‐fibrotic signalling. The aim of this review is to provide a detailed description of the functional properties of MSCs and EVs and their potential clinical applications, with a special focus on pain treatment. The analgesic, anti‐inflammatory and regenerative properties of MSCs and EVs will be discussed for several diseases, such as neuropathic pain, osteoarthritis and spinal cord injury.LINKED ARTICLESThis article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc
Optimal treatment policies for pelvic organ prolapse in women
Authors: Zhuo Yueran , Solak Senay , Harmanli Oz , Jones Keisha A. 
Published: May 2021

ABSTRACTPelvic organ prolapse (POP) is a very common gynecological disorder greatly affecting the quality of life (QoL) of females in the society. Studies have shown that approximately 40% of women in the United States have POP that requires medical intervention. In clinical practice, there are four treatment options for POP: watchful waiting, conservative treatment, reconstructive surgery, and obliterative surgery. In this study, we utilize practical data obtained through surveys and clinical literature and develop a model to help physicians and POP patients dynamically select treatment options in order to maximize a patient's expected future QoL. Results from the model are presented in the form of optimal policy tables, which can be used by physicians and patients by entering several attributes as inputs, such as the patient's age, current observed QoL defined by the severity of POP symptoms, preferences over preserving coital function, and other potential restrictive conditions. The results show significant socioeconomic incentives for potential utilization of optimal treatment policies in POP treatment. We estimate based on QoL to dollar conversions that the expected value of improved QoL for an individual POP patient is around $10,000. When aggregated over the entire POP population seeking treatment, the total annual expected value for the society is at least $675 million under medium‐level valuations of QoL. Although the optimization‐based policies imply an overall increase of about $200 million in annual POP treatment costs, the net positive gains can make this trade‐off an acceptable one.
Behavioural heat‐stress compensation in a cold‐adapted ungulate: Forage‐mediated responses to warming Alpine summers
Authors: Semenzato Paola , Cagnacci Francesca , Ossi Federico , Eccel Emanuele , Morellet Nicolas , Hewison A. J. Mark , Sturaro Enrico , Ramanzin Maurizio 
Published: May 2021

AbstractAlpine large herbivores have developed physiological and behavioural mechanisms to cope with fluctuations in climate and resource availability that may become maladaptive under climate warming. We tested this hypothesis in female Alpine ibex (Capra ibex) by modelling annual and daily movement and activity patterns in relation to temperature, vegetation productivity and reproductive status based on bio‐logging data and climate change projections. In summer, ibex moved upslope, tracking the green wave. Ibex decreased diel activity sharply above a threshold temperature of 13–14°C, indicating thermal stress, but compensated behaviourally by foraging both earlier and later in the day, and by moving further upslope than on cooler days, especially reproductive females. This critical temperature will be exceeded three times as often under climate change projections. Under such scenarios, the altitudinal extent of the area will limit the available habitat providing thermal shelter, potentially impacting performance and population distribution of this emblematic mountain ungulate.
Are Fourth‐Year College Students Better Critical Thinkers than Their First‐Year Peers? Not So Much, and College Major and Ethnicity Matter
Authors: Liu Ou Lydia , Roohr Katrina Crotts , Seybert Jacob M. , Fishtein Daniel 
Published: May 2021

AbstractCritical thinking has become an essential skill required by both higher education and the workforce. Research to date has reported moderate cross‐sectional learning differences in critical thinking as students progress through a 4‐year college. However, retention, differential participation, and students’ low test‐taking motivation possibly confounded conclusions from prior studies. Controlling for such factors, we found a cross‐sectional difference of .24 SDs after 4 years in college (n = 2,381 students, 46 institutions), considerably smaller than what's reported in prior studies. Natural science majors performed the highest and business majors performed the lowest. Minority students achieved only half of the cross‐sectional difference (.18 SDs) of white students (.39 SDs), and only 6% of them scored at the Advanced level, compared to 24% of white students.
Defining dipeptidyl peptidase‐4 inhibitors‐related bullous pemphigoid: A single‐centre retrospective study
Authors: Nieto‐Benito Lula María , Bergón‐Sendín Marta , Pulido‐Pérez Ana , Rosell‐Díaz Ángel Manuel , Parra‐Blanco Verónica , Suárez‐Fernández Ricardo 
Published: May 2021

AbstractBackgroundMany studies have corroborated the association of dipeptidyl peptidase‐4 inhibitors (DPP4i) use with bullous pemphigoid (BP). It has been speculated that this drug‐induced variant presents with a different clinical spectrum than conventional BP.ObjectiveTo determine the prevalence of DPP4i‐induced cases of BP and to evaluate whether gliptin‐related BP has specific clinicopathological and immunological features.MethodsWe conducted a retrospective, observational study of BP cases attended at our centre between January 2000 and June 2020. Epidemiological, clinical, histopathological and laboratory data were collected.ResultsA total of 257 cases of BP were collected; 51 (24.3%) were on treatment with DPP4i. When analysing DPP4i‐induced BP cases, generalized BP was the predominant pattern and scalp/mucosal involvement was found in 13 patients. Gliptin‐related BP cases were associated to a decrease in the eosinophilic infiltrate (p = 0.000) and both the detection rate and concentration of anti‐BP180 IgG were lower (p = 0.004, p = 0.001, respectively) than non‐DPP4i cases.LimitationsRetrospective, single‐centre study.ConclusionOur large DPP4i‐induced BP case series has highlighted that DPP4i‐induced BP is characterized by generalized lesions and scalp involvement. Lower titres of anti‐BP180 antibodies and a decrease in eosinophils infiltrating into the skin may be distinct features of DPP4i‐related BP.
Impacts of invasive Amur honeysuckle, Lonicera maackii, leaf litter on multiple trophic levels of detritus‐based experimental wetlands
Authors: Robison Alexis L. , Berta Josey L. , Mott Cy L. , Regester Kurt J. 
Published: May 2021

Abstract

Wetlands are especially vulnerable to invasive plants because seasonal movements of sediments, water, nutrients, and debris from adjacent terrestrial habitats create ecological conditions suitable for invasion. Lonicera maackii is a relatively abundant and broadly distributed invasive shrub in the eastern U.S.A., yet few studies have simultaneously tested for effects of its leaf litter on multiple trophic levels within wetland food webs.

Hatching success, hatchling survival, and hatchling size of tadpoles (Acris crepitans) were assessed using a laboratory mesocosm experiment with no‐leaf, native‐leaf, and L. maackii‐leaf treatments. In the field, short‐term (c. 3 week) and long‐term (c. 2 years) mesocosm experiments assessed the initial and persistent impacts, respectively, of L. maackii on measures of primary productivity, invertebrate abundance and community structure, and oviposition preference and larval survival of Cope's gray treefrog (Hyla chrysoscelis).

Exposure of eggs to L. maackii leaves reduced body size at hatching and larval survival of newly hatched A. crepitans. In short‐term experiments, L. maackii leaves reduced dissolved oxygen levels, filamentous algal biomass, and macroinvertebrate abundance, and altered macroinvertebrate community structure. In long‐term experiments, duckweed cover was 15× times greater in mesocosms with L. maackii leaf additions. Oviposition by a local population of H. chrysoscelis was 10× lower in both short‐ and long‐term mesocosms with L. maackii present.

Although ecological impacts of L. maackii have been reported for terrestrial systems, our study is the first to demonstrate the simultaneous effects of its leaves on multiple trophic levels within replicated experimental wetlands. The relatively rapid decomposition of L. maackii leaves, and associated pulse of phenolic compounds, is the most likely proximate mechanism of the bottom‐up effects we observed. The mechanisms, timing, and significance of effects is predicted to vary among natural wetlands.

Our study demonstrates multiple ecological impacts of a terrestrial invasive shrub within experimental wetlands. Detailed studies on the specific mechanisms, and their spatial and temporal variability in natural systems, will elucidate management strategies and improve the efficiency of wetland conservation efforts.
Blood in Biafra: Re‐evaluating politics and ethnocultural conflict in the Nigerian‐Biafran War
Authors: Otiono Kikachukwu (Kika) 
Published: May 2021

AbstractIn 1967, just ​seven years after declaring independence from British colonization, a civil war erupted in Nigeria that left millions of civilians dead and the country known as the “Giant of Africa” fractured and reeling. In the decades since the conflict, historians delineated the causes and consequences of what became known as the Nigerian‐Biafran War. The aim of this paper is to examine historical and academic sources about the years leading up to the war in 1967, towards a nuanced understanding of a watershed moment in Nigerian history. The article contends that for Nigeria to progress towards political stability and economic prosperity in the twenty‐first century, the Nigerian‐Biafran War must be re‐imagined as a predictable aftermath of hegemonic colonialism and ethnicism. As such, this paper contributes to the emerging literature on the impact of the civil war on collective grief, ethnocultural relations, economics, and post‐colonial history.
Prediction of future cardiovascular events by Framingham, SCORE and asCVD risk scores is less accurate in HIV‐positive individuals from the HIV‐HEART Study compared with the general population
Authors: Schulz C‐A , Mavarani L , Reinsch N , Albayrak‐Rena S , Potthoff A , Brockmeyer N , Hower M , Erbel R , Jöckel K‐H , Schmidt B , Esser S ,   HIV HEART Aging Study Group and Heinz Nixdorf Recall Investigative Group
Published: May 2021

ObjectivesCardiovascular diseases (CVDs) occur more often in people living with HIV (PLWH) than in the general population. It has been reported that CVD risk scores developed for the general population underestimate the CVD risk in PLWH. Performances of the Framingham Risk Score (FRS), the Systematic Coronary Risk Evaluation (SCORE) and the atherosclerotic cardiovascular disease (asCVD) risk score in PLWH were compared with the general population to quantify score‐specific differences in risk prediction.MethodsHIV‐positive outpatients from the HIV‐HEART (HIVH) study (n = 567) were compared with participants from the population‐based Heinz Nixdorf Recall (HNR) study (n ~ 4440) both recruited from the German Ruhr area. During a follow‐up time of around 5 years, the associations between the FRS and incident CVD and peripheral artery disease (CVD_pAD), SCORE and coronary heart disease (CHD), and asCVD and incident CVD were examined using logistic regression. Score performances were assessed by comparing the areas under the curve (AUCs).ResultsThe mean ages were 52.9 ± 6.7 and 59.1 ± 7.7 years in the HIVH and HNR studies, respectively. There were fewer incident CVD events in the HNR study than in the HIVH study (CVD_pAD: 3.9% vs. 12.1%; CHD: 2.1% vs. 7.8%; CVD: 3.5% vs. 9.9%). Age‐ and sex‐adjusted CVD risk was greater with increasing FRS, SCORE and asCVD in both cohorts, but the scores performed more accurately in the HNR than in HIVH study (AUCs FRS: 0.71 vs. 0.65; SCORE: 0.70 vs. 0.62; asCVD: 0.74 vs. 0.62).ConclusionsAssociations between risk scores and future CVD were observed in both cohorts, but the score performances were less reliable in PLWH than in the general population.
Comparison of pembrolizumab with conventional chemotherapy after first‐line platinum‐based chemotherapy for advanced urothelial carcinoma in real‐world practice: A multicenter retrospective study
Authors: Narita Takuma , Hatakeyama Shingo , Numakura Kazuyuki , Kobayashi Mizuki , Muto Yumina , Saito Mitsuru , Narita Shintaro , Tanaka Toshikazu , Noro Daisuke , Tokui Noriko , Yoneyama Takahiro , Hashimoto Yasuhiro , Habuchi Tomonori , Ohyama Chikara 
Published: May 2021

ObjectivesTo assess the clinical benefit of pembrolizumab as second‐line therapy for advanced urothelial carcinoma.MethodsWe retrospectively compared the effects of pembrolizumab with those of conventional chemotherapy on the prognosis of patients with advanced urothelial carcinoma at six hospitals between January 2004 and August 2020. We compared the oncological outcomes between the patients treated with pembrolizumab and those treated with conventional chemotherapy using Kaplan–Meier curve analysis and multivariate Cox regression analysis with the inverse probability of treatment weighting method.ResultsThe numbers of patients in the pembrolizumab and chemotherapy groups were 121 and 67, respectively. Patients in the pembrolizumab group were significantly older (median 72 vs 66 years, P = 0.001), and had poor Eastern Cooperative Oncology Group performance status (median 1 vs 0, P = 0.001). The unadjusted Kaplan–Meier curve analysis showed no significant differences in the median overall survival from the first‐line chemotherapy (24.7 months vs 16.3 months, P = 0.159). Inverse probability of treatment weighting‐adjusted multivariate Cox proportional hazards analyses showed a significant difference between the pembrolizumab and chemotherapy groups in overall survival (P = 0.003, hazard ratio 0.63).ConclusionsDespite the non‐negligible age difference between the trial and our clinical practice, our study supports the benefit of second‐line pembrolizumab over chemotherapy in real‐world practice.
Nunca Más
Authors: Mong Ambrose 
Published: May 2021

AbstractThis article highlights efforts to promote peace and reconciliation in Guatemala. One of the reconcilers has been Rigoberta Menchú, receiver of the Nobel Peace Prize in 1992. The clergy and laity of the Roman Catholic Church have worked to ensure that the atrocities and violence the people suffered in the past would not happen again – nunca más (never again). The murder of Bishop Juan José Gerardi reveals not only the crimes of the military, but also the resolute commitment of the church in the process toward peace, reconciliation, and the healing of the nation.
Admission respiratory status predicts mortality in COVID‐19
Authors: Chatterjee Neal A. , Jensen Paul N. , Harris Andrew W. , Nguyen Daniel D. , Huang Henry D. , Cheng Richard K. , Savla Jainy J. , Larsen Timothy R. , Gomez Joanne Michelle D. , Du‐Fay‐de‐Lavallaz Jeanne M. , Lemaitre Rozenn N. , McKnight Barbara , Gharib Sina A. , Sotoodehnia Nona 
Published: May 2021

AbstractCOVID‐19 has significant case fatality. Glucocorticoids are the only treatment shown to improve survival, but only among patients requiring supplemental oxygen. WHO advises patients to seek medical care for “trouble breathing,” but hypoxemic patients frequently have no respiratory symptoms. Our cohort study of hospitalized COVID‐19 patients shows that respiratory symptoms are uncommon and not associated with mortality. By contrast, objective signs of respiratory compromise—oxygen saturation and respiratory rate—are associated with markedly elevated mortality. Our findings support expanding guidelines to include at‐home assessment of oxygen saturation and respiratory rate in order to expedite life‐saving treatments patients to high‐risk COVID‐19 patients.
Study of the formation of acid‐based geopolymer networks and their resistance to water by time/temperature treatments
Authors: Jouin Jenny , Celerier Helene , Ouamara Lila , Tessier‐Doyen Nicolas , Rossignol Sylvie 
Published: May 2021

AbstractAcid‐based geopolymers are known for their high temperature resistance and good mechanical performances. Some compositions also exhibit water resistance, which make them suitable for outdoor applications. This work aims to understand accurately the steps occurring during the geopolymerization process and focuses on the type of networks forming at early stages of the reaction. The sample, prepared from metakaolin and phosphoric acid, has been analyzed at different durations and temperatures during its solidification, in order to identify which compounds would crystallize. The structural characterizations have been performed using Fourier transform infrared spectroscopy and X‐ray diffraction. Several Al–O–P compounds and especially AlPO4 polymorphs crystallize in these conditions. They belong to three families of aluminophosphates and are a reliable indication of the amorphous organization of the original sample. The first one is similar to the phases that appear in the phase transition sequences of silica, the second one is composed of AlPO4‐based zeolites, and the last one is characterized by the presence of aluminum in an octahedral network. The transitions between the different phases are also discussed. Finally, the water resistance of the calcined samples is improved, and the release of acidic species in the water is limited even after a calcination at low temperature.
(BaTiO3)1‐x + (Co0.5Ni0.5Nb0.06Fe1.94O4)x nanocomposites: Structure, morphology, magnetic and dielectric properties
Authors: Slimani Yassine , Shirsath Sagar E. , Hannachi Essia , Almessiere Munirah A. , Aouna Moustafa M. , Aldossary Nouf E. , Yasin Ghulam , Baykal Abdulhadi , Ozçelik Bekir , Ercan Ismail 
Published: May 2021

AbstractTwo phase‐based nanocomposites consisting of dielectric barium titanate (BaTiO3 or BTO) and magnetic spinel ferrite Co0.5Ni0.5Nb0.06Fe1.94O4 (CNNFO) have been synthesized through solid state route. Series of (BaTiO3)1‐x + (Co0.5Ni0.5Nb0.06Fe1.94O4)x nanocomposites with x content of 0.00, 0.25, 0.50, 0.75, and 1.00 were considered. The structure has been examined via X‐rays diffraction (XRD) and indicated the occurrence of both perovskite BTO and spinel CNNFO phases in various nanocomposites. A phase transition from tetragonal BTO structure to cubic structure occurs with inclusion of CNNFO phase. The average crystallites size of BTO phase decreases, whereas that for the CNNFO phase increases with increasing x in various nanocomposites. The morphological observations revealed that the porosity is highly reduced, and the connectivity between grains is enhanced with increasing x content. The optical properties have been investigated by UV−vis diffuse reflectance spectroscopy. The deduced band gap energy (Eg) value is found to reduce with increasing the content of spinel ferrite phase. The magnetic as well as the dielectric properties were also investigated. The analysis showed that CNNFO ferrite phase greatly affects the magnetic properties and dielectric response of BTO material. The obtained findings can be useful to enhance the performances of magneto‐dielectric composite‐based systems.