bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whispers in the Wind: Face Mask Sampling for Mycobacterium tuberculosis Detection in Children With Pulmonary Tuberculosis
Authors: Meiwes Lennard , Kontsevaya Irina , Chesov Dumitru , Kulciţkaia Stela , Dreyer Viola , Hillemann Doris , Dlamini Qiniso , Williams Caroline , Barer Michael , Brinkmann Folke , Krüger Renate , Thee Stephanie , Kay Alexander , Mandalakas Anna Maria , Lange Christoph 
Published: May 2024

Abstract

Background
Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods
Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results
Experiments with H37Ra M. tuberculosis strain showed a limit of 95% detection of 3.75 colony-forming units (95% confidence interval, 4.85–3.11) on GeneXpert-Ultra. Ten children with pulmonary tuberculosis participated in the clinical study. M. tuberculosis-specific DNA was detected on none of the face masks.

Conclusions
Pediatric FMS has a low limit of detection for M. tuberculosis-specific DNA in vitro. However, M. tuberculosis DNA was not detected in any of 30 masks worn by children with pulmonary tuberculosis. This suggests that FMS in this form may not be more effective for detecting M. tuberculosis in children with tuberculosis than existing methods.
To Know Me Is to Exonerate Me: Appeals to Character in Defense of the Willowbrook Hepatitis Study
Authors: Lynch John 
Published: May 2024

Abstract
The Willowbrook Hepatitis Study is one of the best-known examples of unethical medical research, but the research has always had defenders. One of the more intriguing defenses continually used was that critics did not know the researchers on the study and, therefore, could not assess their ethics. This essay traces the appeal to the researchers’ characters across published research and archival sources from the 1960s through today. These appeals reflect the observation as old as Aristotle that one of the most potent modes of persuasion is ethos or character. The specific types of character in these appeals develop out of the paternalistic nature of clinical and research practice in the mid-twentieth century. If the individual physician is the locus of medical judgment, then the physician’s character becomes a key concern for bioethics. These appeals still appear and have implications for bioethics in the present day.
Applications of artificial intelligence for machine- and patient-specific quality assurance in radiation therapy: current status and future directions
Authors: Ono Tomohiro , Iramina Hiraku , Hirashima Hideaki , Adachi Takanori , Nakamura Mitsuhiro , Mizowaki Takashi 
Published: May 2024

Abstract
Machine- and patient-specific quality assurance (QA) is essential to ensure the safety and accuracy of radiotherapy. QA methods have become complex, especially in high-precision radiotherapy such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), and various recommendations have been reported by AAPM Task Groups. With the widespread use of IMRT and VMAT, there is an emerging demand for increased operational efficiency. Artificial intelligence (AI) technology is quickly growing in various fields owing to advancements in computers and technology. In the radiotherapy treatment process, AI has led to the development of various techniques for automated segmentation and planning, thereby significantly enhancing treatment efficiency. Many new applications using AI have been reported for machine- and patient-specific QA, such as predicting machine beam data or gamma passing rates for IMRT or VMAT plans. Additionally, these applied technologies are being developed for multicenter studies. In the current review article, AI application techniques in machine- and patient-specific QA have been organized and future directions are discussed. This review presents the learning process and the latest knowledge on machine- and patient-specific QA. Moreover, it contributes to the understanding of the current status and discusses the future directions of machine- and patient-specific QA.
Estimating the proportion of modern contraceptives supplied by the public and private sectors using a Bayesian hierarchical penalized spline model
Authors: Comiskey Hannah , Alkema Leontine , Cahill Niamh 
Published: May 2024

Abstract
Quantifying the public/private-sector supply of contraceptive methods within countries is vital for effective and sustainable family-planning delivery. However, many low- and middle-income countries quantify contraceptive supply using out-of-date Demographic Health Surveys. As an alternative, we propose using a Bayesian, hierarchical, penalized-spline model, with survey input, to produce annual estimates and projections of contraceptive supply-share outcomes. Our approach shares information across countries, accounts for survey observational errors and produces probabilistic projections informed by past changes in supply shares, as well as correlations between supply-share changes across different contraceptive methods. Results may be used to evaluate family-planning program effectiveness and stability.
Inflammatory myofibroblastic tumor of the cecum presenting as acute abdomen, a rare pathology with a rarer presentation
Authors: Molina Gabriel A , Ludeña Carolina , Carrera Paul Alexander , Heredia Andrea E , Jimenez Galo E , Parrales Diana E , Portilla Carolina Alexandra , Martinez Sebastian Nicolay , Ochoa-Andrade Miguel Jacob 
Published: May 2024

Abstract
Inflammatory myofibroblastic tumor is an extremely rare neoplastic lesion with a predilection for aggressive local and recurrent behavior. The tumor tends to occur in the lungs of children and young adults, and although it can develop in older patients and other organs, this is extremely rare. Symptoms are nonspecific and depend on the location and size of the tumor. The gastrointestinal tract is rarely this mass’s primary site of origin, and the cecum is an even rarer location. We present the case of an otherwise healthy 55-year-old female who presented with an acute abdomen and a mass in her abdomen; after successful surgery, she fully recovered. Inflammatory myofibroblastic tumor causing acute abdomen was the final diagnosis.
Comparison of quantitative and qualitative anti-dsDNA assays
Authors: Selvaratnam Rajeevan , Srivastava Pooja , Tacker Danyel H , Thebo Jennifer , Wheeler Sarah E 
Published: May 2024

Abstract

Objective
In evaluation of systemic lupus erythematosus (SLE), anti–double-stranded DNA antibodies (anti-dsDNA) play a significant role in diagnosis, monitoring SLE activity, and assessing prognosis. However, evaluations of the performance and limitations for recently developed methods for anti-dsDNA assessment are sparse.

Methods
Specimens used for antinuclear antibody testing (n = 129) were evaluated for anti-dsDNA assay comparability across 4 medical centers in the United States. The methods compared were Werfen Quanta Lite dsDNA, Zeus Scientific dsDNA Enzyme Immunoassay, Bio-Rad multiplex immunoassay (MIA) dsDNA, ImmunoConcepts Crithidia, and Bio-Rad Laboratories Crithidia.

Results
For quantitative anti-dsDNA measurements, Spearman’s correlation coefficient was highest between Zeus and Werfen (ρ = 0.86; CI, 0.81-0.90; P &lt; .0001). Comparison of MIA to Werfen or Zeus yielded similar results to each other (ρ = 0.58; CI, 0.44-0.68; P &lt; .0001; and ρ = 0.59; CI, 0.46-0.69; P &lt; .0001, respectively), but lower than the correlation between Zeus and Werfen. Positive concordance between assays ranged from 31.4% to 97.1%, and negative concordance between assays ranged from 58.5% to 100%. The detection of anti-dsDNA in those with SLE diagnosis ranged from 50.9% to 77.4% for quantitative assays and 15.1% to 24.5% for Crithidia assays.

Conclusion
Current quantitative anti-dsDNA assays are not interchangeable for patient follow-up. Crithidia-based assays demonstrate high negative concordance and lack positive concordance among the methods.
Optimizing Advanced Trauma Life Support (ATLS®) to Maximize Readiness
Authors: Danford Joseph R , Reyes Florencio , Gurney Jennifer M , Smith Joshua P , Stinner Daniel J 
Published: May 2024

ABSTRACT

Introduction
The Army utilizes Individual Critical Task Lists (ICTLs) to track and ensure competency and deployment readiness of its medical service members. ICTLs are the various skills and procedures that the Army has deemed foundational for each area of concentration (AOC)/military occupational specialty (MOS). While many ICTLs involve the patient care that military medical providers regularly provide, some procedures are not as commonly performed. This, when coupled with lower patient volume at military treatment facilities (MTF), poses a challenge for maintaining skill competency and deployment readiness. Fort Campbell’s Blanchfield Army Community Hospital (BACH) has created a holistic and unique solution to meet many of these standardized requirements and support a ready medical force. By optimizing the Advanced Trauma Life Support (ATLS®) course curriculum to facilitate ICTL completion, BACH has increased its ICTL completion rates, ATLS® course exposure, and streamlined training requirements. The purpose of this article is to describe this best practice and suggest its applicability to other MTFs.

Materials and Methods
By cross-referencing the ATLS® course curriculum and appendices with ICTLs, BACH has augmented ATLS® course certification with the additional completion of 12 ICTLs. This new approach not only increases ICTL completion, but also increases ATLS® curriculum exposure to medical providers, such as Registered Nurses or Nurse Practitioners, who would not typically take ATLS®.

Results
Since starting this new approach in April 2021, 73 military medical personnel have completed the ATLS® course at BACH, with 24 different medical specialties represented. A total of 361 ICTLs have been completed with specific ICTL completion counts ranging from 13 to 48. Each ICTL tested was completed 100% of its annual requirement.

Conclusion
ATLS® is a mandatory joint interoperability standard for military physicians and it is also an Army ICTL for many AOCs/MOSs. Only counting completion of this course as one ICTL is a missed opportunity for the time spent by Army medical providers and limits the exposure of ATLS® to select AOCs/MOSs. This optimized and novel approach has been successful at BACH, suggesting its applicability at other MTFs that serve as ATLS® testing sites.
Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen
Authors: Snapiri Ori , Danziger Chen Rosenberg , Sachs Nimrod , Krause Irit , Zvi Haim Ben , Danino Dana , Kriger Or , Shachor-Meyouhas Yael , Averbuch Dina , Bilavsky Efraim 
Published: May 2024

Abstract
Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.
Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Valdez Hernan , Collinge Mark , Zwillich Samuel H , Toyoizumi Shigeyuki , Kwok Kenneth , Hirose Tomohiro 
Published: May 2024

ABSTRACT

Objectives
We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme.

Methods
Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs/LSCs and incidence rates (patients with events/100 patient-years) of SIEs and HZ were analysed over 75 months.

Results
Median ALCs were generally stable over 75 months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36–75. SIE/HZ incidence rates were higher in patients with ALC &lt;0.5 × 103 cells/mm3 versus those with ALC ≥0.5 × 103 cells/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with/without SIEs or HZ events.

Conclusions
SIE/HZ risk was highest in patients with ALC &lt;0.5 × 103 cells/mm3, supporting this threshold as clinically relevant for defining increased SIE/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn.
Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA
Authors: Cheng Jordan C , Swarup Neeti , Morselli Marco , Huang Wei-Lun , Aziz Mohammad , Caggiano Christa , Kordi Misagh , Patel Abhijit A , Chia David , Kim Yong , Li Feng , Wei Fang , Zaitlen Noah , Krysan Kostyantyn , Dubinett Steve , Pellegrini Matteo , Wong David T W 
Published: May 2024

Abstract
Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the ‘5mCAdpBS-Seq’ workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.
Repression of pervasive antisense transcription is the primary role of fission yeast RNA polymerase II CTD serine 2 phosphorylation
Authors: Boulanger Cédric , Haidara Nouhou , Yague-Sanz Carlo , Larochelle Marc , Jacques Pierre-Étienne , Hermand Damien , Bachand Francois 
Published: May 2024

Abstract
The RNA polymerase II carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats that can be phosphorylated to influence distinct stages of the transcription cycle, including RNA processing. Although CTD-associated proteins have been identified, phospho-dependent CTD interactions have remained elusive. Proximity-dependent biotinylation (PDB) has recently emerged as an alternative approach to identify protein-protein associations in the native cellular environment. In this study, we present a PDB-based map of the fission yeast RNAPII CTD interactome in living cells and identify phospho-dependent CTD interactions by using a mutant in which Ser2 was replaced by alanine in every repeat of the fission yeast CTD. This approach revealed that CTD Ser2 phosphorylation is critical for the association between RNAPII and the histone methyltransferase Set2 during transcription elongation, but is not required for 3′ end processing and transcription termination. Accordingly, loss of CTD Ser2 phosphorylation causes a global increase in antisense transcription, correlating with elevated histone acetylation in gene bodies. Our findings reveal that the fundamental role of CTD Ser2 phosphorylation is to establish a chromatin-based repressive state that prevents cryptic intragenic transcription initiation.
The TIMELESS and PARP1 interaction suppresses replication-associated DNA gap accumulation
Authors: Saldanha Joanne , Rageul Julie , Patel Jinal A , Phi Amy L , Lo Natalie , Park Jennifer J , Kim Hyungjin 
Published: May 2024

Abstract
TIMELESS (TIM) in the fork protection complex acts as a scaffold of the replisome to prevent its uncoupling and ensure efficient DNA replication fork progression. Nevertheless, its underlying basis for coordinating leading and lagging strand synthesis to limit single-stranded DNA (ssDNA) exposure remains elusive. Here, we demonstrate that acute degradation of TIM at ongoing DNA replication forks induces the accumulation of ssDNA gaps stemming from defective Okazaki fragment (OF) processing. Cells devoid of TIM fail to support the poly(ADP-ribosyl)ation necessary for backing up the canonical OF processing mechanism mediated by LIG1 and FEN1. Consequently, recruitment of XRCC1, a known effector of PARP1-dependent single-strand break repair, to post-replicative ssDNA gaps behind replication forks is impaired. Physical disruption of the TIM–PARP1 complex phenocopies the rapid loss of TIM, indicating that the TIM–PARP1 interaction is critical for the activation of this compensatory pathway. Accordingly, combined deficiency of FEN1 and the TIM–PARP1 interaction leads to synergistic DNA damage and cytotoxicity. We propose that TIM is essential for the engagement of PARP1 to the replisome to coordinate lagging strand synthesis with replication fork progression. Our study identifies TIM as a synthetic lethal target of OF processing enzymes that can be exploited for cancer therapy.
Olaparib in recurrent isocitrate dehydrogenase mutant high-grade glioma: A phase 2 multicenter study of the POLA Network
Authors: Esparragosa Vazquez Ines , Sanson Marc , Chinot Olivier L , Fontanilles Maxime , Rivoirard Romain , Thomas-Maisonneuve Laure , Cartalat Stéphanie , Tabouret Emeline , Appay Romain , Bonneville-Levard Alice , Darlix Amélie , Meyronet David , Barritault Marc , Gueyffier François , Remontet Laurent , Maucort-Boulch Delphine , Honnorat Jérôme , Dehais Caroline , Ducray François ,   POLA Network, Desenclos C , Guillain N , Menei P , Rousseau A , Cruel T , Lopez S , Abad M , Hamdan N , Adam C , Parker F , Seizeur R , Quintin-Roué I , Chotard G , Bronnimann C , Ricard D , Godfraind C , Khallil T , Cazals-Hatem D , Faillot T , Gaultier C , Tortel M C , Carpiuc I , Richard P , Aubriot-Lorton H , Ghiringhelli F , Djelad A , Maurage C A , Gueye E M , Labrousse F , Ducray F , Meyronet D , Figarella-Branger D , Chinot O , Bauchet L , Rigau V , Gauchotte G , Taillandier L , Campone M , Loussouarn D , Bourg V , Vandenbos-Burel F , Guillamo J-S , Roger P , Blechet C , Adle-Biassette H , Bielle F , Carpentier A , Dehais C , Milin S , Wager M , Colin P , Diebold M D , Chiforeanu D , Vauleon E , Marguet F , Langlois O , Forest F , Motso-Fotso M J , Andraud M , Lhermitte B , Noel G , Bernier M , Younan N , Rousselot-Denis C , Zemmoura I , Joubert C , Cohen-Moyal E , Uro-Coste E , Dhermain F 
Published: May 2024

Abstract

Background
Based on preclinical studies showing that IDH-mutant (IDHm) gliomas could be vulnerable to PARP inhibition we launched a multicenter phase 2 study to test the efficacy of olaparib monotherapy in this population.

Methods
Adults with recurrent IDHm high-grade gliomas (HGGs) after radiotherapy and at least one line of alkylating chemotherapy were enrolled. The primary endpoint was a 6-month progression-free survival rate (PFS-6) according to response assessment in neuro-oncology criteria. Pre-defined threshold for study success was a PFS-6 of at least 50%.

Results
Thirty-five patients with recurrent IDHm HGGs were enrolled, 77% at ≥ 2nd recurrence. Median time since diagnosis and radiotherapy were 7.5 years and 33 months, respectively. PFS-6 was 31.4% (95% CI [16.9; 49.3%]). Two patients (6%) had an objective response and 14 patients (40%) had a stable disease as their best response. Median PFS and median overall survival were 2.05 and 15.9 months, respectively. Oligodendrogliomas (1p/19q codeleted) had a higher PFS-6 (53.4% vs. 15.7%, P = .05) than astrocytomas while an initial diagnosis of grade 4 astrocytoma tended to be associated with a lower PFS-6 compared to grade 2/3 gliomas (0% vs 31.4%, P = .16). A grade 2 or 3 treatment-related adverse event was observed in 15 patients (43%) and 5 patients (14%), respectively. No patient definitively discontinued treatment due to side effects.

Conclusions
Although it did not meet its primary endpoint, the present study shows that in this heavily pretreated population, olaparib monotherapy was well tolerated and resulted in some activity, supporting further PARP inhibitors evaluation in IDHm HGGs, especially in oligodendrogliomas.