bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal analysis of metachronous double biliary tract cancers
Authors: Omori Yuko , Aoki Shuichi , Ono Yusuke , Kokumai Takashi , Yoshimachi Shingo , Sato Hideaki , Kusaka Akiko , Iseki Masahiro , Douchi Daisuke , Miura Takayuki , Maeda Shimpei , Ishida Masaharu , Mizuma Masamichi , Nakagawa Kei , Mizukami Yusuke , Furukawa Toru , Unno Michiaki 
Published: March 2024

AbstractThe molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC‐related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β‐catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence‐free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5‐year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary†
Authors: Beird Hannah C , Lin Dimitri , Lazar Alexander J , Futreal P Andrew 
Published: March 2024

AbstractGene disruption from double‐strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor TP53. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within TP53 do not correlate with prevalence, intron length, or overall genome‐wide levels of rearrangements. Therefore, these breakpoints appear to be selected for reasons other than to disrupt TP53. A recent article published by Saba et al in The Journal of Pathology illustrates a benefit to having breakpoints within intron 1 using high‐quality matched genomic and transcriptomic osteosarcoma sequencing data as well as in vitro validation. The authors describe how the rearrangement results in relocation of the TP53 promoter region to regions upstream of genes that encode members of cartilage, growth plate development, osteoclast formation, and other TP53‐related pathways. The upregulation of these genes by the TP53 promoter are gain‐of‐function events that are likely to promote tumor development and growth. Therefore, this article presents a potential new paradigm in which a single mutation would result in both the loss of a tumor suppressor and the gain of an oncogenic program. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Exploring variations in recommended first‐choice therapy for complicated urinary tract infections in males: Insights from outpatient settings across age, race, and ethnicity
Authors: Sine Kathryn , Lavoie Thomas , Caffrey Aisling R. , Lopes Vrishali V. , Dosa David , LaPlante Kerry L. , Appaneal Haley J. 
Published: March 2024

AbstractIntroductionThere are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated.ObjectivesWe characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first‐choice antibiotic therapy.MethodsWe conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first‐choice therapy for complicated UTI was defined as use of a recommended first‐line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first‐choice therapy (adjusted odds ratio [aOR] > 1).ResultsWe identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first‐choice therapy (first‐line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18–49 years (aOR 1.07, 95% confidence interval [CI] 1.03–1.11) versus age ≥65 years was the only demographic factor predictive of recommended first‐choice therapy.ConclusionsNearly half of the patients included in this study did not receive recommended first‐choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first‐choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.
Emotional distress and future healthcare utilization in oncology populations: A systematic review
Authors: Kirsch Janae L. , Roche Anne I. , Bronars Carrie , Donovan Kristine A. , Hassett Leslie C. , Ehlers Shawna L. 
Published: March 2024

AbstractObjectiveEmotional distress has been correlated with greater healthcare utilization and economic costs in cancer; however, the prospective relationship between positive distress screens and future healthcare utilization is less clear. Taken together, there is a critical need to synthesize studies examining the prospective relationship between emotional distress and future healthcare use to inform distress management protocols and motivate institutional resource allocation to distress management. The aim of the systematic review is to explore the relationship between emotional distress, measured via validated emotional distress questionnaires, and subsequent healthcare utilization in patients diagnosed with cancer.MethodsA systematic search of seven databases was conducted on 29 March 2022 and updated 3 August 2023. Eligibility criteria were: (1) peer‐reviewed, (2) quantitative or mixed methods, (3) adults (≥18 years) diagnosed with cancer, (4) cancer distress questionnaire(s) completed prior to healthcare utilization, and (5) written in English. Exclusion criteria included: (1) non‐emotional aspects of distress (i.e., spiritual or physical distress), (2) healthcare utilization characterized via economic or monetary variables, and (3) caregiver or non‐cancer populations.ResultsNineteen peer‐reviewed articles were included in the review. There was significant heterogeneity in emotional distress instruments and type of healthcare utilization used. Most studies examining general distress or anxiety found that increased distress was predictive of greater future healthcare utilization.ConclusionThe results suggest that individuals with higher levels of general distress and anxiety are at increased risk for future healthcare utilization.
Characterization of a Deglaciated Sediment Chronosequence in the High Arctic Using Near‐Surface Geoelectrical Monitoring Methods
Authors: Cimpoiasu Mihai O. , Kuras Oliver , Harrison Harry , Wilkinson Paul B. , Meldrum Philip , Chambers Jonathan E. , Liljestrand Dane , Oroza Carlos , Schmidt Steven K. , Sommers Pacifica , Irons Trevor P. , Bradley James A. 
Published: March 2024

ABSTRACTAccelerated climate warming is causing significant reductions in the volume of Arctic glaciers, such that previously ice‐capped bare ground is uncovered, harboring soil development. Monitoring the thermal and hydrologic characteristics of soils, which strongly affect microbial activity, is important to understand the evolution of emerging terrestrial landscapes. We instrumented two sites on the forefield of a retreating Svalbard glacier, representing sediment ages of approximately 5 and 60 years since exposure. Our instrumentation included an ERT array complemented by adjacent point sensor measurements of subsurface temperature and water content. Sediments were sampled at each location and at two more additional sites (120 and 2000 years old) along a chronosequence aligned with the direction of glacial retreat. Analysis suggests older sediments have a lower bulk density and contain fewer large minerals, which we interpret to be indicative of sediment reworking over time. Two months of monitoring data recorded during summer 2021 indicate that the 60‐year‐old sediments are stratified showing more spatially consistent changes in electrical resistivity, whereas the younger sediments show a more irregular structure, with consequences on heat and moisture conductibility. Furthermore, our sensors reveal that young sediments have a higher moisture content, but a lower moisture content variability.
Computational analyses of drug resistance mutations in katG and emb complexes in Mycobacterium tuberculosis
Authors: Basrai Aadam , Blundell Tom L. , Pandurangan Arun Prasad 
Published: March 2024

AbstractThe number of antibiotic resistant pathogens is increasing rapidly, and with this comes a substantial socioeconomic cost that threatens much of the world. To alleviate this problem, we must use antibiotics in a more responsible and informed way, further our understanding of the molecular basis of drug resistance, and design new antibiotics. Here, we focus on a key drug‐resistant pathogen, Mycobacterium tuberculosis, and computationally analyze trends in drug‐resistant mutations in genes of the proteins embA, embB, embC, and katG, which play essential roles in the action of the first‐line drugs ethambutol and isoniazid. We use docking to predict binding modes of isoniazid to katG that agree with suggested binding sites found in our laboratory using cryo‐EM. Using mutant stability predictions, we recapitulate the idea that resistance occurs when katG's heme cofactor is destabilized rather than due to a decrease in affinity to isoniazid. Conversely, we have identified resistance mutations that affect the affinity of ethambutol more drastically than the affinity of the natural substrate of embB. With this, we illustrate that we can distinguish between the two types of drug resistance—cofactor destabilization and drug affinity reduction—suggesting potential uses in the prediction of novel drug‐resistant mutations.
A case of severe Mycobacterium thermoresistibile pneumonia
Authors: Subramaniam Selvaraj , Kanhere Mrudula , Shephard Lisa , Burke Andrew , Saxon Sarah , Geake James 
Published: March 2024

AbstractMycobacterium thermoresistibile is a thermotolerant nontuberculous mycobacterium which can rarely result in human infection. Although immunosuppression has been identified as a risk factor for infection, it is possible that mycobacterial laboratories may have previously under‐recognized M. thermoresistibile as standard mycobacterial incubation temperatures are suboptimal for culture of this organism. Here, we present a case of severe M. thermoresistibile pneumonia associated with achalasia requiring life support in the intensive care unit. We speculated that the interplay between specific host and environmental risk factors contributed to acquisition of infection. Infection with this fastidious organism required prolonged treatment with multiple antimicrobials and adjunctive therapeutic drug monitoring which led to clinical cure despite residual lung injury. We also reviewed literature documenting cases of human infection with M. thermoresistibile. The diagnosis of M. thermoresistibile requires a high degree of clinical suspicion considering its association with immunosuppressive conditions, postulated environmental inoculation and eponymous culture growth characteristics.
Responses of labile organic carbon fractions and mineralized carbon to straw return combined with fertilizer application in the maize–Melilotus officinalis intercropping system
Authors: Zhao Wei , Zhao Hongrui , Li Ruiqi , Hao Shuai , Wang Hongyan , Wang Daqing 
Published: March 2024

AbstractMollisol is crucial for solving food security issues, but long‐term excessive application of chemical fertilizers has led to severe Mollisol degradation in Northeast China, especially a rapid decline in soil organic carbon (SOC). In context of the use of crop‐herbage intercropping and straw return as alternatives for some chemical fertilizers, it is important to understand how crop‐herbage intercropping and straw return combined with chemical fertilizers influence labile organic carbon (LOC) fractions that improve SOC. To address this, this study explored how the combined application of maize (Zea mays L.)–Melilotus officinalis intercropping, straw return, and chemical fertilizers affect LOC fractions and mineralized carbon (MC) from the perspective of physical property‐mediated pathways. Thus, a field experiment with six treatments was established in the Songnen Plain of Northeast China: (1) maize monoculture without chemical fertilizers and straw return (CK), (2) maize monoculture with chemical fertilizers and no straw return (CF), (3) maize monoculture with chemical fertilizers and straw return (CFS), (4) maize–M. officinalis intercropping and straw return combined with full application of chemical fertilizers (CFSM), (5) maize–M. officinalis intercropping and straw return combined with half application of chemical fertilizers (1/2CFSM), and (6) maize–M. officinalis intercropping and straw return without chemical fertilizers (SM). The CF and CFS groups had no effect on bulk density and porosity but reduced specific gravity. The CFSM group increased water contents, porosity, LOC fractions, SOC, MC, and CO2 release rate and decreased bulk density and specific gravity. Compared with the CF group, the 1/2CFSM group enhanced water contents, microbial biomass carbon, and water‐soluble organic carbon (WSOC) to 6.36%, 17.91%, and 11.6%, respectively. We found that maize–M. officinalis intercropping, straw return, and reducing chemical fertilizers application improved LOC fractions to increase SOC by positively affecting bulk density, specific gravity, and water contents. Further analysis indicated that WSOC was a key determinant of SOC and maize yields. These findings provide a strategy to increase SOC and rehabilitate degraded soils through crop‐herbage intercropping and straw return combined with reducing chemical fertilizers application, which will contribute to a sustainable and environmentally friendly agriculture.
Edged beyond thresholds of conventional vulnerabilities: Critical reflections on COVID‐19, women and gender
Authors: McApreko Prize Fourthson , Sedegah Daniella Delali , Premkumar Philippa Jilly Joel , Tuffour Michael 
Published: March 2024

AbstractThough Johan Galtung's extensive application of the term structural violence in peace studies has been a subject of controversy, his rendition remains critical, seminal, and influential in broad spaces of contemporary discourse including Africa's sociocultural engagements. In his epic essay: “Violence, Peace and Peace Research” he reasoned that structural violence is violence that results in harm but is not necessarily caused by any specific identifiable actor and advanced his argument to the proposition that positive peace is the absence of structural violence. This paper probes how structural violence, seen as multiple ways in which economic, social and cultural systems in Africa, specifically Ghana, leverage their cumulative strengths to edge particular populations in this context women, to the brinks and margins of Covid‐19 related risks, thus stretching women's state of affairs beyond the thresholds of traditionally held vulnerabilities. The study unveils how women's disproportionate exposure to COVID‐19 compromises public health to the detriment of human capital. It concludes that making women's rights locally relevant in Africa constitutes an important capital investment in promoting a better human rights regime for social development as the world contemplates a post‐COVID‐19 era, expressed in shared prosperity, collective security, and equity in social justice.
Synthesis and Identification of Heterobivalent Anticancer Compounds Containing Urea and 5‐Arylidene‐2‐Thiohydantoin Motifs
Authors: Whitely Chelsi , Winburn Haley , Li Yangmei 
Published: March 2024

AbstractUrea and thiohydantoin are among the important privileged structures for drug discovery. We have developed a synthetic approach to the high‐throughput synthesis of the heterobivalent compounds containing both urea and 5‐arylidene‐2‐thiohydantoin functional groups. This synthetic methodology was applied to the synthesis of a mixture‐based library containing a total of 5280 compounds in a positional scanning format. The library was screened for its antiproliferative activity against cancer cells using a tetrazolium dye (MTT) based assay. Deconvolution of the library identified six hit compounds exhibiting moderate inhibitory potency against cancer cell proliferation.
Solubility and Stability of Carvedilol in Deep Eutectic Solvents: A Step Towards a Sustainable Pharmaceutical Formulation in the Liquid State
Authors: Lomba Laura , Polo Alejandra , Martínez Nuria , Alejandre Julia , Giner Beatriz 
Published: March 2024

AbstractCarvedilol is used to treat chronic hypertension, chronic stable angina pectoris and concomitant treatment heart failure and class II of the Biopharmaceutics Classification System (low solubility and poor bioavailability). This drug is only formulated as tablets, and liquid oral formulations are not available on the market. In this work, several aqueous eutectic mixtures formed by xylitol, citric acid, sorbitol and glucose (HBD) and choline chloride as HBA have been used to improve the solubility. Additionally, SwissADME was used to obtain physicochemical and pharmacokinetic parameters to further knowledge on the ADME (absorption, distribution, metabolism and excretion) parameters for carvedilol.The results reveal that the solubility of carvedilol increases as the content of water decreases, and the mixture formed by citric acid and choline chloride (CACh10) was the most soluble. The stability study shows that carvedilol in DES is stable during the test time, as the maximum and minimum concentration losses were 19.0 % and 0.2 %, respectively. These results help advance the green and sustainable development of new medicines in the liquid state.
Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity
Authors: Peng Yusheng , Shi Pengmin , Wang Changli , Wei Tangli , Yang Jing , Liao Xiali , Yang Bo , Gao Chuanzhu 
Published: March 2024

AbstractPicoplatin can effectively circumvent cisplatin‐induced resistance through the “steric hindrance effect” of its structure, but there are still problems such as toxicity and side effects, so the search for safer, more efficient platinum analogs is crucial. Here we report three fluorinated pyridine‐containing Pt(IV) complexes employing biotin as an axial ligand to provide targeting functionality. Lipid solubility studies showed that all the synthesized complexes possessed improved lipid‐water partition coefficients, which are beneficial for transmembrane transport of drugs. The DNA binding activity of the compounds was studied using UV titration, fluorescence titration, and PicoGreen staining, demonstrating the presence of potential intercalation and electrostatic interaction binding modes. It probably attributable to planar π‐π interactions provided by the aromatic pyridine ligands. Meanwhile, molecular docking studies showed that the introduction of axial biotin molecules allowed the complexes to effectively target cancer cells, which was simultaneously confirmed by the results of cellular uptake studies. And another docking result showed that the Pt(IV) complexes binds to DNA by minor groove binding. The synthesized complexes exhibited similar cytotoxicity to cisplatin in five cell lines (SW480, HCT116, HepG2, A549 and LO2), with complex 3 being superior to the parent drug, picoplatin.
Synthesis, some Physicochemical and Biomedical Properties of colored Apatite‐Structured Compounds with Mn5+ and Cr5+
Authors: Vasileva Anastasyya A. , Kazakovtsev Stepan A. , Guseinov Davud V. , Ezhevskii Alexander A. , Egorikhina Marfa N. , Aleynik Diana Ya. , Bulanov Evgeny N. 
Published: March 2024

AbstractDevelopment of new non‐toxic pigments of a wide range of applications (from coloring of bone cements to aesthetic cosmetology, including tattooing) of blue and green shades is an urgent task. In the present work, colored compounds with apatite structure were synthesized by solid‐phase method. The obtained products were crystallized in hexagonal syngony of P63/m space group. The alloying elements – chromophores Mn5+ and Cr5+ in tetrahedrally coordinated positions – were responsible for sky‐blue and turquoise colors of the compounds, respectively. The conducted complex study (crystal structure, IR spectroscopy, color measurements, diffuse reflectance spectroscopy, electron paramagnetic resonance, cytotoxicity, surface morphology) of the colored compounds opens new opportunities for the development of alternative pigments of similar color range and expansion of the field of application of pigments based on compounds of apatite structural type. The results of in vitro study of cytotoxicity demonstrated the potential suitability of sky‐blue color compound (Mn‐containing apatite) for further creation of cold pigments on its basis for tattoo ink and bone cement coloring.