bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral and Immune Risk Factors of HIV Rebound After Interruption of Antiretroviral Therapy
Authors: Gianella Sara , Yu Tingting , Wang Rui , Ignacio Caroline , Schanz Merle , Kouyos Roger D , Caballero Gemma , Gaitan Noah C , Rawlings Stephen , Kuster Herbert , Metzner Karin J , Gandhi Rajesh T , Li Jonathan Z , Günthard Huldrych F , Smith Davey M , Chaillon Antoine 
Published: December 2024

Abstract

Background
Identifying risk factors for human immunodeficiency virus (HIV) rebound after treatment interruption is crucial for designing effective remission strategies.

Methods
Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, n = 73) and ACTG study A5345 (n = 44) were analyzed before antiretroviral therapy (ART) interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA &gt;1000 copies/mL).

Results
Late ART initiation was associated with higher rebound risk (shorter time to rebound) as compared to early ART. Higher pre-ART HIV RNA in plasma, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Fewer CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early-treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T cells appeared to be the most relevant risk factors for time to rebound, as indicated by variable selection in multivariable analysis.

Conclusions
These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression.
Clinical Trials Registration. NCT00537966 and NCT03001128.
Tissue-Resident CD8+ T Cells as Mediators of Protective Immunity in Breast Milk Transmission of Human Cytomegalovirus
Authors: Legg Shara B , Moylan David C , Kamau Neema , Latting Misty P , Devdhara Dhruv , Pati Sunil K , Crossman David K , Boppana Suresh B , Kutsch Olaf , Sabbaj Steffanie 
Published: December 2024

Abstract
While the role of breast milk antibodies to protect infants from human cytomegalovirus (HCMV) has been investigated, the role of T-cells has received little attention. We compared the frequency of memory T-cell populations in breast milk between mothers of infants who acquired breast milk HCMV (transmitters) and those with uninfected infants (nontransmitters). Nontransmitter mothers had an increased frequency of CD8+ effector memory T-cells (Tem) in their breast milk. In addition, we describe tissue-resident memory T cells (Trm) in breast milk and demonstrate most were Tem. We present data that nontransmitter mothers have increased frequency of CD8+ Trm in their breast milk when compared to transmitters and that Trm frequency is inversely correlated with breast milk HCMV viral load. Lastly, using scRNA-seq analysis we identified a unique population of T-cells in nontransmitters and demonstrate that these cells comprise CD8+ Trm. These studies suggest that CD8+ Trm may play a role in preventing viral transmission via breast milk to infants.
Validation of the 11+Myco MS-PREP® Method for Determination of Aflatoxins, Fumonisins, Deoxynivalenol, Ochratoxin A, Zearalenone, HT-2, and T-2 Toxins in Cereals, Baby Food, Spices, and Animal Feed by Immunoaffinity Column with LC–MS/MS: AOAC Performance Tested MethodSM 112401
Authors: Leeman Dave , Allan Andrew B , Cameron Helen , Donelly Carol , Tramaseur Adam , Stratton Joanna , MacDonald Susan J 
Published: December 2024

Abstract

Background
The 11+Myco MS-PREP® immunoaffinity column (IAC) contains a gel suspension of monoclonal antibodies specific to the toxins of interest. Following sample extraction, the IAC is used for cleanup and concentration of mycotoxins prior to analysis by LC with tandem mass spectrometry (LC–MS/MS).

Objective
This study evaluated the IAC with LC–MS/MS method for Performance Tested MethodSM certification for simultaneous determination and confirmation of aflatoxins (AF) B1, B2, G1, G2, and M1; deoxynivalenol (DON), fumonisins B1, B2, and B3; ochratoxin A (OTA); T-2; HT-2; and zearalenone (ZON) from corn, wheat, cereal-based baby food (with and without dairy ingredients), paprika, chili powder, and animal feed.

Methods
A single extraction method using acetonitrile-water (1 + 1, by volume) was used for all matrixes. The method developer validated all matrixes and an independent laboratory verified method performance on corn and animal feed. Data were analyzed for recovery, repeatability precision, LOD, LOQ, confirmation of identity, and method selectivity.

Results
Recovery (72–138%) and repeatability (0.46–24%), with the exception of sporadic data points, were within acceptance criteria. LOQ was estimated as AFB1 0.018–0.32 μg/kg, AFB2 0.037–0.28 μg/kg, AFG1 0.019–0.14 μg/kg, AFG2 0.036–0.28 μg/kg, DON 4.0–75 μg/kg, fumonisin B1 4.9–37 μg/kg, fumonisin B2 4.0–32 μg/kg, fumonisin B3 2.0–16 μg/kg, OTA 0.15–4.4 μg/kg, T-2 0.5–7.5 μg/kg, HT-2 0.70–7.5 μg/kg, and ZON 1.3–7.2 μg/kg, depending on matrix. Method performance was verified with reference and QC materials. Selectivity and confirmation of identity were also demonstrated.

Conclusion
The 11+Myco MS-PREP IAC with LC–MS/MS method demonstrated acceptable performance for simultaneous determination of 12 mycotoxins in seven matrixes.

Highlight
The data were reviewed by the AOAC Performance Tested MethodsSM Program and approval was granted for certification of the 11+Myco MS-PREP Method as PTM 112401.
Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake
Authors: Liut Jennifer , Madea Burkhard , Meißner Dirk , Lützen Arne , Javidi Sirous , Hess Cornelius , Krämer Michael 
Published: December 2024

Abstract
The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate [GHB-Pal]) in whole blood as a potential biomarker to extend the detection window of GHB use, e.g. in drug-facilitated sexual assaults. A liquid chromatography–mass spectrometry (LC–MS–MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n = 113) and from narcolepsy patients (n = 10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS–MS) and gas chromatography–mass spectrometry (GC–MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r = 0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approximately 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.
Two-sided function of osteopontin during osteoblast differentiation
Authors: Mardiyantoro Fredy , Chiba Norika , Seong Chang-Hwan , Tada Ryohei , Ohnishi Tomokazu , Nakamura Norifumi , Matsuguchi Tetsuya 
Published: December 2024

Abstract
Osteopontin (OPN) is expressed in various cell types including osteoblasts. OPN expression level is robustly increased during osteoblast differentiation. Although OPN was initially found as a secretory protein (sOPN), recent reports identified the intracellular isoform of OPN (iOPN). Distinct functions of each OPN isoform in osteoblasts, however, are not well established. Here, using the Tet-On inducible expression system, we examined the role of each OPN isoform during osteoblast differentiation. Induced overexpression of wild type OPN (wtOPN), which includes both sOPN and iOPN, significantly increased matrix mineralization and osteogenic marker gene expression during osteogenic differentiation induced by either ascorbic acid or bone morphogenetic protein (BMP) 9. In contrast, these osteogenic differentiation processes were significantly inhibited by the specific overexpression of iOPN. Furthermore, the addition of recombinant OPN or neutralizing anti-OPN antibody to the culture medium exerted promotive or inhibitory effect on osteoblast differentiation, respectively. These data strongly indicate that iOPN exerts inhibitory effects on osteoblast differentiation, whereas sOPN exerts positive effects. We also found that the secretion process of OPN is positively regulated by c-Jun N-terminal kinase (JNK) activity in osteoblasts.
Improvement of bone properties in children with osteogenesis imperfecta after pamidronate: a bone biopsy study
Authors: Farlay Delphine , Cornier Mathilde , Rizzo Sébastien , Cormier-Daire Valérie , Charpié Maelle , Pinto Graziella , Simonnet Hina , Badoud Isabelle , Gerbaix Maude , Chavassieux Pascale , Chapurlat Roland 
Published: December 2024

Abstract
OI, or bone brittle disease, is characterized by increased mineralization of bone matrix independently of clinical severity. So, a beneficial effect of antiresorptive treatments such as bisphosphonates (BP) is questionable. We aim to compare the bone matrix characteristics before and after BP pamidronate (PAM). Fifty-eight children (9 ± 5 yr-old) with OI (Type I, III, IV, V, VI, XI, or unknown) received intravenous PAM for 2 yr and underwent transiliac bone biopsies before (n = 57) and after (n = 35) treatment. Compared with age-matched controls, untreated OI was characterized by cortical and cancellous rarefaction. Two years of PAM in OI patients significantly decreased bone remodeling activity, increased cortical thickness, improved the maturation of both organic and mineral matrix, and most of the nanomechanical properties, despite further increase in the degree of mineralization. Overall, in addition to a gain in bone mass, our results showed for the first time that PAM is able to increase the maturation of mineral crystals and collagen matrix contributing to its antifracture efficacy in OI patients.
Ensuring Pharmaceutical Accountability for Human Rights and Access to Medicines: The Dutch Duty of Care Standard Applied to Pharmaceutical Companies
Authors: Turkie Rosalind , Perehudoff Katrina , Sellin Jennifer , Sainz Aldo 
Published: December 2024

Abstract
To effectively protect the human right to health, the global accountability gap for pharmaceutical companies regarding access to medicines must be addressed. Pharmaceutical companies have no formal obligations under human rights law; however, they do have responsibilities, and some companies (directly or indirectly) undermine the right to health and equitable access to medicines. We propose that pharmaceutical companies can be held accountable for human rights interferences by means of a provision in Dutch tort law containing an ‘unwritten duty of care’, an interpretation which is supported by the international human rights framework and recent Dutch jurisprudence. We propose a concrete example of how this duty could be applied in Dutch courts, which have previously held a private corporation accountable for contributing to dangerous climate change in the Milieudefensie et al. v Royal Dutch Shell case. To establish whether this duty could be applied to pharmaceutical companies, we use the court’s reasoning in Milieudefensie to assess the existence of a global consensus on the need for a pharmaceutical duty of care. We argue that human rights norms and soft law instruments that pharmaceutical companies themselves have endorsed prove that there is a growing consensus regarding the damage associated with excessively priced medicines, and an urgent need to establish a framework for holding pharmaceutical companies accountable for ensuring equitable access to medicines through legal measures.
Real-world impact of the platinum chemotherapy shortage on US patients with advanced cancer
Authors: Reibel Jacob B , Sun Lova L , Parikh Ravi B , Mahmud Nadim , Martin Lainie P , Hubbard Rebecca A , Mamtani Ronac 
Published: December 2024

Abstract
The recent cisplatin and carboplatin (“platinum”) chemotherapy shortage, first announced on February 10, 2023, has impacted cancer patients nationwide. Here, we quantify the extent to which the shortage affected platinum chemotherapy prescribing and short-term mortality. This cohort study included 11 797 adults with advanced solid cancers who initiated first-line therapy during the 1-year period before (February 1, 2022–February 9, 2023) or during (February 10, 2023–January 31, 2024) the platinum shortage. During the shortage, there was a 2.7% absolute reduction in platinum use (95% CI = −4.4% to −0.9%) compared to the previous year. At the peak of the shortage, there was a 15.1% absolute reduction in platinum prescribing (June 2023: 57.8% [95% CI = 53.6% to 62.0%]) compared to 1 year prior (June 2022: 72.9% [95% CI = 70.7% to 75.2%]). There was no difference in mortality before vs during the shortage (adjusted hazard ratio 1.00; 95% CI = 0.94 to 1.07) with median follow-up time of 7.6 months. Further research is required to study shortage impacts on long-term mortality.
Unraveling the clinical–pathological correlations of subjects with isolated and mixed neurodegenerative processes in the National Alzheimer’s Coordinating Center dataset
Authors: Hiya Satomi , Maldonado-Díaz Carolina , Rohde Susan K , Gonzales Mitzi M , Canbeldek Leyla , Kulumani Mahadevan Lakshmi S , Yokoda Raquel T , Sullivan A Campbell , Parker Alicia S , White Charles L , Daoud Elena V , Flores-Almazan Victoria , Crary John F , Farrell Kurt , Walker Jamie M , Richardson Timothy E 
Published: December 2024

Abstract
Although Alzheimer disease neuropathologic change (ADNC) is the most common pathology underlying clinical dementia, the presence of multiple comorbid neuropathologies is increasingly being recognized as a major contributor to the worldwide dementia burden. We analyzed 1051 subjects with specific combinations of isolated and mixed pathologies and conducted multivariate logistic regression analysis on a cohort of 4624 cases with mixed pathologies to systematically explore the independent cognitive contributions of each pathology. Alzheimer disease neuropathologic change and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) were both associated with a primary clinical diagnosis of Alzheimer disease (AD) and were characterized by an amnestic dementia phenotype, while only ADNC associated with logopenic variant primary progressive aphasia (PPA). In subjects with ADNC and comorbid LATE-NC, Lewy body disease, and/or cerebrovascular disease, the clinical phenotype was usually diagnosed during life as “Probable AD.” Conversely, the combination of ADNC with frontotemporal lobar degeneration with TDP-43, progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) resulted in a mixed clinical picture, with variable features of amnestic dementia, PPA subtypes, behavioral variant FTD, PSP syndrome, and CBD syndrome. These findings elucidate the cumulative effects of mixed pathologies and provide insights into interactions between neurodegenerative pathologies contributing to a variety of clinical dementia presentations.
Managing Water Consumption in Colonial Hong Kong: Separate Water Metering, c. 1965–1980s
Authors: Lai Siu-hei , Mok Florence 
Published: December 2024

Abstract
Water troubled administrators of the colonial regime and residents in Hong Kong during the first three decades of the post-war period. The colonial regime attempted to remedy water shortages by exploiting additional water supplies and by improving its administration of water usage. Using archival records in Hong Kong and London, as well as unofficial sources such as local newspapers, this article studies an under-explored demand-side maneuver, separate water metering, introduced by the colonial government in Hong Kong in 1965, and its sociohistorical role in managing water usage. With an improved legibility of water consumption for both local households and the government, separate meterage prompted households to use water more wisely and economically. This article demonstrates that separate meterage expanded the state’s capacity to manage household water consumption and strengthened societal efforts in water conservation. The combination of technology, financial incentives and persuasion—a “pragmatic-persuasive” governing strategy—planted “save water” in the minds of residents which involved households in the water administration to a greater extent. Separate meterage transformed public perceptions of water consumption in the long run and fostered the emergence of civic obligation over water conservation in Hong Kong. This article thereby makes an original contribution to the political and social history of Hong Kong, colonial statecraft, and water management.
(153) CAN LARGE-LANGUAGE MODELS ACCURATELY DISCERN AI-GENERATED SEXUAL MEDICINE SCIENTIFIC LITERATURE FROM HUMAN GENERATED?
Authors: Singh D , Greenberg JW , Shkolnik B , Hellstrom W 
Published: December 2024

Abstract

Introduction
Chat-GPT an iteration of Artificial Intelligence (AI) which utilizes Large-Language Model (LLM) to understand and generate text, has been increasingly employed in scientific literature, healthcare, and education since its release in 2022. While these LLMs offer the possibility of increasing the clarity of scientific writing, they have been met with criticism regarding utility, accuracy, legality, and reliability. To combat potential abuse of these powerful tools, academic institutions have used AI tools to help identify text generated by an LLM. However, no study has currently validated the accuracy and utility of AI in this setting.

Objective
To validate if commercially available AI detector tools can identify potentially AI generated text within published sexual medicine articles. Secondary aims included identifying factors that contribute to an article being flagged as AI generated.

Methods
Phrasly.AI was utilized as the primary AI detector tool that cross-referenced scores from other AI detectors named “ContentAtScale”, “GPTZero”, “ZeroGPT”, “OpenAI”, “CopyLeaks”, “TurnItIn”. Top 20 most cited articles published in the Journal of Sexual Medicine were obtained for the following 5 year intervals: 2004-2008, 2009-2013, 2014-2018, 2019-2024. Positive controls of known AI generated articles were also obtained. Each of these articles and controls were analyzed with Phrasly.AI. The following variables were obtained: type of article, sentences analyzed, number of sentences likely to be AI generated, percent of article AI-generated, country of authorship, and a likelihood AI-generated score (1 = Human, 2 = partial AI, 3 = complete AI). Results were analyzed using program R utilizing binominal regression models to determine likelihood of obtaining an AI-Generated score.

Results
A total of 80 articles in total were analyzed with 5 positive controls. All positive control articles were predicted to be AI-generated. 45% (36/80) articles were flagged as likely AI-Generated. All articles analyzed were published prior to 2022 when the first LLM was released. No significant association was found between the likelihood AI-Generated score and the following variables: country of authorship and the year published of the article. We did observe a significant association between type of article and likelihood of being AI-Generated in our regression model showing review articles had an OR 3.10 (95% 1.19-8.55; p = 0.023).

Conclusions
Current AI detector tools often inaccurately discern human-generated scientific writing as AI-Generated as all articles included in this study were published prior to the releast of Chat-GPT. Review Articles are three times as likely to be flagged as AI-generated. Further validity of the utility and accuracy of these tools is needed prior to their widespread adoption in cross-checking for AI utilization in the construction of scientific literature.

Disclosure
No.
(158) UTILITY OF PRIMARY CARE PHYSICIANS IN A UROLOGY MEN’S HEALTH CLINIC
Authors: Jacobs L , Dhillon H , Patel P 
Published: December 2024

Abstract

Introduction
Urology clinics may receive consultation referrals for clinical issues which do not require surgical specialist management. Additionally, with ongoing expansion of therapeutic options in men’s health, referring family medicine physicians may not be aware of all potential treatment modalities. Delayed time from referral to specialist consultation represents a significant issue in Canadian healthcare. Common referrals from general practice for urology assessment includes erectile dysfunction and testosterone deficiency. Multidisciplinary clinics enable access to care for various men’s health concerns where some may not require urologic surgeon specialist intervention.

Objective
We aim to assess whether men’s health trained primary care providers (PCPs) with foundational training in men’s health working within a multidisciplinary clinic can address common urologic referrals and reduce the need for specialist management of urology clinic referrals.

Methods
A retrospective chart review was performed involving all patients referred by personal primary care providers to urology who were screened by a urologist as appropriate for initial consultation by a PCP at a multidisciplinary men’s health clinic from January 2022 to January 2023 in Winnipeg, Canada. Patient demographics, medical concern, management, time from referral to treatment, and need for urologist follow-up was captured. There were no inclusion or exclusion criteria.

Results
A total of 419 patients were identified. Treatment data for all were collected. 331 patients (79%) were managed by an in-house PCP alone and 88 (21%) required urologist consultation following PCP assessment. De novo erectile dysfunction, low testosterone and orchalgia were the most common issues triaged to PCP initial management. Issues managed by PCP also included penile curvature, functional sexual concerns and lower urinary tract symptoms. Male infertility, penile curvature, and orchalgia were the most prevalent conditions requiring subsequent urologist referral. PCPs were able to initiate non-surgical therapies in a majority of patients. In analysis of treatment by primary referral medical concern, 100% of low testosterone, 96% of erectile dysfunction, and 82% of orchalgia were managed at the PCP level alone and did not require urologic surgeon assessment.

Conclusions
PCPs in a multidisciplinary clinic can provide care for a range of urologic issues and reduce need for urologist consultation. This study demonstrates the utility of PCPs in optimization of urologist consultation. Presenting issues may be predictive of the need for urologist referral.

Disclosure
No.