bluuebunny/crossref_metadata_2025 huggingface dataset:
Listening to Muslim Students’ Voices on the Prevent Duty in British Universities: A Qualitative Study
Authors: Zempi Irene , Tripli Athina
Published: February 2022

The Prevent Duty requires universities in the United Kingdom to identify and report students who might be seen as ‘vulnerable’ to radicalisation. Since its introduction in 2015, the duty has been subject to increasing empirical research in the education sector. However, there has been limited research that specifically explores Muslim students’ perceptions of Prevent in British universities. This paper directly addresses this gap in research by drawing upon the qualitative experiences of 25 university students who self-identified as ‘British Muslims’. Individual, semi-structured interviews were transcribed and analysed using Thematic Analysis. The findings demonstrate the securitisation of higher education and ‘policing’ of Muslim students. The paper draws on Pantazis and Pemberton’s use of the ‘new suspect community’ thesis in order to examine participants’ views and experiences. When analysing the data, three particular themes are especially prominent: as a tool of ‘surveillance’, Prevent hampers freedom of speech, threatens student activism and forces Muslim students to hide their Muslim identity to avoid being labelled as ‘radical’ or ‘vulnerable’ to terrorism. It will be concluded that the ‘surveillance’ function of Prevent is problematic on the grounds that it renders universities ‘modern-day panopticons’.
Effect of the synthesis pH, the nature of the divalent cations and the metal salt concentration on the formation of layered double hydroxides for removal of Cochineal Red A dye from aqueous solutions
Authors: Mendil Rachida , Nasrallah Noureddine
Published: February 2022

In this research work, removal of Cochineal Red A dye from aqueous solution was studied using layered double hydroxide materials prepared by a coprecipitation method at variable pH. The effects of the synthesis pH, the nature of the divalent cations and the total metal salt concentration on the formation of layered double hydroxides and their application to the removal of Cochineal Red A dye from aqueous solution were investigated. The structure of the materials prepared was characterized by X-ray diffraction and Fourier transform infrared. It was found that the nature and content of the bi- and trivalent metal ions in the layered double hydroxide influenced the adsorption. Ni–Fe had 0.96 to 1.70 times more adsorption capacity before reaching its equilibrium adsorption than Zn–Fe prepared at pH 7–9 with 2.2 M of total metal salt concentration. No difference was observed in the amount of Cochineal Red A dye adsorbed onto Zn–Fe prepared at both pH 7–9 and pH 10–11 in the range 1.1–3.3 M of total metal salt concentration. The results show that the increase in the precipitation pH leads to decreasing adsorption capacity. The Cochineal Red A dye adsorption follows the Temkin model for the Ni–Fe and Zn–Fe prepared at pH 7–9 and follows the Langmuir model for the Zn–Fe synthesized at pH 10–11 with high coefficient correlation. The adsorption kinetics data fitted the pseudo-second-order model. A thermodynamic study indicates that the adsorption process is both spontaneous and endothermic in nature.
Hallux Valgus Interphalangeus Measurement: Comparison of the 2 Radiographic Methods
Authors: Nebhani Nimesh , Yatin Trivedy Mihir , Heyes Gavin , Molloy Andrew , Mason Lyndon
Published: February 2022

Background

To determine the reliability of Delta PP (difference in medial and lateral proximal phalanx wall length) compared with HIA (hallux interphalangeal angle) in the assessment of HVI (hallux valgus interphalangeus) in both preoperative and postoperative radiographs.

Methods

This was a retrospective observational study of 186 feet with hallux valgus. The number of cases required to adequately power the study was 128. Preoperative and postoperative hallux alignment were evaluated by 2 different radiological parameters, Delta PP and HIA. Interobserver variability was assessed independently by 2 authors and compared using a intraclass correlation coefficient.

Results

The intraclass correlation coefficient was more than 0.8 for all parameters, thus both HIA and Delta PP measurement provide reliable and reproducible data. Mean HIA significantly increased following surgical correction of hallux valgus. In comparison, the mean Delta PP decreased after correction. This postoperative increase in HIA indicates that preoperative HIA underestimates the magnitude of HVI and therefore is an inaccurate tool for measuring HVI’s contribution to the TVDH (total valgus deformity of the hallux) and to preoperative planning. However, the Delta PP was a greater determinant of the phalanx deformity’s contribution to the TVDH.

Conclusion

The outcome of our study shows that both HIA and Delta PP are reproducible when assessing the HVI deformity; however, Delta PP quantifies the amount of correction obtained more precisely. The additional benefit of measuring the Delta PP is that it allows for accurate planning in determining the dimensions of the medial-based wedge of the Akin osteotomy that needs to be resected.

Levels of Evidence:

Level 4
COVID-19 vaccine hesitancy among health professionals in a tertiary care center at the University of Gondar Specialized Hospital, Ethiopia: A cross-sectional study
Authors: Demeke Chilot Abiyu , Kifle Zemene Demelash , Atsbeha Berhanemeskel Weldegerima , Wondmsigegn Dawit , Yimenu Dawit Kumilachew , Woldeyohanins Alem Endashaw , Kasahun Asmamaw Emagn
Published: February 2022

Background:

COVID-19 is a highly communicable disease that can be transmitted from animal-to-human and human-to-human contacts. It is still now a major global threat for which vaccination remains the ultimate solution to protect it, especially healthcare professionals are the first frontiers to fight against the COVID-19 virus which makes them at higher risk of this disease. Therefore, to reduce the spread of COVID-19, we need to improve the acceptance of COVID-19 vaccines is crucial. The aim of this study was to assess the vaccine hesitancy of the COVID-19 vaccine among health professionals who worked at the University of Gondar Specialized Hospital.

Methods:

A cross-sectional survey was conducted between 1 May and 10 June 2021. And the data were analyzed using Statistical Package for Social Sciences version 26. A chi-square test was conducted and to assess the associations between socio-demographic characteristics, perceived risk of COVID-19, attitude, and acceptance of COVID-19 vaccine, a p-value of less than 0.05 was considered to declare statistical significance.

Results:

We surveyed 319 health professionals with a response rate of 67.87%. Of these, 74.9% (239) were male, and 81.2% (259) of health professionals were perceived exposed to COVID-19 without testing. 87.7% of respondents would like to vaccinate their parents. 66.2% (208) of them have accepted the COVID-19 vaccine. 54.85% (175) of health professionals had a good attitude and 45.8% (146) of health professionals were received the first-round COVID-19 vaccine.

Conclusion:

This study showed that more than 60% of health professionals had good acceptance of COVID-19 vaccination during the pandemic period. Regarding vaccine safety profile may reduce the vaccination in the future. To increase vaccine uptake in response to the COVID-19 pandemic, COVID-19 vaccination programs should be redesigned to remove barriers to vaccine acceptance. Knowledge and attitude toward the COVID-19 vaccine should be promoted.
End of Life Aid Skills for Everyone in Scotland
Authors: Patterson Rebecca M. , Gibb Caroline , Hazelwood Mark A.
Published: February 2022

Families, friends and communities have an important role to play in providing informal support when someone is faced with deteriorating health, caring responsibilities, death or bereavement. However, people can lack the confidence, skills and opportunities to offer this support. Public education is an example of a public health approach to palliative care that can help to develop individual skills and knowledge relating to these issues. In Scotland, the Scottish Partnership for Palliative Care (SPPC) has developed a new public education course called End of Life Aid Skills for Everyone (EASE) which aims to enable people to be more comfortable and confident supporting family/community members with issues they face during dying, death and bereavement. The aim was to design a course that imparts knowledge and skills while supporting development of social networks and avoids presenting professionals as the sole repository of expertise in the area of caring, dying and grieving. The intention was also to establish a sustainable delivery model that didn’t rely too heavily on busy palliative care specialists and which had the potential to bring the course to a diversity of communities. This article outlines the development of the EASE course, from conception to delivery.
Cystic Degeneration of an Atypical Adventitial Bursitis: Case Report and Literature Review
Authors: Poenaru Daniela
Published: February 2022

Adventitial (adventitious) bursae occur as a pathological condition in areas between soft tissues and bone where abnormal friction arises due to professional, traumatic, or sport activity. An atypical localization of an adventitial bursa was noticed on the ulnar margin of the distal forearm in a woman with a mild bone misalignment, as a professional disorder. The clinical presentation was one of subcutaneous mass with mild pain and no local signs of inflammation. A 1-year follow-up visit noted the degeneration of the bursa into a cystic lesion, as proved with a grayscale sonogram, using a 14 MHz linear transducer. This was an unexpected chronic evolution. A quick literature search found either resolution or a chronic course with complications as fibrosis, infection, and ulceration of adventitial bursitis.
Ferroberaunite, Fe2+Fe3+5(PO4)4(OH)5⋅6H2O, a mixed-valence iron member of the beraunite series, from the Gravel Hill mine, Perranzabuloe, Cornwall, England
Authors: Tvrdý Jaromír , Plášil Jakub , Vrtiška Luboš , Sejkora Jiří , Škoda Radek , Dolníček Zdeněk , Petr Martin , Veselovský František
Published: February 2022

The new mineral ferroberaunite, Fe2+Fe3+5(PO4)4(OH)5⋅6H2O (IMA2021-36; symbol: Fbru), occurs in cavities of ‘limonite’ iron ore from the Gravel Hill mine, Perranzabuloe, Cornwall, England. Its flattened prismatic crystals up to 400 μm long are dark green to olive green, transparent to translucent, with a vitreous lustre, pearly on cleavages. The Mohs hardness is ~3–4. The density measured by the flotation method is 2.94(2) g⋅cm–3, the calculated density is 2.907 g⋅cm–3. Ferroberaunite is biaxial (–), with α = 1.736(2), β = 1.765(3), γ = 1.786(5) at 589 nm, 2Vmeas. = 68(3)°, 2Vcalc. = 79°; dispersion of optical axes is strong, r > v; orientation is Y = b; X ≈ a, Z ≈ c. Pleochroism is strong: X = bluish-green >> Z = green > Y = yellow. Electron-microprobe analyses gave the empirical formula (Fe2+0.75Ca0.01Mn0.02Fe3+0.22)Σ1.00(Fe3+4.88Al0.04)Σ4.92(PO4)4O0.11(OH)4.76⋅6H2O. Ferroberaunite is monoclinic, C2/c, with a = 20.8708(3), b = 5.1590(8), c = 19.2263(3) Å, β = 93.3186(17)°, V = 2066.7(3) Å3 and Z = 4. The eight strongest lines in the powder X-ray diffraction pattern are [dmeas, Å (Irel., %) (hkl)]: 10.410 (100) (200), 9.606 (14) (002), 7.271 (11) (20$\bar{2}$), 5.203 (4) (400), 3.467 (12) (600), 3.325 (6) (60$\bar{2}$), 3.201 (6) (006), 2.600 (4) (800). The mineral is isostructural with beraunite, redefined recently as Fe3+6(PO4)4O(OH)4⋅6H2O.
Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort
Authors: Liu Yi , Tan Meng-Shan , Wang Zuo-Teng , Xu Wei , Tan Lan
Published: February 2022

Background

Genetic variations in the inflammatory Caspase-1 gene have been shown associated with cognitive function in elderly individuals and in predisposition to Alzheimer’s disease (AD), but its detailed mechanism before the typical AD onset was still unclear. Our current study evaluated the impact of Caspase-1 common variant rs554344 on the pathological processes of brain amyloidosis, tauopathy, and neurodegeneration.

Methods

Data used in our study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We examined the relationship between Caspase-1 rs554344 allele carrier status with AD-related cerebrospinal fluid (CSF), PET, and MRI measures at baseline by using a multiple linear regression model. We also analyzed the longitudinal effects of this variant on the change rates of CSF biomarkers and imaging data using a mixed effect model.

Results

We found that Caspase-1 variant was significantly associated with FDG PET levels and CSF t-tau levels at baseline in total non-demented elderly group, and especially in mild cognitive impairment (MCI) subgroup. In addition, this variant was also detected associated with CSF p-tau levels in MCI subgroup. The mediation analysis showed that CSF p-tau partially mediated the association between Caspase-1 variant and CSF t-tau levels, accounting for 80% of the total effect.

Conclusions

Our study indicated a potential role of Caspase-1 variant in influencing cognitive function might through changing tau related-neurodegeneration process.
Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate
Authors: Liu Weiyong , Zhu Yunkai , Ye Lei , Zhu Yajuan , Wang Yuhao
Published: February 2022

Background

Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge.

Methods

Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described.

Results

The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n = 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma.

Conclusions

This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.
Influence of type I collagen polymorphisms and risk of anterior cruciate ligament rupture in athletes: a case-control study
Authors: Perini Jamila Alessandra , Lopes Lucas Rafael , Guimarães João Antonio Matheus , Goes Rodrigo Araújo , Pereira Luiz Fernando Alves , Pereira Camili Gomes , Mandarino Marcelo , Villardi Alfredo Marques , de Sousa Eduardo Branco , Cossich Victor Rodrigues Amaral
Published: February 2022

Background

Anterior cruciate ligament (ACL) rupture is a common and severe knee injury in sports and occurs mostly due to noncontact injuries. There is an increasing amount of evidence associating ACL rupture to single nucleotide polymorphisms (SNPs), and SNPs in the collagen type I genes can change its expression and tissue mechanical features. This study aimed to investigate the association between SNPs in COL1A1 and COL1A2 with sports-related ACL tears.

Methods

A total of 338 athletes from multiple sports modalities were analyzed: 146 were diagnosed with ACL rupture or underwent an ACL reconstruction surgery and 192 have no musculoskeletal injuries. SNPs were genotyped using validated TaqMan assays. The association of the polymorphisms with ACL rupture was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI).

Results

The age, sport modality, and training location were associated with an increased risk of a non-contact ACL tear. COL1A2 SNPs (rs42524 CC and rs2621215 GG) were associated with an increased risk of non-contact ACL injury (6 and 4-fold, respectively). However, no significant differences were detected in the distribution of COL1A1 rs1107946 and COL1A2 rs412777 SNPs between cases and controls. There was a protective association with ACL rupture (OR = 0.25; 95% CI = 0.07–0.96) between COL1A1 rs1107946 (GT or TT) and the wildtype genotypes of the three COL1A2 (rs412777, rs42524, rs2621215). COL1A2 rs42524 and rs2621215 SNPs were associated with non-contact ACL risk.

Conclusion

The combined analysis of COL1A1-COL1A2 genotypes suggests a gene-gene interaction in ACL rupture susceptibility.
Newborn thermal care in western Uttar Pradesh — gap analysis between knowledge and practices
Authors: Srivastava Anurag , Saxena Sumit , Srivastava Payal , Mahmood Syed Esam , Pandey Ruchi , Saxena Anju
Published: February 2022

Background

The provision of health care services including maternal and newborn care is a dynamic system of entitlement and obligations among the community, the service providers, and the government. Thermal control remains poor in newborns owing to immaturity of the thermoregulatory center and newborn become vulnerable to hypothermia especially premature babies, intrauterine growth retardation and LBW babies, and even normal babies.This study aimed to assess the knowledge & practices regarding thermal protection their determinants.

Methods

Cross-sectional study was conducted in the Amroha district. The study population comprised women of reproductive age (15 to 49 years) who have delivered a live baby within the past 12 weeks before the conduct of the study. Out of 6 blocks, 2 most populous villages were selected. Total 61 villages from 6 blocks were covered under the study. Knowledge and practices regarding newborn thermal care were expressed in percentages and compared.

Results

The knowledge domain on thermal protection of baby, 60.9% of the respondents were well aware of how to keep baby warm after delivery, 71.4% of respondents knew that baby should be dried soon after birth, 64.9% of the respondents had an idea of time to dry the baby, 69.6% of the respondents knew that baby should be wrapped soon after birth.

Conclusion

The findings of the study provides an insight into the existing knowledge and necessitate a need for quantitative studies in the study area to access knowledge & practices related to thermal protection of newborns. The authors emphasize a need for improving community awareness for the promotion of newborn care and improve the health system to meet the demands of birthing mothers and the needs of newborns.
Use and misuse of prescription stimulants by university students: a cross-sectional survey in the french-speaking community of Belgium, 2018
Authors: Sabbe Martine , Sawchik Javier , Gräfe Mégane , Wuillaume Françoise , De Bruyn Sara , Van Antwerpen Pierre , Van Hal Guido , Desseilles Martin , Hamdani Jamila , Malonne Hugues
Published: February 2022

Background

Misuse of prescription stimulants (PS) has been reported among students to enhance academic performance in Flanders (Belgium). However, PS misuse among students in the French-speaking community is unknown. The main purpose of the study was to estimate the prevalence of medical use and misuse of PS by university students in the French-speaking community (Belgium), and to investigate the reasons and sources associated with PS misuse.

Methods

A cross-sectional online survey was performed in 2018. All university students 18 years and older were invited to participate and asked about PS use, including medical (i.e., used for therapeutic purposes) and nonmedical reasons and sources of PS.

Results

In total, 12 144 students participated in the survey (median age = 21 years, 65.5% female). The estimated prevalence of PS use was 6.9% (ever use) and 5.5% (past-year). Among ever users, 34.7% were classified as medical users and 65.3% as misusers. Lifetime prevalence of misuse was estimated at 4.5%. The most common reason for medical use was treatment of attention disorder (85.9%). Reasons for misuse were mainly to improve concentration (76.1%) or to stay awake and study longer (50.7%). Friends or acquaintances inside the student community and general practitioners were the main sources of PS for misuse (41.5% and 23.5%, respectively).

Conclusions

This study found that rates of misuse of PS in French-speaking universities in Belgium were in line with studies conducted in Flanders and Europe. Academic institutions can use these results to tailor their drug prevention campaigns.
Antiplasmodial and in vitro antioxidant potentials of crude aqueous and methanol extracts of Chasmanthera dependens (Hochst)
Authors: Enenebeaku Conrad Kenechukwu , Ogukwe Cynthia Ekwy , Nweke Christian Okechukwu , Anyado-Nwadike Sylvia Onyinyechi , Obi Martin , Duru Ijeoma Akunna , Enenebeaku Uchechi Emmanuela , Ogidi Odangowei I.
Published: February 2022

Background

Malaria is a major cause of death in tropical countries such as Nigeria. Chasmanthera dependens (Hochst) is a wild plant used by traditional healers for the treatment of malaria and other health challenges. This study evaluated the 'Antiplasmodial and in vitro antioxidant potentials of crude aqueous and methanol extracts of leaves, root and stem of Chasmanthera dependens (Hochst)’.

Results

Methanol extracts of leaves and roots of this plant exhibited higher antimalarial activities than other extracts. The level of parasitemia was significantly (p < 0.05) reduced in the treated animals when compared to untreated ones. Antiplasmodial activities of methanol extracts of roots and stem did not differ significantly (p < 0.05) from their aqueous extracts. An increase in body weight and higher survival rates were recorded in all the treated groups. Scavenging of DPPH, NO, H2O2 radicals and reducing power ability were concentration-dependent. Methanolic extracts of C. dependens root showed the best reducing activity. Phytochemical analyses revealed the presence of tannins, saponins, alkaloids, terpenoids, cardiac glycosides, flavonoids, phenols, phytate and oxalate.

Conclusion

Antimalarial and antioxidant properties of these extracts could be credited to the synergy between the phytoconstituents in this plant. Findings from this study justified the use of this plant in the treatment of malaria and other ailments.
Pore characteristics and corresponding controlling factors of the marine shale gas reservoir in the Wufeng-Longmaxi Formation of the Zhaotong shale gas demonstration area
Authors: Lai Fuqiang , Xia Xiaoxue , Wang Changjiang , Wang Ruyue , Zhong Lulu , Huang Zhaohui , Wang Haitao , Zhu Zhangxiong
Published: February 2022

The shale gas reservoir in the Zhaotong national shale gas demonstration area in the southern margin of the Sichuan Basin is mainly developed in the lower member of the Ordovician Wufeng Formation to the Silurian Longmaxi Formation. Shale pore characteristics are the main indicators for evaluating the quality of shale reservoirs and largely determine shale gas productivity. We have qualitatively and quantitatively analyzed pore types and structures through scanning electron microscopy, CO2/N2 adsorption and high-pressure mercury injection experiments, and nuclear magnetic resonance. The pore types of marine shale gas reservoirs in the study area mainly included organic-matter pores and clay mineral interlamellar pores. The pore diameter of the shale reservoir ranged from 0.5 to 35 nm and was concentrated in the range of 2–10 nm, and the main pores were mesopores. Total organic carbon (TOC) content was positively correlated with fractal dimension, which could be used to quantitatively evaluate the complexity and heterogeneity of reservoir pores. The contents of TOC, clay, and siliceous minerals were the main factors controlling the development of shale micropores. The contents of clay minerals and siliceous minerals determined the storage space of shale gas, whereas micropores and mesopores controlled the adsorption capacity of shale.
Racial differences in survival outcomes for early-stage (T1 tumor) penile cancer: Analysis from the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Candelario Nellowe , Molina Elizabeth , Bourlon Maria Teresa , Kim Simon P. , Kessler Elizabeth R , Spiess Philippe E. , Flaig Thomas W.
Published: February 2022

5

Background: Penile cancer is a rare malignancy that accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors (no invasion the corpora spongiosum, corpora cavernosa or adjacent structures using the AJCC 7th edition staging system) are potentially curable with local surgery. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. Methods: From 2004 to 2016, we identified all patients with T1 (coded as T1, T1a, T1b),N0,M0 penile cancer in the SEER-18 database were included. Univariate Kaplan-Meier analysis and multivariable (adjusting for age, year of diagnosis, race, socioeconomic status, primary tumor site and type of surgery) Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CCS). Results: A total of 4,406 patients were identified with penile cancer; 1,941 patients had T1 disease and were further evaluated (Table). On multivariable analysis, Black (HR: 1.72, CI 1.01- 2.94; p=0.046) and Hispanic individuals (HR: 2.15, CI 1.36- 3.40; p= 0.001) had worse CSS compared to the White men with T1 disease. Logistic regression analysis shows no difference in the application of primary surgical resection by race (p=0.065). In the univariate analysis, patients who underwent primary site surgery had better 5-year CSS (HR: 0.36, CI 0.22-0.60; p <0.001). Among those undergoing primary surgery, the 5-year CSS was superior with excisional biopsy (HR: 0.22, CI 0.12-0.40; p < 0.001) compared to simple/partial removal of the primary tumor. Conclusions: Significant racial disparities in CSS exist in early-stage penile cancer patients. CSS is worse in Black and Hispanic T1 penile cancer patients compared to White patients. CSS is also decreased in those without any primary surgery and in those treated with simple/partial surgical removal compared to excisional biopsy. Further research on the cause of racial disparity outcomes in penile cancer is needed.[Table: see text]
Disparities in prostate cancer: An ethnicity comparative focus among Hispanic Americans versus non-Hispanic whites.
Authors: Recio-Boiles Alejandro , Batai Ken , Cheng Ce , Heimark Ronald , Chipollini Juan
Published: February 2022

23

Background: Prostate cancer (PCa) is a clinically heterogeneous disease and the incidence and mortality risk varies widely among racial/ethnic groups. Among Hispanic American (HA) men, PCa accounts for nearly one-quarter of the total cancer burden; in addition, advanced stage and mortality rates are significantly higher in HA compared to Non-Hispanic White (NHW) men. Despite a decade of declining overall incidence rates, incidence rates of advanced PCa appear to be increasing over time among HA men, a similar pattern seen among Non-Hispanic Blacks (NHB). Methods: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA at diagnosis between 2010 and 2016. HAs were divided into four major subgroups: Mexican/Chicano, Puerto Ricans, Cubans, and Central/South Americans. NHB, Asian, and other racial groups were excluded. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Univariable and multivariable logistic regression models were used to evaluate the association of HA ethnic subgroups with metastatic presentation and primary treatment. Results: A total of 428,829 patients were included with 5,625 (1.3%) being HA. Mexican comprised 51.2% of HAs and presented with higher PSA and Gleason score at diagnosis and more advanced cT, N1 and M1 stage when compared to NHW men and other HA subgroups (all, p < 0.001) (Table). After adjusting for age, PSA, year of diagnosis, cT, N, insurance, income, education, and performance score, Mexican had 1.32 (95%CI: 1.07-1.63, p = 0.01) higher odds of initial metastatic presentation and 0.68 (95%CI: 0.55-0.85, p < 0.001) lower odds of receiving treatment compared to NHW men while no statistically significant difference was seen for the other HA subgroups. Conclusions: Even after accounting for socioeconomic disparities, Mexican men present with a more aggressive disease when compared to NHW and other HA subgroups. Our results warrant further investigations into potential biological factors affecting HA PCa as well as identifications of potential barriers to treatment for vulnerable populations.[Table: see text]
Randomized controlled trial of GnRH antagonist monotherapy versus GnRH agonist plus bicalutamide (CAB) for patients with metastatic hormone-sensitive prostate cancer (mHSPC) (KYUCOG-1401).
Authors: Yokomizo Akira , Morokuma Futoshi , Eto Masatoshi , Shiota Masaki , Matsuyama Hideyasu , Matsumoto Hiroaki , Kamoto Toshiyuki , Terada Naoki , Kawahara Kazuya , Enokida Hideki , Tatarano Shuichi , Fujimoto Naohiro , Higasijima Katsuyoshi , Sakai Hideki , Hakariya Tomoaki , Igawa Tsukasa , Suekane Shigetaka , Kamba Tomomi , Sugiyama Yutaka , Naito Seiji
Published: February 2022

99

Background: To investigate a clinical response of GnRH antagonist monotherapy against CAB therapy for mHSPC. Methods: Histopathological confirmed mHSPC patients were randomly assigned to GnRH antagonist monotherapy group (Group A) and CAB group (Group B). A deferred CAB therapy by adding bicalutamide to GnRH antagonist was performed in Group A after PSA progression. The primary endpoint was PSA progression free survival (PSA-PFS). The secondary endpoints were time to CAB treatment failure (CAB-TTF), radiographic progression free survival (rPFS), overall survival (OS), change of PSA, effect on hormone dynamics, change of bone metabolic markers, effect on lipid metabolism, adverse events (AE). This trial was registered with UMIN-CTR (UMIN000014243). Results: A total of 200 patients (101 patients in Group A and 99 in Group B) were registered from June 2014 to June 2017. The PSA-PFS was significantly better in Group B (HR (95% CI) =1.40 (1.01-1.95), p=0.041) as shown in the table. Time to CAB treatment failure (TTF) tended to be better in Group A, but there was no statistically significant difference in CAB-TTF between two groups (Table). rPFS and OS were also not statistically significant difference (Table). Time to PSA nadir was significantly shorter in Group B (HR (95% CI) = 0.72 (0.54 - 0.97), p = 0.028). The proportion of patients whose serum testosterone did not reach or maintain the castration level was more frequent in Group A (significant difference at 60 weeks, p = 0.046). There was no significant difference in the effect of bone metabolic markers and lipid metabolism between two groups. In terms of AE, injection-site-reaction was more frequent in Group A. Conclusions: LH-RH agonist CAB therapy (Group B) prolonged PSA-PFS compared to LH-RH antagonist monotherapy (Group A), probably due to the higher frequency of insufficient achievement of castration level in Group A. However, a deferred CAB therapy by adding bicalutamide to GnRH antagonist resulted in no difference in CAB-TTF, rPFS and OS. Clinical trial information: UMIN000014243.[Table: see text]
Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (ENZA) + androgen deprivation therapy (ADT) by high or low disease volume and progression to mHSPC (M0 at diagnosis) or de novo mHSPC (M1 at diagnosis): Post hoc analysis of the phase 3 ARCHES trial.
Authors: Armstrong Andrew J. , Iguchi Taro , Azad Arun , Szmulewitz Russell Zelig , Holzbeierlein Jeffrey , Villers Arnauld , Alcaraz Antonio , Alexeev Boris , Shore Neal D. , Gomez-Veiga Francisco , Rosbrook Brad , Zohren Fabian , Yamada Shunsuke , Haas Gabriel P. , Stenzl Arnulf
Published: February 2022

115

Background: In ARCHES (NCT02677896), ENZA + ADT improved radiographic progression-free survival, OS, and other key secondary endpoints vs placebo (PBO) + ADT for pts with mHSPC (also known as metastatic castration-sensitive prostate cancer). Final OS results confirmed a long-term survival benefit with ENZA + ADT (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53, 0.81; p<0.0001). We present post hoc analyses of OS by disease volume and progression to M1 HSPC after initial diagnosis with localized disease (M0) or presentation of de novo mHSPC at initial diagnosis (M1). Methods: Pts with mHSPC (N=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT (n=574) or PBO + ADT (n=576), stratified by disease volume and prior docetaxel use. After unblinding, 180 (31.3%) PBO + ADT-treated pts crossed over to open-label ENZA + ADT. High disease volume was defined per CHAARTED criteria. Medical profiles of pts assessed as MX/unknown metastasis at initial diagnosis (n=213) were further reviewed centrally and adjudicated as having either M0 or M1 disease. Median OS and HRs were estimated by Kaplan-Meier methods and Cox proportional hazards, respectively. Results: Median treatment duration was 40.2 months (mo) for ENZA + ADT and 13.8 mo for PBO + ADT. Inclusive of crossover, 401 (69.6%) PBO + ADT pts had subsequent life-prolonging therapy. OS benefits with ENZA + ADT were seen in all disease volume and M0/M1 populations at a similar magnitude to the overall population (Table). Median OS was not reached in most populations except PBO + ADT pts with high disease volume (45.9 mo; 95% CI 40.1, not estimable [NE]) or high disease volume and M1 disease (43.4 mo; 95% CI 36.4, 49.7) and ENZA + ADT pts with high disease volume and M0 disease (54.2 mo; 95% CI 54.2, NE). Conclusions: Our post hoc analysis demonstrates consistent long-term survival benefit with ENZA + ADT vs PBO + ADT across pts with mHSPC with high and low disease volumes and M0 or M1 disease at initial diagnosis, despite substantial treatment crossover and subsequent therapy use in PBO + ADT pts.[Table: see text]
Association of changing bone metastatic (mets) patterns with dynamics of circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Conteduca Vincenza , Scarpi Emanuela , Rossi Alice , Ferroni Fabio , Gurioli Giorgia , Bleve Sara , Gianni Caterina , Schepisi Giuseppe , Brighi Nicole , Lolli Cristian , Cursano Maria Concetta , Virga Alessandra , Casadei Chiara , Altavilla Amelia , Farolfi Alberto , Ulivi Paola , Barone Domenico , Matteucci Federica , Paganelli Giovanni , De Giorgi Ugo
Published: February 2022

152

Background: Accurate monitoring response of bone mets to treatment is an active need for mCRPC patients (pts). Recently, ctDNA has been showed as an early biomarker efficacy of androgen receptor signaling inhibitor (ARSI) therapy for mCRPC ( Conteduca, Br J Cancer 2020). In this study, we aimed to reveal if ctDNA analysis can permit more reliable prediction of bone mets burden and radiographic progression disease (PD). Methods: In a biomarker study (REC 2192/2013), targeted next generation sequencing was performed to assess ctDNA fraction. Radiographic evidence of bone disease was documented by conventional imaging according to PCWG3 criteria ( Scher, J Clin Oncol 2018), and was classified on the basis of mets number (≤5, 6 -19, ≥20) in oligometastatic (O), diffuse (D), and widespread (W), respectively. Associations were explored both through uni/multivariate logistic regressions. Results: Serial plasma samples and radiographic scans on ARSI treatment were prospectively collected from 73 CRPC with bone mets. Median age was 74 years [interquartile range (IQR) 69-79]. Bone mets patterns were significantly associated with median baseline ctDNA level (O = 0.16, D = 0.33, and W = 0.46, p 0.0003). Similar results were reported on treatment and at PD (p 0.0003 and p 0.0007, respectively). In 24 pts with a progressive worsening of bone mets pattern (O→D→W) compared to pts with no change in bone mets pattern on ARSI, we observed an early meaningful ctDNA rise with a % ctDNA variation from baseline to 3 month therapy of 150.6% (IQR 104.9-210.7) vs 11.1% (IQR 0-36.6), p < 0.0001. Univariate analysis showed that early ctDNA rise was significantly associated with radiographic progression free/overall survival (rPFS/OS): hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.30-3.27, p 0.002, and HR 1.82, 95% CI 1.15-2.88, p 0.01, respectively]. In multivariable analyses including ctDNA variation, changing bone mets pattern, age, performance status, and presence of concomitant visceral mets, ctDNA change at 3 month ARSI resulted the only independent predictor of both rPFS/OS (HR 2.27, 95% CI 1.04-4.94, p 0.027 and HR 2.98, 95% CI 1.31-6.81, p 0.033, respectively). Visceral mets were associated with only OS (HR 3.87, 95% CI 1.76-8.51, p 0.0008). Conclusions: Early ctDNA variation may reflect changes in bone mets pattern on ARSI allowing to track pattern of bone progression and predict outcome. Further studies to validate these findings are warranted.
Molecular testing for prostate cancer in Greek patients.
Authors: Liontos Michael , Kunadis Elena , Svarna Anna , Skafida Efthymia , Fiste Oraianthi , Markellos Christos , Zakopoulou Roubini , Papatheodoridi Alkistis , Andrikopoulou Angeliki , Kaparelou Maria , Koutsoukos Konstantinos , Zagouri Flora , Dimopoulos Meletios A.
Published: February 2022

170

Background: Molecular testing for mutations in genes related to homologous recombination repair (HRR) and microsatellite instability (MSI) is suggested for patients with advanced prostate cancer by international guidelines. Recently, olaparib has been approved for patients with metastatic castration resistant prostate cancer patients that bear mutations in BRCA1/2 genes in Europe. In Greece, molecular testing for prostate cancer patients is not reimbursed. In this setting we describe our experience from investigating the molecular profile of patients with advanced/metastatic disease. Methods: We retrospectively collected clinicopathological data of patients treated in our center for advanced/metastatic prostate cancer whose tumours were subjected to whole exome sequencing analysis for a panel of 58 genes including BRCA1/2. All patients provided written informed consent and the study was approved by the local ethics committee. Results: Tumor samples from 37 patients with advanced or metastatic prostate cancer were analyzed. Median age of the patients was 60.2 years (25th-75th percentile 54.4-63.9 years) and most of them (19/37, 51.4%) were presented with de novo metastatic disease. Clinicopathological characteristics of the patients are presented in the table. Eight samples (21.6%) were evaluated as inadequate to perform further analysis. In the remaining 29 cases, no BRCA1/2 mutations were detected. Instead, 7 patients had mutations in HRR-related genes, including 3 patients with ATM mutations, two in CHEK2, one in CHEK1 and one in RAD50. TP53 mutations were found in 8 patients (21.6%) and PTEN mutations in 2 (5.4%). Newer Hormonal Treatments were used as first-line treatment in mCRPC in 24 patients (64.9%), while 6 received docetaxel. Median PFS in first-line mCRPC was 12.0 months (95% CI 9.7-14.3) in the whole population and did not differ significantly in patients with HRD mutations (11.8 months) or TP53 mutations (11.8 months). Two patients with ATM mutations received olaparib as fourth and fifth line of treatment respectively with stable disease as best response. Conclusions: Biomarker driven targeted therapies are currently available for mCRPC patients. In our cohort, molecular testing was negatively affected by the poor quality of archival tissues in a significant percentage of patients. However, mutations in HRR-related genes were found in almost 20% of patients with possible therapeutic implications. Therefore, it is necessary to have a reimbursed molecular testing for prostate cancer patients in Greece.[Table: see text]
Identification of homologous recombination and repair (HRR) deficiency using circulating tumor DNA (ctDNA) in advanced prostate cancer (aPC).
Authors: Bucheit Leslie A. , Yen Jennifer , Drusbosky Leylah , Barbacioru Catalin , Gnerre Sante , Wang Hao , Artyomenko Alexander , Yabolonovitch Arielle , Fu Yu , Lee Che-Yu , Maliska Max , Helman Elena , Dorshner Michael , Lefterova Martina
Published: February 2022

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Background: ctDNA testing is a non-invasive means to identify genomic alterations in patients with aPC, including BRCA1/2 and other HRR gene alterations, which are targetable by PARP inhibitors (PARPi). However, classes of HRR inactivating mutations, such as copy number loss and large genomic rearrangements (LGRs) are challenging to detect by ctDNA. Here we describe a CLIA-validated plasma-based ctDNA test that identifies copy number loss and LGRs, in addition to SNV and Indels, in HRR genes. We report the landscape of HRR deficiency (HRD) in a clinical population of > 2,000 patients with aPC. Methods: 2932 samples from patients with aPC previously tested as part of clinical care using an 83-gene cfDNA NGS assay (Guardant360) within an 11-month period were reanalyzed for presence of HRD. HRD alterations were defined as copy number loss, LGR (i.e. intergenic or intragenic gene rearrangements) and deleterious SNV/Indel in 7 clinically focused HRR genes ( ATM, BRCA1, BRCA2, CDK12, CHEK2, PALB2, RAD51D). Clinical information, when available, was obtained from test requisition forms. Results: The median age of the analyzed cohort was 73 years (range: 31-100); when known, the majority of patients were tested at disease progression (81%, 2242/2750). In total, an inactivating BRCA1/2 variant was was identified in 26% (605/2932) of reanalyzed patients, comprising BRCA1/2 loss of heterozygosity (LOH) (13.4% of patients), deleterious SNV or Indels (5.5%), homozygous deletions (3.3%) and LGRs (1.1%). The prevalence of patients with any inactivating HRR alteration increased to 38.5% with the expanded 7 gene set. Overall, prevalence of loss-of-function mutations (SNV/Indel, homozygous deletion or LGR) in BRCA2 was 4.5X frequent than in BRCA1 and comparable to previously described prostate cohorts (8.4% and 1.8% compared to 8.6% and 1.1% in tissue, respectively). Conclusions: Genomic profiling by ctDNA identified an HRR alteration landscape comparable to previously characterized tissue cohorts, with enrichment in BRCA2 over BRCA1 inactivating mutations and frequent BRCA1/2 LOH. Patients with aPC may benefit from PARPi eligibility determination using rapid and reliable ctDNA assessment, particularly at progression. Future studies should assess PARPi outcomes for this population.
Efficacy and safety outcomes of darolutamide in patients with nonmetastatic castration-resistant prostate cancer with comorbidities and concomitant medications from ARAMIS.
Authors: Fizazi Karim , Shore Neal D. , Smith Matthew Raymond , Ramos Rodrigo , Jones Robert J. , Niegisch Guenter , Vjaters Egils , Ortiz Jorge A. , Liang Steve , Wang Yuan , Srinivasan Shankar , Sarapohja Toni , Verholen Frank
Published: February 2022

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Background: Patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) are primarily older, have comorbidities, and take concomitant medications. Darolutamide (DARO), a structurally distinct and highly potent androgen receptor inhibitor, significantly reduced the risk of metastasis by ̃2 years and the risk of death by 31% versus placebo (PBO) and demonstrated favorable safety and tolerability in the phase 3 ARAMIS trial. DARO also has low potential for drug−drug interactions. This post hoc analysis of ARAMIS evaluated overall survival (OS) and safety in pts with ongoing comorbidities and concomitant medications. Methods: Pts with nmCRPC were randomized 2:1 to DARO (n=955) or PBO (n=554) while continuing androgen-deprivation therapy. At the final data cutoff (Nov 15, 2019), OS and adverse events (AEs) were evaluated in pts with a median of ≤ and >6 comorbidities or ≤ and >10 concomitant medications in the double-blind period. HRs (95% CIs) were determined from univariate analysis using Cox regression. Results: The majority of pts had ≥6 comorbidities (53%; 795/1509) or received ≥10 concomitant medications (54%; 813/1509). For pts with ≤6 and >6 comorbidities, DARO prolonged OS vs PBO (HR 0.65 and 0.73, respectively). OS benefit of DARO vs PBO was consistent for pts with metabolic, cardiovascular (CV), and other comorbid disorders (HR range: 0.39–0.88). For pts receiving ≤10 and >10 concomitant medications, OS was prolonged with DARO vs PBO (HR 0.76 and 0.66, respectively). Subgroups of pts receiving concomitant medications for gastrointestinal/metabolic disorders, CV disease, urologic disorders, and pain/inflammation achieved similar OS benefit with DARO vs PBO (HR range: 0.45–0.80). Incidence of AEs and AEs leading to treatment discontinuation with DARO was comparable to PBO across subgroups by number of comorbidities and concomitant medications (Table). Conclusions: The OS benefit and safety of DARO remained consistent with that observed in the overall ARAMIS population, even in patients with a high number of comorbidities or concomitant medications. Clinical trial information: NCT02200614. [Table: see text]