bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoonotic Surveillance of Bartonella spp.: Exploring the Public Health Risks in Human Settlements
Authors: Thakur Mukesh , Dolker Stanzin , Wangmo Lenrik K. , Ghosh Avijit , Dhankhar Nikhil , Singh Vinaya K. , Shukla Malay , Rameshkumar Anandhan , Biswal Manisha , Banerjee Dhriti , Joshi Bheem Dutt , Sharma Lalit K. 
Published: December 2024

ABSTRACTIntroductionUrban rodents are reservoirs of zoonotic pathogens, including Bartonella spp., which are transmitted by ectoparasites such as fleas. Zoonotic diseases caused by Bartonella often go undocumented due to confusing or subtle clinical symptoms, lack of awareness and poor diagnosis. This study aimed to assess the prevalence and diversity of Bartonella spp. by screening free‐ranging rodents and their ectoparasites in the unique ecological settings of Alipore Railway Station, Kolkata, India. The station's high passenger traffic and proximity to food stalls create favourable conditions for rodents and fleas to thrive, increasing the risk of zoonotic transmission.MethodsRodents and fleas were identified by morphological features and DNA sequencing. Detection of Bartonella was carried out by DNA sequencing of citrate synthase (gltA) gene. Phylogenetic relationships among the obtained sequences were inferred through phylogenetic tree and haplotype network analyses. Q‐PCR testing from human samples from the surrounding area was performed to confirm the zoonotic transfer potential.ResultsOf 60 rodents, identified as Bandicota indica 28 (46.7%) and Bandicota bengalensis 32 (53.3%), and 110 fleas (Xenopsylla cheopis) were collected. The prevalence of Bartonella infection varied across three different hosts, that is, 32/60 rodents (53.33%), 87/110 fleas (79.1%) and 4/25 human (16%). Phylogenetic analysis revealed four distinct Bartonella lineages comprising 11 novel haplotypes (H1–H11), with haplotype H4 shared between rodents, fleas and humans, indicating active and cross species transmission of Bartonella spp. Haplotype H10, identified as B. rochalimae, was a phylogenetically diverged lineage exclusively found in fleas, suggesting a potentially novel lineage.ConclusionsThe results highlight the significant public health risks posed by Bartonella spp. in densely populated urban areas, particularly in environments like railway stations where human–rodent interactions are frequent. This study underscores the necessity of integrated pest management and surveillance strategies, using molecular tools such as Q‐PCR, to mitigate the risk of zoonotic disease transmission in urban settings.
The prevalence of motility-related genes within the human oral microbiota
Authors: Rocha Sofia T. , Shah Dhara D. , Zhu Qiyun , Shrivastava Abhishek 
Published: December 2024

ABSTRACT

The human oral and nasal microbiota contains approximately 770 cultivable bacterial species. More than 2,000 genome sequences of these bacteria can be found in the expanded Human Oral Microbiome Database (eHOMD). We developed HOMDscrape, a freely available Python software tool to programmatically retrieve and process amino acid sequences and sequence identifiers from BLAST results acquired from the eHOMD website. Using the data obtained through HOMDscrape, the phylogeny of proteins involved in bacterial type 9 secretion system (T9SS)-driven gliding motility, flagellar motility, and type IV pilus-driven twitching motility was constructed. A comprehensive phylogenetic analysis was conducted for all components of the rotary T9SS, a machinery responsible for secreting various enzymes, virulence factors, and enabling bacterial gliding motility. Results revealed that the T9SS outer membrane β-barrel protein SprA of human oral bacteria underwent horizontal evolution. Overall, we catalog motile bacteria that inhabit the human oral microbiota and document their evolutionary connections. These results will serve as a guide for further studies exploring the impact of motility on the shaping of the human oral microbiota.

IMPORTANCE
The human oral microbiota has been extensively studied, and many of the isolated bacteria have genome sequences stored on the human oral microbiome database (eHOMD). Spatial distribution and polymicrobial biofilms are observed in the oral microbiota, but little is understood on how they are influenced by motility. To bridge this gap, we developed a software tool to identify motile bacteria from eHOMD. The results enabled the cataloging of motile bacteria present in the oral microbiota but also provided insight into their evolutionary relationships. This information can guide future research to better understand how bacterial motility shapes the human oral microbiota.
Spatial Distribution Patterns of Pleural Dissemination in Patients With Thymoma and Survival Analysis
Authors: Chang Hao , Li Gaiyan , He Dongjie , Zhu Siying , Jing Yong , Liu Honggang , Li Junting , Wu Peiwen , Shao Qiuju 
Published: December 2024

Background: Thymoma is a common malignancy with low incidence, and pleural metastases are common pattern of recurrence. It is necessary that the spatial location of pleural metastatic lesions be analyzed. This study aimed to analyze the spatial distribution patterns of pleural dissemination in patients with thymoma and evaluate the variables that influence the survival of pleural metastasis in this population.Methods: This retrospective study investigated hospital admissions of patients diagnosed with pleural metastasis from thymoma. The spatial distribution pattern and visualization of the pleural metastases were analyzed after establishing a coordinate system. We further analyzed the survival and influencing factors in patients with pleural metastases from thymoma.Results: The analysis included 56 patients with a cumulative count of 365 pleural metastases, with 351 metastases from Zones 1–5 finally included in the analysis. The spatial distribution of the 285 initially diagnosed pleural metastases was significantly concentrated in Zones 3 and 4 near the lateral half of the spine (56.5%), followed by Zone 5 (17.5%). Collectively, these two components accounted for 74.0% (211/285) of all initial metastatic lesions. The survival rates at 5 years for those who underwent surgery versus nonsurgical treatment were 68.3% and 37.1%, respectively (p = 0.015). Univariate Cox regression analysis showed that surgical intervention reduced the risk of death by 61%.Conclusions: The distribution of pleural metastatic lesions exhibited a nonuniform pattern, primarily concentrated on the spinal aspect below the aortic arch of the costal pleura and the spinal aspect of the diaphragmatic pleura.
Fat‐Free Mass Is Positively Associated With Urine Specific Gravity in Athletes and Active Adults: A Quantitative Review
Authors: Wilson Patrick B. , Winter Ian P. 
Published: December 2024

Background: Urine specific gravity (USG) is a commonly used assessment method to estimate the prevalence of hypohydration, typically based on a common threshold of ≥ 1.020. Some research has shown that USG can vary based on body size and composition, but the evidence to date is limited. This review examined whether an association between fat‐free mass (FFM), a component of body composition, and USG could be detected among published articles that have reported these variables in athletes and physically active individuals.Methods: By searching Google Scholar, the authors identified a large number of published articles (n = 161) reporting anthropometrics and USG. Only articles reporting data on adult samples of athletes or physically active individuals were included. Given differences in body composition and FFM between men and women, articles that did not report data separately for each sex were excluded. Spearman’s rank correlation coefficient (ρ) was used to assess the association between variables.Results: In men, FFM showed a significant, weak‐sized positive association with USG (ρ = 0.36, p < 0.001). Among women, FFM showed a significant, moderate‐sized positive association with USG (ρ = 0.57, p = 0.006). When results were combined independent of sex, the association between FFM and USG remained significant (ρ = 0.38, p  < 0.001).Conclusion: Athletes with larger amounts of FFM are more likely to have elevated USG. Protein and muscle metabolites such as creatinine, urea, and uric acid likely play some role in the observed relationships. If USG continues to be utilized in sport settings, more research is needed to determine if development of FFM‐specific USG thresholds may be more appropriate for determining hydration status.
SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint that Enables Tumor Immune Evasion by Impairing T Cell Cytotoxicity
Authors: Chi Hao , Deng Shouyan , Xu Ke , Zhang Yibo , Song Teng , Yu Jianghong , Wang Yiting , Liu Jiayang , Zhang Yuan , Shi Jiawei , Wang Yungang , Xu Jie 
Published: December 2024

Abstract
T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.
Abstract A004: Broad and synergistic anti-tumor effects of small-molecule inhibitors of hypoxia inducible factors when paired with immune checkpoint blockade
Authors: Salman Shaima , Huang Tina Y. , Hwang Yousang , Kumar Anmol , Dordai Dominic , MacKerell Alexander D. , Semenza Gregg L. 
Published: December 2024

Abstract
Motivation: Hypoxia inducible factors (HIFs) are critical transcriptional regulators that play fundamental roles in adaptive responses to low oxygen, both in normal and disease conditions. Dysregulated activation of HIFs has been implicated in a variety of cancers due to their role in mediating a broad range of key processes including angiogenesis, glycolysis, cell survival, cancer stem cell specification, and metastasis. Methods: In this study, we utilized virtual and cell-based high-throughput screening approaches to identify compounds that disrupt the binding of HIF-1α and HIF-2α to HIF-1β, leading to the suppression of HIF target gene expression. Results: In syngeneic animal models, we observed significant tumor regression when HIF inhibitors are combined with immunotherapy agents in multiple tumor models. The combined treatment enhanced the infiltration of natural killer (NK) cells into the tumor microenvironment. Conclusion: This study highlights the anti-tumor effects of HIF inhibitors and the immune response resulting in sustained tumor regression. The promising outcomes warrant further exploration of these inhibitors as potential cancer treatment agents.
Citation Format: Shaima Salman, Tina Y. Huang, Yousang Hwang, Anmol Kumar, Dominic Dordai, Alexander D. MacKerell, Gregg L. Semenza. Broad and synergistic anti-tumor effects of small-molecule inhibitors of hypoxia inducible factors when paired with immune checkpoint blockade [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A004.
Abstract A022: Discovery of conformationally constrained ALK2 inhibitors for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG)
Authors: Smil David , González-Álvarez Héctor , Ensan Deeba , Wong Jong Fu , Cros Julien , Hoffer Laurent , Kiyota Taira , Wilson Brian J. , Zepeda-Velázquez Carlos A. , Aman Ahmed , Isaac Methvin B. , Xin Tao , Bullock Alex N. , Sampson Peter B. , Al-awar Rima 
Published: December 2024

Abstract
Despite considerable research on new therapeutics to treat DIPG, a universally fatal grade IV pediatric CNS tumor located in the pons region of the brainstem, there has been minimal progress. Somatic missense mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1 gene encoding activin receptor-like kinase-2 (ALK2) are present in approximately 33% of children with DIPG, prompting our initial efforts towards the development of M4K2009, a 3,5-diphenylpyridine ALK2 inhibitor. Looking to improve potency, selectivity, and brain penetration, we subsequently designed, synthesized, and evaluated a first-in-class set of 5- to 7-member ether-linked and 7-member amine-linked conformationally constrained ALK2 inhibitors including M4K2308, M4K2281, M4K2304 and M4K2306. Overall, these new compounds are highly potent (ALK2 IC50 &lt; 10 nM, nanoBRET ALK2 IC50 &lt; 20 nM), selective (&gt;100-fold over ALK5), brain-penetrant (Cbrain,4h/Cplasma,4h &gt; 3, 10 mg/kg, NOD-SCID male mice) and show in vivo exposure (Cplasma,6h = 1−2 µM, 25 mg/kg, NOD-SCID male mice). In particular, M4K2308 displayed a good balance of potency and DMPK properties and is currently undergoing preclinical evaluation by M4K Pharma.
Citation Format: David Smil, Héctor González-Álvarez, Deeba Ensan, Jong Fu Wong, Julien Cros, Laurent Hoffer, Taira Kiyota, Brian J. Wilson, Carlos A. Zepeda-Velázquez, Ahmed Aman, Methvin B. Isaac, Tao Xin, Alex N. Bullock, Peter B. Sampson, Rima Al-awar. Discovery of conformationally constrained ALK2 inhibitors for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A022.
The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development
Authors: Sturgeon Christopher M. , Wagenblast Elvin , Izzo Franco , Papapetrou Eirini P. 
Published: December 2024

Abstract
Transformative technologies to sequence tumor genomes at large scale and single-cell resolution have exposed the repertoire of genetic alterations that are present in leukemia genomes, the timing of their acquisition, and patterns of their co-occurrence. In parallel, single-cell multiomics technologies are allowing us to map the differentiation paths and hierarchical structures of malignant cells and giving us a glimpse into hematopoietic development in prenatal life. We propose that interrogating how the genetic evolution, differentiation hierarchy, and ontogeny of malignant myeloid cells intersect with each other, using new experimental systems and multimodal technologies, will fuel the next generation of research breakthroughs.

Significance:
In recent years, remarkable technological advances have illuminated aspects of the pathogenesis of myeloid malignancies—yet outcomes for patients with these devastating diseases have not significantly improved. We posit that a synthesized view of the three dimensions through which hematopoietic cells transit during their healthy and diseased life—clonal evolution, stem cell hierarchy, and ontogeny—promises high yields in new insights into disease pathogenesis and new therapeutic avenues.
Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study
Authors: Guo Zhen-Ni , Qu Yang , Abuduxukuer Reziya , Jin Hang , Zhang Peng , Wang Jing , Zhang Ke-Jia , Qi Shuang , Zheng Xiang-Yu , Zhang Yu , Gao Jian-Hua , Pan De-Wang , Liu Xiao-Dong , Li Chun-Ying , Chen Li-Ping , Chen Jin-Hua , Gu Ji-Liang , Wang An-Ying , Jiang Ligang , Liu Liang , Jiang Yongfei , Wang Chun-Fei , Jia Yan , Xin Hong , Jiang Chun-Li , Qi Ying-Bin , Hu Xue-Feng , Li Song , Sun Xin , Nguyen Thanh N. , Yang Yi , Wang Lijuan , Chen Yu-Mei , Zhang Xian-Kun , Yuan Zhi-Mei , Ju Dong-Sheng , Cheng Xiao-Ying , Wang Junmin , Li Yang , Gu Yan-Qiu , Zhao Li-Li , Dong Chen-Peng , Liu Li , Teng Rui-Hong , Wang Cui , Liu Xue , Dong Yang , He Ling , Pang Meng 
Published: December 2024

BACKGROUND:
Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

METHODS:
We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals. Serum GFAP and UCH-L1 levels were measured 24 hours after IVT. Cases from 1 hospital were randomly assigned to the training (70%) and testing (30%) cohorts for internal validation. The external validation cohort included patients from the other 15 hospitals. Cutoff levels of GFAP and UCH-L1 for assessing the absence of HT were established in the training cohort and subjected to internal and external verification.

RESULTS:
A total of 1063 patients were included. Both GFAP and UCH-L1 levels were independently associated with HT, infarct volume, and 3-month outcome; levels lower than cutoff (12.6 and 63.1 pg/mL, respectively) excluded patients with HT with a negative predictive value of 98.31% (95% CI, 89.70%–99.91%) and detection sensitivity of 98.08% (95% CI, 88.42%–99.90%) in the training cohort. In the testing and validation cohorts, negative predictive value was 100% (95% CI, 75.93%–100%) and 100% (95% CI, 82.19%–100%), respectively, and the sensitivity was 100% (95% CI, 80.76%–100%) and 100% (95% CI, 77.08%–100%), respectively.

CONCLUSIONS:
Serum GFAP and UCH-L1 levels exhibit high sensitivity and negative predictive value for indicating the absence of HT 24 hours after IVT, which supports their potential role in assessing patients’ condition after IVT.
Recanalization Does Not Always Equate to Reperfusion: No-Reflow Phenomenon After Successful Thrombectomy
Authors: Horie Nobutaka , Inoue Manabu , Morimoto Takeshi , Sadakata Eisaku , Okamura Kazuaki , Morofuji Yoichi , Hara Takeshi , Kuwabara Masashi , Kondo Hiroshi , Ishii Daizo 
Published: December 2024

BACKGROUND:
Thrombectomy for acute large vessel occlusion is a well-established treatment for stroke prevention. However, futile recanalization cases, where no-reflow occurs despite successful recanalization, have been reported. This study aimed to assess cerebral hemodynamics immediately after thrombectomy and their relationship with clinical outcomes.

METHODS:
We prospectively enrolled patients who underwent successful thrombectomy (modified Thrombolysis in Cerebral Infarction [TICI] ≥2b) for internal carotid artery or middle cerebral artery occlusions at Nagasaki University Hospital between January 2021 and December 2023. Preoperative magnetic resonance imaging was performed, followed by flat-panel computed tomography perfusion 30 minutes after recanalization. Areas with cerebral blood flow <45%, Tmax >6 seconds, and cerebral blood volume <34%, 38%, and 42% were analyzed, and hypoperfusion intensity ratio and cerebral blood volume index were calculated using Rapid ANGIO. We assessed the correlation of these parameters with infarct expansion, hemorrhagic transformation, and poor outcomes, defined as modified Rankin Scale scores of 4 to 6, at 3 months.

RESULTS:

A total of 65 cases were analyzed. Infarct expansion, defined as a decrease in Alberta Stroke Program Early CT Score, occurred in 23 cases (12/28 TICI 2b and 11/37 TICI 2c/3). No-reflow, defined as Tmax >6 seconds, was observed in 80% of cases (52/65), regardless of TICI grade. The infarct expansion group in TICI 2b had a significantly larger residual cerebral blood flow <45% area (32.9±30.4 versus 10.6±14.5 mL) and a lower cerebral blood volume index (0.71±0.2 versus 0.92±0.2). Cerebral blood flow <45% (r=−0.57;
P
<0.001) and cerebral blood volume <34% (r=−0.40;
P
=0.001), not Tmax >6 seconds, negatively correlated with postoperative Alberta Stroke Program Early CT Score. In logistic regression analysis, cerebral blood flow <45% was an independent predictor of poor outcomes (adjusted odds ratio, 1.05 [95% CI, 1.00–1.11];
P
=0.039).

CONCLUSIONS:
No-reflow is common after thrombectomy, suggesting that successful recanalization does not always result in immediate tissue reperfusion. Hemodynamic impairment postthrombectomy may persist, highlighting the need for adjunctive treatments.
Ischemic Stroke in Users of Combined Hormonal Contraceptives: A Danish Registry Study
Authors: Letnar Gasper , Andersen Klaus Kaae , Olsen Tom Skyhøj 
Published: December 2024

BACKGROUND:
The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke.

METHODS:
In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30–40- versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized.

RESULTS:
In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62–1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30- to 40- and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50–0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97–1.35]).

CONCLUSIONS:
Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.