bluuebunny/crossref_metadata_2025 huggingface dataset:
Rumen microbiome-driven insight into bile acid metabolism and host metabolic regulation
Authors: Zhang Boyan , Jiang Xianzhe , Yu Yue , Cui Yimeng , Wang Wei , Luo Hailing , Stergiadis Sokratis , Wang Bing
Published: June 2024

Gut microbes play a crucial role in transforming primary bile acids (BAs) into secondary forms, which influence systemic metabolic processes. The rumen, a distinctive and critical microbial habitat in ruminants, boasts a diverse array of microbial species with multifaceted metabolic capabilities. There remains a gap in our understanding of BA metabolism within this ecosystem. Herein, through the analysis of 9371 metagenome-assembled genomes and 329 cultured organisms from the rumen, we identified two enzymes integral to BA metabolism: 3-dehydro-bile acid delta4,6-reductase (baiN) and the bile acid:Na + symporter family (BASS). Both in vitro and in vivo experiments were employed by introducing exogenous BAs. We revealed a transformation of BAs in rumen and found an enzyme cluster, including L-ribulose-5-phosphate 3-epimerase and dihydroorotate dehydrogenase. This cluster, distinct from the previously known BA-inducible operon responsible for 7α-dehydroxylation, suggests a previously unrecognized pathway potentially converting primary BAs into secondary BAs. Moreover, our in vivo experiments indicated that microbial BA administration in the rumen can modulate amino acid and lipid metabolism, with systemic impacts underscored by core secondary BAs and their metabolites. Our study provides insights into the rumen microbiome’s role in BA metabolism, revealing a complex microbial pathway for BA biotransformation and its subsequent effect on host metabolic pathways, including those for glucose, amino acids, and lipids. This research not only advances our understanding of microbial BA metabolism but also underscores its wider implications for metabolic regulation, offering opportunities for improving animal and potentially human health.
Non-Western Agency in Refugee Humanitarianism: Turkey and ‘Operation Provide Comfort’
Authors: İşleyen Beste
Published: June 2024

The evolution of refugee humanitarianism is commonly studied in terms of critical junctures. One such historical moment is the creation of a ‘safe zone’ for Iraqi Kurdish refugees above the 36th parallel of Northern Iraq through the 1991 United Nations (UN) mission known as ‘Operation Provide Comfort.’ The UN intervention is widely accepted as a critical juncture because it marked the beginning of international humanitarianism's extra-territorial phase. ‘Operation Provide Comfort’ brought a paradigm shift in the management of displaced populations by means of introducing “preventive protection” as a novel approach combining protection with control as the idea is to keep refugees in their own countries and offer them help without the need to cross an international border. The standard narrative underlines Western historical priority by attributing the preventive protection to a single source of ideas and processes stemming from the West. Drawing on postcolonial research, this paper argues for recognizing the agency of the non-West in the formulation and execution of the safe haven concept as a historical milestone. More specifically, it demonstrates the pioneering role that Turkey played through international debates and diplomatic action, which culminated into the new episode of refugee humanitarianism. The findings also invite us to revisit current explanations of the evolution of international humanitarian norms by showing the entanglement of refugee protection on the one hand, and domestic and regional questions of ethnicity and counter-insurgency on the other.
Distinguishing risk of curve progression in adolescent idiopathic scoliosis with bone microarchitecture phenotyping: a 6-year longitudinal study
Authors: Yang Kenneth Guangpu , Lee Wayne Yuk-Wai , Hung Alec Lik-Hang , Kumar Anubrat , Chui Elvis Chun-Sing , Hung Vivian Wing-Yin , Cheng Jack Chun-Yiu , Lam Tsz-Ping , Lau Adam Yiu-Chung
Published: June 2024

Low bone mineral density and impaired bone quality have been shown to be important prognostic factors for curve progression in adolescent idiopathic scoliosis (AIS). There is no evidence-based integrative interpretation method to analyze high-resolution peripheral quantitative computed tomography (HR-pQCT) data in AIS. This study aimed to (1) utilize unsupervised machine learning to cluster bone microarchitecture phenotypes on HR-pQCT parameters in girls with AIS, (2) assess the phenotypes’ risk of curve progression and progression to surgical threshold at skeletal maturity (primary cohort), and (3) investigate risk of curve progression in a separate cohort of girls with mild AIS whose curve severity did not reach bracing threshold at recruitment (secondary cohort). Patients were followed up prospectively for 6.22 ± 0.33 years in the primary cohort (n = 101). Three bone microarchitecture phenotypes were clustered by fuzzy C-means at time of peripubertal peak height velocity (PHV). Phenotype 1 had normal bone characteristics. Phenotype 2 was characterized by low bone volume and high cortical bone density, and phenotype 3 had low cortical and trabecular bone density and impaired trabecular microarchitecture. The difference in bone quality among the phenotypes was significant at peripubertal PHV and continued to skeletal maturity. Phenotype 3 had significantly increased risk of curve progression to surgical threshold at skeletal maturity (odd ratio [OR] = 4.88; 95% CI, 1.03–28.63). In the secondary cohort (n = 106), both phenotype 2 (adjusted OR = 5.39; 95% CI, 1.47–22.76) and phenotype 3 (adjusted OR = 3.67; 95% CI, 1.05–14.29) had increased risk of curve progression ≥6° with mean follow-up of 3.03 ± 0.16 years. In conclusion, 3 distinct bone microarchitecture phenotypes could be clustered by unsupervised machine learning on HR-pQCT–generated bone parameters at peripubertal PHV in AIS. The bone quality reflected by these phenotypes was found to have significant differentiating risk of curve progression and progression to surgical threshold at skeletal maturity in AIS.
Examining Income Expectations in the College and Early Post-College Periods: New Distributional Tests of Rational Expectations
Authors: Crossley Thomas F , Gong Yifan , Stinebrickner Ralph , Stinebrickner Todd
Published: June 2024

Using unique longitudinal probabilistic expectations data from the Berea Panel Study, which cover both college and early post-college periods, we examine young adults’ beliefs about their future incomes. We introduce two new approaches to testing whether, ex ante, agents exhibit Rational Expectations. We show that taking into account the additional information about higher moments of individual belief distributions contained in probabilistic expectations data reveals violations of Rational Expectations that are not detected by existing mean-based tests. Empirically, we find that our subjects underestimate the level of uncertainty they face about future incomes.
High-precision imaging of small voids in tunnel lining based on reverse time migration
Authors: Ling Tonghua , Jiang Hao , Zhang Liang , Zhang Sheng , Bei Zhenghao , Long Bin
Published: June 2024

Diseases such as voids behind the initial support of the tunnel will lead to problems such as lining rupture and concrete damage in the tunnel structure, which seriously affects the driving safety in the tunnel. In tunnel construction, ground penetrating radar is frequently employed as a method for detecting hidden defects. However, when the cavity size is small, there will be a large error when the original radar data is directly interpreted, which cannot meet the needs of practical engineering. To enhance the precision in tunnel detection, the Finite-Difference Time-Domain method is used to simulate various small cavities of different shapes located behind the primary support lining of the tunnel, and the study involves examining the electromagnetic response characteristics of different kinds of holes. The migration techniques of KIRCHHOFF, F-K, and reverse time are employed to reconstruct the hole target. Furthermore, digital morphology is employed to enhance the clarity of the image. Finally, the edge detection technology is used to further extract the hole features. After that, small cavities of different shapes are buried in the established outdoor concrete model box and radar detection is carried out. The detection position of the reconstructed radar image and the actual position of the cavity in the model box are verified. The results show that compared with KIRCHHOFF migration and F-K migration, the image processed by reverse time migration is clearer and more intuitive, and can restore the contour of small holes well. The research findings can serve as a reference for the interpretation of radar data of the cavity behind the initial support of the tunnel.
Disentangling genetic diversity of Myotis septentrionalis: population structure, demographic history, and effective population size
Authors: Grimshaw Jenna R , Donner Deahn , Perry Roger , Ford W Mark , Silvis Alex , Garcia Carlos J , Stevens Richard D , Ray David A
Published: June 2024

Myotis septentrionalis (Northern Long-eared Bat) has recently suffered a >90% decline in population size in North America due to white-nose syndrome (WNS). We assessed genetic diversity, population structure, current effective population size, and demographic history of M. septentrionalis distributed across the United States to determine baseline levels pre-WNS. We analyzed RADseq data from 81 individuals from Kentucky, Louisiana, Michigan, Minnesota, North Carolina, Oklahoma, and Wisconsin. Additionally, we examined population genetic structure using discriminant analysis of principal components, fastStructure, and STRUCTURE. We then estimated effective population size and demographic history using fastsimcoal2. Similar levels of genetic diversity were found across all samples. We found no population genetic structure in the varied analyses from these contemporary samples. The best model for demographic history estimated a rapid population expansion followed by a slower expansion approximately 340,000 years ago. The vagility of M. septentrionalis, along with male dispersal and random mating, may provide a buffer against serious bottleneck effects stemming from rapid population declines due to WNS. This research provides a baseline for tracking and monitoring the influence of WNS on genetic diversity such as potential reduced diversity or increased population structuring in the future.
Examining evidence of lung cancer stigma among health-care trainees
Authors: Studts Jamie L , Deffendall Catherine M , McCubbin Shelby L , Hamann Heidi A , Hoover Kaitlyn , Brymwitt Whitney M , Williamson Timothy J
Published: June 2024

Background

Innovations in lung cancer control and care have started to transform the landscape of lung cancer outcomes, but lung cancer stigma and biases have been implicated as a deterrent to realizing the promise of these innovations. Research has documented lung cancer stigma among the general public and lung cancer survivors (self-blame), as well as clinicians across many disciplines. However, studies have not explored lung cancer stigma in health-care trainees. These data seek to address that gap and inform efforts to prevent the emergence or mitigate the presence of lung cancer stigma among future clinicians.

Methods

Using clinical vignettes and a 2x2 factorial design, this investigation evaluated the impact of a history of smoking (yes vs no) and cancer diagnosis (lung vs colorectal) on perceptions of the described patient among 2 groups of preclinical health-care trainees (medical = 94 and nursing = 138). A charitable giving paradigm also asked participants to donate provided funds to 1 of 2 cancer advocacy organizations: one serving the lung cancer community and one serving the colorectal cancer community.

Results

In study 1, results revealed a consistent pattern of statistically significant and medium to large effect size differences regarding stigmatized perceptions (eg, higher stigmatizing behavior, increased pity, greater anger, and less helping) for individuals with a history of smoking but no reliable differences regarding cancer diagnosis. Analysis of data from nursing trainees in study 2 showed a similar pattern of statistically significant and medium to large effects pertaining to stigma behavior and perceptions of individuals who had a history of smoking depicted in the vignettes. The charitable giving paradigm did not identify any reliable difference between the groups in either study.

Conclusions

Findings revealed a consistent pattern of health-care trainee perceptions that varied by smoking status but much less evidence that the cancer diagnosis contributed to different perceptions. This suggests that efforts to integrate consideration of stigma and biases in health-care training needs to adopt an approach that seeks to mitigate or eliminate stigmatizing perceptions and behaviors toward individuals with a history of smoking.
Cancer stigma: the need for policy and programmatic action
Authors: Johnson Sonali Elizabeth , Samson Mélanie
Published: June 2024

Cancer is a stigmatized disease in many countries that impacts the quality of life and mental health of people affected by cancer. This commentary examines some dimensions of cancer stigma and has been developed based on insights from participants in a Union for International Cancer Control program dedicated to cancer patient organizations in low- and middle-income countries. Aimed at program managers and policy makers, this commentary highlights the importance of developing strategies to reduce cancer stigma in cancer control programs in different contexts, working closely with community-based civil society organizations and those with lived experience of cancer to understand, evaluate, and take action regarding the impact of cancer stigma on health-seeking behavior and patients’ quality of life.
Impact of a multicomponent navigation strategy on stigma among people living with HIV and Kaposi’s sarcoma in Kenya: a qualitative analysis
Authors: Collier Sigrid M , Semeere Aggrey , Chemtai Linda , Byakwaga Helen , Lagat Celestine , Laker-Oketta Miriam , Bramante Juliet , Pacheco Ann , Zehtab Morvarid , Strahan Alexis G , Grant Merridy , Bogart Laura M , Bassett Ingrid V , Busakhala Naftali , Opakas Jesse , Maurer Toby , Martin Jeffrey , Kiprono Samson , Freeman Esther E
Published: June 2024

Persons with HIV-associated Kaposi’s sarcoma (KS) experience three co-existing stigmatizing health conditions: skin disease, HIV, and cancer, which contribute to a complex experience of stigmatization and to delays in diagnosis and treatment. Despite the importance of stigma among these patients, there are few proven stigma-reduction strategies for HIV-associated malignancies. Using qualitative methods, we explore how people with HIV-associated KS in western Kenya between August 2022 and 2023 describe changes in their stigma experience after participation in a multicomponent navigation strategy, which included 1) physical navigation and care coordination, 2) video-based education with motivational survivor stories, 3) travel stipend, 4) health insurance enrollment assistance, 5) health insurance stipend, and 6) peer mentorship. A purposive sample of persons at different stages of chemotherapy treatment were invited to participate. Participants described how a multicomponent navigation strategy contributed to increased knowledge and awareness, a sense of belonging, hope to survive, encouragement, and social support, which served as stigma mitigators, likely counteracting the major drivers of intersectional stigma in HIV-associated KS.
Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors
Authors: Loreto Palacio Paola , Pan Xiaokang , Jones Dan , Otero José Javier
Published: June 2024

We report the novel clinical presentation of a primary brain neoplasm in a 30-year-old man with a mass-like area in the anteromedial temporal lobe. Histopathological analysis revealed a low-grade neuroepithelial tumor with cytologically abnormal neurons and atypical glial cells within the cerebral cortex. Molecular analysis showed a previously undescribed FGFR2::DLG5 rearrangement. We discuss the clinical significance and molecular implications of this fusion event, shedding light on its potential impact on tumor development and patient prognosis. Additionally, an extensive review places the finding in this case in the context of protein fusions in brain tumors in general and highlights their diverse manifestations, underlying molecular mechanisms, and therapeutic implications.
The Verbal System of Baritle Neo-Aramaic
Authors: Al-Saka Vean
Published: June 2024

This paper presents a comprehensive study of verbal inflection in the Neo-Aramaic dialect of Baritle (northern Iraq). Similar to other Semitic languages, Baritle uses ‘root and pattern’ morphology and verb roots are generally triliteral. Whereas the core structures of the Baritle verb system align with those found in other North-Eastern Neo-Aramaic languages, Baritle exhibits distinctive variations in several noteworthy aspects. This study of the verbal inflection of Baritle identifies the inflections by number and type. It finds that the verb in Baritle has different functional categories indicating tense, aspect, and mood. It also finds that the verb has various bound pronominals representing the grammatical categories of person, number, and gender of its arguments. This paper documents an endangered language and contributes to the typology of the grammar of natural languages.
A Morphological Reconstruction of T-Stems in Proto-Semitic
Authors: Mellison John
Published: June 2024

A central morphological feature of Semitic languages is the so-called ‘t-stems’ associated with the G, D and C stems. These forms attach a /t/ to the verbal root and often convey reflexive, reciprocal, or mediopassive action. The Semitic languages attest a puzzling mix of prefixed and infixed t-stem forms, and thus it has been challenging to reconstruct the original Proto-Semitic (PS) structure. The general consensus is that PS prefixed the /t/ to the root and the daughter languages underwent a series of complex phonological changes. This study argues that the /t/ was infixed in the G-stem and prefixed in the D-stem in PS. This reconstruction easily accounts for the variety of forms attested in the Semitic languages and only requires paradigm levelling in one stem to account for the attested variety. I argue this by raising problems with the consensus view and presenting inscriptional evidence of systemwide levelling in Northwest Semitic.
Who wrote the first Constitutions of Freemasonry?
Authors: Péter Róbert , Jawerbaum Alejandro Napolitano
Published: June 2024

This article addresses the problematic authorship of The Constitutions of the Free-Masons (1723). Traditionally associated with James Anderson, using stylometry, we examine whether and, if so, where John T. Desaguliers, the prime mover of early English institutionalized Freemasonry, contributed to this publication. Our corpus includes writings by Anderson, Desaguliers, and two contemporary Freemasons used as distractors. The transcribed works contain texts from different genres and of varying lengths. In our methodology, we employ a wide range of robust, multivariate, unsupervised, and cross-validated supervised tests, verified through significance testing, which can hopefully contribute to the establishment of standards for historical authorship attribution. Our results suggest, in line with historical evidence, that the legendary history of the Constitutions was most likely primarily authored by Anderson. However, several of the Charges including the first one ‘Concerning God and religion’, one of the most disputed texts in the history of Freemasonry, are closer to the style of Desaguliers. The General Regulations concerning the organization of the lodges, hitherto attributed to George Payne, played a fundamental role in spreading Freemasonry worldwide. Our analyses show that the stylistic affinity of fifteen of the thirty-nine regulations has a pronounced closeness to Anderson’s style, five align more closely with Desaguliers’ style. The authorship of the rest remains inconclusive partly due to the insufficient length of texts by Payne. These novel findings are also supported by a close reading of the Constitutions and other contemporary primary sources.
Gravitational wave emission from close-in strange quark planets around strange stars with magnetic interactions
Authors: Zhang Xiao-Li , Zou Ze-Cheng , Huang Yong-Feng , Gao Hao-Xuan , Wang Pei , Cui Lang , Liu Xiang
Published: June 2024

According to the strange quark matter hypothesis, strange planets may exist, which are planetary mass objects composed of almost equal numbers of up, down, and strange quarks. A strange planet can revolve around its host strange star in a very close-in orbit. When it finally merges with the host, strong gravitational wave emissions will be generated. Here, the gravitational waveforms are derived for the merging process, taking into account the effects of the strange star’s magnetic field on the dynamics. Effects of the inclination angle are also considered. Templates of the gravitational waveforms are derived. It is found that the magnetic interactions significantly speed up the merging process. Coalescence events of such strange planetary systems occurring in our Galaxy as well as in local galaxies can be effectively detected by current and future gravitational experiments, which may hopefully provide a new method to test the strange quark matter hypothesis and probe the magnetic field of compact stars.
Complete response to capmatinib in a patient with metastatic lung adenocarcinoma harboring CD47-MET fusion: a case report
Authors: Alves de Souza Glaucia , Dornellas Debora Maciel Santana , Campregher Paulo Vidal , Teixeira Carlos Henrique Andrade , Schvartsman Gustavo
Published: June 2024

Comprehensive genomic profiling is highly recommended for treatment decision in nonsquamous, non-small cell lung cancer (NSCLC). However, rare genomic alterations are still being unveiled, with scarce data to guide therapy. Herein, we describe the treatment journey of a 56-year-old, never-smoker Caucasian woman with a metastatic NSCLC harboring a CD47-MET fusion, initially classified as a variant of unknown significance. She had undergone 3 lines of therapy over the course of 3 years, including chemotherapy, immunotherapy, and anti-angiogenic therapy. After reanalysis of her next-generation sequencing data in our service, the fusion was reclassified as likely oncogenic. The patient was started with fourth-line capmatinib, with a good tolerance so far and a complete metabolic response in the active sites of disease, currently ongoing for 18 months. In conclusion, we highlight the sensitivity of a novel MET fusion to capmatinib and emphasize the need for comprehensive panels in NSCLC and molecular tumor board discussions with specialized centers when rare findings arise.
Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results
Authors: Xia Zu-Guang , Lv Fang-Fang , Zhang Qun-Ling , Liu Yi-Zhen , Zhang Sheng-Jian , Liu Chang , Li Xiao-Qiu , Wen Yu , Wu Zhen-Yu , Hong Xiao-Nan , Guo Ye , Cao Jun-Ning
Published: June 2024

Background

Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL).

Methods

Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT).

Results

From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%).

Conclusion

This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance.

ClinicalTrials.gov Identifier

Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.
Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors
Authors: Kondo Tomohiro , Kikuchi Osamu , Yamamoto Yoshihiro , Sunami Tomohiko , Wang Yafeng , Fukuyama Keita , Saito Tomoki , Nakahara Hideto , Minamiguchi Sachiko , Kanai Masashi , Sueyoshi Atsushi , Muto Manabu
Published: June 2024

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (− 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.
A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors
Authors: Dayyani Farshid , Chao Joseph , Lee Fa-Chyi , Taylor Thomas H , Neumann Kristen , Cho May T
Published: June 2024

Background

Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA.

Methods

Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6).

Results

Twenty-seven patients were enrolled. Median age 58 years (24-87), female (n = 14), ECOG 0/1 = 13/14, GC/GEJ = 16/11, and non-Hispanic White/Hispanic/Asian = 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in n = 3 patients (hypertension, thromboembolic event, esophageal perforation; each n = 1). No G5 was observed.

Conclusions

The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.)
Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers
Authors: Belli Carmen , Boscolo Bielo Luca , Repetto Matteo , Crimini Edoardo , Scalia Raimondo , Diana Anna , Orefice Jessica , Ascione Liliana , Pellizzari Gloria , Fusco Nicola , Barberis Massimo , Daniele Bruno , Guerini-Rocco Elena , Curigliano Giuseppe
Published: June 2024

Background

Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents.

Methods

We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group.

Results

Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; P = .95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; P = .4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; P = .9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, P = .27).

Conclusion

HR-/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.
Research gaps in sentinel lymph node biopsy in breast cancer
Authors: Hamdy Omar
Published: June 2024

This commentary focuses on 5 questions that need to be answered when considering sentinel lymph node biopsy in breast cancer, aiming to highlight these issues and provide researchers with ideas to resolve.
Citizens’ trust in Bangladesh Police: A cross-sectional survey on urban population
Authors: Ahsan Abu Hossain Muhammad , Hasan Md Khalid , Rumi Maruf Hasan
Published: June 2024

The study assessed the level of trust in police among urban citizens in Bangladesh and examined the associated factors. An online cross-sectional survey was conducted through mobile phones to collect data from 1,680 respondents using a structured questionnaire. A 9-item scale was developed and validated to measure citizens’ trust in police using procedural- and outcome-based trust models. The urban citizens had a relatively low level of trust in the police. Factors like trust in neighbourhoods, satisfaction with governmental law and order operation, believing positive media reports on police, and personal safety awareness were significantly positively associated with trust in police. In contrast, increasing crime in the residential areas, believing negative media reports on police, and senior citizens were significantly associated with low levels of trust in police. Bangladesh police should adopt pro-people practices with effective implementation of law and order to increase their trust.
How can societally-targeted research funding shape researcher networks and practices?
Authors: Ramos-Vielba Irene , Bloch Carter , Thomas Duncan A , Povlsen Rikke E , Falkenberg Mette L , Stage Andreas K
Published: June 2024

Funding is considered to have a central role in defining the scope, content and direction of public research. However, we lack sufficient understanding of how funding can shape research networks and practices to enhance societal goals. In this paper, we apply a recent approach that explores the societal targeting of funding across four key dimensions: interdisciplinarity, transdisciplinarity, prioritized research problems, and user-oriented outputs. Through in-depth case studies of 12 funded research projects, we explore shaping in these dimensions by contrasting pre- and post-acquisition of a societally targeted project grant based on the accounts of principal investigators (PI). We examine cases across two research areas—renewable energy and food science—in three European countries—Denmark, Netherlands and Norway. Our analysis suggests that societally targeted funding can act as an enabler of inter- and transdisciplinary collaborations and the accumulation of experience to manage them. This funding also encourages research practices that prioritize societal research problems and foster users’ utilization of research outputs while still preserving researcher scientific autonomy. Shaping dynamics are then examined in connection with funding requirements across the four dimensions.
Indoor concentrations of radioactive aerosols from nuclear accidents
Authors: Orabi Momen
Published: June 2024

In previous studies, some of the important factors that affect the spread of radioactive aerosols into indoors were considered. The studies were based on a new CFD approach and provided good descriptions for the deposition of aerosol particles inside small spaces and the penetration of aerosols into buildings through wall cracks. In this article, an application of those studies is implemented, where all the graphical relations that are required to estimate the indoor concentrations of radioactive aerosols from nuclear accidents are provided. This includes the deposition velocities, deposition rate, and the penetration factor. Particular interest is in the Fukushima-Daiichi nuclear power plant accident that took place in Japan in 2011. The aerosols carrying the radioiodine iodine-131 and the radiocesium cesium-134 and cesium-137 are studied. Based on the model’s assumptions, and assuming steady-state air concentrations, the radioactive aerosols’ concentrations in indoor air are about 97% of the concentrations in outdoor air. The applications demonstrate the model to be convenient and practical.
Evaluation of the environmental and structural impacts on urban expansion using airborne geophysical data at Hurghada city, Northern Eastern Desert, Egypt
Authors: El-Qassas Reda Abdu Yousef
Published: June 2024

Airborne gamma-ray spectrometric and magnetic data were processed and interpreted aiming to evaluate the environmental and structural impacts on urban expansion, Hurghada City, Northern Eastern Desert, Egypt. The eastern (coastal area), northern, and southeastern parts of the study area possess the lowest level of absorbed dose rate (ADR) and annual effective dose equivalent (AEDE), which were estimated from the airborne gamma-ray spectral data of this area. Consequently, these parts are considered as suitable sites for urban expansion from the radioactivity point of view. The relatively high level of ADR and AEDE is associated with granitic rocks, some parts of Gabir formation and recent Wadi sediments, situated at southwestern, central, and eastern parts of the study area. The ADR and AEDE of these parts are considered harmful to individuals. Airborne magnetic data were also used to detect major structures that may affect various construction projects in the study area in the future. The NNW–SSE, NW–SE, N–S, and NE–SW trends represent the common structures in the study area. The obtained results of airborne gamma-ray spectrometric and magnetic data illustrated that the urban expansion should not be constructed to the west of the ring road. However, site investigations must be carried out on this part of the study area before starting any construction projects there. The present study proved the important role of airborne gamma-ray spectrometric and magnetic surveys as useful tools to delineate the environmental and structural impacts on urban expansion.
Mexico’s battle with monopolies: reputation-based autonomy and self-undermining effects in antitrust enforcement
Authors: Arslan Melike
Published: June 2024

Despite increased scholarly attention to competition law enforcement against corporate monopolies, our understanding of this topic in developing countries remains very limited. This article addresses this gap by focusing on Mexico, using enforcement statistics, expert interviews and documentary resources. I find that Mexico initially pursued surprisingly high levels of anti-monopoly enforcement, which was followed by an equally surprising decline. Departing from the previous research that emphasized the influence of expert ideas, business power and international models, this study highlights two factors shaping the enforcement of competition law on monopolies in developing country contexts: the strategies employed by newly established competition authorities to foster organizational autonomy through a positive public reputation, and the subsequent self-undermining effects of these strategies. In addition to advancing the existing literature on competition policies, these findings shed light on the factors behind local variations in globally diffused institutions and the limitations of reputation-based bureaucratic autonomy.
Sleep medicine, sleep research, and sleep education: a whole life devoted to sleep
Authors: Billiard Michel
Published: June 2024

This article describes my participation in sleep medicine, sleep research, and sleep education, mainly in Europe, between the years 1970 and 2000.
“Maybe We Should Start Paying the Hours Properly”: State Violence and Ambivalent Moments of Enforced Emancipation of Refugee Women
Authors: Øland Trine
Published: June 2024

Within integration programs and practices, refugee women are repeatedly offered rescue and emancipation. This article explores how emancipation intersects with material and social injustices of integration practices, and how refugee women in particular become subjects for emancipation. It examines the bordering practices of integration and emancipation, and identifies how integration practices symbolize refugee women as, here called, “oppressed,” “spoiled,” “willing,” “surprisingly productive,” or “familiar.” It investigates how these symbolizations circulate in emancipatory practices that are steeped in national imaginaries, as well as in welfare state work ethics. Emancipation is confined to submission to exploitative reproductive work and tied to consumerism. But it also has ambivalent moments around regularizing refugee women’s strategically needed care-work. The article suggests that differential emancipation reproduces complex and violent logics of gendered racial capitalism and coloniality of the Danish welfare state.
XThe Seventeenth Century, Part II
Authors: Stelzer Emily , Baker William , Airey Jennifer , Parry David
Published: June 2024

This chapter contains coverage of poetry, drama, and prose. In order to more conveniently note the contributions of various contributors, this chapter will offer, in lieu of a larger ‘General and Poetry’ section, numerous smaller sections on individual poets. Similarly, prose authors Hobbes, Locke, Aubrey, and Bunyan will each have their own section. This chapter has fourteen sections: 1. Marvell; 2. Herrick; 3. Cowley; 4. Crashaw; 5. Hester Pulter; 6. Rochester; 7. Traherne; 8. Vaughan; 9. Restoration Draman Excluding Dryden; 10. Dryden; 11. Hobbes; 12. Locke; 13. Aubrey; 14. Bunyan. There is no section on Pepys this year. Sections 1, 2, and 5 are by Emily Stelzer; sections 3, 4, 6, 7, 8, 11, 12, and 13 are by William Baker; sections 9 and 10 are by Jennifer Airey; section 14 is by David Parry. William Baker thanks Claudia Keelan, Joseph Sterrett, David Strong, and Helen and Allan Wilcox who made articles and journals, such as Scintilla, available and otherwise assisted.
Unraveling the role of lipid droplets and perilipin 2 in bovine luteal cells
Authors: Plewes Michele R. , Talbott Heather A. , Schott Micah B. , Wood Jennifer R. , Cupp Andrea S. , Davis John S.
Published: June 2024

Steroidogenic tissues contain cytosolic lipid droplets that are important for steroidogenesis. Perilipin 2 (PLIN2), a structural coat protein located on the surface of lipid droplets in mammalian cells, plays a crucial role in regulating lipid droplet formation and contributing to various cellular processes such as lipid storage and energy homeostasis. Herein, we examine the role that PLIN2 plays in regulating progesterone synthesis in the bovine corpus luteum. Utilizing gene array databases and Western blotting, we have delineated the expression pattern of PLIN2 throughout the follicular to luteal transition. Our findings reveal the presence of PLIN2 in both ovarian follicular and steroidogenic luteal cells, demonstrating an increase in its levels as follicular cells transition into the luteal phase. Moreover, the depletion of PLIN2 via siRNA enhanced progesterone production in small luteal cells, whereas adenovirus‐mediated overexpression of both PLIN2 and Perilipin 3 (PLIN3) induced an increase in cytosolic lipid droplet accumulation and decreased hormone‐induced progesterone synthesis in these cells. Lastly, in vivo administration of the luteolytic hormone prostaglandin F2α resulted in an upregulation of PLIN2 mRNA and protein expression, accompanied by a decline in serum progesterone. Our findings highlight the pivotal role of PLIN2 in regulating progesterone synthesis in the bovine corpus luteum, as supported by its dynamic expression pattern during the follicular to luteal transition and its responsiveness to luteotropic and luteolytic hormones. We suggest PLIN2 as a potential therapeutic target for modulating luteal function.
Original Research: Nurses' Knowledge and Attitudes Regarding the Sustainable Development Goals: A Global Study
Authors: Hawkins Janice Evans , Chiu Patrick , Mumba Mercy Ngosa , Gray Sarah E. , Hawkins Robert Joseph
Published: June 2024

Background:

Nurses have a critical role to play in achieving the United Nations' 17 Sustainable Development Goals (SDGs). While Goal 3 (good health and well-being) is of particular importance to nursing, every SDG contributes to the advancement of universal health and well-being. Yet many nurses are unfamiliar with the SDGs and how they relate to everyday nursing practices.

Purpose:

The purpose of this study was to examine RNs' knowledge of and attitudes toward the SDGs.

Methods:

This study used a descriptive correlational cross-sectional design. A convenience sample of RNs from multiple countries completed an anonymous online survey that included eight demographic items and 25 items exploring participants' knowledge of and attitudes toward the SDGs. Descriptive, parametric, and nonparametric statistics were used to analyze the data.

Results:

The majority of nurses in this study perceived themselves as lacking knowledge of the SDGs. Most wanted to know more, including how they could take action to help achieve the goals. Overall, participants agreed that the SDGs are relevant to nursing practice and that nurses are integral to their advancement. Participants who were younger than age 50, those living in the United States, and those who practiced primarily in a clinical or community setting were more likely than others to self-report lower SDG knowledge scores.

Conclusions:

The study findings contribute to our collective understanding of RNs' knowledge and attitudes regarding the SDGs. They can assist nurse educators and leaders worldwide in developing targeted strategies to better inform nurses and prepare them for actions that will advance these goals. Increasing nurses' knowledge of the SDGs, especially as these goals relate to daily clinical practice, may lead to greater nursing engagement and impact.
Skin Pigmentation Affects ViOptix T.Ox Performance in Variably Pigmented Preclinical Model of Flap Ischemia and Congestion
Authors: Westman Amanda M. , Ribaudo Joseph , Butler Michael , Shmuylovich Leonid , Pet Mitchell A.
Published: June 2024

Background:

Free flap monitoring is more difficult in patients with dark skin because ischemia and congestion can be masked by pigmentation. For this reason, adjunct methods such as cutaneous near-infrared spectroscopy are of elevated importance in patients with highly pigmented skin. The purpose of this experiment is to determine if ViOpitx T.Ox performance is affected by cutaneous pigmentation.

Methods:

Swine with naturally occurring areas of nonpigmented and pigmented skin were used. Pigmentation of each animal was assessed using spectrophotometry and histopathology. During normoxemia, tissue oxygenation (StO2) measurements were taken of nonpigmented and pigmented skin using the T.Ox device. A bicolor pedicled rectus abdominis myocutaneous flap was raised, and T.Ox probe was adhered to adjacent areas of opposite coloration on the same flap. StO2 was measured continuously during reversible episodes of flap ischemia and congestion (n = 4 swine, n = 6 flaps).

Results:

There was not a significant difference between baseline StO2 values of nonpigmented (49% ± 7.9%) and pigmented skin (47% ± 6.2%). The absolute change in StO2 was significantly larger during both ischemia (6%) and congestion (16%) in nonpigmented skin compared with adjacent pigmented skin.

Conclusions:

T.Ox detects flap ischemia and congestion in both highly pigmented and nonpigmented skin. However, surgeons need to be aware that StO2 changes related to complete flap ischemia or congestion may be much more subtle than what is seen in nonpigmented skin. This study establishes a novel internally controlled porcine model that isolates the impact of skin pigmentation when assessing cutaneous devices measuring tissue oxygenation.
Assessing the Racial and Ethnic Diversity of Physician Assistant/Associate Program Graduates from 2010 to 2012 and 2019 to 2021
Authors: Ritsema Tamara S. , Herring Jordan R. , Straker Howard O. , Salsberg Edward
Published: June 2024

Introduction

To assess the racial/ethnic diversity of graduates of US Physician Assistant/Associate (PA) programs compared with the diversity of the populations from which they draw students and to assess diversity changes over time among PA graduates.

Methods

We calculated proportion of Black or Hispanic PA graduates nationally and by school between 2010 to 2012 and 2019 to 2021 using the Integrated Postsecondary Education Data System (IPEDS) and compared it with the diversity of the 20 to 35-year-old population using the American Community Survey. We created benchmark populations for each school based on whether the school was public or private, with in-state/out-of-state proportions provided by the Physician Assistant Education Association. A diversity index (DI) was calculated for each program. A DI of 0.5 means that the representation of Black/Hispanic graduates is half their representation in the benchmark population.

Results

Although the numbers of Black/Hispanic graduates increased from 2010 to 2012 to 2019 to 2021, the percentage of Black graduates decreased. Nationally, the DI for Black graduates decreased from 0.28 to 0.23 and the Hispanic DI increased from 0.28 to 0.37 between 2010 to 2012 and 2019 to 2021. Among 213 PA programs included in the 2019 to 2021 dataset, 5 schools had a DI >1.0 for Black graduates and 7 schools had a DI >1.0 for Hispanic graduates.

Discussion

Using the IPEDS data, we found that Black and Hispanic graduates are underrepresented among PA program graduates. The PA education community needs to develop new strategies for diversifying the profession consistent with the new US Supreme Court decision banning race-conscious admissions.