bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaginal Microbiome: Environmental, Biological, and Racial Influences on Gynecological Health Across the Lifespan
Authors: Dubé‐Zinatelli Eleni , Cappelletti Luna , Ismail Nafissa 
Published: December 2024

ABSTRACTThe human vaginal microbiome (VMB) is a complex and unique ecosystem composed of various microorganisms, including bacteria, fungi, archaea, viruses, and candidate phyla radiation. A healthy VMB is often characterized by the presence of Lactobacillus species, which play a crucial role in protecting and maintaining homeostasis within the vaginal environment. When this balance is disrupted, the protection of the vaginal epithelium weakens, leading to a reduction in Lactobacillus species and an increased risk of various gynecological and reproductive health issues. However, this generalized description can lead to misconceptions and an incomplete understanding of vaginal health, as Lactobacillus is not always dominant across all ages and racialized groups. Therefore, this review provides a comprehensive analysis of the environmental, biological, and racial influences on the VMB at each stage of a woman's life, highlighting their implications for gynecological health and offering a holistic understanding of the VMB for all women.
Role of Systemic Immune‐Inflammation Index, Systemic Inflammation Response Index, and Pan‐Immune Inflammation Value in the Prediction of Preeclampsia: A Retrospective Cohort Study
Authors: Özkan Sadullah , Dereli Murat Levent , Firatligil Fahri Burcin , Kurt Dilara , Kurt Ahmet , Sucu Serap Topkara , Sucu Sadun , Celen Sevki , Engin‐Ustun Yaprak 
Published: December 2024

ABSTRACTObjectiveThe aim of the study was to investigate the role of systemic immune‐inflammation index (SII), systemic inflammation response index (SIRI), and pan‐immune inflammation value (PIV) calculated from first trimester complete blood count (CBC) in predicting preeclampsia without (PE) and with severe features (PE‐SF).MethodsThis retrospective cohort study included 126 women with PE, 126 women with PE‐SF, and 126 women with healthy, normotensive pregnancies delivered at a large tertiary referral hospital between 2018 and 2022. The main outcome measures were SII, SIRI, and PIV.ResultsSII scores differed significantly between the control versus PE and control versus PE‐SF groups, while SIRI scores showed a significant difference between the control versus PE and PE versus PE‐SF groups. However, the PIV values showed a significant difference in all three groups. According to the receiver operating characteristic analysis performed for the discriminatory power of SII, SIRI, and PIV, the area under the curve (AUC) values were 0.801, 0.609, and 0.774 for the prediction of PE and 0.535, 0.701, and 0751 for the prediction of PE‐SF, respectively. An SII with a cutoff value of > 620.59×103/µL (sensitivity 81%, specificity 67%) and an SIRI with a cutoff value of > 0.94×103/µL (sensitivity 74%, specificity 69%) had the highest discriminatory power for the prediction of PE and PE‐SF, respectively.ConclusionOur results suggest an association between high SII, PIV, and SIRI results and an increased risk of future PE and could be used as a first trimester screening test to improve decision making in the prediction of PE.
NSQIP surgical risk calculator: a useful adjunct for the urology multidisciplinary meeting
Authors: Wu Hongyi , Guduguntla Arjun , Gyomber Dennis , Niall Owen , Satasivam Prassannah 
Published: December 2024

AbstractBackgroundSurgical risk calculators are not often routinely used in Urology Multidisciplinary Meetings (MDM), and little is known about their impact on clinical decision‐making. The aim of this study is to assess the utility of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator for decision‐making in the Urology MDM setting, with particular consideration given to decisions about surgical candidacy.MethodsWe analysed all adult patients discussed in our Urology MDM with urological conditions whose management plan could potentially include major surgery. During a MDM, a consensus management decision was made prior to the NSQIP score being revealed to blinded team members. Any change in decision after revealing the score was documented, including rationale.ResultsSixty‐three out of 64 eligible cancer cases being discussed at MDM warranted NSQIP scores being revealed to the MDM post initial consensus. 95.2% (n = 60) did not have a change in the MDM management plan after reveal of NSQIP score. The NSQIP score led to a change in the MDM management decision in three cases: two renal cancer cases where management changed to biopsy with view to microwave ablation if positive, and one prostate cancer case, where management changed to recommend against radical prostatectomy.ConclusionThe NSQIP risk calculator was a useful tool and adjunct in the MDM setting. It served as a safety net where surgical risk was not initially properly estimated by team members, and reinforced decisions where there was concordance between NSQIP score and clinical judgement.
Acalabrutinib in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma: Results of the phase 1b open‐label study (ACE‐LY‐003)
Authors: Strati Paolo , Agajanian Richy , Lossos Izidore S. , Coleman Morton , Kridel Robert , Wood Andrew , Lesley Robin , Wun Chuan‐Chuan , Stephens Deborah M. 
Published: December 2024

SummaryPatients with relapsed/refractory (R/R) follicular lymphoma (FL) have limited effective treatment options. Bruton tyrosine kinase inhibitors (BTKis) increase the anti‐tumoural phenotype of tumour‐associated macrophages, providing rationale to combine them with rituximab and lenalidomide (R2). Acalabrutinib, a second‐generation BTKi, has potential to improve R2 efficacy without increasing T‐cell–mediated toxicity due to its lack of interleukin‐2–inducible T‐cell kinase inhibition. Here, we report safety and efficacy from a phase 1b dose‐finding study (NCT02180711) evaluating acalabrutinib plus R2 in patients with R/R FL. Overall, 29 patients received acalabrutinib plus R2 (lenalidomide 15 mg, n = 8; lenalidomide 20 mg, n = 21). At a median acalabrutinib exposure of 21 months, the most common grade ≥3 treatment‐emergent adverse event (TEAE) was neutropenia (37.9%). The incidence of grade ≥3 serious TEAEs was 37.5% and 52.4% in the lenalidomide 15‐mg and 20‐mg cohorts, respectively; overall, the most common were COVID‐19 pneumonia, COVID‐19 infection and pneumonia. Earlier treatment withholdings/reductions were observed in the 20‐mg cohort. With a median follow‐up of 34.1 months, the overall response rate was 75.9%. The complete response rate was 25.0% and 42.9% in the lenalidomide 15‐ and 20‐mg cohorts, respectively. Due to acceptable toxicity and preliminary efficacy, the lenalidomide 20‐mg dose was selected for further investigation.
Atractylodes macrocephala Koidz polysaccharide ameliorates DSS‐induced colitis in mice by regulating the gut microbiota and tryptophan metabolism
Authors: Zhang Qian‐Wen , Yang Meng‐Jiao , Liao Chun‐Yu , Taha Reham , Li Qing‐Yu , Abdelmotalab Mohammed Ismail , Zhao Si‐Yu , Xu Yan , Jiang Zhen‐Zhou , Chu Cheng‐Han , Huang Xin , Jiao Chun‐Hua , Sun Li‐Xin 
Published: December 2024

Background and PurposeUlcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS‐induced colitis, and we aimed to investigate the underlying mechanisms in this study.Experimental ApproachPAMK was used to treat DSS‐induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan‐metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic‐mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.Key ResultsPAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan‐metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.Conclusion and ImplicationsBased on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS‐induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.
The Life and Death of Hydrocarbon Traps in East Greenland: The Charge and Degradation Histories of Laplace Bjerg and the Mols Bjerge
Authors: Andrews Steven D. , Decou Audrey , Marshall John E. A. , Hyden Fiona , Parnell John , Strogen Dominic P. 
Published: December 2024

ABSTRACTThe exhumed hydrocarbon traps of East Greenland provide a superb opportunity to study the evolution of fluid flow in the petroleum systems of the North Atlantic. Following basin inversion during the Cenozoic these structures were exhumed and deeply incised which has allowed them to be observed and mapped in great detail. This study examines the diagenetic history of the Mols Bjerge and Laplace Bjerg exhumed hydrocarbon traps, from the initial charge of Triassic and Jurassic reservoirs, to their eventual uplift and destruction. Detailed petrographic analysis was undertaken on 67 samples collected at representative intervals throughout the structures. Variations in the distribution of diagenetic phases and remnant porosity were investigated. Twenty three samples were also subjected to helium porosity measurement. Bitumen, up to 18%, was recognised in 34 samples, 6 of which were analysed for their form and reflectance. Fluid inclusion data, collected from the nearby Bjørnedal region, helps to constrain the thermal history of the region. Helium porosity and permeability measurements are low, largely below 10% and 2 mD respectively. However, the abundance of bitumen highlights the presence of significantly higher porosity and permeability during hydrocarbon charge. A synthesis of fluid inclusion data and bitumen reflectance, alongside a detailed examination of the paragenetic sequence, demonstrate that hydrocarbon charge occurred in the Eocene, during maximum burial, at which time only a minor reduction in original intergranular porosities had taken place. The destruction of the pore systems occurred due to the degradation of hydrocarbons to bitumen, resulting from heat flow during intrusive events, and subsequent carbonate and limonite cementation during uplift. The original source of the hydrocarbons is unclear. This work highlights that where unaffected by intrusives and uplift, the largely untested Triassic play may still contain viable reservoir intervals at depth on the Norwegian Continental Shelf.
Expansion of the Structure–Activity Relationship Profile of Triaminopyrimidines as Inhibitors of Caspase‐1
Authors: East Amanda , Polasek Callista G. , Miller Elizabeth A. , Ranganathan Srirajkumar , Reda Isabella D. , Patel Aisha , Ahlers Christopher D. , Zingales Sarah K. , Karver Caitlin E. 
Published: December 2024

ABSTRACTCaspase‐1 is a sought‐after therapeutic target for inflammatory conditions due to its role in activation and release of pro‐inflammatory cytokines, but there has been little success getting drugs into the clinic. We have previously shown triaminopyrimidines such as CK‐1‐41 are potent, reversible small molecule inhibitors of caspase‐1, likely binding in an allosteric site within the enzyme. A series of analogs of CK‐1‐41 were synthesized and tested against caspase‐1 to develop a more robust structure–activity relationship profile. In general, alkyl and aryl groups were well tolerated via an ethylene or methylene linkage to the piperazine nitrogen, with IC50 values ranging from 13 to 200 nM. The most potent compounds were methylene linked o‐tolyl (AE‐2‐21) and ethylene linked 4‐trifluoromethylphenyl (AE‐2‐48) with IC50 values of 18 and 13 nM, respectively. Derivatives with electrophilic covalent warheads linked via an amide bond to the piperazine nitrogen were synthesized and characterized. CA‐1‐11 and EM‐1‐10 were semi‐reversible, non‐competitive inhibitors of caspase‐1 with slightly reduced potencies of 134 and 144 nM, respectively. All derivatives docked well into the allosteric site, supporting our hypothesis that this family of caspase‐1 inhibitors function via an allosteric non‐competitive mechanism of inhibition.
Concomitant Upd(14)mat and Trisomy 14 Mosaicism in a Newborn Detected by Whole Genome Sequencing
Authors: Olsen Tilde , Ek Jakob , Bak Mads , Grønskov Karen , Bache Iben , Farholt Stense , Tümer Zeynep 
Published: December 2024

ABSTRACTMaternal uniparental disomy of chromosome 14, upd(14)mat, leads to Temple syndrome (TS), an imprinting disorder characterized by pre‐ and postnatal growth retardation, hypotonia, motor delay, joint laxity, and precocious puberty. The occurrence of upd(14)mat is rare, and it may, in even rarer cases, co‐occur with trisomy 14 mosaicism. To date, only 11 live‐born cases have been reported in the literature. We present a newborn girl with severe hypotonia, global developmental delay, feeding difficulties, dysmorphic features, and cardiac malformations. Using trio whole genome sequencing (WGS) no causative sequence or structural variants were detected. As a chromosomal disorder was suspected the data was further analyzed with a pipeline including analysis of UPD and low‐level mosaicism, which revealed upd(14)mat and low level trisomy 14 mosaicism. This study underscores the significance of advanced genetic testing techniques, thorough data interpretation, and expert clinical evaluation in diagnosing rare disorders with complex molecular mechanisms.
Bilateral Lung Transplantation in Patients With Severe Chest Asymmetry: A Case Series From a Single Center
Authors: Mendogni Paolo , Palleschi Alessandro , Grisorio Giacomo , Mazzucco Alessandra , Diotti Cristina , Morlacchi Letizia Corinna , Rosetti Valeria , Bonitta Gianluca , Nosotti Mario , Rosso Lorenzo 
Published: December 2024

ABSTRACTSuppurative lung diseases leading to end‐stage respiratory failure are typical indications for bilateral lung transplantation (LuTx). Some cases may present severe chest asymmetry because of recurrent infections or previous surgical procedures, and the most used surgical options are single LuTx and contralateral pneumonectomy or bilateral transplantation with graft downsizing. Our purpose is to evaluate our treatment protocols for these patients and review surgical strategies reported by others.We prospectively collected clinical data of patients with significant pleural cavity asymmetry who underwent bilateral LuTx at our center from 2017 to 2022. Clinical reports of all patients who underwent LuTx for end‐stage suppurative disease in the same period were reviewed as the control group.During the study period, 74 patients underwent bilateral LuTx for suppurative disease; seven of them presented with severe thoracic asymmetry, and all of them were extubated by the second postoperative day. The mean intensive care unit stay was 4 days. The postoperative radiological evaluation did not show clustering or atelectasis of the graft implanted in the smaller hemithorax. No perioperative major complications were recorded, and the average length of stay was 23 days. The perioperative course appeared remarkably good, and both the short‐ and long‐term follow‐up were similar to that of the control group.
Advancing Disability Healthcare Solutions Through Privacy‐Preserving Federated Learning With Theme Framework
Authors: Alruwaili Madallah , Siddiqi Muhammad Hameed , Idris Muhammad , Alruwaili Salman , Alanazi Abdullah Saleh , Khan Faheem 
Published: December 2024

ABSTRACTThe application of machine learning, particularly federated learning, in collaborative model training, has demonstrated significant potential for enhancing diversity and efficiency in outcomes. In the healthcare domain, particularly healthcare with disabilities, the sensitive nature of data presents a significant challenge as sharing even the computation on these data can risk exposing personal health information. This research addresses the problem of enabling shared model training for healthcare data—particularly with disabilities decreasing the risk of leaking or compromising sensitive information. Technologies such as federated learning provide solution for decentralised model training but fall short in addressing concerns related to trust building, accountability and control over participation and data. We propose a framework that integrates federated learning with advanced identity management as well as privacy and trust management technologies. Our framework called Theme (Trusted Healthcare Machine Learning Environment) leverages digital identities (e.g., W3C decentralised identifiers and verified credentials) and policy enforcements to regulate participation. This is to ensure that only authorised and trusted entities can contribute to the model training. Additionally, we introduce the mechanisms to track contributions per participant and offer the flexibility for participants to opt out of model training at any point. Participants can choose to be either contributors (providers) or consumers (model users) or both, and they can also choose to participate in subset of activities. This is particularly important in healthcare settings, where individuals and healthcare institutions have the flexibility to control how their data are used without compromising the benefits. In summary, this research work contributes to privacy preserving shared model training leveraging federated learning without exposing sensitive data; trust and accountability mechanisms; contribution tracking per participant for accountability and back‐tracking; and fine‐grained control and autonomy per participant. By addressing the specific needs of healthcare data for people with disabilities or such institutions, the Theme framework offers a robust solution to balance the benefits of shared machine learning with critical need to protecting sensitive data.
Performance variation with pristine and doped high‐k materials via atomic layer deposition
Authors: Jung Eun Su , Yoo JinUk , Choi Tae Min , Lee Hwa Rim , Lee Chae Yeon , Kim Dong Hyun , Pyo Sung Gyu 
Published: December 2024

AbstractThis review examines the performance variations of pristine and doped high‐k materials deposited using atomic layer deposition (ALD). This paper explores the fundamental principles of ALD and its application in creating high‐k materials with superior dielectric properties. High‐k materials such as HfO2, TiO2, and ZrO2 are critical in the semiconductor industry due to their high dielectric constants and ability to improve device performance. The review highlights how doping these materials can further enhance their electrical, chemical, and physical properties, leading to improved device reliability and efficiency. Various dopants and their effects on material characteristics, including dielectric constant, leakage current, and breakdown voltage, are discussed in detail. This paper concludes that ALD, with its precise control over film thickness and uniformity, is essential for the ongoing advancement of semiconductor technology and the development of next‐generation electronic devices.
The Architecture of Adaptive Lignin Biosynthesis Navigating Environmental Stresses in Plants
Authors: Jalal Abdul , Wang Yongli , Cai Chenyang , Ayaz Aliya , Alabbosh Khulood Fahad , Khan Khalid Ali , Han Song , Zhu Daochen 
Published: December 2024

ABSTRACTIn natural ecosystems, plants are under continuous environmental stresses, compromising plants' survival and propagation. Being sessile in nature, plants evolved various signalling pathways to cope with adverse changing environments, and to optimise their adaptation to terrestrial conditions. The plant cell wall, rich in polymers, is actively engaged in the signalling process. In this context, the phenylpropanoid pathway, producing protective secondary metabolites like flavonoids and lignin, played a crucial role in the early plants' colonisation on land. In this review, we highlighted the current knowledge and the impending gaps of lignin biosynthesis in plants, and the hydrophobic and impervious properties of lignin facilitating effective transportation of solutes and water within vascular system along with its significance to protect plants from environmental stressors either abiotic like temperature, drought, salinity and heavy metals or biotic such as herbivorous insects, root‐knot nematodes and phytopathogens. Additionally, the identification of essential biosynthetic genes that play a role in regulating lignin biosynthesis, as well as their contribution to improving stress tolerance through modifications in lignification of cell wall and biochemical mechanisms of lignin in the evolution of land plants are discussed, including the synergistic action of dirigent proteins and laccase in producing monolignol radicals. This discussion provided future research direction to develop genetic engineering approaches to improve lignin in terrestrial plants and develop stress‐tolerant plants that will improve the resilience and survival of plants under challenging environmental conditions.
Regulation of Clusterin in the Heart and Plasma of Mice After Transverse Aortic Constriction
Authors: Turkieh Annie , Weber Lukas , Chwastyniak Maggy , Baydar Simge , Beseme Olivia , Ernst Matthias , Ye Quianling , Amouyel Philippe , Podesser Bruno K. , Kiss Attila , Pinet Florence 
Published: December 2024

ABSTRACTChronic pressure overload induces adverse cardiac remodelling characterised by left ventricular (LV) hypertrophy and fibrosis, leading to heart failure (HF). Identification of new biomarkers for adverse cardiac remodelling enables us to better understand this process and, consequently, to prevent HF. We recently identified clusterin (CLU) as a biomarker of cardiac remodelling and HF after myocardial infarction. The aim of this study was to investigate whether CLU expression is regulated in the heart and could be used as an indicator of adverse cardiac remodelling in response to pressure overload. We quantified CLU in the LV of mice subjected to transverse aortic constriction (TAC) and observed increased CLU mRNA levels and its mature protein form (m‐CLU) compared to the sham. Interestingly, CLU mRNA levels were positively correlated with pro‐hypertrophic (ANP, BNP, B‐MHC), pro‐ and anti‐fibrotic (TGFb, ColI and CILP) genes. In addition, m‐CLU was positively correlated with LV hypertrophy, LV end diastolic and systolic diameters, and negatively correlated with LV ejection fraction. Finally, we observed that m‐CLU levels only increased in TAC mice with severe cardiac remodelling and dysfunction without any significant difference in plasma CLU levels. This is the first study to demonstrate that cardiac expression of CLU is induced in the LV of TAC mice during adverse cardiac remodelling. However, plasma CLU levels could not be used as biomarkers of TAC‐induced cardiac remodelling and dysfunction.