bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of laparoscopic lymphadenectomy for adenocarcinoma of unknown primary incidentally detected as a solitary enlarged lymph node along the common hepatic artery
Authors: Morimoto Tomonori , Hisamori Shigeo , Kinoshita Hiromitsu , Yamada Yosuke , Teramoto Yuki , Sakamoto Takashi , Kasahara Keiko , Okumura Shintaro , Nishigori Tatsuto , Tsunoda Shigeru , Obama Kazutaka 
Published: April 2024

Abstract
Background
Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported.

Case presentation
A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site.

Conclusion
We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP.
Wallace’s line structures seagrass microbiota and is a potential barrier to the dispersal of marine bacteria
Authors: Wainwright Benjamin J. , Leon Josh , Vilela Ernie , Hickman K. J. E. , Caldwell Jensen , Aimone Behlee , Bischoff Porter , Ohran Marissa , Morelli Magnolia W. , Arlyza Irma S. , Marwayana Onny N. , Zahn Geoffrey 
Published: April 2024

AbstractBackgroundThe processes that shape microbial biogeography are not well understood, and concepts that apply to macroorganisms, like dispersal barriers, may not affect microorganisms in the same predictable ways. To better understand how known macro-scale biogeographic processes can be applied at micro-scales,we examined seagrass associated microbiota on either side of Wallace’s line to determine the influence of this cryptic dispersal boundary on the community structure of microorganisms. Communities were examined from twelve locations throughout Indonesia on either side of this theoretical line.ResultsWe found significant differences in microbial community structure on either side of this boundary (R2 = 0.09;P = 0.001), and identified seven microbial genera as differentially abundant on either side of the line, six of these were more abundant in the West, with the other more strongly associated with the East. Genera found to be differentially abundant had significantly smaller minimum cell dimensions (GLM: t923 = 59.50,P < 0.001) than the overall community.ConclusionDespite the assumed excellent dispersal ability of microbes, we were able to detect significant differences in community structure on either side of this cryptic biogeographic boundary. Samples from the two closest islands on opposite sides of the line, Bali and Komodo, were more different from each other than either was to its most distant island on the same side. We suggest that limited dispersal across this barrier coupled with habitat differences are primarily responsible for the patterns observed. The cryptic processes that drive macroorganism community divergence across this region may also play a role in the bigeographic patterns of microbiota.
Recommendations for optimising pilot and feasibility work in surgery
Authors: Fairhurst K. , Potter S. , Blazeby J. M. , Avery K. N. L. 
Published: April 2024

Abstract
Background
Surgical trials are recognised as inherently challenging. Pilot and feasibility studies (PAFS) are increasingly acknowledged as a key method to optimise the design and conduct of randomised trials but remain limited in surgery. We used a mixed methods approach to develop recommendations for how surgical PAFS could be optimised.

Methods
The findings from a quantitative analysis of funded surgical PAFS over a 10-year period and in-depth qualitative interviews with surgeons, methodologists and funders were triangulated and synthesised with available methodological guidance on PAFS.

Results
The synthesis informed the development of an explanatory model describing root causes and compounding challenges that contribute to how and why surgical PAFS is not currently optimised. The four root causes identified include issues relating to (i) understanding the full scope of PAFS; (ii) design and conduct of PAFS; (iii) reporting of PAFS; and (iv) lack of appreciation of the value of PAFS by all stakeholder groups. Compounding challenges relate to both cultural issues and access to and interpretation of available methodological PAFS guidance. The study findings and explanatory model were used to inform the development of a practical guidance tool for surgeons and study teams to improve research practice.

Conclusions
Optimisation of PAFS in surgery requires a cultural shift in research practice amongst funders, academic institutions, regulatory bodies and journal editors, as well as amongst surgeons. Our ‘Top Tips’ guidance tool offers an accessible framework for surgeons designing PAFS. Adoption and utilisation of these recommendations will optimise surgical PAFS, facilitating successful and efficient future surgical trials.
How can we support research participants who stop taking part? Communications guidance developed through public-researcher collaboration
Authors: Cragg William J. , Bishop Liam , Gilberts Rachael , Gregg Michael , Lowdon Terry , Mancini Mary , Martins de Barros Clara , Wheatstone Pete 
Published: April 2024

Abstract
Background
Research study participants can stop taking part early, in various circumstances. Sometimes this experience can be stressful. Providing participants with the information they want or need when they stop could improve participants’ experiences, and may benefit individual studies’ objectives and research in general. A group of public contributors and researchers at the Clinical Trials Research Unit, University of Leeds, aimed to develop a communication template and researcher guidance. This would address how to provide information sensitively around the time when participants stop or significantly reduce their level of participation.

Methods
The project lead used scoping review methods to identify relevant prior evidence and derive a list of potential information topics to communicate to participants who stop taking part. The topic list was reviewed by research professionals and public contributors before finalisation. Further public contributors were identified from a range of networks. The contributors formed a ‘development group’, to work on the detail of the planned resources, and a larger ‘review group’ to review the draft output before finalisation. The involvement was planned so that the development group could shape the direction and pace of the work.

Results
The literature review identified 413 relevant reports, resulting in 94 information topics. The review suggested that this issue has not been well explored previously. Some evidence suggested early-stopping participants are sometimes excluded from important communications (such as study results) without clear justification. The development group agreed early to focus on guidance with reusable examples rather than a template. We took time to explore different perspectives and made decisions by informal consensus. Review group feedback was broadly positive but highlighted the need to improve resource navigability, leading to its final online form.

Conclusions
We co-developed a resource to provide support to research participants who stop taking part. A strength of this work is that several of the public contributors have direct lived experience of stopping research participation. We encourage others to review the resource and consider how they support these participants in their studies. Our work highlights the value of researchers and participants working together, including on complex and ethically challenging topics.
Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model
Authors: Durinova Anna , Smutna Lucie , Barta Pavel , Kamaraj Rajamanikkam , Smutny Tomas , Schmierer Bernhard , Pavek Petr , Trejtnar Frantisek 
Published: April 2024

Abstract
Background
Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of 68Ga- and 99mTc-labeled 15-mer peptide developed to target the vascular endothelial growth factor (VEGF) receptor in oncology radiodiagnostics.

Results
The gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and lower FITC-albumin internalization by the KO cells was detected in accumulation studies. Fluorescent-activated cell sorting was used to separate genetically modified LRP2 KO cell subpopulations. Moreover, flow cytometry with a specific antibody against megalin confirmed LRP2 knockout. The verified KO model identified both 68Ga- and 99mTc-radiolabeled 15-mer peptides as megalin ligands in accumulation studies. We found that both radiolabeled 15-mers enter LRP2 KO HK2 cells to a lesser extent compared to parent cells. Differences in megalin-mediated cellular uptake depending on the radiolabeling were not observed. Using biomolecular docking, the interaction site of the 15-mer with megalin was also described.

Conclusion
The CRISPR/Cas9 knockout of LRP2 in human kidney HK2 cells is an effective approach for the determination of radiopeptide internalization mediated by megalin. This in vitro method provided direct molecular evidence for the cellular uptake of radiolabeled anti-VEGFR 15-mer peptides via megalin.

Graphical abstract
Unusual coexistence of restrictive heart disease and Kallmann syndrome: a case report
Authors: Bennani Ghali , Zahri Soukaina , Khaldi Mohamed , Benouna Ghali , Drighil Abdenasser , Habbal Rachida 
Published: April 2024

Abstract
Background
Kallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature.

Case presentation
We report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth.

Conclusions
Cardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future.
Transition to suicide ideation and attempt among emergency room patients
Authors: Yurdadön Claudio , Bruffaerts Ronny , Sabbe Marc , Demyttenaere Koen , Peeters Elke , Gericke Franco , Voorspoels Wouter 
Published: April 2024

BackgroundSuicidal thoughts and behaviours (STB) represent a persistent and serious public health problem, and suicide is among the leading causes of death worldwide. We focus on predictors of transition rates and time courses through the STB spectrum among psychiatric emergency room (PER) patients.AimsWe aimed to investigate (a) whether currently suicidal patients had prior referrals to the PER, (b) for which reason they were previously referred to the PER and (c) the timing of this referral.MethodWe performed a retrospective study spanning 20 years with 24 815 PER referrals. Descriptive statistics of patients’ sociodemographic and clinical characteristics are provided and expressed as weighted proportions and means. Logistic regression was used to identify risk profiles of patients who had a higher chance of being referred for reasons of STB given their PER history. Multiple imputation and data weighting techniques were implemented.ResultsSTB among PER patients was persistent and led to repeated referrals (up to five times more likely), often within a short period (18% <1 month). Those previously referred for ideation/plan had 66% higher risk of making the transition to suicide attempt, with 25% making this transition within a month after previous referral. This is similar to the transition from depressed mood to suicide ideation/plan.ConclusionsSTBs in PER patients are persistent and lead to repeated referrals, often within a short period, including transitions to more severe forms of STB.
Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer–Associated Germline Pathogenic Variants in Mexico
Authors: Mesa-Chavez Fernanda , Chavarri-Guerra Yanin , Aguilar-y-Mendez Dione , Becerril-Gaitan Andrea , Vaca-Cartagena Bryan F. , Carrillo-Bedoya Araceli , Santiesteban-González Salvador , Aranda-Gutierrez Alejandro , Rodríguez-Faure Andrés , Obregon-Leal Daniela , Quintero-Beuló Gregorio , Rodriguez-Olivares Jose L. , Miaja Melina , Weitzel Jeffrey N. , Villarreal-Garza Cynthia 
Published: April 2024

PURPOSE Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer–associated germline PV carriers in Mexico. METHODS Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. RESULTS Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/ 2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership ( P = .04) and believing GCRA was useful ( P < .001). CONCLUSION Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.
Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses
Authors: Konstantinopoulos Panagiotis A. , Cheng Su-Chun , Lee Elizabeth K. , da Costa Alexandre André B.A. , Gulhan Doga , Wahner Hendrickson Andrea E. , Kochupurakkal Bose , Kolin David L. , Kohn Elise C. , Liu Joyce F. , Penson Richard T. , Stover Elizabeth H. , Curtis Jennifer , Sawyer Hannah , Polak Madeline , Chowdhury Dipanjan , D'Andrea Alan D. , Färkkilä Anniina , Shapiro Geoffrey I. , Matulonis Ursula A. 
Published: April 2024

PURPOSE The multicenter, open-label, randomized phase 2 NCI-9944 study ( NCT02595892 ) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib. RESULTS At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P = .18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P = .06). CONCLUSION The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.
Understanding Labor Market Discrimination Against Transgender People: Evidence from a Double List Experiment and a Survey
Authors: Aksoy Billur , Carpenter Christopher S. , Sansone Dario 
Published: April 2024

Using a double list experiment designed to elicit views free from social desirability bias, we find that support in the United States for transgender people in the labor market is significantly overreported by 8%–10%. After correcting for this overreporting, we still find that over two-thirds of respondents would be comfortable with a transgender manager and support employment nondiscrimination protection for transgender people. However, respondents severely underestimate this level of support. We also show that stated labor market support for transgender people is lower than support for gay, lesbian, and bisexual people. Our results advance our understanding of employment discrimination against transgender people. This paper was accepted by Marie Claire Villeval, behavioral economics and decision analysis. Funding: Financial support from The Vanderbilt LGBTQ+ Policy Lab. is gratefully acknowledged. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.02567 .
Pathophysiology of non-cystic fibrosis bronchiectasis in children and adolescents with asthma: A protocol for systematic review and meta-analysis
Authors: da Silva Natali Caroline , Malagutti Beatriz Cocato , Ladeira Joelia Maria Costa Dias , Grotta Milena Baptistella , Toro Adyleia Aparecida Dalbo Contrera 
Published: April 2024

Background
The pathophysiological mechanisms by which asthma and bronchiectasis are associated are still unclear. The association of these two diseases can result in more severe symptoms and a greater number of exacerbations.

Objective
The aim of this systematic review is to collect evidence of the pathophysiology of non-cystic fibrosis bronchiectasis with associated asthma in children and adolescents, aged 6–18 years old.

Methods
A systematic and comprehensive search will be performed using eight main databases, PubMed, PubMed PMC, BVS/BIREME, Scopus, EMBASE, Cochrane Library, Scielo and Web of Science. Articles will be searched from the earliest available time to July 2023. The studied population will be composed of children and adolescents with asthma and non-cystic fibrosis bronchiectasis. From the data obtained, all articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols Checklist (PRISMA P-2015). In addition, if sufficient data are available, a meta-analysis will be conducted. Two independent reviewers will conduct the studies selection, data extraction, and risk of bias assessment. The outcome measures will be to analyze if non-cystic fibrosis bronchiectasis is related to a specific inflammatory profile.

Discussion
A systematic review will provide better knowledge about the etiopathogenesis and causes of the association between asthma and bronchiectasis and its role in the severity and control of asthma. Identifying, selecting and critically evaluating studies on asthma and bronchiectasis, would be possible to illuminate the characteristics of children and adolescents with associated diagnoses and provide information to help individualized treatments in order to control and prevent complications. The findings of this study will be published in a peer-reviewed journal.

Systematic review registration
The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in July 2023 (registration number CRD42023440355).