bluuebunny/crossref_metadata_2025_split huggingface dataset:
IK-175, an oral AHR inhibitor, as monotherapy and in combination with nivolumab in patients with urothelial carcinoma resistant/refractory to PD-1/L1 inhibitors.
Authors: Aggen David H , McKean Meredith , Hoffman-Censits Jean H. , Lakhani Nehal J. , Alhalabi Omar , Guancial Elizabeth A. , Bashir Babar , Bowman I. Alex , Tan Alan , Lingaraj Trupti , Kim Katherine , Timothy Marissa , Ortiz-Otero Nerymar , Bartolini Wilmin , Kacena Katherine , Santillana Sergio , Luke Jason J. 
Published: June 2024

2599 Background: IK-175 is an oral, selective, small molecule Aryl Hydrocarbon Receptor (AHR) inhibitor. AHR is a ligand-activated transcription factor that binds kynurenine causing gene expression that promotes an immunosuppressive tumor microenvironment, possibly driving resistance to PD-1/L1 inhibitors (CPIs). Urothelial carcinoma (UC) demonstrates increased AHR signaling and nuclear protein localization as shown by gene expression analysis and tissue-based immunohistochemistry. Methods: This is a first-in-human, open-label, multicenter, study of IK-175 monotherapy and with nivolumab initially in solid tumors and for expansion in UC. Dose expansion patients received 1200mg QD of IK-175. Nivolumab was given at 480mg q4w in the combination cohorts. Both monotherapy and combination expansion arms utilized Simon 2-stage designs, and enrolled heavily pretreated UC patients who progressed ≤ 12 weeks of last dose of PD-1/L1 inhibitors (CPIs) and were enriched for nuclear AHR+ tumors by IHC. Study objectives included evaluation of safety, pharmacokinetics, pharmacodynamics, MTD, RP2D and antitumor activity (RECIST 1.1) of IK-175 as a monotherapy and in combination with nivolumab. Results: Fifty-seven UC expansion patients were evaluated for safety. Median age was 69 years (range 26-81), 52/57 (91%) patients received ≥2 lines of prior therapy including CPIs. 5/14 monotherapy and 14/43 combo had nuclear AHR+ tumors. The most common treatment-related AEs were nausea, fatigue, and diarrhea. Infrequent immune-related AEs occurred in <9% of patients and included adrenal insufficiency, proteinuria, rash, pneumonitis, and immune-related arthritis. Significant reduction in tumor target lesions (-30% to -100%) was observed in 6/46 (13%) response-evaluable UC patients (both arms). DCR was 46% and 49% for monotherapy and combination. Confirmed partial responses were observed in 1/13 (7.7%) monotherapy (DoR 22.6 months) and 2/33 (6%) in combo (DoR 4.4 and 7.3 months). Two patients in combo were treated beyond progression (for 4 and 10 months) due to investigator-assessed clinical benefit, including tumor shrinkage of target lesions. Conclusions: IK-175 showed a predictable, consistent safety profile as a monotherapy and in combination with nivolumab. Meaningful clinical benefit and objective, durable, prolonged responses were demonstrated in both monotherapy and combination arms in heavily pretreated UC patients with tumors refractory to CPI and supports further development of this asset in solid tumors. Clinical trial information: NCT04200963 .
Cancer diagnostic service use in people living with HIV in South Africa: A cross-sectional study
Authors: Olago Victor , Nimako Gideon , Bartels Lina , Bohlius Julia , Dhokotera Tafadzwa , Egger Matthias , Singh Elvira , Sengayi-Muchengeti Mazvita 
Published: June 2024

Objective
The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people living with HIV (PLHIV) within South Africa (SA) using national laboratory database.

Design
We linked HIV and cancer laboratory data from 2004–2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis.

Setting
We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA.

Study population
Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004–2014.

Primary and secondary outcomes
We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer.

Results
The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33–48] years for the study population with most cancers in PLHIV diagnosed in females 70.9% [n = 46,313]. Of all the PLHIV and cancer, 25% (n = 16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n = 10,235) travelling to Gauteng. KZN had 46.6% (n = 4,107) of its PLHIV getting cancer diagnosis in Gauteng. Western Cape had 95% (n = 6,200) of PLHIV getting cancer diagnosis within the province.

Conclusions
Our results showed health systems inequalities across provinces in SA with respect to cancer diagnosis. KZN for example had nearly half of the PLHIV getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PLHIV in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country.
Clinical impact of rapid molecular diagnostic tests in patients presenting with viral respiratory symptoms: A systematic literature review
Authors: Mojebi Ali , Wu Ping , Keeping Sam , Hale Braden , Chase Jordan G. , Beaubrun Anne 
Published: June 2024

Background
Molecular tests can detect lower concentrations of viral genetic material over a longer period of respiratory infection than antigen tests. Delays associated with central laboratory testing can result in hospital-acquired transmission, avoidable patient admission, and unnecessary use of antimicrobials, all which may lead to increased cost of patient management. The aim of this study was to summarize comparisons of clinical outcomes associated with rapid molecular diagnostic tests (RMDTs) versus other diagnostic tests for viral respiratory infections.

Methods
A systematic literature review (SLR) conducted in April 2023 identified studies evaluating clinical outcomes of molecular and antigen diagnostic tests for patients suspected of having respiratory viral infections.

Results
The SLR included 21 studies, of which seven and 14 compared RMDTs (conducted at points of care or at laboratories) to standard (non-rapid) molecular tests or antigen tests to detect SARS-CoV-2 and influenza, respectively. In studies testing for SARS-CoV-2, RMDTs led to reductions in time to test results versus standard molecular tests (range of the reported medians: 0.2–3.8 hours versus 4.3–35.9 hours), with similar length of emergency department stay (3.2–8 hours versus 3.7–28.8 hours). Similarly, in studies testing for influenza, RMDTs led to reductions in time to test results versus standard molecular tests (1–3.5 hours versus 18.2–29.2 hours), with similar length of emergency department stay (3.7–11 hours versus 3.8–11.9 hours). RMDTs were found to decrease exposure time of uninfected patients, rate of hospitalization, length of stay at the hospitals, and frequency of unnecessary antiviral and antibacterial therapy, while improving patient flow, compared to other tests.

Conclusions
Compared to other diagnostic tests, RMDTs improve clinical outcomes, test turnaround time, and stewardship by decreasing unnecessary use of antibiotics and antivirals. They also reduce hospital admission and length of stay, which may, in turn, reduce unnecessary exposure of patients to hospital-acquired infections and their associated costs.
Integrating design thinking and implementation science principles in delivering a medication review service in the community pharmacy setting—An implementation testing study
Authors: Mustafa Maali , Hatah Ernieda , Makmor-Bakry Mohd 
Published: June 2024

Background
Medication review (MR) services are evidenced-based practices in which a systematic assessment of a patient’s medication is conducted, primarily aiming to optimize drug therapy and minimize adverse drug events through pharmacist interventions. Although studies show that MR services are effective, the implementation of MR services in Malaysia has been challenging due to several barriers. An MR services blueprint was developed to be adapted to the Malaysian community pharmacy setting as part of tailoring strategies.

Objective
Through utilizing the design thinking triple diamond model and implementation science principles, a powerful guide for healthcare researchers and stakeholders to assist with effective service implementation, this study aimed to evaluate the implementation testing and observe the effectiveness of the developed MR service blueprint.

Method
The study utilizes an effectiveness-implementation Type 3 hybrid implementation science framework conducted from May 2021 to April 2022. Employing a qualitative ethnographic approach, researchers observed pharmacy study sites during the implementation of MR services. Both qualitative and quantitative data were collected across exploration, preparation, testing, and operational phases. Implementation outcomes evaluated include phases, reach, fidelity, acceptability, as well as implementation barriers and strategies. MR intervention outcomes included service characteristics and the number and type of drug-related problems and interventions offered.

Results
17 community pharmacists were invited to pilot the MR service blueprint for six months in their setting. Of this, 78.5% (n = 11) of the pharmacies reached the testing phase, and 36% (n = 4) reached the implementation phase. Fifty-four patients were in the study, giving an implementation reach of 70%. The majority of surveyed patients expressed satisfaction with the service. The total DRP identified was 133, and 64 interventions were provided by the pharmacists. Facilitation strategies such as “Engage stakeholders by creating ownership of the change” and “Equip stakeholders with training” are needed to overcome the barriers.

Conclusion
This study marked the beginning of successful MR service implementation at Malaysian community pharmacies. Future studies with multi-level partnered strategies are required to reach full implementation and sustainability.
Atmospheric plasma treatment of rubber and its effect on surface characteristics
Authors: Ďurišová Silvia , Pajtášová Mariana , Ondrušová Darina , Janík Róbert , Mičicová Zuzana , Dubec Andrej , Pagáčová Jana , Šulcová Jana , Božeková Slavomíra , Vavro Jan , Klepka Tomasz 
Published: June 2024

The changes of rubber blend surface induced by atmospheric plasma at several conditions were studied via FTIR, SEM, contact angle and adhesion measurement. After plasma, the presence of OH, COO- bands of higher intensity was observed, whilst methylene groups reduced. A several formations of weaker agglomeration and cleaning of the surface was recognized. Also an intense decline of contact angles was observed. The plasma induced significantly greater changes at the 0.5 mm position, whereas emission times of 10 s and 30 s did not significantly affect the modifications of the investigated surface.
Bonding over bashing: Discussing LGBTI topics in far-right alternative news media comments sections
Authors: Verhoeven Emma 
Published: June 2024

Abstract
This study investigates virtual community-building practices and discriminatory views in PAL NWS, a Dutch-speaking Belgian far-right alternative news medium, by examining discussions in the comments sections. Thematic analysis was applied to a total of 1,127 comments by 343 users in response to 50 articles about LGBTI topics. The findings show that far-right alternative news sites can function as virtual communities that facilitate polarization. The comments exhibited a high level of hostility towards LGBTI individuals, particularly toward transgender people and public displays of LGBTI inclusion. Furthermore, Muslims were homogeneously perceived as homophobes, and LGBTI topics were understood as (woke) ideological suppression by a dogmatic minority. The results of this study have implications for understanding the dynamics of comments sections on alternative media and the potential for far-right news platforms to facilitate the spread of intolerance.
(De)Gendering (English-Spanish) Translation of Legal Texts
Authors: Vázquez y del Árbol Esther 
Published: June 2024

Abstract
Within Western culture, gender is frequently interpreted in terms of binarism (male versus female), derived from biological sex at birth. Nevertheless, there is an accelerating percentage of non-binary and transgender people, who are not related to binary nomenclature, and they also need to resort to legal documentation and their renderings into other languages. This fact becomes a troublesome issue that must be nowadays solved, especially when translating into Spanish, a grammatical gender language, from English, a non-grammatical gender language. In this paper we will first select a corpus of eight British legal documents representing highly demanded translation briefs. We will then search for 15 problematic lexical items, searching for their lexicographic definitions and translations, and we will later resort to their most feasible translations into the Spanish language, considering both gendered translations and genderless ones. Our research shows how the Spanish language has its own translation techniques, especially paraphrasing, to be able to provide the English-Spanish target readership with binary legal terms, and especially with non-binary ones.
GEOCHEMISTRY AND MINERALOGY OF RARE-EARTH ELEMENTS IN FERRUGINOUS DEPOSITS AND BOTTOM SEDIMENTS OF THE LAPTEV SEA
Authors: КОЛЕСНИК О.Н. , КОЛЕСНИК А.Н. , АСТАХОВ А.С. 
Published: June 2024

Проанализированы геохимические и минералогические аспекты распределения редкоземельных элементов (РЗЭ) в железистых образованиях (ЖО) и донных осадках юго-восточной части моря Лаптевых. Среди ЖО преобладают биоморфозы по трубкам полихет. Общее содержание и распределение РЗЭ в ЖО складывается из соотношения рудного и нерудного вещества. Рудное вещество представлено в основном гидроксидами железа (лимонит). Оно сформировалось в ходе субокислительного диагенеза, усиленного процессами биотурбации, и определяет в ЖО некоторый избыток средних РЗЭ и дефицит церия (Ceан - 0.94). Нерудное вещество поступает в ЖО из терригенных осадков и имеет (алюмо)силикатный состав. Оно определяет в ЖО содержание скандия и является источником зерен минералов РЗЭ, среди которых преобладает монацит-(Ce). Для осадков характерно общее подобие составу РЗЭ в сланцах и во взвеси р. Лена, впадающей в море Лаптевых, при небольшом избытке легких и средних РЗЭ и величине цериевой аномалии, практически равной единице (Ceан - 1.06). В осадках минералы РЗЭ тяготеют к фракциям мельче 63 мкм. Высокое содержание в осадках органического вещества (Сорг - до 2.15 %), имеющего преимущественно терригенный генезис (ОВтер - до 85 %), объясняет дефицит кислорода и общее вялое протекание процессов диагенетического минералообразования со слабым накоплением в ЖО микроэлементов, включая РЗЭ. Суммарное содержание РЗЭ в ЖО ниже, чем в осадках, и составляет в среднем 173 против 206 г/т.
The geochemical and mineralogical aspects of the distribution of rare-earth elements (REE) in ferruginous deposits (FD) and bottom sediments of the southeastern Laptev Sea are analyzed. The FD are dominated by biomorphs developed after polychaete tubes. The REE patterns depend on the proportion of ore and non-ore substances. The ore substance is represented mainly by iron hydroxides (limonite). It is a product of suboxic diagenesis enhanced by bioturbation and determines the slight enrichment of FD in MREE and cerium deficiency (Cean = 0.94). The non-ore substance comes from terrigenous sediments and has an (alumino)silicate composition. It controls the scandium content and is the source of REE mineral grains, among which monazite-(Ce) prevails. The sediments demonstrate a common similarity in REE patterns to shales and suspended material transported to the Laptev Sea by the Lena River, with elevated LREE and MREE contents and the value of Ce anomaly almost equal to unity (Cean = 1.06). In the sediments, REE minerals occur mostly in the silt fraction (<63 μm in size). The high content of organic matter (Corg of up to 2.15%) of predominantly terrigenous origin (OMter of up to 85%) in the sediments explains the oxygen deficiency and weak diagenetic mineral formation with low accumulation of trace elements, including REE, in the FD. The total REE content in the FD is lower than that in the sediments (on average, 173 ppm against 206 ppm).
IMPACT OF SANCTIONS ON EMPLOYMENT AND UNEMPLOYMENT IN RUSSIAN REGIONS: ANALYSIS OF DYNAMICS AND MAIN TRENDS
Authors: Кондратьев Р.А. 
Published: June 2024

Актуальность исследуемой темы обусловлена нарастающим воздействием экономических санкций на социально-экономическое развитие страны. В условиях глобализации экономические санкции становятся инструментом политического и экономического давления, что приводит к значительным изменениям в экономике страны, влияя на уровень занятости и безработицы в различных регионах. Различная степень уязвимости регионов перед лицом санкционной политики требует детального анализа, что делает тему крайне важной для исследования. Оценка влияния санкций на занятость и безработицу позволит выработать рекомендации по смягчению негативных эффектов для социально-экономического развития регионов и страны в целом.
The relevance of the studied topic is due to the growing impact of economic sanctions on the socio-economic development of the country. In the conditions of globalization, economic sanctions become an instrument of political and economic pressure, which leads to significant changes in the country’s economy, affecting the level of employment and unemployment in different regions. The different degree of vulnerability of regions to the sanctions policy requires a detailed analysis, which makes the topic extremely important for the research. Assessing the impact of sanctions on employment and unemployment will make it possible to develop recommendations to mitigate the negative effects on the socio-economic development of regions and the country as a whole.
EURASIAN INTEGRATION: TRANSPORT ASPECT
Authors: Дроздова М.А. 
Published: June 2024

В статье рассматривается транспортный аспект интеграционных процессов в Евразийском регионе, основные проблемы правового регулирования указанной сферы. Автором обосновывается необходимость корректировки существующего подхода к формированию актуальной модели международно-правового регулирования евразийской транспортной интеграции как важной составляющей обеспечения конкурентоспособности России как на региональном, так и на глобальном уровне. Для полноценной реализации евразийского транзитного потенциала, а также для обеспечения технологического суверенитета России необходима гармонизация законодательства стран-партнеров в сфере регламентации применения технологий Индустрии 4.0 в транспортно-логистической отрасли.
The article addresses the integration processes’ transport aspect in the Eurasian region, reviews the main issues of transport and logistics legal regulation of this sphere. The researcher substantiates the need to adjust the existing approach to the development of an actual model of international legal regulation of Eurasian transport integration, since it is an important pillar of ensuring Russia’s competitiveness both at regional and global levels. It is necessary to harmonize the legislation of EAEU and China about use of Industry 4.0 technologies in transport and logistics. It would provide for realization of the Eurasian transit potential, as well as ensuring the Russia’s technological sovereignty.
Education and Training on Organic and Inorganic Waste Management for the Community of RT 1 Bunglai Village
Authors: Syarif Muhammad , Puspitasari Regista Tri , Nurnajwa Nurnajwa , Rafidah Nurhanna , Waskito Agung 
Published: June 2024

Waste is an environmental problem that requires serious handling. The behavior of the people of Bunglai Village RT 01 towards household waste is based on data, namely by burning it at 44%, throwing it carelessly at 34%, burying it in the ground at 18%, and throwing it into the river at 4%. This community behavior causes environmental pollution and disrupts public health. Thus, intervention is needed at the root of the problem, namely the management of organic and inorganic waste. The intervention carried out was Education and Training on Organic and Inorganic Waste Management. The methods used are Ecobricks and Takakura Compost.The results of the intervention in the community showed that there was an increase in knowledge and attitudes. The average value of the pre-test knowledge was 46.61 to 61.30 at the post-test and the average pre-test attitude score was 15.39 to 17.18 at post-test. To see the output, a pre-test and post-test Wilcoxon test was carried out, it was found that the significance value for knowledge was 0.000<0.05 and for attitude it was 0.000<0.05, meaning that there are differences in knowledge and attitudes between before and after the intervention in the form of counseling.
Anterior-Posterior Laxity in Midflexion After Posterior-Stabilized TKA Is Sensitive to MCL Tension in Passive Flexion
Authors: Berube Erin E. , Xiang William , Manzi Joseph E. , Mayman David J. , Westrich Geoffrey H. , Wright Timothy M. , Chalmers Brian P. , Imhauser Carl W. , Sculco Peter K. , Kahlenberg Cynthia A. 
Published: June 2024

Background:
Knee instability in midflexion may contribute to patient dissatisfaction following total knee arthroplasty (TKA). Midflexion instability involves abnormal motions and tissue loading in multiple planes. Therefore, we quantified and compared the tensions carried by the medial and lateral collateral ligaments (MCL and LCL) following posterior-stabilized (PS) TKA through knee flexion, and then compared these tensions with those carried by the native knee. Finally, we examined the relationships between collateral ligament tensions and anterior tibial translation (ATT).

Methods:
Eight cadaveric knees (from 5 male and 3 female donors with a mean age of 62.6 years and standard deviation of 10.9 years) underwent PS TKA. Each specimen was mounted to a robotic manipulator and flexed to 90°. ATT was quantified by applying 30 N of anterior force to the tibia. Tensions carried by the collateral ligaments were determined via serial sectioning. Robotic testing was also conducted on a cohort of 15 healthy native cadaveric knees (from 9 male and 6 female donors with a mean age of 36 years and standard deviation of 11 years). Relationships between collateral ligament tensions during passive flexion and ATT were assessed via linear and nonlinear regressions.

Results:
MCL tensions were greater following PS TKA than in the native knee at 15° and 30° of passive flexion, by a median of ≥27 N (p = 0.002), while the LCL tensions did not differ. Median tensions following PS TKA were greater in the MCL than in the LCL at 15°, 30°, and 90° of flexion, by ≥4 N (p ≤ 0.02). Median tensions in the MCL of the native knee were small (≤11 N) and did not exceed those in the LCL (p ≥ 0.25). A logarithmic relationship was identified between MCL tension and ATT following TKA.

Conclusions:
MCL tensions were greater following PS TKA with this typical nonconforming PS implant than in the native knee. Anterior laxity at 30° of flexion was highly sensitive to MCL tension during passive flexion following PS TKA but not in the native knee.

Clinical Relevance:
Surgeons face competing objectives when performing PS TKA: they can either impart supraphysiological MCL tension to reduce anterior-posterior laxity or maintain native MCL tensions that lead to heightened anterior-posterior laxity, as shown in this study.